Barry Make - Academia.edu (original) (raw)

Papers by Barry Make

European Respiratory Journal, 2010

The aim of the present study was investigate the long-term effect of tiotropium as first maintena... more The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD). A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting beta-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George's Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed. 403 patients (mean+/-sd age 63+/-8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 53+/-12% predicted) received tiotropium and 407 (64+/-8 yrs of age, post-bronchodilator FEV(1) 51+/-12% pred) received placebo. Post-bronchodilator FEV(1) decline was 42+/-4 mL.yr(-1) in the tiotropium group and 53+/-4 mL.yr(-1) in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV(1) was 134 mL higher in the tiotropium group compared to the placebo group (p<0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05+/-0.34 units.yr(-1); p = 0.002). This was particularly significant for the impact (difference of 1.08+/-0.37 units.yr(-1); p = 0.004) and activity (1.44+/-0.40 units.yr(-1); p<0.001) domains, but not for symptoms (0.26+/-0.50 units.yr(-1); p = 0.6). At 48 months, the difference in total score was 4.6 units (p<0.001) with tiotropium compared to placebo. In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.

CHEST Journal, 2013

ABSTRACT COPD Safety of Treatment PostersSESSION TYPE: Original Investigation PosterPRESENTED ON:... more ABSTRACT COPD Safety of Treatment PostersSESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PMPURPOSE: This study was performed to evaluate risk of life-threatening respiratory events (COPD exacerbation-related hospitalizations and respiratory death) during 1 year of treatment with ARF15µg twice daily (ARF) compared with placebo in subjects with moderate-to-severe COPD.METHODS: This was a double blind, randomized, placebo controlled, parallel group study. Subjects meeting inclusion criteria (≥40 years old with COPD, baseline FEV1 ≤50% of predicted, ≥15 pack year smoking history) were randomized to ARF (BROVANA® [arformoterol tartrate] Inhalation Solution, N=420) or placebo (N=421) for 1 year. Subjects remained on other COPD medications except LABAs. Short acting bronchodilators were only withheld prior to visits and inhaled steroids and xanthines were permitted throughout at constant dosage. The primary assessment was time from randomization to a primary event (respiratory death or first COPD exacerbation related hospitalization, whichever occurred first). The hazard ratio and 90%CI comparing ARF to placebo for the primary assessment were estimated using a Cox proportional hazards regression model, with treatment group, baseline smoking status, age, and baseline FEV1 as covariates. Secondary analysis of treatment by covariate interaction for the primary assessment was conducted and is reported here.RESULTS: 466 subjects completed 1 year of treatment. Subjects who prematurely discontinued the study treatment were followed for a primary event for the remainder of the treatment period. 142 primary events occurred in 103 subjects, with majority experiencing a single event. 63 (15.0%) placebo and 40 (9.5%) ARF subjects had at least one primary event. The primary event hazard ratios (HR) by baseline covariates of interest were: current smokers (n=432; HR:0.809), former smokers (n=409; HR:0.445); <65 years old (n=426; HR:0.707), 65 to 75 years old (n=301; HR:0.786) and >75 years old (n=114; HR:0.269); COPD disease severity (% Predicted FEV1): <30% (n=233; HR:0.565), 30-<50% (n=388; HR:0.648) and ≥50% (n=219; HR:0.618).CONCLUSIONS: In this long-term safety study, arformoterol tartrate 15µg BID for 1 year significantly decreased the risk of respiratory death or COPD exacerbation-related hospitalizations compared with placebo irrespective of the smoking status, age, or disease severity.CLINICAL IMPLICATIONS: The results of this study showed that arformoterol tartrate reduced risk of respiratory death and COPD-exacerbations related hospitalizations during 1 year of treatment with Arformoterol tartrate 15µg BID.DISCLOSURE: James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Sunovion Pharmaceuticals Inc Nicola Hanania: Consultant fee, speaker bureau, advisory committee, etc.: Sunovion Pharmaceuticals Inc, Grant monies (from industry related sources): Sunovion Pharmaceuticals Inc (past, completed) Barry Make: Grant monies (from sources other than industry): National HEart, Lung, and Blood Institute, Grant monies (from industry related sources): Boehringer-Ingelheim, Forest, NABI, Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Abbott, AstraZeneca, Boehringer-Ingelheim, Breathe, Coviden, Forest, GSK, Ikaria, Merck, MedImmune, NABI, Novartis, PfizerNo Product/Research Disclosure Information.

