INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Environmental tobacco smoke (ETS) exposure is widespread, affecting most U.S. adults (1). Because it contains potent respiratory irritants, ETS is perceived as a potentially important aggravating factor for adults with asthma. Reflecting this view, national asthma guidelines recommend that people with asthma avoid ETS exposure (4). Clearly, understanding the impact of ETS exposure on asthma health status has important clinical and public policy implications.

Despite the importance of this question, existing data about the effect of ETS exposure on adults with asthma are surprisingly limited. In children, substantial evidence indicates that ETS exposure increases asthma severity (5). Moreover, controlled exposure experiments suggest that acute ETS exposure adversely affects lung function in adult asthmatics (8). Only a few epidemiologic studies have investigated the effects of ETS on adult asthma. These studies suggest a relationship between ETS exposure and both greater respiratory symptoms and medication use (11, 12). In adults, the effects of ETS exposure on asthma severity, health status, and health care utilization, however, have not been well delineated. For our study, we prospectively evaluated the impact of self-reported ETS exposure on a broad array of health outcomes in adults with asthma followed over an 18-mo period.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

We used data collected during a prospective, longitudinal cohort study of adults with asthma recruited from physician practices in northern California. Details of recruitment and interview structure have been previously reported (13) and are summarized below. The study protocol was approved by the University of California, San Francisco, Committee on Human Research.

Physician Recruitment

We selected a random sample from among all certified American Board of Medical Specialty internal medicine and pulmonary specialists (n = 252) and all internal medicine and allergy/immunology specialists (n = 40). We attempted to recruit the entire sample of 92 pulmonologists and 19 allergists who met the study's eligibility criteria of active practice in northern California. Of the eligible physicians, 68 (74%) pulmonologists and 17 (89%) allergists participated. Because some participating physicians ultimately enrolled no patients, the final number of physicians with participating subjects was 57 pulmonologists and 17 allergists.

Subject Recruitment

Each participating pulmonary and allergy physician maintained a registry of people aged 18- 50 yr with outpatient visits for asthma over a prospective 4-wk period. Each person registered by a participating physician was contacted to arrange a telephone interview. In total, there were 698 potential subjects registered. Of these, 84 (12%) declined to participate and 13 (2%) were not successfully contacted, for an overall initial study participation of 601 (86%).

We reinterviewed 539 (90%) of the 601 adults with asthma previously studied at baseline. The interval between baseline and the second interview was 18.6 ± 1.0 mo. Of the 62 subjects not reinterviewed, five died during the interval, 47 declined further study participation, and 10 were lost to follow-up. As previously reported (15), subjects not reinterviewed were younger (36.0 ± 9.2 versus 39.4 ± 8.1 yr, p = 0.003) and more frequently male (45% versus 30%, p = 0.02) than those completing follow-up. There were no statistically significant differences in race or severity-of-asthma (SOA) scores by follow-up status (p > 0.15).

Interviews and Survey Instrument

All subject interviews were performed by a single trained survey worker. The format was a structured, computer-assisted telephone interview covering asthma history, symptoms, and treatment; health status; and demographic variables.

We defined atopic history as subject-reported allergic rhinitis or atopic dermatitis. Family income was ascertained as a series of increments (less than $5,000, $5,001-$10,000, $10,000 increments through $50,000, $50,001-$75,000, and more than $75,000). To convert these ranges to specific income levels, the midincrement value was applied (except for the highest category, where we used a value of $87,500). If the subject was married or living with a domestic partner, we calculated income per adult in the household.

Assessment of Environmental Tobacco Smoke Exposure

Environmental tobacco smoke exposure was assessed at baseline with the following question: "Including home, work, and other locations, have you been regularly exposed to tobacco smoke in the last 12 months? (`Regularly' means on most days or nights)." A second question tapped weekly exposure duration: "Including home, work, and other regular activities, how many hours per week on average are you exposed to other people's tobacco smoke?" At the 18-mo follow-up, these questions were repeated, substituting 18 mo as the time interval. We did not assess biomarkers of ETS exposure.

We defined four groups based on self-reported regular ETS exposure at baseline and 18-mo follow-up: no ETS exposure at either baseline or follow-up, ETS exposure at baseline but none at follow-up, no baseline ETS exposure and newly reported exposure at follow-up, and ETS exposure at baseline with continued exposure at follow-up.

