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Short-term oxygen prescriptions lead to inappropriate long-term use
In past posts for this news organization, I’ve railed against the cost of inappropriate prescriptions for oxygen. A recent review recommended against prescribing oxygen for patients with isolated exertional or nocturnal desaturations, and recently published randomized trials found no demonstrable benefit to oxygen use in the absence of resting hypoxemia. a common practice in clinics where I’ve worked. However, oxygen prescriptions at hospital discharge are a far more pernicious cause of wasted resources.
Prescriptions at hospital discharge, sometimes referred to as short-term oxygen therapy (STOT), account for a large proportion of total oxygen use. Past data have shown that the term “STOT” is a misnomer, as most patients provided with oxygen at discharge are never reevaluated and become long-term oxygen users. The high cost of durable medical equipment related to oxygen delivery prompted the American Thoracic Society and American College of Chest Physicians to recommend postdischarge reassessment of oxygen needs in their Choosing Wisely campaign for adult pulmonary medicine.
A recent study published in the Annals of the American Thoracic Society (Ann ATS) highlights the benefits available if we decide to “choose wisely.” The authors studied patients covered by Veterans Affairs and discharged on STOT between 2006 and 2011. Only 43.6% (287/659) had complete reassessment (oxygen testing at rest and with ambulation) within 90 days. Of those, 124 (43.2%) were eligible for discontinuation via Centers for Medicare & Medicaid Services guidelines. A total of 70.7% (466/659) were tested at rest, and only 15.7% (73/466) had resting hypoxemia. If one accepts the results of the recently published Long-Term Oxygen Treatment Trial, this means that 84.3% (393/466) would be eligible for oxygen discontinuation.
The Ann ATS study provides a blueprint for how we might improve these dismal numbers. There were five separate sites reviewed in their paper. At one site, reassessment occurred in 78.5% of STOT patients and 100% had oxygen discontinued when appropriate. What was their secret? An automatic alert system and a dedicated clinic, coordinator, and respiratory therapist. Also, among the 124 patients who had a full reassessment and no longer qualified for oxygen, 86.3% had it discontinued.
There are countless reasons why STOT is common, but discontinuation is not. Most COPD exacerbations are managed by nonpulmonologists on general medicine wards prior to discharge. In my experience, these physicians are reluctant to release a patient with exertional hypoxia without STOT. They also assume that the pulmonary clinic will do its job during the obligatory outpatient follow-up appointment they schedule with us. At the follow-up, the patient and physician are reluctant to stop therapy because of psychological dependence and therapeutic overconfidence, respectively.
In summary, STOT following hospitalization comprises the majority of all oxygen prescriptions. Historically, the United States provides far more oxygen than other developed countries, and only CMS reimbursement changes have bent the “overprescription” curve. The Ann ATS study shows that a well-designed program at the hospital level can put oxygen decisions back in the hands of providers.
Let’s “choose wisely” and follow what works, or we’ll have only ourselves to blame when reimbursement decisions are taken out of our hands.
A version of this article first appeared on Medscape.com.
In past posts for this news organization, I’ve railed against the cost of inappropriate prescriptions for oxygen. A recent review recommended against prescribing oxygen for patients with isolated exertional or nocturnal desaturations, and recently published randomized trials found no demonstrable benefit to oxygen use in the absence of resting hypoxemia. a common practice in clinics where I’ve worked. However, oxygen prescriptions at hospital discharge are a far more pernicious cause of wasted resources.
Prescriptions at hospital discharge, sometimes referred to as short-term oxygen therapy (STOT), account for a large proportion of total oxygen use. Past data have shown that the term “STOT” is a misnomer, as most patients provided with oxygen at discharge are never reevaluated and become long-term oxygen users. The high cost of durable medical equipment related to oxygen delivery prompted the American Thoracic Society and American College of Chest Physicians to recommend postdischarge reassessment of oxygen needs in their Choosing Wisely campaign for adult pulmonary medicine.
A recent study published in the Annals of the American Thoracic Society (Ann ATS) highlights the benefits available if we decide to “choose wisely.” The authors studied patients covered by Veterans Affairs and discharged on STOT between 2006 and 2011. Only 43.6% (287/659) had complete reassessment (oxygen testing at rest and with ambulation) within 90 days. Of those, 124 (43.2%) were eligible for discontinuation via Centers for Medicare & Medicaid Services guidelines. A total of 70.7% (466/659) were tested at rest, and only 15.7% (73/466) had resting hypoxemia. If one accepts the results of the recently published Long-Term Oxygen Treatment Trial, this means that 84.3% (393/466) would be eligible for oxygen discontinuation.
The Ann ATS study provides a blueprint for how we might improve these dismal numbers. There were five separate sites reviewed in their paper. At one site, reassessment occurred in 78.5% of STOT patients and 100% had oxygen discontinued when appropriate. What was their secret? An automatic alert system and a dedicated clinic, coordinator, and respiratory therapist. Also, among the 124 patients who had a full reassessment and no longer qualified for oxygen, 86.3% had it discontinued.
There are countless reasons why STOT is common, but discontinuation is not. Most COPD exacerbations are managed by nonpulmonologists on general medicine wards prior to discharge. In my experience, these physicians are reluctant to release a patient with exertional hypoxia without STOT. They also assume that the pulmonary clinic will do its job during the obligatory outpatient follow-up appointment they schedule with us. At the follow-up, the patient and physician are reluctant to stop therapy because of psychological dependence and therapeutic overconfidence, respectively.
In summary, STOT following hospitalization comprises the majority of all oxygen prescriptions. Historically, the United States provides far more oxygen than other developed countries, and only CMS reimbursement changes have bent the “overprescription” curve. The Ann ATS study shows that a well-designed program at the hospital level can put oxygen decisions back in the hands of providers.
Let’s “choose wisely” and follow what works, or we’ll have only ourselves to blame when reimbursement decisions are taken out of our hands.
A version of this article first appeared on Medscape.com.
In past posts for this news organization, I’ve railed against the cost of inappropriate prescriptions for oxygen. A recent review recommended against prescribing oxygen for patients with isolated exertional or nocturnal desaturations, and recently published randomized trials found no demonstrable benefit to oxygen use in the absence of resting hypoxemia. a common practice in clinics where I’ve worked. However, oxygen prescriptions at hospital discharge are a far more pernicious cause of wasted resources.
Prescriptions at hospital discharge, sometimes referred to as short-term oxygen therapy (STOT), account for a large proportion of total oxygen use. Past data have shown that the term “STOT” is a misnomer, as most patients provided with oxygen at discharge are never reevaluated and become long-term oxygen users. The high cost of durable medical equipment related to oxygen delivery prompted the American Thoracic Society and American College of Chest Physicians to recommend postdischarge reassessment of oxygen needs in their Choosing Wisely campaign for adult pulmonary medicine.
