COPD

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Most of us have two voice changes in our lifetime: First during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice.

But for some of us, there’s another voice shift, when a disease begins or when our mental health declines.

This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present.

Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida, Tampa’s Health Voice Center and the coprincipal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project.

“We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says.

Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University, Nashville, Tenn., who is working on the NIH project.

You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier.

Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of the University of California, Los Angeles, Laboratory of Computational Neuropsychology.

“You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test.

Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000-30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Dr. Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.”

Dr. Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor.

“The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’ ” says Dr. Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.”

Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things.

“We can hold approximately seven pieces of information in our head at one time,” says Dr. Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

“The goal is not to outperform a ... clinician,” says Dr. Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

“Algorithms have a larger training base,” says Dr. Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.”

So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.
 

Voice disorders (cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone.

Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care.

Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4.5 years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Dr. Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.
 

Neurological and neurodegenerative disorders (Alzheimer’s, Parkinson’s, stroke, ALS) 

For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medicine, New York, and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umms” and a preference for pronouns over nouns.

With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.”

Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Dr. Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says.

Dr. Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, because slurred speech is a highly subjective measure, says Dr. Anderson. AI technology could provide a more objective evaluation.
 

Mood and psychiatric disorders (depression, schizophrenia, bipolar disorders)

No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone.

“We carry a lot of our mood in our voice,” says Dr. Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Dr. Anderson. “These are all something an algorithm can measure.”

Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

The content of speech may also offer clues. In a University of California, Los Angeles, study published in the journal PLoS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer.
 

Respiratory disorders (pneumonia, COPD)

Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Dr. Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough.

Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Dr. Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Dr. Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders.
 

Pediatric voice and speech disorders (speech and language delays, autism)

Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Dr. Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions.

ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Dr. Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.
 

And that’s only the beginning

Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries.

“Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, because it regulates the voice box as well as blood pressure and heart rate. Dr. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals.

“Hopefully, in the next few years, this is going to come to practice,” says Dr. Lerman.

Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Dr. Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Dr. Rameau.

But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Dr. Anderson. “I’m really happy that we are beginning to understand the strength of the voice.”

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

Most of us have two voice changes in our lifetime: First during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice.

But for some of us, there’s another voice shift, when a disease begins or when our mental health declines.

This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present.

Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida, Tampa’s Health Voice Center and the coprincipal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project.

“We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says.

Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University, Nashville, Tenn., who is working on the NIH project.

You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier.

Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of the University of California, Los Angeles, Laboratory of Computational Neuropsychology.

“You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test.

Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000-30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Dr. Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.”

Dr. Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor.

“The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’ ” says Dr. Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.”

Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things.

“We can hold approximately seven pieces of information in our head at one time,” says Dr. Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

“The goal is not to outperform a ... clinician,” says Dr. Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

“Algorithms have a larger training base,” says Dr. Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.”

So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.
 

Voice disorders (cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone.

Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care.

Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4.5 years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Dr. Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.
 

Neurological and neurodegenerative disorders (Alzheimer’s, Parkinson’s, stroke, ALS) 

For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medicine, New York, and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umms” and a preference for pronouns over nouns.

With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.”

Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Dr. Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says.

Dr. Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, because slurred speech is a highly subjective measure, says Dr. Anderson. AI technology could provide a more objective evaluation.
 

Mood and psychiatric disorders (depression, schizophrenia, bipolar disorders)

No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone.

“We carry a lot of our mood in our voice,” says Dr. Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Dr. Anderson. “These are all something an algorithm can measure.”

Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

The content of speech may also offer clues. In a University of California, Los Angeles, study published in the journal PLoS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer.
 

Respiratory disorders (pneumonia, COPD)

Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Dr. Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough.

Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Dr. Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Dr. Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders.
 

Pediatric voice and speech disorders (speech and language delays, autism)

Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Dr. Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions.

ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Dr. Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.
 

And that’s only the beginning

Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries.

“Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, because it regulates the voice box as well as blood pressure and heart rate. Dr. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals.

“Hopefully, in the next few years, this is going to come to practice,” says Dr. Lerman.

Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Dr. Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Dr. Rameau.

But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Dr. Anderson. “I’m really happy that we are beginning to understand the strength of the voice.”

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

Most of us have two voice changes in our lifetime: First during puberty, as the vocal cords thicken and the voice box migrates down the throat. Then a second time as aging causes structural changes that may weaken the voice.

But for some of us, there’s another voice shift, when a disease begins or when our mental health declines.

This is why more doctors are looking into voice as a biomarker – something that tells you that a disease is present.

Vital signs like blood pressure or heart rate “can give a general idea of how sick we are. But they’re not specific to certain diseases,” says Yael Bensoussan, MD, director of the University of South Florida, Tampa’s Health Voice Center and the coprincipal investigator for the National Institutes of Health’s Voice as a Biomarker of Health project.

“We’re learning that there are patterns” in voice changes that can indicate a range of conditions, including diseases of the nervous system and mental illnesses, she says.

Speaking is complicated, involving everything from the lungs and voice box to the mouth and brain. “A breakdown in any of those parts can affect the voice,” says Maria Powell, PhD, an assistant professor of otolaryngology (the study of diseases of the ear and throat) at Vanderbilt University, Nashville, Tenn., who is working on the NIH project.

You or those around you may not notice the changes. But researchers say voice analysis as a standard part of patient care – akin to blood pressure checks or cholesterol tests – could help identify those who need medical attention earlier.

Often, all it takes is a smartphone – “something that’s cheap, off-the-shelf, and that everyone can use,” says Ariana Anderson, PhD, director of the University of California, Los Angeles, Laboratory of Computational Neuropsychology.

“You can provide voice data in your pajamas, on your couch,” says Frank Rudzicz, PhD, a computer scientist for the NIH project. “It doesn’t require very complicated or expensive equipment, and it doesn’t require a lot of expertise to obtain.” Plus, multiple samples can be collected over time, giving a more accurate picture of health than a single snapshot from, say, a cognitive test.

Over the next 4 years, the Voice as a Biomarker team will receive nearly $18 million to gather a massive amount of voice data. The goal is 20,000-30,000 samples, along with health data about each person being studied. The result will be a sprawling database scientists can use to develop algorithms linking health conditions to the way we speak.

