Pulmonary Health Hub

Some nonsleepy patients with coronary artery disease and obstructive sleep apnea (OSA) may receive cardiovascular benefit from continuous positive airway pressure (CPAP) therapy, according to a post hoc analysis of the RICCADSA clinical trial. That study found no benefit among patients overall, but the new analysis found that patients whose heart rate increases (delta heart rate, or dHR) more than average during apnea or hypopnea experienced fewer cardiovascular or cerebrovascular events during apnea or hypopnea when treated with CPAP.

Although RICCADSA showed no benefit, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Sleep Heart Health Study (SHHS) cohorts found that elevated pulse rate response to respiratory events was associated with greater risk of cardiovascular disease (CVD) morbidity and mortality. But the effect was seen only in nonsleepy patients. “We hypothesized that pulse rate response to apneas would predict which patients with OSA may most benefit from CPAP treatment. Now, our study suggests that there is, in fact, a subgroup of nonsleepy patients with OSA for whom CPAP could provide a reduction in risk, specifically those with a higher pulse rate response to their respiratory events,” Ali Azarbarzin, PhD, said in an interview.

Dr. Azarbarzin presented the study at the American Thoracic Society’s virtual international conference (Abstract A1103). He is in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and is assistant professor of medicine at Harvard Medical School, both in Boston.

The study is in line with recent efforts to subgroup OSA patients to determine which are at higher risk of cardiovascular events and other complications, and which are most likely to respond to treatment, according to Esra Tasali, MD, of the University of Chicago, who moderated the session where the study was presented. “The field is really urgently in need of coming up with new methods, and I think this study is getting a handle on that,” said Dr. Tasali in an interview.

“I think that this is really pointing toward a new area that the whole (sleep field) is moving toward, which is better phenotyping of sleep apnea so that we can come up with more personalized treatments,” said Dr. Tasali.

The patients who appeared to gain a cardiovascular benefit from CPAP represented about 16% of trial participants. Dr. Azarbarzin refrained from making clinical recommendations, citing the need for more data. The team next plans to reproduce the findings in additional, larger trials such as the SAVE and ISAACC trials. “Ultimately, our goal is to confirm our findings in a future randomized controlled trial of CPAP by enrolling participants based on their pulse rate response,” said Dr. Azarbarzin.

The RICCADSA study was a single center randomized, controlled trial with 226 patients with coronary artery disease and OSA who were randomized to CPAP or no CPAP treatment. In the overall population, CPAP treatment was not associated with a statistically significant change in repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality (hazard ratio [HR], 0.79; P = .435). That study assumed that the effect of OSA on CVD is similar across all subgroups of dHR.

The mean increase in heart rate was 7.1 beats per minute (BPM; standard deviation, 3.7). Each standard deviation increase in dHR was linked to greater CVD risk (HR, 1.45; P = .029). For each standard deviation decrease in dHR, treatment with CPAP decreased the CVD risk (HR, 0.54; P = .043).

For patients with a low dHR of 4 BPM, the hazard ratio for CVD was 0.8 with no CPAP treatment and 1.2 for CPAP treatment. For those at the mean value of 7 BPM, the HRs were 1.1 and 0.9 respectively. For those with a high dHR, (10 BPM), the hazard ratio was 1.6 without treatment and 0.7 with CPAP.

“We modeled delta heart rate interaction with CPAP, which was significant. What this means is that for someone with a mean delta heart rate of 7 beats per minute, the risk reduction (with CPAP) is similar to what RICCADSA reported. But if you look at those with high delta heart rate, the risk reduction was significantly larger. It was actually a more than 50% reduction of risk with CPAP treatment,” said Dr. Azarbarzin.

Dr. Azarbarzin has consulted for Somnifix and Apnimed and has received grants from Somnifix. Dr. Tasali has no relevant financial disclosures.

Some nonsleepy patients with coronary artery disease and obstructive sleep apnea (OSA) may receive cardiovascular benefit from continuous positive airway pressure (CPAP) therapy, according to a post hoc analysis of the RICCADSA clinical trial. That study found no benefit among patients overall, but the new analysis found that patients whose heart rate increases (delta heart rate, or dHR) more than average during apnea or hypopnea experienced fewer cardiovascular or cerebrovascular events during apnea or hypopnea when treated with CPAP.

Although RICCADSA showed no benefit, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Sleep Heart Health Study (SHHS) cohorts found that elevated pulse rate response to respiratory events was associated with greater risk of cardiovascular disease (CVD) morbidity and mortality. But the effect was seen only in nonsleepy patients. “We hypothesized that pulse rate response to apneas would predict which patients with OSA may most benefit from CPAP treatment. Now, our study suggests that there is, in fact, a subgroup of nonsleepy patients with OSA for whom CPAP could provide a reduction in risk, specifically those with a higher pulse rate response to their respiratory events,” Ali Azarbarzin, PhD, said in an interview.

Dr. Azarbarzin presented the study at the American Thoracic Society’s virtual international conference (Abstract A1103). He is in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and is assistant professor of medicine at Harvard Medical School, both in Boston.

The study is in line with recent efforts to subgroup OSA patients to determine which are at higher risk of cardiovascular events and other complications, and which are most likely to respond to treatment, according to Esra Tasali, MD, of the University of Chicago, who moderated the session where the study was presented. “The field is really urgently in need of coming up with new methods, and I think this study is getting a handle on that,” said Dr. Tasali in an interview.

“I think that this is really pointing toward a new area that the whole (sleep field) is moving toward, which is better phenotyping of sleep apnea so that we can come up with more personalized treatments,” said Dr. Tasali.

The patients who appeared to gain a cardiovascular benefit from CPAP represented about 16% of trial participants. Dr. Azarbarzin refrained from making clinical recommendations, citing the need for more data. The team next plans to reproduce the findings in additional, larger trials such as the SAVE and ISAACC trials. “Ultimately, our goal is to confirm our findings in a future randomized controlled trial of CPAP by enrolling participants based on their pulse rate response,” said Dr. Azarbarzin.

The RICCADSA study was a single center randomized, controlled trial with 226 patients with coronary artery disease and OSA who were randomized to CPAP or no CPAP treatment. In the overall population, CPAP treatment was not associated with a statistically significant change in repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality (hazard ratio [HR], 0.79; P = .435). That study assumed that the effect of OSA on CVD is similar across all subgroups of dHR.

The mean increase in heart rate was 7.1 beats per minute (BPM; standard deviation, 3.7). Each standard deviation increase in dHR was linked to greater CVD risk (HR, 1.45; P = .029). For each standard deviation decrease in dHR, treatment with CPAP decreased the CVD risk (HR, 0.54; P = .043).

For patients with a low dHR of 4 BPM, the hazard ratio for CVD was 0.8 with no CPAP treatment and 1.2 for CPAP treatment. For those at the mean value of 7 BPM, the HRs were 1.1 and 0.9 respectively. For those with a high dHR, (10 BPM), the hazard ratio was 1.6 without treatment and 0.7 with CPAP.

