Pulmonology

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Visits to the emergency department for asthma increase more than a year before a failed inspection by the U.S. Department of Housing and Urban Development (HUD), according to a new study presented at the annual meeting of the American College of Emergency Physicians.

While links between asthma and low-quality housing prone to harboring allergens have been well-documented, the current study takes the extra step of looking at housing down to the level of individual land parcels and suggests that asthma hospital visits can be used to identify hazardous housing earlier.

“Emergency department visits for asthma provide a leading indicator that can be used by health departments or housing authorities to direct housing inspections and remediation of poor housing conditions, track improvements in housing quality, measure housing department performance, support resident grievances, and inform funding allocation decisions,” said the study’s lead researcher, Elizabeth Samuels, MD, who is assistant professor of epidemiology and emergency medicine at Brown University, Providence, R.I.

Researchers retrospectively looked at cases of children and adults in the Greater New Haven area of Connecticut seen at the Yale New Haven Hospital ED for asthma-related problems between March 2013 and August 2017. The region has the fifth-highest prevalence of asthma in the United States, the researchers point out, due to its air quality, pollens, and quality of its housing. More than half of residences were built before 1,940, compared with about 13% nationally. Patient addresses were matched with HUD inspection records.

The review encompassed 11,429 ED visits by 6,366 individuals; 54% were insured by Medicaid, and 42% were Black. Controlling for patient and neighborhood data, researchers found that increased asthma ED visits at the parcel level were associated with decreased HUD inspection scores to a highly significant degree (P < .001).

They also found that there was a relationship in terms of timing between asthma ED visits and inspection scores: asthma ED visits increased more than 1 year before a failed HUD inspection. They also found that asthma ED visits were not elevated at housing units that passed inspection. Using asthma ED visits to predict failed housing inspections produced a specificity rate of 92.3% in an adjusted model, Dr. Samuels noted.

“This approach represents a novel method of early identification of dangerous housing conditions, which could aid in the prevention of asthma-related morbidity and mortality,” Dr. Samuels said.

The investigators noted that, of the parcels with the top three incidence rates of asthma ED visits, “all of them have been closed or demolished.”

In addition to limiting exposure of patients with asthma to the allergens of mold, mice and rats, and cockroaches, improving poor-quality housing earlier could help asthma by reducing stress, she said.

“There is also an increasing evidence base that psychosocial stress increases the risk of asthma attacks, and it’s therefore possible that living in poor housing conditions – often highly stressful situations – drives exacerbation risk via this pathway,” she said. “Synergistic effects between these pathways are also possible or even likely.”

Neeta Thakur, MD, associate professor of medicine at the University of California, San Francisco, who researches asthma, said the findings could lead to a strategy for improving poor-quality housing more quickly. As it is, inspections are too infrequent, often prompted by resident complaints.

“Once the complaints get to a certain threshold, then there might be an inspection that happens, and if there is a periodic review of the buildings, they often happen few and far between,” she said. “We could actually use some of the information that we’re already getting from something like ED visits and see if there is a pattern.”

An important follow-up would be to see whether asthma outcomes improve after housing deficiencies are addressed and whether the predictive capacity of ED visits occurs in other places.

“Would you then see a decline in the ED visit rates from individuals living in those buildings?” Dr. Thakur said. “It’s important to find a leading indicator, but you want to be sure that that leading indicator is useful as something that can be intervened upon.”

Dr. Samuels and Dr. Thakur have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Just uttering the word “mucus” is often sufficient to elicit amusement from those within earshot, but to patients with chronic inflammatory airway diseases, mucus is no laughing matter.

Under normal conditions, mucus plays an important protective role, trapping airway irritants such as smoke, pollen, and particulate matter, which are then moved by cilia out of the airways for expulsion through coughing.

But in cystic fibrosis (CF), for example, mucus hypersecretion can be deadly. The underlying pathology of CF – a mutation in the CFTR gene, which codes for the protein CF transmembrane conductance regulator – leads to buildup in the lungs of abnormally viscous and sticky mucus, resulting in frequent, severe infections (particularly with Pseudomonas aeruginosa), progressive lung damage, and prior to the development of effective disease management, significantly premature death.

Mucus hypersecretion is also a feature of chronic obstructive pulmonary disease (COPD), noted Victor Kim, MD, from Temple University, Philadelphia, Christopher M. Evans, PhD, from the University of Colorado at Denver, Aurora, and Burton F. Dickey, MD, from the University of Texas MD Anderson Cancer Center, Houston.

In COPD, “mucus dysfunction arises from several mechanisms, including excess production due to inflammation, decreased elimination due to impaired ciliary clearance and reduced cough efficiency, and excessive concentration due to smoke-induced dysfunction of transepithelial anion transport resembling CF,” they wrote in an editorial published in the American Journal of Respiratory and Critical Care Medicine.

In patients with idiopathic pulmonary fibrosis, a polymorphism in the enhancer region of MUC5B, a gene that encodes for mucin glycoproteins, results in a 20-fold overexpression of the gene and prominent mucus production that has been shown to parallel lung inflammation and decline in forced vital capacity (FVC).

In patients with asthma, up-regulation of MUC5AC and stimulated mucus secretion conspire to obstruct airways, which can in extreme cases lead to death.
 

‘Short shrift’

Yet until recently, the role of mucus hypersecretion in diseases such as COPD has been largely overlooked, or as Dr. Kim and colleagues put it, “airway mucus often receives short shrift from clinicians.”

“It’s a pretty hot topic in pulmonary medicine today because it has been so neglected for so long,” Dr. Dickey said in an interview with CHEST Physician. “As clinicians we haven’t had a way to identify who needs treatment, which is ridiculous, because many of the people who expectorate a lot, like those with chronic bronchitis, don’t actually have small airway obstruction, and conversely, a lot of asthmatics, who have very serious small airway obstruction, don’t expectorate, so you can’t really tell from symptoms.”

What has changed in recent years is the use of chest CT to image muco-obstructive pathology, commonly called “mucus plugging” in the peripheral airways of patients with COPD and asthma.

“In the last decade or so, we’ve seen the emergence in obstructive lung diseases such as asthma and COPD the use of more objective measures on CT scans, including the problem of mucus plugging, which is unfortunately very common,” Dr. Kim said in an interview.

The discovery of the extent and severity of mucus in obstructive lung diseases has led to new strategies to combat mucus overconcentration, such as hydration, mucolytics, and an intriguing investigational approach to decrease calcium-induced hypersecretion with designer peptides.
 

Mighty mucins

Under normal physiologic conditions mucus is composed largely of water (97%) and salts (2%), with the remainder consisting of entrapped globular proteins (0.7%) and mucins (0.3%), Dr. Dickey explains.

Yet those meager mucins pack a real punch, with the ability to absorb 300 times their mass of water after secretion, creating mucus of optimal consistency and viscoelasticity.

“Personally, I’ve never understood – maybe I should have paid more attention in physics – how a compound can absorb 300-fold its mass, but it does,” he said.

In a recent review article in the journal Clinical and Translational Medicine, Dr. Dickey and colleagues described how good mucus can go bad.

“[H]igh levels of mucin production from inflammatory stimulation (termed ‘mucous metaplasia’), followed by rapid release (together, termed ‘mucus hypersecretion’), can plug airways due to mucus volume expansion. In addition, if available lumenal liquid is insufficient, concentrated mucus of excessive viscoelasticity and adhesivity can cause mucus stasis,” they wrote.
 

Therapeutic strategies

In patients with CF, CFTR modulator therapy has markedly reduced but not eliminated the need for some patients to have mucolytic therapy, which may include dornase alfa, a recombinant human deoxyribonuclease that reduces the viscosity of lung secretions, hypertonic saline inhaled twice daily (for patients 12 and older), mannitol, and physical manipulations to help patients clear mucus. The manipulations can include both manual percussion and the use of devices for high-frequency chest wall oscillation.

Unlike in CF, where treating the underlying genetic pathology can help to resolve the thick, sticky mucus problems and thereby significantly reduce risk of infections and progressive lung damage, treatment of mucus metaplasia or hypersecretion in other diseases is aimed at symptomatic relief; it is still unclear whether symptomatic improvement of mucus overproduction would correlate with other disease-related outcomes, Dr. Kim and Dr. Dickey noted.

Potential therapeutic strategies to reduce excess mucus in the lungs include the use of mucolytic agents to thin secretions for more effective expulsion, decreasing mucus production through the use of an interleukin-13 (IL-13) inhibitor such as the anti-asthma agent dupilumab (Dupixent), and a novel strategy, still in the experimental phase, aimed at “disrupting the fusion of mucin storage granules with the cell membrane, thereby blocking secretion,” wrote Irina Gitlin, PhD, and John Fahy, MD, from the University of California, San Francisco, in Nature.

They were referring to research by Dr. Dickey and colleagues described in the same issue of Nature focusing on the inhibition of calcium-triggered mucus secretion by the use of hydrocarbon-stapled peptides, short chains of amino acids stabilized with a chemical bridge to a hydrocarbon molecule.
 

Knocking secretion down, but not out

The work has centered on decreasing overproduction of mucins with a focus on the signals for mucin production, including IL-13 and interleukin-1 beta, and on the signals for rapid release of mucins, including adenosine 5’-triphosphate (ATP), best known as an intracellular energy-storage module.

“But ATP is also steadily released by ciliated cells in response to the shear stress of tidal breathing, and it tells the neighboring secretory cells to slowly and steadily release mucin. But if the ciliated cells get stressed by any of a number of mechanisms, it can release a lot of ATP, and then the secretory cell can explosively release essentially all of its mucin content,” Dr. Dickey explained.

Other important signals for rapid release of mucins are acetylcholine and histamine, and all three of these agonists – ATP, acetylcholine, and histamine – cause a rise in intracellular calcium, which triggers calcium sensors that then lead to calcium-triggered membrane fusion and secretion.

Working as a postdoc in the Dickey laboratory, Dr. Evans had previously shown that deleting MUC5B in mice led to early development of serious lung abnormalities, some of which were fatal, indicating that MUC5B, a gene that is highly preserved in evolution, is essential for respiratory health.

This observation was later supported by a study of a family with a pattern of hereditary mucin deficiency caused by a homozygous loss-of-function mutation in MUC5B. The main subject in this study was an adult woman with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infections. Her sibling, who also had the biallelic mutation, had extensive sinus disease with nasal polyps. Other siblings who were heterozygous for the mutation were asymptomatic but had mild functional lung impairment.

The trick for the investigators, then, was to figure out how to reduce stimulated release of stored mucins while still preserving normal release of mucins to allow for ciliary clearance of mucus, and Dr. Dickey and colleagues appear to have accomplished this, at least in mice.

They first validated as a potential therapeutic target a protein labeled synaptotagmin-2 (Syt2). Syt2 is a calcium sensor that is an essential part of the system that triggers calcium-triggered secretion. In a model for allergic asthma, mice with Syt2 deleted from airway epithelia had marked reductions in both stimulated mucin secretion and in mucus occlusion in airway lumens, but remained otherwise healthy with normal lung function.

Working with structural biologist Axel Brunger, PhD, from Stanford (Calif.) University, Dr. Dickey and coinvestigators developed and validated a peptide that could specifically inhibit Syt2, and found that it mimicked the action of the Syt2 deletion, preventing mucus occlusion in the allergic asthma model without adversely effecting normal production.
 

Not ready for prime time

Dr. Dickey and colleagues are now working to translate the therapy into a form that can be used in humans, most likely as an aerosol that could be used for acute treatment of patients with mucus plugging from asthma and COPD, and also as a therapy for patients with chronic disease.

“In the chronic situation, what we would hope to do is identify patients with muco-obstructive lung disease – asthma, COPD, cystic fibrosis – who have airway mucus obstruction and then use the inhaled peptide on a regular basis as one part of a program to try to prevent this chronic mucus occlusion,” Dr. Dickey said.

As Dr. Gitlin and Dr. Fahy wrote in their editorial, “by confirming that it is possible to block calcium-regulated mucin secretion, Lai and colleagues have shown the potential of such an approach as a new therapeutic strategy for lung illnesses associated with mucus pathology, including diseases such as asthma and COPD, for which there is a large unmet medical need.”

The study by Dr. Dickey and colleagues was supported by grants from the German Research Foundation, National Institutes of Health and the Cystic Fibrosis Foundation. Dr. Dickey disclosed consulting for Arrowhead Pharmaceuticals. Dr. Kim disclosed personal fees from Medscape and others. Dr. Evans reported no relevant disclosures. Dr. Fahy and Dr. Gitlin are named inventors on patents for mucolytic drugs, and shareholders in Aer Therapeutics.

Just uttering the word “mucus” is often sufficient to elicit amusement from those within earshot, but to patients with chronic inflammatory airway diseases, mucus is no laughing matter.

Under normal conditions, mucus plays an important protective role, trapping airway irritants such as smoke, pollen, and particulate matter, which are then moved by cilia out of the airways for expulsion through coughing.

But in cystic fibrosis (CF), for example, mucus hypersecretion can be deadly. The underlying pathology of CF – a mutation in the CFTR gene, which codes for the protein CF transmembrane conductance regulator – leads to buildup in the lungs of abnormally viscous and sticky mucus, resulting in frequent, severe infections (particularly with Pseudomonas aeruginosa), progressive lung damage, and prior to the development of effective disease management, significantly premature death.

Mucus hypersecretion is also a feature of chronic obstructive pulmonary disease (COPD), noted Victor Kim, MD, from Temple University, Philadelphia, Christopher M. Evans, PhD, from the University of Colorado at Denver, Aurora, and Burton F. Dickey, MD, from the University of Texas MD Anderson Cancer Center, Houston.

In COPD, “mucus dysfunction arises from several mechanisms, including excess production due to inflammation, decreased elimination due to impaired ciliary clearance and reduced cough efficiency, and excessive concentration due to smoke-induced dysfunction of transepithelial anion transport resembling CF,” they wrote in an editorial published in the American Journal of Respiratory and Critical Care Medicine.