A recent study published in the Annals of the American Thoracic Society (Ann ATS) highlights the benefits available if we decide to “choose wisely.” The authors studied patients covered by Veterans Affairs and discharged on STOT between 2006 and 2011. Only 43.6% (287/659) had complete reassessment (oxygen testing at rest and with ambulation) within 90 days. Of those, 124 (43.2%) were eligible for discontinuation via Centers for Medicare & Medicaid Services guidelines. A total of 70.7% (466/659) were tested at rest, and only 15.7% (73/466) had resting hypoxemia. If one accepts the results of the recently published Long-Term Oxygen Treatment Trial, this means that 84.3% (393/466) would be eligible for oxygen discontinuation.
The Ann ATS study provides a blueprint for how we might improve these dismal numbers. There were five separate sites reviewed in their paper. At one site, reassessment occurred in 78.5% of STOT patients and 100% had oxygen discontinued when appropriate. What was their secret? An automatic alert system and a dedicated clinic, coordinator, and respiratory therapist. Also, among the 124 patients who had a full reassessment and no longer qualified for oxygen, 86.3% had it discontinued.
There are countless reasons why STOT is common, but discontinuation is not. Most COPD exacerbations are managed by nonpulmonologists on general medicine wards prior to discharge. In my experience, these physicians are reluctant to release a patient with exertional hypoxia without STOT. They also assume that the pulmonary clinic will do its job during the obligatory outpatient follow-up appointment they schedule with us. At the follow-up, the patient and physician are reluctant to stop therapy because of psychological dependence and therapeutic overconfidence, respectively.
In summary, STOT following hospitalization comprises the majority of all oxygen prescriptions. Historically, the United States provides far more oxygen than other developed countries, and only CMS reimbursement changes have bent the “overprescription” curve. The Ann ATS study shows that a well-designed program at the hospital level can put oxygen decisions back in the hands of providers.
Let’s “choose wisely” and follow what works, or we’ll have only ourselves to blame when reimbursement decisions are taken out of our hands.
A version of this article first appeared on Medscape.com.
List of COVID-19 high-risk comorbidities expanded
The list of medical according to the Centers for Disease Control and Prevention.
The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.
On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”
Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.
The list of medical according to the Centers for Disease Control and Prevention.
The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.
On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”
Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.
The list of medical according to the Centers for Disease Control and Prevention.
The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.
On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”
Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.
New guidelines on antibiotic prescribing focus on shorter courses
An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.
The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.
“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.
According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.
“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”
The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.
“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”
The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.
“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.
Another common reason is habit.
“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”
The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.
“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
Acute bronchitis with COPD exacerbations
Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
Community-acquired pneumonia
The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.
Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
UTIs: Uncomplicated cystitis and pyelonephritis
For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.
This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
Cellulitis
MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.
This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
Continuing to get the message out
Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.
“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”
Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.
Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.
The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.
The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.
“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.
According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.
“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”
The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.
“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”
The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.
“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.
Another common reason is habit.
“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”
The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.
“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
Acute bronchitis with COPD exacerbations
Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
Community-acquired pneumonia
The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.
Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
UTIs: Uncomplicated cystitis and pyelonephritis
For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.
This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
Cellulitis
MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.
This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
Continuing to get the message out
Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.
“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”
Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.
Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.
The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.
The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.
“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.
According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.
“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”
The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.
“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”
The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.
“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.
Another common reason is habit.
“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”
The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.
“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
Acute bronchitis with COPD exacerbations
Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
Community-acquired pneumonia
The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.
Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
UTIs: Uncomplicated cystitis and pyelonephritis
For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.
This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
Cellulitis
MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.
This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
Continuing to get the message out
Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.
“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”
Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.
Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.
The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinically important deterioration predicts poor future outcomes in COPD
Patients with COPD may benefit from stepped-up treatment of short-term disease progression with triple therapy to stave off longer-term exacerbations and all-cause mortality.
, a study based on data from more than 10,000 patients has shown.
For this study, clinically important deterioration (CID) as a measure of COPD is defined as a combination of change in lung function and/or health status, or a first acute moderate to severe COPD exacerbation, wrote MeiLan K. Han, MD, of the University of Michigan, Ann Arbor, and colleagues.
The study was published in ERJ Open Research The investigators analyzed data from the IMPACT trial, a phase III, double-blind, multicenter, 52-week study of symptomatic COPD patients aged 40 years and older.
In the intent-to-treat population, patients with symptomatic COPD and at least one moderate or severe exacerbation in the past year were randomized to a once-daily dose of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg (4,151 patients); FF/VI 100/25 mcg (4,134 patients); or UMEC/VI 62.5/25 mcg using a single dry-power inhaler (2,070 patients).
The researchers explored both the prognostic value of a CID event on future clinical outcomes and the impact of single-inhaler triple versus dual therapy on reducing CID risk. CID was defined as any of the following: moderate/severe exacerbation; deterioration in lung function (defined as a decrease of 100 mL or more from baseline in trough forced expiratory volume per second); or deterioration in health status based on increases of 4.0 units or more on the St George’s Respiratory Questionnaire (SGRQ) total score or 2.0 units or more on the COPD Assessment Test (CAT) score.
Overall, patients with a CID by 28 weeks had significantly increased exacerbation rates after week 28, as well as smaller improvements in lung function and health status at week 52 (P < .001 for all). In addition, CID patients had an increased risk of all-cause mortality after 28 weeks, compared with patients without CID. However, FF/UMEC/VI significantly reduced CID risk, compared with dual therapies, the researchers noted.
Based on the CID SGRQ definition, patients with CID had a 75% increase in moderate to severe exacerbations by week 28 and a 96% in severe exacerbations over weeks 29-52. The increases were similar using the CID CAT definition (72% and 91%, respectively).
Patients with CID also showed significantly reduced improvements in both lung function and health status after 1 year, and a significantly increased risk of all-cause mortality compared to patients without CID.
In comparing triple vs. double therapies, FF/UMEC/VI patients showed significant reductions in CID risk by 52 weeks, compared with patients treated with FF/VI and UMEC/VI. This difference was true across all subgroups, except for the subgroup of patients who were on long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy prior to screening, the researchers said.
In addition, “treatment effect was greater at higher blood eosinophil counts for FF/UMEC/VI versus UMEC/VI,” the researchers noted.
The study findings were limited by several factors including the lack of CID as a primary endpoint, the relatively short 5-month follow-up period, and the use of a symptomatic patient population with an established risk of exacerbation, which could limit generalizability, the researchers noted. However, the findings support the value of preventing short-term CID and adding inhaled corticosteroids (ICS) or bronchodilation for patients in this study population, they said.
