Pulmonary hypertension in chronic obstructive pulmonary disease.

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 (≥ 16h/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.

Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era.

BACKGROUND: Novel therapies have recently become available for pulmonary arterial hypertension. We conducted a study to characterize mortality in a multicenter prospective cohort of patients diagnosed with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension in the modern management era. METHODS AND RESULTS: Between October 2002 and October 2003, 354 consecutive adult patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension (56 incident and 298 prevalent cases) were prospectively enrolled. Patients were followed up for 3 years, and survival rates were analyzed. For incident cases, estimated survival (95% confidence intervals [CIs]) at 1, 2, and 3 years was 85.7% (95% CI, 76.5 to 94.9), 69.6% (95% CI, 57.6 to 81.6), and 54.9% (95% CI, 41.8 to 68.0), respectively. In a combined analysis population (incident patients and prevalent patients diagnosed within 3 years before study entry; n=190), 1-, 2-, and 3-year survival estimates were 82.9% (95% CI, 72.4 to 95.0), 67.1% (95% CI, 57.1 to 78.8), and 58.2% (95% CI, 49.0 to 69.3), respectively. Individual survival analysis identified the following as significantly and positively associated with survival: female gender, New York Heart Association functional class I/II, greater 6-minute walk distance, lower right atrial pressure, and higher cardiac output. Multivariable analysis showed that being female, having a greater 6-minute walk distance, and exhibiting higher cardiac output were jointly significantly associated with improved survival. CONCLUSIONS: In the modern management era, idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension remains a progressive, fatal disease. Mortality is most closely associated with male gender, right ventricular hemodynamic function, and exercise limitation.

Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease.

RATIONALE: Telomere length is considered a marker for biological aging. Chronic obstructive pulmonary disease (COPD) may be associated with premature aging. OBJECTIVES: To test the hypothesis that patients with COPD experience accelerated telomere shortening and that inflammation is linked to this process. METHODS: We measured telomere length, using a quantitative polymerase chain reaction-based method, and plasma levels of various cytokines in 136 patients with COPD, 113 age- and sex-matched smokers, and 42 nonsmokers with normal lung function. MEASUREMENTS AND MAIN RESULTS: Median (range) telomere length ratio was significantly lower in patients with COPD (0.57 [0.23-1.18]) than in control smokers (0.79 [0.34-1.58]) or nonsmokers (0.85 [0.38-1.55]) (P < 0.001). The difference remained highly significant when using logistic regression analysis adjusted for age, sex, and tobacco exposure. Both females and males with COPD had shorter telomere length than same-sex control subjects. Telomere length was related to age in patients and control subjects but was shorter in patients than in control subjects in all age groups. No relationship was found between telomere length and tobacco exposure in patients or control subjects, with no difference between control smokers and nonsmokers. In patients with COPD, telomere length was related to PaO2 (P < 0.001) and PaCO2 (P < 0.001) but not to lung function parameters or the BODE Index. Patients with COPD also had elevated plasma levels of various cytokines, interleukin-6 correlating negatively with telomere length (P < 0.001). CONCLUSIONS: Given that in vivo telomere length reflects cellular turnover and exposure to oxidative and inflammatory damage, our data support accelerated aging in COPD.

Pulmonary hypertension in chronic obstructive pulmonary disease and interstitial lung diseases.

Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases and particularly of chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Owing to its frequency COPD is by far the most common cause of PH. It is generally a mild to moderate PH, pulmonary artery mean pressure (PAP) usually ranging between 20 and 25 mm Hg, but PH may worsen during exercise, sleep, and particularly during exacerbations of the disease. These acute increases in PAP may lead to the development of right heart failure. A small proportion of COPD patients may present "disproportionate" PH defined by a resting PAP >35 to 40 mm Hg. The prognosis is particularly poor in these patients. PH is relatively frequent in advanced ILD and particularly in idiopathic pulmonary fibrosis. As in COPD the diagnosis is suggested by Doppler echocardiography, but the confirmation still requires right heart catheterization. As in COPD, functional (alveolar hypoxia) and morphological factors (vascular remodeling, destruction of the pulmonary parenchyma) explain the elevation of pulmonary vascular resistance that leads to PH. Also as in COPD PH is most often mild to moderate. In ILD the presence of PH predicts a poor prognosis. The treatment of PH relies on long-term oxygen therapy. "New" vasodilator drugs have rarely been used in COPD and ILD patients exhibiting severe PH. In advanced ILD the presence of PH is a supplemental argument for considering lung transplantation.

Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.

RATIONALE: Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors. OBJECTIVES: We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH). METHODS: Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined. MEASUREMENTS AND MAIN RESULTS: Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test. CONCLUSIONS: Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.

[Clinical classification and epidemiology of pulmonary arterial hypertension]. / Classification, épidemiologie et facteurs de risque de l'hypertension artérielle pulmonaire.

Pulmonary arterial hypertension (PAH) is a rare pulmonary vascular disease. PAH includes idiopathic, familial and associated forms of PAH. The minimal prevalence in the adult French general population is 15 cases per million. PAH must be separated from pulmonary hypertension due to left heart diseases, chronic lung diseases and chronic venous thrombo-embolic disease. Idiopathic PAH mostly affects people in their 4th and 5th decades, mainly females, occasionally children and the elderly are affected. Despite major improvement of pharmaceutical treatments during the last 10 years, PAH still bears a poor prognosis. Five-year survival rates are below 75% in patients under appropriate therapy. Main prognostic factors are the level of dyspnoea on exertion, the degree of exercise impairment and signs (clinical and haemodynamic) of right heart failure. When these signs of poor prognosis are persistent treatments must be optimized.

Correlation between high-resolution computed tomography findings and lung function in pulmonary Langerhans cell histiocytosis.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon interstitial lung disease which can lead to serious respiratory failure. The correlation between high-resolution computed tomography (HRCT) findings and lung function have not been studied in depth. OBJECTIVES: To assess the relationship between HRCT findings and lung function in PLCH. METHODS: Since HRCT abnormalities in PLCH consist mainly of nodular opacities and cystic abnormalities, we determined semiquantitative scores of nodular profusion and cystic extent. We therefore assessed the relationship between HRCT abnormalities on one hand and lung function and gas exchange parameters on the other, in patients with PLCH. RESULTS: In our series of 26 consecutive patients, we found no significant correlation between the score of nodular profusion and lung function or gas exchange parameters. The score of cystic extent showed a quite strong and significant correlation with FEV(1)/FVC (r = -0.62; p = 0.01), but also with PaO(2) (r = -0.69; p = 0.001) and carbon monoxide diffusing capacity (r = -0.60; p < 0.01). Furthermore, the patients with a predominant cystic pattern (n = 7) had the highest grade of dyspnea on exertion (p = 0.004), the lowest FEV(1)/FVC ratio (p = 0.02) and the lowest PaO(2) (p = 0.02) compared to patients with a predominant nodular (n = 12) or a mixed pattern (n = 7). CONCLUSIONS: We conclude that in PLCH, the cystic extent on HRCT, but not the nodular profusion, correlates significantly with lung function abnormalities and impairment of gas exchange.

Renal hyporesponsiveness to brain natriuretic peptide: both generation and renal activity of cGMP are decreased in patients with pulmonary hypertension.

We examined the mechanisms of renal resistance to atrial and brain natriuretic peptides (ANP and BNP) in pulmonary hypertension (PH). Compared to eight controls, nine PH patients showed a reduced ability to excrete an acute sodium load despite increased circulating ANP, BNP and cyclic guanosine monophosphate (cGMP), their second messenger. Patients' reduced urinary cGMP/BNP and natriuresis/urinary cGMP ratios demonstrated impaired generation of and reduced renal response to cGMP, respectively. Therefore, PH patients hyporesponsiveness to cardiac natriuretic peptides is likely located both upstream and downstream cGMP generation. Natriuretic peptide signalling pathway disruptions might be accessible to therapy.

Reduced pulsatility does not explain renal hyporesponsiveness to cardiac natriuretic peptides in pulmonary hypertension.

A pulsatile secretory pattern is assumed to improve hormonal efficiency. We examined the short-term time courses of circulating atrial (ANP) and brain natriuretic peptides (BNP) in patients with pulmonary hypertension (PH) and reduced renal efficiency of ANP-BNP, reflected by low natriuresis/ANP or BNP ratios. Compared to controls, we observed a persistence of ANP and BNP pulsatility in PH patients with a similar periodicity of 20min. Pulse amplitude increased proportionally to the rise in mean plasma level observed in patients (around 27%). In PH patients, the decrease in ANP-BNP renal efficiency is not attributable to a loss of the rhythmic pulsatility of these hormones.

Obstructive sleep apnea syndrome and the pulmonary circulation.