“We modeled delta heart rate interaction with CPAP, which was significant. What this means is that for someone with a mean delta heart rate of 7 beats per minute, the risk reduction (with CPAP) is similar to what RICCADSA reported. But if you look at those with high delta heart rate, the risk reduction was significantly larger. It was actually a more than 50% reduction of risk with CPAP treatment,” said Dr. Azarbarzin.

Dr. Azarbarzin has consulted for Somnifix and Apnimed and has received grants from Somnifix. Dr. Tasali has no relevant financial disclosures.

Some nonsleepy patients with coronary artery disease and obstructive sleep apnea (OSA) may receive cardiovascular benefit from continuous positive airway pressure (CPAP) therapy, according to a post hoc analysis of the RICCADSA clinical trial. That study found no benefit among patients overall, but the new analysis found that patients whose heart rate increases (delta heart rate, or dHR) more than average during apnea or hypopnea experienced fewer cardiovascular or cerebrovascular events during apnea or hypopnea when treated with CPAP.

Although RICCADSA showed no benefit, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Sleep Heart Health Study (SHHS) cohorts found that elevated pulse rate response to respiratory events was associated with greater risk of cardiovascular disease (CVD) morbidity and mortality. But the effect was seen only in nonsleepy patients. “We hypothesized that pulse rate response to apneas would predict which patients with OSA may most benefit from CPAP treatment. Now, our study suggests that there is, in fact, a subgroup of nonsleepy patients with OSA for whom CPAP could provide a reduction in risk, specifically those with a higher pulse rate response to their respiratory events,” Ali Azarbarzin, PhD, said in an interview.

Dr. Azarbarzin presented the study at the American Thoracic Society’s virtual international conference (Abstract A1103). He is in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and is assistant professor of medicine at Harvard Medical School, both in Boston.

The study is in line with recent efforts to subgroup OSA patients to determine which are at higher risk of cardiovascular events and other complications, and which are most likely to respond to treatment, according to Esra Tasali, MD, of the University of Chicago, who moderated the session where the study was presented. “The field is really urgently in need of coming up with new methods, and I think this study is getting a handle on that,” said Dr. Tasali in an interview.

“I think that this is really pointing toward a new area that the whole (sleep field) is moving toward, which is better phenotyping of sleep apnea so that we can come up with more personalized treatments,” said Dr. Tasali.

The patients who appeared to gain a cardiovascular benefit from CPAP represented about 16% of trial participants. Dr. Azarbarzin refrained from making clinical recommendations, citing the need for more data. The team next plans to reproduce the findings in additional, larger trials such as the SAVE and ISAACC trials. “Ultimately, our goal is to confirm our findings in a future randomized controlled trial of CPAP by enrolling participants based on their pulse rate response,” said Dr. Azarbarzin.

The RICCADSA study was a single center randomized, controlled trial with 226 patients with coronary artery disease and OSA who were randomized to CPAP or no CPAP treatment. In the overall population, CPAP treatment was not associated with a statistically significant change in repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality (hazard ratio [HR], 0.79; P = .435). That study assumed that the effect of OSA on CVD is similar across all subgroups of dHR.

The mean increase in heart rate was 7.1 beats per minute (BPM; standard deviation, 3.7). Each standard deviation increase in dHR was linked to greater CVD risk (HR, 1.45; P = .029). For each standard deviation decrease in dHR, treatment with CPAP decreased the CVD risk (HR, 0.54; P = .043).

For patients with a low dHR of 4 BPM, the hazard ratio for CVD was 0.8 with no CPAP treatment and 1.2 for CPAP treatment. For those at the mean value of 7 BPM, the HRs were 1.1 and 0.9 respectively. For those with a high dHR, (10 BPM), the hazard ratio was 1.6 without treatment and 0.7 with CPAP.

“We modeled delta heart rate interaction with CPAP, which was significant. What this means is that for someone with a mean delta heart rate of 7 beats per minute, the risk reduction (with CPAP) is similar to what RICCADSA reported. But if you look at those with high delta heart rate, the risk reduction was significantly larger. It was actually a more than 50% reduction of risk with CPAP treatment,” said Dr. Azarbarzin.

Dr. Azarbarzin has consulted for Somnifix and Apnimed and has received grants from Somnifix. Dr. Tasali has no relevant financial disclosures.

Results from the NAVIGATOR study of tezepelumab showed that treatment of adults and adolescents with severe, uncontrolled asthma with the new biologic led to a large reduction in exacerbations requiring hospital stays and ED visits.

Tezepelumab, codeveloped by Amgen and AstraZeneca, has a novel mechanism of action. It blocks thymic stromal lymphopoietin (TSLP), which is a cytokine produced by epithelial cells. TSLP levels correlate with airway obstruction, severity of disease, and glucocorticoid resistance. TSLP is involved in T2 inflammation within the airway, but also plays a role in the interactions between airway cells and immune cells, which doesn’t rely only solely on T2 inflammation. That broad mechanism of action distinguishes tezepelumab from most other biologics for the treatment of asthma, which are more targeted.

“By working at the top of the cascade, tezepelumab helps stop inflammation at a key source. Clinical trials with tezepelumab showed a clinical benefit in patients irrespective of their baseline biomarker level, including patients with low eosinophil levels at baseline,” said Jean-Pierre Llanos-Ackert, MD, who is executive medical director and global medical affairs lead for tezepelumab at Amgen.

The primary endpoint data look robust, according to Praveen Akuthota, MD, who is an associate professor of medicine at the University of California, San Diego, and comoderated the session at the American Thoracic Society’s virtual international conference, where the research was presented. The study was also published on May 13, 2021, in the New England Journal of Medicine. The conference session included updated results.

The drug holds promise, but more study is needed. “The question really will be, how is this drug different from the existing biologics? How much better is this drug in patients who have borderline T2 biomarkers, or even low T2. The study does show some efficacy in patients whose T2 signals may not be as robust. We’ll have to see with ongoing longitudinal data, how this drug positions, compared to the other agents. It’s obviously exciting, though, to have another option, given that we know what our current armamentarium of agents there are still nonresponders,” said Dr. Akuthota in an interview.

The other comoderator in the session, Laura Crotty Alexander, MD, commented: “It seems like it might work possibly even better than some that are directly covering one pathway only. Hopefully, this agent will be efficacious in a broader population than some of the more targeted biologics.” Dr. Alexander is an associate professor of medicine at the University of California, San Diego, and section chief of pulmonary critical care at the Veterans Affairs San Diego Healthcare System.

She pointed out that physicians often think of asthma patients in broad brush terms, as high or low T2, or T2 high and Th1 or neutrophilic or obese, but many patients present a more complicated picture. “There is some overlap across those phenotypes, such that an agent that works really well for one group doesn’t mean that it won’t have an impact, especially clinically, on some of these other phenotypes,” said Dr. Alexander.

Dr. Akuthota agreed. “Having options for patients whose biomarkers are not maybe as clear is, I think, important.”
 

