Publications

STUDY OBJECTIVE

Many persons with asthma self-medicate with widely available and potentially hazardous nonprescription medicines. This study assessed the demographic and clinical covariates of self-treatment with over-the-counter asthma medications (OTCs).

DESIGN AND SETTING

We conducted an analytical investigation using questionnaires and measures of lung function, comparing OTC and prescription medication users. We recruited adults with asthma by public advertisement.

SUBJECTS

We studied 22 exclusive prescription asthma medication users, 15 exclusive OTC users, and 13 other subjects who combined prescription medication use with self-treatment with asthma OTCs. All but one OTC user self-medicated with a nonselective, sympathomimetic metered-dose inhaler.

RESULTS

Taking income, access to care, and self-assessed disease severity into account, male gender was strongly associated with exclusive OTC use alone (odds ratio [OR]=8.9, 95% confidence interval [CI]= 1.3 to 61) and mixed OTC-prescription medication use (OR=9.7, 95% CI=1.1 to 83). The covariates of income, access to care, and self-assessed disease severity provided significant additional explanatory power to the model of exclusive OTC use (model chi2 difference 11.3, 5 df, p<0.05). Pulmonary function was similar among OTC and prescription medication users. However, prescription medication users' self-assessed asthma severity (mild compared to more severe) was associated with postbronchodilator reversibility of FEV1 obstruction (6% vs 18% reversibility, p<0.05) while exclusive OTC users' self-assessed severity showed the reverse pattern (19% vs 8%, p=0.2).

CONCLUSION

Asthma education programs attempting to discourage unregulated bronchodilator use should give consideration to this profile of the "asthmatic-at-risk."

Zinc oxide inhalation causes metal fume fever, a flu-like syndrome common among welders. Proinflammatory pulmonary cytokines play a role in mediating this occupational illness. The goal of this investigation was to characterize early pulmonary cytokine responses after experimental human exposure to inhaled purified zinc oxide fume. We quantified bronchoalveolar lavage (BAL) cytokine concentrations in 15 healthy volunteers 3 hr after inhalation of zinc oxide fume. We compared postexposure cytokine responses with postsham exposure responses in the same 15 subjects. We also compared cytokine responses with those of 14 "late follow-up" subjects previously studied by BAL 20 hr after zinc oxide fume exposure. Zinc oxide exposure was a statistically significant, dose-dependent predictor of increases in BAL TNF (mean exposure-sham difference +/- SE = 9.5 +/- 3.6 pg/mL, P = 0.02), IL-6 (mean exposure-sham difference +/- SE = 5.5 +/- 1.8 pg/mL, P = 0.009), and IL-8 (mean exposure-sham difference +/- SE = 64.1 +/- 23.9 pg/mL, P = 0.02). The TNF response was significantly greater at 3 hr follow-up compared with 20 hr follow-up, after adjusting for smoking status, zinc dose, and BAL macrophages (P = 0.004). Our findings provide evidence for a pulmonary inflammatory response 3 hr after inhalation of zinc oxide fume characterized by dose-dependent increases in BAL proinflammatory cytokine concentrations. These data indicate that TNF plays an important initial role in mediating metal fume fever.

Murine lupus in NZB/NZW F1 (B/W) mice can be retarded by sustained administration of CTLA4Ig and by brief treatment early in life with mAb that block CD40/gp39 interactions. We sought to determine whether brief therapy with CTLA4Ig could provide sustained benefit in B/W mice and whether a synergistic effect could be derived by blockade of both the B7/CD28 and the CD40/gp39 pathways. We found that a short course of CTLA4Ig at the onset of disease produced only short-term benefit. However, when CTLA4Ig was combined with anti-gp39, there was long-lasting inhibition of autoantibody production and renal disease. Ten months after the 2-wk course of therapy, 70% of these mice were alive, compared with only 18% and 0% of those that received only anti-gp39 or CTLA4Ig, respectively. These findings demonstrate that brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways can produce benefit that lasts long after treatment has been discontinued.