For the first 2 years, new data will be collected exclusively via universities and high-volume clinics to control quality and accuracy. Eventually, people will be invited to submit their own voice recordings, creating a crowdsourced dataset. “Google, Alexa, Amazon – they have access to tons of voice data,” says Dr. Bensoussan. “But it’s not usable in a clinical way, because they don’t have the health information.”

Dr. Bensoussan and her colleagues hope to fill that void with advance voice screening apps, which could prove especially valuable in remote communities that lack access to specialists or as a tool for telemedicine. Down the line, wearable devices with voice analysis could alert people with chronic conditions when they need to see a doctor.

“The watch says, ‘I’ve analyzed your breathing and coughing, and today, you’re really not doing well. You should go to the hospital,’ ” says Dr. Bensoussan, envisioning a wearable for patients with COPD. “It could tell people early that things are declining.”

Artificial intelligence may be better than a brain at pinpointing the right disease. For example, slurred speech could indicate Parkinson’s, a stroke, or ALS, among other things.

“We can hold approximately seven pieces of information in our head at one time,” says Dr. Rudzicz. “It’s really hard for us to get a holistic picture using dozens or hundreds of variables at once.” But a computer can consider a whole range of vocal markers at the same time, piecing them together for a more accurate assessment.

“The goal is not to outperform a ... clinician,” says Dr. Bensoussan. Yet the potential is unmistakably there: In a recent study of patients with cancer of the larynx, an automated voice analysis tool more accurately flagged the disease than laryngologists did. 

“Algorithms have a larger training base,” says Dr. Anderson, who developed an app called ChatterBaby that analyzes infant cries. “We have a million samples at our disposal to train our algorithms. I don’t know if I’ve heard a million different babies crying in my life.”

So which health conditions show the most promise for voice analysis? The Voice as a Biomarker project will focus on five categories.
 

Voice disorders (cancers of the larynx, vocal fold paralysis, benign lesions on the larynx)

Obviously, vocal changes are a hallmark of these conditions, which cause things like breathiness or “roughness,” a type of vocal irregularity. Hoarseness that lasts at least 2 weeks is often one of the earliest signs of laryngeal cancer. Yet it can take months – one study found 16 weeks was the average – for patients to see a doctor after noticing the changes. Even then, laryngologists still misdiagnosed some cases of cancer when relying on vocal cues alone.

Now imagine a different scenario: The patient speaks into a smartphone app. An algorithm compares the vocal sample with the voices of laryngeal cancer patients. The app spits out the estimated odds of laryngeal cancer, helping providers decide whether to offer the patient specialist care.

Or consider spasmodic dysphonia, a neurological voice disorder that triggers spasms in the muscles of the voice box, causing a strained or breathy voice. Doctors who lack experience with vocal disorders may miss the condition. This is why diagnosis takes an average of nearly 4.5 years, according to a study in the Journal of Voice, and may include everything from allergy testing to psychiatric evaluation, says Dr. Powell. Artificial intelligence technology trained to recognize the disorder could help eliminate such unnecessary testing.
 

Neurological and neurodegenerative disorders (Alzheimer’s, Parkinson’s, stroke, ALS) 

For Alzheimer’s and Parkinson’s, “one of the first changes that’s notable is voice,” usually appearing before a formal diagnosis, says Anais Rameau, MD, an assistant professor of laryngology at Weill Cornell Medicine, New York, and another member of the NIH project. Parkinson’s may soften the voice or make it sound monotone, while Alzheimer’s disease may change the content of speech, leading to an uptick in “umms” and a preference for pronouns over nouns.

With Parkinson’s, vocal changes can occur decades before movement is affected. If doctors could detect the disease at this stage, before tremor emerged, they might be able to flag patients for early intervention, says Max Little, PhD, project director for the Parkinson’s Voice Initiative. “That is the ‘holy grail’ for finding an eventual cure.”

Again, the smartphone shows potential. In a 2022 Australian study, an AI-powered app was able to identify people with Parkinson’s based on brief voice recordings, although the sample size was small. On a larger scale, the Parkinson’s Voice Initiative collected some 17,000 samples from people across the world. “The aim was to remotely detect those with the condition using a telephone call,” says Dr. Little. It did so with about 65% accuracy. “While this is not accurate enough for clinical use, it shows the potential of the idea,” he says.

Dr. Rudzicz worked on the team behind Winterlight, an iPad app that analyzes 550 features of speech to detect dementia and Alzheimer’s (as well as mental illness). “We deployed it in long-term care facilities,” he says, identifying patients who need further review of their mental skills. Stroke is another area of interest, because slurred speech is a highly subjective measure, says Dr. Anderson. AI technology could provide a more objective evaluation.
 

Mood and psychiatric disorders (depression, schizophrenia, bipolar disorders)

No established biomarkers exist for diagnosing depression. Yet if you’re feeling down, there’s a good chance your friends can tell – even over the phone.

“We carry a lot of our mood in our voice,” says Dr. Powell. Bipolar disorder can also alter voice, making it louder and faster during manic periods, then slower and quieter during depressive bouts. The catatonic stage of schizophrenia often comes with “a very monotone, robotic voice,” says Dr. Anderson. “These are all something an algorithm can measure.”

Apps are already being used – often in research settings – to monitor voices during phone calls, analyzing rate, rhythm, volume, and pitch, to predict mood changes. For example, the PRIORI project at the University of Michigan is working on a smartphone app to identify mood changes in people with bipolar disorder, especially shifts that could increase suicide risk.

The content of speech may also offer clues. In a University of California, Los Angeles, study published in the journal PLoS One, people with mental illnesses answered computer-programmed questions (like “How have you been over the past few days?”) over the phone. An app analyzed their word choices, paying attention to how they changed over time. The researchers found that AI analysis of mood aligned well with doctors’ assessments and that some people in the study actually felt more comfortable talking to a computer.
 

Respiratory disorders (pneumonia, COPD)

Beyond talking, respiratory sounds like gasping or coughing may point to specific conditions. “Emphysema cough is different, COPD cough is different,” says Dr. Bensoussan. Researchers are trying to find out if COVID-19 has a distinct cough.

Breathing sounds can also serve as signposts. “There are different sounds when we can’t breathe,” says Dr. Bensoussan. One is called stridor, a high-pitched wheezing often resulting from a blocked airway. “I see tons of people [with stridor] misdiagnosed for years – they’ve been told they have asthma, but they don’t,” says Dr. Bensoussan. AI analysis of these sounds could help doctors more quickly identify respiratory disorders.
 