The pulmonary hemodynamic consequences of obstructive sleep apneas have been investigated by several groups during the last 30 years. The earlier data have been obtained by measuring the intravascular pulmonary arterial pressure (PAP) and have shown a rise of PAP during apneas, the highest PAP being observed at the end of apneas. Actually, during obstructive apneas the only reliable measurements are those of transmural PAP which increases throughout the apneas, as a consequence of hypoxic vasoconstriction, and decreases after ventilation has resumed. The link between episodic (nighttime) and permanent (daytime) pulmonary hypertension is poorly understood. Recent studies have clearly indicated that daytime hypoxemia, generally due to an associated chronic airflow obstruction, is the major determinant of permanent pulmonary hypertension and cor pulmonale, and that nocturnal hypoxemia is not sufficient per se.

Sleep and chronic obstructive pulmonary disease.

Patients with COPD who are hypoxaemic during wakefulness become more hypoxaemic during sleep. The most severe episodes of nocturnal desaturation generally occur during REM sleep. There is a strong relationship between nocturnal O2 saturation and the level of daytime PaO2: the more pronounced daytime hypoxaemia, the more severe nocturnal hypoxaemia. The worsening of hypoxaemia is due to a variable combination of alveolar hypoventilation and ventilation-perfusion mismatching, alveolar hypoventilation being the predominant mechanism, at least during REM sleep. The consequences of sleep-related hypoxaemia include peaks of pulmonary hypertension due to hypoxic pulmonary vasoconstriction, generally observed in patients with marked daytime hypoxaemia. Cardiac arrhythmias have been described but their clinical relevance has not been established. The prevalence of obstructive sleep apnoea syndrome (OSAS) is not greater in chronic obstructive pulmonary disease (COPD) patients than in the general population, but this association (Overlap Syndrome) is not rare since COPD and OSAS are both frequent diseases. Overlap patients are at a higher risk of developing respiratory insufficiency than are pure OSAS patients. Polysomnography is only indicated in COPD patients who are suspected of having OSAS. The treatment of nocturnal hypoxaemia is conventional O2 therapy (> or = 16/24 h) in COPD patients with marked daytime hypoxaemia (PaO2 < 55-60 mmHg) and conventional O2 therapy plus nocturnal non-invasive ventilation in some patients with marked hypercapnia. At present data are not sufficient for justifying the use of isolated nocturnal oxygen therapy in COPD patients with nocturnal desaturation but with mild daytime hypoxaemia (PaO2 > 60 mmHg).

Evaluation of unattended automated titration to determine therapeutic continuous positive airway pressure in patients with obstructive sleep apnea.

BACKGROUND: Determination of the therapeutic pressure during continuous positive airway pressure (CPAP) therapy is usually performed by a technician during polysomnography. In recent years, several devices for automated adjustment of the therapeutic pressure by the means of computerized algorithms were developed. The aims of the present study were to compare two different devices for automated titration and to verify if unattended automated titration is a feasible strategy to determine the therapeutic CPAP. METHODS: We enrolled 16 consecutive patients with obstructive sleep apnea syndrome (OSAS) defined by an apnea-hypopnea index > 20/h. Automated titration was performed in the hospital using two CPAP devices (Autoset; Resmed; North Ryde, Australia; and Somnosmart; Weinmann; Hamburg, Germany) in random order for 2 consecutive nights, based on different signals for the detection of respiratory events. During titration, there was no direct supervision by a technician, and polysomnography was not recorded. We defined the therapeutic pressure as the 95th percentile of the airway pressure over time (P95). RESULTS: We observed significant differences of the P95 between the two devices, with an average of 7.0 +/- 2.5 cm H(2)O for the Somnosmart and 9.9 +/- 2.6 cm H(2)O for the Autoset (p = 0.005) [mean +/- SD]. There was a considerable lack of agreement between the two devices, with a bias of 3.0 cm H(2)O and limits of agreement ranging from + 9.3 to - 3.2 cm H(2)O. We found no significant correlation between the paired differences of P95 and either indexes of severity of OSAS or lung function variables. CONCLUSION: Automated titration based on the analyses of flow (Autoset) or forced oscillations (Somnosmart) predicted significant different therapeutic pressures for fixed CPAP therapy. Thus, unattended automated titration performed during 1 night of hospital stay with commercially available devices cannot be used to determine accurately the therapeutic CPAP in patients with OSAS.

