Risk Factors for Developing Adenovirus-Associated Post-Infectious Bronchiolitis Obliterans

Background: Risk factors for progression of adenovirus (AdV)-associated bronchiolitis (AdV-B) to post-infectious bronchiolitis obliterans (PIBO) are poorly defined. We aimed to investigate this in a multicenter cohort.

Methods: A multicenter hospital-based analysis included children admitted with AdV-B in Jerusalem during 2016-2022. A case-control analysis included AdV-PIBO patients in Jerusalem during 2005-2023. Cases were compared to randomly assigned controls admitted with AdV-B without progression to AdV-PIBO. Multivariate analysis with logistic regression was used.

Results: The annual incidence of AdV-B admissions and AdV-PIBO increased during 2016-2022, during which 1522 children were admitted with AdV-B and 8 developed AdV-PIBO (0.5%). Of 30 AdV-PIBO cases identified during 2005-2023, available data were compared for 25 of them (72% boys; mean age ± standard deviation 1.2 ± 0.8 years) and 139 controls (66% boys; mean age 1.0 ± 0.6 years, p = 0.5 for age). Jewish ethnicity was more common in the AdV-PIBO versus control group (92% vs. 66%, p = 0.009), as were oxygen supplementation (84% vs. 45%, p < 0.001), noninvasive ventilation (20% vs. 4%, p = 0.004), consolidations on chest X-ray (44% vs. 19%, p = 0.011), and lymphopenia (92% vs. 46%, p < 0.001). Combining Jewish ethnicity, lymphopenia, consolidations, and prolonged admission as independent risk factors yielded positive and negative predictive values of 68.8% and 90.5%, respectively.

Conclusion: These findings emphasize the urgent need for targeted preventive and management strategies. The identification of Jewish ethnicity as a risk factor may imply a genetic contribution to Adv-PIBO risk.