Pediatric voice and speech disorders (speech and language delays, autism)

Babies who later have autism cry differently as early as 6 months of age, which means an app like ChatterBaby could help flag children for early intervention, says Dr. Anderson. Autism is linked to several other diagnoses, such as epilepsy and sleep disorders. So analyzing an infant’s cry could prompt pediatricians to screen for a range of conditions.

ChatterBaby has been “incredibly accurate” in identifying when babies are in pain, says Dr. Anderson, because pain increases muscle tension, resulting in a louder, more energetic cry. The next goal: “We’re collecting voices from babies around the world,” she says, and then tracking those children for 7 years, looking to see if early vocal signs could predict developmental disorders. Vocal samples from young children could serve a similar purpose.
 

And that’s only the beginning

Eventually, AI technology may pick up disease-related voice changes that we can’t even hear. In a new Mayo Clinic study, certain vocal features detectable by AI – but not by the human ear – were linked to a three-fold increase in the likelihood of having plaque buildup in the arteries.

“Voice is a huge spectrum of vibrations,” explains study author Amir Lerman, MD. “We hear a very narrow range.” 

The researchers aren’t sure why heart disease alters voice, but the autonomic nervous system may play a role, because it regulates the voice box as well as blood pressure and heart rate. Dr. Lerman says other conditions, like diseases of the nerves and gut, may similarly alter the voice. Beyond patient screening, this discovery could help doctors adjust medication doses remotely, in line with these inaudible vocal signals.

“Hopefully, in the next few years, this is going to come to practice,” says Dr. Lerman.

Still, in the face of that hope, privacy concerns remain. Voice is an identifier that’s protected by the federal Health Insurance Portability and Accountability Act, which requires privacy of personal health information. That is a major reason why no large voice databases exist yet, says Dr. Bensoussan. (This makes collecting samples from children especially challenging.) Perhaps more concerning is the potential for diagnosing disease based on voice alone. “You could use that tool on anyone, including officials like the president,” says Dr. Rameau.

But the primary hurdle is the ethical sourcing of data to ensure a diversity of vocal samples. For the Voice as a Biomarker project, the researchers will establish voice quotas for different races and ethnicities, ensuring algorithms can accurately analyze a range of accents. Data from people with speech impediments will also be gathered.

Despite these challenges, researchers are optimistic. “Vocal analysis is going to be a great equalizer and improve health outcomes,” predicts Dr. Anderson. “I’m really happy that we are beginning to understand the strength of the voice.”

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

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report is revised annually and is used widely throughout the world as a tool for implementing effective management.

Among the updates in the 2023 GOLD Report, the section on diagnostic criteria added a proposed new category “PRISm,” denoting “preserved ratio impaired spirometry,” encompassing individuals who present with structural lung lesions (for example, emphysema) and/or other physiological abnormalities such as low-normal forced expiratory volume in 1 second (FEV₁), gas trapping, hyperinflation, reduced lung diffusing capacity and/or rapid FEV₁ decline, but without airflow obstruction (FEV₁/FEV ≥ 0.7 post bronchodilation). Some of these “pre-COPD” (chronic obstructive pulmonary disease) individuals, who have a normal ratio but abnormal spirometry are at risk over time of developing airflow obstruction. The best treatment for them, beyond smoking cessation, needs to be determined through research, the report states.
 

Clinical updates

The GOLD 2023 Report also offers proposed clinical guidance, in the absence of high-quality clinical trial evidence, on initial pharmacologic management of COPD. The proposal is based on individual assessment of symptoms and exacerbation risk following use of the ABE Assessment Tool, a revised version of the ABCD Assessment Tool that recognizes the clinical relevance of exacerbations independent of symptom level.

These updates to information and figures pertaining to initial pharmacological treatment and follow-up pharmacological treatment revise the positioning of LABA (long-acting beta₂ agonists) plus LAMA (long-acting muscarinic agonists) and LABA/ICS (inhaled corticosteroids). Among GOLD group A patients with 0 or 1 moderate exacerbations that do not lead to hospital admission, a bronchodilator is recommended.

The recommendation for group B patients is LABA/LAMA with the caveat that single inhaler therapy may be more convenient and effective than multiple inhalers. For group E patients with two or more moderate exacerbations or one or more leading to hospitalization, LABA/LAMA is recommended (with the same inhaler therapy caveat). With blood eosinophil levels at 300 or higher, LABA/LAMA/ICS may be considered.

Commenting on the combination recommendations in a press release, Antonio Anzueto, MD, professor of medicine, pulmonary critical care, University of Texas Health, San Antonio, stated: “From a physician’s perspective, we are always grateful to receive well-vetted and informed recommendations on how we can best utilize available treatment options to provide the most benefit to our patients. The new 2023 GOLD recommendations represent a meaningful change for the treatment of COPD by prioritizing the utilization of a fixed LAMA/LABA combination.”
 

More interventions

In a section on therapeutic interventions to reduce COPD mortality, the report lists studies showing mortality benefits for fixed-dose inhaled triple combinations (LABA + LAMA + ICS) versus dual inhaled long-acting bronchodilations, and for smoking cessation and pulmonary rehabilitation.

Also new is a strong emphasis on inhaler choice, education, and technique training with assessment of inhaler technique and adherence urged as a prerequisite to judging whether current therapy as insufficient. The report summarizes principles guiding inhaler type selection.

The report also added a section on chronic bronchitis, defining it as a common but variable condition in COPD patients with cough and expectorated sputum on a regular basis over a defined period in the absence of other conditions plausibly causing symptoms.

The fact that chronic bronchitis is sometimes found in never-smokers suggests the involvement of other factors such as exposure to inhaled dusts, biomass fuels, chemical fumes, or domestic heating and cooking fuels, according to the report. Gastroesophageal reflux may also be associated with chronic bronchitis.

The report discusses various taxonomic terms for different types of COPD, such as COPD-G for genetically determined COPD, COPD-D for those with abnormal lung development, and COPD-C for COPD associated with cigarette smoking, etc.
 

Change in exacerbations

The report also revises the definition of a COPD exacerbation as “an event characterized by increased dyspnea and/or cough and sputum that worsens in less than 14 days which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and system inflammation caused by infection, pollution, or other insult to the airways.” To overcome limitations conferred by the current grading of COPD exacerbations, the 2023 report proposes a four-step point-of-contact diagnosis and assessment tool.

