Table 1 Studies Reporting Risk of Developing Serious RSV (Laboratory-Confirmed RSV; N = 14)
Study, Year, Country | Design and Population | ETS Exposure | Outcome | Results | Bias Assessment/Comment |
|---|---|---|---|---|---|
Prospective cohort studies in premature infants | Â | ||||
Broughton 2005 United Kingdom [19] | Prospective study of 126 premature infants (GA <32 wks; 40% developed BPD) | Maternal smoking during pregnancy | RSV LRTI (41% hospitalized) | aOR, 4.85 (95% CI, 1.61–14.58); P = 0.005 | No significant bias concerns affecting the relationship of ETS and outcome |
Parental smoking in home | RSV LRTI | NS aOR, 0.81 (95% CI, 0.19–3.37); P = 0.771 | |||
Maternal smoking during pregnancy | Hospital admission (all cause; 56% of admissions were RSV LRTI) | NS aOR, 1.19 (95% CI, 0.20–7.07); P = 0.849 | |||
Parental smoking in home | Hospital admission | aOR, 3.39 (95% CI, 1.08–10.63); P = 0.003 | |||
Maternal smoking during pregnancy | Length of hospital stay | NS, P = 0.150 (OR not reported) | |||
Parental smoking in home | Length of hospital stay | P < 0.001 (OR not reported) | |||
Carbonell-Estrany 2001 Spain [9] | Prospective, longitudinal study of 999 premature infants (GA ≤32 wks) | Days of smoke exposure | RSV hospitalization | aOR, 1.63 (1.05–2.56); P = 0.031 | No significant bias concerns affecting the relationship of ETS and outcome |
Figueras-Aloy 2008 Spain [20] | 2-cohort study of premature infants (GA 32–35 wks); 202 cases hospitalized for RSV and 5239 controls not hospitalized for respiratory illness | Maternal smoking during pregnancy | RSV hospitalization | aOR, 1.61 (95% CI, 1.16–2.25); P = 0.004 | Authors note relatively high loss to follow-up of 12% of children fulfilling inclusion criteria. Both ETS exposure variables were significant in bivariate analysis at P < 0.01, but when included in multivariate model, only prenatal smoking was significant, possibly due to misclassification of ETS exposure |
≤2 smokers in home | RSV hospitalization | NS in multivariate model | |||
|  |  | Significant in bivariate analysis, OR 1.59 (95% CI, 1.12–2.26); P = 0.01 | |||
Law 2004 Canada [10] | Prospective cohort study of 1832 premature infants (GA 33–35 wks) | ≥2 smokers in household | RSV hospitalization | aOR, 1.87 (95% CI, 1.07–3.26); P = 0.027 | No significant bias concerns affecting the relationship of ETS and outcome |
Case–control study in premature infants |  | ||||
Figueras-Aloy 2004 Spain [21] | Case–control study of premature infants (GA 33–35 wks); 186 cases hospitalized for RSV; 371 controls born at same time as cases | Maternal smoking during pregnancy | RSV hospitalization | NS in multivariate model | No significant bias concerns affecting the relationship of ETS and outcome |
|  |  | Significant in bivariate analysis OR, 1.62 (95% CI, 1.08–2.42); P = 0.027 | |||
Maternal smoking at home | RSV hospitalization | NS in bivariate model | |||
|  |  | OR, 1.49 (95% CI, 1.01–2.18); P = 0.055 | |||
≥2 smokers at home | RSV hospitalization | NS in bivariate model | |||
|  |  | OR, 1.41 (95% CI, 0.92–2.14); P = 0.146 | |||
Prospective cohort studies in the general population | Â | ||||
Holberg 1991 US [22] | Prospective birth cohort study of 1179 healthy infants followed for 1 year | Maternal smoking | RSV diagnosed in an office visit | NS in multivariate model | No significant bias concerns affecting the relationship of ETS and outcome |
|  |  | Rate ratio, 1.0 (95% CI, 0.3–3.5) | |||
von Linstow 2008 Denmark [6] | Prospective birth cohort study of 217 children followed for 1 year | Smoking in household | RSV hospitalization | aOR, 5.06 (95% CI, 1.36–18.76); P < 0.02 | No significant bias concerns affecting the relationship of ETS and outcome; to reduce problems with colinearity, only 1–2 variables from each group of covariates (e.g., social variables, smoking parameters) were included in the multivariate model. |