Data may help drive tailored treatments
“This study is a post hoc analysis of data from the IMPACT trial, an RCT examining triple therapy vs ICS/LABA vs LABA/LAMA,” Dr. Han, lead and corresponding author, said in an interview. “In this particular paper, we conducted a treatment independent analysis examining individuals who experienced clinically important deteriorations at week 28 and then compared outcomes at week 52 based on CID status at week 28. Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52, and increased risk of all-cause mortality after week 28 versus patients who were CID free,” she emphasized. “We also saw that FF/UMEC/VI significantly reduced CID risk versus dual therapies.” These data suggest that shorter-term changes are associated with longer term outcomes, and provide important information both for the purposes of clinical trials design as well as patient clinical assessments, she added.
Dr. Han said she was not surprised by the findings. “I think these results are consistent with prior analyses but suggest that short-term outcomes relate to longer-term ones,” she said. However, she stressed the need for individualized treatment.
“While there are relationships between symptoms, lung function, and exacerbations as demonstrated by these analyses, in any individual patient sometimes these three disease axes do not perfectly align,” she explained. Dr. Han’s main message for clinicians in practice is that optimization of triple therapy in patients with severe disease and high risk for exacerbations was associated not only with short-term improvements in symptoms and lung function, but also with longer-term reductions in exacerbations and mortality.
As for additional research, prospective studies using CID as a primary or secondary outcome would help validate the composite outcome in this study, as regulatory agencies have been slow to adopt composite outcomes, Dr. Han said.
Dr. Han disclosed relationships with GlaxoSmithKline, which funded the study, as well as AstraZeneca, Boehringer Ingelheim, Novartis, Sunovion, Mylan, Merck, and Verona.
Patients with COPD may benefit from stepped-up treatment of short-term disease progression with triple therapy to stave off longer-term exacerbations and all-cause mortality.
, a study based on data from more than 10,000 patients has shown.
For this study, clinically important deterioration (CID) as a measure of COPD is defined as a combination of change in lung function and/or health status, or a first acute moderate to severe COPD exacerbation, wrote MeiLan K. Han, MD, of the University of Michigan, Ann Arbor, and colleagues.
The study was published in ERJ Open Research The investigators analyzed data from the IMPACT trial, a phase III, double-blind, multicenter, 52-week study of symptomatic COPD patients aged 40 years and older.
In the intent-to-treat population, patients with symptomatic COPD and at least one moderate or severe exacerbation in the past year were randomized to a once-daily dose of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg (4,151 patients); FF/VI 100/25 mcg (4,134 patients); or UMEC/VI 62.5/25 mcg using a single dry-power inhaler (2,070 patients).
The researchers explored both the prognostic value of a CID event on future clinical outcomes and the impact of single-inhaler triple versus dual therapy on reducing CID risk. CID was defined as any of the following: moderate/severe exacerbation; deterioration in lung function (defined as a decrease of 100 mL or more from baseline in trough forced expiratory volume per second); or deterioration in health status based on increases of 4.0 units or more on the St George’s Respiratory Questionnaire (SGRQ) total score or 2.0 units or more on the COPD Assessment Test (CAT) score.
Overall, patients with a CID by 28 weeks had significantly increased exacerbation rates after week 28, as well as smaller improvements in lung function and health status at week 52 (P < .001 for all). In addition, CID patients had an increased risk of all-cause mortality after 28 weeks, compared with patients without CID. However, FF/UMEC/VI significantly reduced CID risk, compared with dual therapies, the researchers noted.
Based on the CID SGRQ definition, patients with CID had a 75% increase in moderate to severe exacerbations by week 28 and a 96% in severe exacerbations over weeks 29-52. The increases were similar using the CID CAT definition (72% and 91%, respectively).
Patients with CID also showed significantly reduced improvements in both lung function and health status after 1 year, and a significantly increased risk of all-cause mortality compared to patients without CID.
In comparing triple vs. double therapies, FF/UMEC/VI patients showed significant reductions in CID risk by 52 weeks, compared with patients treated with FF/VI and UMEC/VI. This difference was true across all subgroups, except for the subgroup of patients who were on long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy prior to screening, the researchers said.
In addition, “treatment effect was greater at higher blood eosinophil counts for FF/UMEC/VI versus UMEC/VI,” the researchers noted.
The study findings were limited by several factors including the lack of CID as a primary endpoint, the relatively short 5-month follow-up period, and the use of a symptomatic patient population with an established risk of exacerbation, which could limit generalizability, the researchers noted. However, the findings support the value of preventing short-term CID and adding inhaled corticosteroids (ICS) or bronchodilation for patients in this study population, they said.
Data may help drive tailored treatments
“This study is a post hoc analysis of data from the IMPACT trial, an RCT examining triple therapy vs ICS/LABA vs LABA/LAMA,” Dr. Han, lead and corresponding author, said in an interview. “In this particular paper, we conducted a treatment independent analysis examining individuals who experienced clinically important deteriorations at week 28 and then compared outcomes at week 52 based on CID status at week 28. Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52, and increased risk of all-cause mortality after week 28 versus patients who were CID free,” she emphasized. “We also saw that FF/UMEC/VI significantly reduced CID risk versus dual therapies.” These data suggest that shorter-term changes are associated with longer term outcomes, and provide important information both for the purposes of clinical trials design as well as patient clinical assessments, she added.
Dr. Han said she was not surprised by the findings. “I think these results are consistent with prior analyses but suggest that short-term outcomes relate to longer-term ones,” she said. However, she stressed the need for individualized treatment.
“While there are relationships between symptoms, lung function, and exacerbations as demonstrated by these analyses, in any individual patient sometimes these three disease axes do not perfectly align,” she explained. Dr. Han’s main message for clinicians in practice is that optimization of triple therapy in patients with severe disease and high risk for exacerbations was associated not only with short-term improvements in symptoms and lung function, but also with longer-term reductions in exacerbations and mortality.
As for additional research, prospective studies using CID as a primary or secondary outcome would help validate the composite outcome in this study, as regulatory agencies have been slow to adopt composite outcomes, Dr. Han said.
Dr. Han disclosed relationships with GlaxoSmithKline, which funded the study, as well as AstraZeneca, Boehringer Ingelheim, Novartis, Sunovion, Mylan, Merck, and Verona.
Patients with COPD may benefit from stepped-up treatment of short-term disease progression with triple therapy to stave off longer-term exacerbations and all-cause mortality.
, a study based on data from more than 10,000 patients has shown.
For this study, clinically important deterioration (CID) as a measure of COPD is defined as a combination of change in lung function and/or health status, or a first acute moderate to severe COPD exacerbation, wrote MeiLan K. Han, MD, of the University of Michigan, Ann Arbor, and colleagues.
The study was published in ERJ Open Research The investigators analyzed data from the IMPACT trial, a phase III, double-blind, multicenter, 52-week study of symptomatic COPD patients aged 40 years and older.
In the intent-to-treat population, patients with symptomatic COPD and at least one moderate or severe exacerbation in the past year were randomized to a once-daily dose of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg (4,151 patients); FF/VI 100/25 mcg (4,134 patients); or UMEC/VI 62.5/25 mcg using a single dry-power inhaler (2,070 patients).