Telemedicine

Given the constraints brought on by COVID-19 on top of the generally sparse availability of programs and facilities for delivering well-proven pulmonary rehabilitation methods, tele-rehabilitation has been proposed as an alternative to traditional approaches. While the evidence base is still evolving and best practices have not yet been established, the GOLD Report calls for better understanding of barriers to tele-rehabilitation success.

Comorbidities update

The GOLD Report chapter on COPD and comorbidities was also updated, and lists cardiovascular disease, lung cancer, osteoporosis, depression/anxiety, and gastroesophageal reflux disease as common comorbid conditions which may affect prognosis and, in the case of cancer, mortality. The report urges simplicity of treatment to minimize polypharmacy. While annual low-dose CT is recommended for COPD caused by smoking, it is not recommended for COPD caused by smoking; data are insufficient to establish benefit over harm.

While the GOLD Report “COVID-19 and COPD” chapter summarizes current evidence stating that individuals with COPD do not seem to be at substantially greater risk of infection with SARS-CoV-2, it underscores that they are at higher risk of hospitalization for COVID-19 and may be at higher risk for developing severe disease and death.

Many other topics are included in the updated report, among them screening, imaging, vaccinations, adherence to therapy, and surgical and bronchoscopic interventions. In its closing section, the GOLD Report 2023 reiterates its mission, stating: “The GOLD initiative will continue to work with National Leaders and other interested health care professionals to bring COPD to the attention of governments, public health officials, health care workers, and the general public, to raise awareness of the burden of COPD and to develop programs for early detection, prevention and approaches to management.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report is revised annually and is used widely throughout the world as a tool for implementing effective management.

Among the updates in the 2023 GOLD Report, the section on diagnostic criteria added a proposed new category “PRISm,” denoting “preserved ratio impaired spirometry,” encompassing individuals who present with structural lung lesions (for example, emphysema) and/or other physiological abnormalities such as low-normal forced expiratory volume in 1 second (FEV₁), gas trapping, hyperinflation, reduced lung diffusing capacity and/or rapid FEV₁ decline, but without airflow obstruction (FEV₁/FEV ≥ 0.7 post bronchodilation). Some of these “pre-COPD” (chronic obstructive pulmonary disease) individuals, who have a normal ratio but abnormal spirometry are at risk over time of developing airflow obstruction. The best treatment for them, beyond smoking cessation, needs to be determined through research, the report states.
 

Clinical updates

The GOLD 2023 Report also offers proposed clinical guidance, in the absence of high-quality clinical trial evidence, on initial pharmacologic management of COPD. The proposal is based on individual assessment of symptoms and exacerbation risk following use of the ABE Assessment Tool, a revised version of the ABCD Assessment Tool that recognizes the clinical relevance of exacerbations independent of symptom level.

These updates to information and figures pertaining to initial pharmacological treatment and follow-up pharmacological treatment revise the positioning of LABA (long-acting beta₂ agonists) plus LAMA (long-acting muscarinic agonists) and LABA/ICS (inhaled corticosteroids). Among GOLD group A patients with 0 or 1 moderate exacerbations that do not lead to hospital admission, a bronchodilator is recommended.

The recommendation for group B patients is LABA/LAMA with the caveat that single inhaler therapy may be more convenient and effective than multiple inhalers. For group E patients with two or more moderate exacerbations or one or more leading to hospitalization, LABA/LAMA is recommended (with the same inhaler therapy caveat). With blood eosinophil levels at 300 or higher, LABA/LAMA/ICS may be considered.

Commenting on the combination recommendations in a press release, Antonio Anzueto, MD, professor of medicine, pulmonary critical care, University of Texas Health, San Antonio, stated: “From a physician’s perspective, we are always grateful to receive well-vetted and informed recommendations on how we can best utilize available treatment options to provide the most benefit to our patients. The new 2023 GOLD recommendations represent a meaningful change for the treatment of COPD by prioritizing the utilization of a fixed LAMA/LABA combination.”
 

More interventions

In a section on therapeutic interventions to reduce COPD mortality, the report lists studies showing mortality benefits for fixed-dose inhaled triple combinations (LABA + LAMA + ICS) versus dual inhaled long-acting bronchodilations, and for smoking cessation and pulmonary rehabilitation.

Also new is a strong emphasis on inhaler choice, education, and technique training with assessment of inhaler technique and adherence urged as a prerequisite to judging whether current therapy as insufficient. The report summarizes principles guiding inhaler type selection.

The report also added a section on chronic bronchitis, defining it as a common but variable condition in COPD patients with cough and expectorated sputum on a regular basis over a defined period in the absence of other conditions plausibly causing symptoms.

The fact that chronic bronchitis is sometimes found in never-smokers suggests the involvement of other factors such as exposure to inhaled dusts, biomass fuels, chemical fumes, or domestic heating and cooking fuels, according to the report. Gastroesophageal reflux may also be associated with chronic bronchitis.

The report discusses various taxonomic terms for different types of COPD, such as COPD-G for genetically determined COPD, COPD-D for those with abnormal lung development, and COPD-C for COPD associated with cigarette smoking, etc.
 

Change in exacerbations

The report also revises the definition of a COPD exacerbation as “an event characterized by increased dyspnea and/or cough and sputum that worsens in less than 14 days which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and system inflammation caused by infection, pollution, or other insult to the airways.” To overcome limitations conferred by the current grading of COPD exacerbations, the 2023 report proposes a four-step point-of-contact diagnosis and assessment tool.

Telemedicine

Given the constraints brought on by COVID-19 on top of the generally sparse availability of programs and facilities for delivering well-proven pulmonary rehabilitation methods, tele-rehabilitation has been proposed as an alternative to traditional approaches. While the evidence base is still evolving and best practices have not yet been established, the GOLD Report calls for better understanding of barriers to tele-rehabilitation success.

Comorbidities update

The GOLD Report chapter on COPD and comorbidities was also updated, and lists cardiovascular disease, lung cancer, osteoporosis, depression/anxiety, and gastroesophageal reflux disease as common comorbid conditions which may affect prognosis and, in the case of cancer, mortality. The report urges simplicity of treatment to minimize polypharmacy. While annual low-dose CT is recommended for COPD caused by smoking, it is not recommended for COPD caused by smoking; data are insufficient to establish benefit over harm.

