Search Results (35)

Inhaled Treprostinil is the primary treatment of pulmonary hypertension related to interstitial lung disease (PH-ILD). Despite treatment effectiveness in clinical trials, the real-world safety and tolerability of this therapy remains unclear. We conducted a multicenter, retrospective review of adults with PH-ILD who were prescribed inhaled treprostinil. We assessed clinical outcomes, 6 min walk distance (6MWD) and changes in natriuretic peptides (BNP, NT-proBNP), as well as medication tolerance. Eighty-three patients met the inclusion criteria. The 6MWD data was collected but a limited number of patients had results within close proximity to initiation of inhalational treprostinil with only seven patients having assessments within the 3 months prior to initiation as well as 3 months post therapy. Limited 6MWD data is likely due, in part, to coinciding with the COVID pandemic, limiting face-to-face interactions and exercise testing. The majority of our subjects, 63%, had an absolute improvement in their BNP level, over a mean duration of 170 days. However, no significant difference was detected between baseline and follow-up natriuretic peptide levels. Adherence was assessed and the majority (77%) of patients remained on therapy at the time of censoring, with three-quarters (75%) meeting the target dose. Of the 15 patients intolerant to nebulized treprostinil who were transitioned to a dry powder inhaler, the majority (87%) were able to tolerate the other formulation. The medication was well-tolerated with a large percentage of patients remaining on therapy indefinitely and reaching the targeted therapeutic dose. Full article

Background/Objectives: Individual and increasing numbers of comorbidities have been associated with worse outcomes in patients with fibrotic interstitial lung disease (f-ILD). The association and impact of medical comorbidities on patient-reported outcome measures (PROMs) in f-ILD have yet to be reported. Methods: Analysis was conducted using data from a single-center prospective cohort involving 199 patients with f-ILD. All f-ILD diagnoses and severities were screened and enrolled over a three-year study period. Baseline demographics, pulmonary function test (PFT) measures, and survival status were collected. PROMs, including the Chronic Respiratory Questionnaire (CRQ) and the Self-Management Ability Scale (SMAS-30), were assessed at baseline and serially. Thirteen medical comorbidities were evaluated for their prevalence and impact on PROMs and all-cause mortality. Results: Mean age was 69 years, with a female-to-male ratio of 61% vs. 39%. Dyslipidemia (74%) and gastroesophageal reflux disease (GERD) (71%) were the most prevalent comorbidities. Hypertension, diabetes, GERD, pulmonary hypertension (PH), depression, congestive heart failure (CHF), and obstructive sleep apnea (OSA), were independently associated with lower PROM scores along with increasing numbers of concomitant comorbidities. Increasing numbers of comorbidities, as well as specifically diabetes, PH, hypertension, CHF, and OSA, were associated with greater all-cause mortality. Conclusions: Medical comorbidities may independently impact respiratory-related PROMs in patients with f-ILD. These findings highlight the importance of comprehensive comorbidity management in improving quality of life and survival outcomes in patients with f-ILD. Full article

Background and Objectives: Usual interstitial pneumonia (UIP) is associated with progressive fibrosing interstitial lung diseases (PF-ILD) and poor survival in patients with fibrosing interstitial lung disease (FILD). We aimed to investigate the predictors of PF-ILD and survival in patients with FILD-UIP. Materials and Methods: This retrospective study was conducted at a single, tertiary hospital in China. Patients underwent routine follow-up visits every 3 to 6 months according to standard operating procedures (SOPs). Patients with FILD-UIP were further stratified using the proposed PF-ILD criteria. Results: This retrospective study enrolled 150 patients with FILD-UIP between October 2020 and June 2025, with 117 patients completing follow-up for more than 12 months. FILD-UIP was categorized as idiopathic pulmonary fibrosis (IPF) (n = 67) and non-IPF-UIP (n = 50), which included connective tissue disease-associated UIP (n = 29), hypersensitivity pneumonitis-associated UIP (n = 7), and interstitial pneumonia with autoimmune features-associated UIP (n = 14). During the follow-up period, 32 (47.8%) patients with IPF and 19 (38.0%) non-IPF-UIP experienced PF-ILD. Pulmonary hypertension (PH) and predicted percentage of forced vital capacity (FVC%pred) were dependent risk factors for PF-ILD in patients with FILD-UIP, non-IPF-UIP, and IPF. King’s Brief Interstitial Lung Disease (KBILD) is a dependent risk factor for PF-ILD in patients with FILD-UIP and IPF. PF-ILD is similarly associated with poor survival in patients with FILD-UIP, non-IPF-UIP, and IPF. Conclusions: Baseline disease severity is closely associated with the incidence of PF-ILD, with all forms of FILD-UIP at risk of PF-ILD and showing similar outcomes to IPF-UIP/PF-ILD. Full article

