The Denver Aerosol Sources and Health (DASH) Study: Overview and Early Findings.

Improved understanding of the sources of air pollution that are most harmful could aid in developing more effective measures for protecting human health. The Denver Aerosol Sources and Health (DASH) study was designed to identify the sources of ambient fine particulate matter (PM(2.5)) that are most responsible for the adverse health effects of short-term exposure to PM (2.5). Daily 24-hour PM(2.5) sampling began in July 2002 at a residential monitoring site in Denver, Colorado, using both Teflon and quartz filter samplers. Sampling is planned to continue through 2008. Chemical speciation is being carried out for mass, inorganic ionic compounds (sulfate, nitrate and ammonium), and carbonaceous components, including elemental carbon, organic carbon, temperature-resolved organic carbon fractions and a large array of organic compounds. In addition, water soluble metals were measured daily for 12 months in 2003. A receptor-based source apportionment approach utilizing positive matrix factorization (PMF) will be used to identify PM (2.5) source contributions for each 24-hour period. Based on a preliminary assessment using synthetic data, the proposed source apportionment should be able to identify many important sources on a daily basis, including secondary ammonium nitrate and ammonium sulfate, diesel vehicle exhaust, road dust, wood combustion and vegetative debris. Meat cooking, gasoline vehicle exhaust and natural gas combustion were more challenging for PMF to accurately identify due to high detection limits for certain organic molecular marker compounds. Measurements of these compounds are being improved and supplemented with additional organic molecular marker compounds. The health study will investigate associations between daily source contributions and an array of health endpoints, including daily mortality and hospitalizations and measures of asthma control in asthmatic children. Findings from the DASH study, in addition to being of interest to policymakers, by identifying harmful PM(2.5) sources may provide insights into mechanisms of PM effect.

The utility of ambulatory pH monitoring in patients presenting with chronic cough and asthma.

OBJECTIVE: To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough. PATIENTS AND METHODS: The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded. RESULTS: Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0). CONCLUSIONS: The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients.

Interpretation of transbronchial lung biopsies from lung transplant recipients: inter- and intraobserver agreement.

BACKGROUND: Transbronchial lung biopsy results are crucial for the management of lung transplant recipients. Little information is available regarding the reliability and reproducibility of the interpretation of transbronchial lung biopsies. OBJECTIVE: To examine the inter-reader variability between two lung pathologists with expertise in lung transplantation. METHODS: Fifty-nine transbronchial lung biopsy specimens were randomly selected. Active infection had been excluded in all cases. The original interpretations (as per the Lung Rejection Study Group) for acute rejection grade included 19 biopsies scored as A0 (none), 14 scored as A1 (minimal), 12 as A2 (mild), 11 as A3 (moderate) and three as A4 (severe). The pathologists worked independently without clinical information or knowledge of the original interpretation. The specimens were graded using the Lung Rejection Study Group criteria for acute rejection (grades A0 to A4), airway inflammation (grades B0 to B4) and bronchiolitis obliterans (C0 absent and C1 present). Between-reader agreement for each category was analyzed using a Kappa statistic. RESULTS: Because many transplant specialists initiate augmented immunosuppression with biopsy grades of A2 or higher, results for each reader were dichotomized as A0/A1 versus A2/A3/A4. Using this dichotomy, there was only moderate agreement (kappa 0.470, P < 0.001) between readers. For categories B and C, the results were dichotomized for the absence or presence of airway inflammation and bronchiolitis obliterans, respectively. The level of agreement between readers was fair for category B (kappa 0.333, P = 0.014) and poor for category C (kappa 0.166, P = 0.108). The intrareader agreement for acute rejection was substantial (kappa 0.795, P = 0.0001; kappa 0.676, P = 0.0001). CONCLUSIONS: Because the agreement between expert pathologists is only modest, optimum clinical decision-making requires that transbronchial lung biopsy results be used in an integrated clinical context.

Air pollution and retained particles in the lung.