While the GOLD Report “COVID-19 and COPD” chapter summarizes current evidence stating that individuals with COPD do not seem to be at substantially greater risk of infection with SARS-CoV-2, it underscores that they are at higher risk of hospitalization for COVID-19 and may be at higher risk for developing severe disease and death.

Many other topics are included in the updated report, among them screening, imaging, vaccinations, adherence to therapy, and surgical and bronchoscopic interventions. In its closing section, the GOLD Report 2023 reiterates its mission, stating: “The GOLD initiative will continue to work with National Leaders and other interested health care professionals to bring COPD to the attention of governments, public health officials, health care workers, and the general public, to raise awareness of the burden of COPD and to develop programs for early detection, prevention and approaches to management.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report is revised annually and is used widely throughout the world as a tool for implementing effective management.

Among the updates in the 2023 GOLD Report, the section on diagnostic criteria added a proposed new category “PRISm,” denoting “preserved ratio impaired spirometry,” encompassing individuals who present with structural lung lesions (for example, emphysema) and/or other physiological abnormalities such as low-normal forced expiratory volume in 1 second (FEV₁), gas trapping, hyperinflation, reduced lung diffusing capacity and/or rapid FEV₁ decline, but without airflow obstruction (FEV₁/FEV ≥ 0.7 post bronchodilation). Some of these “pre-COPD” (chronic obstructive pulmonary disease) individuals, who have a normal ratio but abnormal spirometry are at risk over time of developing airflow obstruction. The best treatment for them, beyond smoking cessation, needs to be determined through research, the report states.
 

Clinical updates

The GOLD 2023 Report also offers proposed clinical guidance, in the absence of high-quality clinical trial evidence, on initial pharmacologic management of COPD. The proposal is based on individual assessment of symptoms and exacerbation risk following use of the ABE Assessment Tool, a revised version of the ABCD Assessment Tool that recognizes the clinical relevance of exacerbations independent of symptom level.

These updates to information and figures pertaining to initial pharmacological treatment and follow-up pharmacological treatment revise the positioning of LABA (long-acting beta₂ agonists) plus LAMA (long-acting muscarinic agonists) and LABA/ICS (inhaled corticosteroids). Among GOLD group A patients with 0 or 1 moderate exacerbations that do not lead to hospital admission, a bronchodilator is recommended.

The recommendation for group B patients is LABA/LAMA with the caveat that single inhaler therapy may be more convenient and effective than multiple inhalers. For group E patients with two or more moderate exacerbations or one or more leading to hospitalization, LABA/LAMA is recommended (with the same inhaler therapy caveat). With blood eosinophil levels at 300 or higher, LABA/LAMA/ICS may be considered.

Commenting on the combination recommendations in a press release, Antonio Anzueto, MD, professor of medicine, pulmonary critical care, University of Texas Health, San Antonio, stated: “From a physician’s perspective, we are always grateful to receive well-vetted and informed recommendations on how we can best utilize available treatment options to provide the most benefit to our patients. The new 2023 GOLD recommendations represent a meaningful change for the treatment of COPD by prioritizing the utilization of a fixed LAMA/LABA combination.”
 

More interventions

In a section on therapeutic interventions to reduce COPD mortality, the report lists studies showing mortality benefits for fixed-dose inhaled triple combinations (LABA + LAMA + ICS) versus dual inhaled long-acting bronchodilations, and for smoking cessation and pulmonary rehabilitation.

Also new is a strong emphasis on inhaler choice, education, and technique training with assessment of inhaler technique and adherence urged as a prerequisite to judging whether current therapy as insufficient. The report summarizes principles guiding inhaler type selection.

The report also added a section on chronic bronchitis, defining it as a common but variable condition in COPD patients with cough and expectorated sputum on a regular basis over a defined period in the absence of other conditions plausibly causing symptoms.

The fact that chronic bronchitis is sometimes found in never-smokers suggests the involvement of other factors such as exposure to inhaled dusts, biomass fuels, chemical fumes, or domestic heating and cooking fuels, according to the report. Gastroesophageal reflux may also be associated with chronic bronchitis.

The report discusses various taxonomic terms for different types of COPD, such as COPD-G for genetically determined COPD, COPD-D for those with abnormal lung development, and COPD-C for COPD associated with cigarette smoking, etc.
 

Change in exacerbations

The report also revises the definition of a COPD exacerbation as “an event characterized by increased dyspnea and/or cough and sputum that worsens in less than 14 days which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and system inflammation caused by infection, pollution, or other insult to the airways.” To overcome limitations conferred by the current grading of COPD exacerbations, the 2023 report proposes a four-step point-of-contact diagnosis and assessment tool.

Telemedicine

Given the constraints brought on by COVID-19 on top of the generally sparse availability of programs and facilities for delivering well-proven pulmonary rehabilitation methods, tele-rehabilitation has been proposed as an alternative to traditional approaches. While the evidence base is still evolving and best practices have not yet been established, the GOLD Report calls for better understanding of barriers to tele-rehabilitation success.

Comorbidities update

The GOLD Report chapter on COPD and comorbidities was also updated, and lists cardiovascular disease, lung cancer, osteoporosis, depression/anxiety, and gastroesophageal reflux disease as common comorbid conditions which may affect prognosis and, in the case of cancer, mortality. The report urges simplicity of treatment to minimize polypharmacy. While annual low-dose CT is recommended for COPD caused by smoking, it is not recommended for COPD caused by smoking; data are insufficient to establish benefit over harm.

While the GOLD Report “COVID-19 and COPD” chapter summarizes current evidence stating that individuals with COPD do not seem to be at substantially greater risk of infection with SARS-CoV-2, it underscores that they are at higher risk of hospitalization for COVID-19 and may be at higher risk for developing severe disease and death.

Many other topics are included in the updated report, among them screening, imaging, vaccinations, adherence to therapy, and surgical and bronchoscopic interventions. In its closing section, the GOLD Report 2023 reiterates its mission, stating: “The GOLD initiative will continue to work with National Leaders and other interested health care professionals to bring COPD to the attention of governments, public health officials, health care workers, and the general public, to raise awareness of the burden of COPD and to develop programs for early detection, prevention and approaches to management.

