Noninfectious Severe Pulmonary Complications in Immunocompromised Critically Ill Patients

Noninfectious pulmonary complications are a significant cause of morbidity and mortality in immunocompromised patients, particularly in those undergoing hematopoietic stem cell transplantation, solid organ transplantation, chemotherapy, or immunotherapy. These syndromes often mimic infections, leading to delayed diagnosis and inappropriate treatment. Acute complications include peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, drug-induced lung injury, immune checkpoint inhibitor-related pneumonitis, and radiation pneumonitis, while late or chronic complications, such as organizing pneumonia, interstitial lung disease, bronchiolitis obliterans syndrome, and chronic graft-versus-host disease-related lung involvement, typically develop months to years after therapy. Accurate and timely diagnosis is essential, relying on high-resolution CT, bronchoalveolar lavage, and, in selected cases, lung biopsy to differentiate these conditions from infections. Current treatments remain largely empirical, focusing on corticosteroids, supportive intensive care, and immunosuppressive adjustment, although novel strategies, including inhaled hemostatic agents and JAK inhibitors, are emerging. Despite advances in supportive management, late-onset complications remain associated with poor long-term functional outcomes. Future directions include the development of biomarkers, artificial intelligence-assisted radiological tools, and multicenter registries to improve classification, risk stratification, and treatment. In this narrative review, we highlight current evidence around noninfectious pulmonary complications in the critical care setting, diagnosis, and treatment.