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Frail COPD patients at high risk of disability and death
, a prospective cohort study of community-dwelling adults has shown.
“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.
The study was published online Dec. 12 in the journal CHEST®.
SLAS-1 and SLAS-2
Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.
Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.
Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.
Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
Frail or prefrail
Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.
This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.
Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.
Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
Frailty and mortality
Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.
“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.
Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.
Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
Frailty scoring system
Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.
The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.
The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.
A version of this article first appeared on Medscape.com.
, a prospective cohort study of community-dwelling adults has shown.
“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.
The study was published online Dec. 12 in the journal CHEST®.
SLAS-1 and SLAS-2
Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.
Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.
Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.
Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
Frail or prefrail
Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.
This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.
Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.
Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
Frailty and mortality
Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.
“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.
Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.
Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
Frailty scoring system
Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.
The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.
The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.
A version of this article first appeared on Medscape.com.
, a prospective cohort study of community-dwelling adults has shown.
“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.
The study was published online Dec. 12 in the journal CHEST®.
SLAS-1 and SLAS-2
Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.
Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.
Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.
Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
Frail or prefrail
Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.
This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.
Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.
Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
Frailty and mortality
Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.
“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.
Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.
Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
Frailty scoring system
Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.
The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.
The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.
A version of this article first appeared on Medscape.com.
FROM CHEST
Sputum biomarkers may predict COPD exacerbations
Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.
A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST® authored by Charles R. Esther Jr. MD, PhD, and colleagues.
Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?
They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.
Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.
Addressing inflammation
“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,
The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.
The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
Study results
Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).
Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
Sputum tests needed
While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”
Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”
The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.
Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.
A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST® authored by Charles R. Esther Jr. MD, PhD, and colleagues.
Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?
They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.
Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.
Addressing inflammation
“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,
The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.
The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
Study results
Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).
Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
Sputum tests needed
While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”
Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”
The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.
Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.
A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST® authored by Charles R. Esther Jr. MD, PhD, and colleagues.
Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?
They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.
Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.
Addressing inflammation
“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,
The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.
The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
Study results
Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).
Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
Sputum tests needed
While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”
Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”
The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.
FROM THE JOURNAL CHEST®
Rhinosinusitis without nasal polyps lowers QoL in COPD
Concomitant rhinosinusitis without nasal polyps (RSsNP) in patients with chronic obstructive pulmonary disease (COPD) is associated with a poorer, disease-specific, health-related quality of life (HRQoL), a Norwegian study is showing.
“Chronic rhinosinusitis has an impact on patients’ HRQoL,” lead author Marte Rystad Øie, Trondheim (Norway) University Hospital, said in an interview.
“We found that RSsNP in COPD was associated with more psychological issues, higher COPD symptom burden, and overall COPD-related HRQoL after adjusting for lung function, so RSsNP does have clinical relevance and [our findings] support previous studies that have suggested that rhinosinusitis should be recognized as a comorbidity in COPD,” she emphasized.
The study was published in the Nov. 1 issue of Respiratory Medicine.
Study sample
The study sample consisted of 90 patients with COPD and 93 control subjects, all age 40-80 years. “Generic HRQoL was measured with the Norwegian version of the SF-36v2 Health Survey Standard questionnaire,” the authors wrote, and responses were compared between patients with COPD and controls as well as between subgroups of patients who had COPD both with and without RSsNP.
Disease-specific HRQoL was assessed by the Sinonasal Outcome Test-22 (SNOT-22); the St. Georges Respiratory Questionnaire (SGRQ), and the COPD Assessment Test (CAT), and responses were again compared between patients who had COPD with and without RSsNP. In the COPD group, “severe” and “very severe” airflow obstruction was present in 56.5% of patients with RSsNP compared with 38.6% of patients without RSsNP, as Ms. Øie reported.
Furthermore, total SNOT-22 along with psychological subscale scores were both significantly higher in patients who had COPD with RSsNP than those without RSsNP. Among those with RSsNP, the mean value of the total SNOT-22 score was 36.8 whereas the mean value of the psychological subscale score was 22.6. Comparable mean values among patients who had COPD without RSsNP were 9.5 and 6.5, respectively (P < .05).
Total scores on the SGRQ were again significantly greater in patients who had COPD with RSsNP at a mean of 43.3 compared with a mean of 34 in those without RSsNP, investigators observe. Similarly, scores for the symptom and activity domains again on the SGRQ were significantly greater for patients who had COPD with RSsNP than those without nasal polyps. As for the total CAT score, once again it was significantly higher in patients who had COPD with RSsNP at a mean of 18.8 compared with a mean of 13.5 in those without RSsNP (P < .05).
Indeed, patients with RSsNP were four times more likely to have CAT scores indicating the condition was having a high or very high impact on their HRQoL compared with patients without RSsNP (P < .001). As the authors pointed out, having a high impact on HRQoL translates into patients having to stop their desired activities and having no good days in the week.
“This suggests that having RSsNP substantially adds to the activity limitation experienced by patients with COPD,” they emphasized. The authors also found that RSsNP was significantly associated with poorer physical functioning after adjusting for COPD as reflected by SF-36v2 findings, again suggesting that patients who had COPD with concomitant RSsNP have an additional limitation in activity and a heavier symptom burden.
As Ms. Øie explained, rhinosinusitis has two clinical phenotypes: that with nasal polyps and that without nasal polyps, the latter being twice as prevalent. In fact, rhinosinusitis with nasal polyps is associated with asthma, as she pointed out. Given, however, that rhinosinusitis without polyps is amenable to treatment with daily use of nasal steroids, it is possible to reduce the burden of symptoms and psychological stress associated with RSsNP in COPD.
Limitations of the study include the fact that investigators did not assess patients for the presence of any comorbidities that could contribute to poorer HRQoL in this patient population.
The study was funded by Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Concomitant rhinosinusitis without nasal polyps (RSsNP) in patients with chronic obstructive pulmonary disease (COPD) is associated with a poorer, disease-specific, health-related quality of life (HRQoL), a Norwegian study is showing.
“Chronic rhinosinusitis has an impact on patients’ HRQoL,” lead author Marte Rystad Øie, Trondheim (Norway) University Hospital, said in an interview.
“We found that RSsNP in COPD was associated with more psychological issues, higher COPD symptom burden, and overall COPD-related HRQoL after adjusting for lung function, so RSsNP does have clinical relevance and [our findings] support previous studies that have suggested that rhinosinusitis should be recognized as a comorbidity in COPD,” she emphasized.
The study was published in the Nov. 1 issue of Respiratory Medicine.
Study sample
The study sample consisted of 90 patients with COPD and 93 control subjects, all age 40-80 years. “Generic HRQoL was measured with the Norwegian version of the SF-36v2 Health Survey Standard questionnaire,” the authors wrote, and responses were compared between patients with COPD and controls as well as between subgroups of patients who had COPD both with and without RSsNP.
Disease-specific HRQoL was assessed by the Sinonasal Outcome Test-22 (SNOT-22); the St. Georges Respiratory Questionnaire (SGRQ), and the COPD Assessment Test (CAT), and responses were again compared between patients who had COPD with and without RSsNP. In the COPD group, “severe” and “very severe” airflow obstruction was present in 56.5% of patients with RSsNP compared with 38.6% of patients without RSsNP, as Ms. Øie reported.
Furthermore, total SNOT-22 along with psychological subscale scores were both significantly higher in patients who had COPD with RSsNP than those without RSsNP. Among those with RSsNP, the mean value of the total SNOT-22 score was 36.8 whereas the mean value of the psychological subscale score was 22.6. Comparable mean values among patients who had COPD without RSsNP were 9.5 and 6.5, respectively (P < .05).
Total scores on the SGRQ were again significantly greater in patients who had COPD with RSsNP at a mean of 43.3 compared with a mean of 34 in those without RSsNP, investigators observe. Similarly, scores for the symptom and activity domains again on the SGRQ were significantly greater for patients who had COPD with RSsNP than those without nasal polyps. As for the total CAT score, once again it was significantly higher in patients who had COPD with RSsNP at a mean of 18.8 compared with a mean of 13.5 in those without RSsNP (P < .05).
Indeed, patients with RSsNP were four times more likely to have CAT scores indicating the condition was having a high or very high impact on their HRQoL compared with patients without RSsNP (P < .001). As the authors pointed out, having a high impact on HRQoL translates into patients having to stop their desired activities and having no good days in the week.
“This suggests that having RSsNP substantially adds to the activity limitation experienced by patients with COPD,” they emphasized. The authors also found that RSsNP was significantly associated with poorer physical functioning after adjusting for COPD as reflected by SF-36v2 findings, again suggesting that patients who had COPD with concomitant RSsNP have an additional limitation in activity and a heavier symptom burden.
As Ms. Øie explained, rhinosinusitis has two clinical phenotypes: that with nasal polyps and that without nasal polyps, the latter being twice as prevalent. In fact, rhinosinusitis with nasal polyps is associated with asthma, as she pointed out. Given, however, that rhinosinusitis without polyps is amenable to treatment with daily use of nasal steroids, it is possible to reduce the burden of symptoms and psychological stress associated with RSsNP in COPD.
Limitations of the study include the fact that investigators did not assess patients for the presence of any comorbidities that could contribute to poorer HRQoL in this patient population.
The study was funded by Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Concomitant rhinosinusitis without nasal polyps (RSsNP) in patients with chronic obstructive pulmonary disease (COPD) is associated with a poorer, disease-specific, health-related quality of life (HRQoL), a Norwegian study is showing.
“Chronic rhinosinusitis has an impact on patients’ HRQoL,” lead author Marte Rystad Øie, Trondheim (Norway) University Hospital, said in an interview.
“We found that RSsNP in COPD was associated with more psychological issues, higher COPD symptom burden, and overall COPD-related HRQoL after adjusting for lung function, so RSsNP does have clinical relevance and [our findings] support previous studies that have suggested that rhinosinusitis should be recognized as a comorbidity in COPD,” she emphasized.
The study was published in the Nov. 1 issue of Respiratory Medicine.
Study sample
The study sample consisted of 90 patients with COPD and 93 control subjects, all age 40-80 years. “Generic HRQoL was measured with the Norwegian version of the SF-36v2 Health Survey Standard questionnaire,” the authors wrote, and responses were compared between patients with COPD and controls as well as between subgroups of patients who had COPD both with and without RSsNP.
Disease-specific HRQoL was assessed by the Sinonasal Outcome Test-22 (SNOT-22); the St. Georges Respiratory Questionnaire (SGRQ), and the COPD Assessment Test (CAT), and responses were again compared between patients who had COPD with and without RSsNP. In the COPD group, “severe” and “very severe” airflow obstruction was present in 56.5% of patients with RSsNP compared with 38.6% of patients without RSsNP, as Ms. Øie reported.
Furthermore, total SNOT-22 along with psychological subscale scores were both significantly higher in patients who had COPD with RSsNP than those without RSsNP. Among those with RSsNP, the mean value of the total SNOT-22 score was 36.8 whereas the mean value of the psychological subscale score was 22.6. Comparable mean values among patients who had COPD without RSsNP were 9.5 and 6.5, respectively (P < .05).
Total scores on the SGRQ were again significantly greater in patients who had COPD with RSsNP at a mean of 43.3 compared with a mean of 34 in those without RSsNP, investigators observe. Similarly, scores for the symptom and activity domains again on the SGRQ were significantly greater for patients who had COPD with RSsNP than those without nasal polyps. As for the total CAT score, once again it was significantly higher in patients who had COPD with RSsNP at a mean of 18.8 compared with a mean of 13.5 in those without RSsNP (P < .05).
Indeed, patients with RSsNP were four times more likely to have CAT scores indicating the condition was having a high or very high impact on their HRQoL compared with patients without RSsNP (P < .001). As the authors pointed out, having a high impact on HRQoL translates into patients having to stop their desired activities and having no good days in the week.