Epidemiologic evidence associates particulate air pollution with cardiopulmonary morbidity and mortality. The biological mechanisms underlying these associations and the relationship between ambient levels and retained particles in the lung remain uncertain. We examined the parenchymal particle content of 11 autopsy lungs from never-smoking female residents of Mexico City, a region with high ambient particle levels [3-year mean PM(10) (particulate matter < or = 10 microm in aerodynamic diameter)= 66 microg/m(3)], and 11 control residents of Vancouver, British Columbia, Canada, a region with relatively low levels (3-year mean PM(10) = 14 microg/m(3). Autopsy lungs were dissolved in bleach and particles were identified and counted by analytical electron microscopy. Total particle concentrations in the Mexico City lungs were significantly higher [geometric mean = 2,055 (geometric SD = 3.9) x 10(6) particles/g dry lung vs. 279 (1.8) x 10(6) particles/g dry lung] than in lungs from Vancouver residents. Lungs from Mexico City contained numerous chain-aggregated masses of ultrafine carbonaceous spheres, some of which contained sulfur, and aggregates of ultrafine aluminum silicate. These aggregates made up an average of 25% of the total particles by count in the lungs from Mexico City, but were only rarely seen in lungs from Vancouver. These observations indicate for the first time that residence in a region with high levels of ambient particles results in pulmonary retention of large quantities of fine and ultrafine particle aggregates, some of which appear to be combustion products.

Desquamative interstitial pneumonia. Computed tomographic findings before and after treatment with corticosteroids.

Noninvasive methods for diagnosis, assessing prognosis, and following response to treatment in idiopathic pulmonary fibrosis (IPF) have yet to prove their usefulness. We report a patient with desquamative interstitial pneumonia (DIP) in whom computed tomography (CT) suggested the diagnosis by the presence of patchy areas of haziness predominantly in a peripheral distribution. The chest x-ray and physical examinations, and the arterial blood gases showed normal findings after one month of treatment with corticosteroids, at which time the CT scan and lung volumes were still abnormal. At three months, lung volumes and the CT scan were normal. Hazy densities in a peripheral distribution on CT may indicate active IPF associated with a good prognosis.

Hyperinflation in asthma and emphysema. Assessment by pulmonary function testing and computed tomography.

To assess the role of emphysema on the hyperinflation in chronic asthma, we studied 20 subjects with irreversible airflow limitation. Ten of the subjects had asthma and had never smoked; the other ten were cigarette smokers. Pulmonary function testing and chest computed tomography (CT) scans were performed on all subjects. Emphysema was graded using a score based on the percentage of lung involved on CT scan. There was good inter- and intra-observer agreement for the emphysema scores. The median emphysema score was 0 percent in the nonsmoking group and 10 percent in the smoking group. All smokers with a total lung capacity (TLC) of greater than 120 percent predicted had evidence of emphysema on the CT scan. None of the asthmatic subjects with a TLC greater than 120 percent predicted had emphysema identifiable on CT scan. We conclude that chronic asthma with severe hyperinflation does not result in emphysema.

The significance of the persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis.

STUDY OBJECTIVES: Identification of acid-fast bacilli (AFB) in the sputum smear at the completion of tuberculosis therapy is in some settings considered evidence of treatment failure. However, some patients with pulmonary tuberculosis (TB) will have positive smear results with negative sputum culture results at the end of therapy. The objectives of this study were to estimate the prevalence of persisting positive sputum smear results in patients with TB and to identify characteristics that distinguish patients with persistently positive sputum smear results who also had negative sputum culture results from patients identified as treatment failures. DESIGN: A population-based, historical cohort study with nested case control study. SETTING: British Columbia Division of Tuberculosis Control central case registry. PATIENTS: All 428 patients with culture-proven pulmonary TB in British Columbia over 7 years with sputum that was positive for AFB. METHODS: Review of laboratory data of all 428 patients, as well as clinical data of a subset of 30 patients with persistently positive smear results beyond 20 weeks. RESULTS: Sputum smears were positive for AFB in 205 patients (48%) at 4 weeks, in 30 patients (7%) at 20 weeks, and in 12 patients (3%) at 36 weeks. Of the patients with smear results that were persistently positive at 20 weeks, 23 (77%) had negative sputum culture results and 7 (23%) had positive sputum culture results (ie, they were treatment failures). Patients identified as treatment failures had more localized disease as shown on chest radiographs, had less radiographic improvement at follow-up, had a higher prevalence of drug resistance, and were less compliant with medications than patients with persistently positive smear results and negative culture results. No subject with a negative culture result relapsed over the 6- to 48-month observation period. CONCLUSION: Sputum that is persistently positive for AFB in patients in developed countries is more likely to be associated with negative culture results than with treatment failure.

Predictors of bronchial hyperexcitability in grainhandlers.