Promising results

The study included 1,059 patients aged 12-80 who received 210 mg tezepelumab or placebo. Over 52 weeks, the treatment group had a 79% reduction in exacerbations requiring hospitalization or an ED visit, compared with placebo (rate ratio, 0.21; 95% confidence interval, 0.12-0.37), and an 85% reduction in exacerbations requiring hospitalization (RR, 0.15; 95% CI, 0.07-0.33). The drug increased the time to first exacerbation requiring hospitalization that required hospitalization or an ED visit, reducing risk by 65% (hazard ratio, 0.35; 95% CI, 0.22-0.56).

Fewer patients in the treatment group than placebo used asthma-related health care resources, including: ED visits (32 vs. 94), unscheduled visit to a specialist (285 vs. 406), telephone calls to a health care provider (234 vs. 599), ambulance transport (5 vs. 22), and home visits from a health care provider (18 vs. 22). Fewer patients in the tezepelumab group had hospital stays (3.2% vs. 7.0%), and they had a lower total number of hospital days (108 vs. 497) and days in the ICU (0 vs. 31).

The study was funded by Amgen and AstraZeneca. Dr. Llanos-Ackert is an employee of Amgen. Dr. Alexander has no relevant financial disclosures. Dr. Akuthota has consulted for AstraZeneca and participated in their clinical trials.

Results from the NAVIGATOR study of tezepelumab showed that treatment of adults and adolescents with severe, uncontrolled asthma with the new biologic led to a large reduction in exacerbations requiring hospital stays and ED visits.

Tezepelumab, codeveloped by Amgen and AstraZeneca, has a novel mechanism of action. It blocks thymic stromal lymphopoietin (TSLP), which is a cytokine produced by epithelial cells. TSLP levels correlate with airway obstruction, severity of disease, and glucocorticoid resistance. TSLP is involved in T2 inflammation within the airway, but also plays a role in the interactions between airway cells and immune cells, which doesn’t rely only solely on T2 inflammation. That broad mechanism of action distinguishes tezepelumab from most other biologics for the treatment of asthma, which are more targeted.

“By working at the top of the cascade, tezepelumab helps stop inflammation at a key source. Clinical trials with tezepelumab showed a clinical benefit in patients irrespective of their baseline biomarker level, including patients with low eosinophil levels at baseline,” said Jean-Pierre Llanos-Ackert, MD, who is executive medical director and global medical affairs lead for tezepelumab at Amgen.

The primary endpoint data look robust, according to Praveen Akuthota, MD, who is an associate professor of medicine at the University of California, San Diego, and comoderated the session at the American Thoracic Society’s virtual international conference, where the research was presented. The study was also published on May 13, 2021, in the New England Journal of Medicine. The conference session included updated results.

The drug holds promise, but more study is needed. “The question really will be, how is this drug different from the existing biologics? How much better is this drug in patients who have borderline T2 biomarkers, or even low T2. The study does show some efficacy in patients whose T2 signals may not be as robust. We’ll have to see with ongoing longitudinal data, how this drug positions, compared to the other agents. It’s obviously exciting, though, to have another option, given that we know what our current armamentarium of agents there are still nonresponders,” said Dr. Akuthota in an interview.

The other comoderator in the session, Laura Crotty Alexander, MD, commented: “It seems like it might work possibly even better than some that are directly covering one pathway only. Hopefully, this agent will be efficacious in a broader population than some of the more targeted biologics.” Dr. Alexander is an associate professor of medicine at the University of California, San Diego, and section chief of pulmonary critical care at the Veterans Affairs San Diego Healthcare System.

She pointed out that physicians often think of asthma patients in broad brush terms, as high or low T2, or T2 high and Th1 or neutrophilic or obese, but many patients present a more complicated picture. “There is some overlap across those phenotypes, such that an agent that works really well for one group doesn’t mean that it won’t have an impact, especially clinically, on some of these other phenotypes,” said Dr. Alexander.

Dr. Akuthota agreed. “Having options for patients whose biomarkers are not maybe as clear is, I think, important.”
 

Promising results

The study included 1,059 patients aged 12-80 who received 210 mg tezepelumab or placebo. Over 52 weeks, the treatment group had a 79% reduction in exacerbations requiring hospitalization or an ED visit, compared with placebo (rate ratio, 0.21; 95% confidence interval, 0.12-0.37), and an 85% reduction in exacerbations requiring hospitalization (RR, 0.15; 95% CI, 0.07-0.33). The drug increased the time to first exacerbation requiring hospitalization that required hospitalization or an ED visit, reducing risk by 65% (hazard ratio, 0.35; 95% CI, 0.22-0.56).

Fewer patients in the treatment group than placebo used asthma-related health care resources, including: ED visits (32 vs. 94), unscheduled visit to a specialist (285 vs. 406), telephone calls to a health care provider (234 vs. 599), ambulance transport (5 vs. 22), and home visits from a health care provider (18 vs. 22). Fewer patients in the tezepelumab group had hospital stays (3.2% vs. 7.0%), and they had a lower total number of hospital days (108 vs. 497) and days in the ICU (0 vs. 31).

The study was funded by Amgen and AstraZeneca. Dr. Llanos-Ackert is an employee of Amgen. Dr. Alexander has no relevant financial disclosures. Dr. Akuthota has consulted for AstraZeneca and participated in their clinical trials.

Results from the NAVIGATOR study of tezepelumab showed that treatment of adults and adolescents with severe, uncontrolled asthma with the new biologic led to a large reduction in exacerbations requiring hospital stays and ED visits.

Tezepelumab, codeveloped by Amgen and AstraZeneca, has a novel mechanism of action. It blocks thymic stromal lymphopoietin (TSLP), which is a cytokine produced by epithelial cells. TSLP levels correlate with airway obstruction, severity of disease, and glucocorticoid resistance. TSLP is involved in T2 inflammation within the airway, but also plays a role in the interactions between airway cells and immune cells, which doesn’t rely only solely on T2 inflammation. That broad mechanism of action distinguishes tezepelumab from most other biologics for the treatment of asthma, which are more targeted.

“By working at the top of the cascade, tezepelumab helps stop inflammation at a key source. Clinical trials with tezepelumab showed a clinical benefit in patients irrespective of their baseline biomarker level, including patients with low eosinophil levels at baseline,” said Jean-Pierre Llanos-Ackert, MD, who is executive medical director and global medical affairs lead for tezepelumab at Amgen.

The primary endpoint data look robust, according to Praveen Akuthota, MD, who is an associate professor of medicine at the University of California, San Diego, and comoderated the session at the American Thoracic Society’s virtual international conference, where the research was presented. The study was also published on May 13, 2021, in the New England Journal of Medicine. The conference session included updated results.

The drug holds promise, but more study is needed. “The question really will be, how is this drug different from the existing biologics? How much better is this drug in patients who have borderline T2 biomarkers, or even low T2. The study does show some efficacy in patients whose T2 signals may not be as robust. We’ll have to see with ongoing longitudinal data, how this drug positions, compared to the other agents. It’s obviously exciting, though, to have another option, given that we know what our current armamentarium of agents there are still nonresponders,” said Dr. Akuthota in an interview.