“This suggests that having RSsNP substantially adds to the activity limitation experienced by patients with COPD,” they emphasized. The authors also found that RSsNP was significantly associated with poorer physical functioning after adjusting for COPD as reflected by SF-36v2 findings, again suggesting that patients who had COPD with concomitant RSsNP have an additional limitation in activity and a heavier symptom burden.
As Ms. Øie explained, rhinosinusitis has two clinical phenotypes: that with nasal polyps and that without nasal polyps, the latter being twice as prevalent. In fact, rhinosinusitis with nasal polyps is associated with asthma, as she pointed out. Given, however, that rhinosinusitis without polyps is amenable to treatment with daily use of nasal steroids, it is possible to reduce the burden of symptoms and psychological stress associated with RSsNP in COPD.
Limitations of the study include the fact that investigators did not assess patients for the presence of any comorbidities that could contribute to poorer HRQoL in this patient population.
The study was funded by Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COPD Highlights From CHEST 2020
Dr Darcy Marciniuk, of the University of Saskatchewan in Saskatchewan, Canada, discusses essential abstracts in the management of patients with COPD presented at the American College of Chest Physicians' annual meeting, CHEST 2020, which was held virtually this year because of the coronavirus.
Dr Marciniuk reviews new data from a phase 3 ETHOS substudy evaluating lung function decline in patients receiving inhaled corticosteroid (ICS)-containing therapies vs non–ICS-containing therapies. He also discusses a retrospective cohort study using Medicare data from 2012-2017 evaluating the association of noninvasive ventilation at home with risk for death, hospitalizations, and emergency room visits.
Additionally, he highlights a multi-institutional, post hoc analysis of the phase 3 IMPACT trial to estimate cardiovascular event risk following acute exacerbation in patients with COPD.
From another post hoc analysis, this one from the SUMMIT trial comparing fluticasone, vilanterol, and ICS/LABA with placebo, Dr Marciniuk reports on an investigation of all-cause mortality and severe exacerbation risk in a subgroup of patients with a history of exacerbation.
Finally, he highlights a retrospective cohort study using data from the US 2015 Inpatient Sample, which compared outcomes of patients admitted to hospitals with COPD exacerbations with and without mobility impairment.
--
Darcy D. Marciniuk, MD, Master FCCP, Professor, Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatoon, Saskatoon, Saskatchewan, Canada.
Darcy D. Marciniuk, MD, Master FCCP, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: Alberta Lung Association; AstraZeneca; Boehringer Ingelheim; Canadian Foundation for Healthcare Improvement; GlaxoSmithKline; Heath Canada; Lung Association of Saskatchewan; Mylan; Novartis; Saskatchewan Ministry of Health; Saskatchewan Health Authority; Yukon Health and Social Services
Received research funding (managed by University of Saskatchewan) from: AstraZeneca; Boehringer Ingelheim; Canada Health Infoway; Canadian Institute of Health Research; GlaxoSmithKline; Grifols; Lung Association of Saskatchewan; Lung Health Institute of Canada; Novartis; Sanofi; Saskatchewan Health Research Foundation; Schering-Plough
Serve(s) as deputy editor of: CHEST Journal.
Dr Darcy Marciniuk, of the University of Saskatchewan in Saskatchewan, Canada, discusses essential abstracts in the management of patients with COPD presented at the American College of Chest Physicians' annual meeting, CHEST 2020, which was held virtually this year because of the coronavirus.
Dr Marciniuk reviews new data from a phase 3 ETHOS substudy evaluating lung function decline in patients receiving inhaled corticosteroid (ICS)-containing therapies vs non–ICS-containing therapies. He also discusses a retrospective cohort study using Medicare data from 2012-2017 evaluating the association of noninvasive ventilation at home with risk for death, hospitalizations, and emergency room visits.
Additionally, he highlights a multi-institutional, post hoc analysis of the phase 3 IMPACT trial to estimate cardiovascular event risk following acute exacerbation in patients with COPD.
From another post hoc analysis, this one from the SUMMIT trial comparing fluticasone, vilanterol, and ICS/LABA with placebo, Dr Marciniuk reports on an investigation of all-cause mortality and severe exacerbation risk in a subgroup of patients with a history of exacerbation.
Finally, he highlights a retrospective cohort study using data from the US 2015 Inpatient Sample, which compared outcomes of patients admitted to hospitals with COPD exacerbations with and without mobility impairment.
--
Darcy D. Marciniuk, MD, Master FCCP, Professor, Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatoon, Saskatoon, Saskatchewan, Canada.
Darcy D. Marciniuk, MD, Master FCCP, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: Alberta Lung Association; AstraZeneca; Boehringer Ingelheim; Canadian Foundation for Healthcare Improvement; GlaxoSmithKline; Heath Canada; Lung Association of Saskatchewan; Mylan; Novartis; Saskatchewan Ministry of Health; Saskatchewan Health Authority; Yukon Health and Social Services
Received research funding (managed by University of Saskatchewan) from: AstraZeneca; Boehringer Ingelheim; Canada Health Infoway; Canadian Institute of Health Research; GlaxoSmithKline; Grifols; Lung Association of Saskatchewan; Lung Health Institute of Canada; Novartis; Sanofi; Saskatchewan Health Research Foundation; Schering-Plough
Serve(s) as deputy editor of: CHEST Journal.
Dr Darcy Marciniuk, of the University of Saskatchewan in Saskatchewan, Canada, discusses essential abstracts in the management of patients with COPD presented at the American College of Chest Physicians' annual meeting, CHEST 2020, which was held virtually this year because of the coronavirus.
Dr Marciniuk reviews new data from a phase 3 ETHOS substudy evaluating lung function decline in patients receiving inhaled corticosteroid (ICS)-containing therapies vs non–ICS-containing therapies. He also discusses a retrospective cohort study using Medicare data from 2012-2017 evaluating the association of noninvasive ventilation at home with risk for death, hospitalizations, and emergency room visits.
Additionally, he highlights a multi-institutional, post hoc analysis of the phase 3 IMPACT trial to estimate cardiovascular event risk following acute exacerbation in patients with COPD.
From another post hoc analysis, this one from the SUMMIT trial comparing fluticasone, vilanterol, and ICS/LABA with placebo, Dr Marciniuk reports on an investigation of all-cause mortality and severe exacerbation risk in a subgroup of patients with a history of exacerbation.
Finally, he highlights a retrospective cohort study using data from the US 2015 Inpatient Sample, which compared outcomes of patients admitted to hospitals with COPD exacerbations with and without mobility impairment.
--
Darcy D. Marciniuk, MD, Master FCCP, Professor, Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatoon, Saskatoon, Saskatchewan, Canada.
Darcy D. Marciniuk, MD, Master FCCP, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: Alberta Lung Association; AstraZeneca; Boehringer Ingelheim; Canadian Foundation for Healthcare Improvement; GlaxoSmithKline; Heath Canada; Lung Association of Saskatchewan; Mylan; Novartis; Saskatchewan Ministry of Health; Saskatchewan Health Authority; Yukon Health and Social Services
Received research funding (managed by University of Saskatchewan) from: AstraZeneca; Boehringer Ingelheim; Canada Health Infoway; Canadian Institute of Health Research; GlaxoSmithKline; Grifols; Lung Association of Saskatchewan; Lung Health Institute of Canada; Novartis; Sanofi; Saskatchewan Health Research Foundation; Schering-Plough
Serve(s) as deputy editor of: CHEST Journal.
Pulmonary rehabilitation: Similar benefit in both IPF and COPD patients
Patients with idiopathic pulmonary fibrosis (IPF) complete and respond to pulmonary rehabilitation at rates similar to patients with chronic obstructive pulmonary disease (COPD), according to results of a real-world study. The findings reported in an article published in the journal CHEST® reinforce pulmonary rehabilitation’s benefits for this population.
A progressive decline in respiratory and physical function characterizes IPF, with median survival from diagnosis of 3-5 years, according to Claire Nolan, PhD, of Harefield Hospital, Middlesex, England, and colleagues. The effects of pharmacologic therapies on IPF on symptom burden and quality of life are modest, although lung function decline may be slowed. Supporting evidence for pulmonary rehabilitation benefit in IPF is more modest than it is for COPD, for which exercise capacity, dyspnea, and health-related quality of life improvement have been demonstrated.
“We did not design a randomized, controlled trial,” Dr. Nolan said in an interview, “as it was considered unethical by the local ethics committee to withhold pulmonary rehabilitation based on clinical guidance in the United Kingdom.” She pointed out that initial pulmonary rehabilitation trials in COPD included an intervention (pulmonary rehabilitation) and a control (standard medical care) arm.
The study aims were to compare the effects of pulmonary rehabilitation with real-world data between IPF and COPD with respect to magnitude of effect and survival. The authors’ hypothesis was that IPF patients would have a blunted response to pulmonary rehabilitation with reduced completion rates, compared with a matched COPD group, and with increased mortality.
Study details
Investigators use propensity score matching of 163 IPF patients with a control group of 163 patients with COPD referred to pulmonary rehabilitation. Completion rates, responses, and survival status were recorded for 1-year following pulmonary rehabilitation discharge. The 8-week outpatient program was composed of two supervised exercise and education sessions with additional unsupervised home-based exercise each week.
While spirometry data, as expected, showed a higher proportion of IPF patients using supplemental oxygen, pulmonary rehabilitation completion rates were similar for both groups (IPF, 69%; COPD, 63%; P = .24) and there was no between group difference in the number of sessions attended (P = .39). Medical Research Council (muscle strength) (MRC), incremental shuttle walk test (ISW), and Chronic Respiratory Questionnaire total score (CRQ-T) improved significantly in both groups, again with no significant difference between groups.
Over the study course, there was progressive, significant worsening of forced vital capacity percentage, predicted, prescription supplemental oxygen, resting peripheral oxygen saturation, exercise capacity, health-related quality of life and pulmonary rehabilitation adherence across groups of responders (n = 63; 38%), nonresponders (n = 50; 31%) and noncompleters (n = 50; 31%). Among the IPF patients, 6 died before completing pulmonary rehabilitation, with 42 (27%) dying during follow-up.
Benefits of rehabilitation
Multivariable analyses showed that noncompletion and nonresponse were associated with significantly higher risk of all-cause mortality at 1-year. Also, time to all-cause mortality was shorter (P = .001) for noncompleters and nonresponders, compared with completers. A trend toward higher completion rates in the IPF group, compared with the COPD group, may be explained, the researchers explained, by fewer hospitalizations over the prior 12 months in the IPF group.
“Although many programs are designed for people with COPD,” Dr. Nolan and colleagues concluded, “our study demonstrates that people with IPF have similar clinical benefits and completion rates to those with COPD. These data reinforce the importance of referral to and engagement in pulmonary rehabilitation amongst the IPF population.”
These findings, Dr. Nolan emphasized, emerged from a single center, and validation in other settings is needed.
This study was funded by a National Institute for Health Research Doctoral Research Fellowship (2014-07-089) and a Medical Research Council New Investigator Research Grant (98576).
Patients with idiopathic pulmonary fibrosis (IPF) complete and respond to pulmonary rehabilitation at rates similar to patients with chronic obstructive pulmonary disease (COPD), according to results of a real-world study. The findings reported in an article published in the journal CHEST® reinforce pulmonary rehabilitation’s benefits for this population.
A progressive decline in respiratory and physical function characterizes IPF, with median survival from diagnosis of 3-5 years, according to Claire Nolan, PhD, of Harefield Hospital, Middlesex, England, and colleagues. The effects of pharmacologic therapies on IPF on symptom burden and quality of life are modest, although lung function decline may be slowed. Supporting evidence for pulmonary rehabilitation benefit in IPF is more modest than it is for COPD, for which exercise capacity, dyspnea, and health-related quality of life improvement have been demonstrated.