We have studied bronchial hyperexcitability to methacholine (defined as a fall of at least 20 percent in FEV1 at 8 mg/ml or lower) in 504 white male grainhandlers working in terminal elevators in the Port of Vancouver. There was a significant association between bronchial hyperexcitability and level of FEV1; for a 10 percent decrease in percent of predicted FEV1, bronchial hyperexcitability was twice as common. Among those with bronchial hyperexcitability, the PC20 was significantly related to the FEV1. Grainhandlers with immediate skin reactivity to common allergens were twice as likely to have bronchial hyperexcitability. There was a significant increase in the prevalence of bronchial hyperexcitability with increasing duration of employment. Grainhandlers with chest tightness and breathlessness were over twice as likely to have bronchial hyperexcitability. We did not observe an increased prevalence of bronchial hyperexcitability in smokers, and there was no difference between age groups. We conclude that the determinants of bronchial hyperexcitability in this population include baseline FEV1, immediate skin reactivity to common allergens, some respiratory symptoms, and cumulative exposure to grain dust.

Determinants of airway smooth muscle shortening in excised canine lobes.

There is marked heterogeneity of airway narrowing in intraparenchymal airways in response to bronchoconstricting stimuli. We hypothesized that this heterogeneity results from variations in the structure of the airway wall. Freshly excised dog lung lobes were inflated to transpulmonary pressures (PL) of between 5 and 15 cmH2O, and an aerosol containing a high concentration of carbachol was administered. The lobes were fixed and processed for light-microscopic examination and morphometric analysis of membranous airway dimensions. The relationships of smooth muscle shortening to PL and airway dimensions were analyzed using multiple linear regression. The results show that airway smooth muscle shortening was greater at lower PL and in airways with larger internal perimeter and a greater number of folds per internal perimeter and that it was less in airways with greater inner wall area. We conclude that the magnitude and variability of airway smooth muscle shortening and airway narrowing in response to maximal constricting stimuli are influenced by mechanical factors related to airway wall geometry.

Wood smoke exposure and lung adenocarcinoma in non-smoking Mexican women.

OBJECTIVE: To determine the association between long-term exposure to wood smoke from cooking and lung adenocarcinoma in non-smoking Mexican women. METHODS: We reviewed records of hospitalized patients at a chest referral hospital in Mexico City and identified 113 histologically proven lung adenocarcinoma cases in non-smoking women. Four control groups of non-smoking women were also selected: 99 patients with pulmonary tuberculosis (PTB), 110 with interstitial lung disease (ILD), 64 with miscellaneous pulmonary conditions (MISC), and the three control groups combined (COMB) (n = 273). RESULTS: Exposure was assessed on the basis of questionnaire responses at the time of hospital admission. Exposure to wood smoke for more than 50 years, but not for shorter periods, was associated with lung cancer after adjusting for age, education, socio-economic status and environmental tobacco smoke (ETS) exposure. Adjusted odds ratios from the multivariable logistic regression models were 1.4 (95%CI 0.6-2.0) for cases vs. TB controls, 1.9 (95%CI 0.9-4.0) for cases vs. ILD controls, 2.6 (95%CI 1.0-6.3) for cases vs. MISC controls and 1.9 (95%CI 1.1-3.5) for cases vs. COMB controls. CONCLUSION: These findings suggest that long-term exposure to wood smoke from cooking may contribute to the development of lung cancer.

Exposure of chronic obstructive pulmonary disease patients to particles: respiratory and cardiovascular health effects.

To examine hypotheses regarding air pollution health effects, we conducted an exploratory study to evaluate relationships between personal and ambient concentrations of particles with measures of cardiopulmonary health in a sample of patients with chronic obstructive pulmonary disease (COPD). Sixteen currently non-smoking COPD patients (mean age=74) residing in Vancouver were equipped with a particle (PM(2.5)) monitor for seven 24-h periods. Subjects underwent ambulatory heart monitoring, had their lung function and blood pressure (BP) measured, and recorded symptoms and medication use. Ambient PM(2.5), PM(10), sulfate, and gaseous pollutant concentrations were monitored at five sites within the study area. Although no associations between air pollution and lung function were statistically significant, an estimated effect of 3% and 1% declines in daily FEV(1) change (DeltaFEV(1)) for each 10 microg/m(3) increase in ambient PM(10) and PM(2.5), respectively, was observed. Increases of 1 microg/m(3) in personal or ambient sulfate were associated with 1.0% and 0.3% declines in DeltaFEV(1), respectively. Weak associations were observed between particle concentrations and increased supraventricular ectopic heartbeats and with decreased systolic BP. No consistent associations were observed between any particle metric and diastolic BP, heart rate, or heart rate variability (r-MSSD or SDNN), symptom severity, or bronchodilator use. Of the pollutants measured, ambient PM(10) was most consistently associated with health parameters; the use of personal exposures did not improve the strength of any associations or lead to increased effect estimates.

Exposure of chronic obstructive pulmonary disease patients to particulate matter: relationships between personal and ambient air concentrations.

