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Study objectives To assess the influence of inhaled corticosteroids (ICSs) on mortality in COPD patients, which is currently a controversial topic. Setting Manitoba Health maintains a population-wide research database that includes pharmaceutical information. Design and patients We examined mortality in people 90 to 365 days after hospital discharge for COPD, comparing those persons who received inhaled steroids within 90 days of hospital discharge with those who did not. Cox proportional hazards models were used with adjustments for other respiratory drugs, comorbidities, and physician visits before and after hospital discharge. We also compared mortality in patients who received inhaled steroids with those who received other respiratory drugs, but not inhaled steroids, and those who received neither. Using nested case control analysis, we examined the time of receipt of inhaled steroids in relation to fatal events. Results In people > 65 years of age, inhaled steroids were associated with a 25% reduction in mortality between 90 and 365 days after hospital discharge, while mortality increased with bronchodilator use, physician visits, age, and comorbidities. The exclusion of people who had also received a diagnosis of asthma or had received inhaled steroids before hospitalization did not change the result. Inhaled steroids were associated with an even larger mortality reduction in people aged 35 to 64 years. People who received bronchodilators but no steroids had higher mortality than people who received no bronchodilators or received both bronchodilators and inhaled steroids. The reduction in all-cause mortality was largely due to the decreased number of cardiovascular deaths. The receipt of inhaled steroids within 30 days of death was protective, but this was not the case for greater time intervals. Conclusions Therapy with ICSs reduced mortality in COPD patients; the effect was particularly notable for cardiovascular death and was short term in that it was dependent on recent exposure.

Objective: The objective of this cohort study was to determine if complications of pregnancy and labor, characteristics at birth, and exposure to infections influence the incidence of asthma in the first 6 years of life. Design: We identified all children born between 1980 and 1990 in the Province of Manitoba, Canada. We used records of physician contacts (inpatient and outpatient) and services of the universal provincial health insurance plan to follow up 170,960 children from birth to the age of 6 years to identify the first diagnosis of asthma. Information on mothers and siblings was also obtained to determine family history of disease and exposure to infections. Results: During the study period, a diagnosis of asthma was made in 14.1% of children by the age of 6 years. The incidence was higher in boys than in girls, in those with family history of allergic diseases. It was higher in urban than in rural areas, and lowest in those born in winter. Asthma was more likely in those with low birth weight and premature birth. Certain congenital abnormalities and complications of pregnancy and labor also increased the risk of asthma. The risk of asthma increased with maternal age. Both upper and lower respiratory infections increased the risk of subsequent asthma, and this effect was more important than exposure to familial respiratory infections, which also tended to increase asthma risk. The risk of asthma decreased with the number of siblings when siblings had a history of allergic disorders. Conclusions: In addition to genetic influences, intrauterine and labor conditions are determinants of asthma. Exposure to both upper and lower respiratory tract infections increases the risk; these infections do not explain the protective effect associated with the increasing number of siblings.

Objectives Geographic variability in reported prevalences of asthma worldwide could in part relate to interpretation of symptoms and diagnostic biases. Bronchial responsiveness measurements provide objective evidence of a common physiologic characteristic of asthma. We measured bronchial responsiveness using the standardized protocol of the European Community Respiratory Health Survey (ECRHS) in six sites in Canada, and compared prevalences across Canada with international sites. Design Samples of 3,000 to 4,000 adults aged 20 to 44 years were randomly selected in Vancouver, Winnipeg, Hamilton, Montreal, Halifax, and Prince Edward Island, and a mail questionnaire was completed by 18,616 individuals (86.5%). Preselected random subsamples (n = 2,962) attended a research laboratory for examination including more detailed questionnaires, lung function testing including methacholine challenge, and skin testing with 14 allergens. Results Prevalences of bronchial hyperresponsiveness, measured as cumulative dose of methacholine required to produce a 20% fall from the post-saline solution FEV 1 ≤ 1 mg, ranged from 4.9% (95% confidence interval [CI], 1.6 to 8.5) in Halifax to 22.0% (95% CI, 18.1 to 26.0) in Hamilton (median, 10.7%). In all Canadian sites, bronchial hyperresponsiveness was more prevalent in women than in men. Neither the geographic nor gender differences were accounted for by differences in age, smoking, skin test reactivity, or baseline FEV 1. Geographic- and gender-related variability changed little when only bronchial hyperresponsiveness associated with asthma-like symptoms was considered. Conclusions A wide variability in bronchial responsiveness can occur within one country, almost as wide as the range found across all international sites participating in the ECRHS study and not explained by differences in gender, smoking, skin test reactivity, and FEV 1 . While gender variability in the prevalence of bronchial responsiveness is likely due to hormonal and immunologic factors, geographic variability is likely to result from environmental factors.