Health Outcomes

Asthma severity was assessed using a previously validated disease-specific SOA scoring system (13, 16). Total scores range from 0 to 28, with higher scores reflecting more severe asthma. We used the Asthma Quality of Life (QOL) Questionnaire to assess disease-specific QOL (17). This validated, 20-item instrument has a maximum score of 80, which reflects the most negative impact of asthma on QOL. The Medical Outcomes Study SF-36 questionnaire was used to measure health status. The physical and mental component summary scores have been defined from the eight SF-36 subscales by factor analysis (18). They measure physical and mental dimensions of health, respectively. In the general U.S. population, each summary score has a mean of 50 and a standard deviation of 10. Higher scores reflect better health.

We also assessed several other health outcome measures at baseline: subject-reported emergency department visits for asthma (during the past 12 mo), urgent physician visits for asthma (past 12 mo), hospitalizations for asthma (past 12 mo), and health-related restricted activity days (past 4 wk). At follow-up interviews, the same health outcomes were assessed for the intervening 18 mo (health care utilization) or past 4 wk (restricted activity days).

Current Study Sample

To eliminate the potential confounding effect of personal (direct) smoking in this analysis, we excluded all subjects who reported current active cigarette smoking at baseline or follow-up interviews (n = 45). In addition, subjects who reported ever smoking and who quit 5 yr or less before the baseline interview were excluded from this analysis (n = 43). In total, 88 current or recent cigarette smokers were excluded (16% of subjects reinterviewed), leaving 451 subjects for analysis. The subjects excluded because of active smoking were slightly younger than the group studied (37.5 ± 8.0 yr versus 39.8 ± 8.1 yr, p < 0.02). There were no statistically significant differences in sex (70.5% versus 70.3% female), race (61.4% versus 68.7% white), or SOA scores (11.8 ± 6.3 versus 11.2 ± 5.8); for all comparisons, p > 0.20.

Statistical Analysis

Interview data were exported into a PC-SAS-compatible format (SAS Institute, Cary, NC). We tested differences in demographic characteristics and asthma severity among the four groups (unexposed and three categories of ETS-exposed subjects) by the chi-square test for categorical variables, analysis of variance (ANOVA) for continuous, normally distributed variables, and the Kruskal-Wallis test for income, which was non-normally distributed. Tukey's modified t test was used to perform pairwise comparisons of asthma severity between groups.

We assessed the cross-sectional association of ETS exposure and selected health outcomes at baseline. The t test was used to compare asthma severity, asthma-specific QOL, and health status (SF-36 summary scores) between ETS-exposed and unexposed subjects. Using multiple linear regression, we examined the cross-sectional association between ETS exposure and each dependent variable, taking into account the effects of age, sex, race, and income. Multiple logistic regression was used to analyze the association between ETS exposure and emergency department visits ( 1 in the past 12 mo), urgent physician visits ( 1 in the past 12 mo), hospitalizations ( 1 in the past 12 mo), and restricted activity days ( 7 in the past 4 wk), controlling for the same demographic covariates.

We then evaluated the prospective impact of ETS exposure on health outcomes in subjects who reported regular ETS exposure at baseline but none at follow-up, new-onset ETS exposure at follow-up, or continued ETS exposure at both baseline and follow-up. Our study hypotheses were that cessation of ETS exposure would be associated with improved asthma severity and health status; new ETS exposure, with worsening outcomes; and continued exposure, with no change in status.

The paired t test was used to compare follow-up asthma severity, asthma-specific QOL, and health status (SF-36) scores to their baseline values within each ETS exposure category. Multiple linear regression was used to analyze the association between ETS exposure category and follow-up asthma severity after controlling for baseline asthma severity, age, sex, race, and income. The model can be summarized as follows: follow-up asthma severity = ETS exposure cessation + new-onset ETS exposure + continued ETS exposure + baseline asthma severity + demographic covariates. In a similar approach, we used multiple linear regression to evaluate the association between ETS exposure category and follow-up asthma-specific QOL and health status (SF-36). In each analysis, we controlled for either baseline QOL or SF-36 component score, in addition to baseline asthma severity and demographic covariates. To assess ETS exposure dose-response relationships, we repeated the linear regression analyses using six dichotomous variables for 1-2 h/wk and  3 h/wk of ETS exposure in each of the three exposure categories. In these analyses, we controlled for the same covariates.

