Publications

The effect of environmental tobacco smoke (ETS) exposure on adults with asthma has not been well characterized. In a prospective cohort study of 451 nonsmoking adults with asthma, we evaluated the impact of ETS exposure on asthma severity, health status, and health care utilization over 18 mo. There were 129 subjects (29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline exposure and new exposure at follow-up (n = 56, 12%), and exposure at both baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with baseline ETS exposure had greater severity-of-asthma scores (score difference, 1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0) than unexposed subjects. They also had greater odds of emergency department visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR = 1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In longitudinal follow-up, subjects reporting ETS cessation showed improvement in severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1). Environmental tobacco smoke cessation decreased the odds of emergency department visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04-0.97) after adjustment for covariates. Environmental tobacco smoke initiation was associated with greater asthma severity only in subjects with high-level (>= 3 h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self-reported ETS exposure is associated with greater asthma severity, worse health status, and increased health care utilization in adults with asthma.

BACKGROUND

Non-Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization).

METHODS

We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non-Q-wave infarction. Death or nonfatal infarction made up the combined primary end point.

RESULTS

During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P= 0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01).

CONCLUSIONS

Most patients with non-Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective.

Targeting gene therapy vectors to abundant receptors on airway epithelia may allow a significant enhancement of gene delivery and thereby be of particular importance for the gene therapy of cystic fibrosis. Alpha9beta1-integrins are highly expressed throughout the human airway epithelia in vivo, irrespective of any particular clinical status. Aiming to improve the targeting of our non-viral integrin-mediated gene transfer systems to airway epithelia, we searched for a short tenascin C-derived peptide which would bind to these integrins. By utilizing recombinant bacteriophages that display overlapping regions of the third fibronectin type III repeat of tenascin C (TNfn3), we were able to localize its alpha9beta1-integrin binding site to the B-C loop of TNfn3. A synthetic Pro-Leu-Ala-Glu-Ile-Asp-Gly-Ile-Glu-Leu-Thr-Tyr peptide (PLAEIDGIELTY) was shown to displace alpha9beta1-integrin-expressing cells completely from binding to TNfn3. This peptide, therefore, may prove useful both for the examination of the functional importance of alpha9beta1-integrins in vivo and the development of gene therapy vectors or drugs targeting these integrins.