Objectives (1) To correlate structure (CT) with function in pulmonary tuberculosis (TB), and (2) to describe the evolution of structural and functional abnormalities when pulmonary TB is treated with directly observed therapy. Subjects and methods Twenty-five patients with drug-susceptible pulmonary TB, 15 cavitary and 10 noncavitary, were studied prospectively. Conventional CT and pulmonary function testing (spirometry, diffusing capacity, and arterial blood gases) were performed at baseline, and after 1 and 6 months of directly observed therapy. Results All but one patient with noncavitary miliary TB had CT evidence of endobronchial disease, and all patients with cavitary disease had coexistent reduced lung attenuation, the latter presumably a result of gas trapping, hypoxic vasoconstriction, and vascular injury. Functional impairment was minimal and in proportion to the number of diseased segments and cavitary volume. Bronchiectasis was significantly more likely to complicate cavitary than noncavitary disease (64 vs 11%; p Conclusions CT findings correlate well with function in pulmonary TB. Physiologic data were consistent with the concept that pulmonary TB is an endobronchial disease that causes parallel reductions in ventilation and perfusion. This concurrent involvement of both airways and contiguous pulmonary blood supply offers an explanation for the minimal respiratory limitation experienced by these patients despite often extensive lung disease. Supervised therapy of drug-susceptible disease results in minimal structural and functional residua.

Study objective Patients with moderate to severe COPD are frequently prescribed expensive and complicated therapies that require adjustments in usual activities of daily living. However, little is known about factors that are associated with adherence to such treatment. The objective of this study was to identify characteristics of patients who were adherent to long-term home nebulizer therapy. Design Patients were stratified into two adherence groups based on average minutes of nebulizer use each day. A logistic regression model was developed to predict adherence based on baseline variables. A questionnaire was administered to patients to assess reasons for adherence to therapy. Setting Five clinical centers in the United States and Canada. Participants Nine hundred eighty-five patients with moderate to severe COPD enrolled in the Intermittent Positive Pressure Breathing (IPPB) Trial. Interventions Long-term home IPPB and nebulizer therapy. Measurements and results Altogether 50.6% of patients were adherent, and 49.4% were nonadherent. Among baseline variables, good adherence was predicted by white race, married status, abstinence from cigarettes and alcohol, serum theophylline level ≥9 μg/mL, more severe dyspnea, and reduced FEV 1 (p Conclusions Sociodemographic, physiologic, and quality of life variables were associated with adherence to long-term nebulizer therapy. (CHEST 1995; 108:394-400)

Objective: To assess changes in the severity of physician-diagnosed asthma between 1983 and 1988. Design: Cross-sectional studies examining the frequency of markers of asthma severity: hospitalizations, ICU admissions, hospital emergency department visits, multiple physician contacts, and referrals to specialists in patients aged 0 to 14 years, 14 to 34 years, and ≥35 years separately. Setting: Physicians' claims data from the universal Provincial Health Insurance Plan for fiscal years 1983 and 1988. Patients: All patients with the diagnosis of asthma, bronchitis, and COPD identified from the Manitoba Health database. Measurements: The markers of severity were related to the prevalence of patients seeing a physician and receiving a diagnostic label of asthma, COPD, or bronchitis. Results: The number of patients with physician-diagnosed asthma increased by 36.4% over the 5 years. In 1983, 11% of asthmatics were hospitalized during the year and 8% were hospitalized in 1988 (–2.5%; 95% confidence interval [CI], –3.2 to –1.8%). During both years, about 75% of the patients hospitalized were in hospital once only. Mean and median duration of hospital stay declined. The percentage of asthmatics seen in the hospital emergency departments declined slightly in all age groups, the total being 21% in 1983 and 18% in 1988 (–3.5%; 95% CI, –4.5 to –2.5%). About one third of the patients with asthma were seen only once by a physician during both of the years examined, 43 to 45% of them being seen on three or more occasions during both years. Referrals to specialists for all asthmatics increased from 12 to 14% (1.9%; 95% CI, 1.0 to 2.8%) from 1983 to 1988. This was almost entirely due to an increase from 11 to 16% (5.1%; 95% CI, 4.0 to 6.2%) in the youngest age group, an increase not accompanied by an increase in any other marker of severity. Changes in asthma severity were similar to changes in the severity in patients with bronchitis and COPD. Conclusion: No increase in severity of asthma was seen between 1983 and 1988, but the prevalence of the diagnostic label of asthma increased substantially.