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition with limited treatment options and associated with high mortality rates. Inhaled treprostinil (iTre) is the only approved therapy for PH-ILD and has been shown to improve exercise capacity and delay disease progression. However, the conventional outpatient titration schedule requires 8–16 weeks to achieve therapeutic dosing, which may delay clinical benefit in those with advanced disease. We conducted a retrospective study of six patients with severe PH-ILD admitted to a tertiary academic center for initiation of iTre using a rapid inpatient uptitration protocol. iTre was started at 3 breaths four times daily (QID) and increased by 2 additional breaths every 12–24 h as tolerated, aiming for ≥9–12 breaths QID within one week under close monitoring. All six patients achieved target dosing without dose reduction or interruption. At three-month follow-up, mean pulmonary artery pressure decreased from 42 ± 5.5 to 35.2 ± 4.5 mmHg, pulmonary vascular resistance from 8.0 ± 1.2 to 6.0 ± 0.9 WU, and cardiac index increased from 2.05 ± 0.13 to 2.15 ± 0.12 L/min/m². No readmissions occurred within 90 days. This study demonstrates that rapid inpatient uptitration of iTre in severe PH-ILD is feasible and well-tolerated, with preliminary evidence of short-term hemodynamic improvement. Full article

Background: The prevalence of pulmonary hypertension (PH) in patients who are positive for myositis-specific antibody (MSA) and myositis-associated antibody (MAA) remains unclear. Methods: We conducted a retrospective study of patients with an age of 18 years or older diagnosed with myositis interstitial lung disease (ILD) at our university’s ILD clinic between 2019 and 2022. Echocardiographic PH was defined by tricuspid regurgitation velocity (TRV) ≥ 2.9 m/s on transthoracic echocardiography (TTE) consistent with intermediate probability of PH using 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. We grouped patients based on low probability of PH vs. intermediate to high probability of PH. We examined 6 min walk test (6MWT) data, pulmonary function tests (PFTs), all-cause mortality, and rate of lung transplantation. We also evaluated patients who were on immunosuppression vs. those not on immunosuppression. Results: The intermediate to high probability of PH group had a higher prevalence of dermato-specific antibodies (14.2% vs. 34.5%, p = 0.048). Specifically, MDA-5 was found to be more prevalent in patients with intermediate to high probability of PH (7.1% vs. 24.1%, p = 0.040). There was no difference in 6MWT parameters between groups (363.2 ± 115.6 m vs. 294.9 ± 147.5 m, p = 0.108). FVC and DLCO were lower in patients with intermediate to high probability of PH (71.3 ± 22.4 L vs. 58.8 ± 16.7 L, p = 0.037; 56.3 ± 21.8 mL/min/mmHg vs. 36.9 ± 15.5 mL/min/mmHg, p = 0.003). The all-cause mortality and rate of lung transplantation was higher in the intermediate to high probability of PH group (5.4% vs. 20.7%, p = 0.041, 0% vs. 6.9%, p = 0.049). There was no difference in all-cause mortality between patients who were on immunosuppression vs. those who were not on immunosuppression in patients with intermediate to high probability of PH (33.3% vs. 7.1%; p = 0.169). Conclusions: Patients with MSA/MAA may have an increased risk of PH with reduced lung function, higher mortality, and greater rate of lung transplantation. Our study further elucidates the growing body of evidence that dermato-specific antibodies, such as MDA-5 are associated with an increased risk of PH. Further research is needed to investigate the role of PH and immunosuppression in these patients. Full article

