Criteria favouring group 1 versus group 3 pulmonary hypertension (PH) #

Criteria favouring group 1 versus group 3 pulmonary hypertension (PH) #

Source publication
Article
Full-text available
Pulmonary hypertension (PH) frequently complicates the course of patients with various forms of chronic lung disease (CLD). CLD-associated PH (CLD-PH) is invariably associated with reduced functional ability, impaired quality of life, greater oxygen requirements and an increased risk of mortality. The aetiology of CLD-PH is complex and multifactori...

Similar publications

Article
Full-text available
The purpose of this review paper is to set an augmentation approach and exemplify distribution of augmentation works in Simplex method. The augmentation approach is classified into three forms whereby it comprises addition, substitution and integration. From the diversity study, the result shows that substitution approach appeared to be the highest...

Citations

... Patients with severe COPD-PH had more microvascular muscularization, intimal fibrosis, and medial hypertrophy than those with moderate COPD-PH; as measured by a modified version of the vascular assessment score for PH in animal models [35]. The vascular lesions morphologically resemble those in idiopathic PAH [36]. ...
Article
Full-text available
Microvascular dysfunction progressing to pulmonary hypertension can be a primary cause of right ventricular failure or a secondary cause because of an underlying systemic illness. Little is known regarding the etiology and epidemiology of coronary microvascular dysfunction in pulmonary hypertension. Despite this limitation, its presence has been described in patients with pulmonary hypertension. This review focuses on the pathogenesis of cardiac and pulmonary microvascular dysfunction in pulmonary hypertension. Additionally, this review provides a contemporary assessment on the diagnosis and treatment of microvascular dysfunction in patients in pulmonary hypertension. This topic is important to raise awareness of microvascular dysfunction in the coronary and pulmonary circulation, so that future studies will investigate its impact on the pulmonary hypertension patient cohort.
... COPD-PH must be confirmed by right heart catheterisation and there is evidence that PH is present in a substantial proportion of COPD patients with a prevalence between 30% and 70% [18]. mPAP may increase at a rate of 1 mmHg year −1 ; however, with large individual differences [21,22], and usually manifests at the advanced stages of COPD. Actually, 90% of GOLD stage IV patients have mPAP >20 mmHg [22]. ...
Article
Full-text available
COPD is a heterogeneous disease with multiple clinical phenotypes. COPD endotypes can be determined by different expressions of hypoxia-inducible factors (HIFs), which, in combination with individual susceptibility and environmental factors, may cause predominant airway or vascular changes in the lung. The pulmonary vascular phenotype is relatively rare among COPD patients and characterised by out-of-proportion pulmonary hypertension (PH) and low diffusing capacity of the lung for carbon monoxide, but only mild-to-moderate airway obstruction. Its histologic feature, severe remodelling of the small pulmonary arteries, can be mediated by HIF-2 overexpression in experimental PH models. HIF-2 is not only involved in the vascular remodelling but also in the parenchyma destruction. Endothelial cells from human emphysema lungs express reduced HIF-2α levels, and the deletion of pulmonary endothelial Hif-2 α leads to emphysema in mice. This means that both upregulation and downregulation of HIF-2 have adverse effects and that HIF-2 may represent a molecular “switch” between the development of the vascular and airway phenotypes in COPD. The mechanisms of HIF-2 dysregulation in the lung are only partly understood. HIF-2 levels may be controlled by NAD(P)H oxidases via iron- and redox-dependent mechanisms. A better understanding of these mechanisms may lead to the development of new therapeutic targets.
... Other studies have not identified a strong correlation between PH and forced vital capacity (FVC) or radiographic fibrosis on high-resolution computed tomography (HRCT), implying that parenchymal destruction is not the single aetiology for PH progression [10]. Adverse outcomes have been observed in IPF patients with mPAP ⩾25 mmHg, including increased risk for acute exacerbations [11,12]. ...
... endothelin, serotonin) and transcription factors like hypoxia-inducible factor-1. Intimal hyperplasia is particularly common in COPD, which can notably share morphological changes very similar to those seen in idiopathic PAH [12,21]. ...
... Optimisation of the underlying disease and treatment of RV dysfunction and hypoventilation syndromes remain the key steps in management. Patients with PH disproportionate to their lung parenchymal impairment should be referred to specialist PH centres with expertise in both conditions for further assessment [12]. ...
