Discussion
Identifying the factors increasing the risk of development of severe bronchiolitis in patients without chronic disease is important in terms of standardizing the frequency of follow-ups of bronchiolitis patients and hospitalization indications, and the decision to intervene early in at-risk patients. The purpose of the present study was to determine individual, familial, and environmental predictive risk factors for the development of severe bronchiolitis in healthy-appearing cases of acute bronchiolitis with no previous history of chronic disease.
In a study of children with bronchiolitis requiring mechanical ventilation, Mansbach et al.6 found that 61% of cases assessed as severe bronchiolitis and given respiratory support with CPAP or intubation were boys, and 39% were girls. Robledo-Aceves et al.3 investigated risk factors for severe bronchiolitis in the emergency department and observed that 60.5% of severe bronchiolitis cases were boys. Similarly in the present study, boys constituted 60% of the cases valuated as severe bronchiolitis, and girls 40%, no statistically significant difference being observed with the mild-moderate patient group.
Robledo-Aceves et al.3 reported a mean age of 6.60 months in their cases of severe bronchiolitis, but observed no significant difference compared to the control group. Mansbach et al.6 a significantly higher mechanical ventilation requirement in the first six months, and especially in patients younger than two months, compared to the control group. In their study of risk factors for respiratory decompensation, Dadlez et al.8reported a mean age of 4.2 months in a group developing respiratory failure and 7.2 months in a group with no respiratory failure, the difference being statistically significant. They authors also identified age less than six months as a significant predictor of respiratory decompensation. In the present study, the mean age of the cases with severe bronchiolitis was 6.50 months, and that of the mild-moderate bronchiolitis cases was 6.07, the difference not being statistically significant.
Dadlez et al.8 determined no statistically significant difference in weight-for-age z-scores between groups developing and not developing respiratory failure. Weight-for-age z-scores of -0.87 in cases of severe bronchiolitis and -0.30 in mild-moderate cases were determined in the present study (p<0.001). In addition, multivariate logistic regression analysis identified a low weight-for-age z-score as an independent predictor of development of severe bronchiolitis, increasing the risk of development 0.56-fold.
In a study of the severity of respiratory syncytial virus (RSV) infection and breastfeeding, Nishimura et al.9determined a more severe clinical course among non-breastfed young infants, and reported that breastfeeding exhibited a protective effect. Mansbach et al.6 determined a history of breastfeeding in 57% of cases of severe bronchiolitis and in 61% of a control group, although the difference was not statistically significant. Similarly in the present study, a history of breastfeeding only was present in 74.1% of cases in the severe bronchiolitis group, and in 75.2% of the mild-moderate group, the difference also not being statistically significant.
Semple et al.10 reported a mean gestation time of 35.8 weeks in cases requiring mechanical ventilation support compared to 38 weeks in a control group, the difference being statistically significant. Coşkun et al.11 investigated risk factors for intensive care requirements among children with bronchiolitis and determined a mean gestation period of 37.9 weeks in a group followed-up in intensive care and of 38.2 weeks in a control group, the difference not being significant. Mean gestation in the severe bronchiolitis group in the present study was 38.2 weeks, compared to 38.3 weeks in the mild-moderate bronchiolitis group. The difference was not significant (p=0.602).
Mansbach et al.6 reported a previous history of bronchiolitis attacks in 19% of severe bronchiolitis cases and in 23% of a control group, the difference not being significant. In the present study, a previous history of bronchiolitis attacks was observed in 36.5% of severe bronchiolitis cases, significantly higher than in mild-moderate cases at 27.1% (p=0.004). At multivariate logistic regression analysis, a history of frequent previous bronchiolitis attacks emerged as an independent predictor of severe bronchiolitis development, increasing the risk 1.84-fold.
Mansbach et al.6 reported no significant difference in familial history of asthma, being observed in 32% of a severe bronchiolitis group and 31% of a control group. A family history of asthma was determined in 9.5% of the severe bronchiolitis group and 11.6% of the mild-moderate bronchiolitis group, and the difference was not significant (p=0.240).
Hasegawa et al.12 investigated risk factors necessitating intensive care are reported exposure to cigarette smoke in 17% of patients transferred to intensive care due to clinical worsening and in 13% of a control group. The difference was not significant. Mansbach et al.6 reported exposure to cigarette smoke in 11% of a group with severe bronchiolitis and in 13% of a control group. The difference was significant. Robledo-Aceves et al.3 described exposure to cigarette smoke as a single independent risk factor associated with severe bronchiolitis. In the present study, rates of exposure to cigarette smoke associated with active maternal smoking were 20% in the severe bronchiolitis group and 11.3% in the mild-moderate group, and the difference was statistically significant (p=0.046). However, exposure to cigarette smoke was not identified as an independent predictor of severe bronchiolitis development at multivariate logistic regression analysis.