Objectives: Lung transplantation (LT) is a rescue therapy for end-stage pulmonary diseases, including systemic autoimmune diseases. The aim of this study was to analyse the evolution of patients with systemic sclerosis (SSc) who, after undergoing LT, become negative for antinuclear antibodies (ANA) and to assess whether they have different clinical and prognostic characteristics than patients who do not become negative. Material and Methods: A retrospective, descriptive analysis was performed over a cohort of patients with a diagnosis of SSc, who underwent unilateral or bilateral LT between 2006 and 2021 at the Vall d’Hebron University Hospital. Clinical and analytical data were obtained from these patients by reviewing their electronic medical records. Two groups of patients were compared: those who tested negative for ANA after LT and those who did not. Statistical analysis was performed with SPSS Statistics 20.0. Results: Eighteen patients were included. The most frequent indication for LT was interstitial lung disease (ILD) combined with pulmonary hypertension (PH), in 13 (72%) patients. All had ANA before the LT (n = 18), and regarding specific SSc autoantibodies, anti-topoisomerase I was presented in 44% (n = 8), anti-U11/U12RNP in 17% (n = 3), anti-RNA Polymerase III in 11.1% (n = 2), anti-Ro52 in 11% (n = 2) and anti-centromere in 6% of individuals (n = 1). 39% (n = 7) of the patients had negative post-LT ANA, 44% (n = 8) had declining titres, and 17% (n = 3) had stable ANA titres. Titres did not increase in any case after LT. Those patients who became ANA-negative after LT were those who had significantly lower titres before LT. No statistically significant differences between groups were found related to pre-LT clinical characteristics, immunosuppressive regimen applied after LT, or in post-LT outcomes. A non-significant trend towards better survival was observed in patients who became ANA negative, with a cumulative survival at 5 years of 85.7% compared to 72.7% among those who remained ANA-positive. Conclusions: Most patients with SSc clear ANA or reduce their levels after LT. A trend towards better survival was observed in this group, compared to the group of transplanted patients who remained positive. Full article

Background: Pulmonary hypertension (PH) is a frequent complication in patients with interstitial lung disease (ILD); its occurrence results in significant morbidity and mortality. Currently approved treatment options for PH-ILD include inhaled prostacyclin therapy, although this approach may be insufficient in patients who have developed simultaneous right ventricular failure. Moreover, there is no available treatment algorithm regarding the optimal therapy and timing of lung transplant referral for PH-ILD patients based on disease severity. Design/Methods: In this study, we created such a tool to guide PH-specific therapy in PH-ILD patients, especially as further treatment strategies are developed. We developed a 4-point PH-ILD Severity score that integrated both subjective and objective information (WHO FC, CI, TAPSE, PVR) from retrospective analysis of 57 PH-ILD patients. Results: A score of 3 or greater in the PH-ILD Severity score yielded an AUC of 0.831 (p < 0.001) for the composite endpoint of clinical worsening (hospitalization due to a cardiopulmonary indication; decrease in 6 min walk distance by >15% at 2 consecutive visits; all-cause mortality; lung transplantation). Conclusions: Further confirmation and evolution of this PH-ILD Severity score will assist in the development of optimal treatment plans in ILD patients diagnosed with concomitant PH. Full article