Mot time-series studies of particulate air pollution and acute health outcomes assess exposure of the study population using fixed-site outdoor measurements. To address the issue of exposure misclassification, we evaluate the relationship between ambient particle concentrations and personal exposures of a population expected to be at risk of particle health effects. Sampling was conducted within the Vancouver metropolitan area during April-September 1998. Sixteen subjects (non-smoking, ages 54-86) with physician-diagnosed chronic obstructive pulmonary disease (COPD) wore personal PM2.5 monitors for seven 24-hr periods, randomly spaced approximately 1.5 weeks apart. Time-activity logs and dwelling characteristics data were also obtained for each subject. Daily 24-hr ambient PM10 and PM2.5 concentrations were measured at five fixed sites spaced throughout the study region. SO4(2-), which is found almost exclusively in the fine particle fraction and which does not have major indoor sources, was measured in all PM2.5 samples as an indicator of accumulation mode particulate matter of ambient origin. The mean personal and ambient PM2.5 concentrations were 18 micrograms/m3 and 11 micrograms/m3, respectively. In analyses relating personal and ambient measurements, ambient concentrations were expressed either as an average of the values obtained from five ambient monitoring sites for each day of personal sampling, or as the concentration obtained at the ambient site closest to each subject's home. The mean personal to ambient concentration ratio of all samples was 1.75 (range = 0.24 to 10.60) for PM2.5, and 0.75 (range = 0.09 to 1.42) for SO4(2-). Regression analyses were conducted for each subject separately and on pooled data. The median correlation (Pearson's r) between personal and average ambient PM2.5 concentrations was 0.48 (range = -0.68 to 0.83). Using SO4(2-) as the exposure metric, the median r between personal and average ambient concentrations was 0.96 (range = 0.66 to 1.0). Use of the closest ambient site did not improve the median correlation of the group for either PM2.5 or SO4(2-). All pooled analyses resulted in lower correlation coefficients than the median correlation coefficient of individual regressions. Personal SO4(2-) was more highly correlated with all ambient measures than PM2.5. Inclusion of time-activity and dwelling characteristics data did not result in a useful predictive regression model for PM2.5 personal exposure, but improved the model fit from simply regressing against ambient concentration (R2 = 0.27). The model for SO4(2-) was predictive (R2 = 0.82), as personal exposures were largely explained by ambient levels. These results indicate a relatively low correlation between personal exposure and ambient PM2.5 that is not improved by assigning exposure to the closest ambient monitor. The correlation between personal exposure and ambient concentration is high, however, when using SO4(2-), an indicator of accumulation mode particulate matter of ambient origin.

Immediate skin reactivity and its relationship to age, sex, smoking, and occupational exposure.

To evaluate potential predictors of atopy, 3353 workers from various occupations were classified according to airborne exposures into three groups: (1) 1213 control workers with no measurable exposures, (2) 815 workers with gas and fume exposure, and (3) 1325 workers with organic dust exposure. Atopic status was determined by prick skin testing with common allergens. Workers exposed to organic dusts had a lower prevalence of skin test reactivity than either controls or gas- and fume-exposed workers. Skin test reactivity also decreased with age and was higher in nonwhite workers compared to white workers. No difference in skin test reactivity was seen between female and male workers, nor between smoking and nonsmoking workers. A logistic regression analysis that controlled for the correlation between the predictive factors confirmed the results of the crude analyses. It is suggested that atopic workers exposed to organic dusts might selectively leave the industry.

Symptoms and pulmonary function in western red cedar workers related to duration of employment and dust exposure.

Measurements of total dust concentration were made in a western red cedar sawmill that employed 701 workers. Both area sampling and personal sampling of total dust were done over an 8-hr shift corresponding to job descriptions and locations to assign each worker an exposure level. A total of 652 (93%) of the workers completed a respiratory-occupational questionnaire and performed spirometry, of whom 334 were assigned an exposure level. Dust exposure ranged from undetectable to 6.0 mg/m3 with a median exposure level of 0.2 mg/m3. Only 10% of the workers with an assigned exposure level were exposed to more than 1.0 mg/m3. Work-related asthma, defined as symptoms of asthma which improved on days off work, was reported by 52 workers (8.0%) and was more prevalent after 10 or more yr of employment. Chronic cough, dyspnea, persistent wheeze, and physician-diagnosed asthma were unrelated to either work duration or exposure. Levels of forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1.0) were lower with dust concentrations greater than 2.0 mg/m3, controlling for age and smoking; maximum mid-expiratory flow rate (FEF25-75%) and FEV1.0/FVC were unrelated to dust exposure concentration. Work-related symptoms of eye irritation were seen more commonly with exposure to dust concentrations of 3.0 mg/m3 or more. It is concluded that symptoms of work-related asthma in red cedar workers are more common after 10 yr of exposure, and that levels of pulmonary function are lower with higher wood dust exposures.