Dry powder ipratropium bromide is as safe and effective as metered-dose inhaler formulation: a cumulative dose-response study in chronic obstructive pulmonary disease patients.

A multi-center, open, randomized, 2-way crossover study was conducted with chronic obstructive pulmonary disease (COPD) patients to compare the safety and efficacy of cumulative doses of ipratropium bromide administered from a pressurized metered-dose inhaler (MDI) or from a breath-activated dry powder inhaler (DPI). Enrolled in the study were 39 patients with moderate to severe COPD and who showed a > or= 15% increase in baseline forced expiratory volume in the first second (FEV(1)) after 80 microg of ipratropium bromide. Thirty-six patients were evaluable for efficacy analysis, and 38 patients were included in the safety analysis group. A significant improvement in pulmonary function was observed following inhalation of cumulative doses of ipratropium bromide (from 20 to 320 microg), but no statistically significant difference was found between the 2 formulations. The dose-response curves were similar. There was no statistical difference in area-under-the-curve during the 180 min period after the last dose for any of the pulmonary function variables. Overall, effects on pulse rate, blood pressure, and QT interval on electrocardiogram were no different between the devices. Six mild adverse events occurred in 4 patients: ventricular ectopic beats on electrocardiogram at 270 min with MDI, bad taste with both MDI and DPI, slight transient increase in blood pressure in the same patient during each study day with both MDI and DPI. Two moderate adverse events occurred in 2 patients: transient ventricular ectopic beats on electrocardiograms with DPI at 270 min, moderate bronchospasm with MDI at 200 min. Patients expressed a preference for DPI, which was found to have a better acceptability and appeared to be easier to use than MDI. The new lactose powder formulation of ipratropium bromide inhaled via the breath-activated DPI is a safe and effective alternative to the chlorofluorocarbon-propelled MDI.

[COPD: from early symptoms to chronic respiratory failure]. / Bronchopneumopathie chronique obstructive: des premiers symptômes a l'insuffisance respiratoire chronique.

COPD is a frequent and progressive disease, which can lead to severe respiratory impairment. Smoking is the main causal factor. Therefore, respiratory symptoms should not be underestimated in smokers. Chronic cough, chronic sputum, persistent dyspnea on exercise (even for sustained efforts) need further investigations. Each smoker has to be considered as potentially having COPD. Lung function measurements are required in these patients.

[Pulmonary function tests in chronic obstructive pulmonary disease]. / Explorations fonctionnelles respiratoires dans la bronchopneumopathie chronique obstructive.

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on the presence of chronic airflow limitation poorly reversible or not reversible at all, defined by an FEV1/FVC ratio less than 70%. Stages of severity of COPD are defined according to the level of post-bronchodilator FEV1: > 80% of the predicted value (stage I); 50-80% (stage II); 30-50% (stage III); < 30% (stage IV). Accordingly, the measurement of pulmonary volumes (spirometry) is required for the diagnosis but also for the follow-up of COPD patients. The investigations which are required depend on the severity of COPD: spirometry and flow-volume curves during forced expiration are sufficient in stage I; measurement of static lung volumes and bronchodilator reversibility testing are required in stage II. Arterial blood gases should be measured in stages III and IV. Pulse oxymetry and 6minute walk test (6MWT) are recommended from stage II. For appreciating the severity of COPD and for the follow-up of patients it is recommended to evaluate other variables than FEV1: results of the 6MWT, level of dyspnea, body mass index. The results of FEV1 and of these variables are included in the recently developed BODE index. Measurement of CO transfer capacity is recommended in the presence of emphysema; cardiopulmonary exercise testing (bicycle) is recommended before initiating exercise training.

Role for interleukin-6 in COPD-related pulmonary hypertension.

