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.

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.

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 misclassification and threshold concentrations in time series analyses of air pollution health effects.

Linear, no-threshold relationships are typically reported for time series studies of air pollution and mortality. Since regulatory standards and economic valuations typically assume some threshold level, we evaluated the fundamental question of the impact of exposure misclassification on the persistence of underlying personal-level thresholds when personal data are aggregated to the population level in the assessment of exposure-response relationships. As an example, we measured personal exposures to two particle metrics, PM2.5 and sulfate (SO4(2-)), for a sample of lung disease patients and compared these with exposures estimated from ambient measurements Previous work has shown that ambient:personal correlations for PM2.5 are much lower than for SO4(2-), suggesting that ambient PM2.5 measurements misclassify exposures to PM2.5. We then developed a method by which the measured:estimated exposure relationships for these patients were used to simulate personal exposures for a larger population and then to estimate individual-level mortality risks under different threshold assumptions. These individual risks were combined to obtain the population risk of death, thereby exhibiting the prominence (and the value) of the threshold in the relationship between risk and estimated exposure. Our results indicated that for poorly classified exposures (PM2.5 in this example) population-level thresholds were apparent at lower ambient concentrations than specified common personal thresholds, while for well-classified exposures (e.g., SO4(2-)), the apparent thresholds were similar to these underlying personal thresholds. These results demonstrate that surrogate metrics that are not highly correlated with personal exposures obscure the presence of thresholds in epidemiological studies of larger populations, while exposure indicators that are highly correlated with personal exposures can accurately reflect underlying personal thresholds.

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.

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.

Community study using a polymerase chain reaction panel to determine the prevalence of common respiratory viruses in asthmatic and nonasthmatic children.

We developed a sensitive polymerase chain reaction (PCR) panel, suitable for the detection of seven common respiratory viruses, to study the prevalence of viruses in nasal swabs obtained from clinically stable asthmatic children (n = 21), non-physician diagnosed asthmatic children with exercise-induced bronchoconstriction (EIB) (n = 16), and nonasthmatic, non-EIB controls (n = 33). The PCR panel detected viruses in 43/70 (61.4%) specimens but there were no significant differences in prevalence of these viruses between the three groups of children. These results indicate that clinically stable asthmatic and nonasthmatic children frequently harbor viruses in the upper respiratory tract.

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.

Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma.

We prospectively recruited patients admitted to the hospital with severe asthma to comprehensively evaluate the association of historical and physiologic features with the risk of near-fatal asthma (NFA). A case-control study design was used. All patients admitted with NFA (cases) were identified prospectively and compared with asthma patients admitted during the same period without respiratory failure (controls). Nineteen cases (age: 40.2 +/- 12.0 yr) (mean +/- SD) and 80 controls (age: 36 +/- 13.5 yr) were enrolled. Duration of asthma, gender, smoking status, ethnicity, and prevalence of atopy were similar in the case and control groups. More than 80% of patients in both groups reported worsening symptoms for more than 48 h before admission, and more than 50% were worse for longer than 7 d. There was no difference in degree of airways obstruction or bronchial hyperresponsiveness (PC20). Perception of dyspnea was similar in the cases and controls, but among cases the males had greater impairment than the females (Borg score: 1.9 +/- 1. 4 versus 3.9 +/- 1.2: p = 0.05). Univariate analysis identified a history of previous mechanical ventilation (OR: 27.5; 95% CI: 6.60 to 113.7), admission to the intensive care unit (ICU) (OR: 9.9; 95% CI: 3.0 to 32.9), history of worse asthma during January and February (OR: 3.5; 95% CI: 1.0 to 11.8), and use of air-conditioning (OR: 15.0; 95% CI: 1.3 to 166) as risk factors for NFA. Of concern was the dependence of most patients (59.8%) on the emergency department (ED) for initial care, and the small number of cases (16%) in which patients visited a physician before admission to the hospital. We have confirmed risk factors identified previously in retrospective studies of fatal and NFA, and have also shown that hospitalized patients with asthma, irrespective of severity of their asthma, share several characteristics, especially in terms of their failure to respond to worsening asthma.

Long term cigarette smoke exposure does not increase airway responsiveness in rats.

To ascertain whether chronic cigarette smoke exposure induces increased airway responsiveness, we performed methacholine response tests in Sprague-Dawley rats by calculating pulmonary resistance after nebulization of saline followed by an increasing concentration of methacholine. We also calculated the concentration of methacholine which doubled the baseline resistance (R200). Tests were performed at baseline and after 2, 4, 8, and 12 months of exposure to the smoke of seven cigarettes per day, 5 days each week; control animals were exposed to room air. At the completion of the study, there were 13 rats in the smoke-exposed group and 7 rats remaining in the control group. Airway morphology was assessed using a point counting technique. We found that (1) chronic exposure to cigarette smoke did not alter either the baseline resistance or the R200; (2) the saline baseline resistance decreased over time in the control animals; and (3) at the 12-month time point, smokers with increased baseline airway resistance had greater amounts of airway smooth muscle compared with the smoke-exposed animals without increased resistance. We conclude that in this animal model, long term exposure to cigarette smoke did not alter the response to methacholine but did increase airway smooth muscle and baseline resistance in some but not all animals.

Acute effects of ambient inhalable particles in asthmatic and nonasthmatic children.

