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Published on: May 13, 2020
Childhood Interstitial Lung Disease (chILD) Associated With Toxic Chemical Inhalation Exposures: A State-of-the-Art
William Hadley1,2, Robin Lacagnina1, Irfan Rahman2
1Department of Pediatrics, Division of Pediatric Pulmonology, University of Rochester Medical Center, Rochester, New York, USA.
Insights
Toxic chemical inhalation can cause childhood interstitial lung diseases (chILD) with common airway-centric injury patterns. Long-term lung function impairment is suggested, necessitating further research.
Area of Science:
- Pediatric Pulmonology
- Environmental Health
- Toxicology
Background:
- The lungs' direct environmental exposure makes them vulnerable to inhaled toxins.
- Childhood interstitial lung diseases (chILD) are rare, heterogeneous pediatric lung conditions.
- Few studies link chemical inhalation to chILD, highlighting a knowledge gap.
Purpose of the Study:
- To review and assess childhood interstitial lung diseases (chILD) syndromes resulting from toxic chemical inhalation exposures.
- To identify common clinical, radiographic, and histopathologic features of toxic inhalation-induced chILD.
- To evaluate the long-term pulmonary function implications of these exposures.
Main Methods:
- Searched PubMed and Embase databases for studies on toxic chemical inhalation, pediatric subjects, and chILD.
- Applied inclusion/exclusion criteria to 201 identified studies, ultimately including 74.
- Two independent reviewers applied the criteria to ensure study selection accuracy.
Main Results:
- The review focused on humidifier disinfectant-associated lung disease (HD-ILD) and e-cigarette, or vaping product associated, lung injury (EVALI).
- Common symptoms included cough, shortness of breath, and hypoxemia; radiographic findings showed centrilobular nodules and ground-glass opacities with subpleural sparing.
- Histopathology revealed airway-centric injury with foamy macrophages and subpleural sparing; oxidized lipids were identified as biomarkers.
Conclusions:
- chILD syndromes from toxic inhalation share common airway-centric radiographic and histopathologic features.
- Persistent lung function impairment is suggested, particularly after high-dose or repeated exposures.
- Further monitoring and reporting are crucial for understanding pathogenesis and long-term effects of toxic inhalation-induced chILD.
Rationale:
The 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.
Methods:
PubMed 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.
Results:
Two 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.
Conclusions:
ChILD 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.
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