The researchers explored both the prognostic value of a CID event on future clinical outcomes and the impact of single-inhaler triple versus dual therapy on reducing CID risk. CID was defined as any of the following: moderate/severe exacerbation; deterioration in lung function (defined as a decrease of 100 mL or more from baseline in trough forced expiratory volume per second); or deterioration in health status based on increases of 4.0 units or more on the St George’s Respiratory Questionnaire (SGRQ) total score or 2.0 units or more on the COPD Assessment Test (CAT) score.
Overall, patients with a CID by 28 weeks had significantly increased exacerbation rates after week 28, as well as smaller improvements in lung function and health status at week 52 (P < .001 for all). In addition, CID patients had an increased risk of all-cause mortality after 28 weeks, compared with patients without CID. However, FF/UMEC/VI significantly reduced CID risk, compared with dual therapies, the researchers noted.
Based on the CID SGRQ definition, patients with CID had a 75% increase in moderate to severe exacerbations by week 28 and a 96% in severe exacerbations over weeks 29-52. The increases were similar using the CID CAT definition (72% and 91%, respectively).
Patients with CID also showed significantly reduced improvements in both lung function and health status after 1 year, and a significantly increased risk of all-cause mortality compared to patients without CID.
In comparing triple vs. double therapies, FF/UMEC/VI patients showed significant reductions in CID risk by 52 weeks, compared with patients treated with FF/VI and UMEC/VI. This difference was true across all subgroups, except for the subgroup of patients who were on long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy prior to screening, the researchers said.
In addition, “treatment effect was greater at higher blood eosinophil counts for FF/UMEC/VI versus UMEC/VI,” the researchers noted.
The study findings were limited by several factors including the lack of CID as a primary endpoint, the relatively short 5-month follow-up period, and the use of a symptomatic patient population with an established risk of exacerbation, which could limit generalizability, the researchers noted. However, the findings support the value of preventing short-term CID and adding inhaled corticosteroids (ICS) or bronchodilation for patients in this study population, they said.
Data may help drive tailored treatments
“This study is a post hoc analysis of data from the IMPACT trial, an RCT examining triple therapy vs ICS/LABA vs LABA/LAMA,” Dr. Han, lead and corresponding author, said in an interview. “In this particular paper, we conducted a treatment independent analysis examining individuals who experienced clinically important deteriorations at week 28 and then compared outcomes at week 52 based on CID status at week 28. Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52, and increased risk of all-cause mortality after week 28 versus patients who were CID free,” she emphasized. “We also saw that FF/UMEC/VI significantly reduced CID risk versus dual therapies.” These data suggest that shorter-term changes are associated with longer term outcomes, and provide important information both for the purposes of clinical trials design as well as patient clinical assessments, she added.
Dr. Han said she was not surprised by the findings. “I think these results are consistent with prior analyses but suggest that short-term outcomes relate to longer-term ones,” she said. However, she stressed the need for individualized treatment.
“While there are relationships between symptoms, lung function, and exacerbations as demonstrated by these analyses, in any individual patient sometimes these three disease axes do not perfectly align,” she explained. Dr. Han’s main message for clinicians in practice is that optimization of triple therapy in patients with severe disease and high risk for exacerbations was associated not only with short-term improvements in symptoms and lung function, but also with longer-term reductions in exacerbations and mortality.
As for additional research, prospective studies using CID as a primary or secondary outcome would help validate the composite outcome in this study, as regulatory agencies have been slow to adopt composite outcomes, Dr. Han said.
Dr. Han disclosed relationships with GlaxoSmithKline, which funded the study, as well as AstraZeneca, Boehringer Ingelheim, Novartis, Sunovion, Mylan, Merck, and Verona.
FROM ERJ OPEN RESEARCH
Cannabinoids may pose death risk for older patients with COPD
, compared with nonusers, findings from a large study have shown.
Synthetic cannabinoids drugs, such as nabilone and dronabinol, have been approved by the Food and Drug Administration for nausea and vomiting caused by chemotherapy. But their off-label use by adults with COPD to help manage chronic musculoskeletal pain, insomnia, and refractory dyspnea is on the rise, wrote Nicholas T. Vozoris, MD, of the University of Toronto and colleagues.
Cannabinoids may actually contribute to negative respiratory outcomes among individuals with COPD through several possible mechanisms including causing sedation, inducing anxiety, and provoking respiratory muscle weakness, they said.
“Possible adverse respiratory effects of cannabinoids may occur with greater likelihood among older adults (in whom COPD is more prevalent), as this group is known to less efficiently metabolise drugs,” they noted.
In a retrospective, population-based cohort study published in Thorax the researchers identified 185,876 adults aged 66 years and older with COPD using health administrative database information from 2006 to 2016. New cannabinoid users (those starting nabilone or dronabinol) were matched with control nonusers (defined as new users of noncannabinoid drugs). Individuals receiving palliative care, or having a diagnosis of cancer or HIV, were excluded because these are settings where synthetic cannabinoids may be prescribed for nausea or vomiting, and these patients are more likely to be in a poorer state of health.
Overall, new cannabinoid users had significantly higher all-cause mortality rates, compared with nonusers (hazard ratio, 1.64). The effects was greater in high-dose users.
Daniel R. Ouellette, MD, associate professor of medicine at Wayne State University and a senior staff physician at Henry Ford Hospital, both in Detroit, commented that this study has value for clinicians. “Many states are liberalizing cannabinoid use, and it is important to know the health effects of this type of drug on patients with chronic respiratory disease,” he noted. “The study is somewhat surprising. While one might have expected adverse consequences in patients with COPD who inhaled smoke from cannabinoids, it is somewhat unexpected that oral use would be associated with adverse consequences.” He added, “Pain in older adults is a complex problem. Cannabinoids are often recommended for pain in the general community, but pain per se is not a primary symptom for most patients with COPD from their respiratory problems. Physicians treating patients with COPD should diagnose the cause of the pain and provide appropriate treatment.”
Dose makes a difference
All-cause mortality increased by 231% and hospitalization for COPD or pneumonia increased by 178% among new users of higher-dose cannabinoids, compared with nonusers. Higher dose was defined in this study as more than 1.5mg/day of nabilone. No significant differences appeared in new users vs. nonusers in hospitalization for COPD or pneumonia at lower doses, and no significant differences appeared overall in outpatient respiratory exacerbations, emergency department visits for COPD or pneumonia, or COPD- or pneumonia-related mortality.
Potential limitations and implications
“The fact that COPD- or pneumonia-related mortality was not observed to occur with significantly greater rates among cannabinoid users with COPD may suggest that the increased all-cause mortality finding was not being driven by adverse respiratory-related drug effects, as we hypothesized, and instead was possibly a result of unresolved confounding,” the researchers noted.