In patients with idiopathic pulmonary fibrosis, a polymorphism in the enhancer region of MUC5B, a gene that encodes for mucin glycoproteins, results in a 20-fold overexpression of the gene and prominent mucus production that has been shown to parallel lung inflammation and decline in forced vital capacity (FVC).

In patients with asthma, up-regulation of MUC5AC and stimulated mucus secretion conspire to obstruct airways, which can in extreme cases lead to death.
 

‘Short shrift’

Yet until recently, the role of mucus hypersecretion in diseases such as COPD has been largely overlooked, or as Dr. Kim and colleagues put it, “airway mucus often receives short shrift from clinicians.”

“It’s a pretty hot topic in pulmonary medicine today because it has been so neglected for so long,” Dr. Dickey said in an interview with CHEST Physician. “As clinicians we haven’t had a way to identify who needs treatment, which is ridiculous, because many of the people who expectorate a lot, like those with chronic bronchitis, don’t actually have small airway obstruction, and conversely, a lot of asthmatics, who have very serious small airway obstruction, don’t expectorate, so you can’t really tell from symptoms.”

What has changed in recent years is the use of chest CT to image muco-obstructive pathology, commonly called “mucus plugging” in the peripheral airways of patients with COPD and asthma.

“In the last decade or so, we’ve seen the emergence in obstructive lung diseases such as asthma and COPD the use of more objective measures on CT scans, including the problem of mucus plugging, which is unfortunately very common,” Dr. Kim said in an interview.

The discovery of the extent and severity of mucus in obstructive lung diseases has led to new strategies to combat mucus overconcentration, such as hydration, mucolytics, and an intriguing investigational approach to decrease calcium-induced hypersecretion with designer peptides.
 

Mighty mucins

Under normal physiologic conditions mucus is composed largely of water (97%) and salts (2%), with the remainder consisting of entrapped globular proteins (0.7%) and mucins (0.3%), Dr. Dickey explains.

Yet those meager mucins pack a real punch, with the ability to absorb 300 times their mass of water after secretion, creating mucus of optimal consistency and viscoelasticity.

“Personally, I’ve never understood – maybe I should have paid more attention in physics – how a compound can absorb 300-fold its mass, but it does,” he said.

In a recent review article in the journal Clinical and Translational Medicine, Dr. Dickey and colleagues described how good mucus can go bad.

“[H]igh levels of mucin production from inflammatory stimulation (termed ‘mucous metaplasia’), followed by rapid release (together, termed ‘mucus hypersecretion’), can plug airways due to mucus volume expansion. In addition, if available lumenal liquid is insufficient, concentrated mucus of excessive viscoelasticity and adhesivity can cause mucus stasis,” they wrote.
 

Therapeutic strategies

In patients with CF, CFTR modulator therapy has markedly reduced but not eliminated the need for some patients to have mucolytic therapy, which may include dornase alfa, a recombinant human deoxyribonuclease that reduces the viscosity of lung secretions, hypertonic saline inhaled twice daily (for patients 12 and older), mannitol, and physical manipulations to help patients clear mucus. The manipulations can include both manual percussion and the use of devices for high-frequency chest wall oscillation.

Unlike in CF, where treating the underlying genetic pathology can help to resolve the thick, sticky mucus problems and thereby significantly reduce risk of infections and progressive lung damage, treatment of mucus metaplasia or hypersecretion in other diseases is aimed at symptomatic relief; it is still unclear whether symptomatic improvement of mucus overproduction would correlate with other disease-related outcomes, Dr. Kim and Dr. Dickey noted.

Potential therapeutic strategies to reduce excess mucus in the lungs include the use of mucolytic agents to thin secretions for more effective expulsion, decreasing mucus production through the use of an interleukin-13 (IL-13) inhibitor such as the anti-asthma agent dupilumab (Dupixent), and a novel strategy, still in the experimental phase, aimed at “disrupting the fusion of mucin storage granules with the cell membrane, thereby blocking secretion,” wrote Irina Gitlin, PhD, and John Fahy, MD, from the University of California, San Francisco, in Nature.

They were referring to research by Dr. Dickey and colleagues described in the same issue of Nature focusing on the inhibition of calcium-triggered mucus secretion by the use of hydrocarbon-stapled peptides, short chains of amino acids stabilized with a chemical bridge to a hydrocarbon molecule.
 

Knocking secretion down, but not out

The work has centered on decreasing overproduction of mucins with a focus on the signals for mucin production, including IL-13 and interleukin-1 beta, and on the signals for rapid release of mucins, including adenosine 5’-triphosphate (ATP), best known as an intracellular energy-storage module.

“But ATP is also steadily released by ciliated cells in response to the shear stress of tidal breathing, and it tells the neighboring secretory cells to slowly and steadily release mucin. But if the ciliated cells get stressed by any of a number of mechanisms, it can release a lot of ATP, and then the secretory cell can explosively release essentially all of its mucin content,” Dr. Dickey explained.

Other important signals for rapid release of mucins are acetylcholine and histamine, and all three of these agonists – ATP, acetylcholine, and histamine – cause a rise in intracellular calcium, which triggers calcium sensors that then lead to calcium-triggered membrane fusion and secretion.

Working as a postdoc in the Dickey laboratory, Dr. Evans had previously shown that deleting MUC5B in mice led to early development of serious lung abnormalities, some of which were fatal, indicating that MUC5B, a gene that is highly preserved in evolution, is essential for respiratory health.

This observation was later supported by a study of a family with a pattern of hereditary mucin deficiency caused by a homozygous loss-of-function mutation in MUC5B. The main subject in this study was an adult woman with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infections. Her sibling, who also had the biallelic mutation, had extensive sinus disease with nasal polyps. Other siblings who were heterozygous for the mutation were asymptomatic but had mild functional lung impairment.

The trick for the investigators, then, was to figure out how to reduce stimulated release of stored mucins while still preserving normal release of mucins to allow for ciliary clearance of mucus, and Dr. Dickey and colleagues appear to have accomplished this, at least in mice.

They first validated as a potential therapeutic target a protein labeled synaptotagmin-2 (Syt2). Syt2 is a calcium sensor that is an essential part of the system that triggers calcium-triggered secretion. In a model for allergic asthma, mice with Syt2 deleted from airway epithelia had marked reductions in both stimulated mucin secretion and in mucus occlusion in airway lumens, but remained otherwise healthy with normal lung function.

Working with structural biologist Axel Brunger, PhD, from Stanford (Calif.) University, Dr. Dickey and coinvestigators developed and validated a peptide that could specifically inhibit Syt2, and found that it mimicked the action of the Syt2 deletion, preventing mucus occlusion in the allergic asthma model without adversely effecting normal production.
 

Not ready for prime time

Dr. Dickey and colleagues are now working to translate the therapy into a form that can be used in humans, most likely as an aerosol that could be used for acute treatment of patients with mucus plugging from asthma and COPD, and also as a therapy for patients with chronic disease.

“In the chronic situation, what we would hope to do is identify patients with muco-obstructive lung disease – asthma, COPD, cystic fibrosis – who have airway mucus obstruction and then use the inhaled peptide on a regular basis as one part of a program to try to prevent this chronic mucus occlusion,” Dr. Dickey said.

As Dr. Gitlin and Dr. Fahy wrote in their editorial, “by confirming that it is possible to block calcium-regulated mucin secretion, Lai and colleagues have shown the potential of such an approach as a new therapeutic strategy for lung illnesses associated with mucus pathology, including diseases such as asthma and COPD, for which there is a large unmet medical need.”

The study by Dr. Dickey and colleagues was supported by grants from the German Research Foundation, National Institutes of Health and the Cystic Fibrosis Foundation. Dr. Dickey disclosed consulting for Arrowhead Pharmaceuticals. Dr. Kim disclosed personal fees from Medscape and others. Dr. Evans reported no relevant disclosures. Dr. Fahy and Dr. Gitlin are named inventors on patents for mucolytic drugs, and shareholders in Aer Therapeutics.

Just uttering the word “mucus” is often sufficient to elicit amusement from those within earshot, but to patients with chronic inflammatory airway diseases, mucus is no laughing matter.

Under normal conditions, mucus plays an important protective role, trapping airway irritants such as smoke, pollen, and particulate matter, which are then moved by cilia out of the airways for expulsion through coughing.

But in cystic fibrosis (CF), for example, mucus hypersecretion can be deadly. The underlying pathology of CF – a mutation in the CFTR gene, which codes for the protein CF transmembrane conductance regulator – leads to buildup in the lungs of abnormally viscous and sticky mucus, resulting in frequent, severe infections (particularly with Pseudomonas aeruginosa), progressive lung damage, and prior to the development of effective disease management, significantly premature death.

Mucus hypersecretion is also a feature of chronic obstructive pulmonary disease (COPD), noted Victor Kim, MD, from Temple University, Philadelphia, Christopher M. Evans, PhD, from the University of Colorado at Denver, Aurora, and Burton F. Dickey, MD, from the University of Texas MD Anderson Cancer Center, Houston.

In COPD, “mucus dysfunction arises from several mechanisms, including excess production due to inflammation, decreased elimination due to impaired ciliary clearance and reduced cough efficiency, and excessive concentration due to smoke-induced dysfunction of transepithelial anion transport resembling CF,” they wrote in an editorial published in the American Journal of Respiratory and Critical Care Medicine.

In patients with idiopathic pulmonary fibrosis, a polymorphism in the enhancer region of MUC5B, a gene that encodes for mucin glycoproteins, results in a 20-fold overexpression of the gene and prominent mucus production that has been shown to parallel lung inflammation and decline in forced vital capacity (FVC).

In patients with asthma, up-regulation of MUC5AC and stimulated mucus secretion conspire to obstruct airways, which can in extreme cases lead to death.
 

‘Short shrift’

Yet until recently, the role of mucus hypersecretion in diseases such as COPD has been largely overlooked, or as Dr. Kim and colleagues put it, “airway mucus often receives short shrift from clinicians.”

“It’s a pretty hot topic in pulmonary medicine today because it has been so neglected for so long,” Dr. Dickey said in an interview with CHEST Physician. “As clinicians we haven’t had a way to identify who needs treatment, which is ridiculous, because many of the people who expectorate a lot, like those with chronic bronchitis, don’t actually have small airway obstruction, and conversely, a lot of asthmatics, who have very serious small airway obstruction, don’t expectorate, so you can’t really tell from symptoms.”

What has changed in recent years is the use of chest CT to image muco-obstructive pathology, commonly called “mucus plugging” in the peripheral airways of patients with COPD and asthma.

“In the last decade or so, we’ve seen the emergence in obstructive lung diseases such as asthma and COPD the use of more objective measures on CT scans, including the problem of mucus plugging, which is unfortunately very common,” Dr. Kim said in an interview.

The discovery of the extent and severity of mucus in obstructive lung diseases has led to new strategies to combat mucus overconcentration, such as hydration, mucolytics, and an intriguing investigational approach to decrease calcium-induced hypersecretion with designer peptides.
 

Mighty mucins

Under normal physiologic conditions mucus is composed largely of water (97%) and salts (2%), with the remainder consisting of entrapped globular proteins (0.7%) and mucins (0.3%), Dr. Dickey explains.

Yet those meager mucins pack a real punch, with the ability to absorb 300 times their mass of water after secretion, creating mucus of optimal consistency and viscoelasticity.

“Personally, I’ve never understood – maybe I should have paid more attention in physics – how a compound can absorb 300-fold its mass, but it does,” he said.

In a recent review article in the journal Clinical and Translational Medicine, Dr. Dickey and colleagues described how good mucus can go bad.

“[H]igh levels of mucin production from inflammatory stimulation (termed ‘mucous metaplasia’), followed by rapid release (together, termed ‘mucus hypersecretion’), can plug airways due to mucus volume expansion. In addition, if available lumenal liquid is insufficient, concentrated mucus of excessive viscoelasticity and adhesivity can cause mucus stasis,” they wrote.
 

Therapeutic strategies

In patients with CF, CFTR modulator therapy has markedly reduced but not eliminated the need for some patients to have mucolytic therapy, which may include dornase alfa, a recombinant human deoxyribonuclease that reduces the viscosity of lung secretions, hypertonic saline inhaled twice daily (for patients 12 and older), mannitol, and physical manipulations to help patients clear mucus. The manipulations can include both manual percussion and the use of devices for high-frequency chest wall oscillation.

Unlike in CF, where treating the underlying genetic pathology can help to resolve the thick, sticky mucus problems and thereby significantly reduce risk of infections and progressive lung damage, treatment of mucus metaplasia or hypersecretion in other diseases is aimed at symptomatic relief; it is still unclear whether symptomatic improvement of mucus overproduction would correlate with other disease-related outcomes, Dr. Kim and Dr. Dickey noted.

Potential therapeutic strategies to reduce excess mucus in the lungs include the use of mucolytic agents to thin secretions for more effective expulsion, decreasing mucus production through the use of an interleukin-13 (IL-13) inhibitor such as the anti-asthma agent dupilumab (Dupixent), and a novel strategy, still in the experimental phase, aimed at “disrupting the fusion of mucin storage granules with the cell membrane, thereby blocking secretion,” wrote Irina Gitlin, PhD, and John Fahy, MD, from the University of California, San Francisco, in Nature.

They were referring to research by Dr. Dickey and colleagues described in the same issue of Nature focusing on the inhibition of calcium-triggered mucus secretion by the use of hydrocarbon-stapled peptides, short chains of amino acids stabilized with a chemical bridge to a hydrocarbon molecule.
 

Knocking secretion down, but not out

The work has centered on decreasing overproduction of mucins with a focus on the signals for mucin production, including IL-13 and interleukin-1 beta, and on the signals for rapid release of mucins, including adenosine 5’-triphosphate (ATP), best known as an intracellular energy-storage module.

“But ATP is also steadily released by ciliated cells in response to the shear stress of tidal breathing, and it tells the neighboring secretory cells to slowly and steadily release mucin. But if the ciliated cells get stressed by any of a number of mechanisms, it can release a lot of ATP, and then the secretory cell can explosively release essentially all of its mucin content,” Dr. Dickey explained.

