Hypertension In Interstitial Lung Disease Research Articles

Pulmonary hypertension in interstitial lung disease: a systematic review and meta-analysis

Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances. What are the diagnostic evaluation, epidemiology, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in current literature? Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any aetiology. The definition of PH was based on the investigators' criteria. 302 studies were included, with varying diagnostic evaluation used to define PH. Commonly used diagnostic tests were right heart catheterisation (RHC) (56%) and transthoracic echocardiogram (TTE) (50%). The pooled prevalence for PH in general ILD populations was 36% (95%CI 30-42%) using RHC, and 34% (95%CI 29-38%) using TTE. Lower diffusion capacity for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide were consistently associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular haemodynamic and 6-minute walk distance. PH is a common complication in ILD with significant health impacts. A standardised definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate endpoints in future PH interventional trials in ILD.

Pulmonary Hypertension in Interstitial Lung Diseases and Rare Interstitial Lung Diseases

Pulmonary Hypertension in Interstitial Lung Diseases and Rare Interstitial Lung Diseases

Evolution of pulmonary hypertension in interstitial lung disease: a journey through past, present, and future.

Interstitial lung diseases (ILD) are a spectrum of disorders often complicated by pulmonary hypertension (PH) in its course. The pathophysiologic mechanism of WHO group 3 PH is different to other forms of PH. The advent of PH is a harbinger for adverse events like mortality and morbidity, implying that the PH component of disease expedites deteriorated clinical outcomes. In fact, WHO group 3 PH due to ILD has the worse prognosis among all groups of PH. Hence, early detection of PH by a comprehensive screening method is paramount. Given considerable overlap in clinical manifestations between ILD and PH, early detection of PH is often elusive. Despite, the treatment of PH due to ILD has been frustrating until recently. Clinical trials utilizing PAH-specific pulmonary vasodilators have been ongoing for years without desired results. Eventually, the INCREASE study (2018) demonstrated beneficial effect of inhaled Treprostinil to treat PH in ILD. In view of this pioneering development, a paradigm shift in clinical approach to this disease phenotype is happening. There is a renewed vigor to develop a well validated screening tool for early detection and management. Currently inhaled Treprostinil is the only FDA approved therapy to treat this phenotype, but emergence of a therapy has opened a plethora of research toward new drug developments. Regardless of all these recent developments, the overall outlook still remains grim in this condition. This review article dwells on the current state of knowledge of pre-capillary PH due to ILD, especially its diagnosis and management, the recent progresses, and future evolutions in this field.

Pulmonary Hypertension in Interstitial Lung Disease: Updates in Disease, Diagnosis, and Therapeutics.

Pulmonary hypertension is a debilitating condition that frequently develops in the setting of interstitial lung disease, likely related to chronic alveolar hypoxemia and pulmonary vascular remodeling. This disease process is likely to be identified more frequently by providers given recent advancements in definitions and diagnostic modalities, and provides practitioners with emerging opportunities to improve patient outcomes and quality of life. Despite years of data suggesting against the efficacy of pulmonary vasodilator therapy in patients with pulmonary hypertension due to interstitial lung disease, new data have emerged identifying promising advancements in therapeutics. The authors present to you a comprehensive review of pulmonary hypertension in interstitial lung disease, reviewing our current understanding of pathophysiology, updates in diagnostic approaches, and highlights of recent clinical trials which provide an effective approach for medical management.

Pulmonary Hypertension in Interstitial Lung Disease: Management Options to Move Beyond Supportive Care.

This review delineates current diagnostic and management strategies for pulmonary hypertension due to interstitial lung disease (PH-ILD). The INCREASE trial, a phase III multicenter, randomized, placebo-controlled trial demonstrated both improved 6-min walk distance and decreased disease progression with inhaled treprostinil. This pivotal trial led to inhaled treprostinil becoming the first FDA approved medication for treatment of PH-ILD. The availability of this treatment has generated subsequent recommendations for the screening for PH in patients with ILD. As a result, it is becoming increasingly important for clinicians to gain awareness and familiarity with the evolving management options for PH-ILD. The management of PH-ILD has its roots in goal-directed treatment of the underlying lung disease. However, recent medication advances and ongoing clinical studies are opening opportunities for more disease-specific treatment.

