ABSTRACT
Rationale: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. Objectives: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. Methods: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. Measurements and Main Results: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV1 of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (ß, -8.29; 95% confidence interval [CI], -14.80 to -1.77), higher St. George's Respiratory Questionnaire Total Score (ß, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. Conclusions: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD outcomes.
Subject(s)
Allergens/adverse effects , Dust/immunology , Environmental Exposure/adverse effects , Hypersensitivity/etiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Adult , Aged , Aged, 80 and over , Allergens/immunology , Disease Progression , Female , Humans , Hypersensitivity/diagnosis , Hypersensitivity/epidemiology , Hypersensitivity/immunology , Male , Middle Aged , Prevalence , Prognosis , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/immunology , Severity of Illness IndexABSTRACT
Rationale: Indoor particulate matter is associated with worse chronic obstructive pulmonary disease (COPD) outcomes. It remains unknown whether reductions of indoor pollutants improve respiratory morbidity. Objectives: To determine whether placement of active portable high-efficiency particulate air cleaners can improve respiratory morbidity in former smokers. Methods: Eligible former smokers with moderate-to-severe COPD received active or sham portable high-efficiency particulate absolute air cleaners and were followed for 6 months in this blinded randomized controlled trial. The primary outcome was 6-month change in St. George's Respiratory Questionnaire (SGRQ). Secondary outcomes were exacerbation risk, respiratory symptoms, rescue medication use, and 6-minute-walk distance (6MWD). Intention-to-treat analysis included all subjects, and per-protocol analysis included adherent participants (greater than 80% use of air cleaner). Measurements and Main Results: A total of 116 participants were randomized, of which 84.5% completed the study. There was no statistically significant difference in total SGRQ score, but the active filter group had greater reduction in SGRQ symptom subscale (ß, -7.7 [95% confidence interval (CI), -15.0 to -0.37]) and respiratory symptoms (Breathlessness, Cough, and Sputum Scale, ß, -0.8 [95% CI, -1.5 to -0.1]); and lower rate of moderate exacerbations (incidence rate ratio, 0.32 [95% CI, 0.12-0.91]) and rescue medication use (incidence rate ratio, 0.54 [95% CI, 0.33-0.86]) compared with sham group (all P < 0.05). In per-protocol analysis, there was a statistically significant difference in primary outcome between the active filter versus sham group (SGRQ, ß -4.76 [95% CI, -9.2 to -0.34]) and in moderate exacerbation risk, Breathlessness, Cough, and Sputum Scale, and 6MWD. Participants spending more time indoors were more likely to have treatment benefit. Conclusions: This is the first environmental intervention study conducted among former smokers with COPD showing potential health benefits of portable high-efficiency particulate absolute air cleaners, particularly among those with greater adherence and spending a greater time indoors.
Subject(s)
Air Filters , Air Pollution, Indoor/prevention & control , Pulmonary Disease, Chronic Obstructive/rehabilitation , Adult , Aged , Aged, 80 and over , Disease Progression , Double-Blind Method , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Treatment Outcome , Walk TestABSTRACT
CONTEXT: Secondhand smoke exposure (SHSe) affects up to half of all children in the United States. Many studies have identified factors associated with in-home SHSe, but few have contrasted these factors between households with and without residential smokers. In the latter case, exposure occurs from only external sources that enter the home, such as visitors or environmental incursion. OBJECTIVE: Among children with SHSe at home, to examine demographic and psychosocial differences between households with and without residential smokers. DESIGN: Baseline analysis of an observational cohort. SETTING: Baltimore City, Maryland. PARTICIPANTS: A total of 157 children with asthma, aged 5 to 12 years. MEASURES: At-home airborne nicotine, caregiver-reported depression, asthma-related quality of life, functional social support, and demographics. Univariable comparisons were performed between SHS-exposed households with and without residential smokers. Multivariable logistic regression models were fit to examine associations between measured factors and absence of residential smokers. RESULTS: Children (78.3%) had at-home SHSe. Of these, 40.7% lived in households without residential smokers. Compared with households with residential smokers, these caregivers endorsed stronger beliefs in SHS harms and also worse functional social support and asthma-related stress, despite no differences in asthma morbidity. In adjusted models, SHS-exposed children with caregivers in the lowest tertile of functional social support (adjusted odds ratio, 3.50; 95% confidence interval, 1.12-10.99), asthma-related quality of life (2.90; 1.06-7.95), and those living alone (5.28; 1.26-22.15) had at least twice higher odds of having exclusively external SHSe than the highest tertile (P trends < .05). CONCLUSIONS: In-home SHS exposure remains alarmingly high in urban environments. However, a substantial proportion of this exposure appears to be occurring only from external sources that enter the home. Caregivers in these homes had higher desire but lower agency to avoid SHSe, driven by lack of functional support and physical isolation. Public policies targeting these factors may help remediate exposure in this especially vulnerable population.