Article
Full-text available
Pulmonary hypertension (PH) is a recognised and significant complication of chronic lung disease (CLD) and hypoxia (referred to as group 3 PH) that is associated with increased morbidity, decreased quality of life and worse survival. The prevalence and severity of group 3 PH varies within the current literature, with the majority of CLD-PH patients tending to have non-severe disease. The aetiology of this condition is multifactorial and complex, while the prevailing pathogenetic mechanisms include hypoxic vasoconstriction, parenchymal lung (and vascular bed) destruction, vascular remodelling and inflammation. Comorbidities such as left heart dysfunction and thromboembolic disease can further confound the clinical picture. Noninvasive assessment is initially undertaken in suspected cases ( e.g. cardiac biomarkers, lung function, echocardiogram), while haemodynamic evaluation with right heart catheterisation remains the diagnostic gold standard. For patients with suspected severe PH, those with a pulmonary vascular phenotype or when there is uncertainty regarding further management, referral to specialist PH centres for further investigation and definitive management is mandated. No disease-specific therapy is currently available for group 3 PH and the focus of management remains optimisation of the underlying lung therapy, along with treating hypoventilation syndromes as indicated.
... However in Group 3 PH many clinicians will use a mPAP of 35 mmHg to define severe disease. 32 This corresponds to an echocardiographic PASP of 54 mmHg. 31 Thus lowering the definition of PH, will technically increase the number of patients with probable PH in our study, though the number of patients with clinically severe disease will likely remain the same. ...
Article
Full-text available
There are an estimated 155 million survivors of tuberculosis (TB). Clinical experience suggests that post‐pulmonary tuberculosis lung disease (PTLD) is an important cause of group 3 pulmonary hypertension (PH). However, TB is not listed as a cause of PH in most guidelines. A cross‐sectional, community‐based study was conducted in non‐health care seeking adults who had successfully completed TB treatment. Subjects underwent questionnaires, spirometry, a six‐minute walk distance test (6MWD) and transthoracic echocardiography (TTE). Screen probable PH was defined on TTE as an estimated pulmonary artery peak systolic pressure (PASP) of ≥40mmHg. One hundred adults (71 males) were enrolled, with a mean age of 42 years (SD 13.8 years) and a median of one TB episode (IQR: 1 ‐2). Co‐morbidities included hypertension (21%), diabetes (16%), HIV (10%) and asthma/COPD (5%). Only 25% had no residual symptoms after TB. Probable PH was found in 9%, while 7% had borderline raised PASP values (PASP 35‐40mmHg). An association was found between PH and the number of previous TB episodes, with each additional episode of TB increasing the odds of PH‐post‐TB 2.13‐fold (CI 1.17‐3.88; P=0.013). All of those found to have PH were smokers or ex‐smokers yielding an unadjusted odds ratio for PH‐post‐TB of 3.67 (95%CI 0.77‐17.46). There was no statistical difference in spirometry or 6MWD, between those with and without PH. Neither symptoms nor co‐morbidities demonstrated significant association with PH. PH after TB was a common finding in this community‐based population. Further research is needed to confirm and determine the significance of these findings. This article is protected by copyright. All rights reserved.
... The underlying molecular mechanisms of COPD pathology include increased oxidative and nitrosative stress, an imbalance between proteolytic activity and anti-proteolytic defense, persistent inflammation in the lung, uncontrolled autophagy, enhanced apoptosis and/or accelerated lung aging [4,7]. In addition to respiratory symptoms, most COPD patients suffer from mild to moderate pulmonary hypertension (PH) [8,9]. We have previously described the essential role of the inducible nitric oxide synthase (iNOS) in the development and reversal of tobacco smoke-induced emphysema and PH in mice [10]. ...
Article
Full-text available
Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. In addition to chronic bronchitis and emphysema, patients often develop at least mild pulmonary hypertension (PH). We previously demonstrated that inhibition of inducible nitric oxide synthase (iNOS) prevents and reverses emphysema and PH in mice. Interestingly, strong iNOS upregulation was found in alveolar epithelial type II cells (AECII) in emphysematous murine lungs, and peroxynitrite, which can be formed from iNOS-derived NO, was shown to induce AECII apoptosis in vitro. However, the specific cell type(s) that drive(s) iNOS-dependent lung regeneration in emphysema/PH has (have) not been identified yet. Aim: we tested whether iNOS knockout in AECII affects established elastase-induced emphysema in mice. Methods: four weeks after a single intratracheal instillation of porcine pancreatic elastase for the induction of emphysema and PH, we induced iNOS knockout in AECII in mice, and gave an additional twelve weeks for the potential recovery. Results: iNOS knockout in AECII did not reduce elastase-induced functional and structural lung changes such as increased lung compliance, decreased mean linear intercept and increased airspace, decreased right ventricular function, increased right ventricular systolic pressure and increased pulmonary vascular muscularization. In vitro, iNOS inhibition did not reduce apoptosis of AECII following exposure to a noxious stimulus. Conclusion: taken together, our data demonstrate that iNOS deletion in AECII is not sufficient for the regeneration of emphysematous murine lungs, and suggest that iNOS expression in pulmonary vascular or stromal cells might be critically important in this regard.
