A year of research emphasizes the significance of collaboration, standardized approaches, and targeted therapies in rare pulmonary diseases.
This article was originally published at HCP Live. It has been lightly edited.
Exciting advances in childhood interstitial lung disease (chILD) research exhibit the importance of collaboration, standardized approaches, and targeted therapies for improved outcomes. Simultaneously, studies focusing on non–cystic fibrosis (CF) bronchiectasis and primary ciliary dyskinesia (PCD) contribute to better understanding and management of these conditions.
The research review led by Andrew Barber, MD, Department of Pediatrics, Virginia Commonwealth University, and investigators, further states the progress in these fields highlights the ongoing commitment to enhancing knowledge and care for pediatric lung diseases.1
chILD is a group of rare disorders characterized by diffuse radiographic changes and impaired gas exchange. Despite advances, chILD remains challenging due to its rarity and heterogeneity, and clinicians' limited understanding of disease mechanisms. Collaboration and standardization are crucial for further progress in this dynamic field.2
The research letter emphasizes the significance of collaboration among clinicians and investigators in the study of chILD. Clinical and research networks in North America, Europe, and Australia/New Zealand have worked together to define conditions and approaches to diagnosis and treatment.
The InPedILD trial serves as a hallmark example, involving 64 sites in 23 countries.
Studies focusing on specific chILD disorders shed light on mechanisms and potential treatments. In one, investigators focused on Rubinstein-Taybi syndrome (RTS) and its pathogenicity. Other investigations explored known disorders like ABCA3 deficiency, neuroendocrine hyperplasia of infancy (NEHI), and e-cigarette or vaping use-associated lung injury, seeking biomarkers and disease insights.
According to the review, gistopathologic diagnosis is denoted as crucial when imaging and genetic testing alone cannot suffice. Innovative techniques like transbronchial cryobiopsy offers potential alternatives for obtaining diagnostic lung tissue specimens.
As understanding of rare diseases improves, targeted therapies gain prominence, reducing reliance on nonspecific anti-inflammatory medications. A personalized approach holds promise for better patient outcomes, the review authors explained.
The research on RTS revealed its genetic basis, caused by alterations in the CREBBP or EP300 gene. The syndrome is characterized by specific facial features, broad thumbs and toes, short stature, and intellectual disability.
Bradford et al conducted a study involving 3 patients with RTS, all showing CT images with consolidated densities overlying ground glass opacities. Lung histopathology revealed proteinaceous material accumulation, fibrosis, and increased alveolar macrophages. Immunofluorescent staining suggested disruptions in surfactant metabolism or persistent myofibroblast activation as potential mechanisms.
Additional studies improved the understanding of known disorders. The heterogeneity of lung disease due to ABCA3 deficiency was explored by correlating genotypes with RNA expression in lung specimens. NEHI, an idiopathic form of chILD, was studied in a mouse model that demonstrated the involvement of excess neuropeptides from pulmonary neuroendocrine cells, suggesting a therapeutic potential.
Evaluations of biomarkers in chILD, such as elevated TARC/CCL17 levels, offer opportunities for diagnosis and monitoring. Cryobiopsy proves to be a valuable diagnostic tool in chILD, providing larger tissue samples for analysis, according to the review.
Advancements in targeted therapies are exemplified by cases of primary immune regulatory disorders treated with specific approaches, rather than nonspecific anti-inflammatory medications. Other studies investigate lung injury associated with e-cigarettes and develop a classification system for airway casts in plastic bronchitis, facilitating treatment decisions.
Finally, the landmark InPedILD trial evaluated nintedanib in pediatric lung fibrosis, providing critical dosing and safety data and setting a precedent for large-scale clinical trials in chILD patients.
Studies focusing on non-CF bronchiectasis and PCD contributed to better management and diagnosis of related conditions in 2022: