Lung biopsy strategies for childhood interstitial lung disease: Indications and techniques

Childhood interstitial lung disease comprises a heterogeneous group of rare disorders where diffuse parenchymal involvement can cause chronic respiratory morbidity, pulmonary hypertension and death. Although advances in high-resolution computed tomography, immunological workup and genetic testing have improved diagnostic precision, many children remain undiagnosed after comprehensive non-invasive evaluation, and the role, timing and technique of lung biopsy remain challenging. First, this narrative review summarizes the timing for performing tissue diagnosis in childhood interstitial lung disease, emphasizing the concept of incremental value; histology is most useful when it is expected to identify a treatable disease, distinguish inflammatory- from fibrosis-predominant patterns or resolve major diagnostic conflicts after multidisciplinary team discussion. Second, we compared surgical lung biopsy, transbronchial lung biopsy and transbronchial lung cryobiopsy in terms of specimen architecture, diagnostic yield, complication profile and pediatric-specific limitations and outline key histopathological and immunopathological patterns that influence decisions regarding the use of immunosuppressive or targeted therapy, supportive care and timing of transplant referral. Finally, we propose a pragmatic multidisciplinary team-based framework that integrates disease severity, imaging distribution and center expertise to individualize the decision regarding biopsy and choice of technique. Surgical lung biopsy remains the reference standard for most cases of undifferentiated childhood interstitial lung disease, whereas transbronchial lung cryobiopsy may serve as a minimally invasive alternative in carefully selected older children at experienced centers. Future priorities include multicentre collaboration, standardized pediatric biopsy protocols and integration of histology with imaging, genetics and digital/multi-omics approaches to refine prognostic stratification and guide precision treatment.