In normal conscious humans, when a brief hypoxic ventilatory stimulus is followed immediately by breathing 100% O2, ventilation during hyperoxia gradually declines to baseline prehypoxic levels without an undershoot. During the decline, ventilation is greater than baseline in the absence of hypoxia and hypercapnia. This has been interpreted as evidence of decay of short-term potentiation (STP) or afterdischarge. It is not known whether the intensity of the stimulus that activates STP influences the time course of its decay. Therefore we studied STP decay in nine normal adults after administration of placebo (P) and almitrine (A) in a single-blind manner on 2 separate days. On each day, three runs consisting of 45 s of isocapnic hypoxia (end-tidal PO2 = 55 mm Hg) followed by 2 min of hyperoxia were conducted while ventilation (VI) was measured breath by breath. Baseline VT did not differ between A and P, but at the end of hypoxia, VI with A was 169 +/- 14% (SE) of baseline while VI with P was 132 +/- 7% of baseline (p0.05). Immediately after hyperoxia was instituted, VI fell abruptly, the fall being 36% of baseline for A and 15% for P. This probably represented the withdrawal of peripheral chemoreceptor input. Thereafter, VI declined slowly toward baseline, and the time course of this decline did not differ between P and A. Our results indicate that within the limits we studied, the increase of the intensity of the discharge of the peripheral chemoreceptors during hypoxia does not influence STP decay.

We attempted to assess recent changes in the prevalence of physician-diagnosed asthma and the possible influence of diagnostic exchange on these trends. The routinely collected data of the provincial Health Insurance Plan (physicians' claims) were used to determine the annual prevalence of physician-diagnosed asthma in Manitoba. Results indicate that the prevalence of physician-diagnosed asthma increased for all age groups in both male and female subjects between 1980 and 1990. The average increases were the highest in the age group 5 to 14 years for both sexes. The average increases varied with age and there were significant differences between the two sexes. There was evidence of increasing diagnostic exchange, that is, a tendency to label patients with asthma instead of alternative diagnoses. This was particularly prominent in those younger than 35 years of age. However, the increased prevalence of physician-diagnosed asthma, even for the younger population, cannot be fully explained by diagnostic exchange.

Eleven patients with severe COPD were examined to determine whether tolerance to s 2 -agonists developed after long-term inhalation therapy with these agents. Before the study all patients were on regular treatment with inhaled salbutamol for six months. At the beginning of the study, response of FEV 1 to inhaled salbutamol was measured. Dose-response curves were measured after three weeks of treatment with ipratropium bromide and again after a three-week course of inhaled salbutamol. After ipratropium bromide treatment, responses to low doses of salbutamol tended to be larger than after salbutamol treatment, but differences were not significant. Three hours after the last inhalation of salbutamol the FEV 1 was lower on days 1 and 42 than on day 21. We conclude that long-term inhalation therapy with s 2 -agonists in patients with COPD decreases the duration of the bronchodilation produced by the same agents but does not affect the peak response. (Chest 1990; 97:280–84)

Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1.Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV1 decline in COPD patients, and whether this relationship is modified by gender and smoking.Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV1 of 2.42 +/- 0.19% compared with placebo (p Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV1 among those who completed these randomized clinical trials.

To identify characteristics associated with respiratory symptoms due to an episode of air pollution.Mail survey.In October 1992, the population of the city of Winnipeg was exposed to elevated levels of particulate matter (total and10 microm size), carbon monoxide, nitrogen dioxide, and volatile organic compounds due to smoke from adjacent fields where farmers were burning agricultural residue (straw and stubble).We surveyed 428 participants in the ongoing Lung Health Study (35 to 64 years old, both sexes) with mild to moderate airways obstruction (mean FEV1 percent predicted 73+/-12%), and a high level of airways hyperreactivity (23% of men and 37% of women).While 37% of subjects were not bothered by smoke at all, 42% reported that symptoms (cough, wheezing, chest tightness, shortness of breath) developed or became worse due to the air pollution episode and 20% reported that they had breathing trouble. Those with symptoms were more likely to be female than male and were more likely to be ex-smokers than smokers. Subjects with asthma and chronic bronchitis were also more likely affected. The degree of airways obstruction and the level of bronchial hyperresponsiveness were not associated with increased susceptibility.Gender, smoking habit, and respiratory symptoms but not bronchial hyperresponsiveness or the degree of airways obstruction are factors influencing susceptibility to symptoms due to air pollution in adult smokers and former smokers.

In 140 adult patients with FEV1 greater than or equal to 60 percent predicted referred because of suspected asthma, we compared responses to methacholine and isocapnic cold-air hyperventilation. Most challenges were accomplished on the same day, cold air always being done first. The cold-air test employed a single episode of hyperventilation (target, 30 times the FEV1), and subsequent FEV1 changes were noted, a decrease of 10 percent being defined as a positive test result. For methacholine, subjects inhaled aerosols of increasing concentrations and the dose associated with a 20 percent decline in FEV1 (PC20) was noted; positive tests were defined as a 20 percent decrease at concentrations less than or equal to 8 mg/ml. Of the 140 patients, 65 had negative results on both challenges. Twelve patients had positive results on cold-air testing but negative responses to methacholine, and 17 had the opposite result. Among patients with positive results to either test, there was a significant correlation (p less than 0.001) between change in FEV1 with cold air and log PC20, but there was considerable scatter, the results of one test accounting for 25 percent of the variability in the other. Some scatter may have been related to the methods we used, but much was probably due to the patients themselves. Neither test should be used on an exclusive basis to make the diagnosis of asthma.