The other comoderator in the session, Laura Crotty Alexander, MD, commented: “It seems like it might work possibly even better than some that are directly covering one pathway only. Hopefully, this agent will be efficacious in a broader population than some of the more targeted biologics.” Dr. Alexander is an associate professor of medicine at the University of California, San Diego, and section chief of pulmonary critical care at the Veterans Affairs San Diego Healthcare System.

She pointed out that physicians often think of asthma patients in broad brush terms, as high or low T2, or T2 high and Th1 or neutrophilic or obese, but many patients present a more complicated picture. “There is some overlap across those phenotypes, such that an agent that works really well for one group doesn’t mean that it won’t have an impact, especially clinically, on some of these other phenotypes,” said Dr. Alexander.

Dr. Akuthota agreed. “Having options for patients whose biomarkers are not maybe as clear is, I think, important.”
 

Promising results

The study included 1,059 patients aged 12-80 who received 210 mg tezepelumab or placebo. Over 52 weeks, the treatment group had a 79% reduction in exacerbations requiring hospitalization or an ED visit, compared with placebo (rate ratio, 0.21; 95% confidence interval, 0.12-0.37), and an 85% reduction in exacerbations requiring hospitalization (RR, 0.15; 95% CI, 0.07-0.33). The drug increased the time to first exacerbation requiring hospitalization that required hospitalization or an ED visit, reducing risk by 65% (hazard ratio, 0.35; 95% CI, 0.22-0.56).

Fewer patients in the treatment group than placebo used asthma-related health care resources, including: ED visits (32 vs. 94), unscheduled visit to a specialist (285 vs. 406), telephone calls to a health care provider (234 vs. 599), ambulance transport (5 vs. 22), and home visits from a health care provider (18 vs. 22). Fewer patients in the tezepelumab group had hospital stays (3.2% vs. 7.0%), and they had a lower total number of hospital days (108 vs. 497) and days in the ICU (0 vs. 31).

The study was funded by Amgen and AstraZeneca. Dr. Llanos-Ackert is an employee of Amgen. Dr. Alexander has no relevant financial disclosures. Dr. Akuthota has consulted for AstraZeneca and participated in their clinical trials.

Adults in their 30s, 40s and 50s with chronic obstructive pulmonary disease (COPD) experience significant morbidity and excess mortality from the disease, results of a population-based study show.

Among adults aged 35-55 years with COPD in Ontario in a longitudinal population cohort study, the overall mortality rate was fivefold higher, compared with other adults in the same age range without COPD.

In contrast, the mortality rate among adults 65 years and older with COPD was 2.5-fold higher than that of their peers without COPD, reported Alina J. Blazer, MSc, MD, a clinical and research fellow at the University of Toronto.

“Overall, our study has shown that younger adults with COPD experience significant morbidity, as evidence by their elevated rates of health care use and excess mortality from their disease. This study provides further evidence that so-called ‘early’ COPD is not a benign disease, and suggests that we should focus clinical efforts on identifying COPD in younger patients, in the hopes that earlier intervention may improve their current health, reduce resource utilization, and prevent further disease progression,” she said during a minisymposium at the American Thoracic Society’s virtual international conference (Abstract A1131).

COPD is widely regarded as a disease affecting only older adults, but it can also occur in those younger than 65, and although it is commonly assumed that COPD diagnosed earlier in life will be milder in severity, this assumption has not been fully explored in real-world settings, Dr. Blazer said.

She and her colleagues conducted a study to examine disease burden as measured by health services utilization and mortality among younger adults with COPD, and compared the rates with those of older adults with COPD.

The sample for this study included 194,759 adults with COPD aged 35-55 years in Ontario in 2016. COPD was identified from health administrative data for three or more outpatient claims or one or more hospitalization claims for COPD over a 2-year period.

For context, the data were compared with those for 496,2113 COPD patients aged 65 years and older.

They found that, compared with their peers without the disease, younger adults had a 3.1-fold higher rate of hospitalization for any cause, a 2.2-fold higher rate of all-cause ED visits, and a 1.7-fold higher rate of outpatient visits for any cause.

In contrast, the comparative rates for seniors with versus without COPD were 2.1-fold, 1.8-fold, and 1.4-fold, respectively.

As noted before, the mortality rate for younger adults with COPD was 5-fold higher than for those without COPD, compared with 2.5-fold among older adults with COPD versus those without.
 

Earlier diagnosis, follow-up

“A very important talk,” commented session comoderator Valerie Press, MD, MPH, from the University of Chicago. “I know that there’s a lot of work to be done in earlier diagnosis in general, and I think starting with the younger population is a really important area.”

She asked Dr. Blazer about the possibility of asthma codiagnosis or misdiagnosis in the younger patients.

“We use a very specific, validated case definition in the study that our group has used before, and the specificity is over 96% for physician-diagnosed COPD, at the expense of sensitivity, so if anything we probably underestimated the rate of COPD in our study,” Dr. Blazer said.

Audience member Sherry Rogers, MD, an allergist and immunologist in private practice in Syracuse, N.Y., asked whether the investigators could determine what proportion of the excess mortality they saw was attributable to COPD.

“This was looking at all-cause mortality, so we don’t know that it’s necessarily all attributable to COPD per se but perhaps also to COPD-attributable comorbidities,” Dr. Blazer said. “It would be important to piece out the actual causes of mortality that are contributing to that elevated [morality] in that population.”

She added that the next step could include examining rates of specialty referrals and pharmacotherapy to see whether younger patients with COPD are receiving appropriate care, and to ascertain how they are being followed.

The study was supported by the University of Toronto and Sunnybrook Research Institute. Dr. Blazer reported no conflicts of interest to disclose.

Adults in their 30s, 40s and 50s with chronic obstructive pulmonary disease (COPD) experience significant morbidity and excess mortality from the disease, results of a population-based study show.

Among adults aged 35-55 years with COPD in Ontario in a longitudinal population cohort study, the overall mortality rate was fivefold higher, compared with other adults in the same age range without COPD.

In contrast, the mortality rate among adults 65 years and older with COPD was 2.5-fold higher than that of their peers without COPD, reported Alina J. Blazer, MSc, MD, a clinical and research fellow at the University of Toronto.

“Overall, our study has shown that younger adults with COPD experience significant morbidity, as evidence by their elevated rates of health care use and excess mortality from their disease. This study provides further evidence that so-called ‘early’ COPD is not a benign disease, and suggests that we should focus clinical efforts on identifying COPD in younger patients, in the hopes that earlier intervention may improve their current health, reduce resource utilization, and prevent further disease progression,” she said during a minisymposium at the American Thoracic Society’s virtual international conference (Abstract A1131).

COPD is widely regarded as a disease affecting only older adults, but it can also occur in those younger than 65, and although it is commonly assumed that COPD diagnosed earlier in life will be milder in severity, this assumption has not been fully explored in real-world settings, Dr. Blazer said.

She and her colleagues conducted a study to examine disease burden as measured by health services utilization and mortality among younger adults with COPD, and compared the rates with those of older adults with COPD.