Subject(s)
Asthma/physiopathology , Environmental Exposure/adverse effects , Family Characteristics , Smokers/statistics & numerical data , Tobacco Smoke Pollution/adverse effects , Asthma/epidemiology , Baltimore/epidemiology , Child , Child, Preschool , Cohort Studies , Environmental Exposure/statistics & numerical data , Female , Humans , Male , Tobacco Smoke Pollution/statistics & numerical data , Urban Population/statistics & numerical dataABSTRACT
In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.
Subject(s)
Asthma/drug therapy , Asthma/therapy , Biofeedback, Psychology , Medication Adherence , Nebulizers and Vaporizers , Administration, Inhalation , Adult , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Peak Expiratory Flow Rate , Prospective StudiesABSTRACT
OBJECTIVES: Secondhand smoke (SHS) and other air pollutants adversely affect the health of pregnant women and infants. A feasibility study aimed at reducing air pollution in homes of pregnant women or infants living with a smoker was completed. METHODS: In collaboration with the Baltimore City Health Department, women ≥ 18 years of age and either pregnant nonsmokers, or post-partum (any smoking status) with an infant age 0-12 months were recruited. Homes had at least one smoker. Intervention included two air purifiers and secondhand smoke education. Outcomes included feasibility, change in fine particulate matter (PM2.5), air nicotine, and salivary cotinine pre- and post-intervention. RESULTS: Fifty women were enrolled (mean age 27 years, 92% African American, 71% single, 94% Medicaid eligible, 34% reported smoking) and 86% completed the study. Of the 50 women, 32 had infants and 18 were pregnant at time of enrollment. Post- intervention, 70% of participants reported smokers were less likely to smoke indoors, and 77% had at least one air purifier turned on at the final visit. Participant satisfaction was high (91%) and 98% would recommend air purifiers. Indoor PM2.5 was significantly decreased (P < 0.001). Salivary cotinine was significantly decreased for non-smoking women (P < 0.01) but not infants, and no significant change in air nicotine occurred (P = 0.6). CONCLUSIONS: Air purifiers with SHS education is a feasible intervention in homes of women and infants. These data demonstrate reduction in indoor PM2.5 and salivary cotinine in non-smoking adults. Air purifiers are not an alternative for smoking cessation and a home/ car smoking ban. Smoking cessation should be strongly encouraged for all pregnant women, and nonsmoking mothers with infants should be counseled to completely avoid SHS exposure. This study provides support for a future intervention evaluating clinical endpoints.