Mansbach et al.6 reported an independent association between maternal smoking during pregnancy and severe bronchiolitis requiring CPAP and/or intubation. Robledo-Aceves et al.3 determined smoking during pregnancy in 7.5% of the severe bronchiolitis group and 6.7% of the mild-moderate group, the difference being insignificant. Rates of maternal smoking during pregnancy in the present study were 16.5% in the severe bronchiolitis group and 9% in the mild-moderate group. The difference was also not significant (p=0.050).
Coşkun et al.11 reported a higher number of siblings among a group followed-up in intensive care compared to a control group, although the difference was not significant. In the present study, 12.9% of severe bronchiolitis cases and 26.5% of mild-moderate cases were only children (p=0.010). However, this did not emerge as an independent predictor of severe bronchiolitis development. Robledo-Aceves et al.3 reported that 71.6% of a severe bronchiolitis group and 42.5% of a control group lived in crowded conditions, and that this was linked to severe bronchiolitis. The number of members of the household in the present study was higher in the severe bronchiolitis group than in the mild-moderate group (p=0.011). However, this did not emerge as an independent predictor of severe bronchiolitis at multivariate logistic regression analysis.
Mansbach et al.6 reported a significantly higher rate of reduced feeding in the severe bronchiolitis group, at 63%, compared to 41% in the control group. They also reported an independent association between reduced feeding and severe bronchiolitis requiring mechanical ventilation. Rates of oral feeding in the present study were 76.5% in the severe bronchiolitis cases and 62% in the mild-moderate bronchiolitis cases (p=0.016). However, this did not emerge as an independent predictor of severe bronchiolitis at multivariate logistic regression analysis.
Semple et al.10 reported times between onset of symptoms and admission to hospital of 3.1 days in a group developing respiratory insufficiency receiving mechanical ventilation support, of 3.6 days in a group given oxygen support only, and of 4.2 days in a group not given oxygen support, although the difference was not statistically significant. DeVincenzo et al.13reported an approximate time of four days between onset of symptoms and admission, but did not evaluate this as significant in terms of intensive care requirement and respiratory insufficiency. The relevant findings in the present study were 4.04 days in the severe bronchiolitis group and 4.90 days in the mild-moderate bronchiolitis group (p=0.017). A short time between onset of symptoms and admission was identified as an independent predictive parameter in the development of severe bronchiolitis, increasing the risk of severe bronchiolitis 0.62-fold.
Hasegawa et al.12 reported similar onset durations of respiratory difficulty, one of the findings of clinical worsening, between a group requiring intensive care and another with no such requirement. In Mansbach et al.’s study6, 39% of severe bronchiolitis cases experienced respiratory difficulty for less than one day before presentation, compared to 26% of the control group, and an independent association was determined with mechanical ventilation requirement. In the present study, the time elapsing between onset of symptoms and worsening of findings was 2.78 days in the sever bronchiolitis group and 4.29 days in the mild-moderate group (p<0.001). However, this did not emerge as an independent predictive parameter in the development of severe bronchiolitis at multivariate logistic regression analysis.
Tourniaire et al.14 investigated whether Hb concentrations were a factor in clinical worsening, and reported mean Hb values of 11.1 g/dL in a group with severe bronchiolitis and 12 g/dL in a control group, the difference being statistically significant. They also determined that cases Hb values lower than 10 g/dL resulted in long-term respiratory support requirements. Mean Hb values in the present study were 10.83 g/dL in the severe bronchiolitis group and 11.19 g/dL in the mild-moderate group (p=0.021). Low Hb values also emerged as an independent predictive parameter in severe bronchiolitis development at logistic regression analysis, increasing the risk of severe bronchiolitis 0.72-fold. We think that low Hb may result in worsening of the manifestation in bronchiolitis patients by reducing oxygen transport capacity.
In conclusion, we observed a higher risk of severe bronchiolitis development in individuals with a low weight-for-age z-score, with a short time elapsing between onset of symptoms and admission, with a larger number of previous attacks, and with low hemoglobin. We think that consideration and identification of these risk factors will serve as a guide to clinicians in the early determination of cases of severe bronchiolitis.