Risk Factors for Post-infectious Bronchiolitis Obliterans in Children: A Systematic Review and Meta-Analysis

Abstract

BackgroundPost-infectious bronchiolitis obliterans (PIBO) is a long-term sequela after an initial insult to the lower respiratory tract. A comprehensive understanding of the factors that contribute to a high risk of developing PIBO is important to help define therapeutic strategies and improve prognosis.MethodsWe performed a systematic review of published literature available in the online databases including PubMed, Embase, Web of Science, CNKI, Wan Fang, and VIP, with the last search updated on 27 January 2022. Observational studies and case-control studies that provide sufficient data to examine associations between potential risk factors and PIBO were included. Pooled odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) and heterogeneity were calculated.ResultsA total of 14 risk factors were selected from 9 studies included in the analysis. The strongest risk factors were hypoxemia, mechanical ventilation, tachypnea, and wheezing. Hypoxemia conferred the greatest risk with pooled OR of 21.54 (95% CI: 10–46.36, p < 0.001). Mechanical ventilation ranked second (pooled OR 14.61, 95% CI: 7.53–28.35, p < 0.001). Use of γ-globulin, use of glucocorticoids, co-infection of bacteria, a history of wheezing, and being male were other prominent risk factors. The effects of premature birth, allergic rhinitis, and imaging finding (pulmonary consolidation, atelectasis, pleural effusion) are less clear and require further confirmation. Cases that developing PIBO had a lower age compared with controls (MD, −8.76 months, 95% CI: −16.50 to −1.02, p = 0.03). No significant differences were observed in the duration of fever (MD, 1.74 days, 95% CI: −0.07 to 3.54, p = 0.06). Children diagnosed with PIBO had higher LDH levels (MD, 264.69 U/L, 95% CI: 67.43 to 461.74, p = 0.008) and duration of hospitalization (MD, 4.50 days, 95% CI: 2.63 to 6.37, p < 0.001).ConclusionIn this study, we found that the strongest risk factors for PIBO were hypoxemia, mechanical ventilation, tachypnea, and wheezing. Use of glucocorticoids, γ-globulin, co-infection of bacteria, a history of wheezing, and being male may also play a role. The factors discussed above can inform the generation of a clinical prediction model for the developing PIBO in children.

A Diagnostic Nomogram for Early Prediction of Post-Infectious Bronchiolitis Obliterans in Severe Pneumonia

“…Li et al 19 found that inpatient days indicated a statistically significant difference between the PIBO and non-PIBO group, and the mean length of hospital stay was 16.3±10.6 days in children with PIBO compared with 10.9±8.2 days in the non-PIBO group. This is similar to our findings, which showed that the mean length of hospital stay was 15 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) days in the PIBO group compared to 10 (7-13) days in the non-PIBO group.…”

“…Our results showed that age was a risk factor for predicting PIBO; hence, children tended to develop PIBO at a lower age. A meta-analysis by Liu et al 16 showed that compared with older children, younger children were more likely to develop PIBO, and most PIBO patients were younger than 3 years. Huang found that the average age at PIBO diagnosis was 17.71 (7-91) months.…”

Worldwide Bronchiolitis obliterans research: A bibliometric analysis of the published literature between 2002 and 2022

“…In contrast, glucocorticoids, gamma globulin, bacterial co-infection, and a history of wheezing and male are also considered to be among the contributing factors. [ 50 ] Lactatedehydrogenase levels, pleural effusion, hypoxemia, gender, and mechanical ventilation have been noted as risk factors for PIBO in Korean patients. [ 51 ] Persistent wheezing and acute respiratory failure in Chinese children with adenovirus pneumonia is an independent risk factor for PIBO.…”

Human bocavirus respiratory infection: Tracing the path from viral replication and virus‐cell interactions to diagnostic methods

“…No reports of serious short-term complications, such as postinfectious chronic lung disease, have been documented in severe cases of HBoV1 ALRI, in contrast to adenovirus, influenza and Bordetella pertussis. 70,71 However, the association between HBoV1 and medium or long-term recurrence of wheezing remains unknown.…”