Background: Treprostinil has demonstrated effectiveness in treating Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD). However, tolerability remains a clinical challenge. Identifying factors influencing tolerability is important, given the adverse outcomes of PAH and PH-ILD and the potential of treprostinil to slow disease progression. Objective: This study was undertaken to identify tolerance factors and develop a predictive scoring system. Methods: A retrospective analysis of 65 patients (37 PAH, 28 PH-ILD) was conducted using patient history, pulmonary function tests (PFTs), transthoracic echocardiograms (TTEs), and right heart catheterizations (RHCs). Of these, 67.7% (n = 44) tolerated treprostinil, while 32.3% (n = 21) were intolerant. Results: Patients who tolerated treprostinil had better pulmonary function, with a higher forced expiratory volume in one second/forced vital capacity (FEV₁/FVC) ratio (82.27 ± 16.06 vs. 72.86 ± 17.76, p = 0.037) and superior right ventricular function, as indicated by higher tricuspid annular plane systolic excursion (TAPSE: 2.05 ± 0.37 vs. 1.64 ± 0.42, p < 0.001), higher cardiac index (CI: 2.51 ± 0.67 vs. 2.03 ± 0.53, p = 0.003), and improved functional status (p < 0.001). The Inhaled Treprostinil Intolerance Score (ITIS), incorporating TAPSE < 1.6, CI < 2, FEV₁/FVC < 70%, and WHO functional class (FC) 3 or 4, demonstrated strong predictive accuracy (cutoff ≥ 2, AUC = 0.884 ± 0.048, p < 0.001). Predictive performance was stronger in PAH patients (AUC = 0.921 ± 0.053) than PH-ILD (AUC = 0.833 ± 0.093, p < 0.001). Conclusions: These findings demonstrate the importance of clinical parameters in predicting treprostinil tolerance. Further investigation is warranted to refine the scoring system, particularly for PH-ILD patients. Full article

Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of lung fibrosis with cardiac MRI-derived measures of right ventricular (RV) function improves the diagnostic accuracy of PH in patients with ILD. Methods: We retrospectively analyzed 72 ILD patients who underwent chest CT, cardiac MRI, and right heart catheterization (RHC). Lung fibrosis was quantified using a Gaussian Histogram Normalized Correlation (GHNC) software that computed the proportions of diseased lung, ground-glass opacity (GGO), honeycombing, reticulation, consolidation, and emphysema. MRI was used to assess RV end-systolic volume (RVESV), ejection fraction, and RV longitudinal strain. PH was defined as a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg and pulmonary vascular resistance ≥ 3 Wood units on RHC. Results: Compared to patients without PH, those with PH (n = 21) showed significantly reduced RV strain (−13.4 ± 5.1% vs. −16.4 ± 5.2%, p = 0.026) and elevated RVESV (74.2 ± 18.3 mL vs. 59.5 ± 14.2 mL, p = 0.003). CT-derived indices also differed significantly: diseased lung area (56.4 ± 17.2% vs. 38.4 ± 12.5%, p < 0.001), GGO (11.8 ± 3.6% vs. 8.65 ± 4.3%, p = 0.005), and honeycombing (17.7 ± 4.9% vs. 12.8 ± 6.4%, p = 0.0027) were all more prominent in the PH group. In receiver operating characteristic curve analysis, diseased lung area demonstrated an area under the curve of 0.778 for detecting PH. This increased to 0.847 with the addition of RVESV, and further to 0.854 when RV strain was included. Combined models showed significant improvement in risk reclassification: net reclassification improvement was 0.700 (p = 0.002) with RVESV and 0.684 (p = 0.004) with RV strain; corresponding IDI values were 0.0887 (p = 0.03) and 0.1222 (p = 0.01), respectively. Conclusions: Combining CT-based fibrosis quantification with cardiac MRI-derived RV functional assessment enhances the non-invasive diagnosis of PH in ILD patients. This integrated imaging approach significantly improves diagnostic precision and may facilitate earlier, more targeted interventions in the management of ILD-associated PH. Full article

Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited treatment options for pulmonary hypertension in patients with interstitial lung disease (PH-ILD), this study aimed to evaluate the use of sotatercept in CTD-PAH patients with concomitant ILD. Methods: Eligible patients (n = 7) had a confirmed diagnosis of CTD-PAH with concomitant ILD. The patients were already receiving background PAH therapy. Baseline hemodynamic and clinical measurements were reassessed after 24 weeks of sotatercept therapy. The variables assessed included six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), echocardiographic right ventricular systolic pressure (eRVSP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, and supplemental oxygen requirements. Results: The study included seven patients with a mean age of 57 years (range: 39–73 years). After 24 weeks, the mean 6MWT distance increased from 211 m to 348 m (p < 0.01). Mean PVR decreased from 7.77 WU at baseline to 4.53 WU (p < 0.01). Mean eRVSP decreased from 79.43 mmHg to 54.14 mmHg (p < 0.01). NT-proBNP decreased from 3056.86 pg/mL to 1404.29 pg/mL (p < 0.01). The WHO functional class and supplemental oxygen requirements improved in all patients. Conclusions: Sotatercept was tolerated in patients with CTD-PAH and ILD, with no evidence of adverse respiratory effects. When added to foundational PAH therapy, sotatercept resulted in significant improvements across multiple parameters. These findings suggest that sotatercept may be a promising therapeutic option as an adjunctive treatment in this patient population. Full article

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of 16 patients with non-severe PH-ILD were divided into two groups based on changes in PVR during exercise: a dynamic PVR group (n = 10), characterized by an increase in PVR with exertion, and a static PVR group (n = 6), with no increase in PVR with exercise. The dynamic PVR group received inhaled treprostinil, while the static PVR group was monitored off therapy. Baseline and 16-week follow-up values were compared within each group. At 16 weeks, the dynamic PVR group demonstrated significant improvements in mean 6 min walk distance (6MWD) (+32.5 m, p < 0.05), resting PVR (−1.04 WU, p < 0.05), resting mean pulmonary arterial pressure (mPAP) (−5.8 mmHg, p < 0.05), exercise PVR (−1.7 WU, p < 0.05), exercise mPAP (−13 mmHg, p < 0.05), and estimated right ventricular systolic pressure (−9.2 mmHg, p < 0.05). In contrast, the static PVR group remained clinically stable. These observations suggest that an exercise-induced increase in PVR, identified through Level 3 CPET, may help select patients with non-severe PH-ILD who are more likely to benefit from early initiation of inhaled treprostinil. Full article

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and concomitant interstitial lung disease (ILD) are particularly challenging to manage due to concerns about ventilation–perfusion mismatch with systemic vasodilators. In this case series, we evaluated the effects of selexipag in eight prostacyclin-naïve CTD-PAH patients with concomitant ILD. Clinical, functional, and laboratory data were collected at baseline and after 16 weeks of treatment. After 16 weeks of treatment, the mean six-minute walk distance increased by 101.75 m (p < 0.05), and the mean estimated right ventricular systolic pressure decreased significantly (p < 0.05). Mean N-terminal pro b-type natriuretic peptide levels declined by 63%, though this reduction did not reach statistical significance. Importantly, supplemental oxygen requirements trended downward (p < 0.05) and pulmonary function tests remained stable. Pulmonary vasodilators have long been unsuccessfully studied in PH-ILD patients until the INCREASE trial. While other systemic agents used in PAH have not shown as much success as inhaled treprostinil in treating PH-ILD, our case series highlights the potential role of selexipag in patients with concomitant CTD-PAH and ILD. Further investigation of selexipag in pure Group 3 PH-ILD patients is warranted. Full article