Other important signals for rapid release of mucins are acetylcholine and histamine, and all three of these agonists – ATP, acetylcholine, and histamine – cause a rise in intracellular calcium, which triggers calcium sensors that then lead to calcium-triggered membrane fusion and secretion.

Working as a postdoc in the Dickey laboratory, Dr. Evans had previously shown that deleting MUC5B in mice led to early development of serious lung abnormalities, some of which were fatal, indicating that MUC5B, a gene that is highly preserved in evolution, is essential for respiratory health.

This observation was later supported by a study of a family with a pattern of hereditary mucin deficiency caused by a homozygous loss-of-function mutation in MUC5B. The main subject in this study was an adult woman with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infections. Her sibling, who also had the biallelic mutation, had extensive sinus disease with nasal polyps. Other siblings who were heterozygous for the mutation were asymptomatic but had mild functional lung impairment.

The trick for the investigators, then, was to figure out how to reduce stimulated release of stored mucins while still preserving normal release of mucins to allow for ciliary clearance of mucus, and Dr. Dickey and colleagues appear to have accomplished this, at least in mice.

They first validated as a potential therapeutic target a protein labeled synaptotagmin-2 (Syt2). Syt2 is a calcium sensor that is an essential part of the system that triggers calcium-triggered secretion. In a model for allergic asthma, mice with Syt2 deleted from airway epithelia had marked reductions in both stimulated mucin secretion and in mucus occlusion in airway lumens, but remained otherwise healthy with normal lung function.

Working with structural biologist Axel Brunger, PhD, from Stanford (Calif.) University, Dr. Dickey and coinvestigators developed and validated a peptide that could specifically inhibit Syt2, and found that it mimicked the action of the Syt2 deletion, preventing mucus occlusion in the allergic asthma model without adversely effecting normal production.
 

Not ready for prime time

Dr. Dickey and colleagues are now working to translate the therapy into a form that can be used in humans, most likely as an aerosol that could be used for acute treatment of patients with mucus plugging from asthma and COPD, and also as a therapy for patients with chronic disease.

“In the chronic situation, what we would hope to do is identify patients with muco-obstructive lung disease – asthma, COPD, cystic fibrosis – who have airway mucus obstruction and then use the inhaled peptide on a regular basis as one part of a program to try to prevent this chronic mucus occlusion,” Dr. Dickey said.

As Dr. Gitlin and Dr. Fahy wrote in their editorial, “by confirming that it is possible to block calcium-regulated mucin secretion, Lai and colleagues have shown the potential of such an approach as a new therapeutic strategy for lung illnesses associated with mucus pathology, including diseases such as asthma and COPD, for which there is a large unmet medical need.”

The study by Dr. Dickey and colleagues was supported by grants from the German Research Foundation, National Institutes of Health and the Cystic Fibrosis Foundation. Dr. Dickey disclosed consulting for Arrowhead Pharmaceuticals. Dr. Kim disclosed personal fees from Medscape and others. Dr. Evans reported no relevant disclosures. Dr. Fahy and Dr. Gitlin are named inventors on patents for mucolytic drugs, and shareholders in Aer Therapeutics.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

NASHVILLE – The first multicenter randomized controlled trial of a home-based rehabilitation program for patients with chronic obstructive pulmonary disease (COPD) showed highly positive results, according to findings presented at the annual meeting of the American College of Chest Physicians (CHEST).

At the end of 12 weeks, those randomly assigned to the intervention had a significant and clinically meaningful improvement in all domains of the Chronic Respiratory Questionnaire (CRQ), including activity levels and emotional well-being, reported Roberto P. Benzo, MD, a consultant in the division of pulmonary and critical care medicine, Mayo Clinic, Rochester, Minn.

Presenting soon-to-be-published data, Dr. Benzo said that the intervention is based on a tablet-based app. On the tablet, the patient finds a daily schedule of exercises and videos to guide performance. The tablet is programmed to upload data captured from an activity monitor and pulse oximeter. Along with documentation of app usage, this information can then be downloaded for the remote coach to review with the patient.

The primary outcome of the randomized study were the physical and emotional domains of the CRQ quality of life, but a long list of secondary outcomes – including physical activity, symptoms of depression, sleep quality, and health care utilization, such as emergency room visits – was also analyzed.

In addition to the significant benefit on the primary outcomes, the home-based rehabilitation program relative to a wait list for intervention was associated with benefit or a trend for benefit on essentially every outcome measured. Health care utilization was a possible exception, but even then, the absolute number of visits was lower in the treatment arm.

“With a study period of only 12 weeks, we were limited to our ability to show a difference in emergency room visits,” said Dr. Benzo, who also noted that the study was conducted during the COVID-19 pandemic, when hospital visits were already occurring at a lower than usual rate. Based on the other findings, he suspects that a reduction in health care utilization could also be shown in more typical circumstances, particularly with a longer follow-up.

In the study, 375 patients with COPD were randomly assigned to a home health care regimen delivered by an app with remote coaching or to a wait list and usual care. The median age was 69 years. Fifty-nine percent were women. The median FEV₁ at enrollment was 45% of predicted.

The patients were able to access their own data to monitor their progress at any time, not just at the time of coaching, but contact with the remote coach occurred on a weekly basis. Patients rated their level of energy, how they felt generally, and their progress toward daily goals, which was also captured on the app and could be discussed with the coach during the review of the previous week’s activity.

At 12 weeks, the favorable 0.54-point change (P < .001) and 0.51 change (P < .001) in the physical and emotional summary scores, respectively, met the criteria for a clinically meaningful change, Dr. Benzo reported. There were also significantly favorable changes from baseline and relative to controls in CRQ domains of self-management, sleep quality, and depression (all P ≤ .01).

Other data collected are supportive. For example, Dr. Benzo reported that those in the rehabilitation group took 624 more steps on average per day than those in the control group. The experimental group also spent nearly an hour more performing moderate or greater levels of activity.

“The app promotes behavioral change,” said Dr. Benzo, who said that this “completely home-based model” of rehabilitation is likely to be cost-effective given the relatively low costs of remote coaching and reasonable costs of the activity monitor, tablet, and other equipment.

Importantly, home-based rehabilitation is a billable practice under currently available CPT codes, according to Dr. Benzo, who believes this approach is not only effective but “feasible and practical.”

Two clinicians active in the care of patients with COPD believe this approach could fulfill an unmet need if further validated. Andrew Berman, MD, professor of medicine, New Jersey Medical School, Newark, thinks the premise is sound.

“Digital competency is still a big issue as is access to adequate quality Internet, but this could be a very useful approach for many individuals, and it avoids visits to a center, which could be a big advantage for patients,” Dr. Berman said.

Abebaw M. Johannes, PhD, a professor of physical therapy at Azusa Pacific University, Azusa, Calif., agreed. He said that home-based remote coaching could be a way of overcoming the current hurdles of participating in institutional-based programs

“This is clearly an unmet need in COPD,” he said.

The development of more effective and patient-friendly programs is what was driving this research, according to Dr. Benzo. He cited data suggesting that only about 30% of patients with COPD are participating in rehabilitation programs once discharged from the hospital despite the evidence that they can improve quality of life. For many of these patients, a home-based program might be the answer.

Dr. Benzo, Dr. Berman, and Dr. Johannes reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE – The first multicenter randomized controlled trial of a home-based rehabilitation program for patients with chronic obstructive pulmonary disease (COPD) showed highly positive results, according to findings presented at the annual meeting of the American College of Chest Physicians (CHEST).

At the end of 12 weeks, those randomly assigned to the intervention had a significant and clinically meaningful improvement in all domains of the Chronic Respiratory Questionnaire (CRQ), including activity levels and emotional well-being, reported Roberto P. Benzo, MD, a consultant in the division of pulmonary and critical care medicine, Mayo Clinic, Rochester, Minn.

Presenting soon-to-be-published data, Dr. Benzo said that the intervention is based on a tablet-based app. On the tablet, the patient finds a daily schedule of exercises and videos to guide performance. The tablet is programmed to upload data captured from an activity monitor and pulse oximeter. Along with documentation of app usage, this information can then be downloaded for the remote coach to review with the patient.

The primary outcome of the randomized study were the physical and emotional domains of the CRQ quality of life, but a long list of secondary outcomes – including physical activity, symptoms of depression, sleep quality, and health care utilization, such as emergency room visits – was also analyzed.

In addition to the significant benefit on the primary outcomes, the home-based rehabilitation program relative to a wait list for intervention was associated with benefit or a trend for benefit on essentially every outcome measured. Health care utilization was a possible exception, but even then, the absolute number of visits was lower in the treatment arm.

“With a study period of only 12 weeks, we were limited to our ability to show a difference in emergency room visits,” said Dr. Benzo, who also noted that the study was conducted during the COVID-19 pandemic, when hospital visits were already occurring at a lower than usual rate. Based on the other findings, he suspects that a reduction in health care utilization could also be shown in more typical circumstances, particularly with a longer follow-up.

In the study, 375 patients with COPD were randomly assigned to a home health care regimen delivered by an app with remote coaching or to a wait list and usual care. The median age was 69 years. Fifty-nine percent were women. The median FEV₁ at enrollment was 45% of predicted.

The patients were able to access their own data to monitor their progress at any time, not just at the time of coaching, but contact with the remote coach occurred on a weekly basis. Patients rated their level of energy, how they felt generally, and their progress toward daily goals, which was also captured on the app and could be discussed with the coach during the review of the previous week’s activity.

At 12 weeks, the favorable 0.54-point change (P < .001) and 0.51 change (P < .001) in the physical and emotional summary scores, respectively, met the criteria for a clinically meaningful change, Dr. Benzo reported. There were also significantly favorable changes from baseline and relative to controls in CRQ domains of self-management, sleep quality, and depression (all P ≤ .01).

Other data collected are supportive. For example, Dr. Benzo reported that those in the rehabilitation group took 624 more steps on average per day than those in the control group. The experimental group also spent nearly an hour more performing moderate or greater levels of activity.

“The app promotes behavioral change,” said Dr. Benzo, who said that this “completely home-based model” of rehabilitation is likely to be cost-effective given the relatively low costs of remote coaching and reasonable costs of the activity monitor, tablet, and other equipment.

Importantly, home-based rehabilitation is a billable practice under currently available CPT codes, according to Dr. Benzo, who believes this approach is not only effective but “feasible and practical.”

Two clinicians active in the care of patients with COPD believe this approach could fulfill an unmet need if further validated. Andrew Berman, MD, professor of medicine, New Jersey Medical School, Newark, thinks the premise is sound.

“Digital competency is still a big issue as is access to adequate quality Internet, but this could be a very useful approach for many individuals, and it avoids visits to a center, which could be a big advantage for patients,” Dr. Berman said.

Abebaw M. Johannes, PhD, a professor of physical therapy at Azusa Pacific University, Azusa, Calif., agreed. He said that home-based remote coaching could be a way of overcoming the current hurdles of participating in institutional-based programs

“This is clearly an unmet need in COPD,” he said.

The development of more effective and patient-friendly programs is what was driving this research, according to Dr. Benzo. He cited data suggesting that only about 30% of patients with COPD are participating in rehabilitation programs once discharged from the hospital despite the evidence that they can improve quality of life. For many of these patients, a home-based program might be the answer.

Dr. Benzo, Dr. Berman, and Dr. Johannes reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE – The first multicenter randomized controlled trial of a home-based rehabilitation program for patients with chronic obstructive pulmonary disease (COPD) showed highly positive results, according to findings presented at the annual meeting of the American College of Chest Physicians (CHEST).

At the end of 12 weeks, those randomly assigned to the intervention had a significant and clinically meaningful improvement in all domains of the Chronic Respiratory Questionnaire (CRQ), including activity levels and emotional well-being, reported Roberto P. Benzo, MD, a consultant in the division of pulmonary and critical care medicine, Mayo Clinic, Rochester, Minn.

Presenting soon-to-be-published data, Dr. Benzo said that the intervention is based on a tablet-based app. On the tablet, the patient finds a daily schedule of exercises and videos to guide performance. The tablet is programmed to upload data captured from an activity monitor and pulse oximeter. Along with documentation of app usage, this information can then be downloaded for the remote coach to review with the patient.

The primary outcome of the randomized study were the physical and emotional domains of the CRQ quality of life, but a long list of secondary outcomes – including physical activity, symptoms of depression, sleep quality, and health care utilization, such as emergency room visits – was also analyzed.

In addition to the significant benefit on the primary outcomes, the home-based rehabilitation program relative to a wait list for intervention was associated with benefit or a trend for benefit on essentially every outcome measured. Health care utilization was a possible exception, but even then, the absolute number of visits was lower in the treatment arm.

“With a study period of only 12 weeks, we were limited to our ability to show a difference in emergency room visits,” said Dr. Benzo, who also noted that the study was conducted during the COVID-19 pandemic, when hospital visits were already occurring at a lower than usual rate. Based on the other findings, he suspects that a reduction in health care utilization could also be shown in more typical circumstances, particularly with a longer follow-up.

In the study, 375 patients with COPD were randomly assigned to a home health care regimen delivered by an app with remote coaching or to a wait list and usual care. The median age was 69 years. Fifty-nine percent were women. The median FEV₁ at enrollment was 45% of predicted.

The patients were able to access their own data to monitor their progress at any time, not just at the time of coaching, but contact with the remote coach occurred on a weekly basis. Patients rated their level of energy, how they felt generally, and their progress toward daily goals, which was also captured on the app and could be discussed with the coach during the review of the previous week’s activity.

At 12 weeks, the favorable 0.54-point change (P < .001) and 0.51 change (P < .001) in the physical and emotional summary scores, respectively, met the criteria for a clinically meaningful change, Dr. Benzo reported. There were also significantly favorable changes from baseline and relative to controls in CRQ domains of self-management, sleep quality, and depression (all P ≤ .01).