“We did not design a randomized, controlled trial,” Dr. Nolan said in an interview, “as it was considered unethical by the local ethics committee to withhold pulmonary rehabilitation based on clinical guidance in the United Kingdom.” She pointed out that initial pulmonary rehabilitation trials in COPD included an intervention (pulmonary rehabilitation) and a control (standard medical care) arm.
The study aims were to compare the effects of pulmonary rehabilitation with real-world data between IPF and COPD with respect to magnitude of effect and survival. The authors’ hypothesis was that IPF patients would have a blunted response to pulmonary rehabilitation with reduced completion rates, compared with a matched COPD group, and with increased mortality.
Study details
Investigators use propensity score matching of 163 IPF patients with a control group of 163 patients with COPD referred to pulmonary rehabilitation. Completion rates, responses, and survival status were recorded for 1-year following pulmonary rehabilitation discharge. The 8-week outpatient program was composed of two supervised exercise and education sessions with additional unsupervised home-based exercise each week.
While spirometry data, as expected, showed a higher proportion of IPF patients using supplemental oxygen, pulmonary rehabilitation completion rates were similar for both groups (IPF, 69%; COPD, 63%; P = .24) and there was no between group difference in the number of sessions attended (P = .39). Medical Research Council (muscle strength) (MRC), incremental shuttle walk test (ISW), and Chronic Respiratory Questionnaire total score (CRQ-T) improved significantly in both groups, again with no significant difference between groups.
Over the study course, there was progressive, significant worsening of forced vital capacity percentage, predicted, prescription supplemental oxygen, resting peripheral oxygen saturation, exercise capacity, health-related quality of life and pulmonary rehabilitation adherence across groups of responders (n = 63; 38%), nonresponders (n = 50; 31%) and noncompleters (n = 50; 31%). Among the IPF patients, 6 died before completing pulmonary rehabilitation, with 42 (27%) dying during follow-up.
Benefits of rehabilitation
Multivariable analyses showed that noncompletion and nonresponse were associated with significantly higher risk of all-cause mortality at 1-year. Also, time to all-cause mortality was shorter (P = .001) for noncompleters and nonresponders, compared with completers. A trend toward higher completion rates in the IPF group, compared with the COPD group, may be explained, the researchers explained, by fewer hospitalizations over the prior 12 months in the IPF group.
“Although many programs are designed for people with COPD,” Dr. Nolan and colleagues concluded, “our study demonstrates that people with IPF have similar clinical benefits and completion rates to those with COPD. These data reinforce the importance of referral to and engagement in pulmonary rehabilitation amongst the IPF population.”
These findings, Dr. Nolan emphasized, emerged from a single center, and validation in other settings is needed.
This study was funded by a National Institute for Health Research Doctoral Research Fellowship (2014-07-089) and a Medical Research Council New Investigator Research Grant (98576).
Patients with idiopathic pulmonary fibrosis (IPF) complete and respond to pulmonary rehabilitation at rates similar to patients with chronic obstructive pulmonary disease (COPD), according to results of a real-world study. The findings reported in an article published in the journal CHEST® reinforce pulmonary rehabilitation’s benefits for this population.
A progressive decline in respiratory and physical function characterizes IPF, with median survival from diagnosis of 3-5 years, according to Claire Nolan, PhD, of Harefield Hospital, Middlesex, England, and colleagues. The effects of pharmacologic therapies on IPF on symptom burden and quality of life are modest, although lung function decline may be slowed. Supporting evidence for pulmonary rehabilitation benefit in IPF is more modest than it is for COPD, for which exercise capacity, dyspnea, and health-related quality of life improvement have been demonstrated.
“We did not design a randomized, controlled trial,” Dr. Nolan said in an interview, “as it was considered unethical by the local ethics committee to withhold pulmonary rehabilitation based on clinical guidance in the United Kingdom.” She pointed out that initial pulmonary rehabilitation trials in COPD included an intervention (pulmonary rehabilitation) and a control (standard medical care) arm.
The study aims were to compare the effects of pulmonary rehabilitation with real-world data between IPF and COPD with respect to magnitude of effect and survival. The authors’ hypothesis was that IPF patients would have a blunted response to pulmonary rehabilitation with reduced completion rates, compared with a matched COPD group, and with increased mortality.
Study details
Investigators use propensity score matching of 163 IPF patients with a control group of 163 patients with COPD referred to pulmonary rehabilitation. Completion rates, responses, and survival status were recorded for 1-year following pulmonary rehabilitation discharge. The 8-week outpatient program was composed of two supervised exercise and education sessions with additional unsupervised home-based exercise each week.
While spirometry data, as expected, showed a higher proportion of IPF patients using supplemental oxygen, pulmonary rehabilitation completion rates were similar for both groups (IPF, 69%; COPD, 63%; P = .24) and there was no between group difference in the number of sessions attended (P = .39). Medical Research Council (muscle strength) (MRC), incremental shuttle walk test (ISW), and Chronic Respiratory Questionnaire total score (CRQ-T) improved significantly in both groups, again with no significant difference between groups.
Over the study course, there was progressive, significant worsening of forced vital capacity percentage, predicted, prescription supplemental oxygen, resting peripheral oxygen saturation, exercise capacity, health-related quality of life and pulmonary rehabilitation adherence across groups of responders (n = 63; 38%), nonresponders (n = 50; 31%) and noncompleters (n = 50; 31%). Among the IPF patients, 6 died before completing pulmonary rehabilitation, with 42 (27%) dying during follow-up.
Benefits of rehabilitation
Multivariable analyses showed that noncompletion and nonresponse were associated with significantly higher risk of all-cause mortality at 1-year. Also, time to all-cause mortality was shorter (P = .001) for noncompleters and nonresponders, compared with completers. A trend toward higher completion rates in the IPF group, compared with the COPD group, may be explained, the researchers explained, by fewer hospitalizations over the prior 12 months in the IPF group.
“Although many programs are designed for people with COPD,” Dr. Nolan and colleagues concluded, “our study demonstrates that people with IPF have similar clinical benefits and completion rates to those with COPD. These data reinforce the importance of referral to and engagement in pulmonary rehabilitation amongst the IPF population.”
These findings, Dr. Nolan emphasized, emerged from a single center, and validation in other settings is needed.
This study was funded by a National Institute for Health Research Doctoral Research Fellowship (2014-07-089) and a Medical Research Council New Investigator Research Grant (98576).
FROM THE JOURNAL CHEST®
Novel bronchoscopic interventions appear promising for patients with COPD
Several emerging bronchoscopic treatments have the potential to improve the quality of life for patients with chronic obstructive pulmonary disease, an investigator reported at the annual meeting of the American College of Chest Physicians.
Targeted lung denervation is one promising novel therapeutic option that is safe and may improve clinical outcomes according to investigator Christian Ghattas, MD.
Data from an ongoing phase 3 randomized controlled trial may provide new information on the efficacy of targeted lung denervation in patients with chronic obstructive pulmonary disease (COPD), said Dr. Ghattas, assistant professor of medicine and associate program director for the interventional pulmonary fellowship at The Ohio State University Medical Center in Columbus.
“Outcome data of longer follow-up on previously treated patients will provide us with more information on the durability and the effect of this treatment,” Dr. Ghattas said in an online presentation at the CHEST meeting, which was held virtually this year.
Meanwhile, a few compelling bronchoscopic treatment modalities for patients with chronic bronchitis are in earlier stages of clinical development. “Larger randomized, controlled trials are ongoing to confirm the available data and to evaluate treatment durability,” said Dr. Ghattas.
Targeted lung denervation
The targeted lung denervation system under study (dNerva®, Nuvaira Inc.) involves the use of a radiofrequency catheter to ablate the peribronchial branches of the vagus nerve, Dr. Ghattas said.
The goal of disrupting pulmonary nerve input is to achieve sustained bronchodilation and reduce mucous secretion, thereby simulating the effect of anticholinergic drugs, he added.
In pilot studies, the targeted lung denervation system demonstrated its feasibility and safety, while modifications to the system reduced the rate of serious adverse events, according to Dr. Ghattas.
In the AIRFLOW-1 study, which evaluated the safety of the latest generation version of the system, 30 patients with COPD were randomized to targeted lung denervation at one of two doses, 29 or 32 watts.
Of those 30 patients, 29 (96.7%) had procedural success, meaning the catheter was inserted, guided to its intended location, and removed intact with no reported in-hospital serious adverse events, according to results published in Respiration.
There was no difference between arms in the primary endpoint, which was the rate of adverse airway effects requiring intervention that were associated with targeted lung denervation, investigators reported. Four such events occurred, in 3 of 15 patients treated with 32 watts and 1 of 15 patients treated with 29 watts.
Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group (P = .6). However, serious gastric events were noted in five patients, prompting safety improvements and procedural enhancements that reduced both gastrointestinal and airway events, according to the study report.
Further data are available from AIRFLOW-2, a randomized, sham-controlled trial enrolling patients with symptomatic COPD.
In that study, targeted lung denervation plus optimal drug treatment led to fewer respiratory adverse events of interest, including hospitalizations for COPD exacerbation, according to a report on the study that appears in The American Journal of Respiratory and Critical Care Medicine.
Respiratory adverse events occurred in 32% of treated patients versus 71% of sham-treated patients in a predefined 3- to 6.5-month postprocedure window, the report says.
Currently underway is AIRFLOW-3, a randomized study of targeted lung denervation versus sham procedure in patients with COPD. The study has a primary outcome measure of moderate or severe COPD exacerbations over 12 months and is slated to enroll 480 patients.
To be eligible for AIRFLOW-3, patients must have had at least two moderate or one severe COPD exacerbation in the previous year, Dr. Ghattas said.
Metered cryospray
One novel intervention with the potential to benefit patients with chronic bronchitis is metered cryospray (RejuvenAir), which works by delivering liquid nitrogen to the tracheobronchial airways, according to Dr. Ghattas.
This targeted delivery ablates abnormal epithelium, facilitating the regeneration of healthy mucosa, according to investigators in a recently published single-arm prospective trial.
Metered cryospray was safe, feasible, and linked to clinically meaningful improvements in patient-reported outcomes among patients with COPD, according to authors of the study, which appears in the European Respiratory Journal.
In the study, 34 of 35 participants received three treatments 4-6 weeks apart.
Investigators reported that at 3 months there were significant reductions in the COPD Assessment Test that were durable to 6 months, and changes in the St. George’s Respiratory Questionnaire and the Leicester Cough Questionnaire that were durable to 9 months.
There were 14 serious adverse events, none of which were device- or procedure related, according to investigators.
An ongoing randomized study called SPRAY-CB is comparing metered cryospray to sham procedure in an anticipated 210 patients with COPD with chronic bronchitis.
Bronchial rheoplasty
Bronchial rheoplasty (RheOx, Gala Therapeutics), is another promising intervention under investigation for the treatment of chronic bronchitis, according to Dr. Ghattas.
This system delivers nonthermal pulsed electrical energy, Dr. Ghattas said, with the intention of ablating goblet cells in the airways.
“The preclinical studies have demonstrated epithelial ablation, followed by regeneration of normalized epithelium,” he said in his presentation.
In 12-month results of multicenter clinical trial, bronchial rheoplasty was technically feasible and safe, with reductions in goblet cell hyperplasia and changes in patient-reported quality of life seen following the procedure, investigators reported in The American Journal of Respiratory and Critical Care Medicine.
The mean goblet cell hyperplasia score was reduced by 39% from baseline to treatment, according to study results. Four procedure-related serious adverse events were observed through 6 months, and there were no procedure- or device-related serious adverse events over the next 6 months. Mild hemoptysis occurred in 47% of patients, investigators reported.
A larger randomized, double-blind prospective trial with a sham control arm is underway and will include 270 patients, according to Dr. Ghattas. “We’re going to have to wait for the results,” he said.