Using multiple logistic regression analysis, we assessed the prospective relationship between ETS exposure category and subject-reported emergency department visits ( 1 visit over the 18-mo follow-up period), urgent physician visits ( 1 visit over follow-up), hospitalizations ( 1 over follow-up), and restricted activity ( 7 d in the 4 wk before interview). In all models, we controlled for baseline asthma severity, age, sex, race, and income.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Environmental Tobacco Smoke Exposure Prevalence

We analyzed data for 451 nonsmoking adults with asthma at baseline and 18-mo follow-up. Nearly one-third of subjects (29%; 95% CI, 25-33%) reported some regular ETS exposure during the study interval. Of the 129 subjects who reported ETS exposure at any point, 43 (10% of all subjects) reported exposure at baseline but not at follow-up, 56 (12%) indicated no exposure at baseline and new exposure over the follow-up period, and 30 (7%) reported exposure both at baseline and follow-up.

Subject Characteristics by Exposure Category

We compared baseline demographic and clinical characteristics among four groups of subjects: no reported ETS exposure at either interview, ETS exposure at baseline but none at follow-up, no ETS exposure at baseline with new exposure over the follow-up period, and exposure at both baseline and follow-up interviews (Table 1). Reported income was higher in subjects reporting no ETS exposure (median, $31,250) or exposure at both interviews (median, $28,125) than in the other two exposed groups (median, $22,500), but these differences did not achieve conventional statistical significance (p = 0.085). Baseline SOA scores were significantly different among the subject groups overall (p = 0.04; Table 2). Subjects reporting baseline exposure but none at follow-up had higher mean SOA scores (13.6 ± 5.8) than those with no ETS exposure (10.9 ± 5.7) by Tukey's t test, p < 0.05. In pairwise comparisons, there were no significant differences in asthma severity between the other groups. As shown in Table 1, there were no statistically significant differences in the other variables analyzed (p  0.20 in all cases).

Exposure and Asthma Status: Cross-sectional Analysis

We analyzed the association of self-reported regular ETS exposure at baseline with selected measures of asthma status. Subjects who reported regular ETS exposure had higher SOA scores than those without ETS exposure (mean score difference, 1.7; 95% CI, 0.2-3.1), corresponding to a 28% standard score change. Exposed subjects also had worse asthma-specific QOL scores than unexposed subjects (mean score difference, 3.5; 95% CI, 0.03-7.0). Also, ETS-exposed subjects had worse SF-36 physical component summary scores than those without exposure (mean score difference, 3.0; 95% CI, 0.0-6.0). There were no statistical differences in mental component summary scores in ETS-exposed versus unexposed subjects (mean score difference, 0.5; 95% CI, 1.5 to 2.5). In multiple linear regression analysis adjusting for demographic characteristics, ETS exposure remained cross-sectionally associated with greater asthma severity (p = 0.03), worse asthma-specific QOL (p = 0.04), and worse physical summary scores (p = 0.04).

Regular ETS exposure reported at baseline was associated with increased health care utilization, even after adjusting for demographic characteristics in multiple logistic regression analysis (Table 3). Reported ETS exposure was associated with increased risk of emergency department visits (OR = 2.1), urgent physician visits (OR = 1.9), and hospitalizations (OR = 1.9) for asthma in the last 12 mo. These cross-sectional analyses were not adjusted for illness severity because asthma severity could function as a causal intermediate between ETS exposure and health care utilization. However, including asthma severity as a predictor had only a small effect on the point estimates for emergency department visits (OR = 1.9), urgent physician visits (OR = 1.6), and hospitalizations (OR = 1.6).

Exposure Cessation: Longitudinal Analysis

Among the subjects (n = 43) who reported baseline ETS exposure but none at follow-up, SOA scores improved after ETS exposure cessation (mean score reduction, 3.2; 95% CI, 4.4 to 2.0; Table 2). At follow-up, there was also improvement in asthma-specific QOL (mean score reduction, 5.7; 95% CI, 9.6 to 1.8) and SF-36 physical component summary scores (mean score increase, 5.3; 95% CI, 2.6-8.1). There was no statistically significant change in follow-up mental component summary scores (mean score increase, 0.8; 95% CI, 1.9 to 3.6).

