Childhood Interstitial Lung Disease (chILD) Associated With Toxic Chemical Inhalation Exposures: A State-of-the-Art Review.

rationaleThe lung is uniquely positioned for chemical inhalation exposures considering its direct communication with the environment. Childhood interstitial lung diseases (chILD) syndrome is a rare and heterogeneous group of pediatric lung diseases. Despite common inhalation exposures, few studies have associated chemical inhalation exposures with chILD. The purpose of this review was to assess for chILD syndromes following toxic chemical inhalation exposures.

methodsPubMed and Embase databases were searched with the following inclusion criteria: (1) toxic chemical inhalation exposure, (2) pediatric subjects, and (3) chILD syndrome. Studies were excluded due to incorrect (1) study design, (2) patient population, and/or (3) outcome.

resultsTwo hundred and one studies were identified, of which 142 articles were retrieved, with 74 articles included after inclusion/exclusion criteria were applied by two independent reviewers. Most of the evidence stemmed from two pandemics: humidifier disinfectant associated lung disease (HD-ILD; n = 27) and e-cigarette, or vaping product associated, lung injury (EVALI; n = 45). Common signs and symptoms included cough, shortness of breath, hypoxemia, and inspiratory crackles. Common radiographic findings included centrilobular nodules and ground-glass opacities with subpleural sparing. Histopathologic features included airway-centric injury/inflammation with foamy macrophages, as well as subpleural sparing. Oxidized lipids were common plasma biomarkers associated with both HD-ILD and EVALI. Long-term pulmonary function testing suggests a restrictive phenotype in HD-ILD but variable phenotypes in EVALI.

conclusionsChILD syndromes secondary to toxic chemical inhalation exposures manifest with common radiographic and histopathologic findings of airway-centric disease with subpleural sparing. Long-term monitoring is under-reported in toxic chemical inhalation chILD syndromes but suggests persistent lung function impairment, especially after high-dose, repeated exposures. Additional monitoring, evaluation, and reporting of chILD syndromes secondary to chemical inhalation exposure are needed to better understand its complex pathogenesis and long-term lung function implications.