The study findings were limited by several factors including the inability to prove causation in an observational study, and the potential for confounding based on unmeasured differences between cannabinoid users and nonusers, the researchers said. “Our findings may not be generalizable to all individuals with COPD, as our study included only those aged 66 years and older, and our COPD identification algorithm, while highly specific, had modest sensitivity,” they added. However, the results were strengthened by the large study population and suggest that cannabinoids are not contraindicated for older adults with COPD, the researchers said. “There can be legitimate reasons for using cannabinoids in this population, such as to help treat chemotherapy-related nausea and vomiting, and possibly for end-of-life care,” they emphasized.
The study findings serve to inform clinicians of the significantly increased mortality risk when older adults with COPD initiate cannabinoids, and “this information should be discussed with patients and incorporated in prescribing decision-making and management plans,” along with consideration of using lower doses when possible to minimize adverse events, they concluded.
The study was supported by The Lung Association – Ontario Grant Review/Grant-In-Aid. The researchers had no financial conflicts to disclose.
, compared with nonusers, findings from a large study have shown.
Synthetic cannabinoids drugs, such as nabilone and dronabinol, have been approved by the Food and Drug Administration for nausea and vomiting caused by chemotherapy. But their off-label use by adults with COPD to help manage chronic musculoskeletal pain, insomnia, and refractory dyspnea is on the rise, wrote Nicholas T. Vozoris, MD, of the University of Toronto and colleagues.
Cannabinoids may actually contribute to negative respiratory outcomes among individuals with COPD through several possible mechanisms including causing sedation, inducing anxiety, and provoking respiratory muscle weakness, they said.
“Possible adverse respiratory effects of cannabinoids may occur with greater likelihood among older adults (in whom COPD is more prevalent), as this group is known to less efficiently metabolise drugs,” they noted.
In a retrospective, population-based cohort study published in Thorax the researchers identified 185,876 adults aged 66 years and older with COPD using health administrative database information from 2006 to 2016. New cannabinoid users (those starting nabilone or dronabinol) were matched with control nonusers (defined as new users of noncannabinoid drugs). Individuals receiving palliative care, or having a diagnosis of cancer or HIV, were excluded because these are settings where synthetic cannabinoids may be prescribed for nausea or vomiting, and these patients are more likely to be in a poorer state of health.
Overall, new cannabinoid users had significantly higher all-cause mortality rates, compared with nonusers (hazard ratio, 1.64). The effects was greater in high-dose users.
Daniel R. Ouellette, MD, associate professor of medicine at Wayne State University and a senior staff physician at Henry Ford Hospital, both in Detroit, commented that this study has value for clinicians. “Many states are liberalizing cannabinoid use, and it is important to know the health effects of this type of drug on patients with chronic respiratory disease,” he noted. “The study is somewhat surprising. While one might have expected adverse consequences in patients with COPD who inhaled smoke from cannabinoids, it is somewhat unexpected that oral use would be associated with adverse consequences.” He added, “Pain in older adults is a complex problem. Cannabinoids are often recommended for pain in the general community, but pain per se is not a primary symptom for most patients with COPD from their respiratory problems. Physicians treating patients with COPD should diagnose the cause of the pain and provide appropriate treatment.”
Dose makes a difference
All-cause mortality increased by 231% and hospitalization for COPD or pneumonia increased by 178% among new users of higher-dose cannabinoids, compared with nonusers. Higher dose was defined in this study as more than 1.5mg/day of nabilone. No significant differences appeared in new users vs. nonusers in hospitalization for COPD or pneumonia at lower doses, and no significant differences appeared overall in outpatient respiratory exacerbations, emergency department visits for COPD or pneumonia, or COPD- or pneumonia-related mortality.
Potential limitations and implications
“The fact that COPD- or pneumonia-related mortality was not observed to occur with significantly greater rates among cannabinoid users with COPD may suggest that the increased all-cause mortality finding was not being driven by adverse respiratory-related drug effects, as we hypothesized, and instead was possibly a result of unresolved confounding,” the researchers noted.
The study findings were limited by several factors including the inability to prove causation in an observational study, and the potential for confounding based on unmeasured differences between cannabinoid users and nonusers, the researchers said. “Our findings may not be generalizable to all individuals with COPD, as our study included only those aged 66 years and older, and our COPD identification algorithm, while highly specific, had modest sensitivity,” they added. However, the results were strengthened by the large study population and suggest that cannabinoids are not contraindicated for older adults with COPD, the researchers said. “There can be legitimate reasons for using cannabinoids in this population, such as to help treat chemotherapy-related nausea and vomiting, and possibly for end-of-life care,” they emphasized.
The study findings serve to inform clinicians of the significantly increased mortality risk when older adults with COPD initiate cannabinoids, and “this information should be discussed with patients and incorporated in prescribing decision-making and management plans,” along with consideration of using lower doses when possible to minimize adverse events, they concluded.
The study was supported by The Lung Association – Ontario Grant Review/Grant-In-Aid. The researchers had no financial conflicts to disclose.
, compared with nonusers, findings from a large study have shown.
Synthetic cannabinoids drugs, such as nabilone and dronabinol, have been approved by the Food and Drug Administration for nausea and vomiting caused by chemotherapy. But their off-label use by adults with COPD to help manage chronic musculoskeletal pain, insomnia, and refractory dyspnea is on the rise, wrote Nicholas T. Vozoris, MD, of the University of Toronto and colleagues.
Cannabinoids may actually contribute to negative respiratory outcomes among individuals with COPD through several possible mechanisms including causing sedation, inducing anxiety, and provoking respiratory muscle weakness, they said.
“Possible adverse respiratory effects of cannabinoids may occur with greater likelihood among older adults (in whom COPD is more prevalent), as this group is known to less efficiently metabolise drugs,” they noted.
In a retrospective, population-based cohort study published in Thorax the researchers identified 185,876 adults aged 66 years and older with COPD using health administrative database information from 2006 to 2016. New cannabinoid users (those starting nabilone or dronabinol) were matched with control nonusers (defined as new users of noncannabinoid drugs). Individuals receiving palliative care, or having a diagnosis of cancer or HIV, were excluded because these are settings where synthetic cannabinoids may be prescribed for nausea or vomiting, and these patients are more likely to be in a poorer state of health.
Overall, new cannabinoid users had significantly higher all-cause mortality rates, compared with nonusers (hazard ratio, 1.64). The effects was greater in high-dose users.
Daniel R. Ouellette, MD, associate professor of medicine at Wayne State University and a senior staff physician at Henry Ford Hospital, both in Detroit, commented that this study has value for clinicians. “Many states are liberalizing cannabinoid use, and it is important to know the health effects of this type of drug on patients with chronic respiratory disease,” he noted. “The study is somewhat surprising. While one might have expected adverse consequences in patients with COPD who inhaled smoke from cannabinoids, it is somewhat unexpected that oral use would be associated with adverse consequences.” He added, “Pain in older adults is a complex problem. Cannabinoids are often recommended for pain in the general community, but pain per se is not a primary symptom for most patients with COPD from their respiratory problems. Physicians treating patients with COPD should diagnose the cause of the pain and provide appropriate treatment.”