Cessation of ETS exposure over the follow-up period remained strongly predictive of improved asthma severity after controlling for baseline asthma severity and demographic characteristics in multiple linear regression analysis (p = 0.0003). The adjusted decrease in SOA score (1.9 points; 95% CI, 0.9-3.0) represents 33% of one standard deviation. After controlling for covariates, ETS cessation was also associated with improvement in SF-36 physical component summary scores (p = 0.05). In the multivariate analysis, asthma-specific QOL scores were no longer statistically associated with ETS after exposure ended (p > 0.20).

To evaluate a potential dose-response relationship, we assessed the association between self-reported weekly hours of ETS exposure and health status after adjusting for covariates (Table 4). In subjects with baseline ETS exposure for 1-2 h/ wk, cessation of ETS exposure was associated with improved follow-up SOA scores (p < 0.05). Similarly, subjects with 3 h or more of weekly ETS exposure had improved asthma severity at follow-up (p = 0.002). Subjects with high-level weekly ETS exposure at baseline also had improved SF-36 physical component summary scores after cessation, but this association was of borderline statistical significance (p = 0.08). There was no demonstrable ETS dose-response relationship for asthma-specific QOL.

When we examined the impact of ETS exposure cessation on health care utilization, subjects who reported baseline ETS exposure and subsequent cessation had a reduced probability of emergency department visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations for asthma at follow-up (OR = 0.2; 95% CI, 0.04-0.97) after controlling for baseline asthma severity and demographic characteristics. There was no statistical association between ETS cessation and urgent physician visits (OR = 0.6; 95% CI, 0.3-1.4) or restricted activity days (OR = 0.8; 95% CI, 0.4-1.7).

Exposure Initiation: Longitudinal Analysis

For subjects who reported no baseline ETS exposure and new exposure over the 18-mo follow-up period, there were no statistically significant changes in follow-up SOA scores (mean score change, 0.2 ± SE 0.5), asthma-specific QOL scores (1.3 ± SE 1.8), SF-36 physical component summary scores (0.5 ± SE 1.4), or mental summary scores (0.6 ± SE 1.1), with p > 0.40 in all cases. There was also no association between new ETS exposure and reported emergency department visits (OR = 0.9; 95% CI, 0.4-1.8), urgent physician visits (OR = 1.0; 95% CI, 0.5-2.0), or hospitalizations for asthma at follow-up (OR = 0.6; 95% CI, 0.2-1.9). In addition, there was no effect on restricted activity days (p > 0.70).

Although there was no statistical association with new ETS exposure defined dichotomously, newly exposed subjects who reported ETS exposure for 3 h/wk or more had higher SOA scores at follow-up after adjusting for covariates (p = 0.04) as shown in Table 4. Also, subjects in the highest weekly exposure group had worse asthma-specific QOL at follow-up (p = 0.02). There was, however, no parallel association between high-level weekly exposure and emergency department visits (p > 0.8), urgent physician visits (p > 0.20), or hospitalizations (p > 0.50).

Continued Exposure: Longitudinal Analysis

We evaluated the 30 subjects reporting ETS exposure throughout the study period to determine whether their asthma status changed at follow-up. At 18-mo follow-up, there was no significant change in SOA scores (mean score reduction, 0.4 ± SE 0.8), asthma-specific QOL scores (0.5 ± SE 2.7), SF-36 physical component summary scores (1.1 ± SE 1.6), or mental summary scores (0.7 ± SE 1.9), with p  0.50 in all cases. Furthermore, there was no statistical association between continued ETS exposure and health care utilization or activity restriction at follow-up relative to unexposed subjects (p > 0.80 in all cases).

In the subgroup reporting 1-2 h of ongoing weekly ETS exposure, asthma-specific QOL was significantly worse at follow-up (p = 0.002) after adjustment for covariates (Table 4). There was, however, no evidence of a dose-response relationship among those with 3 h or more of exposure. We found no impact of ETS exposure duration on asthma severity or physical summary score (p > 0.20). The 1-2 h ongoing ETS exposure category was, however, associated with worse SF-36 mental component summary scores at follow-up ( = 5.5, p = 0.002; data not shown in table).