Response to letter to the editor "noninvasive determinants of pulmonary hypertension in interstitial lung disease".

Response to letter to the editor "noninvasive determinants of pulmonary hypertension in interstitial lung disease".

Noninvasive determinants of pulmonary hypertension in interstitial lung disease.

Pulmonary hypertension (PH) in interstitial lung disease (ILD) is associated with increased mortality and impaired exertional capacity. Right heart catheterization is the diagnostic standard for PH but is invasive and not readily available. Noninvasive physiologic evaluation may predict PH in ILD. Forty-fourpatients with PHand ILD (PH-ILD) were compared with 22 with ILDalone (non-PH ILD). Six-minwalk distance (6MWD, 223 ± 131vs. 331 ± 125 m, p = 0.02) and diffusing capacity for carbon monoxide (DLCO, 33 ± 14% vs. 55 ± 21%, p < 0.001) were lower in patients with PH-ILD. PH-ILD patients exhibited a lower gas-exchange derived pulmonary vascular capacitance (GXCAP, 251 ± 132vs. 465 ± 282 mL × mmHg, p < 0.0001) and extrapolated maximum oxygen uptake (VO2max) (56 ± 32% vs. 84 ± 37%, p = 0.003). Multivariate analysis was performed to determine predictors of VO2 max. GXCAP was the only variable that predicted extrapolated VO2 max among PH-ILD and non-PH ILD patients. Receiver operating characteristic curve analysis assessed the ability of individual noninvasive variables to distinguish between PH-ILD and non-PH ILD patients. GXCAP (area under the curve[AUC] 0.85 ± 0.04, p < 0.0001) and delta ETCO2 (AUC 0.84 ± 0.04, p < 0.0001) were the strongest predictors of PH-ILD. A CART analysis selected GXCAP, estimated right ventricular systolic pressure (eRVSP) by echocardiogram, and FVC/DLCO ratio as predictive variables for PH-ILD. With this analysis, the AUC improved to 0.94 (sensitivity of 0.86 and sensitivity of 0.93). Patients with a GXCAP ≤ 416 mL × mmHg had an 82% probability of PH-ILD. Patients with GXCAP ≤ 416 mL × mmHg and high FVC/DLCO ratio >1.7 had an 80% probability of PH-ILD. Patients with GXCAP ≤ 416 mL × mmHg and an elevated eRVSP by echocardiogram >43 mmHg had 100% probability of PH-ILD. The incorporation of GXCAP with either eRVSP or FVC/DLCO ratio distinguishes between PH-ILD and non-PH-ILD with high probability and may therefore assist in determining the need to proceed with a diagnostic right heart catheterizationand potential initiation of pulmonary arterial hypertension-directed therapy in PH-ILD patients.

Prevalence and Risk Factors of Pulmonary Arterial Hypertension in Interstitial Lung Diseases: A Cross-sectional Study