Dose makes a difference
All-cause mortality increased by 231% and hospitalization for COPD or pneumonia increased by 178% among new users of higher-dose cannabinoids, compared with nonusers. Higher dose was defined in this study as more than 1.5mg/day of nabilone. No significant differences appeared in new users vs. nonusers in hospitalization for COPD or pneumonia at lower doses, and no significant differences appeared overall in outpatient respiratory exacerbations, emergency department visits for COPD or pneumonia, or COPD- or pneumonia-related mortality.
Potential limitations and implications
“The fact that COPD- or pneumonia-related mortality was not observed to occur with significantly greater rates among cannabinoid users with COPD may suggest that the increased all-cause mortality finding was not being driven by adverse respiratory-related drug effects, as we hypothesized, and instead was possibly a result of unresolved confounding,” the researchers noted.
The study findings were limited by several factors including the inability to prove causation in an observational study, and the potential for confounding based on unmeasured differences between cannabinoid users and nonusers, the researchers said. “Our findings may not be generalizable to all individuals with COPD, as our study included only those aged 66 years and older, and our COPD identification algorithm, while highly specific, had modest sensitivity,” they added. However, the results were strengthened by the large study population and suggest that cannabinoids are not contraindicated for older adults with COPD, the researchers said. “There can be legitimate reasons for using cannabinoids in this population, such as to help treat chemotherapy-related nausea and vomiting, and possibly for end-of-life care,” they emphasized.
The study findings serve to inform clinicians of the significantly increased mortality risk when older adults with COPD initiate cannabinoids, and “this information should be discussed with patients and incorporated in prescribing decision-making and management plans,” along with consideration of using lower doses when possible to minimize adverse events, they concluded.
The study was supported by The Lung Association – Ontario Grant Review/Grant-In-Aid. The researchers had no financial conflicts to disclose.
FROM THORAX
CDC: Vaccinated people can gather indoors without masks
People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.
“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”
According to the new guidance, people who are at least 2 weeks out from their last dose can:
- Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
- Avoid quarantine and testing following exposure to someone if they remain asymptomatic.
However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:
- Wear masks and physically distance in public settings and around people at high risk for severe disease.
- Wear masks and physically distance when visiting unvaccinated people from more than one household.
- Avoid medium- and large-sized gatherings.
- Avoid travel.
People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.
“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”
Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.
"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.
But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”
For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”
Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.
“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”
A version of this article first appeared on WebMD.com.
People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.
“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”
According to the new guidance, people who are at least 2 weeks out from their last dose can:
- Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
- Avoid quarantine and testing following exposure to someone if they remain asymptomatic.
However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:
- Wear masks and physically distance in public settings and around people at high risk for severe disease.
- Wear masks and physically distance when visiting unvaccinated people from more than one household.
- Avoid medium- and large-sized gatherings.
- Avoid travel.
People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.
“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”
Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.
"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.
But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”
For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”
Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.
“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”
A version of this article first appeared on WebMD.com.
People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.
“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”
According to the new guidance, people who are at least 2 weeks out from their last dose can:
- Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
- Avoid quarantine and testing following exposure to someone if they remain asymptomatic.
However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:
- Wear masks and physically distance in public settings and around people at high risk for severe disease.
- Wear masks and physically distance when visiting unvaccinated people from more than one household.
- Avoid medium- and large-sized gatherings.
- Avoid travel.
People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.
“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”
Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.
"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.
But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”
For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”
Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.
“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”
A version of this article first appeared on WebMD.com.
Asthma-COPD overlap linked to occupational pollutants
The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“ features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.
The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”
“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”
A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”
In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.
Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.
Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”
While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.
To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”
Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”
For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.
Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.
The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“ features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.
The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”
“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”
A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”
In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.
Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.
Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”
While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.
To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”
Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”
For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.
Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.
The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“ features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.
The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”
“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”
A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”
In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.
Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.
Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”
While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.
To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”
Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”
For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.
Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.
FROM AAAAI 2021
Patients with asthma and COPD lost ground in accessing care
Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.
The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.
“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.
Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
Insurance coverage up, patients losing ground
During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.
For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.
Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.
After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.
For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.
So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.
“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
Insurance is no guarantee to access
Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.
“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.
At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.
Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.
“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.
“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”
The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.
Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.
The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.
“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.
Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
Insurance coverage up, patients losing ground
During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.
For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.
Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.
After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.
For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.
So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.
“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
Insurance is no guarantee to access
Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.
“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.
At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.
Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.
“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.
“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”
The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.
Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.
The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.
“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.
Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
Insurance coverage up, patients losing ground
During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.
For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.
Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.
After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.
For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.
So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.
“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
Insurance is no guarantee to access
Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.
“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.
At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.
Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.
“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.
“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”
The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.
FROM CHEST
Inhaled hyaluronan may bring sigh of relief to COPD patients
(COPD), findings of a new study suggest.
HMW-HA was associated with a significantly shorter duration of noninvasive positive-pressure ventilation (NIPPV), lower systemic inflammatory markers, and lower measured peak airway pressure, compared with placebo, reported lead author Flavia Galdi, MD, of Campus Bio-Medico University Hospital, Rome, and colleagues.
“HMW-HA is a naturally occurring sugar that is abundant in the extracellular matrix, including in the lung,” the investigators wrote in Respiratory Research. “[It] has been used routinely, together with hypertonic saline, in cystic fibrosis patients [for several years] with no reported side effects; rather, it improves tolerability and decreases the need for bronchodilators in these patients.”
According to Robert A. Sandhaus, MD, PhD, FCCP, of National Jewish Health, Denver, the role of hyaluronan in lung disease was first recognized decades ago.
“Data stretching back into the 1970s has identified decreases in hyaluronan content in emphysematous lung tissue, protection of lung connective tissue from proteolysis by hyaluronan, and potential therapeutic roles for hyaluronan in a variety of disease, especially of the lungs,” he said in an interview.
For patients with COPD, treatment with HMW-HA may provide benefit by counteracting an imbalance in diseased lung tissue, wrote Dr. Galdi and colleagues.
“Emerging evidence suggests that imbalance between declining HMW-HA levels, and increasing smaller fragments of hyaluronan may contribute to chronic airway disease pathogenesis,” they wrote. “This has led to the hypothesis that exogenous supplementation of HMW-HA may restore hyaluronan homeostasis in favor of undegraded molecules, inhibit inflammation and loss of lung function, and ameliorate COPD progression.”