Great progress has been made in the treatment of pulmonary arterial hypertension (WHO group 1 PAH) over the past two decades, which has significantly improved the morbidity and mortality in this patient population. Likewise, the more recent availability of antifibrotic medications for interstitial lung disease (ILD) have also been effective in slowing down the progression of disease. There is no known cure for either of these disease states. When this combination coexists, treatment can be challenging. Interstitial lung disease is a heterogenous group of chronic inflammatory and/or fibrotic parenchymal lung disorders. A subset of patients with ILD, not related to connective tissue disease, can initially present with inflammatory-predominant disease which progresses to irreversible fibrosis. This population of patients is also at risk for developing pulmonary hypertension (PH) or World Health Organization (WHO) group 3 PH. This coexistence of ILD and PH is associated with early morbidity and mortality. The early identification, diagnosis, and treatment of this combination of ILD and PH is vital. Medications available for both ILD and PH require an individualized approach with the intention of slowing down disease progression. Referral to expert centers for clinical trials and transplant evaluation is recommended. The combination of PH-ILD can be challenging to diagnose and treat effectively. Patients require a thorough clinical evaluation to enable the most accurate diagnosis. A vital part of that evaluation is the early recognition of PH. Medications can help improve disease progression along with clinical trials that will further improve our gaps in knowledge. Full article

Pulmonary hypertension associated with interstitial lung disease (ILD-PH) frequently complicates the course of patients with fibrotic ILD. In this narrative review, the authors assess current diagnostic tools and management considerations in ILD-PH patients. ILD-PH is associated with increased morbidity and mortality and may be suggested by the presence of symptoms out of proportion to the extent of the ILD. There are other clues to the presence of PH in the context of ILD including the need for supplemental oxygen, a reduced DLCO especially if accompanied by a disproportionately higher forced vital capacity, imaging demonstrating an enlarged pulmonary artery or a dilated right ventricle, or objective evidence of a reduced exercise capacity. While echocardiography is one screening tool, right heart catheterization remains the gold standard for the diagnosis of PH. When appropriate, treatment with inhaled treprostinil, or possibly other pulmonary vasodilators, may be indicated. Full article

Objectives: To investigate the role of blood eosinophils in predicting PH in end-stage lung disease. Methods: We conducted a retrospective study of adults with CF, COPD, and ILD who underwent RHC during lung transplant evaluations (2010–2022). Patients were classified by the 2022 ECS/ERS PH guidelines with pulmonary function and laboratory tests, including hemograms. The eosinophil threshold was set at 0.30 G/L. Results: We analyzed 663 patients (n = 89 CF, n = 294 COPD, and n = 280 ILD). Severe PH was more common in ILD (16%) than in CF (4%) and COPD (7%) (p = 0.0002), with higher eosinophil levels in ILD (p = 0.0002). No significant correlation was found between eosinophil levels and hemodynamic parameters (PAPm, PVR, and CI) across CF, COPD, and ILD (PAPm: p = 0.3974, p = 0.4400 and p = 0.2757, respectively; PVR: p = 0.6966, p = 0.1489 and p = 0.1630, respectively; CI: p = 0.9474, p = 0.5705 and p = 0.5945, respectively), nor was a correlation observed in patients not receiving OCS. Linear regression analysis confirmed the lack of association (PAPm: p = 0.3355, p = 0.8552 and p = 0.4146, respectively; PVR: p = 0.6924, p = 0.8935 and p = 0.5459, respectively; CI: p = 0.4260, p = 0.9289 and p = 0.5364, respectively), controlling for 6-MWD, Nt-proBNP, and ICS/OCS dosages. ROC analysis indicated eosinophils were ineffective in distinguishing PH severity levels across these diseases (AUC 0.54, 0.51, and 0.53, respectively). The analysis of eosinophil levels measured 18 ± 6 months prior to baseline found no predictive correlation with the presence of PH either. Eosinophil levels did not differ significantly among PH groups, but eosinophilic COPD was linked to more unclassified PH, higher CO, and greater lung volumes than non-eosinophilic COPD. Conclusions: In our cohort of end-stage CF, COPD, and ILD patients, blood eosinophilia did not predict the presence of PH but was associated with hemodynamic parameters and lung volumes in COPD. Full article