Obstructive sleep apnea (OSA) was associated with both impaired functional performance during exercise and overall worse outcomes in patients with chronic obstructive pulmonary disease (COPD), based on data from 34 adults.

Individuals with COPD are at increased risk for hospital readmissions and disease exacerbations, Patricia Faria Camargo, PhD, of Federal University of São Carlos (Brazil), and colleagues wrote. These patients often have concomitant obstructive sleep apnea, which itself can promote adverse cardiovascular events, but the impact of the overlap of these two conditions on clinical outcomes has not been explored.

In a study published in Heart & Lung, the researchers recruited 17 adults with COPD only and 17 with OSA and COPD. At baseline, patients underwent pulmonary function tests, echocardiography, and polysomnography to confirm their OSA and COPD diagnoses.

The primary endpoint was the impact of OSA on functional performance and cardiac autonomic control in COPD patients, based on measures of heart rate variability and the 6-minute walk test (6MWT). Participants were followed for 1 year, with telephone contacts every 3 months. A secondary endpoint was the number of exacerbations, hospitalizations, and deaths. At baseline, OSA-COPD patients had worse polysomnographic function, compared with COPD patients; they also tended to be older and have higher body mass index, but other demographics were similar between the groups.

Overall, patients in the OSA-COPD group had significantly greater functional impairment, compared with the COPD group (P = .003), as measured by the 6MWT. The OSA-COPD patients also showed significantly worse autonomic response during exercise, compared with the COPD group.

A lower work load during exercise and the interaction between group and time factors suggests that OSA impacts the exercise capacity of COPD patients, the researchers said. Notably, however, neither age nor body mass index was associated with functional performance in the OSA-COPD group.

Patients in the OSA-COPD group also were significantly more likely to experience exacerbations during the study period, compared with the COPD-only group (67.4% vs. 23.5; P = .03). However, the severity of COPD was similar between the groups, which further illustrates that OSA can impair functional performance in COPD patients, the researchers said.

The findings were limited by several factors including the small sample size and restricted collection of follow-up data during the pandemic, the researchers noted. However, the results support previous studies, and suggest that overlapping OSA and COPD produces worse outcomes.

“Future studies can confirm our findings, providing new clinical evidences to the assessment of sleep quality in COPD patients and its implications for the general health status of these individuals, in addition to contributing to more assertive clinical and therapeutic alternative support the need for more research into the mechanisms behind this overlap in larger samples to develop treatment alternatives,” they concluded.

The study was supported by the Federal University of Sao Carlos. The researchers had no financial conflicts to disclose.
 

Obstructive sleep apnea (OSA) was associated with both impaired functional performance during exercise and overall worse outcomes in patients with chronic obstructive pulmonary disease (COPD), based on data from 34 adults.

Individuals with COPD are at increased risk for hospital readmissions and disease exacerbations, Patricia Faria Camargo, PhD, of Federal University of São Carlos (Brazil), and colleagues wrote. These patients often have concomitant obstructive sleep apnea, which itself can promote adverse cardiovascular events, but the impact of the overlap of these two conditions on clinical outcomes has not been explored.

In a study published in Heart & Lung, the researchers recruited 17 adults with COPD only and 17 with OSA and COPD. At baseline, patients underwent pulmonary function tests, echocardiography, and polysomnography to confirm their OSA and COPD diagnoses.

The primary endpoint was the impact of OSA on functional performance and cardiac autonomic control in COPD patients, based on measures of heart rate variability and the 6-minute walk test (6MWT). Participants were followed for 1 year, with telephone contacts every 3 months. A secondary endpoint was the number of exacerbations, hospitalizations, and deaths. At baseline, OSA-COPD patients had worse polysomnographic function, compared with COPD patients; they also tended to be older and have higher body mass index, but other demographics were similar between the groups.

Overall, patients in the OSA-COPD group had significantly greater functional impairment, compared with the COPD group (P = .003), as measured by the 6MWT. The OSA-COPD patients also showed significantly worse autonomic response during exercise, compared with the COPD group.

A lower work load during exercise and the interaction between group and time factors suggests that OSA impacts the exercise capacity of COPD patients, the researchers said. Notably, however, neither age nor body mass index was associated with functional performance in the OSA-COPD group.

Patients in the OSA-COPD group also were significantly more likely to experience exacerbations during the study period, compared with the COPD-only group (67.4% vs. 23.5; P = .03). However, the severity of COPD was similar between the groups, which further illustrates that OSA can impair functional performance in COPD patients, the researchers said.

The findings were limited by several factors including the small sample size and restricted collection of follow-up data during the pandemic, the researchers noted. However, the results support previous studies, and suggest that overlapping OSA and COPD produces worse outcomes.

“Future studies can confirm our findings, providing new clinical evidences to the assessment of sleep quality in COPD patients and its implications for the general health status of these individuals, in addition to contributing to more assertive clinical and therapeutic alternative support the need for more research into the mechanisms behind this overlap in larger samples to develop treatment alternatives,” they concluded.

The study was supported by the Federal University of Sao Carlos. The researchers had no financial conflicts to disclose.
 

Obstructive sleep apnea (OSA) was associated with both impaired functional performance during exercise and overall worse outcomes in patients with chronic obstructive pulmonary disease (COPD), based on data from 34 adults.

Individuals with COPD are at increased risk for hospital readmissions and disease exacerbations, Patricia Faria Camargo, PhD, of Federal University of São Carlos (Brazil), and colleagues wrote. These patients often have concomitant obstructive sleep apnea, which itself can promote adverse cardiovascular events, but the impact of the overlap of these two conditions on clinical outcomes has not been explored.

In a study published in Heart & Lung, the researchers recruited 17 adults with COPD only and 17 with OSA and COPD. At baseline, patients underwent pulmonary function tests, echocardiography, and polysomnography to confirm their OSA and COPD diagnoses.

The primary endpoint was the impact of OSA on functional performance and cardiac autonomic control in COPD patients, based on measures of heart rate variability and the 6-minute walk test (6MWT). Participants were followed for 1 year, with telephone contacts every 3 months. A secondary endpoint was the number of exacerbations, hospitalizations, and deaths. At baseline, OSA-COPD patients had worse polysomnographic function, compared with COPD patients; they also tended to be older and have higher body mass index, but other demographics were similar between the groups.