Dr. Ghattas reported serving as a site principal investigator for clinical trials involving the bronchoscopic interventions he discussed, including AIRFLOW-3 (evaluating the targeted lung denervation system), SPRAY-CB (metered cryospray), and RheSolve (bronchial rheoplasty).
Several emerging bronchoscopic treatments have the potential to improve the quality of life for patients with chronic obstructive pulmonary disease, an investigator reported at the annual meeting of the American College of Chest Physicians.
Targeted lung denervation is one promising novel therapeutic option that is safe and may improve clinical outcomes according to investigator Christian Ghattas, MD.
Data from an ongoing phase 3 randomized controlled trial may provide new information on the efficacy of targeted lung denervation in patients with chronic obstructive pulmonary disease (COPD), said Dr. Ghattas, assistant professor of medicine and associate program director for the interventional pulmonary fellowship at The Ohio State University Medical Center in Columbus.
“Outcome data of longer follow-up on previously treated patients will provide us with more information on the durability and the effect of this treatment,” Dr. Ghattas said in an online presentation at the CHEST meeting, which was held virtually this year.
Meanwhile, a few compelling bronchoscopic treatment modalities for patients with chronic bronchitis are in earlier stages of clinical development. “Larger randomized, controlled trials are ongoing to confirm the available data and to evaluate treatment durability,” said Dr. Ghattas.
Targeted lung denervation
The targeted lung denervation system under study (dNerva®, Nuvaira Inc.) involves the use of a radiofrequency catheter to ablate the peribronchial branches of the vagus nerve, Dr. Ghattas said.
The goal of disrupting pulmonary nerve input is to achieve sustained bronchodilation and reduce mucous secretion, thereby simulating the effect of anticholinergic drugs, he added.
In pilot studies, the targeted lung denervation system demonstrated its feasibility and safety, while modifications to the system reduced the rate of serious adverse events, according to Dr. Ghattas.
In the AIRFLOW-1 study, which evaluated the safety of the latest generation version of the system, 30 patients with COPD were randomized to targeted lung denervation at one of two doses, 29 or 32 watts.
Of those 30 patients, 29 (96.7%) had procedural success, meaning the catheter was inserted, guided to its intended location, and removed intact with no reported in-hospital serious adverse events, according to results published in Respiration.
There was no difference between arms in the primary endpoint, which was the rate of adverse airway effects requiring intervention that were associated with targeted lung denervation, investigators reported. Four such events occurred, in 3 of 15 patients treated with 32 watts and 1 of 15 patients treated with 29 watts.
Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group (P = .6). However, serious gastric events were noted in five patients, prompting safety improvements and procedural enhancements that reduced both gastrointestinal and airway events, according to the study report.
Further data are available from AIRFLOW-2, a randomized, sham-controlled trial enrolling patients with symptomatic COPD.
In that study, targeted lung denervation plus optimal drug treatment led to fewer respiratory adverse events of interest, including hospitalizations for COPD exacerbation, according to a report on the study that appears in The American Journal of Respiratory and Critical Care Medicine.
Respiratory adverse events occurred in 32% of treated patients versus 71% of sham-treated patients in a predefined 3- to 6.5-month postprocedure window, the report says.
Currently underway is AIRFLOW-3, a randomized study of targeted lung denervation versus sham procedure in patients with COPD. The study has a primary outcome measure of moderate or severe COPD exacerbations over 12 months and is slated to enroll 480 patients.
To be eligible for AIRFLOW-3, patients must have had at least two moderate or one severe COPD exacerbation in the previous year, Dr. Ghattas said.
Metered cryospray
One novel intervention with the potential to benefit patients with chronic bronchitis is metered cryospray (RejuvenAir), which works by delivering liquid nitrogen to the tracheobronchial airways, according to Dr. Ghattas.
This targeted delivery ablates abnormal epithelium, facilitating the regeneration of healthy mucosa, according to investigators in a recently published single-arm prospective trial.
Metered cryospray was safe, feasible, and linked to clinically meaningful improvements in patient-reported outcomes among patients with COPD, according to authors of the study, which appears in the European Respiratory Journal.
In the study, 34 of 35 participants received three treatments 4-6 weeks apart.
Investigators reported that at 3 months there were significant reductions in the COPD Assessment Test that were durable to 6 months, and changes in the St. George’s Respiratory Questionnaire and the Leicester Cough Questionnaire that were durable to 9 months.
There were 14 serious adverse events, none of which were device- or procedure related, according to investigators.
An ongoing randomized study called SPRAY-CB is comparing metered cryospray to sham procedure in an anticipated 210 patients with COPD with chronic bronchitis.
Bronchial rheoplasty
Bronchial rheoplasty (RheOx, Gala Therapeutics), is another promising intervention under investigation for the treatment of chronic bronchitis, according to Dr. Ghattas.
This system delivers nonthermal pulsed electrical energy, Dr. Ghattas said, with the intention of ablating goblet cells in the airways.
“The preclinical studies have demonstrated epithelial ablation, followed by regeneration of normalized epithelium,” he said in his presentation.
In 12-month results of multicenter clinical trial, bronchial rheoplasty was technically feasible and safe, with reductions in goblet cell hyperplasia and changes in patient-reported quality of life seen following the procedure, investigators reported in The American Journal of Respiratory and Critical Care Medicine.
The mean goblet cell hyperplasia score was reduced by 39% from baseline to treatment, according to study results. Four procedure-related serious adverse events were observed through 6 months, and there were no procedure- or device-related serious adverse events over the next 6 months. Mild hemoptysis occurred in 47% of patients, investigators reported.
A larger randomized, double-blind prospective trial with a sham control arm is underway and will include 270 patients, according to Dr. Ghattas. “We’re going to have to wait for the results,” he said.
Dr. Ghattas reported serving as a site principal investigator for clinical trials involving the bronchoscopic interventions he discussed, including AIRFLOW-3 (evaluating the targeted lung denervation system), SPRAY-CB (metered cryospray), and RheSolve (bronchial rheoplasty).
Several emerging bronchoscopic treatments have the potential to improve the quality of life for patients with chronic obstructive pulmonary disease, an investigator reported at the annual meeting of the American College of Chest Physicians.
Targeted lung denervation is one promising novel therapeutic option that is safe and may improve clinical outcomes according to investigator Christian Ghattas, MD.
Data from an ongoing phase 3 randomized controlled trial may provide new information on the efficacy of targeted lung denervation in patients with chronic obstructive pulmonary disease (COPD), said Dr. Ghattas, assistant professor of medicine and associate program director for the interventional pulmonary fellowship at The Ohio State University Medical Center in Columbus.
“Outcome data of longer follow-up on previously treated patients will provide us with more information on the durability and the effect of this treatment,” Dr. Ghattas said in an online presentation at the CHEST meeting, which was held virtually this year.
Meanwhile, a few compelling bronchoscopic treatment modalities for patients with chronic bronchitis are in earlier stages of clinical development. “Larger randomized, controlled trials are ongoing to confirm the available data and to evaluate treatment durability,” said Dr. Ghattas.
Targeted lung denervation
The targeted lung denervation system under study (dNerva®, Nuvaira Inc.) involves the use of a radiofrequency catheter to ablate the peribronchial branches of the vagus nerve, Dr. Ghattas said.
The goal of disrupting pulmonary nerve input is to achieve sustained bronchodilation and reduce mucous secretion, thereby simulating the effect of anticholinergic drugs, he added.
In pilot studies, the targeted lung denervation system demonstrated its feasibility and safety, while modifications to the system reduced the rate of serious adverse events, according to Dr. Ghattas.
In the AIRFLOW-1 study, which evaluated the safety of the latest generation version of the system, 30 patients with COPD were randomized to targeted lung denervation at one of two doses, 29 or 32 watts.
Of those 30 patients, 29 (96.7%) had procedural success, meaning the catheter was inserted, guided to its intended location, and removed intact with no reported in-hospital serious adverse events, according to results published in Respiration.
There was no difference between arms in the primary endpoint, which was the rate of adverse airway effects requiring intervention that were associated with targeted lung denervation, investigators reported. Four such events occurred, in 3 of 15 patients treated with 32 watts and 1 of 15 patients treated with 29 watts.
Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group (P = .6). However, serious gastric events were noted in five patients, prompting safety improvements and procedural enhancements that reduced both gastrointestinal and airway events, according to the study report.
Further data are available from AIRFLOW-2, a randomized, sham-controlled trial enrolling patients with symptomatic COPD.
In that study, targeted lung denervation plus optimal drug treatment led to fewer respiratory adverse events of interest, including hospitalizations for COPD exacerbation, according to a report on the study that appears in The American Journal of Respiratory and Critical Care Medicine.
Respiratory adverse events occurred in 32% of treated patients versus 71% of sham-treated patients in a predefined 3- to 6.5-month postprocedure window, the report says.
Currently underway is AIRFLOW-3, a randomized study of targeted lung denervation versus sham procedure in patients with COPD. The study has a primary outcome measure of moderate or severe COPD exacerbations over 12 months and is slated to enroll 480 patients.
To be eligible for AIRFLOW-3, patients must have had at least two moderate or one severe COPD exacerbation in the previous year, Dr. Ghattas said.
Metered cryospray
One novel intervention with the potential to benefit patients with chronic bronchitis is metered cryospray (RejuvenAir), which works by delivering liquid nitrogen to the tracheobronchial airways, according to Dr. Ghattas.
This targeted delivery ablates abnormal epithelium, facilitating the regeneration of healthy mucosa, according to investigators in a recently published single-arm prospective trial.
Metered cryospray was safe, feasible, and linked to clinically meaningful improvements in patient-reported outcomes among patients with COPD, according to authors of the study, which appears in the European Respiratory Journal.
In the study, 34 of 35 participants received three treatments 4-6 weeks apart.
Investigators reported that at 3 months there were significant reductions in the COPD Assessment Test that were durable to 6 months, and changes in the St. George’s Respiratory Questionnaire and the Leicester Cough Questionnaire that were durable to 9 months.
There were 14 serious adverse events, none of which were device- or procedure related, according to investigators.
An ongoing randomized study called SPRAY-CB is comparing metered cryospray to sham procedure in an anticipated 210 patients with COPD with chronic bronchitis.
Bronchial rheoplasty
Bronchial rheoplasty (RheOx, Gala Therapeutics), is another promising intervention under investigation for the treatment of chronic bronchitis, according to Dr. Ghattas.
This system delivers nonthermal pulsed electrical energy, Dr. Ghattas said, with the intention of ablating goblet cells in the airways.
“The preclinical studies have demonstrated epithelial ablation, followed by regeneration of normalized epithelium,” he said in his presentation.
In 12-month results of multicenter clinical trial, bronchial rheoplasty was technically feasible and safe, with reductions in goblet cell hyperplasia and changes in patient-reported quality of life seen following the procedure, investigators reported in The American Journal of Respiratory and Critical Care Medicine.
The mean goblet cell hyperplasia score was reduced by 39% from baseline to treatment, according to study results. Four procedure-related serious adverse events were observed through 6 months, and there were no procedure- or device-related serious adverse events over the next 6 months. Mild hemoptysis occurred in 47% of patients, investigators reported.
A larger randomized, double-blind prospective trial with a sham control arm is underway and will include 270 patients, according to Dr. Ghattas. “We’re going to have to wait for the results,” he said.
Dr. Ghattas reported serving as a site principal investigator for clinical trials involving the bronchoscopic interventions he discussed, including AIRFLOW-3 (evaluating the targeted lung denervation system), SPRAY-CB (metered cryospray), and RheSolve (bronchial rheoplasty).
FROM CHEST 2021
Sepsis multiplies in-hospital mortality risk in COPD
Although slightly fewer than 1% of hospitalizations for chronic obstructive pulmonary disease (COPD) are complicated by sepsis, this complication increases the risk for in-hospital mortality fivefold, investigators who studied a representative national sample found.