B103. COPD: MECHANISMS OF DISEASE PROGRESSION AND EXACERBATION, 2012

Proceedings of the American Thoracic Society, 2008

Comorbidities such as cardiac disease, diabetes mellitus, hypertension, osteoporosis, and psychol... more Comorbidities such as cardiac disease, diabetes mellitus, hypertension, osteoporosis, and psychological disorders are commonly reported in patients with chronic obstructive pulmonary disease (COPD) but with great variability in reported prevalence. Tobacco smoking is a risk factor for many of these comorbidities as well as for COPD, making it difficult to draw conclusions about the relationship between COPD and these comorbidities. However, recent large epidemiologic studies have confirmed the independent detrimental effects of these comorbidities on patients with COPD. On the other hand, many of these comorbidities are now considered to be part of the commonly prevalent nonpulmonary sequelae of COPD that are relevant not only to the understanding of the real burden of COPD but also to the development of effective management strategies.

COPD, 2005

This issue of the COPD: Journal of Chronic Obstructive Pulmonary Disease presents the papers from... more This issue of the COPD: Journal of Chronic Obstructive Pulmonary Disease presents the papers from the “Workshop on Minimal Clinically Important Differences in COPD” held in Bal Harbour, Florida, on January 11-13, 2004. The goals of this meeting were to: discuss the ...

International Journal of Chronic Obstructive Pulmonary Disease, 2015

There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exace... more There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables. The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex. Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX). Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol). SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk.

Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, 2014

COPD patients have a great burden of comorbidity. However, it is not well established whether thi... more COPD patients have a great burden of comorbidity. However, it is not well established whether this is due to shared risk factors such as smoking, if they impact patients exercise capacity and quality of life, or whether there are racial disparities in their impact on COPD. We analyzed data from 10,192 current and ex-smokers with (cases) and without COPD (controls) from the COPDGene® cohort to establish risk for COPD comorbidities adjusted for pertinent covariates. In adjusted models, we examined comorbidities prevalence and impact in African-Americans (AA) and Non-Hispanic Whites (NHW). Comorbidities are more common in COPD compared to those with normal spirometry (controls), and the risk persists after adjustments for covariates including pack-years smoked. After adjustment for confounders, eight conditions were independently associated with worse exercise capacity, quality of life and dyspnea. There were racial disparities in the impact of comorbidities on exercise capacity, dyspnea and quality of life, presence of osteoarthritis and gastroesophageal reflux disease having a greater negative impact on all three outcomes in AAs than NHWs (p<0.05 for all interaction terms). Individuals with COPD have a higher risk for comorbidities than controls, an important finding shown for the first time comprehensively after accounting for confounders. Individual comorbidities are associated with worse exercise capacity, quality of life, and dyspnea, in African-Americans compared to non-Hispanic Whites.

Chest, 1998

1. Chest. 1998 May;113(5 Suppl):289S-344S. Mechanical ventilation beyond the intensive care unit.... more 1. Chest. 1998 May;113(5 Suppl):289S-344S. Mechanical ventilation beyond the intensive care unit. Report of a consensus conference of the American College of Chest Physicians. Make BJ, Hill NS, Goldberg AI, Bach JR, Criner ...

Respiratory Medicine, 2008

New England Journal of Medicine, 1986

Some patients with chronic airflow obstruction experience dyspnea with mild arm exercise but not ... more Some patients with chronic airflow obstruction experience dyspnea with mild arm exercise but not with more-intense leg exercise. To investigate why these patients have limited endurance during arm exertion, we studied ventilatory responses to exercise with unsupported arms in 12 patients with chronic airflow obstruction (mean [+/- SD] forced expiratory volume in one second, 0.68 +/- 0.28 liters). Unloaded leg cycling was also studied for comparison. In the five patients who had the most severe airflow obstruction, arm exercise was limited by dyspnea after 3.3 +/- 0.7 minutes, and dyssynchronous thoracoabdominal breathing developed. In the other seven patients, arm exercise was limited by the sensation of muscle fatigue after 6.1 +/- 2.0 minutes (P less than 0.05), and dyssynchronous breathing did not occur. None of the 12 patients had dyssynchronous breathing during unloaded leg cycling. Maximal transdiaphragmatic pressure, a measure of diaphragmatic fatigue, declined similarly after arm and leg exercise in both groups. During unsupported arm work, the accessory muscles of inspiration help position the torso and arms. We hypothesize that the extra demand placed on these muscles during arm exertion leads to early fatigue, an increased load on the diaphragm, and dyssynchronous thoracoabdominal inspirations. This sequence may contribute to dyspnea and limited endurance during upper-extremity exercise.