The sample for this study included 194,759 adults with COPD aged 35-55 years in Ontario in 2016. COPD was identified from health administrative data for three or more outpatient claims or one or more hospitalization claims for COPD over a 2-year period.

For context, the data were compared with those for 496,2113 COPD patients aged 65 years and older.

They found that, compared with their peers without the disease, younger adults had a 3.1-fold higher rate of hospitalization for any cause, a 2.2-fold higher rate of all-cause ED visits, and a 1.7-fold higher rate of outpatient visits for any cause.

In contrast, the comparative rates for seniors with versus without COPD were 2.1-fold, 1.8-fold, and 1.4-fold, respectively.

As noted before, the mortality rate for younger adults with COPD was 5-fold higher than for those without COPD, compared with 2.5-fold among older adults with COPD versus those without.
 

Earlier diagnosis, follow-up

“A very important talk,” commented session comoderator Valerie Press, MD, MPH, from the University of Chicago. “I know that there’s a lot of work to be done in earlier diagnosis in general, and I think starting with the younger population is a really important area.”

She asked Dr. Blazer about the possibility of asthma codiagnosis or misdiagnosis in the younger patients.

“We use a very specific, validated case definition in the study that our group has used before, and the specificity is over 96% for physician-diagnosed COPD, at the expense of sensitivity, so if anything we probably underestimated the rate of COPD in our study,” Dr. Blazer said.

Audience member Sherry Rogers, MD, an allergist and immunologist in private practice in Syracuse, N.Y., asked whether the investigators could determine what proportion of the excess mortality they saw was attributable to COPD.

“This was looking at all-cause mortality, so we don’t know that it’s necessarily all attributable to COPD per se but perhaps also to COPD-attributable comorbidities,” Dr. Blazer said. “It would be important to piece out the actual causes of mortality that are contributing to that elevated [morality] in that population.”

She added that the next step could include examining rates of specialty referrals and pharmacotherapy to see whether younger patients with COPD are receiving appropriate care, and to ascertain how they are being followed.

The study was supported by the University of Toronto and Sunnybrook Research Institute. Dr. Blazer reported no conflicts of interest to disclose.

Adults in their 30s, 40s and 50s with chronic obstructive pulmonary disease (COPD) experience significant morbidity and excess mortality from the disease, results of a population-based study show.

Among adults aged 35-55 years with COPD in Ontario in a longitudinal population cohort study, the overall mortality rate was fivefold higher, compared with other adults in the same age range without COPD.

In contrast, the mortality rate among adults 65 years and older with COPD was 2.5-fold higher than that of their peers without COPD, reported Alina J. Blazer, MSc, MD, a clinical and research fellow at the University of Toronto.

“Overall, our study has shown that younger adults with COPD experience significant morbidity, as evidence by their elevated rates of health care use and excess mortality from their disease. This study provides further evidence that so-called ‘early’ COPD is not a benign disease, and suggests that we should focus clinical efforts on identifying COPD in younger patients, in the hopes that earlier intervention may improve their current health, reduce resource utilization, and prevent further disease progression,” she said during a minisymposium at the American Thoracic Society’s virtual international conference (Abstract A1131).

COPD is widely regarded as a disease affecting only older adults, but it can also occur in those younger than 65, and although it is commonly assumed that COPD diagnosed earlier in life will be milder in severity, this assumption has not been fully explored in real-world settings, Dr. Blazer said.

She and her colleagues conducted a study to examine disease burden as measured by health services utilization and mortality among younger adults with COPD, and compared the rates with those of older adults with COPD.

The sample for this study included 194,759 adults with COPD aged 35-55 years in Ontario in 2016. COPD was identified from health administrative data for three or more outpatient claims or one or more hospitalization claims for COPD over a 2-year period.

For context, the data were compared with those for 496,2113 COPD patients aged 65 years and older.

They found that, compared with their peers without the disease, younger adults had a 3.1-fold higher rate of hospitalization for any cause, a 2.2-fold higher rate of all-cause ED visits, and a 1.7-fold higher rate of outpatient visits for any cause.

In contrast, the comparative rates for seniors with versus without COPD were 2.1-fold, 1.8-fold, and 1.4-fold, respectively.

As noted before, the mortality rate for younger adults with COPD was 5-fold higher than for those without COPD, compared with 2.5-fold among older adults with COPD versus those without.
 

Earlier diagnosis, follow-up

“A very important talk,” commented session comoderator Valerie Press, MD, MPH, from the University of Chicago. “I know that there’s a lot of work to be done in earlier diagnosis in general, and I think starting with the younger population is a really important area.”

She asked Dr. Blazer about the possibility of asthma codiagnosis or misdiagnosis in the younger patients.

“We use a very specific, validated case definition in the study that our group has used before, and the specificity is over 96% for physician-diagnosed COPD, at the expense of sensitivity, so if anything we probably underestimated the rate of COPD in our study,” Dr. Blazer said.

Audience member Sherry Rogers, MD, an allergist and immunologist in private practice in Syracuse, N.Y., asked whether the investigators could determine what proportion of the excess mortality they saw was attributable to COPD.

“This was looking at all-cause mortality, so we don’t know that it’s necessarily all attributable to COPD per se but perhaps also to COPD-attributable comorbidities,” Dr. Blazer said. “It would be important to piece out the actual causes of mortality that are contributing to that elevated [morality] in that population.”

She added that the next step could include examining rates of specialty referrals and pharmacotherapy to see whether younger patients with COPD are receiving appropriate care, and to ascertain how they are being followed.

The study was supported by the University of Toronto and Sunnybrook Research Institute. Dr. Blazer reported no conflicts of interest to disclose.

The benefits of a triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist combination extend to patients with moderate as well as severe chronic obstructive pulmonary disease (COPD).

That’s according to investigators in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

In a subanalysis of data on patients with moderate COPD who were enrolled in the comparison trial, the single-inhaler combination of the inhaled corticosteroid (ICS) budesonide, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta₂ agonist (LABA) formoterol fumarate (BGF) showed benefits in terms of COPD exacerbations, lung function, symptoms, and quality-of-life compared with either of two dual therapy combinations (glycopyrrolate or budesonide with formoterol [GFF/BFF]).

“A moderate benefit:risk ratio was demonstrated in patients with moderate COPD, consistent with the results of the overall ETHOS population, indicating the results of the ETHOS study were not driven by patients with severe or very severe COPD,” wrote Gary T. Ferguson, MD, from the Pulmonary Research Institute of Southeast Michigan in Farmington Hills, and colleagues. Their poster was presented during the American Thoracic Society’s virtual international conference. (Abstract A2244).

As reported at ATS 2020, in the overall ETHOS population of 8,509 patients with moderate to very severe COPD the annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320-mcg and 160-mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, Klaus F. Rabe, MD, PhD, of LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues found.
 

Subanalysis details

At the 2021 iteration of ATS, ETHOS investigator Dr. Ferguson and colleagues reported results for 613 patients with moderate COPD assigned to BGF 320 mcg, 604 assigned to BGF 160 mcg, 596 assigned to GFF, and 614 randomized to BFF.