Introduction: Interstitial Lung Diseases (ILD) is associated with inflammatory and/or fibrotic changes in the lungs. Pulmonary Arterial Hypertension (PAH) is a complication of many end-stage lung diseases due to the re-modelling of pulmonary vasculature associated with hypoxia leading to pulmonary vascular resistance. The Association of PAH in ILD contributes significantly to high morbidity and mortality. ILD being a progressive disease it is difficult to predict when the PAH will set in. Aim: To assess the clinical and radiological profiles of patients with ILD and to associate these with the severity of PAH. Materials and Methods: The present cross-sectional study was conducted in the Department of Respiratory Medicine at GSL Medical College on 23 patients with ILD from 1st October 2019 to 31st august 2021, in GSL medical college and hospital, Andhra Pradesh. Each patient was subjected to chest X-ray (CXR), Electrocardiogram (ECG), and 2-Dimensional Echocardiogram (2D ECHO). Evidence of PAH in any one investigation was considered. In ECG reports evidence of right ventricular enlargement (R&gt;S in V1/V2 and right axis deviation &gt;110 degrees, R=11 mm) was considered as PAH. CXR showing dilatation of the pulmonary artery with an increased cardiothoracic ratio was considered as PAH. A 2-D ECHO was performed to estimate the right arterial pressure and evidence of pulmonary arterial systemic pressure of &gt;40 mmHg was considered as PAH. All the data were statistically analysed by using IBM Statistical Package for Social Sciences (SPSS) version 20.0. Results: Fifty-two percent of the population constituted females, and the mean age of the whole population was 59.7±14.4 years and the majority of them (65%) belonged to upper lower socioeconomic class. Usual Interstitial Pneumonia (UIP) was the most common pattern observed accounting for 57%. Prevalence of PAH was 65% and a longer duration of symptoms, 57% of the population had grade 3 of Modified Medical Research Council (MMRC) and 52.17% covered less than 200 meters in the 6-Minute Walk Test (6MWT). Oxygen desaturation after 6MWT was observed to be the contributing factor for the development of severe pulmonary hypertension in ILD patients. Conclusion: Factors like delayed seeking of medical care, co-morbidity like hypertension, higher grades of dyspnoea at the time of presentation, shorter 6MWD, and post-walk oxygen saturation were found to be predictors of pulmonary artery hypertension in patients with ILD. Early recognition of these risk factors in patients with ILD and the prompt treatment of the disease can reduce the development of severe PAH.

Computed tomography measurement of pulmonary artery size in interstitial lung disease to evaluate pulmonary hypertension

Aim: To evaluate whether pulmonary artery size is indicator of pulmonary hypertension in patients with interstitial lung disease.Objective: To measure main pulmonary artery size in interstitial lung disease on CT. To compare these measurements with 2Decho findings in diagnosing the pulmonary hypertension.Materials and Methods Type of study: Prospective studyDuration of study: 1st June 2021 to 1st September 2022 Results and Conclusion: 30 patients with interstitial lung disease with suspicion of pulmonary hypertension were subjected to CT scan Among the 22 patients with dilated pulmonary artery, 64% were found to show signs of probable pulmonary hypertension on 2DEcho and remaining 36% patients were found to be negative.In the remaining 8 patients who were not having dilated pulmonary artery, only one patient showed signs of pulmonary hypertension on 2 Decho. Dilated pulmonary artery was correlated positively with 2Decho findings in pearson correlation of coefficient.Thus, dilated pulmonary artery can raise a suspicion of pulmonary hypertension in interstitial lung diseases. Therefore, pulmonary artery diameter is key for screening of suspected pulmonary hypertension

Pulmonary hypertension in interstitial lung disease: Clinical trial design and endpoints: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative-Group 3 Pulmonary Hypertension.

Pulmonary hypertension (PH) associated with interstitial lung disease (ILD) is an attractive target for clinical trials of PH medications. There are many factors that need to be considered to prime such studies for success. The patient phenotype most likely to respond to the intervention requires weighing the extent of the parenchymal lung disease against the severity of the hemodynamic impairment. The inclusion criteria should not be too restrictive, thus enabling recruitment. The trial should be of sufficient duration to meet the chosen endpoint which should reflect how the patient feels, functions, or survives. This paper summarizes prior studies in PH-ILD and provides a framework of the type of studies to be considered. Inclusion criteria, clinical trial endpoints, and pharmacovigilance in the context of PH-ILD trials are also addressed. Through lessons learnt from prior studies, suggestionsand guidance for future clinical trials in PH-ILD are also provided.