Maternal smoking during pregnancy | RSV hospitalization | NS in multivariate model (OR not reported) | |||
| Â | Â | Significant in univariate model | |||
|  |  | OR, 4.19 (95% CI, 1.21–14.53); P = 0.024 | |||
Case–control studies in the general population |  | ||||
Bulkow 2002 US [12] | Case–control study of Alaska native children aged <3 years with 204 cases and 338 controls | Smoker in household | RSV hospitalization | NS in multivariate model | Unclear risk of ETS exposure misclassification because of high prevalence of smoking and frequency of indoor visiting among households during winter RSV season; low risk of other types |
|  |  | Significant in bivariate analysis, OR, 1.61; P ≤ 0.018 | |||
Gurkan 2000 Turkey [23] | Case–control study of 28 cases and 30 controls aged 2–18 months | ▪Nonsmoking parents ▪Only smoker mother ▪Only smoker father ▪Both parents smokers | RSV bronchiolitis admitted to the ED Serum cotinine assessed during ED visit and 1 month later | Significant differences in cases vs. controls (P < 0.05) for all ETS exposure variables; however, only father smoker was more prevalent in the control than case group | No multivariate analysis performed (confounding bias) |
|  |  | Significant differences in cases vs. controls (P < 0.05) in cotinine levels for both parents smokers vs. both parents nonsmokers and for only mother smoker vs. both parents nonsmokers in the control group | |||
Hall 1984 US [24] | Case–control study of 29 cases and 58 controls hospitalized with non respiratory acute illness | Smoking in household | RSV hospitalization | Significant difference in smoking in household in cases (76%) vs. controls (40%) (P < 0.05) | No multivariate analysis performed (confounding bias) |
Hayes 1989 American Samoa [25] | Case–control study of children aged <1 year (20 cases and 15 well controls) | Smoker in household | RSV hospitalization (53% laboratory-confirmed) | Significant difference in smoker in household in cases (92%) vs. well controls (53%) (P = 0.04) | No multivariate analysis performed (confounding bias)53% of hospitalizations were laboratory-confirmed RSV |
Nielsen 2003 Denmark [5] | Case–control study of 1252 cases in children aged <2 years and 5 controls for each case | Maternal smoking during pregnancy from the Medical Birth Register | RSV hospitalization | aOR, 1.56 (95% CI, 1.32–1.98) | No significant bias concerns affecting the relationship of ETS and outcome |
Reeve 2006 Australia [11] | Case–control study with 271 cases and 542 controls (median age 6 mo) | Maternal smoking | RSV hospitalization | NS in main multivariate modelBivariate OR not reported CART analysis performed to define groups that are most homogeneous with regard to the outcome of RSV hospitalization. CART analysis found that smoking was a risk factor in children with birthweight >2500 g and single mothers (41.0% hospitalized vs. 26.9% for single nonsmoking mothers)Smoking was not significant for any other group | Analysis was weakened by reliance on a questionnaire that did not seek to quantify ETS exposure and by the absence of laboratory confirmation of ETS exposure.63 participants were excluded due to data unavailability (37 of these were missing the mother’s smoking status and 47 had proven RSV), although the missing data were not statistically significant |
Stensballe 2006 Denmark [26] | Case–control study of 2564 cases and 12 816 controls from birth to 18 months | Any maternal smoking during pregnancy and lactation | RSV hospitalization | aOR, 1.35 (95% CI, 1.20–1.52); P < 0.001 | No significant bias concerns affecting the relationship of ETS and outcome |