Other data collected are supportive. For example, Dr. Benzo reported that those in the rehabilitation group took 624 more steps on average per day than those in the control group. The experimental group also spent nearly an hour more performing moderate or greater levels of activity.

“The app promotes behavioral change,” said Dr. Benzo, who said that this “completely home-based model” of rehabilitation is likely to be cost-effective given the relatively low costs of remote coaching and reasonable costs of the activity monitor, tablet, and other equipment.

Importantly, home-based rehabilitation is a billable practice under currently available CPT codes, according to Dr. Benzo, who believes this approach is not only effective but “feasible and practical.”

Two clinicians active in the care of patients with COPD believe this approach could fulfill an unmet need if further validated. Andrew Berman, MD, professor of medicine, New Jersey Medical School, Newark, thinks the premise is sound.

“Digital competency is still a big issue as is access to adequate quality Internet, but this could be a very useful approach for many individuals, and it avoids visits to a center, which could be a big advantage for patients,” Dr. Berman said.

Abebaw M. Johannes, PhD, a professor of physical therapy at Azusa Pacific University, Azusa, Calif., agreed. He said that home-based remote coaching could be a way of overcoming the current hurdles of participating in institutional-based programs

“This is clearly an unmet need in COPD,” he said.

The development of more effective and patient-friendly programs is what was driving this research, according to Dr. Benzo. He cited data suggesting that only about 30% of patients with COPD are participating in rehabilitation programs once discharged from the hospital despite the evidence that they can improve quality of life. For many of these patients, a home-based program might be the answer.

Dr. Benzo, Dr. Berman, and Dr. Johannes reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Gregory A. Hood, MD, remembers a patient of his who was perpetually dubious about COVID-19 – and then couldn’t be saved.

“I spoke to him on many occasions about the dangers of COVID, but he just didn’t believe me,” said Dr. Hood, an internist in Lexington, Ky. “He just didn’t give me enough time to help him. He waited to let me know he was ill with COVID and took days to pick up the medicine. Unfortunately, he then passed away.”
 

The rise of the skeptical patient

It can be extremely frustrating for doctors when patients question or disbelieve their physician’s medical advice and explanations. And many physicians resent the amount of time they spend trying to explain or make their case, especially during a busy day. But patients’ skepticism about the validity of some treatments seems to be increasing.

“Patients are now more likely to have their own medical explanation for their complaint than they used to, and that can be bad for their health,” Dr. Hood said.

Dr. Hood sees medical cynicism as part of Americans’ growing distrust of experts, leveraged by easy access to the internet. “When people Google, they tend to look for support of their opinions, rather than arrive at a fully educated decision.”

Only about half of patients believe their physicians “provide fair and accurate treatment information all or most of the time,” according to a 2019 survey by the Pew Research Center.

Patients’ distrust has become more obvious during the COVID-19 pandemic, said John Schumann, MD, an internist with Oak Street Health, a practice with more than 500 physicians and other providers in 20 states, treating almost exclusively Medicare patients.

“The skeptics became more entrenched during the pandemic,” said Dr. Schumann, who is based in Tulsa, Okla. “They may think the COVID vaccines were approved too quickly, or believe the pandemic itself is a hoax.”

“There’s a lot of antiscience rhetoric now,” Dr. Schumann added. “I’d say about half of my patients are comfortable with science-based decisions and the other half are not.”
 

What are patients mistrustful about?

Patients’ suspicions of certain therapies began long before the pandemic. In dermatology, for example, some patients refuse to take topical steroids, said Steven R. Feldman, MD, a dermatologist in Winston-Salem, N.C.

“Their distrust is usually based on anecdotal stories they read about,” he noted. “Patients in other specialties are dead set against vaccinations.”

In addition to refusing treatments and inoculations, some patients ask for questionable regimens mentioned in the news. “Some patients have demanded hydroxychloroquine or Noromectin, drugs that are unproven in the treatment of COVID,” Dr. Schumann said. “We refuse to prescribe them.”

Dr. Hood said patients’ reluctance to follow medical advice can often be based on cost. “I have a patient who was more willing to save $20 than to save his life. But when the progression of his test results fit my predictions, he became more willing to take treatments. I had to wait for the opportune moment to convince him.”

Many naysayer patients keep their views to themselves, and physicians may be unaware that the patients are stonewalling. A 2006 study estimated that about 10%-16% of primary care patients actively resist medical authority.

Dr. Schumann cited patients who don’t want to hear an upsetting diagnosis. “Some patients might refuse to take a biopsy to see if they have cancer because they don’t want to know,” he said. “In many cases, they simply won’t get the biopsy and won’t tell the doctor that they didn’t.”
 

Sometimes skeptics’ arguments have merit

Some patients’ concerns can be valid, such as when they refuse to go on statins, said Zain Hakeem, DO, a physician in Austin, Tex.

“In some cases, I feel that statins are not necessary,” he said. “The science on statins for primary prevention is not strong, although they should be used for exceedingly high-risk patients.”

Certain patients, especially those with chronic conditions, do a great deal of research, using legitimate sources on the Web, and their research is well supported.

However, these patients can be overconfident in their conclusions. Several studies have shown that with just a little experience, people can replace beginners’ caution with a false sense of competence.

For example, “Patients may not weigh the risks correctly,” Dr. Hakeem said. “They can be more concerned about the risk of having their colon perforated during a colonoscopy, while the risk of cancer if they don’t have a colonoscopy is much higher.”

Some highly successful people may be more likely to trust their own medical instincts. When Steve Jobs, the founder of Apple, was diagnosed with pancreatic cancer in 2003, he put off surgery for 9 months while he tried to cure his disease with a vegan diet, acupuncture, herbs, bowel cleansings, and other remedies he read about. He died in 2011. Some experts believe that delay hastened his death.

Of course, not all physicians’ diagnoses or treatments are correct. One study indicated doctors’ diagnostic error rate could be as high as 15%. And just as patients can be overconfident in their conclusions, so can doctors. Another study found that physicians’ stated confidence in their diagnosis was only slightly affected by the inaccuracy of that diagnosis or the difficulty of the case.
 

Best ways to deal with cynical patients

Patients’ skepticism can frustrate doctors, reduce the efficiency of care delivery, and interfere with recovery. What can doctors do to deal with these problems?

1. Build the patient’s trust in you. “Getting patients to adhere to your advice involves making sure they feel they have a caring doctor whom they trust,” Dr. Feldman said.

“I want to show patients that I am entirely focused on them,” he added. “For example, I may rush to the door of the exam room from my last appointment, but I open the door very slowly and deliberately, because I want the patient to see that I won’t hurry with them.”

2. Spend time with the patient. Familiarity builds trust. Dr. Schumann said doctors at Oak Street Health see their patients an average of six to eight times a year, an unusually high number. “The more patients see their physicians, the more likely they are to trust them.”

3. Keep up to date. “I make sure I’m up to date with the literature, and I try to present a truthful message,” Dr. Hood said. “For instance, my research showed that inflammation played a strong role in developing complications from COVID, so I wrote a detailed treatment protocol aimed at the inflammation and the immune response, which has been very effective.”

4. Confront patients tactfully. Patients who do research on the Web don’t want to be scolded, Dr. Feldman said. In fact, he praises them, even if he doesn’t agree with their findings. “I might say: ‘What a relief to finally find patients who’ve taken the time to educate themselves before coming here.’ ”

Dr. Feldman is careful not to dispute patients’ conclusions. “Debating the issues is not an effective approach to get patients to trust you. The last thing you want to tell a patient is: ‘Listen to me! I’m an expert.’ People just dig in.”

However, it does help to give patients feedback. “I’m a big fan of patients arguing with me,” Dr. Hakeem said. “It means you can straighten out misunderstandings and improve decision-making.”

5. Explain your reasoning. “You need to communicate clearly and show them your thinking,” Dr. Hood said. “For instance, I’ll explain why a patient has a strong risk for heart attack.”

6. Acknowledge uncertainties. “The doctor may present the science as far more certain than it is,” Dr. Hakeem said. “If you don’t acknowledge the uncertainties, you could break the patient’s trust in you.”

7. Don’t use a lot of numbers. “Data is not a good tool to convince patients,” Dr. Feldman said. “The human brain isn’t designed to work that way.”

If you want to use numbers to show clinical risk, Dr. Hakeem advisd using natural frequencies, such as 10 out of 10,000, which is less confusing to the patient than the equivalent percentage of 0.1%.

It can be helpful to refer to familiar concepts. One way to understand a risk is to compare it with risks in daily life, such as the dangers of driving or falling in the shower, Dr. Hakeem added.

Dr. Feldman often refers to another person’s experience when presenting his medical advice. “I might say to the patient: ‘You remind me of another patient I had. They were sitting in the same chair you’re sitting in. They did really well on this drug, and I think it’s probably the best choice for you, too.’ ”

8. Adopt shared decision-making. This approach involves empowering the patient to become an equal partner in medical decisions. The patient is given information through portals and is encouraged to do research. Critics, however, say that most patients don’t want this degree of empowerment and would rather depend on the doctor’s advice.

Conclusion

It’s often impossible to get through to a skeptical patient, which can be disheartening for doctors. “Physicians want to do what is best for the patient, so when the patient doesn’t listen, they may take it personally,” Dr. Hood said. “But you always have to remember, the patient is the one with disease, and it’s up to the patient to open the door.”

Still, some skeptical patients ultimately change their minds. Dr. Schumann said patients who initially declined the COVID vaccine eventually decided to get it. “It often took them more than a year. but it’s never too late.”

A version of this article first appeared on Medscape.com.

Gregory A. Hood, MD, remembers a patient of his who was perpetually dubious about COVID-19 – and then couldn’t be saved.

“I spoke to him on many occasions about the dangers of COVID, but he just didn’t believe me,” said Dr. Hood, an internist in Lexington, Ky. “He just didn’t give me enough time to help him. He waited to let me know he was ill with COVID and took days to pick up the medicine. Unfortunately, he then passed away.”
 

The rise of the skeptical patient

It can be extremely frustrating for doctors when patients question or disbelieve their physician’s medical advice and explanations. And many physicians resent the amount of time they spend trying to explain or make their case, especially during a busy day. But patients’ skepticism about the validity of some treatments seems to be increasing.

“Patients are now more likely to have their own medical explanation for their complaint than they used to, and that can be bad for their health,” Dr. Hood said.

Dr. Hood sees medical cynicism as part of Americans’ growing distrust of experts, leveraged by easy access to the internet. “When people Google, they tend to look for support of their opinions, rather than arrive at a fully educated decision.”

Only about half of patients believe their physicians “provide fair and accurate treatment information all or most of the time,” according to a 2019 survey by the Pew Research Center.

Patients’ distrust has become more obvious during the COVID-19 pandemic, said John Schumann, MD, an internist with Oak Street Health, a practice with more than 500 physicians and other providers in 20 states, treating almost exclusively Medicare patients.

“The skeptics became more entrenched during the pandemic,” said Dr. Schumann, who is based in Tulsa, Okla. “They may think the COVID vaccines were approved too quickly, or believe the pandemic itself is a hoax.”

“There’s a lot of antiscience rhetoric now,” Dr. Schumann added. “I’d say about half of my patients are comfortable with science-based decisions and the other half are not.”
 

What are patients mistrustful about?

Patients’ suspicions of certain therapies began long before the pandemic. In dermatology, for example, some patients refuse to take topical steroids, said Steven R. Feldman, MD, a dermatologist in Winston-Salem, N.C.

“Their distrust is usually based on anecdotal stories they read about,” he noted. “Patients in other specialties are dead set against vaccinations.”

In addition to refusing treatments and inoculations, some patients ask for questionable regimens mentioned in the news. “Some patients have demanded hydroxychloroquine or Noromectin, drugs that are unproven in the treatment of COVID,” Dr. Schumann said. “We refuse to prescribe them.”

Dr. Hood said patients’ reluctance to follow medical advice can often be based on cost. “I have a patient who was more willing to save $20 than to save his life. But when the progression of his test results fit my predictions, he became more willing to take treatments. I had to wait for the opportune moment to convince him.”

Many naysayer patients keep their views to themselves, and physicians may be unaware that the patients are stonewalling. A 2006 study estimated that about 10%-16% of primary care patients actively resist medical authority.

Dr. Schumann cited patients who don’t want to hear an upsetting diagnosis. “Some patients might refuse to take a biopsy to see if they have cancer because they don’t want to know,” he said. “In many cases, they simply won’t get the biopsy and won’t tell the doctor that they didn’t.”
 

Sometimes skeptics’ arguments have merit

Some patients’ concerns can be valid, such as when they refuse to go on statins, said Zain Hakeem, DO, a physician in Austin, Tex.

“In some cases, I feel that statins are not necessary,” he said. “The science on statins for primary prevention is not strong, although they should be used for exceedingly high-risk patients.”

Certain patients, especially those with chronic conditions, do a great deal of research, using legitimate sources on the Web, and their research is well supported.

However, these patients can be overconfident in their conclusions. Several studies have shown that with just a little experience, people can replace beginners’ caution with a false sense of competence.

For example, “Patients may not weigh the risks correctly,” Dr. Hakeem said. “They can be more concerned about the risk of having their colon perforated during a colonoscopy, while the risk of cancer if they don’t have a colonoscopy is much higher.”

Some highly successful people may be more likely to trust their own medical instincts. When Steve Jobs, the founder of Apple, was diagnosed with pancreatic cancer in 2003, he put off surgery for 9 months while he tried to cure his disease with a vegan diet, acupuncture, herbs, bowel cleansings, and other remedies he read about. He died in 2011. Some experts believe that delay hastened his death.

Of course, not all physicians’ diagnoses or treatments are correct. One study indicated doctors’ diagnostic error rate could be as high as 15%. And just as patients can be overconfident in their conclusions, so can doctors. Another study found that physicians’ stated confidence in their diagnosis was only slightly affected by the inaccuracy of that diagnosis or the difficulty of the case.
 

Best ways to deal with cynical patients

Patients’ skepticism can frustrate doctors, reduce the efficiency of care delivery, and interfere with recovery. What can doctors do to deal with these problems?

