Shenar Dinkha

Bronchiolitis obliterans syndrome (BOS) is a pulmonary manifestation of chronic graft-versus-host disease (GVHD) that can occur as a complication in up to 14% of hematopoietic stem cell transplantation (HSCT) recipients. First-line therapy for BOS includes inhaled fluticasone, azithromycin, and montelukast (FAM) in combination with systemic corticosteroids, with or without additional immunosuppressive agents. Although ruxolitinib is a promising second-line therapy for GVHD, pulmonary involvement remains difficult to treat. We describe a 24-year-old male with a history of B-cell acute lymphoblastic leukemia (B-ALL) who underwent HSCT and developed skin, oral mucosa, and upper gastrointestinal GVHD. After nine months of treatment with corticosteroid therapy and ruxolitinib, he developed dyspnea, hypoxia, and cough. Pulmonary function testing showed severe obstruction, leading to a diagnosis of BOS. Progressive disease occurred despite treatment with first- and second-line therapies. FAM therapy was continued, and sirolimus was added as an adjunct therapy with ruxolitinib as a third-line therapy, which resulted in improvement in radiologic and clinical parameters such as pulmonary function testing (PFT). This case highlights the use of adjunctive sirolimus with ruxolitinib as a potential third-line treatment option for steroid-refractory and ruxolitinib-refractory BOS associated with GVHD.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant extra-articular manifestation of rheumatoid arthritis that contributes to morbidity, functional limitation, exertional dyspnea, fatigue and reduced quality of life. Current pharmacologic therapies address inflammatory and fibrotic pathways but do not target deconditioning, ventilatory inefficiency, skeletal muscle dysfunction or the high burden of anxiety, depression, impaired emotional well-being and reduced daily functioning. Objective: To synthesize the evidence supporting the use of structured exercise and pulmonary rehabilitation (PR) on functional, psychological and quality of life outcomes in RA-ILD patients by integrating findings from RA-ILD cohorts, interstitial lung disease (ILD) PR trials, and rheumatoid arthritis (RA) exercise interventions. Methods: A structured narrative review was conducted using PubMed, Scopus, and Web of Science (1990–2025). Of the 1240 identified records, 32 studies met inclusion criteria, comprising 4 RA-ILD observational cohorts, 17 ILD PR trials and 11 RA exercise trials. No randomized controlled trials specifically evaluating PR in RA-ILD were identified. Available evidence was extrapolated from studies in general ILD and RA populations. Mechanistic and physiological literature was included to contextualize findings. Results: RA and ILD cohorts demonstrated markedly reduced six-minute walk distance, impaired diffusing capacity, exertional desaturation, fatigue, high anxiety and depression, and diminished daily function. Across seventeen PR trials, patients with idiopathic, autoimmune-associated, and fibrotic ILD showed improvements in exercise capacity, ventilatory efficiency, dyspnea, fatigue, psychological distress, emotional well-being, and health-related quality of life. Eleven RA exercise studies demonstrated improved aerobic capacity, strength, lean mass, fatigue, psychological outcomes (including anxiety), and function, with no increase in disease activity. Conclusions: Evidence from ILD PR and RA exercise literature suggest that structured rehabilitation has the potential, alongside pharmacological therapy, to address functional limitation, dyspnea, fatigue and psychological distress and overall quality of life in RA-ILD, though disease-specific trials are needed.