Journal of Psychosomatic Research, 2011

Journal Of Chronic Fatigue Syndrome, 1997

Journal of Allergy and Clinical Immunology, 2003

Proceedings of The American Thoracic Society, 2007

The effectiveness of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary... more The effectiveness of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) remains controver- sial. Randomized controlled trials, meta-analyses, medication with- drawal studies, and observational reports have examined this ques- tion, with mixed results. Observational studies have been subject to criticism because of study design involving immortal time bias. Some randomized controlled trials suggest small benefits in lung

Academic Radiology, 1995

We assessed the value of quantitative high-resolution computed tomography (CT) as a diagnostic an... more We assessed the value of quantitative high-resolution computed tomography (CT) as a diagnostic and prognostic tool in smoking-related emphysema. We performed an inception cohort study of 14 patients referred with emphysema. The diagnosis of emphysema was based on a compatible history, physical examination, chest radiograph, CT scan of the lung, and pulmonary physiologic evaluation. As a group, those who underwent exercise testing were hyperinflated (percentage predicted total lung capacity +/- standard error of the mean = 133 +/- 9%), and there was evidence of air trapping (percentage predicted respiratory volume = 318 +/- 31%) and airflow limitation (forced expiratory volume in 1 sec [FEV1] = 40 +/- 7%). The exercise performance of the group was severely limited (maximum achievable workload = 43 +/- 6%) and was characterized by prominent ventilatory, gas exchange, and pulmonary vascular abnormalities. The quantitative CT index was markedly elevated in all patients (76 +/- 9; n = 14; normal < 4). There were correlations between this quantitative CT index and measures of airflow limitation (FEV1 r2 = .34, p = 09; FEV1/forced vital capacity r2 = .46, p = .04) and between maximum workload achieved (r2 = .93, p = .0001) and maximum oxygen utilization (r2 = .83, p = .0007). Quantitative chest CT assessment of disease severity is correlated with the degree of airflow limitation and exercise impairment in pulmonary emphysema.

American Journal of Respiratory and Critical Care Medicine, 2011

American Journal of Respiratory and Critical Care Medicine, 2013

JAMA internal medicine, Jan 22, 2015

Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary dis... more Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n ...

The European respiratory journal, Jan 28, 2015

European Respiratory Journal, 2010

The aim of the present study was investigate the long-term effect of tiotropium as first maintena... more The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD). A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting beta-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George's Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed. 403 patients (mean+/-sd age 63+/-8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 53+/-12% predicted) received tiotropium and 407 (64+/-8 yrs of age, post-bronchodilator FEV(1) 51+/-12% pred) received placebo. Post-bronchodilator FEV(1) decline was 42+/-4 mL.yr(-1) in the tiotropium group and 53+/-4 mL.yr(-1) in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV(1) was 134 mL higher in the tiotropium group compared to the placebo group (p<0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05+/-0.34 units.yr(-1); p = 0.002). This was particularly significant for the impact (difference of 1.08+/-0.37 units.yr(-1); p = 0.004) and activity (1.44+/-0.40 units.yr(-1); p<0.001) domains, but not for symptoms (0.26+/-0.50 units.yr(-1); p = 0.6). At 48 months, the difference in total score was 4.6 units (p<0.001) with tiotropium compared to placebo. In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.