1. Build the patient’s trust in you. “Getting patients to adhere to your advice involves making sure they feel they have a caring doctor whom they trust,” Dr. Feldman said.

“I want to show patients that I am entirely focused on them,” he added. “For example, I may rush to the door of the exam room from my last appointment, but I open the door very slowly and deliberately, because I want the patient to see that I won’t hurry with them.”

2. Spend time with the patient. Familiarity builds trust. Dr. Schumann said doctors at Oak Street Health see their patients an average of six to eight times a year, an unusually high number. “The more patients see their physicians, the more likely they are to trust them.”

3. Keep up to date. “I make sure I’m up to date with the literature, and I try to present a truthful message,” Dr. Hood said. “For instance, my research showed that inflammation played a strong role in developing complications from COVID, so I wrote a detailed treatment protocol aimed at the inflammation and the immune response, which has been very effective.”

4. Confront patients tactfully. Patients who do research on the Web don’t want to be scolded, Dr. Feldman said. In fact, he praises them, even if he doesn’t agree with their findings. “I might say: ‘What a relief to finally find patients who’ve taken the time to educate themselves before coming here.’ ”

Dr. Feldman is careful not to dispute patients’ conclusions. “Debating the issues is not an effective approach to get patients to trust you. The last thing you want to tell a patient is: ‘Listen to me! I’m an expert.’ People just dig in.”

However, it does help to give patients feedback. “I’m a big fan of patients arguing with me,” Dr. Hakeem said. “It means you can straighten out misunderstandings and improve decision-making.”

5. Explain your reasoning. “You need to communicate clearly and show them your thinking,” Dr. Hood said. “For instance, I’ll explain why a patient has a strong risk for heart attack.”

6. Acknowledge uncertainties. “The doctor may present the science as far more certain than it is,” Dr. Hakeem said. “If you don’t acknowledge the uncertainties, you could break the patient’s trust in you.”

7. Don’t use a lot of numbers. “Data is not a good tool to convince patients,” Dr. Feldman said. “The human brain isn’t designed to work that way.”

If you want to use numbers to show clinical risk, Dr. Hakeem advisd using natural frequencies, such as 10 out of 10,000, which is less confusing to the patient than the equivalent percentage of 0.1%.

It can be helpful to refer to familiar concepts. One way to understand a risk is to compare it with risks in daily life, such as the dangers of driving or falling in the shower, Dr. Hakeem added.

Dr. Feldman often refers to another person’s experience when presenting his medical advice. “I might say to the patient: ‘You remind me of another patient I had. They were sitting in the same chair you’re sitting in. They did really well on this drug, and I think it’s probably the best choice for you, too.’ ”

8. Adopt shared decision-making. This approach involves empowering the patient to become an equal partner in medical decisions. The patient is given information through portals and is encouraged to do research. Critics, however, say that most patients don’t want this degree of empowerment and would rather depend on the doctor’s advice.

Conclusion

It’s often impossible to get through to a skeptical patient, which can be disheartening for doctors. “Physicians want to do what is best for the patient, so when the patient doesn’t listen, they may take it personally,” Dr. Hood said. “But you always have to remember, the patient is the one with disease, and it’s up to the patient to open the door.”

Still, some skeptical patients ultimately change their minds. Dr. Schumann said patients who initially declined the COVID vaccine eventually decided to get it. “It often took them more than a year. but it’s never too late.”

A version of this article first appeared on Medscape.com.

Gregory A. Hood, MD, remembers a patient of his who was perpetually dubious about COVID-19 – and then couldn’t be saved.

“I spoke to him on many occasions about the dangers of COVID, but he just didn’t believe me,” said Dr. Hood, an internist in Lexington, Ky. “He just didn’t give me enough time to help him. He waited to let me know he was ill with COVID and took days to pick up the medicine. Unfortunately, he then passed away.”
 

The rise of the skeptical patient

It can be extremely frustrating for doctors when patients question or disbelieve their physician’s medical advice and explanations. And many physicians resent the amount of time they spend trying to explain or make their case, especially during a busy day. But patients’ skepticism about the validity of some treatments seems to be increasing.

“Patients are now more likely to have their own medical explanation for their complaint than they used to, and that can be bad for their health,” Dr. Hood said.

Dr. Hood sees medical cynicism as part of Americans’ growing distrust of experts, leveraged by easy access to the internet. “When people Google, they tend to look for support of their opinions, rather than arrive at a fully educated decision.”

Only about half of patients believe their physicians “provide fair and accurate treatment information all or most of the time,” according to a 2019 survey by the Pew Research Center.

Patients’ distrust has become more obvious during the COVID-19 pandemic, said John Schumann, MD, an internist with Oak Street Health, a practice with more than 500 physicians and other providers in 20 states, treating almost exclusively Medicare patients.

“The skeptics became more entrenched during the pandemic,” said Dr. Schumann, who is based in Tulsa, Okla. “They may think the COVID vaccines were approved too quickly, or believe the pandemic itself is a hoax.”

“There’s a lot of antiscience rhetoric now,” Dr. Schumann added. “I’d say about half of my patients are comfortable with science-based decisions and the other half are not.”
 

What are patients mistrustful about?

Patients’ suspicions of certain therapies began long before the pandemic. In dermatology, for example, some patients refuse to take topical steroids, said Steven R. Feldman, MD, a dermatologist in Winston-Salem, N.C.

“Their distrust is usually based on anecdotal stories they read about,” he noted. “Patients in other specialties are dead set against vaccinations.”

In addition to refusing treatments and inoculations, some patients ask for questionable regimens mentioned in the news. “Some patients have demanded hydroxychloroquine or Noromectin, drugs that are unproven in the treatment of COVID,” Dr. Schumann said. “We refuse to prescribe them.”

Dr. Hood said patients’ reluctance to follow medical advice can often be based on cost. “I have a patient who was more willing to save $20 than to save his life. But when the progression of his test results fit my predictions, he became more willing to take treatments. I had to wait for the opportune moment to convince him.”

Many naysayer patients keep their views to themselves, and physicians may be unaware that the patients are stonewalling. A 2006 study estimated that about 10%-16% of primary care patients actively resist medical authority.

Dr. Schumann cited patients who don’t want to hear an upsetting diagnosis. “Some patients might refuse to take a biopsy to see if they have cancer because they don’t want to know,” he said. “In many cases, they simply won’t get the biopsy and won’t tell the doctor that they didn’t.”
 

Sometimes skeptics’ arguments have merit

Some patients’ concerns can be valid, such as when they refuse to go on statins, said Zain Hakeem, DO, a physician in Austin, Tex.

“In some cases, I feel that statins are not necessary,” he said. “The science on statins for primary prevention is not strong, although they should be used for exceedingly high-risk patients.”

Certain patients, especially those with chronic conditions, do a great deal of research, using legitimate sources on the Web, and their research is well supported.

However, these patients can be overconfident in their conclusions. Several studies have shown that with just a little experience, people can replace beginners’ caution with a false sense of competence.

For example, “Patients may not weigh the risks correctly,” Dr. Hakeem said. “They can be more concerned about the risk of having their colon perforated during a colonoscopy, while the risk of cancer if they don’t have a colonoscopy is much higher.”

Some highly successful people may be more likely to trust their own medical instincts. When Steve Jobs, the founder of Apple, was diagnosed with pancreatic cancer in 2003, he put off surgery for 9 months while he tried to cure his disease with a vegan diet, acupuncture, herbs, bowel cleansings, and other remedies he read about. He died in 2011. Some experts believe that delay hastened his death.

Of course, not all physicians’ diagnoses or treatments are correct. One study indicated doctors’ diagnostic error rate could be as high as 15%. And just as patients can be overconfident in their conclusions, so can doctors. Another study found that physicians’ stated confidence in their diagnosis was only slightly affected by the inaccuracy of that diagnosis or the difficulty of the case.
 

Best ways to deal with cynical patients

Patients’ skepticism can frustrate doctors, reduce the efficiency of care delivery, and interfere with recovery. What can doctors do to deal with these problems?

1. Build the patient’s trust in you. “Getting patients to adhere to your advice involves making sure they feel they have a caring doctor whom they trust,” Dr. Feldman said.

“I want to show patients that I am entirely focused on them,” he added. “For example, I may rush to the door of the exam room from my last appointment, but I open the door very slowly and deliberately, because I want the patient to see that I won’t hurry with them.”

2. Spend time with the patient. Familiarity builds trust. Dr. Schumann said doctors at Oak Street Health see their patients an average of six to eight times a year, an unusually high number. “The more patients see their physicians, the more likely they are to trust them.”

3. Keep up to date. “I make sure I’m up to date with the literature, and I try to present a truthful message,” Dr. Hood said. “For instance, my research showed that inflammation played a strong role in developing complications from COVID, so I wrote a detailed treatment protocol aimed at the inflammation and the immune response, which has been very effective.”

4. Confront patients tactfully. Patients who do research on the Web don’t want to be scolded, Dr. Feldman said. In fact, he praises them, even if he doesn’t agree with their findings. “I might say: ‘What a relief to finally find patients who’ve taken the time to educate themselves before coming here.’ ”

Dr. Feldman is careful not to dispute patients’ conclusions. “Debating the issues is not an effective approach to get patients to trust you. The last thing you want to tell a patient is: ‘Listen to me! I’m an expert.’ People just dig in.”

However, it does help to give patients feedback. “I’m a big fan of patients arguing with me,” Dr. Hakeem said. “It means you can straighten out misunderstandings and improve decision-making.”

5. Explain your reasoning. “You need to communicate clearly and show them your thinking,” Dr. Hood said. “For instance, I’ll explain why a patient has a strong risk for heart attack.”

6. Acknowledge uncertainties. “The doctor may present the science as far more certain than it is,” Dr. Hakeem said. “If you don’t acknowledge the uncertainties, you could break the patient’s trust in you.”

7. Don’t use a lot of numbers. “Data is not a good tool to convince patients,” Dr. Feldman said. “The human brain isn’t designed to work that way.”

If you want to use numbers to show clinical risk, Dr. Hakeem advisd using natural frequencies, such as 10 out of 10,000, which is less confusing to the patient than the equivalent percentage of 0.1%.

It can be helpful to refer to familiar concepts. One way to understand a risk is to compare it with risks in daily life, such as the dangers of driving or falling in the shower, Dr. Hakeem added.

Dr. Feldman often refers to another person’s experience when presenting his medical advice. “I might say to the patient: ‘You remind me of another patient I had. They were sitting in the same chair you’re sitting in. They did really well on this drug, and I think it’s probably the best choice for you, too.’ ”

8. Adopt shared decision-making. This approach involves empowering the patient to become an equal partner in medical decisions. The patient is given information through portals and is encouraged to do research. Critics, however, say that most patients don’t want this degree of empowerment and would rather depend on the doctor’s advice.

Conclusion

It’s often impossible to get through to a skeptical patient, which can be disheartening for doctors. “Physicians want to do what is best for the patient, so when the patient doesn’t listen, they may take it personally,” Dr. Hood said. “But you always have to remember, the patient is the one with disease, and it’s up to the patient to open the door.”

Still, some skeptical patients ultimately change their minds. Dr. Schumann said patients who initially declined the COVID vaccine eventually decided to get it. “It often took them more than a year. but it’s never too late.”

A version of this article first appeared on Medscape.com.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This article was originally published Oct. 8 on Medscape Editor-In-Chief Eric Topol’s “Ground Truths” column on Substack. 

A recent piece in The Economist about masks, and how at least half of the people in Japan are planning to continue to use masks indefinitely (where there was never a mandate), prompts a deeper look into what has been the secret of Japan’s extraordinary success in the pandemic. Over time it has the least cumulative deaths per capita of any major country in the world. That’s without a zero-Covid policy or any national lockdowns, which is why I have not included China as a comparator.

Before we get into that data, let’s take a look at the age pyramids for Japan and the United States. The No. 1 risk factor for death from COVID-19 is advanced age, and you can see that in Japan about 25% of the population is age 65 and older, whereas in the United States that proportion is substantially reduced at 15%. Sure there are differences in comorbidities such as obesity and diabetes, but there is also the trade-off of a much higher population density in Japan.

Besides masks, which were distributed early on by the government to the population in Japan, there was the “Avoid the 3Cs” cluster-busting strategy, widely disseminated in the spring of 2020, leveraging Pareto’s 80-20 principle, long before there were any vaccines available. For a good portion of the pandemic, the Ministry of Foreign Affairs of Japan maintained a strict policy for border control, which while hard to quantify, may certainly have contributed to its success.

Besides these factors, once vaccines became available, Japan got the population with the primary series to 83% rapidly, even after getting a late start by many months compared with the United States, which has peaked at 68%. That’s a big gap.

But that gap got much worse when it came to boosters. Ninety-five percent of Japanese eligible compared with 40.8% of Americans have had a booster shot. Of note, that 95% in Japan pertains to the whole population. In the United States the percentage of people age 65 and older who have had two boosters is currently only 42%. I’ve previously reviewed the important lifesaving impact of two boosters among people age 65 and older from five independent studies during Omicron waves throughout the world.

Now let’s turn to cumulative fatalities in the two countries. There’s a huge, nearly ninefold difference, per capita. Using today’s Covid-19 Dashboard, there are cumulatively 45,533 deaths in Japan and 1,062,560 American deaths. That translates to 1 in 2,758 people in Japan compared with 1 in 315 Americans dying of COVID.

And if we look at excess mortality instead of confirmed COVID deaths, that enormous gap doesn’t change.

Obviously it would be good to have data for other COVID outcomes, such as hospitalizations, ICUs, and Long COVID, but they are not accessible.

Comparing Japan, the country that has fared the best, with the United States, one of the worst pandemic outcome results, leaves us with a sense that Prof Ian MacKay’s “Swiss cheese model” is the best explanation. It’s not just one thing. Masks, consistent evidence-based communication (3Cs) with attention to ventilation and air quality, and the outstanding uptake of vaccines and boosters all contributed to Japan’s success.

