Asthma and lower airway disease
In utero smoke exposure and impaired response to inhaled corticosteroids in children with asthma

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Background

Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in children with asthma.

Objectives

To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma and whether IUS modifies the response to treatment with inhaled corticosteroids (ICSs).

Methods

To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma, we performed a repeated-measures analysis of methacholine PC20 data from the Childhood Asthma Management Program, a 4-year, multicenter, randomized, double-masked, placebo-controlled trial of 1041 children age 5 to 12 years comparing the long-term efficacy of ICS with mast cell stabilizing agents or placebo.

Results

Although improvement was seen in both groups, children with asthma and IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared with unexposed children (P = .01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC20 compared with untreated children (1.25-fold increase; 95% CI, 1.03-1.50; P = .02), the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04-fold increase, 95% CI, 0.65-1.68; P = .88).

Conclusion

In utero smoke exposure reduces age-related improvements in airway responsiveness among children with asthma. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women.

Section snippets

Methods

Details of the Childhood Asthma Management Program (CAMP) trial have been described elsewhere.15, 16 Briefly, CAMP is a multicenter, randomized, double-masked clinical trial to compare the long-term effectiveness and safety of 3 inhaled treatments for asthma: budesonide, nedocromil, and placebo. CAMP enrolled 1041 children age 5 to 12 years with mild-moderate asthma at 8 clinical centers between December 1993 and September 1995. Asthma was defined by the presence of asthma symptoms or the use

Results

All children with asthma in CAMP (n = 1041) had baseline methacholine challenge tests. Methacholine challenge testing was completed for 92%, 90%, 85%, and 82% of the cohort at 8, 20, 32, and 44 months after randomization, respectively. Baseline characteristics were generally similar between children with and without methacholine challenge data at 44 months. Children who were missing PC20 measurements were more likely to have been recruited from 3 of the clinical sites (Albuquerque, Boston,

Discussion

Inhaled corticosteroids are both commonly prescribed and efficacious for the treatment of asthma in children and adults. They have been shown to reduce airway responsiveness, asthma symptoms, need for breakthrough bronchodilator therapy, and exacerbation rates.14, 19 However, there is considerable between-subject variability in clinical response to inhaled corticosteroids, including patients who manifest partial to substantial steroid resistance necessitating escalation of treatment dose.20

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    The Childhood Asthma Management Program is supported by contracts NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 with the National Heart, Lung, and Blood Institute and General Clinical Research Center grants M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036 from the National Center for Research Resources. B.A.R. is a recipient of a Mentored Clinical Scientist Development Award from NHLBI/NIH (K08 HL074193).

    Disclosure of potential conflict of interest: R. T. Cohen has received research support from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the Philadelphia Health and Education Corp, and Trustees of the Alumni/ae Association of the Women's Medical College of Pennsylvania. B. A. Raby is an editor for UpToDate. A. L. Fuhlbrigge was previously a consultant, advisory board member, and speaker for Merck and is currently a consultant for GlaxoSmithKline. B. A. Rosner has received research support from the National Institutes of Health. R. S. Zeiger is a consultant for Aerocrine, AstraZeneca, Genentech, GlaxoSmithKline, MedImmune, and Merck and has received research support (through Kaiser Permanente) from AstraZeneca, Aerocrine, Genentech, GlaxoSmithKline, and Merck. The rest of the authors have declared that they have no conflict of interest.

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