Subject(s)
Air Filters/statistics & numerical data , Air Pollution, Indoor/prevention & control , Smoking Prevention/methods , Tobacco Smoke Pollution/prevention & control , Adult , Baltimore , Feasibility Studies , Female , Humans , Infant , Infant, Newborn , Pregnancy , Smoking Cessation/methods , Young AdultABSTRACT
Exposure to nitrogen dioxide (NO2), a byproduct of combustion, is associated with poor asthma control in children. We sought to determine whether gas-fueled kitchen appliance use is associated with 24-h indoor NO2 concentrations and whether these concentrations are associated with asthma morbidity in children. Children aged 5-12 years old with asthma were eligible. Mean 24-h NO2 concentration was measured in the kitchen over a four-day sampling period and gas stove use was captured in time activity diaries. The relationship between stove and oven use and daily NO2 concentration was analyzed. Longitudinal analysis assessed the effect of daily NO2 exposure on symptoms, inhaler use, and lung function. Multivariate models were adjusted for age, sex, season, and maternal education. Thirty children contributed 126 participant days of sampling. Mean indoor 24-h NO2 concentration was 58(48)ppb with a median (range) of 45(12-276)ppb. All homes had gas stoves and furnaces. Each hour of kitchen appliance use was associated with an 18ppb increase in 24-h NO2 concentration. In longitudinal multivariate analysis, each ten-fold increase in previous-day NO2 was associated with increased nighttime inhaler use (OR = 4.9, p = 0.04). There were no associations between NO2 and lung function or asthma symptoms. Higher previous-day 24-h concentration of NO2 is associated with increased nighttime inhaler use in children with asthma.
Subject(s)
Air Pollutants/adverse effects , Air Pollution, Indoor/adverse effects , Asthma/epidemiology , Cooking/methods , Environmental Exposure , Nitrogen Dioxide/adverse effects , Asthma/chemically induced , Baltimore/epidemiology , Child , Child, Preschool , Environmental Monitoring , Female , Humans , Longitudinal Studies , Male , Morbidity , Multivariate Analysis , Nitrogen Dioxide/analysis , SeasonsABSTRACT
This study aims to determine the impact of physical activity on asthma symptom reporting among children living in an inner city. Among 147 children aged 5-12 years with physician-diagnosed asthma, we assessed asthma symptoms using twice-daily diaries and physical activity using the physical activity questionnaire for children during three 8-day periods (baseline, 3 and 6 months). Linear, logistic, and quasi-poisson regression models were used to determine the association between physical activity and asthma symptoms; adjusting for age, sex, race, BMI, caregiver's education, asthma severity, medication use, and season. A 1-unit increase in PAQ score was significantly associated with reporting more nocturnal symptoms [risk ratio (RR): 1.03; 95% CI 1.00-1.06], daytime symptoms (RR: 1.04; 95% CI 1.00-1.09), being bothered by asthma (RR: 1.05; 95% CI 1.00-1.09), and trouble breathing (RR: 1.05; 95% CI 1.00-1.10). Level of physical activity should be taken into account in clinical management of asthma and epidemiological studies of asthma symptom burden.
Subject(s)
Asthma/complications , Exercise/physiology , Asthma/diagnosis , Asthma/physiopathology , Child , Child, Preschool , Female , Forced Expiratory Volume , Humans , Longitudinal Studies , Male , Medical Records , Severity of Illness Index , Surveys and Questionnaires , Symptom Assessment , Time Factors , Urban Population , Vital CapacityABSTRACT
OBJECTIVE: This study aimed to describe food and nutrient intake for low-income, urban African American children and adolescents, to highlight the need for further nutrition intervention programs and appropriate tools to address overweight and obesity. METHODS: This was a cross-sectional study using interviewer-administered single 24-hour dietary recalls. Participants were low-income African American boys and girls aged 5-16 years or their caregivers in Baltimore City. Frequency of food consumption and dietary intakes were analyzed by gender and age groups. RESULTS: Eighty-one participants were included for analysis. Mean daily energy intakes exceeded Dietary Reference Intakes (DRIs) from 10% to 71% across all gender-age groups: 2304 kcal for children aged 5-8 years; 2429 kcal and 2732 kcal for boys and girls aged 9-13 years, respectively; and 3339 kcal and 2846 kcal for boys and girls aged 14-16 years, respectively. The most frequently reported consumed foods were sweetened drinks, chips, candies, and milk across all age groups. The majority of participants (79-100%) did not meet the DRIs for dietary fiber and vitamin E across all gender-age groups. Milk accounted for 14%, 17%, and 21% of energy, fat, and protein intake, respectively, among children 5-8 years of age, while pizza was the top source of energy, fat, and protein (11%, 13%, and 18%, respectively) among 14-to 16-year-old adolescents. Sweetened drinks and sweetened juices were major sources of sugar, contributing 33% for 5-8 year olds, 29% for 9-13 year olds, and 35% for 14-16 year olds. CONCLUSIONS: Mean daily energy intake exceeded dietary recommendations across all gender-age groups. This study has provided previously unavailable information on diet and highlights foods to be targeted in nutrition intervention programs.