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Our study indicates that self-reported ETS exposure is common among adults with asthma recruited from subspecialty medical practices and, importantly, is associated with worse health outcomes. In cross-sectional analyses, subject-reported regular ETS exposure was associated with greater asthma severity, worse asthma-specific QOL, worse physical health status, and increased health care utilization for asthma. The subjects reporting cessation of ETS exposure over the 18-mo follow-up period experienced reduction in asthma severity, improved physical health status, and decreased health care utilization, consistent with improved asthma status. Conversely, subjects reporting the heaviest levels of newly initiated ETS exposure over the follow-up period had worsening of asthma severity and asthma-specific QOL. Overall, these results support the hypothesis that ETS exposure adversely impacts asthma severity and asthma-related health outcomes.

Previous epidemiologic evidence strongly supports the negative effect of ETS exposure on asthma control in children (5, 19). Asthmatic children exposed to ETS have more respiratory symptoms (5, 24), more acute asthma exacerbations (5), worse lung function (5, 24, 25), increased bronchial hyperresponsiveness (7, 24), and more health care utilization (6).

In adults, however, the association between ETS exposure and asthma status has been less clear. Several epidemiologic studies have found an association between ETS exposure and increased risk of developing asthma (28). In one of the few studies in adults with established asthma, ETS-exposed asthmatics required more medications and had worse lung function than those without exposure (11). There was, however, no convincing effect of ETS exposure on emergency department visits or hospitalizations. Furthermore, a panel study of adult asthmatics found an increased risk of dyspnea and restricted activity in ETS-exposed subjects (12). The present study provides important additional evidence linking ETS exposure with increased asthma severity and worse health status in adults with established asthma.

Controlled experimental studies support the biologic plausibility of ETS-associated worsening of asthma. Environmental tobacco smoke contains a complex mixture of chemicals, including known respiratory irritants such as ammonia, formaldehyde, and sulfur dioxide (32). In chamber exposure experiments, investigators have studied the impact of acute ETS exposure on asthmatic subjects. Dahms and colleagues (8) found a significant decrement (approximately 20%) in FEV₁ and FVC after exposure for 1 h. Similarly, subjects with baseline airway hyperresponsiveness experienced nearly a 10% decrement in FEV₁ after experimental ETS exposure (9). Another study found that one-third of asthmatics had a greater-than-20% decline in FEV₁ after chamber exposure (10). The same group demonstrated that pretreatment with bronchodilators prevented the acute decline in FEV₁ in previously reactive subjects (33). Other studies, however, have found no effect of acute chamber ETS exposure on lung function in asthmatic subjects (34, 35). Interpretation of these controlled exposure studies is hampered by small sample size, differing subject inclusion criteria, and variation in chamber exposure methodology. Nonetheless, these experimental studies support a modest adverse effect of acute ETS exposure on lung function.

The current study has several limitations. First, our study sample of adults with asthma was drawn from pulmonary and allergy practices and may differ significantly from the general population of asthmatics. For example, asthmatics treated by specialists appear to have more severe asthma than those seen by generalists (36). As a result, our findings may overestimate the impact of ETS exposure on asthmatics in general, especially those with mild disease. Second, our study relied on self-reported ETS exposure and did not assess biomarkers of tobacco exposure. Numerous studies have demonstrated modest correlations between self-reported ETS exposure and biomarker levels, such as urine cotinine (1, 37). We cannot, however, exclude some systematic misclassification of ETS exposure status. For example, subjects with poor asthma status might be more likely to perceive and report ETS exposure, whereas asthmatics with mild disease severity might underreport ETS exposure.

Finally, the prevalence of ETS exposure is likely to be lower in California than other U.S. locations. California time- activity data from 1990 (32) indicate that the workplace accounted for the largest proportion of overall ETS exposure (46% for males, 35% for females). Since January 1, 1995, California legislation has prohibited smoking in most workplaces, including all restaurants (32). Because smoke-free workplaces are associated with reduced ETS exposure (38), we expect that overall ETS exposure levels have probably declined in California in recent years. As a result, our estimation of ETS exposure prevalence likely underestimates the U.S. prevalence. Also, this general reduction in public smoking would tend to attenuate the impact of ETS on asthma health status, making the effects we attempted to observe harder to detect.

Our study demonstrates that self-reported ETS exposure is associated with greater asthma severity, worse health status, and increased health care utilization in adults with asthma who receive care in subspecialty practices. Perhaps most important from a health promotion perspective, reduction of ETS exposure is associated with improvement in asthma-related health status and reduction in health care utilization. Based on these results, health care providers should routinely assess their patients' exposure to ETS and, as national guidelines recommend, encourage its avoidance.