Baseline demographic and clinical characteristics were similar among the groups, including age, sex, smoking status, mean COPD Assessment Test (CAT) score, mean blood eosinophil count, ICS use at screening, exacerbations in the previous year, mean postbronchodilator forced expiratory volume in 1 second (FEV₁) percentage of predicted, and mean postbronchodilator percentage reversibility.

A modified intention-to-treat (ITT) analysis showed that the rate of moderate or severe exacerbations over 52 weeks with BGF 320 mcg was 21% lower than with GFF (P = .0123), but only 4% lower than with BFF, a difference that was not statistically significant.

The BGF 160-mg dose was associated with a 30% reduction in exacerbations vs. GFF (P = .0002), and with a nonsignificant reduction of 15% compared with BFF.

­There was a numerical but not statistically significant improvement from baseline at week 24 in morning pre-dose trough FEV₁ between the BGF 320-mcg dose and GFF (difference 47 mL), and a significant improvement (90 mL) with BGF compared with BFF (P = .0006). The BGF 160-mcg dose was associated with a larger improvement (89 mL) compared with BFF (P = .0004) but not with GFF.

The FEV₁ area under the curve (AUC) of receiver operating characteristics from 0 to 4 hours was superior with BGF at both doses compared with both GFF and BFF.

Patients who used BGF 320 mcg also used significantly less rescue medication over 24 weeks compared with patients who used GFF (P < .0001) or BFF (P = .0001). There were no significant differences in rescue medication use between the BGF 160-mg dose and either of the dual therapy combinations.

Time to clinically important deterioration – defined as a greater than ­100 mL decrease in trough FEV₁, or a ­4 units increase in St. George’s Respiratory Questionnaire total score, or a treatment-emergent moderate/severe COPD exacerbation occurring up to week 52 – was significantly longer with the 320-mcg but not 160-mcg BGF dose compared with GFF (P = .0295) or BFF (P = .0172).
 

Safety

Treatment-emergent adverse events (TEAEs) occurred in about two-thirds of patients in each trial arm, although TEAEs related to study treatment were more common with the two triple-therapy combinations and with BFF than with GFF.

TEAEs leading to study discontinuation occurred in 5.5% of patients on BGF 320 mcg, 4% on BGF 160 mcg, 4.5% on GFF, and 3.2% on BFF.

Confirmed major adverse cardiovascular events occurred in 0.8% and 1.5% in the BGF 320- and 160-mcg groups, respectively, in 1.8% of patients in the GFF arm, and 1.5% in the BFF arm.

Confirmed pneumonia was seen in 2.6% of patients in each BGF arm, 2.2% in the GFF arm, and 3.6% in the BFF arm.
 

Selected population

In a comment, David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, noted that the enrollment criteria for ETHOS tended to skew the population toward patients with severe disease.

In the trial, all patients were receiving at least two inhaled maintenance therapies at the time of screening, and had a postbronchodilator ratio of FEV₁ to forced vital capacity of less than 0.7, with a postbronchodilator FEV₁ of 25%-65% of the predicted normal value. The patients all had a smoking history of at least 10 pack-years and a documented history of at least one moderate or severe COPD exacerbation in the year before screening.

“The question was whether they would see the same results in people with more moderate impairment, and the answer in this subanalysis is ‘yes.’ The findings weren’t identical between patients with severe and moderate disease, but there were similarities with what was seen in the overall ETHOS study,” he said.

The ETHOS Trial was supported by Pearl Therapeutics. Dr. Ferguson reported grants, personal fees, and nonfinancial support from AstraZeneca during the conduct of the study; and grants, fees, and nonfinancial support from Pearl and others. Dr. Mannino reports recruitment to an advisory board for AstraZeneca.

The benefits of a triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist combination extend to patients with moderate as well as severe chronic obstructive pulmonary disease (COPD).

That’s according to investigators in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

In a subanalysis of data on patients with moderate COPD who were enrolled in the comparison trial, the single-inhaler combination of the inhaled corticosteroid (ICS) budesonide, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta₂ agonist (LABA) formoterol fumarate (BGF) showed benefits in terms of COPD exacerbations, lung function, symptoms, and quality-of-life compared with either of two dual therapy combinations (glycopyrrolate or budesonide with formoterol [GFF/BFF]).

“A moderate benefit:risk ratio was demonstrated in patients with moderate COPD, consistent with the results of the overall ETHOS population, indicating the results of the ETHOS study were not driven by patients with severe or very severe COPD,” wrote Gary T. Ferguson, MD, from the Pulmonary Research Institute of Southeast Michigan in Farmington Hills, and colleagues. Their poster was presented during the American Thoracic Society’s virtual international conference. (Abstract A2244).

As reported at ATS 2020, in the overall ETHOS population of 8,509 patients with moderate to very severe COPD the annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320-mcg and 160-mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, Klaus F. Rabe, MD, PhD, of LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues found.
 

Subanalysis details

At the 2021 iteration of ATS, ETHOS investigator Dr. Ferguson and colleagues reported results for 613 patients with moderate COPD assigned to BGF 320 mcg, 604 assigned to BGF 160 mcg, 596 assigned to GFF, and 614 randomized to BFF.

Baseline demographic and clinical characteristics were similar among the groups, including age, sex, smoking status, mean COPD Assessment Test (CAT) score, mean blood eosinophil count, ICS use at screening, exacerbations in the previous year, mean postbronchodilator forced expiratory volume in 1 second (FEV₁) percentage of predicted, and mean postbronchodilator percentage reversibility.

A modified intention-to-treat (ITT) analysis showed that the rate of moderate or severe exacerbations over 52 weeks with BGF 320 mcg was 21% lower than with GFF (P = .0123), but only 4% lower than with BFF, a difference that was not statistically significant.

The BGF 160-mg dose was associated with a 30% reduction in exacerbations vs. GFF (P = .0002), and with a nonsignificant reduction of 15% compared with BFF.

­There was a numerical but not statistically significant improvement from baseline at week 24 in morning pre-dose trough FEV₁ between the BGF 320-mcg dose and GFF (difference 47 mL), and a significant improvement (90 mL) with BGF compared with BFF (P = .0006). The BGF 160-mcg dose was associated with a larger improvement (89 mL) compared with BFF (P = .0004) but not with GFF.

The FEV₁ area under the curve (AUC) of receiver operating characteristics from 0 to 4 hours was superior with BGF at both doses compared with both GFF and BFF.

Patients who used BGF 320 mcg also used significantly less rescue medication over 24 weeks compared with patients who used GFF (P < .0001) or BFF (P = .0001). There were no significant differences in rescue medication use between the BGF 160-mg dose and either of the dual therapy combinations.

Time to clinically important deterioration – defined as a greater than ­100 mL decrease in trough FEV₁, or a ­4 units increase in St. George’s Respiratory Questionnaire total score, or a treatment-emergent moderate/severe COPD exacerbation occurring up to week 52 – was significantly longer with the 320-mcg but not 160-mcg BGF dose compared with GFF (P = .0295) or BFF (P = .0172).
 