Among nearly 7 million hospitalizations in which the primary diagnosis was COPD, nearly 65,000 (0.93%) patients experienced sepsis as a complication. In all, 31% of patients with COPD and sepsis were discharged from the hospital to another care facility, and 19% of patients died in hospital, report Harshil Shah, MD, from Guthrie Corning (N.Y.) Hospital and colleagues.
“Our study highlights the need for better risk stratification in patients with COPD developing sepsis to improve the outcomes. Further studies are warranted to consider factoring some of the modifiable factors into account and to ameliorate the outcomes of sepsis during COPD hospitalizations,” Dr. Shah and colleagues write in a poster presented during the at the annual meeting of the American College of Chest Physicians, held virtually this year.
COPD has been associated with increased risk for sepsis because of the use of corticosteroids, underlying comorbidities, and, potentially, because of impaired barrier function, the authors note.
Nationwide sample
To determine the effects of sepsis and predictors of poor outcomes among patients hospitalized for COPD, the investigators used standard diagnostic codes to identify patients with a primary diagnosis of COPD from the Nationwide Inpatient Sample for the period 2007 through 2018 and sepsis from codes in secondary fields in the International Classification of Diseases (9th/10th Editions) Clinical Modification.
They identified a total of 6,940,615 hospitalizations in which the primary diagnosis was COPD; in 64,748 of those cases, sepsis was a complication.
As noted, the in-hospital death rate, one of two primary outcomes, was 19% for patients with COPD and sepsis, and the rate of discharge to other facilities was 31%.
In analysis adjusted for confounding factors, sepsis was associated with an odds ratio for mortality of 4.9 (P < .01) and an OR for discharge to a facility of 2.2 (P < .01).
With regard to trends, the investigators saw that, although the adjusted odds for in-hospital mortality remained stable over time, discharge to facilities increased significantly. In 2007, the adjusted OR was 2.2, whereas in 2018, it was 2.6 (P for trend = .02).
Predictors of in-hospital mortality among patients with sepsis included increasing age (OR, not shown), White ethnicity (OR, 1.2), treatment in the Northeast region (OR, 1.4), disseminated intravascular coagulation (OR, 3.7), pneumococcal infection (OR, 1.2), congestive heart failure (OR, 1.2), and renal failure (OR, 1.4; P < .01 for all comparisons).
Mortality risk for many patients
A COPD specialist who was not involved in the study told this news organization that sepsis is an uncommon but serious complication, not just for patients with COPD but also for those with other severe illnesses.
“Sepsis has a high risk for mortality whether a person has COPD or not,” commented David M. Mannino III MD, FCCP, FERS, professor of medicine at the University of Kentucky, Lexington, and a cofounder and co–medical director of the COPD Foundation.
“It’s not surprising that sepsis is lethal in this population; the question is, if you have COPD, are you more likely to have sepsis? And I think the answer is probably yes. The connection there is that people with COPD have a higher risk for pneumonia, and pneumonia itself is probably one of the biggest risk factors, or certainly an important risk factor, for the development of sepsis,” he said in an interview.
It would be interesting to see the relationship between sepsis and in-hospital mortality for patients with other chronic diseases or people without COPD, he said, and he would have liked to have seen more detailed information about trends over time than Dr. Shah and colleagues provided.
No funding source for the study was reported. Dr. Shah and colleagues and Dr. Mannino have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although slightly fewer than 1% of hospitalizations for chronic obstructive pulmonary disease (COPD) are complicated by sepsis, this complication increases the risk for in-hospital mortality fivefold, investigators who studied a representative national sample found.
Among nearly 7 million hospitalizations in which the primary diagnosis was COPD, nearly 65,000 (0.93%) patients experienced sepsis as a complication. In all, 31% of patients with COPD and sepsis were discharged from the hospital to another care facility, and 19% of patients died in hospital, report Harshil Shah, MD, from Guthrie Corning (N.Y.) Hospital and colleagues.
“Our study highlights the need for better risk stratification in patients with COPD developing sepsis to improve the outcomes. Further studies are warranted to consider factoring some of the modifiable factors into account and to ameliorate the outcomes of sepsis during COPD hospitalizations,” Dr. Shah and colleagues write in a poster presented during the at the annual meeting of the American College of Chest Physicians, held virtually this year.
COPD has been associated with increased risk for sepsis because of the use of corticosteroids, underlying comorbidities, and, potentially, because of impaired barrier function, the authors note.
Nationwide sample
To determine the effects of sepsis and predictors of poor outcomes among patients hospitalized for COPD, the investigators used standard diagnostic codes to identify patients with a primary diagnosis of COPD from the Nationwide Inpatient Sample for the period 2007 through 2018 and sepsis from codes in secondary fields in the International Classification of Diseases (9th/10th Editions) Clinical Modification.
They identified a total of 6,940,615 hospitalizations in which the primary diagnosis was COPD; in 64,748 of those cases, sepsis was a complication.
As noted, the in-hospital death rate, one of two primary outcomes, was 19% for patients with COPD and sepsis, and the rate of discharge to other facilities was 31%.
In analysis adjusted for confounding factors, sepsis was associated with an odds ratio for mortality of 4.9 (P < .01) and an OR for discharge to a facility of 2.2 (P < .01).
With regard to trends, the investigators saw that, although the adjusted odds for in-hospital mortality remained stable over time, discharge to facilities increased significantly. In 2007, the adjusted OR was 2.2, whereas in 2018, it was 2.6 (P for trend = .02).
Predictors of in-hospital mortality among patients with sepsis included increasing age (OR, not shown), White ethnicity (OR, 1.2), treatment in the Northeast region (OR, 1.4), disseminated intravascular coagulation (OR, 3.7), pneumococcal infection (OR, 1.2), congestive heart failure (OR, 1.2), and renal failure (OR, 1.4; P < .01 for all comparisons).
Mortality risk for many patients
A COPD specialist who was not involved in the study told this news organization that sepsis is an uncommon but serious complication, not just for patients with COPD but also for those with other severe illnesses.
“Sepsis has a high risk for mortality whether a person has COPD or not,” commented David M. Mannino III MD, FCCP, FERS, professor of medicine at the University of Kentucky, Lexington, and a cofounder and co–medical director of the COPD Foundation.
“It’s not surprising that sepsis is lethal in this population; the question is, if you have COPD, are you more likely to have sepsis? And I think the answer is probably yes. The connection there is that people with COPD have a higher risk for pneumonia, and pneumonia itself is probably one of the biggest risk factors, or certainly an important risk factor, for the development of sepsis,” he said in an interview.
It would be interesting to see the relationship between sepsis and in-hospital mortality for patients with other chronic diseases or people without COPD, he said, and he would have liked to have seen more detailed information about trends over time than Dr. Shah and colleagues provided.
No funding source for the study was reported. Dr. Shah and colleagues and Dr. Mannino have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although slightly fewer than 1% of hospitalizations for chronic obstructive pulmonary disease (COPD) are complicated by sepsis, this complication increases the risk for in-hospital mortality fivefold, investigators who studied a representative national sample found.
Among nearly 7 million hospitalizations in which the primary diagnosis was COPD, nearly 65,000 (0.93%) patients experienced sepsis as a complication. In all, 31% of patients with COPD and sepsis were discharged from the hospital to another care facility, and 19% of patients died in hospital, report Harshil Shah, MD, from Guthrie Corning (N.Y.) Hospital and colleagues.
“Our study highlights the need for better risk stratification in patients with COPD developing sepsis to improve the outcomes. Further studies are warranted to consider factoring some of the modifiable factors into account and to ameliorate the outcomes of sepsis during COPD hospitalizations,” Dr. Shah and colleagues write in a poster presented during the at the annual meeting of the American College of Chest Physicians, held virtually this year.
COPD has been associated with increased risk for sepsis because of the use of corticosteroids, underlying comorbidities, and, potentially, because of impaired barrier function, the authors note.
Nationwide sample
To determine the effects of sepsis and predictors of poor outcomes among patients hospitalized for COPD, the investigators used standard diagnostic codes to identify patients with a primary diagnosis of COPD from the Nationwide Inpatient Sample for the period 2007 through 2018 and sepsis from codes in secondary fields in the International Classification of Diseases (9th/10th Editions) Clinical Modification.
They identified a total of 6,940,615 hospitalizations in which the primary diagnosis was COPD; in 64,748 of those cases, sepsis was a complication.
As noted, the in-hospital death rate, one of two primary outcomes, was 19% for patients with COPD and sepsis, and the rate of discharge to other facilities was 31%.
In analysis adjusted for confounding factors, sepsis was associated with an odds ratio for mortality of 4.9 (P < .01) and an OR for discharge to a facility of 2.2 (P < .01).
With regard to trends, the investigators saw that, although the adjusted odds for in-hospital mortality remained stable over time, discharge to facilities increased significantly. In 2007, the adjusted OR was 2.2, whereas in 2018, it was 2.6 (P for trend = .02).
Predictors of in-hospital mortality among patients with sepsis included increasing age (OR, not shown), White ethnicity (OR, 1.2), treatment in the Northeast region (OR, 1.4), disseminated intravascular coagulation (OR, 3.7), pneumococcal infection (OR, 1.2), congestive heart failure (OR, 1.2), and renal failure (OR, 1.4; P < .01 for all comparisons).
Mortality risk for many patients
A COPD specialist who was not involved in the study told this news organization that sepsis is an uncommon but serious complication, not just for patients with COPD but also for those with other severe illnesses.
“Sepsis has a high risk for mortality whether a person has COPD or not,” commented David M. Mannino III MD, FCCP, FERS, professor of medicine at the University of Kentucky, Lexington, and a cofounder and co–medical director of the COPD Foundation.
“It’s not surprising that sepsis is lethal in this population; the question is, if you have COPD, are you more likely to have sepsis? And I think the answer is probably yes. The connection there is that people with COPD have a higher risk for pneumonia, and pneumonia itself is probably one of the biggest risk factors, or certainly an important risk factor, for the development of sepsis,” he said in an interview.
It would be interesting to see the relationship between sepsis and in-hospital mortality for patients with other chronic diseases or people without COPD, he said, and he would have liked to have seen more detailed information about trends over time than Dr. Shah and colleagues provided.
No funding source for the study was reported. Dr. Shah and colleagues and Dr. Mannino have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Life-threatening paradoxical bronchospasm may escape recognition in patients with COPD or asthma
according to a researcher who reviewed spirometry test results from U.S. military veterans.
Nearly 1.5% of the tests met the criteria for paradoxical bronchospasm, which refers to airway constriction that may rapidly occur after inhalation of a short-acting beta2 agonist (SABA) such as albuterol.
However, none of those reports alluded to paradoxical bronchospasm, said investigator Malvika Kaul, MD, fellow in the department of pulmonary and critical care at the University of Illinois at Chicago and the Jesse Brown Veterans Affairs Medical Center, also in Chicago.
“Paradoxical bronchospasm was neither recognized nor reported in any spirometry test results,” Dr. Kaul said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
By recognizing paradoxical bronchospasm, health care providers could address its clinical implications and identify potential alternative management options, according to Dr. Kaul.
“We hope in the future, education of clinicians about this phenomena is emphasized,” Dr. Kaul said in her presentation.
Recognizing paradoxical bronchospasm
In an interview, Dr. Kaul said she began researching paradoxical bronchospasm after encountering a patient who had an acute reaction to albuterol during a pulmonary function test.
“I was not taught about it, and I wasn’t recognizing that pattern very frequently in my patients,” she said.
Prescribing information for Food and Drug Administration–approved SABAs include a warning that life-threatening paradoxical bronchospasm may occur, said Dr. Kaul.
