Advanced pulmonary sarcoidosis.

Pulmonary Hypertension: From an Orphan Disease to a Public Health Problem

Since the recognition of nitric oxide (NO) as a key endothelial-derived vasodilator molecule in 1987, the field of NO research has expanded to encompass many areas of biomedical research. It is now well established that NO is an important signaling molecule throughout the body. The therapeutic potential of inhaled NO as a selective pulmonary vasodilator was suggested in a lamb model of pulmonary hypertension and in patients with pulmonary hypertension in 1991.1,2 Because NO is scavenged by hemoglobin (Hb) on diffusing into the blood and is thereby rapidly inactivated, the vasodilatory effect of inhaled NO is limited largely to the lung. This is in contrast to intravenously infused vasodilators that can cause systemic vasodilation and severe systemic arterial hypotension. Recent data indicate that inhaled NO can be applied in various diseases. For example, studies suggest that inhaled NO is a safe and effective agent to determine the vasodilatory capacity of the pulmonary vascular bed. This article summarizes the pharmacology and physiology of inhaled NO and reviews the current uses of inhaled NO for the treatment, evaluation, and prevention of cardiovascular and respiratory diseases. ### Chemistry of NO Gas NO is a colorless, odorless gas that is only slightly soluble in water.3 NO and its oxidative byproducts (eg, NO2 and N2O4) are produced by the partial oxidation of atmospheric nitrogen in internal combustion engines, in the burning cinder cones of cigarettes, and in lightning storms. Medical-grade NO gas is produced under carefully controlled conditions, diluted with pure nitrogen, and stored in the absence of oxygen. The recent article by Williams4 provides a review of the chemistry of NO. ### Therapeutic Versus Endogenous NO Concentrations in the Airway Although early studies of inhaled NO in the treatment of pulmonary hypertension used concentrations of 5 to 80 ppm, it has since been realized that concentrations >20 ppm provide little additional …

The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart–Lung Transplant Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant

Pulmonary hypertension (PH) is a common complication of advanced chronic obstructive pulmonary disease (COPD) and is defined by a mean pulmonary artery pressure (PAP) ≥ 25 mm Hg at rest in the supine position. Owing to its frequency, COPD is a common cause of PH; in fact, it is the second most frequent cause of PH, just after left heart diseases. PH is due to the elevation of pulmonary vascular resistance, which is caused by functional and morphological factors, chronic alveolar hypoxia being the most important. In COPD PH is generally mild to moderate, PAP usually ranging between 25 and 35 mm Hg in a stable state of the disease. A small proportion of COPD patients may present a severe or “disproportionate” PH with a resting PAP > 35–40 mm Hg. The prognosis is particularly poor in these patients. In COPD PH worsens during exercise, sleep and severe exacerbations of the disease, and these acute increases in afterload may favour the development of right heart failure. The diagnosis of PH relies on Doppler echocardiography, and right heart catheterization is needed in a minority of patients. Treatment of PH in COPD relies on long-term oxygen therapy (≥16 h/day) which generally stabilizes or at least attenuates the progression of PH. Vasodilator drugs, which are commonly used in idiopathic pulmonary arterial hypertension, have rarely been used in COPD, and we lack studies in this field. Patients with severe PH should be referred to a specialist PH centre where the possibility of inclusion in a controlled clinical trial should be considered.

25-Year-Old Woman With Increasing Abdominal Girth and Shortness of Breath

The implantable cardioverter defibrillator: technology, indications, and impact on cardiovascular survival

See related article, pages 1323–1330 Serotonin (5-HT, 5-hydroxytryptamine) has long been recognized as one of the most potent naturally occurring pulmonary vasoconstrictors.1 It was first implicated in the pathogenesis of pulmonary arterial hypertension (PAH) after an outbreak of the disease in Switzerland in the 1960’s among patients taking aminorex fumarate, an appetite suppressant that inhibits serotonin uptake by platelets.2 Since that time further outbreaks of PAH have been identified in Europe and the USA associated with the use of fenfluramine-derivate anorexigens,3–5 eventually leading to their withdrawal from the world market in 1997. Although this was, at least in retrospect, a predictable tragedy, it has ironically opened avenues of research into the biology of serotonin signaling in PAH. As fenfluramine-derivatives are substrates for the serotonin transporter (5-HTT, SERT) proteins,6 this suggests that abnormal SERT expression or functional activity could play a role in the pathogenesis of PAH. There is now a body of evidence supporting this hypothesis that provides hope for the development of effective therapeutic strategies targeting specific components of this signaling pathway in patients with these diseases. Most of the serotonin produced in the body is secreted by enterochromaffin cells of the intestine into the portal circulation where it is partially metabolized by the liver. However, levels of free circulating serotonin are maintained in the low nanomolar range through energy-dependent SERT-mediated transport into platelets. This led some researchers to hypothesize that fenfluramines might cause PAH by increasing free plasma levels of serotonin. However, this hypothesis is inconsistent with the observation that chronic treatment with fenfluramine-derivatives if anything reduces plasma levels of serotonin.6 This suggests that other SERT-related effects promote PAH in susceptible patients. This is supported by the observation that patients with idiopathic PAH have increased frequency of the so called L-type polymorphism …

ECG patterns to predict pulmonary arterial hypertension in patients with severe tricuspid regurgitation

Worldwide Physician Education and Training in Pulmonary Hypertension: Pulmonary Vascular Disease: The Global Perspective

To be EndMT or not to be, that is the question in pulmonary hypertension.