There is another factor to add to that model – Paxlovid. Its benefit of reducing hospitalizations and deaths for people over age 65 is unquestionable.

That’s why I had previously modified the Swiss cheese model to add Paxlovid.

But in the United States, where 15% of the population is 65 and older, they account for over 75% of the daily death toll, still in the range of 400 per day. Here, with a very high proportion of people age 65 and older left vulnerable without boosters, or primary vaccines, Paxlovid is only being given to less than 25% of the eligible (age 50+), and less people age 80 and older are getting Paxlovid than those age 45. The reasons that doctors are not prescribing it – worried about interactions for a 5-day course and rebound – are not substantiated.

Bottom line: In the United States we are not protecting our population anywhere near as well as Japan, as grossly evident by the fatalities among people at the highest risk. There needs to be far better uptake of boosters and use of Paxlovid in the age 65+ group, but the need for amped up protection is not at all restricted to this age subgroup. Across all age groups age 18 and over there is an 81% reduction of hospitalizations with two boosters with the most updated CDC data available, through the Omicron BA.5 wave.

No less the previous data through May 2022 showing protection from death across all ages with two boosters

And please don’t forget that around the world, over 20 million lives were saved, just in 2021, the first year of vaccines.

We can learn so much from a model country like Japan. Yes, we need nasal and variant-proof vaccines to effectively deal with the new variants that are already getting legs in places like XBB in Singapore and ones not on the radar yet. But right now we’ve got to do far better for people getting boosters and, when a person age 65 or older gets COVID, Paxlovid. Take a look at the Chris Hayes video segment when he pleaded for Americans to get a booster shot. Every day that vaccine waning of the U.S. population exceeds the small percentage of people who get a booster, our vulnerability increases. If we don’t get that on track, it’s likely going to be a rough winter ahead.

Dr. Topol is director of the Scripps Translational Science Institute in La Jolla, Calif. He has received research grants from the National Institutes of Health and reported conflicts of interest involving Dexcom, Illumina, Molecular Stethoscope, Quest Diagnostics, and Blue Cross Blue Shield Association. A version of this article appeared on Medscape.com.

This article was originally published Oct. 8 on Medscape Editor-In-Chief Eric Topol’s “Ground Truths” column on Substack. 

A recent piece in The Economist about masks, and how at least half of the people in Japan are planning to continue to use masks indefinitely (where there was never a mandate), prompts a deeper look into what has been the secret of Japan’s extraordinary success in the pandemic. Over time it has the least cumulative deaths per capita of any major country in the world. That’s without a zero-Covid policy or any national lockdowns, which is why I have not included China as a comparator.

Before we get into that data, let’s take a look at the age pyramids for Japan and the United States. The No. 1 risk factor for death from COVID-19 is advanced age, and you can see that in Japan about 25% of the population is age 65 and older, whereas in the United States that proportion is substantially reduced at 15%. Sure there are differences in comorbidities such as obesity and diabetes, but there is also the trade-off of a much higher population density in Japan.

Besides masks, which were distributed early on by the government to the population in Japan, there was the “Avoid the 3Cs” cluster-busting strategy, widely disseminated in the spring of 2020, leveraging Pareto’s 80-20 principle, long before there were any vaccines available. For a good portion of the pandemic, the Ministry of Foreign Affairs of Japan maintained a strict policy for border control, which while hard to quantify, may certainly have contributed to its success.

Besides these factors, once vaccines became available, Japan got the population with the primary series to 83% rapidly, even after getting a late start by many months compared with the United States, which has peaked at 68%. That’s a big gap.

But that gap got much worse when it came to boosters. Ninety-five percent of Japanese eligible compared with 40.8% of Americans have had a booster shot. Of note, that 95% in Japan pertains to the whole population. In the United States the percentage of people age 65 and older who have had two boosters is currently only 42%. I’ve previously reviewed the important lifesaving impact of two boosters among people age 65 and older from five independent studies during Omicron waves throughout the world.

Now let’s turn to cumulative fatalities in the two countries. There’s a huge, nearly ninefold difference, per capita. Using today’s Covid-19 Dashboard, there are cumulatively 45,533 deaths in Japan and 1,062,560 American deaths. That translates to 1 in 2,758 people in Japan compared with 1 in 315 Americans dying of COVID.

And if we look at excess mortality instead of confirmed COVID deaths, that enormous gap doesn’t change.

Obviously it would be good to have data for other COVID outcomes, such as hospitalizations, ICUs, and Long COVID, but they are not accessible.

Comparing Japan, the country that has fared the best, with the United States, one of the worst pandemic outcome results, leaves us with a sense that Prof Ian MacKay’s “Swiss cheese model” is the best explanation. It’s not just one thing. Masks, consistent evidence-based communication (3Cs) with attention to ventilation and air quality, and the outstanding uptake of vaccines and boosters all contributed to Japan’s success.

There is another factor to add to that model – Paxlovid. Its benefit of reducing hospitalizations and deaths for people over age 65 is unquestionable.

That’s why I had previously modified the Swiss cheese model to add Paxlovid.

But in the United States, where 15% of the population is 65 and older, they account for over 75% of the daily death toll, still in the range of 400 per day. Here, with a very high proportion of people age 65 and older left vulnerable without boosters, or primary vaccines, Paxlovid is only being given to less than 25% of the eligible (age 50+), and less people age 80 and older are getting Paxlovid than those age 45. The reasons that doctors are not prescribing it – worried about interactions for a 5-day course and rebound – are not substantiated.

Bottom line: In the United States we are not protecting our population anywhere near as well as Japan, as grossly evident by the fatalities among people at the highest risk. There needs to be far better uptake of boosters and use of Paxlovid in the age 65+ group, but the need for amped up protection is not at all restricted to this age subgroup. Across all age groups age 18 and over there is an 81% reduction of hospitalizations with two boosters with the most updated CDC data available, through the Omicron BA.5 wave.

No less the previous data through May 2022 showing protection from death across all ages with two boosters

And please don’t forget that around the world, over 20 million lives were saved, just in 2021, the first year of vaccines.

We can learn so much from a model country like Japan. Yes, we need nasal and variant-proof vaccines to effectively deal with the new variants that are already getting legs in places like XBB in Singapore and ones not on the radar yet. But right now we’ve got to do far better for people getting boosters and, when a person age 65 or older gets COVID, Paxlovid. Take a look at the Chris Hayes video segment when he pleaded for Americans to get a booster shot. Every day that vaccine waning of the U.S. population exceeds the small percentage of people who get a booster, our vulnerability increases. If we don’t get that on track, it’s likely going to be a rough winter ahead.

Dr. Topol is director of the Scripps Translational Science Institute in La Jolla, Calif. He has received research grants from the National Institutes of Health and reported conflicts of interest involving Dexcom, Illumina, Molecular Stethoscope, Quest Diagnostics, and Blue Cross Blue Shield Association. A version of this article appeared on Medscape.com.

This article was originally published Oct. 8 on Medscape Editor-In-Chief Eric Topol’s “Ground Truths” column on Substack. 

A recent piece in The Economist about masks, and how at least half of the people in Japan are planning to continue to use masks indefinitely (where there was never a mandate), prompts a deeper look into what has been the secret of Japan’s extraordinary success in the pandemic. Over time it has the least cumulative deaths per capita of any major country in the world. That’s without a zero-Covid policy or any national lockdowns, which is why I have not included China as a comparator.

Before we get into that data, let’s take a look at the age pyramids for Japan and the United States. The No. 1 risk factor for death from COVID-19 is advanced age, and you can see that in Japan about 25% of the population is age 65 and older, whereas in the United States that proportion is substantially reduced at 15%. Sure there are differences in comorbidities such as obesity and diabetes, but there is also the trade-off of a much higher population density in Japan.

Besides masks, which were distributed early on by the government to the population in Japan, there was the “Avoid the 3Cs” cluster-busting strategy, widely disseminated in the spring of 2020, leveraging Pareto’s 80-20 principle, long before there were any vaccines available. For a good portion of the pandemic, the Ministry of Foreign Affairs of Japan maintained a strict policy for border control, which while hard to quantify, may certainly have contributed to its success.

Besides these factors, once vaccines became available, Japan got the population with the primary series to 83% rapidly, even after getting a late start by many months compared with the United States, which has peaked at 68%. That’s a big gap.

But that gap got much worse when it came to boosters. Ninety-five percent of Japanese eligible compared with 40.8% of Americans have had a booster shot. Of note, that 95% in Japan pertains to the whole population. In the United States the percentage of people age 65 and older who have had two boosters is currently only 42%. I’ve previously reviewed the important lifesaving impact of two boosters among people age 65 and older from five independent studies during Omicron waves throughout the world.

Now let’s turn to cumulative fatalities in the two countries. There’s a huge, nearly ninefold difference, per capita. Using today’s Covid-19 Dashboard, there are cumulatively 45,533 deaths in Japan and 1,062,560 American deaths. That translates to 1 in 2,758 people in Japan compared with 1 in 315 Americans dying of COVID.

And if we look at excess mortality instead of confirmed COVID deaths, that enormous gap doesn’t change.

Obviously it would be good to have data for other COVID outcomes, such as hospitalizations, ICUs, and Long COVID, but they are not accessible.

Comparing Japan, the country that has fared the best, with the United States, one of the worst pandemic outcome results, leaves us with a sense that Prof Ian MacKay’s “Swiss cheese model” is the best explanation. It’s not just one thing. Masks, consistent evidence-based communication (3Cs) with attention to ventilation and air quality, and the outstanding uptake of vaccines and boosters all contributed to Japan’s success.

There is another factor to add to that model – Paxlovid. Its benefit of reducing hospitalizations and deaths for people over age 65 is unquestionable.

That’s why I had previously modified the Swiss cheese model to add Paxlovid.

But in the United States, where 15% of the population is 65 and older, they account for over 75% of the daily death toll, still in the range of 400 per day. Here, with a very high proportion of people age 65 and older left vulnerable without boosters, or primary vaccines, Paxlovid is only being given to less than 25% of the eligible (age 50+), and less people age 80 and older are getting Paxlovid than those age 45. The reasons that doctors are not prescribing it – worried about interactions for a 5-day course and rebound – are not substantiated.

Bottom line: In the United States we are not protecting our population anywhere near as well as Japan, as grossly evident by the fatalities among people at the highest risk. There needs to be far better uptake of boosters and use of Paxlovid in the age 65+ group, but the need for amped up protection is not at all restricted to this age subgroup. Across all age groups age 18 and over there is an 81% reduction of hospitalizations with two boosters with the most updated CDC data available, through the Omicron BA.5 wave.

No less the previous data through May 2022 showing protection from death across all ages with two boosters

And please don’t forget that around the world, over 20 million lives were saved, just in 2021, the first year of vaccines.

We can learn so much from a model country like Japan. Yes, we need nasal and variant-proof vaccines to effectively deal with the new variants that are already getting legs in places like XBB in Singapore and ones not on the radar yet. But right now we’ve got to do far better for people getting boosters and, when a person age 65 or older gets COVID, Paxlovid. Take a look at the Chris Hayes video segment when he pleaded for Americans to get a booster shot. Every day that vaccine waning of the U.S. population exceeds the small percentage of people who get a booster, our vulnerability increases. If we don’t get that on track, it’s likely going to be a rough winter ahead.

Dr. Topol is director of the Scripps Translational Science Institute in La Jolla, Calif. He has received research grants from the National Institutes of Health and reported conflicts of interest involving Dexcom, Illumina, Molecular Stethoscope, Quest Diagnostics, and Blue Cross Blue Shield Association. A version of this article appeared on Medscape.com.

EVIDENCE SUMMARY

Early Dx didn’t improve smoking cessation rates or treatment outcomes

A 2016 evidence report and systematic review for the US Preventive Services Task Force (USPSTF) identified no studies directly comparing the effectiveness of COPD screening on patient outcomes, so the authors looked first at studies on the outcomes of screening, followed by studies exploring the effects of early treatment.¹

The authors identified 5 fair-quality RCTs (N = 1694) addressing the effect of screening asymptomatic patients for COPD with spirometry on the outcome of smoking cessation. One trial (n = 561) found better 12-month smoking cessation rates in patients who underwent spirometry screening and were given their “lung age” (13.6% vs 6.4% not given a lung age; P < .005; number needed to treat [NNT] = 14). However, a similar study (n = 542) published a year later found no significant difference in quit rates with or without “lung age” discussions (10.9% vs 13%, respectively; P not significant). In the other 3 studies, screening produced no significant effect on smoking cessation rates.¹

As for possible early treatment benefits, the review authors identified only 1 RCT (n = 1175) that included any patients with mild COPD (defined as COPD with a forced expiratory volume in 1 second [FEV₁] ≥ 80% of predicted normal value). It assessed treatment with inhaled corticosteroids (ICS) in patients with mild COPD who continued to smoke. The trial did not record symptoms (if any) at intake. ICS therapy reduced the frequency of COPD exacerbations (relative risk = 0.63; 95% CI, 0.47-0.85), although patients with milder COPD benefitted little in absolute terms (by 0.02 exacerbations/year).¹ The review authors further noted that data were insufficient to make definitive statements about the effect of ICS on dyspnea or health-related quality of life.

But later diagnosis is associated with poorer outcomes

Two recent, large retrospective observational cohort studies, however, have examined the impact of an early vs late COPD diagnosis in patients with dyspnea or other symptoms of COPD.^2,3 A later diagnosis was associated with worse outcomes.

