Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities ...taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases.
Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH.
The use of drugs that target endothelium‐dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Pulmonary Hypertension Due to Left Heart Diseases Vachiéry, Jean-Luc, MD; Adir, Yochai, MD, MHA; Barberà, Joan Albert, MD, PhD ...
Journal of the American College of Cardiology,
12/2013, Volume:
62, Issue:
25
Journal Article, Conference Proceeding
Peer reviewed
Open access
Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a ...subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term “out-of-proportion” PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon “out-of-proportion” PH and to distinguish “isolated post-capillary PH” from “post-capillary PH with a pre-capillary component” on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pulmonary Hypertension in Chronic Lung Diseases Seeger, Werner, MD; Adir, Yochai, MD; Barberà, Joan Albert, MD ...
Journal of the American College of Cardiology,
12/2013, Volume:
62, Issue:
25
Journal Article, Conference Proceeding
Peer reviewed
Open access
Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary ...hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure mPAP <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index CI <2.0 l/min/m2 ; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The “severe PH group” includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The symptoms of such patients cannot be explained by lung mechanical disturbances alone. Because it is not always easy to distinguish patients with PAH and COPD (group 1) from patients with PH caused ...by COPD (group 3), the Fifth World Symposium on Pulmonary Hypertension suggested some specific diagnostic criteria to aid clinicians in the differential diagnosis. ...about 50% of patients with COPD selected for lung transplant or lung volume reduction surgery had mPAP values greater than 25 mm Hg (52, 58, 64, 65). According to current guidelines (51), potential indications for RHC in advanced lung disease include 1) proper diagnosis or exclusion of PH in candidates for surgical treatments (transplant, lung volume reduction), 2) suspected PAH or chronic thromboembolic pulmonary hypertension, 3) episodes of right ventricular failure, and 4) inconclusive echocardiographic findings in cases with a high level of suspicion and potential therapeutic implications. ...besides the small cohort of patients with COPD with the pulmonary vascular phenotype, there may be a much larger, clinically heterogeneous group of patients with COPD with mild pulmonary vascular disease but a steep PAP increase during exercise, causing severe dyspnea.
Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic ...pulmonary vasoconstriction and impair gas exchange in this condition.
To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH.
We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration.
Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval 95% CI, -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline.
In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).
A pulmonary hypertension (PH) registry (Spanish Registry of Pulmonary Arterial Hypertension) was undertaken to analyse prevalence, incidence and survival of pulmonary arterial hypertension (PAH) and ...chronic thromboembolic pulmonary hypertension (CTEPH) in Spain, and to assess the applicability of recent survival prediction equations. Voluntary reporting of previously diagnosed and incident PAH or CTEPH cases (July 2007-June 2008) was performed. Demographic, functional and haemodynamic variables were evaluated. 866 patients with PAH and 162 with CTEPH were included. PAH associated with toxic oil syndrome and pulmonary veno-occlusive disease were reported for the first time in a PAH registry. Estimated prevalences were as follows: PAH, 16 and CTEPH, 3.2 cases per million adult inhabitants (MAI). Estimated incidences were as follows: PAH, 3.7 and CTEPH, 0.9 cases per MAI per yr. 1-, 3- and 5-yr survival was 87%, 75% and 65%, respectively, with no differences between PAH and CTEPH. Male sex, right atrial pressure and cardiac index were independent predictors of death. Matching between observed survival and that predicted by different equations was closer when the characteristics of the cohorts were similar. Epidemiology and survival of PAH patients in the Spanish registry are similar to recent registries. Characteristics of the population from which survival prediction equations are derived influence their applicability to a different cohort. CTEPH is much less prevalent than PAH, although has a similar survival rate.
Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of ...PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the ...scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term "exercise pulmonary hypertension" may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions. Exercise pulmonary hypertension is associated with the presence of a modest elevation of resting mean PAP and requires clinical follow-up, particularly if risk factors for pulmonary hypertension are present. There is a lack of robust clinical evidence on targeted medical therapy for exercise pulmonary hypertension.
Pulmonary hypertension (PH) is a frequent and important complication of chronic obstructive pulmonary disease (COPD). It is associated with worse clinical courses with more frequent exacerbation ...episodes, shorter survival, and greater need of health resources. PH is usually of moderate severity and progresses slowly, without altering right ventricular function in the majority of cases. Nevertheless, a reduced subgroup of patients may present disproportionate PH, with pulmonary artery pressure (PAP) largely exceeding the severity of respiratory impairment. These patients may represent a group with an exaggerated vascular impairment (pulmonary vascular phenotype) to factors that induce PH in COPD or be patients in whom idiopathic pulmonary arterial hypertension (PAH) coexist. The present review addresses the current definition and classification of PH in COPD, the distinction among the different phenotypes of pulmonary vascular disease that might present in COPD patients, and the therapeutic approach to PH in COPD based on the available scientific evidence. Keywords: chronic lung disease, pulmonary circulation, vascular remodeling, pulmonary arterial pressure
Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training ...for pulmonary hypertension (PH) patients.An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms.In studies (784 PH patients in total, including six randomised controlled trials, three controlled trials, 10 prospective cohort studies and four meta-analyses), exercise training has been shown to improve exercise capacity, muscular function, quality of life and possibly right ventricular function and pulmonary haemodynamics. Nevertheless, further studies are needed to confirm these data, to investigate the impact on risk profiles and to identify the most advantageous training methodology and underlying pathophysiological mechanisms.As exercise training appears to be effective, cost-efficient and safe, but is scarcely reimbursed, support from healthcare institutions, commissioners of healthcare and research funding institutions is greatly needed. There is a strong need to establish specialised rehabilitation programmes for PH patients to enhance patient access to this treatment intervention.
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