... Low-temperature exposure causes an increased metabolic rate and oxygen demand in broilers, and the lung and cardiovascular system are highly stressed, which increases oxidative stress and tissue damage in broilers and leads to hypoxia. The hypoxic response causes lung endothelial injury or dysfunction, which increases the cell proliferation and extracellular matrix synthesis that contribute to pulmonary fibrosis and pulmonary vascular remodeling and leads to pulmonary arterial hypertension (PAH) [1][2][3]. PAH in broilers is a hypoxia problem caused by stress factors, such as low ambient temperature. PAH leads to substandard slaughter weights and a large increase in mortality and culling rates. ...
Article
Full-text available
Chinese herbal medicine plays an important role in regulating the nutritional metabolism of poultry and maintaining or improving normal physiological functions and animal health. The present study investigated the effects of dietary supplementation with Qiling Jiaogulan Powder (QLJP) on pulmonary fibrosis and pulmonary arteriole remodeling in low temperature-exposed broilers. Seven-day-old Ross 308 broilers (n = 240) were reared adaptively to 14 days of age. The broilers were randomly divided into six groups: A control group (basal diet and normal feeding temperature); model group (basal diet); low-, medium- and high-dose QLJP groups (basal diet supplemented with 1 g/kg, 2 g/kg, 4 g/kg QLJP); and L-Arg group (basal diet supplemented with 10 g/kg L-arginine). Additionally, all the broilers, except the broilers in the control group, from the age of 14 days old, had a house temperature continuously lowered by 2 °C each day until it reached 12 °C at 21 days of age, and the low temperature was maintained until the end of the experiment. There were four replicates per group and 10 birds per replicate. The results showed that the structure of the lung tissue was clearer and basically intact in the broilers in the QLJP groups, with a small number of collagen fibers formed, and the content of hydroxyproline (HYP) was significantly reduced. QLJP improved pulmonary arteriole lesions, such as tunica media thickening, intimal hyperplasia, arterial wall hypertrophy, and lumen narrowing. QLJP reduced the relative media thickness (%) and relative medial area (%) of the pulmonary arteriole, and significantly decreased the expression level of the alpha-smooth muscle actin (α-SMA) protein in pulmonary arteriole, which alleviated pulmonary arteriole remodeling. The quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) results showed that QLJP treatment significantly reduced the gene and protein levels of transforming growth factor-beta l (TGF-β1) and Smad2 in the lung and downregulated the gene and protein levels of collagen type I alpha 1 (COL1A1) and matrix metalloproteinase 2 (MMP2). In conclusion, the results of our study suggested that dietary supplementation with QLJP improved pulmonary fibrosis and pulmonary arteriole remodeling by inhibiting the expression of genes related to the TGF-β1/Smad2 signaling pathway and inhibited the occurrence and development of pulmonary arterial hypertension in low-temperature-exposed broilers.
... The overall prevalence of a mean PAP ≥ 25 mmHg in COPD is estimated Open Access *Correspondence: gabor.kovacs@medunigraz.at to be around 10% [6]. Although severe PH is rare, mild to moderate forms of pulmonary vascular disease (PVD) are quite frequent [7,8]. Despite normal or mildly elevated pulmonary arterial pressures at rest, hemodynamic response to exercise may be abnormal in these patients, which could substantially contribute to their symptoms and impaired exercise capacity [5,9,10]. ...