Pulmonary hypertension in interstitial lung disease: an area of unmet clinical need.

Pulmonary hypertension (PH) is present in an important proportion of patients with interstitial lung diseases (ILDs), encompassing a large, heterogeneous group of diffuse parenchymal lung diseases. Development of ILD-related PH is associated with reduced exercise capacity, increased need for supplemental oxygen, decreased quality of life and earlier death. Diagnosis of ILD-related PH is important and requires a high index of suspicion. Noninvasive diagnostic assessment can suggest the presence of PH, although right heart catheterisation remains the gold standard to confirm the diagnosis and to assess its severity. A comprehensive assessment is needed to make sure reversible causes of PH have been ruled out, including thromboembolic events, untreated hypoxaemia and sleep disordered breathing. The results of trials concerning pulmonary vasodilators in this particular patient group have been disappointing and, in some cases, were even associated with an increased risk of harm. Newer strategies such as medications administered through inhalation and combinations with antifibrotic drugs show encouraging results. Moreover, unravelling the role of the vasculature in the pathophysiology of pulmonary fibrosis and ILD-related PH may potentially unlock new therapeutic opportunities.

Clinical assessment for pulmonary hypertension in interstitial lung disease.

Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD), as its development confers a poor prognosis. There are no specific recommendations for methods of assessment for PH in ILD populations. To determine current assessment practices for PH in an Australian ILD centre. In the Austin Health ILD database, 162 consecutive patients with idiopathic pulmonary fibrosis or connective tissue disease-associated ILD were identified and retrospectively evaluated for methods of PH assessment with transthoracic echocardiography (TTE), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and right heart catheterisation (RHC) in relation to patient demographic and physiological parameters. The median follow-up was 30 (14.4-56.4) months. At baseline, vital capacity was 80.0 ± 18.4% predicted, and diffusing capacity for carbon monoxide was 59.6 ± 15.2% predicted. Evaluation for PH was performed in 147 (90.7%) patients, among whom 105 (64.8%) had TTE performed at least once. At the initial TTE, 33.7% patients had high probability of PH, defined as RVSP >40 mmHg + RAp and/or right ventricular dysfunction. At the time of the most recent TTE, these criteria were met in 45 (52.3%) patients. Elevated serum NT-proBNP levels during the first year were observed in 47 (38.8%) patients. Only 14 (8.6%) patients had RHC. Our institutional PH assessment practice in ILD demonstrates a substantial prevalence of probable PH at baseline. As new therapies emerge for the treatment of PH in ILD, well-defined screening practices are important in this population for early identification and optimal management.

Clinical significance of pulmonary hypertension in interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's innovative drug development initiative-Group 3 pulmonary hypertension.

Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in‐depth papers on specific topics pertaining to PH‐ILD.

Clinical Assessment for Pulmonary Hypertension in Interstitial Lung Disease

Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD), as its development confers a poor prognosis. There are no specific recommendations for methods of assessment for PH in ILD populations. This study aimed to determine current assessment practices for PH in an Australian ILD centre.

Pulmonary hypertension in interstitial lung disease: screening, diagnosis and treatment.

Pulmonary vascular disease resulting in pulmonary hypertension in the context of interstitial lung disease (PH-ILD) is a common complication that presents many challenges in clinical practice. Despite recent advances, the pathogenetic interplay between parenchymal and vascular disease in ILD is not fully understood. This review provides an overview of the current knowledge and recent advances in the field. Clinical trials employing the phosphodiesterase-5-inhibitor sildenafil delivered negative results whereas riociguat showed harmful effects in the PH-ILD population. More recently, inhaled treprostinil showed positive effects on the primary endpoint (six-min walk-distance) in the largest prospective randomized placebo-controlled trial to date in this patient population. Additionally, a pilot trial of ambulatory inhaled nitric oxide suggests beneficial effects based on the novel endpoint of actigraphy. In view of these novel developments this review provides an overview of the status quo of screening, diagnosis and management of pulmonary vascular disease and PH in patients with ILD.