In the first study, researchers in Sweden identified patients older than 40 years who had received a new diagnosis of COPD between 2000 and 2014.² They examined electronic health record data for 6 different “indicators” of COPD during the 5 years prior to date of diagnosis: pneumonia, other respiratory disease, oral steroids, antibiotics for respiratory infection, prescribed drugs for respiratory symptoms, and lung function measurement. Researchers categorized patients as early diagnosis (if they had ≤ 2 indicators prior to diagnosis) or late diagnosis (≥ 3 indicators prior to diagnosis). Compared with early diagnosis (n = 3870), late diagnosis (n = 8827) was associated with

• a higher annual rate of exacerbations within the first 2 years after diagnosis (2.67 vs 1.41; hazard ratio [HR] = 1.89; 95% CI, 1.83-1.96; P < .0001; number of early diagnoses needed to prevent 1 exacerbation in 1 year = 79),
• shorter time to first exacerbation (HR = 1.61; 95% CI, 1.54-1.69; P < .0001), and
• higher direct health care costs (by €1500 per year; no P value given).

Mortality was not different between the groups (HR = 1.04; 95% CI, 0.98-1.11; P = .18).

The second investigation was a similarly designed retrospective observational cohort study using a large UK database.³ Researchers enrolled patients who were at least 40 years old and received a new diagnosis of COPD between 2011 and 2014.

Continue to: Researchers examined electronic...

Researchers examined electronic health record data in the 5 years prior to diagnosis for 7 possible indicators of early COPD: pneumonia, respiratory disease other than pneumonia, chest radiograph, prescription of oral steroids, prescription of antibiotics for lung infection, prescription to manage respiratory disease symptoms, and lung function measurement. Researchers categorized patients as early diagnosis (≥ 2 indicators prior to diagnosis) or late diagnosis (≥ 3 indicators prior to diagnosis). Compared with early diagnosis (n = 3375), late diagnosis (n = 6783) was associated with a higher annual rate of exacerbations over 3-year follow-up (1.09 vs 0.57; adjusted HR = 1.68; 95% CI, 1.59-1.79; P < .0001; or 1 additional exacerbation in 192 patients in 1 year), shorter mean time to first exacerbation (HR = 1.46; 95% CI: 1.38-1.55; P < .0001), and a higher risk of hospitalization within 3 years (rate ratio = 1.18; 95% CI, 1.08-1.28; P = .0001). The researchers did not evaluate for mortality.

Even smoking cessation rates were not improved by an early COPD diagnosis.

Importantly, patients in the late COPD diagnosis group in both trials had higher rates of other severe illnesses that cause dyspnea, including cardiovascular disease and other pulmonary diseases. As a result, dyspnea of other etiologies may have contributed to both the later diagnoses and the poorer clinical outcomes of the late-­diagnosis group. Both studies had a high risk of lead-time bias.

Recommendations from others

In 2016, the USPSTF gave a “D” rating (moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits) to screening asymptomatic adults without respiratory symptoms for COPD.⁴ Likewise, the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report did not recommend routine screening with spirometry but did advocate trying to make an accurate diagnosis using spirometry in patients with risk factors for COPD and chronic, progressive symptoms.⁵

Editor’s takeaway

Reasonably good evidence failed to find a benefit from an early COPD diagnosis. Even smoking cessation rates were not improved. Without better disease-modifying treatments, spirometry—the gold standard for confirming a COPD diagnosis—should not be used for screening asymptomatic patients.

EVIDENCE SUMMARY

Early Dx didn’t improve smoking cessation rates or treatment outcomes

A 2016 evidence report and systematic review for the US Preventive Services Task Force (USPSTF) identified no studies directly comparing the effectiveness of COPD screening on patient outcomes, so the authors looked first at studies on the outcomes of screening, followed by studies exploring the effects of early treatment.¹

The authors identified 5 fair-quality RCTs (N = 1694) addressing the effect of screening asymptomatic patients for COPD with spirometry on the outcome of smoking cessation. One trial (n = 561) found better 12-month smoking cessation rates in patients who underwent spirometry screening and were given their “lung age” (13.6% vs 6.4% not given a lung age; P < .005; number needed to treat [NNT] = 14). However, a similar study (n = 542) published a year later found no significant difference in quit rates with or without “lung age” discussions (10.9% vs 13%, respectively; P not significant). In the other 3 studies, screening produced no significant effect on smoking cessation rates.¹

As for possible early treatment benefits, the review authors identified only 1 RCT (n = 1175) that included any patients with mild COPD (defined as COPD with a forced expiratory volume in 1 second [FEV₁] ≥ 80% of predicted normal value). It assessed treatment with inhaled corticosteroids (ICS) in patients with mild COPD who continued to smoke. The trial did not record symptoms (if any) at intake. ICS therapy reduced the frequency of COPD exacerbations (relative risk = 0.63; 95% CI, 0.47-0.85), although patients with milder COPD benefitted little in absolute terms (by 0.02 exacerbations/year).¹ The review authors further noted that data were insufficient to make definitive statements about the effect of ICS on dyspnea or health-related quality of life.

But later diagnosis is associated with poorer outcomes

Two recent, large retrospective observational cohort studies, however, have examined the impact of an early vs late COPD diagnosis in patients with dyspnea or other symptoms of COPD.^2,3 A later diagnosis was associated with worse outcomes.

In the first study, researchers in Sweden identified patients older than 40 years who had received a new diagnosis of COPD between 2000 and 2014.² They examined electronic health record data for 6 different “indicators” of COPD during the 5 years prior to date of diagnosis: pneumonia, other respiratory disease, oral steroids, antibiotics for respiratory infection, prescribed drugs for respiratory symptoms, and lung function measurement. Researchers categorized patients as early diagnosis (if they had ≤ 2 indicators prior to diagnosis) or late diagnosis (≥ 3 indicators prior to diagnosis). Compared with early diagnosis (n = 3870), late diagnosis (n = 8827) was associated with

• a higher annual rate of exacerbations within the first 2 years after diagnosis (2.67 vs 1.41; hazard ratio [HR] = 1.89; 95% CI, 1.83-1.96; P < .0001; number of early diagnoses needed to prevent 1 exacerbation in 1 year = 79),
• shorter time to first exacerbation (HR = 1.61; 95% CI, 1.54-1.69; P < .0001), and
• higher direct health care costs (by €1500 per year; no P value given).

Mortality was not different between the groups (HR = 1.04; 95% CI, 0.98-1.11; P = .18).

The second investigation was a similarly designed retrospective observational cohort study using a large UK database.³ Researchers enrolled patients who were at least 40 years old and received a new diagnosis of COPD between 2011 and 2014.

Continue to: Researchers examined electronic...

Researchers examined electronic health record data in the 5 years prior to diagnosis for 7 possible indicators of early COPD: pneumonia, respiratory disease other than pneumonia, chest radiograph, prescription of oral steroids, prescription of antibiotics for lung infection, prescription to manage respiratory disease symptoms, and lung function measurement. Researchers categorized patients as early diagnosis (≥ 2 indicators prior to diagnosis) or late diagnosis (≥ 3 indicators prior to diagnosis). Compared with early diagnosis (n = 3375), late diagnosis (n = 6783) was associated with a higher annual rate of exacerbations over 3-year follow-up (1.09 vs 0.57; adjusted HR = 1.68; 95% CI, 1.59-1.79; P < .0001; or 1 additional exacerbation in 192 patients in 1 year), shorter mean time to first exacerbation (HR = 1.46; 95% CI: 1.38-1.55; P < .0001), and a higher risk of hospitalization within 3 years (rate ratio = 1.18; 95% CI, 1.08-1.28; P = .0001). The researchers did not evaluate for mortality.

Even smoking cessation rates were not improved by an early COPD diagnosis.

Importantly, patients in the late COPD diagnosis group in both trials had higher rates of other severe illnesses that cause dyspnea, including cardiovascular disease and other pulmonary diseases. As a result, dyspnea of other etiologies may have contributed to both the later diagnoses and the poorer clinical outcomes of the late-­diagnosis group. Both studies had a high risk of lead-time bias.

Recommendations from others

In 2016, the USPSTF gave a “D” rating (moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits) to screening asymptomatic adults without respiratory symptoms for COPD.⁴ Likewise, the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report did not recommend routine screening with spirometry but did advocate trying to make an accurate diagnosis using spirometry in patients with risk factors for COPD and chronic, progressive symptoms.⁵

Editor’s takeaway

Reasonably good evidence failed to find a benefit from an early COPD diagnosis. Even smoking cessation rates were not improved. Without better disease-modifying treatments, spirometry—the gold standard for confirming a COPD diagnosis—should not be used for screening asymptomatic patients.

EVIDENCE SUMMARY

Early Dx didn’t improve smoking cessation rates or treatment outcomes

A 2016 evidence report and systematic review for the US Preventive Services Task Force (USPSTF) identified no studies directly comparing the effectiveness of COPD screening on patient outcomes, so the authors looked first at studies on the outcomes of screening, followed by studies exploring the effects of early treatment.¹

The authors identified 5 fair-quality RCTs (N = 1694) addressing the effect of screening asymptomatic patients for COPD with spirometry on the outcome of smoking cessation. One trial (n = 561) found better 12-month smoking cessation rates in patients who underwent spirometry screening and were given their “lung age” (13.6% vs 6.4% not given a lung age; P < .005; number needed to treat [NNT] = 14). However, a similar study (n = 542) published a year later found no significant difference in quit rates with or without “lung age” discussions (10.9% vs 13%, respectively; P not significant). In the other 3 studies, screening produced no significant effect on smoking cessation rates.¹

As for possible early treatment benefits, the review authors identified only 1 RCT (n = 1175) that included any patients with mild COPD (defined as COPD with a forced expiratory volume in 1 second [FEV₁] ≥ 80% of predicted normal value). It assessed treatment with inhaled corticosteroids (ICS) in patients with mild COPD who continued to smoke. The trial did not record symptoms (if any) at intake. ICS therapy reduced the frequency of COPD exacerbations (relative risk = 0.63; 95% CI, 0.47-0.85), although patients with milder COPD benefitted little in absolute terms (by 0.02 exacerbations/year).¹ The review authors further noted that data were insufficient to make definitive statements about the effect of ICS on dyspnea or health-related quality of life.

But later diagnosis is associated with poorer outcomes

Two recent, large retrospective observational cohort studies, however, have examined the impact of an early vs late COPD diagnosis in patients with dyspnea or other symptoms of COPD.^2,3 A later diagnosis was associated with worse outcomes.

In the first study, researchers in Sweden identified patients older than 40 years who had received a new diagnosis of COPD between 2000 and 2014.² They examined electronic health record data for 6 different “indicators” of COPD during the 5 years prior to date of diagnosis: pneumonia, other respiratory disease, oral steroids, antibiotics for respiratory infection, prescribed drugs for respiratory symptoms, and lung function measurement. Researchers categorized patients as early diagnosis (if they had ≤ 2 indicators prior to diagnosis) or late diagnosis (≥ 3 indicators prior to diagnosis). Compared with early diagnosis (n = 3870), late diagnosis (n = 8827) was associated with

• a higher annual rate of exacerbations within the first 2 years after diagnosis (2.67 vs 1.41; hazard ratio [HR] = 1.89; 95% CI, 1.83-1.96; P < .0001; number of early diagnoses needed to prevent 1 exacerbation in 1 year = 79),
• shorter time to first exacerbation (HR = 1.61; 95% CI, 1.54-1.69; P < .0001), and
• higher direct health care costs (by €1500 per year; no P value given).

Mortality was not different between the groups (HR = 1.04; 95% CI, 0.98-1.11; P = .18).

The second investigation was a similarly designed retrospective observational cohort study using a large UK database.³ Researchers enrolled patients who were at least 40 years old and received a new diagnosis of COPD between 2011 and 2014.

Continue to: Researchers examined electronic...

Researchers examined electronic health record data in the 5 years prior to diagnosis for 7 possible indicators of early COPD: pneumonia, respiratory disease other than pneumonia, chest radiograph, prescription of oral steroids, prescription of antibiotics for lung infection, prescription to manage respiratory disease symptoms, and lung function measurement. Researchers categorized patients as early diagnosis (≥ 2 indicators prior to diagnosis) or late diagnosis (≥ 3 indicators prior to diagnosis). Compared with early diagnosis (n = 3375), late diagnosis (n = 6783) was associated with a higher annual rate of exacerbations over 3-year follow-up (1.09 vs 0.57; adjusted HR = 1.68; 95% CI, 1.59-1.79; P < .0001; or 1 additional exacerbation in 192 patients in 1 year), shorter mean time to first exacerbation (HR = 1.46; 95% CI: 1.38-1.55; P < .0001), and a higher risk of hospitalization within 3 years (rate ratio = 1.18; 95% CI, 1.08-1.28; P = .0001). The researchers did not evaluate for mortality.

Even smoking cessation rates were not improved by an early COPD diagnosis.

Importantly, patients in the late COPD diagnosis group in both trials had higher rates of other severe illnesses that cause dyspnea, including cardiovascular disease and other pulmonary diseases. As a result, dyspnea of other etiologies may have contributed to both the later diagnoses and the poorer clinical outcomes of the late-­diagnosis group. Both studies had a high risk of lead-time bias.

Recommendations from others

In 2016, the USPSTF gave a “D” rating (moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits) to screening asymptomatic adults without respiratory symptoms for COPD.⁴ Likewise, the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report did not recommend routine screening with spirometry but did advocate trying to make an accurate diagnosis using spirometry in patients with risk factors for COPD and chronic, progressive symptoms.⁵

Editor’s takeaway

Reasonably good evidence failed to find a benefit from an early COPD diagnosis. Even smoking cessation rates were not improved. Without better disease-modifying treatments, spirometry—the gold standard for confirming a COPD diagnosis—should not be used for screening asymptomatic patients.

A symptom-based screening tool can identify 2-year-olds at increased risk of asthma, persistent symptoms of wheeze, and health care burden by the age of 5, according to researchers.

The validated CHILDhood Asthma Risk Tool (CHART) determines high, moderate, or low risk of asthma based on symptoms reported before the age of 3 years. It also recommends follow-up.

Potentially, CHART could be used “to identify children who need monitoring, timely symptom control, and introduction of preventive therapies,” said Padmaja Subbarao, MD, MSc, associate chief of clinical research at the Hospital for Sick Children, Toronto, and colleagues in JAMA Network Open.

