Pat G. Camp

Airway Wall Thickening and Emphysema Show Independent Familial Aggregation in Chronic Obstructive Pulmonary Disease

RATIONALE It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families. OBJECTIVES To determine whether airway wall thickening and emphysema (1) make independent contributions to the severity of COPD and (2) show independent aggregation in families of individuals with COPD. METHODS Index cases with COPD and their smoking siblings underwent spirometry and were offered high-resolution computed tomography scans of the thorax to assess the severity of airway wall thickening and emphysema. MEASUREMENTS AND MAIN RESULTS A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non-COPD-related thoracic disease. Airway wall thickness correlated with pack-years smoked (P < or = 0.001) and symptoms of chronic bronchitis (P < 0.001). FEV(1) (expressed as % predicted) was independently associated with airway wall thickness at a lumen perimeter of 10 mm (P = 0.0001) and 20 mm (P = 0.0013) and emphysema at -950 Hounsfield units (P < 0.0001). There was independent familial aggregation of both the emphysema (adjusted odds ratio, 2.1; 95% confidence interval, 1.1-4.0; P < or = 0.02) and airway disease phenotypes (P < 0.0001) of COPD. CONCLUSIONS Airway wall thickening and emphysema make independent contributions to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes.

A pooled analysis of FEV1, decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.

Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis

BackgroundRecent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men. Whether female adult smokers are biologically more susceptible to COPD is unknown. This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.MethodsA systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.ResultsOf the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants). There was heterogeneity in gender-related results across the studies. However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers. Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008). Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).ConclusionAs female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers. Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings.

Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.

BACKGROUND COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

Quantifying the Extent of Emphysema: Factors Associated with Radiologists' Estimations and Quantitative Indices of Emphysema Severity Using the ECLIPSE Cohort

RATIONALE AND OBJECTIVES This study investigated what factors radiologists take into account when estimating emphysema severity and assessed quantitative computed tomography (CT) measurements of low attenuation areas. MATERIALS AND METHODS CT scans and spirometry were obtained on 1519 chronic obstructive pulmonary disease (COPD) subjects, 269 smoker controls, and 184 nonsmoker controls from the Evaluation of COPD Longitudinally to Indentify Surrogate Endpoints (ECLIPSE) study. CT scans were analyzed using the threshold technique (%<-950HU) and a low attenuation cluster analysis. Two radiologists scored emphysema severity (0 to 5 scale), described the predominant type and distribution of emphysema, and the presence of suspected small airways disease. RESULTS The percent low attenuation area (%LAA) and visual scores of emphysema severity correlated well (r = 0.77, P < .001). %LAA, low attenuation cluster analysis, and absence of radiologist described gas trapping, distribution, and predominant type of emphysema were predictors of visual scores of emphysema severity (all P < .001). CT scans scored as showing regions of gas trapping had smaller lesions for a similar %LAA than those without (P < .001). CONCLUSIONS Visual estimates of emphysema are not only determined by the extent of LAA, but also by lesion size, predominant type, and distribution of emphysema and presence/absence of areas of small airways disease. A computer analysis of low attenuation cluster size helps quantitative algorithms discriminate low attenuation areas from gas trapping, image noise, and emphysema.

Sex Differences in Emphysema and Airway Disease in Smokers

BACKGROUND The authors of previous reports have suggested that women are more susceptible to cigarette smoke and to an airway-predominant COPD phenotype rather than an emphysema-predominant COPD phenotype. The purpose of this study was to test for sex differences in COPD phenotypes by using high-resolution CT (HRCT) scanning in male and female smokers with and without COPD. METHODS All subjects completed spirometry and answered an epidemiologic respiratory questionnaire. Inspiratory HRCT scans were obtained on 688 smokers enrolled in a family-based study of COPD. Emphysema was assessed by using a density mask with a cutoff of -950 Hounsfield units to calculate the low-attenuation area percentage (LAA%) and by the fractal value D, which is the slope of a power law analysis defining the relationship between the number and size of the emphysematous lesions. Airway wall thickness was assessed by calculating the square root of the airway wall area (SQRTWA) and the percentage of the total airway area taken by the airway wall (WA%) relative to the internal perimeter. RESULTS Women had a similar FEV(1) (women, 65.5% +/- 31.9% predicted; men, 62.1% +/- 30.4% predicted; p = 0.16) but fewer pack-years of cigarette smoking (women, 37.8 +/- 19.7 pack-years; men, 47.8 +/- 27.4 pack-years; p < 0.0001). Men had a greater LAA% (24% +/- 12% vs 20% +/- 11%, respectively; p < 0.0001) and larger emphysematous spaces than women, and these differences persisted after adjusting for covariates (weight, pack-years of smoking, current smoking status, center of enrollment, and FEV(1) percent predicted; p = 0.0006). Women had a smaller SQRTWA and WA% after adjusting for covariates (p < 0.0001). CONCLUSION Male smokers have more emphysema than female smokers, but female smokers do not show increased wall thickness compared with men.

COPD phenotypes in biomass smoke- versus tobacco smoke-exposed Mexican women

We hypothesised that biomass smoke exposure is associated with an airway-predominant chronic obstructive pulmonary disease (COPD) phenotype, while tobacco-related COPD is associated with an emphysema-predominant phenotype. In this cross-sectional study, female never-smokers with COPD and biomass exposure (n=21) and female ex-cigarette smokers with COPD without biomass exposure (n=22) completed computed tomography (CT) at inspiration and expiration, pulmonary function, blood gas, exercise tolerance, and quality of life measures. Two radiologists scored the extent of emphysema and air trapping on CT. Quantitative emphysema severity and distribution and airway wall thickness were calculated using specialised software. Women in the tobacco group had significantly more emphysema than the biomass group (radiologist score 2.3 versus 0.7, p=0.001; emphysema on CT 27% versus 19%, p=0.046; and a larger size of emphysematous spaces, p=0.006). Women in the biomass group had significantly more air trapping than the tobacco group (radiologist score 2.6 and 1.5, respectively; p=0.02) and also scored lower on the symptom, activities and confidence domains of the quality of life assessment and had lower oxygen saturation at rest and during exercise (p<0.05). Biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure, suggesting an airway-predominant phenotype. Biomass smoke causes less emphysema but more air trapping than tobacco smoke: airway-predominant COPD phenotype? http://ow.ly/rHdju

Executive Summary: Prevention of Acute Exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline

COPD is a common disease with substantial associated morbidity and mortality. Patients with COPD usually have a progression of airflow obstruction that is not fully reversible and can lead to a history of progressively worsening breathlessness, affecting daily activities and health-related quality of life.1-3 COPD is the fourth leading cause of death in Canada4 and the third leading cause of death in the United States where it claimed 133,965 lives in 2009.5 In 2011, 12.7 million US adults were estimated to have COPD.6 However, approximately 24 million US adults have evidence of impaired lung function, indicating an underdiagnosis of COPD.7 Although 4% of Canadians aged 35 to 79 years self-reported having been given a diagnosis of COPD, direct measurements of lung function from the Canadian Health Measures Survey indicate that 13% of Canadians have a lung function score indicative of COPD.4 COPD is also costly. In 2009, COPD caused 8 million office visits, 1.5 million ED visits, 715,000 hospitalizations, and 133,965 deaths in the United States.8 In 2010, US costs for COPD were projected to be approximately

A Canadian, multicentre, randomized clinical trial of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease: rationale and methods.

49.9 billion, including

Pulmonary rehabilitation in Canada: A report from the Canadian Thoracic Society COPD Clinical Assembly

29.5 billion in direct health-care expenditures,