If paradoxical bronchospasm occurs, the patient should discontinue the medication immediately and start on alternative therapy, according to the available prescribing information for albuterol sulfate.
Paradoxical bronchospasm has been linked to worsened respiratory outcomes, including more frequent exacerbations, in patients with obstructive lung diseases, according to Dr. Kaul.
Two previous large studies pegged the prevalence of paradoxical bronchospasm at around 4.5% in patients with COPD or asthma, but “it has not been reported or addressed in high-risk population, such as veterans who have high prevalence of obstructive lung diseases like COPD,” Dr. Kaul said.
Latest study results
Dr. Kaul described a retrospective analysis of 1,150 pre- and postbronchodilator spirometry tests conducted in patients with COPD or asthma at the Jesse Brown VA Medical Center between 2017 and 2020.
A positive paradoxical bronchodilator response was defined as a decrease of least 12% and 200 mL in forced expiratory volume in 1 second and forced vital capacity from baseline after four puffs of albuterol were inhaled, Dr. Kaul said.
Out of 18 reviewed spirometry results that met the criteria, none of the test results reported or recognized paradoxical bronchospasm, according to Dr. Kaul.
Those meeting the criteria were predominantly COPD patients, according to Dr. Kaul, who said 12 had an underlying diagnosis COPD, 4 had asthma, and 2 had COPD and asthma.
Of the 18 patients, 13 were African American, and all but 1 of the 18 patients had a current or past smoking history, according to reported data.
A history of obstructive sleep apnea was reported in nine patients, and history of gastroesophageal reflux disease was also reported in nine patients. Eleven patients had emphysema.
Greater awareness needed
Results of this study emphasize the need to recognize potential cases paradoxical bronchospasm in clinical practice, as well as a need for more research, according to Allen J. Blaivas, DO, FCCP, chair of the CHEST Airway Disorders NetWork.
“It’s something to be on the alert for, and certainly be aware that, if your patient is telling you that they feel worse, we shouldn’t just pooh-pooh it,” said Dr. Blaivas, who is medical director of the intensive care unit at the East Orange campus of the VA New Jersey Health Care System.
Further research could focus on breaking down whether patients with suspected paradoxical bronchospasm are using metered-dose inhalers or nebulizers, whether or not they are also taking inhaled corticosteroids, and whether prospective testing can confirm paradoxical bronchospasm in patients who report tightness after using a SABA, he said in an interview.
Dr. Kaul and coauthor Israel Rubinstein, MD had no relevant relationships to disclose. Dr. Blaivas had no relevant relationships to disclose.
according to a researcher who reviewed spirometry test results from U.S. military veterans.
Nearly 1.5% of the tests met the criteria for paradoxical bronchospasm, which refers to airway constriction that may rapidly occur after inhalation of a short-acting beta2 agonist (SABA) such as albuterol.
However, none of those reports alluded to paradoxical bronchospasm, said investigator Malvika Kaul, MD, fellow in the department of pulmonary and critical care at the University of Illinois at Chicago and the Jesse Brown Veterans Affairs Medical Center, also in Chicago.
“Paradoxical bronchospasm was neither recognized nor reported in any spirometry test results,” Dr. Kaul said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
By recognizing paradoxical bronchospasm, health care providers could address its clinical implications and identify potential alternative management options, according to Dr. Kaul.
“We hope in the future, education of clinicians about this phenomena is emphasized,” Dr. Kaul said in her presentation.
Recognizing paradoxical bronchospasm
In an interview, Dr. Kaul said she began researching paradoxical bronchospasm after encountering a patient who had an acute reaction to albuterol during a pulmonary function test.
“I was not taught about it, and I wasn’t recognizing that pattern very frequently in my patients,” she said.
Prescribing information for Food and Drug Administration–approved SABAs include a warning that life-threatening paradoxical bronchospasm may occur, said Dr. Kaul.
If paradoxical bronchospasm occurs, the patient should discontinue the medication immediately and start on alternative therapy, according to the available prescribing information for albuterol sulfate.
Paradoxical bronchospasm has been linked to worsened respiratory outcomes, including more frequent exacerbations, in patients with obstructive lung diseases, according to Dr. Kaul.
Two previous large studies pegged the prevalence of paradoxical bronchospasm at around 4.5% in patients with COPD or asthma, but “it has not been reported or addressed in high-risk population, such as veterans who have high prevalence of obstructive lung diseases like COPD,” Dr. Kaul said.
Latest study results
Dr. Kaul described a retrospective analysis of 1,150 pre- and postbronchodilator spirometry tests conducted in patients with COPD or asthma at the Jesse Brown VA Medical Center between 2017 and 2020.
A positive paradoxical bronchodilator response was defined as a decrease of least 12% and 200 mL in forced expiratory volume in 1 second and forced vital capacity from baseline after four puffs of albuterol were inhaled, Dr. Kaul said.
Out of 18 reviewed spirometry results that met the criteria, none of the test results reported or recognized paradoxical bronchospasm, according to Dr. Kaul.
Those meeting the criteria were predominantly COPD patients, according to Dr. Kaul, who said 12 had an underlying diagnosis COPD, 4 had asthma, and 2 had COPD and asthma.
Of the 18 patients, 13 were African American, and all but 1 of the 18 patients had a current or past smoking history, according to reported data.
A history of obstructive sleep apnea was reported in nine patients, and history of gastroesophageal reflux disease was also reported in nine patients. Eleven patients had emphysema.
Greater awareness needed
Results of this study emphasize the need to recognize potential cases paradoxical bronchospasm in clinical practice, as well as a need for more research, according to Allen J. Blaivas, DO, FCCP, chair of the CHEST Airway Disorders NetWork.
“It’s something to be on the alert for, and certainly be aware that, if your patient is telling you that they feel worse, we shouldn’t just pooh-pooh it,” said Dr. Blaivas, who is medical director of the intensive care unit at the East Orange campus of the VA New Jersey Health Care System.
Further research could focus on breaking down whether patients with suspected paradoxical bronchospasm are using metered-dose inhalers or nebulizers, whether or not they are also taking inhaled corticosteroids, and whether prospective testing can confirm paradoxical bronchospasm in patients who report tightness after using a SABA, he said in an interview.
Dr. Kaul and coauthor Israel Rubinstein, MD had no relevant relationships to disclose. Dr. Blaivas had no relevant relationships to disclose.
according to a researcher who reviewed spirometry test results from U.S. military veterans.
Nearly 1.5% of the tests met the criteria for paradoxical bronchospasm, which refers to airway constriction that may rapidly occur after inhalation of a short-acting beta2 agonist (SABA) such as albuterol.
However, none of those reports alluded to paradoxical bronchospasm, said investigator Malvika Kaul, MD, fellow in the department of pulmonary and critical care at the University of Illinois at Chicago and the Jesse Brown Veterans Affairs Medical Center, also in Chicago.
“Paradoxical bronchospasm was neither recognized nor reported in any spirometry test results,” Dr. Kaul said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
By recognizing paradoxical bronchospasm, health care providers could address its clinical implications and identify potential alternative management options, according to Dr. Kaul.
“We hope in the future, education of clinicians about this phenomena is emphasized,” Dr. Kaul said in her presentation.
Recognizing paradoxical bronchospasm
In an interview, Dr. Kaul said she began researching paradoxical bronchospasm after encountering a patient who had an acute reaction to albuterol during a pulmonary function test.
“I was not taught about it, and I wasn’t recognizing that pattern very frequently in my patients,” she said.
Prescribing information for Food and Drug Administration–approved SABAs include a warning that life-threatening paradoxical bronchospasm may occur, said Dr. Kaul.
If paradoxical bronchospasm occurs, the patient should discontinue the medication immediately and start on alternative therapy, according to the available prescribing information for albuterol sulfate.
Paradoxical bronchospasm has been linked to worsened respiratory outcomes, including more frequent exacerbations, in patients with obstructive lung diseases, according to Dr. Kaul.
Two previous large studies pegged the prevalence of paradoxical bronchospasm at around 4.5% in patients with COPD or asthma, but “it has not been reported or addressed in high-risk population, such as veterans who have high prevalence of obstructive lung diseases like COPD,” Dr. Kaul said.
Latest study results
Dr. Kaul described a retrospective analysis of 1,150 pre- and postbronchodilator spirometry tests conducted in patients with COPD or asthma at the Jesse Brown VA Medical Center between 2017 and 2020.
A positive paradoxical bronchodilator response was defined as a decrease of least 12% and 200 mL in forced expiratory volume in 1 second and forced vital capacity from baseline after four puffs of albuterol were inhaled, Dr. Kaul said.
Out of 18 reviewed spirometry results that met the criteria, none of the test results reported or recognized paradoxical bronchospasm, according to Dr. Kaul.
Those meeting the criteria were predominantly COPD patients, according to Dr. Kaul, who said 12 had an underlying diagnosis COPD, 4 had asthma, and 2 had COPD and asthma.
Of the 18 patients, 13 were African American, and all but 1 of the 18 patients had a current or past smoking history, according to reported data.
A history of obstructive sleep apnea was reported in nine patients, and history of gastroesophageal reflux disease was also reported in nine patients. Eleven patients had emphysema.
Greater awareness needed
Results of this study emphasize the need to recognize potential cases paradoxical bronchospasm in clinical practice, as well as a need for more research, according to Allen J. Blaivas, DO, FCCP, chair of the CHEST Airway Disorders NetWork.
“It’s something to be on the alert for, and certainly be aware that, if your patient is telling you that they feel worse, we shouldn’t just pooh-pooh it,” said Dr. Blaivas, who is medical director of the intensive care unit at the East Orange campus of the VA New Jersey Health Care System.
Further research could focus on breaking down whether patients with suspected paradoxical bronchospasm are using metered-dose inhalers or nebulizers, whether or not they are also taking inhaled corticosteroids, and whether prospective testing can confirm paradoxical bronchospasm in patients who report tightness after using a SABA, he said in an interview.
Dr. Kaul and coauthor Israel Rubinstein, MD had no relevant relationships to disclose. Dr. Blaivas had no relevant relationships to disclose.
FROM CHEST 2021
COPD: Higher mortality with low baseline CO diffusing capacity
Patients with a baseline DLCO (diffusing capacity for carbon monoxide) of < 60% of predicted have more severe disease clinical expression with higher mortality risk, according to a long-term observational study of Global Initiative for Obstructive Lung Disease (GOLD) I chronic obstructive pulmonary disease (COPD) patients. Clarifying mechanisms of low DLCO may help clinicians direct interventions toward ameliorating the low capacity, Juan Pablo de Torres, MD, and colleagues wrote in the journal CHEST®.
Defining increased risk
“Can a DLCO threshold help define an increased risk of death and a different clinical presentation in GOLD I patients?” the researchers questioned. For evaluation of COPD, the GOLD does not currently promote the use of DLCO, and the clinical and prognostic utility of a low DLCO has not been studied, the authors noted.
Several COPD studies, however, have shown associations between low DLCO values and reduced exercise capacity, increased symptoms, risk of severe exacerbations, and mortality. The patients included in these studies, however, have generally had moderate to severe airflow limitation, and have not had postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.70 and an FEV1 ≥ 80%, defined by GOLD as COPD spirometric stage I. These mild obstruction GOLD I patients, in large epidemiological studies, do have increased risk of death. But it is often assumed, Dr. de Torres and colleagues noted, that “mild” suggests a good prognosis. They propose that a simple DLCO measurement could help identify those GOLD I patients with “worse overall COPD compromise and an increased risk of death.” Importantly, GOLD I represents the largest percentage of patients with airflow limitation that epidemiological studies have identified.