Safety

Treatment-emergent adverse events (TEAEs) occurred in about two-thirds of patients in each trial arm, although TEAEs related to study treatment were more common with the two triple-therapy combinations and with BFF than with GFF.

TEAEs leading to study discontinuation occurred in 5.5% of patients on BGF 320 mcg, 4% on BGF 160 mcg, 4.5% on GFF, and 3.2% on BFF.

Confirmed major adverse cardiovascular events occurred in 0.8% and 1.5% in the BGF 320- and 160-mcg groups, respectively, in 1.8% of patients in the GFF arm, and 1.5% in the BFF arm.

Confirmed pneumonia was seen in 2.6% of patients in each BGF arm, 2.2% in the GFF arm, and 3.6% in the BFF arm.
 

Selected population

In a comment, David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, noted that the enrollment criteria for ETHOS tended to skew the population toward patients with severe disease.

In the trial, all patients were receiving at least two inhaled maintenance therapies at the time of screening, and had a postbronchodilator ratio of FEV₁ to forced vital capacity of less than 0.7, with a postbronchodilator FEV₁ of 25%-65% of the predicted normal value. The patients all had a smoking history of at least 10 pack-years and a documented history of at least one moderate or severe COPD exacerbation in the year before screening.

“The question was whether they would see the same results in people with more moderate impairment, and the answer in this subanalysis is ‘yes.’ The findings weren’t identical between patients with severe and moderate disease, but there were similarities with what was seen in the overall ETHOS study,” he said.

The ETHOS Trial was supported by Pearl Therapeutics. Dr. Ferguson reported grants, personal fees, and nonfinancial support from AstraZeneca during the conduct of the study; and grants, fees, and nonfinancial support from Pearl and others. Dr. Mannino reports recruitment to an advisory board for AstraZeneca.

The benefits of a triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist combination extend to patients with moderate as well as severe chronic obstructive pulmonary disease (COPD).

That’s according to investigators in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

In a subanalysis of data on patients with moderate COPD who were enrolled in the comparison trial, the single-inhaler combination of the inhaled corticosteroid (ICS) budesonide, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta₂ agonist (LABA) formoterol fumarate (BGF) showed benefits in terms of COPD exacerbations, lung function, symptoms, and quality-of-life compared with either of two dual therapy combinations (glycopyrrolate or budesonide with formoterol [GFF/BFF]).

“A moderate benefit:risk ratio was demonstrated in patients with moderate COPD, consistent with the results of the overall ETHOS population, indicating the results of the ETHOS study were not driven by patients with severe or very severe COPD,” wrote Gary T. Ferguson, MD, from the Pulmonary Research Institute of Southeast Michigan in Farmington Hills, and colleagues. Their poster was presented during the American Thoracic Society’s virtual international conference. (Abstract A2244).

As reported at ATS 2020, in the overall ETHOS population of 8,509 patients with moderate to very severe COPD the annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320-mcg and 160-mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, Klaus F. Rabe, MD, PhD, of LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues found.
 

Subanalysis details

At the 2021 iteration of ATS, ETHOS investigator Dr. Ferguson and colleagues reported results for 613 patients with moderate COPD assigned to BGF 320 mcg, 604 assigned to BGF 160 mcg, 596 assigned to GFF, and 614 randomized to BFF.

Baseline demographic and clinical characteristics were similar among the groups, including age, sex, smoking status, mean COPD Assessment Test (CAT) score, mean blood eosinophil count, ICS use at screening, exacerbations in the previous year, mean postbronchodilator forced expiratory volume in 1 second (FEV₁) percentage of predicted, and mean postbronchodilator percentage reversibility.

A modified intention-to-treat (ITT) analysis showed that the rate of moderate or severe exacerbations over 52 weeks with BGF 320 mcg was 21% lower than with GFF (P = .0123), but only 4% lower than with BFF, a difference that was not statistically significant.

The BGF 160-mg dose was associated with a 30% reduction in exacerbations vs. GFF (P = .0002), and with a nonsignificant reduction of 15% compared with BFF.

­There was a numerical but not statistically significant improvement from baseline at week 24 in morning pre-dose trough FEV₁ between the BGF 320-mcg dose and GFF (difference 47 mL), and a significant improvement (90 mL) with BGF compared with BFF (P = .0006). The BGF 160-mcg dose was associated with a larger improvement (89 mL) compared with BFF (P = .0004) but not with GFF.

The FEV₁ area under the curve (AUC) of receiver operating characteristics from 0 to 4 hours was superior with BGF at both doses compared with both GFF and BFF.

Patients who used BGF 320 mcg also used significantly less rescue medication over 24 weeks compared with patients who used GFF (P < .0001) or BFF (P = .0001). There were no significant differences in rescue medication use between the BGF 160-mg dose and either of the dual therapy combinations.

Time to clinically important deterioration – defined as a greater than ­100 mL decrease in trough FEV₁, or a ­4 units increase in St. George’s Respiratory Questionnaire total score, or a treatment-emergent moderate/severe COPD exacerbation occurring up to week 52 – was significantly longer with the 320-mcg but not 160-mcg BGF dose compared with GFF (P = .0295) or BFF (P = .0172).
 

Safety

Treatment-emergent adverse events (TEAEs) occurred in about two-thirds of patients in each trial arm, although TEAEs related to study treatment were more common with the two triple-therapy combinations and with BFF than with GFF.

TEAEs leading to study discontinuation occurred in 5.5% of patients on BGF 320 mcg, 4% on BGF 160 mcg, 4.5% on GFF, and 3.2% on BFF.

Confirmed major adverse cardiovascular events occurred in 0.8% and 1.5% in the BGF 320- and 160-mcg groups, respectively, in 1.8% of patients in the GFF arm, and 1.5% in the BFF arm.

Confirmed pneumonia was seen in 2.6% of patients in each BGF arm, 2.2% in the GFF arm, and 3.6% in the BFF arm.
 

Selected population

In a comment, David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, noted that the enrollment criteria for ETHOS tended to skew the population toward patients with severe disease.

In the trial, all patients were receiving at least two inhaled maintenance therapies at the time of screening, and had a postbronchodilator ratio of FEV₁ to forced vital capacity of less than 0.7, with a postbronchodilator FEV₁ of 25%-65% of the predicted normal value. The patients all had a smoking history of at least 10 pack-years and a documented history of at least one moderate or severe COPD exacerbation in the year before screening.

“The question was whether they would see the same results in people with more moderate impairment, and the answer in this subanalysis is ‘yes.’ The findings weren’t identical between patients with severe and moderate disease, but there were similarities with what was seen in the overall ETHOS study,” he said.

The ETHOS Trial was supported by Pearl Therapeutics. Dr. Ferguson reported grants, personal fees, and nonfinancial support from AstraZeneca during the conduct of the study; and grants, fees, and nonfinancial support from Pearl and others. Dr. Mannino reports recruitment to an advisory board for AstraZeneca.

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.

Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.

In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.

(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)

“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
 

GOLD standard

The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.

They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.

