Search Results (29)

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

Background: Systemic sclerosis-associated pulmonary hypertension (SSc-PH) is widely recognized as the most severe subtype of connective tissue disease-associated pulmonary hypertension (CTD-PH), particularly in patients with complicating factors such as interstitial lung disease (ILD) and biventricular failure. This condition is associated with the poorest clinical outcomes among PH subtypes, presenting significant challenges in both management and prognosis. Despite the use of conventional therapies, including intravenous administration of epoprostenol, a promising prostacyclin analogue, treatment outcomes for SSc-PH remain suboptimal. While epoprostenol has demonstrated efficacy in reducing pulmonary arterial pressures, its clinical application is often constrained by the risk of ventilation–perfusion (V-Q) mismatch, particularly at higher doses. Case presentation: We report the case of a 73-year-old woman with SSc-PH complicated by ILD, who experienced progressive hemodynamic deterioration despite receiving optimized therapy with intravenous epoprostenol. Efforts to escalate the dose of epoprostenol were limited by the development of severe V-Q mismatch, precluding further dose increases. In light of these challenges, inhaled treprostinil was introduced as an adjunctive therapy. There were significant improvements in her pulmonary hypertension and hemodynamic parameters, ultimately allowing the discontinuation of intravenous dobutamine and stabilization of her hemodynamics, as well as her respiratory function, exercise capacity, and quality of life. Conclusions: This case highlights the potential clinical utility of combining inhaled treprostinil with intravenous epoprostenol for the treatment of SSc-PH in patients with concurrent ILD. By addressing the limitations associated with high-dose intravenous prostacyclin therapy, this combination approach may represent a promising therapeutic strategy for improving outcomes in this difficult-to-treat patient population. Further investigation is warranted to establish the efficacy and feasibility of this combination therapy in larger cohorts of patients with SSc-PH and associated ILD. Full article

Chronic lung diseases such as Chronic Obstructive Pulmonary Disease, Interstitial Lung Disease (ILD), and Pulmonary Hypertension (PH) are characterized by progressive symptoms such as dyspnea, fatigue, and muscle weakness, often leading to physical inactivity, and reduced quality of life. Many patients also experience significantly impaired exercise tolerance. While pulmonary, cardiovascular, respiratory, and peripheral muscle dysfunction contribute to exercise limitations, recent evidence suggests that hypoxia and impairments in cerebral oxygenation may also play a role in exercise intolerance. This narrative review (i) summarizes studies investigating cerebral oxygenation responses during exercise in patients with different types of chronic lung diseases and (ii) discusses possible mechanisms behind the blunted cerebral oxygenation during exercise reported in many of these conditions; however, the extent of cerebral desaturation and the intensity at which it occurs can vary. These differences depend on the specific pathophysiology of the lung disease and the presence of comorbidities. Notably, reduced cerebral oxygenation during exercise in fibrotic-ILD has been linked with the development of dyspnea and early exercise termination. Understanding the effects of chronic lung disease on cerebral oxygenation during exercise may improve our understanding of exercise intolerance mechanisms and help identify therapeutic strategies to enhance brain health and exercise capacity in these patients. Full article

Pulmonary hypertension (PH) in interstitial lung disease (ILD) is relatively common, affecting up to 50% of patients with idiopathic pulmonary fibrosis (IPF). It occurs more frequently in advanced fibrotic ILD, although it may also complicate milder disease and carries significant clinical implications in terms of morbidity and mortality. Key pathological processes driving ILD-PH include hypoxic pulmonary vasoconstriction and pulmonary vascular remodelling. While current understanding of the complex cell signalling pathways and molecular mechanisms underlying ILD-PH remains incomplete, there is evidence for an interplay between the disease pathogenesis of fibrotic ILD and PH, with interest in the role of the pulmonary endothelium in driving pulmonary fibrogenesis more recently. This review examines key clinical trials in ILD-PH therapeutics, including recent research showing promise for the treatment of both ILD-PH and the underlying pulmonary fibrotic process, further supporting the hypothesis of interrelated pathogenesis. Other important management considerations are discussed, including the value of accurate phenotyping in ILD-PH and the success of the “pulmonary vascular” phenotype. This article highlights the close and interconnected nature of fibrotic ILD and PH disease pathogenesis, a perspective likely to improve our understanding and therapeutic approach to this complex condition in the future. Full article

Pulmonary hypertension (PH) associated with interstitial lung disease (ILD) (PH-ILD) significantly worsens clinical symptoms and survival, with no effective treatment available. This case report presents the successful treatment of PH-ILD with inhaled iloprost in a patient with idiopathic pulmonary fibrosis (IPF). The patient, a 68-year-old female, was diagnosed with IPF in 2018 and was maintained on pirfenidone. She experienced stable disease until March 2023, when she developed progressive exertional dyspnea, despite stability indicated by a computed tomography (CT) scan, without progression. Transthoracic echocardiography (TTE) and right heart catheterization (RHC) confirmed PH-ILD with a mean pulmonary artery pressure (mPAP) of 43 mmHg. Due to the ineffectiveness of sildenafil and a CT scan indicating stable IPF, a repeat RHC was performed, which showed a worsening of PH (mPAP 62 mmHg). Consequently, inhaled iloprost, at a dosage of 10 mcg every eight hours, was added to the existing antifibrotic agent. After two months, the patient experienced reduced exertional dyspnea and home oxygen requirements. By the seventh month, pulmonary function tests, the six-minute walk test, and RHC parameters (mPAP 37 mmHg) showed marked improvements. This case suggests that inhaled iloprost may be beneficial for managing PH-ILD. Further research is needed to confirm the efficacy of iloprost in PH-ILD treatment. Full article

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n = 558). Our PH cohort (n = 121) showed a significantly higher prevalence of overall weak positive MSAs/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p < 0.001). Notably, MSAs/MAAs were found in PH patients both with and without ILD, though more prevalent in those with ILD. Anti-synthetase and anti-overlap syndrome antibodies were the most common. Our study is the first to systematically show a high MSA/MAA prevalence in PH without IIM presentation. This highlights the need to consider PH when diagnosing MSA/MAA-associated conditions. We recommend MSA/MAA screening for newly diagnosed PH, especially in those with ILD, for early detection and potential immunomodulatory treatment. Further research should explore the link between MSAs/MAAs and PH, and the value of monitoring patients with weak MSA/MAA positivity over time. Full article

Background/Objectives: Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods: This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results: We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions: Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death. Full article