Severe pulmonary hypertension in histiocytosis X

Diminished exercise capacity in advanced pulmonary histiocytosis X does not appear to be related to ventilatory limitation but may be related to pulmonary vascular dysfunction. Pulmonary hemodynamics and respiratory function were studied in 21 consecutive patients with advanced pulmonary histiocytosis X, and compared with parameters of patients with other severe chronic lung diseases (29 patients with chronic obstructive pulmonary disease and 14 patients with idiopathic pulmonary fibrosis). All patients with pulmonary histiocytosis X displayed severe pulmonary hypertension: mean pulmonary arterial pressure, 59 +/- 4 mm Hg; cardiac index, 2.6 +/- 0.8 L/min/m(2); and total vascular pulmonary resistance, 25 +/- 3 IU/m(2) (p < 0.05, as compared with patients with other chronic lung diseases). Pa(O(2)) was similar in the three groups, whereas FEV(1) was lower in patients with other chronic lung diseases (p < 0.05). In contrast to other chronic lung diseases, the degree of pulmonary hypertension was not related to variables of pulmonary function in pulmonary histiocytosis X. Histopathology was available for 12 patients with pulmonary histiocytosis X and revealed proliferative vasculopathy involving muscular arteries and veins, with prominent venular involvement. Two consecutive lung samples (taken before and after the occurrence of pulmonary hypertension) were available for six patients with pulmonary histiocytosis X, and showed that pulmonary vasculopathy worsened, whereas parenchymal and bronchiolar lesions remained relatively unchanged. These results indicate that pulmonary hypertension in pulmonary histiocytosis X might be related to an intrinsic pulmonary vascular disease, in which the pulmonary circulation is involved independent of small airway and lung parenchyma injury.     

Bosentan in pulmonary arterial hypertension secondary to scleroderma

OBJECTIVE:. To assess the efficacy and tolerability of bosentan in pulmonary arterial hypertension secondary to systemic sclerosis (SSc-PAH) including patients with restrictive lung disease. METHODS: We retrospectively reviewed 23 SSc-PAH patients with PAH at baseline [PA systolic pressure (PASP) >or= 45 mm Hg by echocardiogram or mean PA pressure > 25 mm Hg at rest by cardiac catheterization], World Health Organization (WHO) functional classes II-IV, and with data available for 18 months. Bosentan dose was 62.5 mg twice daily for 1 month then 125 mg twice daily. Outcomes were WHO functional class, PASP, and pulmonary function tests (PFT) at 3-month intervals for 18 months. RESULTS: WHO class at baseline 3.1 +/- 0.1 (mean +/- SE); 3 months, 2.5 +/- 0.2*; 6 months, 2.4 +/- 0.2*; 9 months, 2.5 +/- 0.2* (*p < 0.02 vs baseline, n = 21 to 23), indicating clinical improvement at 9 months. After 9 months, results were not significant versus baseline. Reduction in WHO class by at least one rank was 57% at 3 months; none worsened. After 9 months, WHO class tended to worsen compared to baseline. Baseline PASP was 54 +/- 2 mm Hg (n = 23) and did not change significantly with therapy. Restriction (total lung capacity 76% +/- 4% of predicted) and reduced diffusing capacity (39% +/- 3% of predicted) were unchanged during therapy. Abnormal transaminases in 2 patients (9%) necessitated discontinuing drug in both. CONCLUSION: Bosentan is clinically beneficial in patients with SSc-PAH including patients with restrictive lung disease, but pulmonary hemodynamics and PFT results remained stable during treatment.     

Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease.

Patients with cystic fibrosis (CF) and advanced pulmonary disease have pulmonary limitation of exercise, often associated with arterial oxygen desaturation. Improving oxygenation during exercise by providing supplemental oxygen may improve exercise performance in these patients. To test this, we performed graded exercise stress tests in 22 CF patients with severe pulmonary disease (mean PaO2, 64 +/- 2 mm Hg [+/- SE]; PaCO2 46 +/- 2 mm Hg; RV/TLC, 57 +/- 4 percent; FEV1, 38 +/- 4 percent of predicted; FEF25-75%, 13 +/- 2 percent of predicted; median age, 26 years) and compared them to 21 controls (RV/TLC, 27 +/- 4 percent; FEV1, 112 +/- 2 percent of predicted; FEF25-75%, 80 +/- 4 percent of predicted; median age, 29 years). Each subject performed graded exercise stress tests while breathing FIO2 of 0.21 and FIO2 of 0.30. Subjects were blinded to the composition of the inspired gas, and the order of testing was randomized. We found that CF subjects exercised longer, had a higher maximal VO2, higher O2 pulse, and less arterial oxygen desaturation when receiving supplemental O2. Control subjects exercised longer when breathing supplemental O2 but had no significant change in maximal VO2, O2 pulse, or SaO2. Both CF and control subjects had increased end-tidal PCO2 when exercising while breathing supplemental O2. We conclude that CF patients with advanced pulmonary disease have increased exercise tolerance and aerobic capacity when exercising while breathing supplemental O2.     