Health effects of air pollution due to coal combustion in the Chestnut Ridge region of Pennsylvania: cross-section survey of children.

A cross-sectional study of 4,071 children aged 6-11 yr of age from a rural region of Western Pennsylvania was conducted in spring of 1979. Standardized children's questionnaires were distributed to the parents and returned by the children to school, where spirometry was performed. The region was divided into low-, moderate-, and high-pollution areas on the basis of the 1974-1978, 3-hr, 24-hr, and annual averages for sulfur dioxide (SO2). Seventeen monitoring stations in the region and a triangulation procedure were used to estimate centroid levels in each geographic residence area. After adjusting the respiratory symptom response outcomes and the pulmonary function levels for known predictors, no significant association was noted for level of SO2. However, the highest exposure categories were only slightly above the present annual and 24-hr National Air Quality Standards for SO2. We conclude that at levels of exposure to which these children were exposed, only by study of potentially sensitive subsets or measures of acute response would it be possible to detect respiratory outcomes associated with ambient air pollution.

Positive matrix factorization of PM2.5 - eliminating the effects of gas/particle partitioning of semivolatile organic compounds.

Gas-phase concentrations of semi-volatile organic compounds (SVOCs) were calculated from gas/particle (G/P) partitioning theory using their measured particle-phase concentrations. The particle-phase data were obtained from an existing filter measurement campaign (27 January 2003-2 October 2005) as a part of the Denver Aerosol Sources and Health (DASH) study, including 970 observations of 71 SVOCs (Xie et al., 2013). In each compound class of SVOCs, the lighter species (e.g. docosane in n alkanes, fluoranthene in PAHs) had higher total concentrations (gas + particle phase) and lower particle-phase fractions. The total SVOC concentrations were analyzed using positive matrix factorization (PMF). Then the results were compared with source apportionment results where only particle-phase SVOC concentrations were used (particle only-based study; Xie et al., 2013). For the particle only-based PMF analysis, the factors primarily associated with primary or secondary sources (n alkane, EC/sterane and inorganic ion factors) exhibit similar contribution time series (r = 0.92-0.98) with their corresponding factors (n alkane, sterane and nitrate+sulfate factors) in the current work. Three other factors (light n alkane/PAH, PAH and summer/odd n alkane factors) are linked with pollution sources influenced by atmospheric processes (e.g. G/P partitioning, photochemical reaction), and were less correlated (r = 0.69-0.84) with their corresponding factors (light SVOC, PAH and bulk carbon factors) in the current work, suggesting that the source apportionment results derived from particle-only SVOC data could be affected by atmospheric processes. PMF analysis was also performed on three temperature-stratified subsets of the total SVOC data, representing ambient sampling during cold (daily average temperature < 10 °C), warm (≥ 10 °C and ≤ 20 °C) and hot (> 20 °C) periods. Unlike the particle only-based study, in this work the factor characterized by the low molecular weight (MW) compounds (light SVOC factor) exhibited strong correlations (r = 0.82-0.98) between the full data set and each sub-data set solution, indicating that the impacts of G/P partitioning on receptor-based source apportionment could be eliminated by using total SVOC concentrations.

Indoor solid fuel combustion and tuberculosis: is there an association?

OBJECTIVES: To assess the strength of evidence in published articles for an association between indoor solid fuel combustion and tuberculosis. METHODS: PubMed, a private database and Google Scholar were searched up to May 2008, as was the Cochrane Library (2008, issue 4), to identify articles on the association between indoor air pollution and tuberculous infection, tuberculosis disease and tuberculosis mortality. Each article initially chosen as acceptable for inclusion was reviewed for data extraction by three different reviewers using a standard format. Strength of evidence was determined by pre-determined criteria. RESULTS: The full texts of 994 articles were examined for a final selection of 10 possible articles, of which six met the inclusion criteria. All articles investigated the association between exposure to solid fuel (coal and biomass) smoke and tuberculosis disease. Three (50%) of the six studies included in the systematic review showed a significant effect of exposure to solid fuel combustion and tuberculosis disease-one high-quality case-control study and two cross-sectional studies. CONCLUSION: Despite the plausibility of an association, available original studies looking at this issue do not provide sufficient evidence of an excess risk of tuberculosis due to exposure to indoor coal or biomass combustion. Because the number of studies identified was small, new studies are needed before more definitive conclusions can be reached.