The researchers enrolled 360 GOLD stage I COPD patients, recording their age, sex, pack-years’ history, body mass index, dyspnea, lung function measurements, exercise capacity, BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, and history of exacerbations, and followed them for a mean of 109 months. They identified a cutoff DLCO value for all-cause mortality, compared the clinical and physiological characteristics of patients above and below the threshold, and explored the predictive power of that cutoff value.
All-cause mortality difference
The mean age in the overall population studied was 63 years (31% were women), with 43% active smokers, and pack-years history of 45. Overall mortality was 11% during the follow-up period. The predominantly male population was mildly overweight, had few comorbidities, normal FEV1 values, mild dyspnea, normal 6-minute walk distance, and very few exacerbations.
Analysis showed a DLCO cutoff value of < 60% was associated with a significant all-cause mortality differential (DLCO ≥ 60%: 9% vs. DLCO < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with DLCO < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-minute walk distance, and higher BODE index. Adjusted Cox multiple regression analysis confirmed that a DLCO < 60% was associated with an all-cause mortality hazard ratio [HR] of 3.37, (95% confidence interval, 1.35-8.39; P = .009).
Multiorgan loss of tissue
The researchers found that patients with baseline DLCO < 60% were more likely to be women (46% versus 28%), and to have a lower BMI (25 vs. 27), higher pack-year history (54 vs. 43), the same spirometric values but lower IC/TLC ratio (.37 vs. .40), a lower walk distance (443 vs. 485 meters), higher dyspnea (MRC score 1.1 vs. .7), similar exacerbation rate, higher BODE index (.5 vs. .2) and higher mortality than patients with higher DLCO % predicted values. This group, Dr. de Torres and colleagues suggest, represents a multiorgan loss of tissue, a phenotype associated with worse clinical outcomes and prognosis.
“Low DLCO in these patients,” Dr. de Torres said in an interview, “could mainly be secondary to coexistent emphysema, which is the most common cause of low DLCO in this population. Also possible, but less likely, is coexistent pulmonary hypertension.” He noted further that “This study opens the door to research specifically testing if such is the case, and if it is, for clinicians to use available therapies to prevent adverse outcomes.”
Comorbidity burden
Patients with GOLD I COPD die more often of cardiovascular disease instead of underlying lung disease, according to Richard H. Zou, MD, and Jessica Bon, MD, of the University of Pittsburgh, in an accompanying editorial in the journal CHEST.
Increased mortality rates, they suggest, may be related to higher comorbidity burden, particularly comorbidities associated with cardiovascular-related health. Subclinical cardiovascular disease is a common comorbidity in COPD, and concomitant endothelial dysfunction has been associated with both cardiovascular disease and early emphysema in smokers. They may have disproportionately reduced DLCO levels because of parenchymal destruction.
“This study suggests that DLCO can be used to identify patients with GOLD I COPD at increased death risk and that individuals with mild airflow obstruction with DLCO <60% predicted are a clinical phenotype distinct from those with higher DLCO levels,” Dr. Zhou and Dr. Bon concluded.
The researchers and the editorialists declared that they had no disclosures. One of the three cohorts assessed in the current study (CHAIN cohort in Spain) received funding from AstraZeneca.
Patients with a baseline DLCO (diffusing capacity for carbon monoxide) of < 60% of predicted have more severe disease clinical expression with higher mortality risk, according to a long-term observational study of Global Initiative for Obstructive Lung Disease (GOLD) I chronic obstructive pulmonary disease (COPD) patients. Clarifying mechanisms of low DLCO may help clinicians direct interventions toward ameliorating the low capacity, Juan Pablo de Torres, MD, and colleagues wrote in the journal CHEST®.
Defining increased risk
“Can a DLCO threshold help define an increased risk of death and a different clinical presentation in GOLD I patients?” the researchers questioned. For evaluation of COPD, the GOLD does not currently promote the use of DLCO, and the clinical and prognostic utility of a low DLCO has not been studied, the authors noted.
Several COPD studies, however, have shown associations between low DLCO values and reduced exercise capacity, increased symptoms, risk of severe exacerbations, and mortality. The patients included in these studies, however, have generally had moderate to severe airflow limitation, and have not had postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.70 and an FEV1 ≥ 80%, defined by GOLD as COPD spirometric stage I. These mild obstruction GOLD I patients, in large epidemiological studies, do have increased risk of death. But it is often assumed, Dr. de Torres and colleagues noted, that “mild” suggests a good prognosis. They propose that a simple DLCO measurement could help identify those GOLD I patients with “worse overall COPD compromise and an increased risk of death.” Importantly, GOLD I represents the largest percentage of patients with airflow limitation that epidemiological studies have identified.
The researchers enrolled 360 GOLD stage I COPD patients, recording their age, sex, pack-years’ history, body mass index, dyspnea, lung function measurements, exercise capacity, BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, and history of exacerbations, and followed them for a mean of 109 months. They identified a cutoff DLCO value for all-cause mortality, compared the clinical and physiological characteristics of patients above and below the threshold, and explored the predictive power of that cutoff value.
All-cause mortality difference
The mean age in the overall population studied was 63 years (31% were women), with 43% active smokers, and pack-years history of 45. Overall mortality was 11% during the follow-up period. The predominantly male population was mildly overweight, had few comorbidities, normal FEV1 values, mild dyspnea, normal 6-minute walk distance, and very few exacerbations.
Analysis showed a DLCO cutoff value of < 60% was associated with a significant all-cause mortality differential (DLCO ≥ 60%: 9% vs. DLCO < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with DLCO < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-minute walk distance, and higher BODE index. Adjusted Cox multiple regression analysis confirmed that a DLCO < 60% was associated with an all-cause mortality hazard ratio [HR] of 3.37, (95% confidence interval, 1.35-8.39; P = .009).
Multiorgan loss of tissue
The researchers found that patients with baseline DLCO < 60% were more likely to be women (46% versus 28%), and to have a lower BMI (25 vs. 27), higher pack-year history (54 vs. 43), the same spirometric values but lower IC/TLC ratio (.37 vs. .40), a lower walk distance (443 vs. 485 meters), higher dyspnea (MRC score 1.1 vs. .7), similar exacerbation rate, higher BODE index (.5 vs. .2) and higher mortality than patients with higher DLCO % predicted values. This group, Dr. de Torres and colleagues suggest, represents a multiorgan loss of tissue, a phenotype associated with worse clinical outcomes and prognosis.
“Low DLCO in these patients,” Dr. de Torres said in an interview, “could mainly be secondary to coexistent emphysema, which is the most common cause of low DLCO in this population. Also possible, but less likely, is coexistent pulmonary hypertension.” He noted further that “This study opens the door to research specifically testing if such is the case, and if it is, for clinicians to use available therapies to prevent adverse outcomes.”
Comorbidity burden
Patients with GOLD I COPD die more often of cardiovascular disease instead of underlying lung disease, according to Richard H. Zou, MD, and Jessica Bon, MD, of the University of Pittsburgh, in an accompanying editorial in the journal CHEST.
Increased mortality rates, they suggest, may be related to higher comorbidity burden, particularly comorbidities associated with cardiovascular-related health. Subclinical cardiovascular disease is a common comorbidity in COPD, and concomitant endothelial dysfunction has been associated with both cardiovascular disease and early emphysema in smokers. They may have disproportionately reduced DLCO levels because of parenchymal destruction.
“This study suggests that DLCO can be used to identify patients with GOLD I COPD at increased death risk and that individuals with mild airflow obstruction with DLCO <60% predicted are a clinical phenotype distinct from those with higher DLCO levels,” Dr. Zhou and Dr. Bon concluded.
The researchers and the editorialists declared that they had no disclosures. One of the three cohorts assessed in the current study (CHAIN cohort in Spain) received funding from AstraZeneca.
Patients with a baseline DLCO (diffusing capacity for carbon monoxide) of < 60% of predicted have more severe disease clinical expression with higher mortality risk, according to a long-term observational study of Global Initiative for Obstructive Lung Disease (GOLD) I chronic obstructive pulmonary disease (COPD) patients. Clarifying mechanisms of low DLCO may help clinicians direct interventions toward ameliorating the low capacity, Juan Pablo de Torres, MD, and colleagues wrote in the journal CHEST®.
Defining increased risk
“Can a DLCO threshold help define an increased risk of death and a different clinical presentation in GOLD I patients?” the researchers questioned. For evaluation of COPD, the GOLD does not currently promote the use of DLCO, and the clinical and prognostic utility of a low DLCO has not been studied, the authors noted.
Several COPD studies, however, have shown associations between low DLCO values and reduced exercise capacity, increased symptoms, risk of severe exacerbations, and mortality. The patients included in these studies, however, have generally had moderate to severe airflow limitation, and have not had postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.70 and an FEV1 ≥ 80%, defined by GOLD as COPD spirometric stage I. These mild obstruction GOLD I patients, in large epidemiological studies, do have increased risk of death. But it is often assumed, Dr. de Torres and colleagues noted, that “mild” suggests a good prognosis. They propose that a simple DLCO measurement could help identify those GOLD I patients with “worse overall COPD compromise and an increased risk of death.” Importantly, GOLD I represents the largest percentage of patients with airflow limitation that epidemiological studies have identified.
The researchers enrolled 360 GOLD stage I COPD patients, recording their age, sex, pack-years’ history, body mass index, dyspnea, lung function measurements, exercise capacity, BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, and history of exacerbations, and followed them for a mean of 109 months. They identified a cutoff DLCO value for all-cause mortality, compared the clinical and physiological characteristics of patients above and below the threshold, and explored the predictive power of that cutoff value.
All-cause mortality difference
The mean age in the overall population studied was 63 years (31% were women), with 43% active smokers, and pack-years history of 45. Overall mortality was 11% during the follow-up period. The predominantly male population was mildly overweight, had few comorbidities, normal FEV1 values, mild dyspnea, normal 6-minute walk distance, and very few exacerbations.
Analysis showed a DLCO cutoff value of < 60% was associated with a significant all-cause mortality differential (DLCO ≥ 60%: 9% vs. DLCO < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with DLCO < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-minute walk distance, and higher BODE index. Adjusted Cox multiple regression analysis confirmed that a DLCO < 60% was associated with an all-cause mortality hazard ratio [HR] of 3.37, (95% confidence interval, 1.35-8.39; P = .009).
Multiorgan loss of tissue
The researchers found that patients with baseline DLCO < 60% were more likely to be women (46% versus 28%), and to have a lower BMI (25 vs. 27), higher pack-year history (54 vs. 43), the same spirometric values but lower IC/TLC ratio (.37 vs. .40), a lower walk distance (443 vs. 485 meters), higher dyspnea (MRC score 1.1 vs. .7), similar exacerbation rate, higher BODE index (.5 vs. .2) and higher mortality than patients with higher DLCO % predicted values. This group, Dr. de Torres and colleagues suggest, represents a multiorgan loss of tissue, a phenotype associated with worse clinical outcomes and prognosis.
“Low DLCO in these patients,” Dr. de Torres said in an interview, “could mainly be secondary to coexistent emphysema, which is the most common cause of low DLCO in this population. Also possible, but less likely, is coexistent pulmonary hypertension.” He noted further that “This study opens the door to research specifically testing if such is the case, and if it is, for clinicians to use available therapies to prevent adverse outcomes.”
Comorbidity burden
Patients with GOLD I COPD die more often of cardiovascular disease instead of underlying lung disease, according to Richard H. Zou, MD, and Jessica Bon, MD, of the University of Pittsburgh, in an accompanying editorial in the journal CHEST.
Increased mortality rates, they suggest, may be related to higher comorbidity burden, particularly comorbidities associated with cardiovascular-related health. Subclinical cardiovascular disease is a common comorbidity in COPD, and concomitant endothelial dysfunction has been associated with both cardiovascular disease and early emphysema in smokers. They may have disproportionately reduced DLCO levels because of parenchymal destruction.