BACKGROUND: Pulmonary artery remodeling triggered by alveolar hypoxia is considered the main mechanism of pulmonary hypertension (PH) in COPD patients. We hypothesized that the risk for PH in COPD is increased by an elevation in the proinflammatory cytokines interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and IL-1beta, as well as by specific genetic polymorphisms of these cytokines. METHODS: We assessed cytokine plasma levels and the polymorphisms G(-174)C IL-6, C(-511)T IL-1beta, and A(-2518)G MCP-1 in 148 COPD patients (recruited at two centers) with right heart catheterization data and 180 control subjects including smokers and nonsmokers. Human pulmonary artery smooth muscle cells (PA-SMCs) were cultured for IL-6 messenger RNA assays under normoxic and hypoxic conditions. RESULTS: Patients with PH (mean pulmonary artery pressure [PAP], >or= 25 mm Hg) had lower Pao(2) and higher plasma IL-6 values than those without PH; there were no differences in terms of pulmonary function test results or CT scan emphysema scores. Plasma IL-6 correlated with mean PAP (r = 0.39; p < 0.001) and was included in a multiple stepwise regression analysis, with mean PAP as the dependent variable. In patients with the IL-6 GG genotype, the mean PAP value was significantly higher and PH was more common than in CG or CC patients (adjusted odds ratio, 4.32; 95% confidence interval, 1.96 to 9.54). Exposure to 4 h of hypoxia led to an about twofold increase in IL-6 messenger RNA in cultured human PA-SMCs. CONCLUSIONS: Inflammation, most likely involving IL-6, may contribute substantially to PH complicating COPD.

Overlap syndrome: obstructive sleep apnea in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome (SAHS) are both common diseases affecting respectively 10 and 5% of the adult population over 40 years of age, and their coexistence, which is denominated overlap syndrome, can be expected to occur in about 0.5% of this population. A recent epidemiologic study has shown that the prevalence of SAHS is not higher in COPD than in the general population, and that the coexistence of the two conditions is due to chance and not through a pathophysiologic linkage between these two diseases. Patients with overlap have a more important sleep-related O(2) desaturation than do patients with COPD with the same degree of bronchial obstruction. They have an increased risk of developing hypercapnic respiratory insufficiency and pulmonary hypertension when compared with patients with SAHS alone and with patients with "usual" COPD. In patients with overlap, hypoxemia, hypercapnia, and pulmonary hypertension can be observed in the presence of mild to moderate bronchial obstruction, which is different from "usual" COPD. Therapy of the overlap syndrome consists of nasal continuous positive airway pressure or nocturnal noninvasive ventilation (NIV), with or without associated nocturnal O(2). Patients who are markedly hypoxemic during daytime (Pa(O(2)) < 55-60 mm Hg) should be given conventional long-term O(2) therapy in addition to nocturnal ventilation.

Spontaneous short-term variations of circulating endothelin-1 in pulmonary hypertension.

Endothelin-1 (ET-1) is overexpressed in pulmonary arteries of pulmonary hypertension (PH) patients and contributes to the sustained vasoconstriction, remodeling process, and thrombosis of vessels that underlie development and progression of this disease. Increased circulating ET-1 correlates with markers of PH severity, and ET-1 is regarded as a potential diagnostic and prognostic biomarker in PH. Because the within-individual variability measured in PH patients and in healthy subjects contributes to determine the biomarker predictive value and must be taken into account to establish cutoff values, we determined the short-term variability of circulating ET-1 in controls and in PH patients.

Pulmonary arterial hypertension in France: results from a national registry.

RATIONALE: Pulmonary arterial hypertension (PAH) is an orphan disease for which the trend is for management in designated centers with multidisciplinary teams working in a shared-care approach. OBJECTIVE: To describe clinical and hemodynamic parameters and to provide estimates for the prevalence of patients diagnosed for PAH according to a standardized definition. METHODS: The registry was initiated in 17 university hospitals following at least five newly diagnosed patients per year. All consecutive adult (> or = 18 yr) patients seen between October 2002 and October 2003 were to be included. MAIN RESULTS: A total of 674 patients (mean +/- SD age, 50 +/- 15 yr; range, 18-85 yr) were entered in the registry. Idiopathic, familial, anorexigen, connective tissue diseases, congenital heart diseases, portal hypertension, and HIV-associated PAH accounted for 39.2, 3.9, 9.5, 15.3, 11.3, 10.4, and 6.2% of the population, respectively. At diagnosis, 75% of patients were in New York Heart Association functional class III or IV. Six-minute walk test was 329 +/- 109 m. Mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance index were 55 +/- 15 mm Hg, 2.5 +/- 0.8 L/min/m(2), and 20.5 +/- 10.2 mm Hg/L/min/m(2), respectively. The low estimates of prevalence and incidence of PAH in France were 15.0 cases/million of adult inhabitants and 2.4 cases/million of adult inhabitants/yr. One-year survival was 88% in the incident cohort. CONCLUSIONS: This contemporary registry highlights current practice and shows that PAH is detected late in the course of the disease, with a majority of patients displaying severe functional and hemodynamic compromise.