Pulmonary hypertension can occur as an isolated disease affecting the lung vessels only, in association with underlying hypoxic lung disorders, or due to chronic thromboembolic disease. Pulmonary hypertension caused by pulmonary venous congestion will not be focused on in this review. Regardless of the underlying disease, chronic cor pulmonale is associated with progressive clinical deterioration and a poor prognosis in most cases. The aim of specific therapies for pulmonary hypertension is to reduce pulmonary vascular resistance and thereby improve right ventricular function. Currently, three classes of drugs (prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors) are approved for the treatment of pulmonary arterial hypertension (PAH) in a defined patient population (group I according to the recent WHO classification). However, these medications may also lower pulmonary vascular resistance in patients with associated lung diseases (e.g. chronic obstructive pulmonary disease or lung fibrosis) and significant pulmonary hypertension, for whom these drugs are not yet approved. As non-selective vasodilators may induce gas-exchange disturbances, which preclude their long term use in these patients, such substances should be avoided in the hypoxemic patient. In this article we provide an update of the current understanding of hypoxia- and non-hypoxia-related pulmonary hypertension, addressing both the pathophysiological understanding of different disease aetiologies as well as the therapeutic options currently available.

Pulmonary hypertension (PH) is an important complication of chronic parenchymal lung diseases. The current definition of PH requires an abnormal resting mean pulmonary arterial pressure >20 mmHg during right heart catheterization (RHC). The most common chronic lung conditions that cause PH are chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), but PH can occur in the context of other parenchymal lung diseases including combined pulmonary fibrosis and emphysema (CPFE), sarcoidosis, lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH). PH that occurs due to chronic lung diseases or chronic hypoxia (high altitude or severe sleep-disordered breathing) comprises Group 3 PH, whereas conditions such as sarcoidosis, LAM, and PLCH have multiple or multifactorial mechanisms and are classified into Group 5 PH.

Mild-to-moderate pulmonary hypertension is a common complication of chronic lung diseases. Very few patients have severe pulmonary hypertension; if that is the case, it may be due to co-morbidities or correspond to a particular phenotype. Although pulmonary hypertension has little or no involvement in exercise limitation, it is an independent prognostic factor for survival. The first stage of diagnosis of pulmonary hypertension in chronic lung disease is to establish a level of high, intermediate, or low probability using Doppler echocardiography according to the European Society of Cardiology/European Respiratory Society Guidelines. To determine the cause of pulmonary hypertension, it may be necessary to perform a comprehensive search for the most frequent respiratory and cardiovascular diseases. There are few, but important, indications for right heart catheterization in chronic lung diseases. The main indications are candidates for lung transplantation, suspicion of pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension, and when pulmonary haemodynamics are likely to have significant therapeutic implications. The underlying respiratory disease or associations of diseases should be treated according to current guidelines before concluding that a patient has severe pulmonary hypertension. Non-invasive ventilation and long-term oxygen therapy in hypercapnic and hypoxaemic patients, respectively, improve pulmonary haemodynamics. With the exception of cardiovascular co-morbidities, pharmacotherapies for high blood pressure and for left heart diseases are not recommended to treat pulmonary hypertension due to chronic lung diseases. Pulmonary arterial hypertension-approved therapies are not recommended in pulmonary hypertension due to chronic lung diseases.

Chronic obstructive pulmonary disease significantly affects the quality of life, considerably limiting the physical capabilities of patients and is one of the main causes of morbidity and mortality in modern society. Currently, the problem of the comorbidity for the patients with chronic obstructive pulmonary disease is very relevant. The most common in patients of this category is hypertension. Today, it has been established that disorders in the immune system are detected in a very large group of diseases, including both chronic obstructive pulmonary disease and hypertension. The purpose of the study was to evaluate the dynamics of inflammatory markers in the patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease in combination with hypertension under the influence of treatment. Material and methods. The results of the study are based on data from a comprehensive survey of 170 patients aged 40 to 65 years with chronic obstructive pulmonary disease, of which 123 had pulmonary hypertension (of which 87 had stage II hypertension and 36 were without hypertension) and 47 people were without pulmonary hypertension. The patients were chosen in the period from 2015 to 2018 on the basis of the municipal institution "Zaporizhzhia regional clinical hospital" of the Zaporizhzhia regional council. Results and discussion. The results of this study indicate the role of inflammation, or rather the levels of hs-CRP and IL-6, in the pathogenesis of pulmonary hypertension in patients with chronic obstructive pulmonary disease. The level of hs-CRP among the patients with pulmonary hypertension on a background of chronic obstructive pulmonary disease made up 10.46 [6,24 ; 15,30] mg/l and was significantly higher as against the values in the group of patients with chronic obstructive pulmonary disease without pulmonary hypertension and compared with group of healthy persons. The increase in the level of IL-6 in the group of patients having pulmonary hypertension with chronic obstructive pulmonary disease is significantly higher by 57 % compared to the value in the group of chronic obstructive pulmonary disease without pulmonary hypertension and by 7.4 times the value in the group of healthy individuals (p <0.05). Comparing the subgroups of patients, and depending on the variant of exacerbation of chronic obstructive pulmonary disease, the level of hs-CRP and IL-6 was considerably higher in the subgroup with the infectious type of exacerbation compared with the subgroup of the non-infectious type of exacerbation of chronic obstructive pulmonary disease. Conclusion. After 12 months of treatment, when roflumilast was added to the basic therapy, we revealed a statistically significant difference in the levels of IL-6, hs-CRP and IL-10 in the plasma of patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease combined with hypertension