CHEST Journal, 2013

ABSTRACT COPD Safety of Treatment PostersSESSION TYPE: Original Investigation PosterPRESENTED ON:... more ABSTRACT COPD Safety of Treatment PostersSESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PMPURPOSE: This study was performed to evaluate risk of life-threatening respiratory events (COPD exacerbation-related hospitalizations and respiratory death) during 1 year of treatment with ARF15µg twice daily (ARF) compared with placebo in subjects with moderate-to-severe COPD.METHODS: This was a double blind, randomized, placebo controlled, parallel group study. Subjects meeting inclusion criteria (≥40 years old with COPD, baseline FEV1 ≤50% of predicted, ≥15 pack year smoking history) were randomized to ARF (BROVANA® [arformoterol tartrate] Inhalation Solution, N=420) or placebo (N=421) for 1 year. Subjects remained on other COPD medications except LABAs. Short acting bronchodilators were only withheld prior to visits and inhaled steroids and xanthines were permitted throughout at constant dosage. The primary assessment was time from randomization to a primary event (respiratory death or first COPD exacerbation related hospitalization, whichever occurred first). The hazard ratio and 90%CI comparing ARF to placebo for the primary assessment were estimated using a Cox proportional hazards regression model, with treatment group, baseline smoking status, age, and baseline FEV1 as covariates. Secondary analysis of treatment by covariate interaction for the primary assessment was conducted and is reported here.RESULTS: 466 subjects completed 1 year of treatment. Subjects who prematurely discontinued the study treatment were followed for a primary event for the remainder of the treatment period. 142 primary events occurred in 103 subjects, with majority experiencing a single event. 63 (15.0%) placebo and 40 (9.5%) ARF subjects had at least one primary event. The primary event hazard ratios (HR) by baseline covariates of interest were: current smokers (n=432; HR:0.809), former smokers (n=409; HR:0.445); <65 years old (n=426; HR:0.707), 65 to 75 years old (n=301; HR:0.786) and >75 years old (n=114; HR:0.269); COPD disease severity (% Predicted FEV1): <30% (n=233; HR:0.565), 30-<50% (n=388; HR:0.648) and ≥50% (n=219; HR:0.618).CONCLUSIONS: In this long-term safety study, arformoterol tartrate 15µg BID for 1 year significantly decreased the risk of respiratory death or COPD exacerbation-related hospitalizations compared with placebo irrespective of the smoking status, age, or disease severity.CLINICAL IMPLICATIONS: The results of this study showed that arformoterol tartrate reduced risk of respiratory death and COPD-exacerbations related hospitalizations during 1 year of treatment with Arformoterol tartrate 15µg BID.DISCLOSURE: James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Sunovion Pharmaceuticals Inc Nicola Hanania: Consultant fee, speaker bureau, advisory committee, etc.: Sunovion Pharmaceuticals Inc, Grant monies (from industry related sources): Sunovion Pharmaceuticals Inc (past, completed) Barry Make: Grant monies (from sources other than industry): National HEart, Lung, and Blood Institute, Grant monies (from industry related sources): Boehringer-Ingelheim, Forest, NABI, Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Abbott, AstraZeneca, Boehringer-Ingelheim, Breathe, Coviden, Forest, GSK, Ikaria, Merck, MedImmune, NABI, Novartis, PfizerNo Product/Research Disclosure Information.

B103. COPD: MECHANISMS OF DISEASE PROGRESSION AND EXACERBATION, 2012

Proceedings of the American Thoracic Society, 2008

Comorbidities such as cardiac disease, diabetes mellitus, hypertension, osteoporosis, and psychol... more Comorbidities such as cardiac disease, diabetes mellitus, hypertension, osteoporosis, and psychological disorders are commonly reported in patients with chronic obstructive pulmonary disease (COPD) but with great variability in reported prevalence. Tobacco smoking is a risk factor for many of these comorbidities as well as for COPD, making it difficult to draw conclusions about the relationship between COPD and these comorbidities. However, recent large epidemiologic studies have confirmed the independent detrimental effects of these comorbidities on patients with COPD. On the other hand, many of these comorbidities are now considered to be part of the commonly prevalent nonpulmonary sequelae of COPD that are relevant not only to the understanding of the real burden of COPD but also to the development of effective management strategies.

COPD, 2005

This issue of the COPD: Journal of Chronic Obstructive Pulmonary Disease presents the papers from... more This issue of the COPD: Journal of Chronic Obstructive Pulmonary Disease presents the papers from the “Workshop on Minimal Clinically Important Differences in COPD” held in Bal Harbour, Florida, on January 11-13, 2004. The goals of this meeting were to: discuss the ...

International Journal of Chronic Obstructive Pulmonary Disease, 2015

There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exace... more There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables. The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex. Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX). Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol). SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk.

Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, 2014

COPD patients have a great burden of comorbidity. However, it is not well established whether thi... more COPD patients have a great burden of comorbidity. However, it is not well established whether this is due to shared risk factors such as smoking, if they impact patients exercise capacity and quality of life, or whether there are racial disparities in their impact on COPD. We analyzed data from 10,192 current and ex-smokers with (cases) and without COPD (controls) from the COPDGene® cohort to establish risk for COPD comorbidities adjusted for pertinent covariates. In adjusted models, we examined comorbidities prevalence and impact in African-Americans (AA) and Non-Hispanic Whites (NHW). Comorbidities are more common in COPD compared to those with normal spirometry (controls), and the risk persists after adjustments for covariates including pack-years smoked. After adjustment for confounders, eight conditions were independently associated with worse exercise capacity, quality of life and dyspnea. There were racial disparities in the impact of comorbidities on exercise capacity, dyspnea and quality of life, presence of osteoarthritis and gastroesophageal reflux disease having a greater negative impact on all three outcomes in AAs than NHWs (p<0.05 for all interaction terms). Individuals with COPD have a higher risk for comorbidities than controls, an important finding shown for the first time comprehensively after accounting for confounders. Individual comorbidities are associated with worse exercise capacity, quality of life, and dyspnea, in African-Americans compared to non-Hispanic Whites.

