Idiopathic pulmonary fibrosis (IPF) remains a progressive and fatal disease despite major advances in antifibrotic therapy. Pirfenidone and nintedanib slow lung function decline, and the PDE4B inhibitor nerandomilast and treprostinil have recently shown promise as next-generation treatments. However, current therapies neither halt nor reverse disease progression, and tolerability issues often limit adherence. We compared the antifibrotic activity and plasma levels of nintedanib administered by either oral gavage or dietary supplementation in a rat model of pulmonary fibrosis. Male Sprague-Dawley rats received intratracheal bleomycin (1 U/kg) on days 0 and 4. From day 7 to day 28, animals were treated with nintedanib (100 mg/kg/day) by either oral gavage or medicated chow. Lung weight, fibrosis biomarkers (procollagen-I, metalloproteinase-7 or MMP7, WNT1-inducible signaling pathway protein or WISP-1), epithelial injury marker KL-6, target engagement biomarkers (Fibroblast Growth Factor 2 or FGF-2, Vascular Endothelial Growth Factor or VEGF), plasma drug levels, and histological fibrosis scores were evaluated. Both administration regimens significantly reduced procollagen-I, WISP-1 and KL-6, and histological fibrosis scores. Oral gavage produced approximately fourfold-higher peak plasma concentrations of nintedanib 30 min after dosing, whereas dietary administration resulted in lower, more stable plasma levels with reduced variability while resulting in comparable antifibrotic efficacy. In conclusion, nintedanib retained robust antifibrotic activity when administered via dietary supplementation despite lower, but continuous, active plasma concentrations. Collectively, these findings indicate that optimizing drug delivery and absorption kinetics may achieve sustained therapeutic efficacy while reducing unnecessary exposure to supratherapeutic concentrations, thereby potentially improving tolerability.

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is associated with substantial morbidity and mortality. Lung transplantation remains the definitive therapy for selected patients; however, severe pulmonary vascular dysfunction and hemodynamic instability may complicate transplant candidacy and pre-transplant management. The role of parenteral prostacyclin therapy as a bridge to transplantation in this population remains poorly defined. The primary objective of this retrospective case series was to evaluate the utility of parenteral treprostinil as a bridge therapy for lung transplantation in 14 patients with severe PH-ILD from 2018 to 2025. Secondary objectives were to describe subsequent changes in clinical outcomes, including hemodynamic parameters measured by right heart catheterization, echocardiographic findings, the six-minute walk distance, oxygen requirements, the need for veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and successful lung transplantation. Parenteral treprostinil was associated with significant improvements in pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and BNP levels, while pulmonary capillary wedge pressure, cardiac output, cardiac index, and oxygen requirements remained stable following therapy initiation. Echocardiography demonstrated improvement in right ventricular dilation and right ventricular dysfunction. Most patients were successfully bridged to lung transplantation, while only two patients died prior to transplantation. In selected patients with severe PH-ILD, parenteral treprostinil may improve pulmonary hemodynamics and facilitate a successful bridge to lung transplantation without worsening oxygenation.

Pediatric pulmonary arterial hypertension is a progressive vasculopathy with substantial early mortality. Subcutaneous treprostinil is an established prostacyclin-pathway therapy for higher-risk disease, but long-term pediatric data from Latin American referral centers remain limited. This retrospective cohort included all nine consecutive children with World Symposium on Pulmonary Hypertension Group 1 pulmonary arterial hypertension who initiated subcutaneous treprostinil at a Colombian referral center and were followed from diagnosis until death or last known contact. Outcomes included survival, pediatric risk category transitions, N-terminal pro-B-type natriuretic peptide levels, tricuspid annular plane systolic excursion, systolic pulmonary artery pressure, eccentricity index, and structured patient-/caregiver-reported domains. Exploratory comparisons were performed by maintenance dose (≤ 60 vs. > 60 ng/kg/min) and therapy duration. Kaplan-Meier survival at 1, 3, and 5 years was 88.9%, 55.6%, and 55.6%, respectively. Eccentricity index decreased from a median of 2.8 at diagnosis to 1.5 at 5 years, with paired comparisons showing reductions at 1 and 3 years. By Year 5, four of five children with paired risk data had transitioned to a lower pediatric risk category. Doses > 60 ng/kg/min were associated descriptively with more favorable final risk profiles, whereas structured patient-/caregiver-reported domains showed heterogeneous patterns; schooling was the only domain with a statistically detectable association by both dose and duration. In this small Latin American referral-center cohort, subcutaneous treprostinil treatment was accompanied by favorable risk transitions and stabilization of right ventricular geometry among long-term survivors. These findings are exploratory and should be interpreted in light of the small sample size, retrospective design, missing longitudinal data, and potential confounding by disease severity, survival, and treatment escalation.