“This study suggests that DLCO can be used to identify patients with GOLD I COPD at increased death risk and that individuals with mild airflow obstruction with DLCO <60% predicted are a clinical phenotype distinct from those with higher DLCO levels,” Dr. Zhou and Dr. Bon concluded.
The researchers and the editorialists declared that they had no disclosures. One of the three cohorts assessed in the current study (CHAIN cohort in Spain) received funding from AstraZeneca.
FROM THE JOURNAL CHEST®
Earliest 9/11 responders have higher COPD rates
The earliest responders to reach the site of the destroyed twin towers of the World Trade Center on Sept. 11, 2001, are at highest risk for chronic obstructive pulmonary disease and asthma/COPD overlap (ACO) among all those who worked at the site. The 9/11 attack was the deadliest terrorist attack on American soil.
The findings come from a case-control study that included nearly 18,000 emergency responders and volunteers. The investigators found that those who arrived at the site within 48 hours had an approximately 30% higher risk of developing COPD than those who arrived later, after adjustment for smoking and obesity, reported Rafael E de la Hoz, MD, a professor of environmental medicine, public health, and medicine at Mount Sinai Medical Center, New York, and colleagues.
“In this largest World Trade Center occupational cohort, spirometrically defined COPD and ACO were both modestly but significantly associated with World Trade Center exposure intensity, but the association seemed driven by the overlap,” he said in a narrated poster presentation during the European Respiratory Society 2021 International Congress.
“Around the world, we rely on our emergency workers to help when disasters occur,” commented Arzu Yorgancıoğlu, MD, professor and head of the department of pulmonology at Celal Bayar University, Manisa, Turkey, who was not involved in the study.
“This study shows how important it is to keep monitoring the health of workers, like those who attended the World Trade Center site 20 years ago, as occupational exposure to pollutants can lead to COPD. What we can learn from research like this is not only how best to care for emergency workers who operate in dangerous conditions but also how we can protect them in their work in the future,” she said.
Inconsistent findings
Fire and police personnel, emergency medical workers, construction workers, and others who labored amid the lingering pall of toxic dust and smoke at the World Trade Center site have developed asthma and other lower respiratory tract diseases over the ensuing decades.
“As the occupational cohorts age, there are concerns about chronic, longer latency, and disabling respiratory disease,” Dr. de la Hoz and colleagues wrote.
There have been inconsistent reports about the potential associations between COPD and ACO and the intensity of occupational exposure at the World Trade Center site. This prompted the investigators to further explore these associations using spirometry-defined disease.
They assessed data on 17,996 former World Trade Center site workers who had undergone at least two good-quality spirometric evaluations from 2002 to 2018.
To be classified as having COPD, workers had to have fixed airway obstruction. Those in the ACO subgroup were also required to have prebronchodilator obstruction with forced expiratory volume in 1 second of more than 400 mL in response to bronchodilation.
The patients were matched for sex and height within 5 cm using a 1:4 nested case-control design. Missing data were imputed.
Earliest arrivals paid the highest penalty
Of the total cohort, 85.4% were men, and 85.6% were overweight or obese. A total of 586 workers (3.3%) met the case definition for having COPD; 258 (1.4%) met the definition for having ACO.
The investigators found that the prevalence of self-reported ACO was six times higher than the prevalence of spirometry-confirmed disease. Among those who reported an onset date, 56.7% reported having asthma before COPD; the remainder reported having COPD first.
In analyses adjusted for age, sex, cohort entry period, smoking status, body mass index, metabolic syndrome parameters, and eosinophil levels, both COPD and ACO were significantly associated with early arrival at the World Trade Center site, with an adjusted odds ratio for COPD of 1.3 (95% confidence interval, 1.03-1.64), and an OR for ACO of 1.66 (95% CI, 1.1-2.49).
There was no significant interaction between early site arrival and smoking status.
The association between early exposure and COPD was no longer significant when those with ACO were excluded, the authors noted.
“We also observed that COPD more often followed asthma in these workers than the reverse, suggesting that asthma may have been on the path to COPD in most workers affected by the inhaled toxicants at the disaster site,” Dr. de la Hoz and colleagues wrote.
In addition, “our data suggest that self-reported physician diagnoses of COPD, asthma, and ACO are poorly correlated with objective data in this cohort,” they concluded.
The study was supported by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The authors and Dr. Yorgancıoğlu disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The earliest responders to reach the site of the destroyed twin towers of the World Trade Center on Sept. 11, 2001, are at highest risk for chronic obstructive pulmonary disease and asthma/COPD overlap (ACO) among all those who worked at the site. The 9/11 attack was the deadliest terrorist attack on American soil.
The findings come from a case-control study that included nearly 18,000 emergency responders and volunteers. The investigators found that those who arrived at the site within 48 hours had an approximately 30% higher risk of developing COPD than those who arrived later, after adjustment for smoking and obesity, reported Rafael E de la Hoz, MD, a professor of environmental medicine, public health, and medicine at Mount Sinai Medical Center, New York, and colleagues.
“In this largest World Trade Center occupational cohort, spirometrically defined COPD and ACO were both modestly but significantly associated with World Trade Center exposure intensity, but the association seemed driven by the overlap,” he said in a narrated poster presentation during the European Respiratory Society 2021 International Congress.
“Around the world, we rely on our emergency workers to help when disasters occur,” commented Arzu Yorgancıoğlu, MD, professor and head of the department of pulmonology at Celal Bayar University, Manisa, Turkey, who was not involved in the study.
“This study shows how important it is to keep monitoring the health of workers, like those who attended the World Trade Center site 20 years ago, as occupational exposure to pollutants can lead to COPD. What we can learn from research like this is not only how best to care for emergency workers who operate in dangerous conditions but also how we can protect them in their work in the future,” she said.
Inconsistent findings
Fire and police personnel, emergency medical workers, construction workers, and others who labored amid the lingering pall of toxic dust and smoke at the World Trade Center site have developed asthma and other lower respiratory tract diseases over the ensuing decades.
“As the occupational cohorts age, there are concerns about chronic, longer latency, and disabling respiratory disease,” Dr. de la Hoz and colleagues wrote.
There have been inconsistent reports about the potential associations between COPD and ACO and the intensity of occupational exposure at the World Trade Center site. This prompted the investigators to further explore these associations using spirometry-defined disease.
They assessed data on 17,996 former World Trade Center site workers who had undergone at least two good-quality spirometric evaluations from 2002 to 2018.
To be classified as having COPD, workers had to have fixed airway obstruction. Those in the ACO subgroup were also required to have prebronchodilator obstruction with forced expiratory volume in 1 second of more than 400 mL in response to bronchodilation.
The patients were matched for sex and height within 5 cm using a 1:4 nested case-control design. Missing data were imputed.
Earliest arrivals paid the highest penalty
Of the total cohort, 85.4% were men, and 85.6% were overweight or obese. A total of 586 workers (3.3%) met the case definition for having COPD; 258 (1.4%) met the definition for having ACO.
The investigators found that the prevalence of self-reported ACO was six times higher than the prevalence of spirometry-confirmed disease. Among those who reported an onset date, 56.7% reported having asthma before COPD; the remainder reported having COPD first.
In analyses adjusted for age, sex, cohort entry period, smoking status, body mass index, metabolic syndrome parameters, and eosinophil levels, both COPD and ACO were significantly associated with early arrival at the World Trade Center site, with an adjusted odds ratio for COPD of 1.3 (95% confidence interval, 1.03-1.64), and an OR for ACO of 1.66 (95% CI, 1.1-2.49).
There was no significant interaction between early site arrival and smoking status.
The association between early exposure and COPD was no longer significant when those with ACO were excluded, the authors noted.
“We also observed that COPD more often followed asthma in these workers than the reverse, suggesting that asthma may have been on the path to COPD in most workers affected by the inhaled toxicants at the disaster site,” Dr. de la Hoz and colleagues wrote.
In addition, “our data suggest that self-reported physician diagnoses of COPD, asthma, and ACO are poorly correlated with objective data in this cohort,” they concluded.
The study was supported by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The authors and Dr. Yorgancıoğlu disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The earliest responders to reach the site of the destroyed twin towers of the World Trade Center on Sept. 11, 2001, are at highest risk for chronic obstructive pulmonary disease and asthma/COPD overlap (ACO) among all those who worked at the site. The 9/11 attack was the deadliest terrorist attack on American soil.
The findings come from a case-control study that included nearly 18,000 emergency responders and volunteers. The investigators found that those who arrived at the site within 48 hours had an approximately 30% higher risk of developing COPD than those who arrived later, after adjustment for smoking and obesity, reported Rafael E de la Hoz, MD, a professor of environmental medicine, public health, and medicine at Mount Sinai Medical Center, New York, and colleagues.
“In this largest World Trade Center occupational cohort, spirometrically defined COPD and ACO were both modestly but significantly associated with World Trade Center exposure intensity, but the association seemed driven by the overlap,” he said in a narrated poster presentation during the European Respiratory Society 2021 International Congress.
“Around the world, we rely on our emergency workers to help when disasters occur,” commented Arzu Yorgancıoğlu, MD, professor and head of the department of pulmonology at Celal Bayar University, Manisa, Turkey, who was not involved in the study.
“This study shows how important it is to keep monitoring the health of workers, like those who attended the World Trade Center site 20 years ago, as occupational exposure to pollutants can lead to COPD. What we can learn from research like this is not only how best to care for emergency workers who operate in dangerous conditions but also how we can protect them in their work in the future,” she said.
Inconsistent findings
Fire and police personnel, emergency medical workers, construction workers, and others who labored amid the lingering pall of toxic dust and smoke at the World Trade Center site have developed asthma and other lower respiratory tract diseases over the ensuing decades.
“As the occupational cohorts age, there are concerns about chronic, longer latency, and disabling respiratory disease,” Dr. de la Hoz and colleagues wrote.
There have been inconsistent reports about the potential associations between COPD and ACO and the intensity of occupational exposure at the World Trade Center site. This prompted the investigators to further explore these associations using spirometry-defined disease.
They assessed data on 17,996 former World Trade Center site workers who had undergone at least two good-quality spirometric evaluations from 2002 to 2018.
To be classified as having COPD, workers had to have fixed airway obstruction. Those in the ACO subgroup were also required to have prebronchodilator obstruction with forced expiratory volume in 1 second of more than 400 mL in response to bronchodilation.
The patients were matched for sex and height within 5 cm using a 1:4 nested case-control design. Missing data were imputed.
Earliest arrivals paid the highest penalty
Of the total cohort, 85.4% were men, and 85.6% were overweight or obese. A total of 586 workers (3.3%) met the case definition for having COPD; 258 (1.4%) met the definition for having ACO.
The investigators found that the prevalence of self-reported ACO was six times higher than the prevalence of spirometry-confirmed disease. Among those who reported an onset date, 56.7% reported having asthma before COPD; the remainder reported having COPD first.
In analyses adjusted for age, sex, cohort entry period, smoking status, body mass index, metabolic syndrome parameters, and eosinophil levels, both COPD and ACO were significantly associated with early arrival at the World Trade Center site, with an adjusted odds ratio for COPD of 1.3 (95% confidence interval, 1.03-1.64), and an OR for ACO of 1.66 (95% CI, 1.1-2.49).
There was no significant interaction between early site arrival and smoking status.
The association between early exposure and COPD was no longer significant when those with ACO were excluded, the authors noted.
“We also observed that COPD more often followed asthma in these workers than the reverse, suggesting that asthma may have been on the path to COPD in most workers affected by the inhaled toxicants at the disaster site,” Dr. de la Hoz and colleagues wrote.
In addition, “our data suggest that self-reported physician diagnoses of COPD, asthma, and ACO are poorly correlated with objective data in this cohort,” they concluded.
The study was supported by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The authors and Dr. Yorgancıoğlu disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.