Subject(s)
Diet , Feeding Behavior , Adolescent , Black or African American , Baltimore , Child , Child, Preschool , Diet Records , Female , Food Analysis , Humans , Male , PovertyABSTRACT
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. George's 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.
Subject(s)
Occupational Exposure , Pulmonary Disease, Chronic Obstructive/epidemiology , Aged , Disease Progression , Effect Modifier, Epidemiologic , Female , Humans , Male , Middle Aged , Multivariate Analysis , Quality of Life , Smoking/epidemiologyABSTRACT
OBJECTIVE: Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude. METHODS: We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis. RESULTS: Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis. CONCLUSIONS: We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays.
Subject(s)
Air Pollutants/adverse effects , Biomass , Bronchitis, Chronic/epidemiology , Rural Population , Smoking/adverse effects , Urbanization/trends , Adult , Bronchitis, Chronic/etiology , Female , Humans , Male , Middle Aged , Peru/epidemiology , Prevalence , Risk Factors , Smoking/epidemiology , SpirometryABSTRACT
Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.
Subject(s)
Asthma/pathology , Bronchial Hyperreactivity/pathology , NF-E2-Related Factor 2/metabolism , Tight Junctions/immunology , Zonula Occludens-1 Protein/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Asthma/chemically induced , Asthma/immunology , Cadherins/metabolism , Chalcones/pharmacology , Cytokines/immunology , Cytokines/metabolism , Cytoprotection , Cytoskeletal Proteins/genetics , Epithelial Cells/metabolism , Inflammation/immunology , Kelch-Like ECH-Associated Protein 1 , Lung/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-E2-Related Factor 2/genetics , Ovalbumin , Oxidative Stress/immunology , Respiratory Mucosa/cytology , Th2 Cells/immunologyABSTRACT
Our goal was to investigate whether obesity increases susceptibility to the adverse effects of indoor particulate matter on respiratory morbidity among individuals with chronic obstructive pulmonary disease (COPD). Participants with COPD were studied at baseline, 3 and 6 months. Obesity was defined as a body mass index ≥30â kg·m(-2). At each time point, indoor air was sampled for 5-7 days and particulate matter (PM) with an aerodynamic size ≤2.5â µm (PM2.5) and 2.5-10â µm (PM2.5-10) was measured. Respiratory symptoms, health status, rescue medication use, exacerbations, blood biomarkers and exhaled nitric oxide were assessed simultaneously. Of the 84 participants enrolled, 56% were obese and all were former smokers with moderate-to-severe COPD. Obese participants tended to have less severe disease as assessed by Global Initiative for Chronic Obstructive Pulmonary Disease stage and fewer pack-years of smoking. There was evidence that obesity modified the effects of indoor PM on COPD respiratory outcomes. Increases in PM2.5 and PM2.5-10 were associated with greater increases in nocturnal symptoms, dyspnoea and rescue medication use among obese versus non-obese participants. The impact of indoor PM on exacerbations, respiratory status and wheeze also tended to be greater among obese versus non-obese participants, as were differences in airway and systemic inflammatory responses to indoor PM. We found evidence that obesity was associated with exaggerated responses to indoor fine and coarse PM exposure among individuals with COPD.
