Published online June 1, 2007
PEDIATRICS Vol. 119 No. 6 June 2007, pp. 1210-1212 (doi:10.1542/10.1542/peds.2007-0869)
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COMMENTARY

Maternal Smoking, Asthma, and Bronchiolitis: Clear-Cut Association or Equivocal Evidence?

Eric A.F. Simões, MB, BS, DCH, MD

Department of Pediatrics, University of Colorado at Denver and Health Sciences Center and Children's Hospital, Denver, Colorado

Although there is no doubt that secondhand environmental tobacco smoke exposure contributes to lower respiratory tract infection (LRTI) in infants and young children in developing countries1 and industrialized nations,2,3 the evidence for a specific effect on respiratory syncytial virus (RSV) LRTI is less clear.4 It is the equivocal nature of the evidence for the role of smoking affecting the severity of RSV bronchiolitis that has, in part, prevented the American Academy of Pediatrics from strongly advocating smoking as a risk factor when considering prophylaxis with palivizumab for previously premature infants of 32 to 35 weeks’ gestation.5–7

In this issue of Pediatrics, Carroll et al8 present probably the largest population-based study of term infants with bronchiolitis to determine the association between maternal asthma, maternal smoking, and the incidence and severity of bronchiolitis. In their cohort of >100000 mother-infant dyads, >20% of the infants had 1 health care visit for bronchiolitis. Maternal smoking increased the risk of bronchiolitis by 14%, maternal asthma raised it by 39%, and both together raised it by 47%. Infants of mothers with asthma who smoked had a higher risk for emergency department visits and hospitalizations. Although maternal smoking increased the risk of prolonged hospitalization by 19%, if the mother was smoking and had asthma the increased risk was 38%. Given the enormous size of the study encompassing the vast majority of children, infants, and mothers enrolled in the Tennessee Medicaid program between 1995 and 2003, this would seem to be compelling evidence for an association between maternal smoking and bronchiolitis.

Despite the enormous size of this study, the results must be tempered with an understanding of the study limitations, which were acknowledged by the authors. The major limitation is that other risk factors that are well known to be associated with hospitalization for RSV or bronchiolitis—such as an index of crowding that includes the number of sibling and adults in the household, day-care exposure, or day-care exposure of siblings or the presence of siblings <5 years of age, birth during the first half of the RSV season, and a putative risk factor (breastfeeding)—were not included in these analyses.4 In an examination of atopic risk factors, although a maternal history of asthma was considered, that of other relatives or other conditions such as atopic dermatitis or allergic rhinitis in first-degree relatives was not included in the analysis.9 Finally, a diagnosis of bronchiolitis does not equate to RSV, although in RSV season the majority of bronchiolitis admissions (perhaps 60%–80%) would be caused by RSV.

An initial study in Rochester, New York,10 conducted between 1974 and 1976, suggested that there is a significant difference between children hospitalized with RSV and controls in the amount of environmental tobacco smoke exposure (76% vs 40%, respectively; P < .01). In that study, unfortunately, no multivariate analysis was performed. A subsequent case-control study of 53 subjects with bronchiolitis and 106 matched controls showed an increased risk of bronchiolitis in families with ≥1 smoker.11 In this study, a multivariate analysis that included a socioeconomic index, breastfeeding, crowding, number of siblings in the home, and a family history of asthma showed a significant effect of passive smoke exposure in those with or without a family history of asthma.11 Several other prospective case-control studies from Sweden,12 Finland,13 and Oakland, California,14 showed no effect, but they were designed to examine risk factors for the development of subsequent asthma and did not analyze many risk factors for RSV hospitalization. In a large case-control study from Denmark15 that was designed to examine risk factors for RSV hospitalization, smoking during pregnancy was one of the significant factors on multivariate analysis (odds ratio: 1.56; 95% confidence interval: 1.32–1.98). Recent studies from Alaska16 and Australia17 showed a significant effect on univariate analysis (P = .018 and .0004, respectively) but did not show the same effect on multivariate analysis. In the study from Alaska, risk factors included breastfeeding, crowding, siblings in the home, and day-care exposure but did not include siblings in day care or maternal history of asthma or other family members with atopy.16 In contrast, the case-control study from Australia did not examine any of the other well-known risk factors but examined risk factors not commonly known to be associated with RSV hospitalization. Not surprisingly, the multivariate analysis showed no effect of smoking in this population.17

Should one then look at prospective cohort studies to provide this answer? Clearly the most important was the one conducted in Tucson, Arizona. In this large study of 1179 infants that examined risk factors for the development of RSV LRTI,18 a multivariate analysis showed no significant effect of environmental tobacco smoke exposure. In a more recent nested case-control study from the Danish birth cohort9 that involved 2564 infants and children who were hospitalized with RSV and 12816 age-matched controls (followed from birth to 18 months of age), tobacco smoke exposure was shown to be unequivocally associated with an increased risk of hospitalization with RSV (odds ratio: 1.35; 95% confidence interval: 1.20–1.52). In this study, in which individual-level patient data were obtained and every one of the known and suspected risk factors described above was included,4 environmental tobacco exposure was shown to increase the risk of hospitalization in infants in each of the age groups examined: 0 to 5, 6 to 11, and 12 to 18 months of age.9 This study also established the role of an atopic disposition for hospitalization of infants with RSV bronchiolitis: the adjusted relative risk of RSV hospitalization in the offspring was 1.11 for maternal atopic dermatitis, 1.72 for maternal asthma, and 1.23 for paternal asthma.

In none of the above-mentioned case-control or cohort studies, or from the study by Carroll et al,8 was the major question answered: Does environmental tobacco smoke exposure in prematurely born infants increase their risk for RSV hospitalization? In fact, the Carroll et al study excluded such children and focused on "normal" children. Two prospective cohort studies from Spain (in infants <32 weeks’ gestation),19,20 1 study from Germany (in infants <35 weeks’ gestation),21 1 study from Canada (in infants 33–35 weeks’ gestation),22 and a case-control study from Spain (in infants 33–35 weeks’ gestation)23 have addressed this issue in premature infants. All of these recent studies included most of the known risk factors for RSV hospitalization. Only 2 of these 5 studies, both from Spain,19,22 showed an independent risk for environmental tobacco smoke exposure on RSV hospitalizations. The article by Carroll et al8 and both the large Danish studies9,15 fairly convincingly support the role of environmental tobacco smoke exposure as an important risk factor for development of severe RSV disease leading to hospitalization. However, neither of these studies addressed the critical question to which pediatricians would like to know the answer: Is the premature infant at such a high risk of RSV hospitalization from prematurity alone, and does tobacco smoke exposure increase this risk further?


   FOOTNOTES
 
Accepted Mar 19, 2007.

Address correspondence to Eric A.F. Simões, MB, BS, DCH, MD, Children's Hospital, 1056 E 19th Ave, B070, Denver, CO 80218. E-mail: eric.simoes{at}uchsc.edu

The author has indicated he has no financial relationships relevant to this article to disclose.

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.


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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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