Andrew J. Belli

In-Home Air Pollution Is Linked to Respiratory Morbidity in Former Smokers with Chronic Obstructive Pulmonary Disease

RATIONALE The effect of indoor air pollutants on respiratory morbidity among patients with chronic obstructive pulmonary disease (COPD) in developed countries is uncertain. OBJECTIVES The first longitudinal study to investigate the independent effects of indoor particulate matter (PM) and nitrogen dioxide (NO(2)) concentrations on COPD morbidity in a periurban community. METHODS Former smokers with COPD were recruited and indoor air was monitored over a 1-week period in the participants bedroom and main living area at baseline, 3 months, and 6 months. At each visit, participants completed spirometry and questionnaires assessing respiratory symptoms. Exacerbations were assessed by questionnaires administered at clinic visits and monthly telephone calls. MEASUREMENTS AND MAIN RESULTS Participants (n = 84) had moderate or severe COPD with a mean FEV1 of 48.6% predicted. The mean (± SD) indoor PM(2.5) and NO(2) concentrations were 11.4 ± 13.3 µg/m(3) and 10.8 ± 10.6 ppb in the bedroom, and 12.2 ± 12.2 µg/m(3) and 12.2 ± 11.8 ppb in the main living area. Increases in PM(2.5) concentrations in the main living area were associated with increases in respiratory symptoms, rescue medication use, and risk of severe COPD exacerbations. Increases in NO(2) concentrations in the main living area were independently associated with worse dyspnea. Increases in bedroom NO(2) concentrations were associated with increases in nocturnal symptoms and risk of severe COPD exacerbations. CONCLUSIONS Indoor pollutant exposure, including PM(2.5) and NO(2), was associated with increased respiratory symptoms and risk of COPD exacerbation. Future investigations should include intervention studies that optimize indoor air quality as a novel therapeutic approach to improving COPD health outcomes.

Effects of Allergic Phenotype on Respiratory Symptoms and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease

RATIONALE Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment. OBJECTIVES To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD. METHODS Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort. Subjects from NHANES III with COPD (n = 1,381) defined as age > 40 years, history of smoking, FEV1/FVC < 0.70, and no diagnosis of asthma were identified. The presence of an allergic phenotype (n = 296) was defined as self-reported doctor diagnosed hay fever or allergic upper respiratory symptoms. In CODE, former smokers with COPD (n = 77) were evaluated for allergic sensitization defined as a detectable specific IgE to perennial allergens. Bivariate and multivariate models were used to determine whether an allergic phenotype was associated with respiratory symptoms and exacerbations. MEASUREMENTS AND MAIN RESULTS In NHANES III, multivariate analysis revealed that individuals with allergic phenotype were more likely to wheeze (odds ratio [OR], 2.1; P < 0.01), to have chronic cough (OR, 1.9; P = 0.01) and chronic phlegm (OR, 1.5; P < 0.05), and to have increased risk of COPD exacerbation requiring an acute doctor visit (OR, 1.7; P = 0.04). In the CODE cohort, multivariate analysis revealed that sensitized subjects reported more wheeze (OR, 5.91; P < 0.01), more nighttime awakening due to cough (OR, 4.20; P = 0.03), increased risk of COPD exacerbations requiring treatment with antibiotics (OR, 3.79; P = 0.02), and acute health visits (OR, 11.05; P < 0.01). An increasing number of sensitizations was associated with a higher risk for adverse health outcomes. CONCLUSIONS Among individuals with COPD, evidence of an allergic phenotype is associated with increased respiratory symptoms and risk of COPD exacerbations.

Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

RATIONALE Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. OBJECTIVES To determine the impact of occupational exposures on COPD morbidity. METHODS A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. Georges Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. MEASUREMENTS AND MAIN RESULTS An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). CONCLUSIONS Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

Indoor particulate matter exposure is associated with increased black carbon content in airway macrophages of former smokers with COPD

INTRODUCTION Exposure to fine particulate matter (PM2.5) is associated with worse morbidity in individuals with COPD. Inhaled PM is phagocytosed by airway macrophages (AM), and black carbon measured in AM may serve as a biomarker of air pollution exposure. As there is little data on how indoor PM exposure may influence AM black carbon content in those with respiratory disease, we investigated the association of indoor PM2.5 concentration to AM black carbon content in adults with COPD. METHODS Former smokers (>10 pack-years smoking history, quit date >1 year prior to enrollment) older than 40 years of age with moderate-severe COPD were eligible. Indoor air PM2.5 concentrations were measured over 5-7 days at baseline, 3 month, and 6 month intervals. Sputum induction was performed during clinic visits concordant with home monitoring. A total of 50 macrophages per sputum specimen were photographed and quantified using appropriate software by trained staff blinded to PM concentrations. Longitudinal analyses using generalized estimating equations were used to assess the relationship between indoor PM exposure and AM black carbon content. RESULTS Participants (n=20) were older (mean (SD) age 67 (4) years), predominantly Caucasian (85%) and male (70%), with an average smoking history of 52 pack-years and mean (SD) quit date of 13 (9) years prior to enrollment. The majority of daily time was reported to be spent indoors (>23h). Mean indoor PM2.5 concentration was 12.8 (13.5)µg/m(3). The mean area of black carbon quantified in airway macrophages was 1.2 (0.7)µm(2). In multivariate cross-sectional and longitudinal analyses, each 10µg/m(3) increase in indoor PM2.5 was significantly associated with a 0.26µm(2) and 0.19µm(2) increase in airway macrophage black carbon total area, respectively (p<0.05). CONCLUSION Higher indoor PM2.5 concentration is associated with an increase in black carbon content of AM in individuals with COPD. These data support the potential for AM black carbon content to be a useful non-invasive biomarker of exposure to indoor PM.