Article
Full-text available
Background Pulmonary hypertension (PH) is a frequent complication in COPD and it is associated with decreased exercise capacity and poor prognosis. We hypothesized that even in COPD patients without significant PH at rest, abnormal pulmonary hemodynamics during exercise affect exercise capacity. Methods Consecutive COPD patients with clinically indicated right heart catheterization and resting mean pulmonary arterial pressure (mPAP) < 25 mmHg and age- and sex-matched controls with the same limits of pulmonary hemodynamics but no chronic lung disease who underwent clinical work-up including invasive hemodynamic assessment during exercise, were retrospectively analyzed. Chi-square tests were used to evaluate differences between groups for categorical data and Fisher’s exact test or Mann–Whitney-U-tests for continuous variables. Associations were analyzed with Spearman rank correlation tests. Results We included n = 26 COPD patients (female/male: 16/10, 66 ± 11 yr, FEV1: 56 ± 25%predicted) and n = 26 matched controls (FEV1: 96 ± 22%predicted). At rest, COPD patients presented with slightly increased mPAP (21 (18–23) vs. 17 (14–20) mmHg, p = 0.022), and pulmonary vascular resistance (PVR) [2.5 (1.9–3.0) vs. 1.9 (1.5–2.4) WU, p = 0.020] as compared to controls. During exercise, COPD patients reached significantly higher mPAP [47 (40–52) vs. 38 (32–44) mmHg, p = 0.015] and PVR [3.1 (2.2–3.7) vs. 1.7 (1.1–2.9) WU, p = 0.028] values despite lower peak exercise level [50 (50–75) vs. 100 (75–125) Watt, p = 0.002]. The mPAP/cardiac output slope was increased in COPD vs. controls [6.9 (5.5–10.9) vs. 3.7 (2.4–7.4) mmHg/L/min, p = 0.007] and negatively correlated with both peak oxygen uptake (r = − 0.46, p = 0.007) and 6-min walk distance (r = − 0.46, p = 0.001). Conclusion Even in the absence of significant PH at rest, COPD patients reveal characteristic abnormalities in pulmonary hemodynamics during exercise, which may represent an important exercise-limiting factor.
... However, there were no differences in reported serious adverse events or death between both treatment groups. The lack of mandated RHC-confirmed PH could have played a role in the negative results of some of these clinical trials, especially in the aforementioned studies of sildenafil, although there have been a number of negative studies where RHC was mandatory to confirm the diagnosis of PH. 1,16 The largest randomized controlled study targeting PH-ILD, the INCREASE study, included 346 patients equally randomized between inhaled treprostinil and placebo. 17 The study met its primary endpoint of change in the 6-minute walk distance at 16 weeks. ...
... Should all patients with PH by the prevailing definition be included in any given clinical trial? 16,19,20 Should clinical trialists look to enrich by only including the most severe patients? The downside of a high hemodynamic bar is that this will impact recruitment and limit the generalizability beyond a highly select group of patients. ...
Article
Full-text available
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, suggestions and guidance for future clinical trials in PH-ILD are also provided. This article is protected by copyright. All rights reserved.
... Pulmonary hypertension (PH) in chronic lung disease (CLD), such as idiopathic pulmonary fibrosis (IPF) portends a poor prognosis, impairing the median survival time to 2.5-5 years after diagnosis [1]. Recent epidemiological studies reported a 32-84% prevalence of PH in patients with IPF, and PH seems to develop over time in most patients with IPF [2]. ...
Article
Full-text available
Background Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients with IPF and the potential mechanism implicated. Methods Pulmonary arteries, lung tissue and serum of control subjects (n = 20), IPF (n = 20) and PH associated to IPF (n = 20) were used to study the expression and localization of IL-11 and IL-11Rα. Two models of IL-11 and bleomycin-induced lung fibrosis associated to PH were used in Tie2-GFP transgenic mice to evaluate the contribution of IL-11 and endothelial cells to pulmonary artery remodeling. The effect of IL-11 and soluble IL-11Rα on human pulmonary artery endothelial cells and smooth muscle cell transformations and proliferation were analyzed. Results IL-11 and IL-11Rα were over-expressed in pulmonary arteries and serum of patients with PH associated to IPF vs IPF patients without PH. Recombinant mice (rm)IL-11 induced lung fibrosis and PH in Tie2-GFP mice, activating in vivo EnMT as a contributor of pulmonary artery remodeling and lung fibrosis. Transient transfection of siRNA-IL-11 reduced lung fibrosis and PH in Tie2-GFP bleomycin model. Human (h)rIL-11 and soluble hrIL-11Rα induced endothelial to mesenchymal transition (EnMT) and pulmonary artery smooth muscle cell to myofibroblast-like transformation, cell proliferation and senescence in vitro. Conclusions IL-11 and IL-11Rα are overexpressed in pulmonary arteries of PH associated to IPF patients, and contributes to pulmonary artery remodeling and PH.
... The reasons for these differences are unclear but may be related to worst PF in the patients with CLD-PH. Compared with several other disease types, patients with CLD-PH might be older, have worse hemodynamics, and have relatively more underlying diseases or complications (23,24). The PF subscale was used to examine a person's perceived limitation in performing any physical activity (18). ...
Article
Full-text available
Background Significantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes. Methods A total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups. Results Patients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up. Conclusion Patients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management.