Pulmonary hypertension in patients with interstitial pneumonia with autoimmune features.

Pulmonary hypertension in interstitial lung diseases is associated with increased mortality and hospitalizations and reduced exercise capacity. Interstitial pneumonia with autoimmune features (IPAF) is a recently described interstitial lung disease. The characteristics of pulmonary hypertension in IPAF patients are unknown. We sought to characterize patients with IPAF based on their echocardiographic probability of pulmonary hypertension and compare patients with and without pulmonary hypertension identified by right heart catheterization. We conducted a retrospective study of patients seen in the interstitial lung disease clinic from 2015 to 2018. Forty-seven patients with IPAF were identified. Patients were classified into low, intermediate and high echocardiographic pulmonary hypertension probabilities. A sub-group analysis of patients with pulmonary hypertension and without pulmonary hypertension (IPAF-PH vs. IPAF-no PH) identified by right heart catheterization was also performed. Linear regression analysis was performed to study the association between 6-min-walk-distance (6MWD) and pulmonary vascular resistance (PVR) while adjusting for age and body mass index. Right ventricular hypertrophy (>5 mm), right ventricular enlargement (>41 mm) and right ventricular systolic dysfunction defined as fractional area change% ≤35 was present in 76%, 24%, and 39% of patients, respectively. Pulmonary hypertension was identified in 12.7% of patients. IPAF-PH patients had higher mean pulmonary artery pressure and lower cardiac output compared to the IPAF-no PH group (34 mmHg vs. 19 mmHg, p = 0.002 and 4.0 vs. 5.7 L/min, p = 0.023, respectively). Lower 6MWD was associated with higher PVR on regression analysis (p = 0.002). Pulmonologists should be aware that a significant number of IPAF patients may develop pulmonary hypertension. Reduced 6MWD may suggest the presence of pulmonary hypertension in IPAF patients.

Desaturation on 6-Min Walk Test: A Test with High Negative Predictive Value to Rule Out Pulmonary Hypertension in Interstitial Lung Diseases

Introduction: Pulmonary hypertension (PH) is one of the major complications of interstitial lung diseases (ILDs) that contributes to increased morbidity and mortality. Predicting and promptly diagnosing PH may improve the outcome in these patients. We evaluated the utility of 6-min walk test (6MWT) to predict PH earlier in the course of ILDs. Patients and Methods: A total of 113 patients diagnosed with ILD as per standard investigation protocols were included in this observational study. Patients were evaluated with 6MWT, pulmonary function tests, and two-dimensional echocardiogram. Patients having mean pulmonary arterial pressure >25 mmHg were labeled as PH, and 4% drop from pretest oxygen saturation was considered as significant desaturation. Results: It was observed that 40% of patients with desaturation on 6MWT had PH. None of the patients without significant desaturation had PH. Conclusion: Desaturation on 6MWT is not an early predictor of PH, which is one of the major complications of ILDs. However, it has a high negative predictive value in the prediction of PH in patients with ILD.

Pulmonary hypertension in interstitial lung disease: Limitations of echocardiography compared to cardiac catheterization.

In interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well-characterized ILD cohort. Two hundred and sixty-five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and low (<2.8 m/s) probabilities of PH were evaluated against RHC testing. RHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as 'low probability' of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH. In patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC.

Pulmonary Hypertension in Interstitial Lung Disease: Ege University Experience

Pulmonary Hypertension in Interstitial Lung Disease: Ege University Experience

What Is the Incidence of Pulmonary Hypertension in Interstitial Lung Disease? How to Manage the Treatment? Is There Any Effect of Pulmonary Hypertension on Prognosis?

What Is the Incidence of Pulmonary Hypertension in Interstitial Lung Disease? How to Manage the Treatment? Is There Any Effect of Pulmonary Hypertension on Prognosis?