Subject(s)
Air Pollution, Indoor/analysis , Disease Susceptibility , Obesity/complications , Particulate Matter/adverse effects , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/etiology , Aged , Air Pollutants , Biomarkers/blood , Body Height , Body Mass Index , Body Weight , Environmental Exposure , Environmental Monitoring , Female , Forced Expiratory Volume , Health Status , Humans , Inflammation , Male , Middle Aged , Particle Size , Risk Factors , Smoking , SpirometryABSTRACT
BACKGROUND: It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD). We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use. METHODS: We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno. We defined COPD as a post-bronchodilator FEV1/FVC < 70%. RESULTS: Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001). Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%). Rather, we found that PARs of COPD varied by setting. In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively). In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%. CONCLUSIONS: The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking. This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas.
Subject(s)
Pulmonary Disease, Chronic Obstructive/epidemiology , Residence Characteristics , Adult , Aged , Altitude , Biomass , Female , Forced Expiratory Volume , Fossil Fuels , Humans , Longitudinal Studies , Lung/physiopathology , Male , Middle Aged , Peru/epidemiology , Predictive Value of Tests , Prevalence , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Risk Assessment , Risk Factors , Rural Health , Smoking/adverse effects , Smoking/epidemiology , Spirometry , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Urban Health , Urbanization , Vital CapacityABSTRACT
BACKGROUND: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. OBJECTIVE: We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4(+) lymphocytes for association with asthma. METHODS: eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. RESULTS: Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3/GSDMB variants with asthma (combined P = 2.9 × 10(-8)). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N-acetyl-α-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+) lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. CONCLUSIONS: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.
Subject(s)
Asthma , CD4-Positive T-Lymphocytes/immunology , Fatty Acid Desaturases , Genome-Wide Association Study , Polymorphism, Single Nucleotide , alpha-N-Acetylgalactosaminidase , Asthma/epidemiology , Asthma/genetics , Asthma/immunology , Asthma/pathology , CD4-Positive T-Lymphocytes/pathology , Child , Child, Preschool , Costa Rica , Double-Blind Method , Fatty Acid Desaturases/genetics , Fatty Acid Desaturases/immunology , Female , Humans , Male , alpha-N-Acetylgalactosaminidase/genetics , alpha-N-Acetylgalactosaminidase/immunologyABSTRACT
Previous research has found evidence of an association between indoor air pollution and asthma morbidity in children. Environmental intervention studies have been performed to examine the role of household environmental interventions in altering indoor air pollution concentrations and improving health. Previous environmental intervention studies have found only modest effects on health outcomes and it is unclear if the health benefits provided by environmental modification are comparable with those provided by medication. Traditionally, the statistical analysis of environmental intervention studies has involved performing two intention-to-treat analyses that separately estimate the effect of the environmental intervention on health and the effect of the environmental intervention on indoor air pollution concentrations. We propose a principal stratification approach to examine the extent to which an environmental intervention's effect on health outcomes coincides with its effect on indoor air pollution. We apply this approach to data from a randomized air cleaner intervention trial conducted in a population of asthmatic children living in Baltimore, Maryland, USA. We find that among children for whom the air cleaner reduced indoor particulate matter concentrations, the intervention resulted in a meaningful improvement of asthma symptoms with an effect generally larger than previous studies have shown. A key benefit of using principal stratification in environmental intervention studies is that it allows investigators to estimate causal effects of the intervention for sub-groups defined by changes in the indoor air pollution concentration.