Overall, patients in the OSA-COPD group had significantly greater functional impairment, compared with the COPD group (P = .003), as measured by the 6MWT. The OSA-COPD patients also showed significantly worse autonomic response during exercise, compared with the COPD group.

A lower work load during exercise and the interaction between group and time factors suggests that OSA impacts the exercise capacity of COPD patients, the researchers said. Notably, however, neither age nor body mass index was associated with functional performance in the OSA-COPD group.

Patients in the OSA-COPD group also were significantly more likely to experience exacerbations during the study period, compared with the COPD-only group (67.4% vs. 23.5; P = .03). However, the severity of COPD was similar between the groups, which further illustrates that OSA can impair functional performance in COPD patients, the researchers said.

The findings were limited by several factors including the small sample size and restricted collection of follow-up data during the pandemic, the researchers noted. However, the results support previous studies, and suggest that overlapping OSA and COPD produces worse outcomes.

“Future studies can confirm our findings, providing new clinical evidences to the assessment of sleep quality in COPD patients and its implications for the general health status of these individuals, in addition to contributing to more assertive clinical and therapeutic alternative support the need for more research into the mechanisms behind this overlap in larger samples to develop treatment alternatives,” they concluded.

The study was supported by the Federal University of Sao Carlos. The researchers had no financial conflicts to disclose.
 

A multidisciplinary care bundle for chronic obstructive pulmonary disease (COPD) significantly reduced all-cause hospital readmissions at 30, 60, and 90 days, based on data from approximately 300 patients.

COPD remains a leading cause of mortality and a leading contributor to health care costs, but data suggest that adoption of an interdisciplinary care bundle could reduce hospital readmission for COPD patients, Sibyl Cherian, PharmD, BCPS, of Overlook Medical Center, Summit, N.J., and colleagues wrote. The Centers for Medicare & Medicaid Services has introduced both penalties and bundled payments for hospitals with excess all-cause readmission rates after hospitalizations, but more data are needed on the ability of a COPD care bundle to reduce readmission for COPD.

In a study published in the Journal of the American Pharmacists Association, the researchers assigned 127 individuals with COPD to a COPD care bundle arm and 189 to a control arm for treatment at a single center. The standard of care group was admitted between Jan. 1 and Dec. 31, 2017; the COPD care bundle group was admitted between Jan. 1 and Dec. 31, 2018. The mean age of the participants across both groups was 72 years, and more than 70% of patients in each group were White. The COPD care bundle was managed by a team including pulmonologists, hospitalists, care managers, advanced practice nurses, pharmacists, respiratory care practitioners, physical therapists, documentation specialists, quality improvement experts, social workers, and dietitians.

The primary outcome was 30-day all-cause readmission among adults with acute exacerbation of COPD.

Overall, the rate of 30-day all-cause readmissions was significantly lower in the COPD care bundle arm versus the control arm (11.8% vs. 21.7%; P = .017). Similar differences appeared between the care bundle group and control group for all-cause readmissions at 60 days (8.7% vs. 18%; P = .013) and 90 days (4.7% vs. 19.6%; P < .001).

Reasons for reduced readmissions after implementation of the COPD care bundle included pulmonary follow-up appointments of 7 days or less, significantly increased physical therapy consults, and significant escalation of COPD maintenance therapy, the researchers wrote.

Notably, pharmacists consulted with 68.5% of patients overall and assisted with access to outpatient medications for 45.7% of those in the care bundle arm, the researchers wrote. Patients in the COPD care bundle group were significantly more likely to have an escalation in maintenance therapy versus the control patients (44.9% vs. 22.2%; P < .001), which illustrates the importance of interventions by pharmacists in escalating therapy to reduce readmissions.

The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the lack of data on the need for therapy escalation in the control group and by the lack of controlling for socioeconomic status, which is a known risk factor for hospital readmission.

However, the results support the value of a COPD care bundle for reducing readmissions, and that such a bundle can be replicated at other hospitals, although more research is needed to evaluate the impact of other COPD care strategies, they emphasized.

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

A multidisciplinary care bundle for chronic obstructive pulmonary disease (COPD) significantly reduced all-cause hospital readmissions at 30, 60, and 90 days, based on data from approximately 300 patients.

COPD remains a leading cause of mortality and a leading contributor to health care costs, but data suggest that adoption of an interdisciplinary care bundle could reduce hospital readmission for COPD patients, Sibyl Cherian, PharmD, BCPS, of Overlook Medical Center, Summit, N.J., and colleagues wrote. The Centers for Medicare & Medicaid Services has introduced both penalties and bundled payments for hospitals with excess all-cause readmission rates after hospitalizations, but more data are needed on the ability of a COPD care bundle to reduce readmission for COPD.

In a study published in the Journal of the American Pharmacists Association, the researchers assigned 127 individuals with COPD to a COPD care bundle arm and 189 to a control arm for treatment at a single center. The standard of care group was admitted between Jan. 1 and Dec. 31, 2017; the COPD care bundle group was admitted between Jan. 1 and Dec. 31, 2018. The mean age of the participants across both groups was 72 years, and more than 70% of patients in each group were White. The COPD care bundle was managed by a team including pulmonologists, hospitalists, care managers, advanced practice nurses, pharmacists, respiratory care practitioners, physical therapists, documentation specialists, quality improvement experts, social workers, and dietitians.

The primary outcome was 30-day all-cause readmission among adults with acute exacerbation of COPD.

Overall, the rate of 30-day all-cause readmissions was significantly lower in the COPD care bundle arm versus the control arm (11.8% vs. 21.7%; P = .017). Similar differences appeared between the care bundle group and control group for all-cause readmissions at 60 days (8.7% vs. 18%; P = .013) and 90 days (4.7% vs. 19.6%; P < .001).

Reasons for reduced readmissions after implementation of the COPD care bundle included pulmonary follow-up appointments of 7 days or less, significantly increased physical therapy consults, and significant escalation of COPD maintenance therapy, the researchers wrote.

Notably, pharmacists consulted with 68.5% of patients overall and assisted with access to outpatient medications for 45.7% of those in the care bundle arm, the researchers wrote. Patients in the COPD care bundle group were significantly more likely to have an escalation in maintenance therapy versus the control patients (44.9% vs. 22.2%; P < .001), which illustrates the importance of interventions by pharmacists in escalating therapy to reduce readmissions.