Interstitial lung disease-associated pulmonary hypertension (ILD-PH) is a frequent and life-limiting complication of fibrotic lung disease, associated with substantial morbidity, impaired functional capacity, and significantly reduced survival. Under-recognition remains common due to overlapping symptoms with ILD, evolving hemodynamic definitions, and the limited accuracy of current noninvasive screening tools. ILD-PH prevalence varies widely across ILD subtypes, ranging from 3-15% in early disease to more than 60% in lung transplant candidates. Even modest elevations in mean pulmonary artery pressure are prognostically meaningful, while right ventricular dysfunction represents a key determinant of mortality. Pathophysiology reflects a complex interaction between parenchymal fibrosis, chronic hypoxemia, endothelial injury, and progressive pulmonary vascular remodeling. Diagnostic evaluation requires a multimodal approach, with right heart catheterization remaining essential for definitive confirmation. Historically, vasodilator therapies have shown limited benefit; however, inhaled treprostinil has demonstrated improvements in exercise capacity, biomarkers, and clinical worsening, establishing the first evidence-based treatment for ILD-PH. Additional inhaled and targeted agents are in development, and the role of combination therapy is an emerging area of investigation. Optimal management also includes supplemental oxygen, pulmonary rehabilitation, and timely evaluation for lung transplantation. ILD-PH represents a distinct vascular phenotype requiring early detection and tailored treatment strategies. Continued advances in screening algorithms, precision therapeutics, and mechanistic research are critical to transforming ILD-PH from a terminal complication into a modifiable component of the ILD spectrum.

Pulmonary arterial hypertension (PAH), a progressive disease, is characterized by increased pulmonary vascular resistance (PVR) and leads to right ventricular failure and premature death. PAH therapies aim to reduce PVR; however, these treatments as vasodilators may also result in reduced systemic vascular resistance and mean arterial pressure (MAP), leading to clinical or symptomatic hypotension. Low MAP can limit the administration of optimal dosage of PAH drugs. Midodrine, an oral alpha-1 adrenergic agonist, as a promising intervention, can potentially increase mean MAP and improve tolerance to PAH therapies.

Prostacyclin analogues are effective treatments in pulmonary arterial hypertension (PAH), especially in advanced stages. Treprostinil, a stable prostacyclin analogue, can be administered as subcutaneous and intravenous infusions, oral extended-release tablets and inhalation. Inhalation offers several advantages over other routes of administration, including direct access to the lungs for localized therapy, reduced infection risk, and a painless, convenient mode of delivery. However, small lipophilic molecules like treprostinil are absorbed into the bloodstream within minutes after inhalation, resulting in a short duration of action in the lungs and systemic side effects. To address these limitations, we developed a novel strategy involving a double treprostinil prodrug tailored for pulmonary delivery. The prodrug consists of treprostinil di-esterified at its carboxylic acid with a polyethylene glycol (PEG) chain, and at its C11 hydroxyl group with butyric acid. The prodrug exhibited sustained treprostinil release in bronchoalveolar lavage fluid and serum, supporting its suitability for pulmonary delivery. It was cleaved by initial hydrolysis of the PEG chain, followed by subsequent cleavage of the short-chain fatty acid. Ex vivo studies in isolated pulmonary artery rings showed a delayed and prolonged vasorelaxation effect of the conjugate compared to the free drug. In vivo studies demonstrated significant lung retention, with detectable quantities of the compound remaining in the lungs 24 h after administration, and a markedly reduced peak serum concentration following inhalation. This double-prodrug approach represents a promising strategy for improving PAH treatment by optimizing local, sustained treprostinil delivery while minimizing systemic exposure.

Pulmonary arterial hypertension (PAH) is a progressive illness that may require therapy with parenteral prostacyclin pathway agents (PPA) (epoprostenol and treprostinil). These parenteral PPA's are continuous ambulatory infusions that require a high level of skill and knowledge to maintain safety and effectiveness. Depending on the clinical context, transition to oral prostacyclin receptor agonist therapy (selexipag) is sometimes pursued. To prevent abrupt withdrawal from parenteral PPA's, overlap transitions are typically used. This report describes 35 inpatient, rapid transitions from parenteral PPA's to oral selexipag. Planned hospital admissions for transition were common (n = 27, 77%), and all patients successfully transitioned without a return to parenteral PPA's in the immediate post-transition period. Most patients transitioned due to difficulties with current parenteral PPA therapy (n = 20, 57%), followed by an improved clinical status on parenteral PPA therapy (n = 8, 23%). The median length of transition was 36 h (IQR 24-48 h) and hospital stay was 3 days (IQR 2-6 days). Following transition, the cohort demonstrated stability in PAH-specific risk scores and functional status. All patients survived to outpatient pulmonary hypertension follow up (median 5.5 weeks, IQR 1.4-9.6 weeks), and the majority were alive at 1-year post-transition (n = 32, 91%). Based on these results, we conclude that transition from parenteral PPA's to selexipag can be done in the inpatient setting safely, quickly, and effectively.

Pulmonary hypertension associated with idiopathic pulmonary fibrosis (PH-IPF) is a frequent and clinically relevant complication that worsens exercise capacity, quality of life, and survival. This narrative review summarizes the epidemiology, pathophysiology, diagnostic approach, and therapeutic landscape of PH-IPF. The development of PH in IPF reflects the combined effects of fibrotic parenchymal destruction, pulmonary vascular remodeling, hypoxic vasoconstriction, endothelial dysfunction, and altered vascular signaling. Diagnosis remains challenging because symptoms often overlap with those of advanced fibrotic lung disease and non-invasive tools have limited sensitivity; right heart catheterization remains the diagnostic gold standard. Antifibrotic agents are central to IPF management but have no established role as PH-targeted therapies. Most pulmonary arterial hypertension therapies have failed to show benefit in PH-IPF or have raised safety concerns, with ambrisentan and riociguat associated with harm. Inhaled treprostinil is currently the only approved therapy with randomized evidence of efficacy in PH associated with interstitial lung disease, including IPF. Supportive care, optimization of comorbidities, referral to expert centers, and timely lung transplantation evaluation remain essential components of management.