Although increases in inhalable particle (PM10) concentrations have been associated with acute reductions in the level of lung function and increased symptom reporting in children, including children with asthma, it is not clear whether these effects occur largely in asthmatic children, or even whether asthmatic children are more likely to experience these effects than children without asthma. To address these points, the following subgroups of children were selected from a survey population of all 2,200 elementary school children (6 to 13 yr of age) in a pulp mill community on the west coast of Vancouver Island: (1) all children with physician-diagnosed asthma (n = 75 participated), (2) all children with an exercise-induced fall in FEV1 without diagnosed asthma (n = 57), (3) all children with airway obstruction (FEV1/FVC < 0.76) without either of the above (n = 18), and (4) control children without any of the above (n = 56). The children were followed for as long as 18 mo with twice daily measurements of peak expiratory flow (PEF) and daily symptom diary recording. Maximum daily PM10 concentration was 159 microm/m3 (median, 22.1), but only 8 d (1.2%) had concentrations above 100 microg/m3. In an analysis that accounted for time-varying covariates, and serially correlated and missing data, for the entire sample of children, increases in PM10 were associated with reductions in PEF and increased reporting of cough, phlegm production, and sore throat. For the subgroup of children with diagnosed asthma, PEF in the time period with the highest PM10 concentrations fell by an estimated 0.55 L/min (95% CI, 0.06 to 1.05) for a 10 microg/m3 PM10 increase above the mean daily PM10 concentration of 27.3 microg/m3 and the odds of reported cough increased by 8% (95% CI, 0 to 16%); no consistent effects were observed in the other groups of children. It is concluded that children experience reductions in PEF and increased symptoms after increases in relatively low ambient PM10 concentrations, and that children with diagnosed asthma are more susceptible to these effects than are other children.

A longitudinal analysis of pulmonary function in rats during a 12 month cigarette smoke exposure.

We wanted to examine the longitudinal effects of chronic cigarette smoke exposure, and to determine whether the chronic alterations in pulmonary function induced by long-term cigarette smoke exposure in an animal model could be predicted by initial or early alterations in function. A group of Sprague Dawley rats was exposed to the smoke of 7 cigarettes x day(-1) for 5 days x week(-1) during a total period of 12 months. Lung volume, flow-volume curves and pressure-volume curves were recorded at baseline, and after 2, 4, 8 and 12 months of smoke exposure. A control group of rats was subjected to the same regimen of testing, but was not exposed to smoke. Thirteen rats completed the study in the smoke-exposed group and seven rats in the control group. We found that chronic exposure to cigarette smoke produced early abnormalities in pulmonary function, with the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio showing an acceleration of ageing effect, particularly between 4 and 8 months of exposure. In this model, although the two groups had significantly different airflow after 12 months, the initial values in each group were remarkably similar, and we could not identify any pulmonary function test which had predictive value. We conclude that longitudinal studies of cigarette smoke exposure in this rat model allow better characterization of the nature and time course of the effects of smoking on the lung.

Effect of ambient ozone exposure on lung function in farm workers.

Effects of ozone exposure on outdoor farm workers in the Fraser Valley of British Columbia, Canada, were investigated. Fifty-eight workers underwent spirometry daily before and after each 8- to 14-h workday from June 23 to August 26, 1993. The mean daily maximum (1 h) ambient ozone concentration was 40 ppb (range: 13 to 84 ppb). Concentrations of acid aerosols and fine particulates, potential confounders of ozone effects, were very low. In individual regressions of evening FEV1 and FVC on maximum daily ozone concentration, 47 of 53 workers with valid data (46 of 53 for FVC) had negative slopes. The average slopes (weighted by the inverse SE of the regression coefficients) were -3.3 and -4.7 ml for FEV1 and FVC, respectively, for each ppb increase in ozone (p < 0.001). Following correction for an individual's mean lung function level, date, and temperature, regression of either the afternoon or the daily change (afternoon-morning) corrected for the morning measurement of FEV1 and FVC on ozone showed similar magnitudes of effect. These associations were still apparent on the following morning, suggesting a persistent ozone effect. These results indicate that exposure of a population of outdoor workers to ambient ozone concentrations below 85 ppb is associated with decreased lung function over the day, which persists to the following day.

Shape and position of the complete dose-response curve for inhaled methacholine in normal subjects.

Plateaus on the inhalation concentration-response curve have been described in normal subjects and patients with mild asthma. To determine the prevalence of plateaus on inhalation concentration-response curves, and the position of the curves in normal subjects, we measured complete dose-response curves for methacholine (1 mg/ml to 256 mg/ml) in 73 nonatopic, nonsmoking, nonasthmatic normal subjects between the ages of 20 and 76 yr. Measurements included FEV1, maximal expiratory flow at 50% and 30% of vital capacity on partial and complete forced expiratory flow-volume curves (Vmax50p, Vmax50c, Vmax30p, Vmax30c) and pulmonary resistance (RL). Plateau responses, EC50 values and slopes were measured. Plateaus were present in 25, 27, 24, 34, 35, and 16 subjects for FEV1, Vmax50c, Vmax30c, Vmax50p, Vmax30p, and RL, respectively. In those who achieved a plateau, the mean maximal decrease in FEV1 (+/- SD) was 21 +/- 8%, in Vmax50c it was 46 +/- 16%, in Vmax50p it was 67 +/- 12%, in Vmax30c it was 58 +/- 21%, and in Vmax30p it was 75 +/- 15%, and the increase in RL was 213 +/- 89%. In summary, the results of this study showed that easily identifiable plateaus develop on the inhalation concentration-response curves of approximately 40% of normal subjects after only moderate decreases in maximum flow and increases in RL. Maximal response at the plateau was greater on partial flow-volume curves and at lower lung volumes (30% versus 50% of VC). Comparison of these data with data from patients at risk for airway hyperresponsiveness will allow definition of the mechanisms leading to airway hyperresponsiveness.