The main purpose of this study was clinical variables associated with severe bronchiolitis in children in tropical middle-income countries with bronchiolitis. Our study shows that RSV and parental smoking were independent predictors of severe bronchiolitis. While some predictors of severity, such as age, comorbidities, and maybe initial signs of respiratory distress, cannot be modified, others as RSV isolation and parental smoking are potentially modifiable by interventions such as futures vaccines or palivizumab in high-risk population or smoking cessation interventions in parents. Respect to the association between RSV and severity, previous studies in other populations had revealed the importance of RSV as a predictor of the severity of the disease. Dumas, et al analyzed data from two prospective, multicenter cohorts of children younger than 2 years hospitalized with bronchiolitis, one in the USA (2007–2010 winter seasons, n = 2207), and one in Finland (2008–2010 winter seasons, n = 408). Using latent class analysis, found that in the profiles with wheezing at ED presentation and profile with the most severely ill group with the longer hospital were associated with a higher probability of RSV infection in USA and Finland. (14). Rodriguez et al, in a retrospective cohort study of 6344 children with acute lower respiratory infection in Colombia, during 2 years (2009–2011), found that mixed RSV-adenovirus was a predictor of severe disease (RR 2.09; CI 95% 1.60–2.73; P < 0.001). DeVicenzo et al, in a sample of 141 infants < 24 months old without previous chronic cardiac or lung disease or prematurity, in Tennessee found that higher nasal RSV load was an independent predictor of longer hospitalization. A 1-log higher RSV load predicted a 0.8-da longer hospitalization, reflects the higher RSV load that occur earlier in the disease (15–17). Mansbasch et al, in a prospective cohort of 2207 infants of 16 US hospital without excluding patients previous chronic cardiac or lung disease or prematurity, also found that patients with RSV have a higher proportion of patient with severity and prolonged LOS (> 3 days) than patients with only HSV infection but less than RSV + HRV infection ( 48% vs 28% vs 54%, p < 0.001), and in the multivariate model presence of RSV + HRV was an independent predictor of length of stay > 3 days among children with severe bronchiolitis(18). Rodríguez-Martínez in 303 infants with acute bronchiolitis in Bogota, also found that RSV isolation correlated with a hospital stay of 5 or more days (OR 1.92, CI 95% 1.02 to 3.73)(19). The actual evidence supports a strong association between decreased cellular immunity and severe RSV bronchiolitis, suggesting that a maturation-related defect of the cellular immune system facilitates severe RSV. A low level of cellular and humoral immunity would explain that higher viral titers are found in infants with the most severe illness (20).
In our study, exposure to cigarette smoking was an independent risk factor associated with severe bronchiolitis. This result is consistent with those from previous studies that reported children’s exposure to maternal cigarette smoking increased the risk of hospitalization in infants and young children with bronchiolitis. Robledo-Aceves et al, in a retrospective study, in Mexico, included 134 children 2 years or younger with severe viral bronchiolitis, and 134 healthy age-matched. Its study report that exposure to cigarette smoking was independently associated with hospitalization for severe bronchiolitis in the multivariate analysis (OR, 3.5; 95% CI, 1.99–6.18; P = .0001). Bradley et al, in a prospective study of 206 hospitalized infants, all under 12 months old with bronchiolitis in Missouri, found that maternal smoking were independent predictors of reduced O2 Saturation (OR, 2.3; 95% CI, -0.05, − 4.66; P = .05)(21). Chatzimichael et at, in 40 consecutive infants with bronchiolitis aged from 6 to 24 months in Greece, found using a multivariate regression analysis that exposure to environmental tobacco smoke (OR = 2.2, 95% CI = 1.1–3.6) showed significant association with severe bronchiolitis and prolonged hospitalization (22). Farzana et al, in Farzana in a case-control study of 128 infants with bronchiolitis ( 64 cases and 64 controls) found that parental smoking carried 2.8 times the risk of developing severe bronchiolitis ( OR 2.8,95% CI 1.36 t-5.72). Cigarette smoke exposure decreased cyclic adenosine monophosphate levels and increased phosphodiesterase-4 enzymatic activity, resulting in increased airway hyperresponsiveness, which may explain the potential mechanism by which smoke exposure decreases lung function and severe bronchiolitis (23).
Limitations.
Our study has limitations. First, since this study was based on medical records review, we cannot include other variables such as environmental pollution and genetic factors, and residual confounding cannot be excluded. Second, the study was conducted in a tertiary referral hospital, and therefore the patients included represent the high spectrum of severity, limiting the generalization of results to other contexts. However, the similarity of our population in terms of clinical characteristics, risk factors, and seasonality of bronchiolitis in our country with previous reports suggest strength and consistency in our results(5, 19). Third, in our study, we used an immunofluorescence assay for the diagnosis of RSV infections that, despite being widely available, being easy to perform, but we did not determine the RSV genomic load, and also we did not test for viruses. This can generate some differential misclassification bias, which could have overestimated the true association between RSV isolation and the outcome variable, however, the previous evidence in other populations had confirmed this association being plausibility our results.