Subject(s)
Air Pollution, Indoor/prevention & control , Asthma/epidemiology , Data Interpretation, Statistical , Models, Statistical , Particulate Matter/analysis , Air Pollution, Indoor/adverse effects , Asthma/prevention & control , Baltimore , Child , Female , Humans , Male , Markov Chains , Monte Carlo MethodABSTRACT
OBJECTIVE: We sought to understand if pediatrician characteristics and asthma assessment and treatment varied in association with the proportion of African-American and Latino children in the pediatrician's practice. METHODS: We conducted a cross-sectional survey of 500 American Academy of Pediatrics members between November 2005 and May 2006. Standardized vignettes were used to test how different indicators of a patient's asthma status affect pediatrician asthma assessments and recommendations. Linear and logistic regression models were used to examine the association of pediatrician assessments and treatment recommendations for these vignettes, respectively, with the proportion of reported African-American and Latino children seen in their practice. RESULTS: There were 270 respondents (response rate = 54%). Based on pediatrician-reported percentage of minority patients, there were no differences in board certification status, recognition of poorly controlled asthma nor in the likelihood of appropriately increasing long-term controller medications to treat poorly controlled asthma (p > 0.05 for all analyses). CONCLUSIONS: Caring primarily for minority children by AAP pediatricians appears unrelated to training qualifications or in their reported knowledge of how to appropriately assess and treat asthma. Therefore, studies of asthma care disparities should focus on understanding the knowledge-base of non-AAP pediatric providers who care for minority populations and exploring other potential contributory provider-level factors (e.g. communication skills).
Subject(s)
Asthma/ethnology , Healthcare Disparities/ethnology , Pediatrics , Specialization , Black or African American , Androstadienes/therapeutic use , Asthma/diagnosis , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Certification , Data Collection , Female , Fluticasone , Healthcare Disparities/statistics & numerical data , Hispanic or Latino , Humans , Male , Minority Groups , Physicians , Racial GroupsABSTRACT
RATIONALE: The effect of endotoxin on asthma morbidity in urban populations is unclear. OBJECTIVES: To determine if indoor pollutant exposure modifies the relationships between indoor airborne endotoxin and asthma health and morbidity. METHODS: One hundred forty-six children and adolescents with persistent asthma underwent repeated clinical assessments at 0, 3, 6, 9, and 12 months. Home visits were conducted at the same time points for assessment of airborne nicotine, endotoxin, and nitrogen dioxide (NO2) concentrations. The effect of concomitant pollutant exposure on relationships between endotoxin and asthma outcomes were examined in stratified analyses and statistical models with interaction terms. MEASUREMENTS AND MAIN RESULTS: Both air nicotine and NO2 concentrations modified the relationships between airborne endotoxin and asthma outcomes. Among children living in homes with no detectable air nicotine, higher endotoxin was inversely associated with acute visits and oral corticosteroid bursts, whereas among those in homes with detectable air nicotine, endotoxin was positively associated with these outcomes (interaction P value = 0.004 and 0.07, respectively). Among children living in homes with lower NO2 concentrations (<20 ppb), higher endotoxin was positively associated with acute visits, whereas among those living in homes with higher NO2 concentrations, endotoxin was negatively associated with acute visit (interaction P value = 0.05). NO2 also modified the effect of endotoxin on asthma symptom outcomes in a similar manner. CONCLUSIONS: The effects of household airborne endotoxin exposure on asthma are modified by coexposure to air nicotine and NO2, and these pollutants have opposite effects on the relationships between endotoxin and asthma-related outcomes.
Subject(s)
Air Pollutants/adverse effects , Air Pollution, Indoor/adverse effects , Asthma/etiology , Endotoxins/adverse effects , Inhalation Exposure/adverse effects , Nicotine/adverse effects , Nitrogen Dioxide/adverse effects , Adolescent , Air Pollutants/analysis , Air Pollution, Indoor/analysis , Asthma/therapy , Baltimore , Child , Child, Preschool , Endotoxins/analysis , Environmental Monitoring , Female , Follow-Up Studies , Humans , Inhalation Exposure/analysis , Male , Models, Statistical , Nicotine/analysis , Nitrogen Dioxide/analysis , Prospective Studies , Urban HealthABSTRACT
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.
Subject(s)
Hypersensitivity/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/immunology , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Multivariate Analysis , Nutrition Surveys , Phenotype , Respiratory Sounds/geneticsABSTRACT
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 participant's 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.