ObjectiveTo analyse the clinical features of AECOPD (acute exacerbation of chronic obstructive pulmonary disease) at different altitudes and GOLD (global initiative of chronic obstructive lung disease) stages in high-altitude regions.MethodThis was a retrospective cross-sectional study. Patients diagnosed with AECOPD through pulmonary function tests and hospitalised in People’s Hospital of the Tibet Autonomous Region from September 2018 to March 2024 were included. Patients were divided into three groups according to their native residential altitude prior to onset: low-altitude group (169 cases, 2700–3700 m), mid-altitude group (77 cases, 3700–4000 m) and high-altitude group (97 cases, 4000–4800 m). Patients were also classified into three groups according to their FEV1%pred in pulmonary function test on admission: mild (91 cases, FEV1%pred ≥80%), moderate (171 cases, 50%≤FEV1%pred <80%) and severe/very severe (81 cases, FEV1%pred <50%).Result(1) Altitude comparison: the mid-altitude group showed lower values for age (66.49±8.13 years), hospital length of stay (9.79±3.20 days) and time since diagnosis (1.89±1.73 years) compared with the low-altitude group. On the other hand, the mid-altitude group showed higher SPO2 (82.35±5.17%) and pulmonary fibrosis prevalence (40.26%) than the low-altitude group. The high-altitude group had higher rates of emphysema (56.70%) and pulmonary hypertension (51.55%) compared with the low-altitude group. The high-altitude group showed lower levels of B-type natriuretic peptide (BNP) (185.76±195.19 pg/mL), red blood cell count (RBC) (5.77±0.97×1012/L), D-dimer (D-D) (1.01±1.33 mg/L) and fibrinogen degradation product (FDP) (3.11±1.38 mg/L) than the low-altitude group. The high-altitude group had a longer time since diagnosis (2.63±3.39 years) than the mid-altitude group and lower SPO2 (80.01±7.60%), rate of pulmonary fibrosis (22.68%) and BNP level (185.76±195.19 pg/mL) compared with the mid-altitude group. These differences were statistically significant (p<0.05). No significant differences were found for other variables between altitude groups (p>0.05). (2) GOLD staging comparison: the moderate group had higher values for the time since diagnosis (2.61±2.95 years), prevalence of emphysema (50.29%), pulmonary fibrosis (28.07%), pulmonary hypertension (45.61%), cor pulmonale (40.94%), and levels of C-reactive protein (CRP) (23.89±34.01 mg/L) and procalcitonin (PCT) (0.32±0.71 ng/mL) than the mild group. The moderate and severe/very severe groups had lower SPO2 (80.77±6.71%, 78.38±8.31%) than the mild group. The severe/very severe group had higher rates of emphysema (54.31%), pulmonary bullae (28.40%), pulmonary hypertension (59.26%), cor pulmonale (56.79%), and levels of CRP (20.92±29.92 mg/L) and PCT (0.81±3.43 ng/mL) than the mild group. The severe/very severe group had a shorter time since diagnosis (2.27±1.97 years) than the moderate group. The severe/very severe group also had a higher percentage of males (72.84%), pulmonary hypertension (59.26%), cor pulmonale (56.79%), and levels of BNP (392.50±728.31 pg/mL) and PCT (0.81±3.43 ng/mL) compared with the moderate group. These differences were statistically significant (p<0.05). No significant differences were found for other variables between GOLD groups (p>0.05).ConclusionIn high-altitude regions, as the altitude increases, body mass index, the proportion of male patients, rate of emphysema and pulmonary hypertension become more prominent in AECOPD patients. Higher GOLD stages are associated with longer hospital stays, higher smoking indices and greater prevalence of emphysema, pulmonary fibrosis, pulmonary hypertension and cor pulmonale. Lower SPO2 is associated with higher levels of RBC, haemoglobin, haematocrit (HCT), CRP, PCT, white blood cell count and neutrophil%. However, as native residential altitude increases, BNP, RBC, HCT, D-D and FDP decrease.