The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the lack of data on the need for therapy escalation in the control group and by the lack of controlling for socioeconomic status, which is a known risk factor for hospital readmission.

However, the results support the value of a COPD care bundle for reducing readmissions, and that such a bundle can be replicated at other hospitals, although more research is needed to evaluate the impact of other COPD care strategies, they emphasized.

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

A multidisciplinary care bundle for chronic obstructive pulmonary disease (COPD) significantly reduced all-cause hospital readmissions at 30, 60, and 90 days, based on data from approximately 300 patients.

COPD remains a leading cause of mortality and a leading contributor to health care costs, but data suggest that adoption of an interdisciplinary care bundle could reduce hospital readmission for COPD patients, Sibyl Cherian, PharmD, BCPS, of Overlook Medical Center, Summit, N.J., and colleagues wrote. The Centers for Medicare & Medicaid Services has introduced both penalties and bundled payments for hospitals with excess all-cause readmission rates after hospitalizations, but more data are needed on the ability of a COPD care bundle to reduce readmission for COPD.

In a study published in the Journal of the American Pharmacists Association, the researchers assigned 127 individuals with COPD to a COPD care bundle arm and 189 to a control arm for treatment at a single center. The standard of care group was admitted between Jan. 1 and Dec. 31, 2017; the COPD care bundle group was admitted between Jan. 1 and Dec. 31, 2018. The mean age of the participants across both groups was 72 years, and more than 70% of patients in each group were White. The COPD care bundle was managed by a team including pulmonologists, hospitalists, care managers, advanced practice nurses, pharmacists, respiratory care practitioners, physical therapists, documentation specialists, quality improvement experts, social workers, and dietitians.

The primary outcome was 30-day all-cause readmission among adults with acute exacerbation of COPD.

Overall, the rate of 30-day all-cause readmissions was significantly lower in the COPD care bundle arm versus the control arm (11.8% vs. 21.7%; P = .017). Similar differences appeared between the care bundle group and control group for all-cause readmissions at 60 days (8.7% vs. 18%; P = .013) and 90 days (4.7% vs. 19.6%; P < .001).

Reasons for reduced readmissions after implementation of the COPD care bundle included pulmonary follow-up appointments of 7 days or less, significantly increased physical therapy consults, and significant escalation of COPD maintenance therapy, the researchers wrote.

Notably, pharmacists consulted with 68.5% of patients overall and assisted with access to outpatient medications for 45.7% of those in the care bundle arm, the researchers wrote. Patients in the COPD care bundle group were significantly more likely to have an escalation in maintenance therapy versus the control patients (44.9% vs. 22.2%; P < .001), which illustrates the importance of interventions by pharmacists in escalating therapy to reduce readmissions.

The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the lack of data on the need for therapy escalation in the control group and by the lack of controlling for socioeconomic status, which is a known risk factor for hospital readmission.

However, the results support the value of a COPD care bundle for reducing readmissions, and that such a bundle can be replicated at other hospitals, although more research is needed to evaluate the impact of other COPD care strategies, they emphasized.

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

The slope of the alveolar plateau on the single-breath nitrogen test (SBN₂) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.

In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.

The SBN₂ has been used to detect early SAD, but few studies have examined the relationship between SBN₂ measures and lung function decline over time, they said.

In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.

The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.

COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.

In a multinomial regression model, one SBN₂ index, the slope of alveolar plateau (N₂-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV₁) decline, with a decrease of 7.93 mL/year for each one-unit change in N₂-slope.

The N₂-slope also was significantly associated with an increased risk of COPD, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.

Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.

The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.

The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.

However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN₂ test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.

The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.

The slope of the alveolar plateau on the single-breath nitrogen test (SBN₂) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.

In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.

The SBN₂ has been used to detect early SAD, but few studies have examined the relationship between SBN₂ measures and lung function decline over time, they said.

In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.

The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.

COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.

In a multinomial regression model, one SBN₂ index, the slope of alveolar plateau (N₂-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV₁) decline, with a decrease of 7.93 mL/year for each one-unit change in N₂-slope.

The N₂-slope also was significantly associated with an increased risk of COPD, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.

Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.

The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.

The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.

However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN₂ test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.

The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.

The slope of the alveolar plateau on the single-breath nitrogen test (SBN₂) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.

In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.

The SBN₂ has been used to detect early SAD, but few studies have examined the relationship between SBN₂ measures and lung function decline over time, they said.

In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.

The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.

COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.

In a multinomial regression model, one SBN₂ index, the slope of alveolar plateau (N₂-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV₁) decline, with a decrease of 7.93 mL/year for each one-unit change in N₂-slope.

The N₂-slope also was significantly associated with an increased risk of COPD, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.

Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.

The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.

The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.

However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN₂ test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.

The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.

NASHVILLE, Tenn. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O₂ saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

NASHVILLE, Tenn. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O₂ saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

NASHVILLE, Tenn. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O₂ saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

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

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

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

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

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

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

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

Medications and treatment goals for patients with COPD

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

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

Vaccines and pulmonary rehabilitation recommended

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Medications and treatment goals for patients with COPD

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

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

Vaccines and pulmonary rehabilitation recommended

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Medications and treatment goals for patients with COPD

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

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

Vaccines and pulmonary rehabilitation recommended

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

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

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

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

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

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

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

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

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

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

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

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

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

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

‘Short shrift’

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

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

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

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

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

Mighty mucins

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

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

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

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

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

Therapeutic strategies

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

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

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

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

Knocking secretion down, but not out

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

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

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

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

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

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

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

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

Not ready for prime time

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

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

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

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

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

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

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

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

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

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

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

‘Short shrift’

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

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

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

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

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

Mighty mucins

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

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

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

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

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

Therapeutic strategies

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

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

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

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

Knocking secretion down, but not out

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

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

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

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

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

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

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

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

Not ready for prime time

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

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

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

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

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

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

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

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

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

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

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

‘Short shrift’

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

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

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

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

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

Mighty mucins

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

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

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

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

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

Therapeutic strategies

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

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

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

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

Knocking secretion down, but not out

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

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

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

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

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

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

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

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

Not ready for prime time

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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