Mesenchymal stem cells (MSCs), a type of pluripotent stem cells, exhibit remarkable therapeutic properties in the treatment of various diseases. Recent findings on the development of respiratory illnesses indicate that local MSCs might transform into myofibroblasts, thereby resulting in the emergence of respiratory disorders. Nonetheless, both preclinical and clinical studies on autologous or allogeneic MSC infusion reveal that MSCs can mitigate the onset of respiratory disease by controlling inflammation, restoring impaired tissues, modifying the ECM, and regulating stress-induced cell death after implantation. Furthermore, a variety of animal models have been created to explore the underlying mechanisms of various respiratory illnesses and assess the early-stage efficacy of MSC treatment in these conditions. In summary, the article examines the divergent functions of MSCs in respiratory illnesses and summarizes current perspectives on their therapeutic mechanisms in these diseases.

[This corrects the article DOI: 10.1002/pul2.70317.].

Treprostinil palmitil (TP) inhalation powder (TPIP), an investigational formulation of the treprostinil prodrug TP, was designed to provide prolonged pulmonary vasodilation with once-daily administration. In this phase 2 study (NCT05176951), adults with pulmonary hypertension associated with interstitial lung disease (PH-ILD) were randomized 3:1 to receive TPIP (n = 29) or placebo (n = 10) for 16 weeks. TPIP was up-titrated from 80 µg to each patient's maximum tolerated dose (≤ 640 µg). Study endpoints were safety and tolerability (primary); pharmacokinetics of TP and treprostinil (secondary); and clinical worsening, change from baseline in 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (exploratory). Maximum TPIP dose (640 µg) once daily was achieved by 79.3% of patients. TPIP was well tolerated in this study, with a safety profile generally consistent with previously reported route-specific treatment-emergent adverse events (TEAEs) of inhaled treprostinil, such as cough and dyspnea. TEAEs occurred in 93.1% and 90.0% of patients on TPIP and placebo, respectively. Most TEAEs were mild or moderate in both groups. In patients on TPIP and placebo, TEAEs leading to treatment discontinuation occurred in 4 (13.8%) and 3 (30.0%) patients, respectively, and serious AEs occurred in 6 (20.7%) and 4 (40.0%) patients, respectively. Following the 640 µg TPIP dose, the treprostinil elimination half-life was 7.1 h. In TPIP and placebo groups, clinical worsening was observed in 3 (10.3%) and 5 (50.0%) patients, respectively. Trends for improvement were observed in 6MWD and NT-proBNP with TPIP treatment. These results suggest that TPIP may be a suitable once-daily treatment for PH-ILD.

Bronchopulmonary dysplasia (BPD) is characterized by impaired lung development and persistent respiratory morbidity. BPD comprises three primary phenotypes: parenchymal, airway, and pulmonary vascular disease. Parenchymal disease involves disrupted alveolar growth, emphysema, hyperinflation, inflammation, and fibrosis, leading to impaired gas exchange. Airway disease, including airway malacia and subglottic stenosis, causes airflow obstruction and increased work of breathing. Pulmonary vascular disease involves abnormal vascular remodeling and increased pulmonary vascular resistance, which contributes to the development of pulmonary hypertension. Imaging plays a central role in evaluating these phenotypes which may occur independently or overlap with other phenotypes. Advanced MRI techniques enable non-invasive assessment of lung structure, ventilation, perfusion, airway shape and dynamics, vascular remodeling, and ventricular morphology and function. Imaging-based phenotyping can enhance disease monitoring, risk stratification, and help to inform personalized management strategies in infants with BPD.