Новые методы лечения и международные регистры улучшают жизнь детей с редкими заболеваниями легких

BARCELONA, Spain — For children living with rare respiratory conditions, fighting a disease involves two battles. “The first is the physical illness,” said Natalia Maeva, patient representative from Bulgaria, at the European Respiratory Society (ERS) 2026 International Congress. “The second is living in a world where so few people can understand what you are suffering every day. Sometimes the second battle can be as difficult as the first.” From diagnostic delays to geographic disparities in access to specialized centers, young patients with rare, interstitial, and cystic lung diseases face severe challenges. However, emerging research into interorgan communication, innovative single-cell modeling, and expanding collaborative registries are improving the clinical landscape. Interorgan Communication While target therapies such as cystic fibrosis transmembrane conductance regulator CFTR modulators have improved CF management by stabilizing lung function, they have limited impact on extrapulmonary manifestations such as pancreatic insufficiency and CF-related liver disease. Organs or cells in an organ can send signals, including immune cells, inflammatory markers, danger signals, and hormones, that are received by other organs, explained Marcus Mall, MD, professor and director of the Department of Pediatric Respiratory Medicine at Charité – Universitätsmedizin Berlin in Berlin, Germany. “Studying these directions will be important to get a better mechanistic understanding of pathogenesis.” Epidemiologic data from the European Cystic Fibrosis Registry of over 14,000 patients reveals that severe pancreatic disease increases the risk for severe lung disease (forced expiratory volume in 1 second < 40%) to an extent similar to chronic Pseudomonas infection. Conversely, severe lung inflammation leads to systemic spillover of inflammatory cytokines (such as interleukin [IL] 1, IL-6, and TNF), inducing stress responses and fibrotic remodeling in distant organs. Using single-cell RNA sequencing and deeply phenotyped pediatric cohorts, such as the trajectories of CF disease cohort, Mall’s group demonstrated that highly expressing CFTR cells are depleted across tissues in CF, but effective CFTR modulator therapy restores these cell populations and dampens inflammatory cell-cell interactions in both the airway and gastrointestinal epithelia. Modeling Rare Diseases in the Lab To develop targeted therapies for rare fibrotic and cystic lung conditions, researchers must recreate complex human tissues in the laboratory. Stefan Marciniak, PhD, professor of respiratory cell biology at the University of Cambridge, Cambridge, England, shared how his laboratory develops three-dimensional (3D) embryonic organoid models and applies advanced clustered regularly interspaced short palindromic repeats (CRISPR) technologies to model monogenic lung diseases. “Standard 2D [two-dimensional] cell lines are very poor models of type 2 pneumocytes,” Marciniak explained. By culturing human embryonic organoids into 3D spheres, the cells form lamellar bodies — the defining intracellular structures that store and secrete pulmonary surfactant. Using base editing and CRISPR interference (CRISPRi), Marciniak’s team introduced patient-specific point mutations. In these mutated organoids, surfactant mislocalizes to the cell surface rather than remaining inside lamellar bodies, disrupting cellular polarity and providing a high-throughput platform for drug screening. Similarly, in Birt-Hogg-Dubé syndrome, a genetic cystic lung disease caused by mutations in folliculin, loss of folliculin leads to abnormal nuclear translocation of the transcription factor EB (TFEB), driving cystic changes and increasing long-term renal cancer risk. By knocking out folliculin in organoid models, researchers are running parallel drug and genetic screens to identify small molecules capable of retaining TFEB in the cytosol, aiming to prevent cystic progression and tumorigenesis. International Registries and Networks Because childhood interstitial lung diseases (chILD) are ultra-rare, with an estimated incidence of just four to eight cases per million children annually, single centers rarely see more than a handful of cases per year. To generate robust clinical evidence, cross-border collaboration has become indispensable. “Childhood interstitial lung disease is too rare and diverse for any single center to generate robust evidence,” said Honorata Marczak, MD, pediatric pulmonologist at the Department of Pediatric Pneumology and Allergy, Medical University of Warsaw in Warsaw, Poland. She said the European Management Platform for chILD now connects over 1400 patients and more than 100 collaborating centers across 30 countries, linking longitudinal registry data with shared biobanks. New Challenges As medical advancements allow children with rare genetic lung conditions to survive into adulthood, new clinical management challenges are emerging. “Predicted life expectancy is almost close to normal,” Mall said. “But some of the aging-related health problems we see are related to therapy, such as kidney dysfunction from long-term aminoglycoside use, obesity from modulators, or elevated rates of colon cancer.” Mall said that pediatricians must focus on initiating disease-modifying therapies as early as possible, including in infants and potentially in utero, to preserve organ function before irreversible structural damage occurs. Maeva, Mall, Marciniak, and Marczak reported no relevant financial conflicts of interest. Manuela Callari is a freelance science journalist specializing in human and planetary health. Her work has been published in The Medical Republic, Rare Disease Advisor, New Scientist,  The Guardian, MIT Technology Review, and others.