To test this hypothesis, the investigators screened 44 patients with a history of acute exacerbations of COPD necessitating NIPPV, ultimately excluding 3 patients because of heart failure. Following 1:1 randomization, 20 patients received HMW-HA while 21 received placebo, each twice daily, in conjunction with NIPPV and standard medical therapy. Treatment continued until NIPPV failure or liberation from NIPPV. Most patients received NIPPV in the hospital; however, home/chronic NIPPV was given to four patients in the placebo group and three patients in the HMW-HA group.
The primary outcome was duration of NIPPV. Secondary outcomes included markers of systemic inflammation associated with acute exacerbations of COPD and respiratory physiology parameters. Adverse events were also reported.
Results showed that patients treated with HMW-HA were liberated sooner from NIPPV than were those who received placebo (mean, 5.2 vs 6.4 days; P < .037). Similarly, patients in the HMW-HA group had significantly shorter hospital stay, on average, than those in the placebo group (mean, 7.2 vs 10.2 days; P = .039). Median values followed a similar pattern.
“These data suggest that HMW-HA shortened the duration of acute respiratory failure, need for NIPPV and, consequently, hospital length of stay in these patients,” the investigators wrote.
Secondary outcomes further supported these therapeutic benefits. Compared with placebo, HMW-HA was associated with significantly lower peak pressure and greater improvements in both pCO2/FiO2 ratio and inflammatory markers. No adverse events were reported.
Further analyses involving human bronchial epithelial cell cultures offered some mechanistic insight. Using micro-optical coherence tomography imaging, the investigators found that HMW-HA treatment was associated with “a prominent effect on mucociliary transport” in cell cultures derived from COPD patients and in healthy nonsmoker cell cultures exposed to cigarette smoke extract.
“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” the investigators concluded, noting a “clinically meaningful salutary effect” on duration of NIPPV.
Dr. Galdi and colleagues went on to predict that benefits in a real-world patient population could be even more meaningful.
“Since the serum samples were collected at the end of NIPPV, HMW-HA–treated patients were on average sampled a day earlier than placebo-treated patients (because they were liberated from NIPPV a day earlier on average),” the investigators wrote. “Thus, HMW-HA treatment effects may have been underestimated in our study.”
According to Dr. Sandhaus, “The current report, while a relatively small single-center study, is well controlled and the results suggest that inhaled hyaluronan decreased time on noninvasive ventilation, decreased hospital stay duration, and decreased some mediators of inflammation.”
He also suggested that HMW-HA may have a role in the prophylactic setting.
“The limitations of this pilot study are appropriately explored by the authors but do not dampen the exciting possibility that this therapeutic approach may hold promise not only in severe exacerbations of COPD but potentially for the prevention of such exacerbations,” Dr. Sandhaus said.
Jerome O. Cantor, MD, FCCP, of St. John’s University, New York, who previously conducted a pilot study for using lower molecular weight hyaluronan in COPD and published a review on the subject, said that more studies are necessary.
“Further clinical trials are needed to better determine the role of hyaluronan as an adjunct to existing therapies for COPD exacerbations,” he said.
The study was supported by the National Institutes of Health. The investigators and Dr. Sandhaus declared no conflicts of interest. Dr. Cantor disclosed a relationship with MatRx Therapeutics.
(COPD), findings of a new study suggest.
HMW-HA was associated with a significantly shorter duration of noninvasive positive-pressure ventilation (NIPPV), lower systemic inflammatory markers, and lower measured peak airway pressure, compared with placebo, reported lead author Flavia Galdi, MD, of Campus Bio-Medico University Hospital, Rome, and colleagues.
“HMW-HA is a naturally occurring sugar that is abundant in the extracellular matrix, including in the lung,” the investigators wrote in Respiratory Research. “[It] has been used routinely, together with hypertonic saline, in cystic fibrosis patients [for several years] with no reported side effects; rather, it improves tolerability and decreases the need for bronchodilators in these patients.”
According to Robert A. Sandhaus, MD, PhD, FCCP, of National Jewish Health, Denver, the role of hyaluronan in lung disease was first recognized decades ago.
“Data stretching back into the 1970s has identified decreases in hyaluronan content in emphysematous lung tissue, protection of lung connective tissue from proteolysis by hyaluronan, and potential therapeutic roles for hyaluronan in a variety of disease, especially of the lungs,” he said in an interview.
For patients with COPD, treatment with HMW-HA may provide benefit by counteracting an imbalance in diseased lung tissue, wrote Dr. Galdi and colleagues.
“Emerging evidence suggests that imbalance between declining HMW-HA levels, and increasing smaller fragments of hyaluronan may contribute to chronic airway disease pathogenesis,” they wrote. “This has led to the hypothesis that exogenous supplementation of HMW-HA may restore hyaluronan homeostasis in favor of undegraded molecules, inhibit inflammation and loss of lung function, and ameliorate COPD progression.”
To test this hypothesis, the investigators screened 44 patients with a history of acute exacerbations of COPD necessitating NIPPV, ultimately excluding 3 patients because of heart failure. Following 1:1 randomization, 20 patients received HMW-HA while 21 received placebo, each twice daily, in conjunction with NIPPV and standard medical therapy. Treatment continued until NIPPV failure or liberation from NIPPV. Most patients received NIPPV in the hospital; however, home/chronic NIPPV was given to four patients in the placebo group and three patients in the HMW-HA group.
The primary outcome was duration of NIPPV. Secondary outcomes included markers of systemic inflammation associated with acute exacerbations of COPD and respiratory physiology parameters. Adverse events were also reported.
Results showed that patients treated with HMW-HA were liberated sooner from NIPPV than were those who received placebo (mean, 5.2 vs 6.4 days; P < .037). Similarly, patients in the HMW-HA group had significantly shorter hospital stay, on average, than those in the placebo group (mean, 7.2 vs 10.2 days; P = .039). Median values followed a similar pattern.
“These data suggest that HMW-HA shortened the duration of acute respiratory failure, need for NIPPV and, consequently, hospital length of stay in these patients,” the investigators wrote.
Secondary outcomes further supported these therapeutic benefits. Compared with placebo, HMW-HA was associated with significantly lower peak pressure and greater improvements in both pCO2/FiO2 ratio and inflammatory markers. No adverse events were reported.
Further analyses involving human bronchial epithelial cell cultures offered some mechanistic insight. Using micro-optical coherence tomography imaging, the investigators found that HMW-HA treatment was associated with “a prominent effect on mucociliary transport” in cell cultures derived from COPD patients and in healthy nonsmoker cell cultures exposed to cigarette smoke extract.
“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” the investigators concluded, noting a “clinically meaningful salutary effect” on duration of NIPPV.
Dr. Galdi and colleagues went on to predict that benefits in a real-world patient population could be even more meaningful.
“Since the serum samples were collected at the end of NIPPV, HMW-HA–treated patients were on average sampled a day earlier than placebo-treated patients (because they were liberated from NIPPV a day earlier on average),” the investigators wrote. “Thus, HMW-HA treatment effects may have been underestimated in our study.”
According to Dr. Sandhaus, “The current report, while a relatively small single-center study, is well controlled and the results suggest that inhaled hyaluronan decreased time on noninvasive ventilation, decreased hospital stay duration, and decreased some mediators of inflammation.”
He also suggested that HMW-HA may have a role in the prophylactic setting.
“The limitations of this pilot study are appropriately explored by the authors but do not dampen the exciting possibility that this therapeutic approach may hold promise not only in severe exacerbations of COPD but potentially for the prevention of such exacerbations,” Dr. Sandhaus said.
Jerome O. Cantor, MD, FCCP, of St. John’s University, New York, who previously conducted a pilot study for using lower molecular weight hyaluronan in COPD and published a review on the subject, said that more studies are necessary.
“Further clinical trials are needed to better determine the role of hyaluronan as an adjunct to existing therapies for COPD exacerbations,” he said.
The study was supported by the National Institutes of Health. The investigators and Dr. Sandhaus declared no conflicts of interest. Dr. Cantor disclosed a relationship with MatRx Therapeutics.
(COPD), findings of a new study suggest.
HMW-HA was associated with a significantly shorter duration of noninvasive positive-pressure ventilation (NIPPV), lower systemic inflammatory markers, and lower measured peak airway pressure, compared with placebo, reported lead author Flavia Galdi, MD, of Campus Bio-Medico University Hospital, Rome, and colleagues.
“HMW-HA is a naturally occurring sugar that is abundant in the extracellular matrix, including in the lung,” the investigators wrote in Respiratory Research. “[It] has been used routinely, together with hypertonic saline, in cystic fibrosis patients [for several years] with no reported side effects; rather, it improves tolerability and decreases the need for bronchodilators in these patients.”
According to Robert A. Sandhaus, MD, PhD, FCCP, of National Jewish Health, Denver, the role of hyaluronan in lung disease was first recognized decades ago.
“Data stretching back into the 1970s has identified decreases in hyaluronan content in emphysematous lung tissue, protection of lung connective tissue from proteolysis by hyaluronan, and potential therapeutic roles for hyaluronan in a variety of disease, especially of the lungs,” he said in an interview.
For patients with COPD, treatment with HMW-HA may provide benefit by counteracting an imbalance in diseased lung tissue, wrote Dr. Galdi and colleagues.
“Emerging evidence suggests that imbalance between declining HMW-HA levels, and increasing smaller fragments of hyaluronan may contribute to chronic airway disease pathogenesis,” they wrote. “This has led to the hypothesis that exogenous supplementation of HMW-HA may restore hyaluronan homeostasis in favor of undegraded molecules, inhibit inflammation and loss of lung function, and ameliorate COPD progression.”
To test this hypothesis, the investigators screened 44 patients with a history of acute exacerbations of COPD necessitating NIPPV, ultimately excluding 3 patients because of heart failure. Following 1:1 randomization, 20 patients received HMW-HA while 21 received placebo, each twice daily, in conjunction with NIPPV and standard medical therapy. Treatment continued until NIPPV failure or liberation from NIPPV. Most patients received NIPPV in the hospital; however, home/chronic NIPPV was given to four patients in the placebo group and three patients in the HMW-HA group.
The primary outcome was duration of NIPPV. Secondary outcomes included markers of systemic inflammation associated with acute exacerbations of COPD and respiratory physiology parameters. Adverse events were also reported.
Results showed that patients treated with HMW-HA were liberated sooner from NIPPV than were those who received placebo (mean, 5.2 vs 6.4 days; P < .037). Similarly, patients in the HMW-HA group had significantly shorter hospital stay, on average, than those in the placebo group (mean, 7.2 vs 10.2 days; P = .039). Median values followed a similar pattern.
“These data suggest that HMW-HA shortened the duration of acute respiratory failure, need for NIPPV and, consequently, hospital length of stay in these patients,” the investigators wrote.
Secondary outcomes further supported these therapeutic benefits. Compared with placebo, HMW-HA was associated with significantly lower peak pressure and greater improvements in both pCO2/FiO2 ratio and inflammatory markers. No adverse events were reported.
Further analyses involving human bronchial epithelial cell cultures offered some mechanistic insight. Using micro-optical coherence tomography imaging, the investigators found that HMW-HA treatment was associated with “a prominent effect on mucociliary transport” in cell cultures derived from COPD patients and in healthy nonsmoker cell cultures exposed to cigarette smoke extract.
“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” the investigators concluded, noting a “clinically meaningful salutary effect” on duration of NIPPV.
Dr. Galdi and colleagues went on to predict that benefits in a real-world patient population could be even more meaningful.
“Since the serum samples were collected at the end of NIPPV, HMW-HA–treated patients were on average sampled a day earlier than placebo-treated patients (because they were liberated from NIPPV a day earlier on average),” the investigators wrote. “Thus, HMW-HA treatment effects may have been underestimated in our study.”
According to Dr. Sandhaus, “The current report, while a relatively small single-center study, is well controlled and the results suggest that inhaled hyaluronan decreased time on noninvasive ventilation, decreased hospital stay duration, and decreased some mediators of inflammation.”
He also suggested that HMW-HA may have a role in the prophylactic setting.
“The limitations of this pilot study are appropriately explored by the authors but do not dampen the exciting possibility that this therapeutic approach may hold promise not only in severe exacerbations of COPD but potentially for the prevention of such exacerbations,” Dr. Sandhaus said.
Jerome O. Cantor, MD, FCCP, of St. John’s University, New York, who previously conducted a pilot study for using lower molecular weight hyaluronan in COPD and published a review on the subject, said that more studies are necessary.
“Further clinical trials are needed to better determine the role of hyaluronan as an adjunct to existing therapies for COPD exacerbations,” he said.
The study was supported by the National Institutes of Health. The investigators and Dr. Sandhaus declared no conflicts of interest. Dr. Cantor disclosed a relationship with MatRx Therapeutics.
FROM RESPIRATORY RESEARCH
New COPD mortality risk model includes imaging-derived variables
All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.
Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.
An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.
“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV1 [forced expiratory volume at 1 second], [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.
In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.
Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.
Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV1 (less than 20), and older age (80 years and older) were the strongest predictors of mortality.
The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.
The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV1 values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.
However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.
The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.
Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.
An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.
“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV1 [forced expiratory volume at 1 second], [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.
In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.
Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.
Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV1 (less than 20), and older age (80 years and older) were the strongest predictors of mortality.
The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.
The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV1 values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.
However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.
The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.
Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.
An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.
“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV1 [forced expiratory volume at 1 second], [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.
In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.
Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.
Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV1 (less than 20), and older age (80 years and older) were the strongest predictors of mortality.
The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.
The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV1 values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.
However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.
The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
FROM CHRONIC OBSTRUCTIVE PULMONARY DISEASES