The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.

They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.

The investigators found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).

In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.

In women, however, only age was significantly predictive for cardiac disease.

“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
 

Reassuring data

David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.

“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”

Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.

“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.

The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.

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

Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.

Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.

In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.

(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)

“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
 

GOLD standard

The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.

They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.

The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.

They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.

The investigators found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).

In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.

In women, however, only age was significantly predictive for cardiac disease.

“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
 

Reassuring data

David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.

“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”

Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.

“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.

The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.

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

Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.

Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.

In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.

(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)

“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
 

GOLD standard

The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.

They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.

The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.

They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.

The investigators found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).

In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.

In women, however, only age was significantly predictive for cardiac disease.

“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
 

Reassuring data

David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.

“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”

Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.

“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.

The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.

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

A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.

Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.

Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.

A critical care specialist who was not involved in the study said that the results are concerning but not surprising.

“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.

The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
 

Retrospective analysis

Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.

Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).

In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).

Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
 

‘Mechanisms unclear’

“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”

They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”

Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.

No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.

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

A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.

Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.

Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.

A critical care specialist who was not involved in the study said that the results are concerning but not surprising.

“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.

The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
 

Retrospective analysis

Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.

Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).

In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).

Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
 

‘Mechanisms unclear’

“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”

They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”

Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.

No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.

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

A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.

Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.

Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.

A critical care specialist who was not involved in the study said that the results are concerning but not surprising.

“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.

The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
 

Retrospective analysis

Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.

Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).

In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).

Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
 

‘Mechanisms unclear’

“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”

They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”

Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.

No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.

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

Just 1 week after it looked like the COVID-19 situation in children might be taking another turn for the worse, the number of new pediatric cases dropped to its lowest level since October, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The week of May 7-13 saw just under 49,000 new cases reported in U.S. children, down from 72,000 the week before and the lowest number recorded since the week of Oct. 9-15, 2020, the AAP and CHA said in their weekly COVID-19 report. During the week of April 30 to May 6 – the same week Rhode Island reported a large backlog of cases and increased its total by 30% – the number of new cases went up slightly after 2 weeks of declines.

Other positive indicators come in the form of the proportion of cases occurring in children. The cumulative percentage of cases in children since the start of the pandemic remained at 14.0% for a second consecutive week, and the proportion of new cases in children held at 24.0% and did not increase for the first time in 6 weeks, based on data from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

The total number of child COVID-19 cases reported in these jurisdictions is now up to 3.9 million, for a cumulative rate of 5,187 cases per 100,000 children in the United States. Among the states, total counts range from a low of 4,070 in Hawaii to 475,619 in California. Hawaii also has the lowest rate at 1,357 per 100,000 children, while the highest, 9,778 per 100,000, can be found in Rhode Island, the AAP and CHA said.

Deaths in children continue to accumulate at a relatively slow pace, with two more added during the week of May 7-13, bringing the total to 308 for the entire pandemic in 43 states, New York City, Puerto Rico, and Guam. Children’s share of the mortality burden is currently 0.06%, a figure that has not changed since mid-December, and the death rate for children with COVID-19 is 0.01%, according to the report.

Almost two-thirds (65%) of all deaths have occurred in just nine states – Arizona (31), California (21), Colorado (13), Georgia (10), Illinois (18), Maryland (10), Pennsylvania (10), Tennessee (10), and Texas (52) – and New York City (24), while eight states have not reported any deaths yet, the two groups said.

[email protected]

Just 1 week after it looked like the COVID-19 situation in children might be taking another turn for the worse, the number of new pediatric cases dropped to its lowest level since October, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The week of May 7-13 saw just under 49,000 new cases reported in U.S. children, down from 72,000 the week before and the lowest number recorded since the week of Oct. 9-15, 2020, the AAP and CHA said in their weekly COVID-19 report. During the week of April 30 to May 6 – the same week Rhode Island reported a large backlog of cases and increased its total by 30% – the number of new cases went up slightly after 2 weeks of declines.

Other positive indicators come in the form of the proportion of cases occurring in children. The cumulative percentage of cases in children since the start of the pandemic remained at 14.0% for a second consecutive week, and the proportion of new cases in children held at 24.0% and did not increase for the first time in 6 weeks, based on data from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

The total number of child COVID-19 cases reported in these jurisdictions is now up to 3.9 million, for a cumulative rate of 5,187 cases per 100,000 children in the United States. Among the states, total counts range from a low of 4,070 in Hawaii to 475,619 in California. Hawaii also has the lowest rate at 1,357 per 100,000 children, while the highest, 9,778 per 100,000, can be found in Rhode Island, the AAP and CHA said.

Deaths in children continue to accumulate at a relatively slow pace, with two more added during the week of May 7-13, bringing the total to 308 for the entire pandemic in 43 states, New York City, Puerto Rico, and Guam. Children’s share of the mortality burden is currently 0.06%, a figure that has not changed since mid-December, and the death rate for children with COVID-19 is 0.01%, according to the report.

Almost two-thirds (65%) of all deaths have occurred in just nine states – Arizona (31), California (21), Colorado (13), Georgia (10), Illinois (18), Maryland (10), Pennsylvania (10), Tennessee (10), and Texas (52) – and New York City (24), while eight states have not reported any deaths yet, the two groups said.

[email protected]

Just 1 week after it looked like the COVID-19 situation in children might be taking another turn for the worse, the number of new pediatric cases dropped to its lowest level since October, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The week of May 7-13 saw just under 49,000 new cases reported in U.S. children, down from 72,000 the week before and the lowest number recorded since the week of Oct. 9-15, 2020, the AAP and CHA said in their weekly COVID-19 report. During the week of April 30 to May 6 – the same week Rhode Island reported a large backlog of cases and increased its total by 30% – the number of new cases went up slightly after 2 weeks of declines.

Other positive indicators come in the form of the proportion of cases occurring in children. The cumulative percentage of cases in children since the start of the pandemic remained at 14.0% for a second consecutive week, and the proportion of new cases in children held at 24.0% and did not increase for the first time in 6 weeks, based on data from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

The total number of child COVID-19 cases reported in these jurisdictions is now up to 3.9 million, for a cumulative rate of 5,187 cases per 100,000 children in the United States. Among the states, total counts range from a low of 4,070 in Hawaii to 475,619 in California. Hawaii also has the lowest rate at 1,357 per 100,000 children, while the highest, 9,778 per 100,000, can be found in Rhode Island, the AAP and CHA said.

Deaths in children continue to accumulate at a relatively slow pace, with two more added during the week of May 7-13, bringing the total to 308 for the entire pandemic in 43 states, New York City, Puerto Rico, and Guam. Children’s share of the mortality burden is currently 0.06%, a figure that has not changed since mid-December, and the death rate for children with COVID-19 is 0.01%, according to the report.

Almost two-thirds (65%) of all deaths have occurred in just nine states – Arizona (31), California (21), Colorado (13), Georgia (10), Illinois (18), Maryland (10), Pennsylvania (10), Tennessee (10), and Texas (52) – and New York City (24), while eight states have not reported any deaths yet, the two groups said.

[email protected]

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.