“The implementation of CHART as a first-step screening tool in general practice could promote timely treatment control and, in turn, improve quality of life for patients and reduce the clinical and economic burden of asthma,” they wrote.

Dr. Subbarao and colleagues developed CHART using data from parent questionnaires and 3- and 5-year clinic visits in the CHILD study. Children were categorized as “high risk” when they experienced two or more episodes of wheeze annually at both 3 and 5 years of age, concurrent with ED visits, hospitalizations, asthma medication, or frequent dry cough. Children with only cough episodes or with cough episodes plus one episode of wheeze in the past 12 months were categorized as “low risk.”

“Our unique approach to classification of wheeze symptoms is important because it helps busy practitioners identify the smaller subset of children with more frequent or severe wheezing episodes who have a higher probability of continued symptoms and impaired lung function in adult life among most children with infrequent wheeze,” Dr. Sabbarao and coauthors said.

Their diagnostic study to evaluate CHART’s predictive capacity showed that the tool had the highest proportion of true-positive asthma at 5 years (sensitivity, 50.0%), compared with physicians’ diagnosis at 3 years (sensitivity, 43.5%), and positive standardized modified Asthma Predictive Index (mAPI) at 3 years (sensitivity, 24.4%).

CHART also outperformed physician assessments and mAPI for predicting persistent wheeze at 5 years and provided the highest predictive capacity for subsequent health care use at 5 years of age. The study showed that it identified 20% more children with emergency department visits or hospitalizations than the standardized mAPI (sensitivity 45.5% vs. 25.0%), and approximately 10% more at-risk children than physician diagnosis.

“These findings are especially important given that many hospitalizations are avoidable if appropriate treatment and management of asthma are implemented at primary care,” Dr. Subbarao and colleagues wrote.

CHART has been validated in two external cohorts: a general-population cohort of 2,185 children from the Raine Study in Australia at 5 years of age; and the other a high-risk cohort of 349 children from the Canadian Asthma Primary Prevention Study at 7 years of age.

“We want to highlight the importance of periodic monitoring of wheeze symptoms and simplify the identification of high-risk children for primary care providers and parents or caregivers,” said Dr. Subbarao, who is director of the CHILD study and professor of pediatrics at the University of Toronto.

The tool “does not identify the underlying biology, which could impact the efficacy of our current standard asthma treatment,” Dr. Subbarao emphasized. CHART has not been tested in low-prevalence settings or in countries in which the term “wheeze” is not commonly recognized, she added.

“CHART helps you focus your crystal ball a little bit, look into the future, and see what’s going to happen,” said Harold Farber, MD, a pediatric pulmonologist who was not involved in the study. “It’s useful even if it just confirms what I’m already doing clinically.”

Dr. Farber, who is professor of pediatrics at Baylor College of Medicine and the Texas Children’s Hospital, Houston, cautioned that the predictive value of CHART is based on the diagnosis of asthma, and that this can differ across health care communities. “Between the extremes and what’s considered borderline, there’s a lot of diagnostic variation in what we call asthma,” he explained in an interview. “The diagnosis is, to some extent, subjective.”

However, Dr. Farber agreed that two or more wheezing episodes in the past 12 months – enough to require treatment – puts a child at very high risk for future wheezing. “Kids with a bunch of wheezing problems at 3 years are likely to have wheezing problems at 5. We have to think about what we can do for a toddler today to keep him from wheezing later.”

CHART is simple to use, the investigators said. The information needed can be easily gathered through interviews and parent-reported questionnaires, then put into the electronic medical record to flag children at high risk for further investigation, and well as those at low or moderate risk for monitoring.

Parents and caregivers can also use CHART to document symptoms every 6 months in children older than 1 year of age, said Dr. Subbarao. This information can be brought to the attention of the doctor “to facilitate a deeper discussion,” she suggested.

This study was funded by the Canadian Institutes of Health Research, Allergy, Genes and Environment Network of Centers of Excellence; Don and Debbie Morrison; Women’s and Children Health Research Institute; and Canada Research Chairs. Dr Subbarao reported having no potential conflicts of interest. Coauthor Vanessa Breton, PhD, disclosed being employed by F. Hoffmann-La Roche Ltd., and coauthor Elinor Simons, MD, PhD, reported membership on the Sanofi-Genzyme Data Monitoring Board. No other conflicts of interest were reported by the study authors. Dr Farber disclosed having no potential conflicts of interest.

A symptom-based screening tool can identify 2-year-olds at increased risk of asthma, persistent symptoms of wheeze, and health care burden by the age of 5, according to researchers.

The validated CHILDhood Asthma Risk Tool (CHART) determines high, moderate, or low risk of asthma based on symptoms reported before the age of 3 years. It also recommends follow-up.

Potentially, CHART could be used “to identify children who need monitoring, timely symptom control, and introduction of preventive therapies,” said Padmaja Subbarao, MD, MSc, associate chief of clinical research at the Hospital for Sick Children, Toronto, and colleagues in JAMA Network Open.

“The implementation of CHART as a first-step screening tool in general practice could promote timely treatment control and, in turn, improve quality of life for patients and reduce the clinical and economic burden of asthma,” they wrote.

Dr. Subbarao and colleagues developed CHART using data from parent questionnaires and 3- and 5-year clinic visits in the CHILD study. Children were categorized as “high risk” when they experienced two or more episodes of wheeze annually at both 3 and 5 years of age, concurrent with ED visits, hospitalizations, asthma medication, or frequent dry cough. Children with only cough episodes or with cough episodes plus one episode of wheeze in the past 12 months were categorized as “low risk.”

“Our unique approach to classification of wheeze symptoms is important because it helps busy practitioners identify the smaller subset of children with more frequent or severe wheezing episodes who have a higher probability of continued symptoms and impaired lung function in adult life among most children with infrequent wheeze,” Dr. Sabbarao and coauthors said.

Their diagnostic study to evaluate CHART’s predictive capacity showed that the tool had the highest proportion of true-positive asthma at 5 years (sensitivity, 50.0%), compared with physicians’ diagnosis at 3 years (sensitivity, 43.5%), and positive standardized modified Asthma Predictive Index (mAPI) at 3 years (sensitivity, 24.4%).

CHART also outperformed physician assessments and mAPI for predicting persistent wheeze at 5 years and provided the highest predictive capacity for subsequent health care use at 5 years of age. The study showed that it identified 20% more children with emergency department visits or hospitalizations than the standardized mAPI (sensitivity 45.5% vs. 25.0%), and approximately 10% more at-risk children than physician diagnosis.

“These findings are especially important given that many hospitalizations are avoidable if appropriate treatment and management of asthma are implemented at primary care,” Dr. Subbarao and colleagues wrote.

CHART has been validated in two external cohorts: a general-population cohort of 2,185 children from the Raine Study in Australia at 5 years of age; and the other a high-risk cohort of 349 children from the Canadian Asthma Primary Prevention Study at 7 years of age.

“We want to highlight the importance of periodic monitoring of wheeze symptoms and simplify the identification of high-risk children for primary care providers and parents or caregivers,” said Dr. Subbarao, who is director of the CHILD study and professor of pediatrics at the University of Toronto.

The tool “does not identify the underlying biology, which could impact the efficacy of our current standard asthma treatment,” Dr. Subbarao emphasized. CHART has not been tested in low-prevalence settings or in countries in which the term “wheeze” is not commonly recognized, she added.

“CHART helps you focus your crystal ball a little bit, look into the future, and see what’s going to happen,” said Harold Farber, MD, a pediatric pulmonologist who was not involved in the study. “It’s useful even if it just confirms what I’m already doing clinically.”

Dr. Farber, who is professor of pediatrics at Baylor College of Medicine and the Texas Children’s Hospital, Houston, cautioned that the predictive value of CHART is based on the diagnosis of asthma, and that this can differ across health care communities. “Between the extremes and what’s considered borderline, there’s a lot of diagnostic variation in what we call asthma,” he explained in an interview. “The diagnosis is, to some extent, subjective.”

However, Dr. Farber agreed that two or more wheezing episodes in the past 12 months – enough to require treatment – puts a child at very high risk for future wheezing. “Kids with a bunch of wheezing problems at 3 years are likely to have wheezing problems at 5. We have to think about what we can do for a toddler today to keep him from wheezing later.”

CHART is simple to use, the investigators said. The information needed can be easily gathered through interviews and parent-reported questionnaires, then put into the electronic medical record to flag children at high risk for further investigation, and well as those at low or moderate risk for monitoring.

Parents and caregivers can also use CHART to document symptoms every 6 months in children older than 1 year of age, said Dr. Subbarao. This information can be brought to the attention of the doctor “to facilitate a deeper discussion,” she suggested.

This study was funded by the Canadian Institutes of Health Research, Allergy, Genes and Environment Network of Centers of Excellence; Don and Debbie Morrison; Women’s and Children Health Research Institute; and Canada Research Chairs. Dr Subbarao reported having no potential conflicts of interest. Coauthor Vanessa Breton, PhD, disclosed being employed by F. Hoffmann-La Roche Ltd., and coauthor Elinor Simons, MD, PhD, reported membership on the Sanofi-Genzyme Data Monitoring Board. No other conflicts of interest were reported by the study authors. Dr Farber disclosed having no potential conflicts of interest.

A symptom-based screening tool can identify 2-year-olds at increased risk of asthma, persistent symptoms of wheeze, and health care burden by the age of 5, according to researchers.

The validated CHILDhood Asthma Risk Tool (CHART) determines high, moderate, or low risk of asthma based on symptoms reported before the age of 3 years. It also recommends follow-up.

Potentially, CHART could be used “to identify children who need monitoring, timely symptom control, and introduction of preventive therapies,” said Padmaja Subbarao, MD, MSc, associate chief of clinical research at the Hospital for Sick Children, Toronto, and colleagues in JAMA Network Open.

“The implementation of CHART as a first-step screening tool in general practice could promote timely treatment control and, in turn, improve quality of life for patients and reduce the clinical and economic burden of asthma,” they wrote.

Dr. Subbarao and colleagues developed CHART using data from parent questionnaires and 3- and 5-year clinic visits in the CHILD study. Children were categorized as “high risk” when they experienced two or more episodes of wheeze annually at both 3 and 5 years of age, concurrent with ED visits, hospitalizations, asthma medication, or frequent dry cough. Children with only cough episodes or with cough episodes plus one episode of wheeze in the past 12 months were categorized as “low risk.”

“Our unique approach to classification of wheeze symptoms is important because it helps busy practitioners identify the smaller subset of children with more frequent or severe wheezing episodes who have a higher probability of continued symptoms and impaired lung function in adult life among most children with infrequent wheeze,” Dr. Sabbarao and coauthors said.

Their diagnostic study to evaluate CHART’s predictive capacity showed that the tool had the highest proportion of true-positive asthma at 5 years (sensitivity, 50.0%), compared with physicians’ diagnosis at 3 years (sensitivity, 43.5%), and positive standardized modified Asthma Predictive Index (mAPI) at 3 years (sensitivity, 24.4%).

CHART also outperformed physician assessments and mAPI for predicting persistent wheeze at 5 years and provided the highest predictive capacity for subsequent health care use at 5 years of age. The study showed that it identified 20% more children with emergency department visits or hospitalizations than the standardized mAPI (sensitivity 45.5% vs. 25.0%), and approximately 10% more at-risk children than physician diagnosis.

“These findings are especially important given that many hospitalizations are avoidable if appropriate treatment and management of asthma are implemented at primary care,” Dr. Subbarao and colleagues wrote.

CHART has been validated in two external cohorts: a general-population cohort of 2,185 children from the Raine Study in Australia at 5 years of age; and the other a high-risk cohort of 349 children from the Canadian Asthma Primary Prevention Study at 7 years of age.

“We want to highlight the importance of periodic monitoring of wheeze symptoms and simplify the identification of high-risk children for primary care providers and parents or caregivers,” said Dr. Subbarao, who is director of the CHILD study and professor of pediatrics at the University of Toronto.

The tool “does not identify the underlying biology, which could impact the efficacy of our current standard asthma treatment,” Dr. Subbarao emphasized. CHART has not been tested in low-prevalence settings or in countries in which the term “wheeze” is not commonly recognized, she added.

“CHART helps you focus your crystal ball a little bit, look into the future, and see what’s going to happen,” said Harold Farber, MD, a pediatric pulmonologist who was not involved in the study. “It’s useful even if it just confirms what I’m already doing clinically.”

Dr. Farber, who is professor of pediatrics at Baylor College of Medicine and the Texas Children’s Hospital, Houston, cautioned that the predictive value of CHART is based on the diagnosis of asthma, and that this can differ across health care communities. “Between the extremes and what’s considered borderline, there’s a lot of diagnostic variation in what we call asthma,” he explained in an interview. “The diagnosis is, to some extent, subjective.”

However, Dr. Farber agreed that two or more wheezing episodes in the past 12 months – enough to require treatment – puts a child at very high risk for future wheezing. “Kids with a bunch of wheezing problems at 3 years are likely to have wheezing problems at 5. We have to think about what we can do for a toddler today to keep him from wheezing later.”

CHART is simple to use, the investigators said. The information needed can be easily gathered through interviews and parent-reported questionnaires, then put into the electronic medical record to flag children at high risk for further investigation, and well as those at low or moderate risk for monitoring.

Parents and caregivers can also use CHART to document symptoms every 6 months in children older than 1 year of age, said Dr. Subbarao. This information can be brought to the attention of the doctor “to facilitate a deeper discussion,” she suggested.

This study was funded by the Canadian Institutes of Health Research, Allergy, Genes and Environment Network of Centers of Excellence; Don and Debbie Morrison; Women’s and Children Health Research Institute; and Canada Research Chairs. Dr Subbarao reported having no potential conflicts of interest. Coauthor Vanessa Breton, PhD, disclosed being employed by F. Hoffmann-La Roche Ltd., and coauthor Elinor Simons, MD, PhD, reported membership on the Sanofi-Genzyme Data Monitoring Board. No other conflicts of interest were reported by the study authors. Dr Farber disclosed having no potential conflicts of interest.