Chest, 1998

1. Chest. 1998 May;113(5 Suppl):289S-344S. Mechanical ventilation beyond the intensive care unit.... more 1. Chest. 1998 May;113(5 Suppl):289S-344S. Mechanical ventilation beyond the intensive care unit. Report of a consensus conference of the American College of Chest Physicians. Make BJ, Hill NS, Goldberg AI, Bach JR, Criner ...

Respiratory Medicine, 2008

New England Journal of Medicine, 1986

Some patients with chronic airflow obstruction experience dyspnea with mild arm exercise but not ... more Some patients with chronic airflow obstruction experience dyspnea with mild arm exercise but not with more-intense leg exercise. To investigate why these patients have limited endurance during arm exertion, we studied ventilatory responses to exercise with unsupported arms in 12 patients with chronic airflow obstruction (mean [+/- SD] forced expiratory volume in one second, 0.68 +/- 0.28 liters). Unloaded leg cycling was also studied for comparison. In the five patients who had the most severe airflow obstruction, arm exercise was limited by dyspnea after 3.3 +/- 0.7 minutes, and dyssynchronous thoracoabdominal breathing developed. In the other seven patients, arm exercise was limited by the sensation of muscle fatigue after 6.1 +/- 2.0 minutes (P less than 0.05), and dyssynchronous breathing did not occur. None of the 12 patients had dyssynchronous breathing during unloaded leg cycling. Maximal transdiaphragmatic pressure, a measure of diaphragmatic fatigue, declined similarly after arm and leg exercise in both groups. During unsupported arm work, the accessory muscles of inspiration help position the torso and arms. We hypothesize that the extra demand placed on these muscles during arm exertion leads to early fatigue, an increased load on the diaphragm, and dyssynchronous thoracoabdominal inspirations. This sequence may contribute to dyspnea and limited endurance during upper-extremity exercise.

Journal of Psychosomatic Research, 2011

Journal Of Chronic Fatigue Syndrome, 1997

Journal of Allergy and Clinical Immunology, 2003

Proceedings of The American Thoracic Society, 2007

The effectiveness of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary... more The effectiveness of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) remains controver- sial. Randomized controlled trials, meta-analyses, medication with- drawal studies, and observational reports have examined this ques- tion, with mixed results. Observational studies have been subject to criticism because of study design involving immortal time bias. Some randomized controlled trials suggest small benefits in lung

Academic Radiology, 1995

We assessed the value of quantitative high-resolution computed tomography (CT) as a diagnostic an... more We assessed the value of quantitative high-resolution computed tomography (CT) as a diagnostic and prognostic tool in smoking-related emphysema. We performed an inception cohort study of 14 patients referred with emphysema. The diagnosis of emphysema was based on a compatible history, physical examination, chest radiograph, CT scan of the lung, and pulmonary physiologic evaluation. As a group, those who underwent exercise testing were hyperinflated (percentage predicted total lung capacity +/- standard error of the mean = 133 +/- 9%), and there was evidence of air trapping (percentage predicted respiratory volume = 318 +/- 31%) and airflow limitation (forced expiratory volume in 1 sec [FEV1] = 40 +/- 7%). The exercise performance of the group was severely limited (maximum achievable workload = 43 +/- 6%) and was characterized by prominent ventilatory, gas exchange, and pulmonary vascular abnormalities. The quantitative CT index was markedly elevated in all patients (76 +/- 9; n = 14; normal < 4). There were correlations between this quantitative CT index and measures of airflow limitation (FEV1 r2 = .34, p = 09; FEV1/forced vital capacity r2 = .46, p = .04) and between maximum workload achieved (r2 = .93, p = .0001) and maximum oxygen utilization (r2 = .83, p = .0007). Quantitative chest CT assessment of disease severity is correlated with the degree of airflow limitation and exercise impairment in pulmonary emphysema.

American Journal of Respiratory and Critical Care Medicine, 2011

American Journal of Respiratory and Critical Care Medicine, 2013

JAMA internal medicine, Jan 22, 2015

Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary dis... more Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n ...

The European respiratory journal, Jan 28, 2015