Frequency and mechanism of daytime pulmonary hypertension in patients with obstructive sleep apnoea syndrome

In order to study the frequency and the mechanisms of daytime pulmonary hypertension (PH) in obstructive sleep apnoea syndrome (OSAS) lung function tests, blood gas analysis and right-heart catheterization were performed in 46 consecutive patients. OSAS was assessed by polysomnography. 9 patients only (20%) had PH (mean pulmonary artery pressure (Ppa) greater than or equal to 20 mmHg). Patients with PH had lower daytime PaO2 (60.8 +/- 7.6 vs. 76.2 +/- 9.4 mmHg; p less than 0.001), higher daytime PaCO2 (44.8 +/- 4.2 vs. 38.0 +/- 4.0 mmHg; p less than 0.001), lower forced vital capacity (FVC) and forced expiratory volume (FEV1) (p less than 0.001), but the severity of OSAS was not different whether PH was present or not (apnoea index: 62 +/- 34 hour in the PH group vs. 65 +/- 40 hour, apnoea + hypopnoea index 102 +/- 33 hour in the PH group vs. 86 +/- 36 hour, lowest sleep SaO2: 59 +/- 21% in the PH group vs. 66 +/- 18%). There were significant correlations between Ppa and: daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), FEV1 (r = -0.52; p less than 0.001) but not between Ppa and apnoea index, apnoea + hypopnoea index, lowest sleep SaO2. PH and daytime hypoxaemia were associated either with chronic airway obstruction or with severe obesity.     

Sleep quality, carbon dioxide responsiveness and hypoxaemic patterns in nocturnal hypoxaemia due to chronic obstructive pulmonary disease (COPD) without daytime hypoxaemia.

In order to clarify whether nocturnal hypoxaemia (arterial oxygen saturation, SaO2 < 90%) may exist in the long-term before daytime hypoxaemia (PaO2 < 8.0 kPa) occurs in chronic obstructive pulmonary disease (COPD), 21 patients with stable severe COPD without daytime hypoxaemia (PaO2 > or = 8.0 kPa) were studied prospectively. Subjects were monitored twice by polysomnography (PSG) 12 months apart. Spirometry was performed, and diffusion capacity (DLCO) and hypercapnic respiratory drive response delta PI0.1 delta PCO2(-1)) were measured during the daytime in conjunction with polysomnography. At the start of the study our subjects had FEV1 %P (FEV1 as a percentage of predicted value) of 26.1 +/- 7.2%, a mean nocturnal nadir SaO2 of 83 +/- 5%, and a mean SaO2 during nocturnal hypoxaemic episodes of 88.0 +/- 0.7%. The patients' delta PI0.1 delta PCO2(-1) was 1.8 +/- 1.4 cm H2O kPa-1 (within the normal range). For the entire study group, no significant change in any lung function or blood gas parameter was noted during the year of observation, and nocturnal SaO2 remained unaltered. Stage I sleep decreased (P < 0.05) after 12 months. Prolonged stage I sleep was associated with nocturnal hypoxaemia at the second PSG. Five subjects developed daytime hypoxaemia and they showed poorer lung function but similar nocturnal hypoxaemia and delta PI0.1 delta PCO2(-1) level compared to the rest of the patients. Patients with sudden SaO2 dips had more pronounced nocturnal hypoxaemia and prolonged wakefulness than 'non-dippers'. In conclusion, the mean level of nocturnal hypoxaemia may persist unaltered for at least 1 yr. COPD patients with exclusively nocturnal hypoxaemia have a hypercapnic drive response within the normal range. Prolonged nocturnal hypoxaemia and reduced whole night oxygenation are associated with increased superficial sleep. Sleep fragmentation and high carbon dioxide sensitivity may be important defence mechanisms against sleep-related hypoxaemia. The appearance of daytime hypoxaemia is preceded by a substantial deterioration in lung function, but by only a minor deterioration of nocturnal hypoxaemia.     

Increased arginase activity in cystic fibrosis airways

RATIONALE: Airway nitric oxide concentrations are reduced in cystic fibrosis (CF). Arginases compete for L-arginine, the substrate of nitric oxide synthesis. OBJECTIVES: We hypothesized that increased arginase activity may be one factor contributing to nitric oxide deficiency in CF. MEASUREMENTS: We therefore studied sputum arginase activity, exhaled nitric oxide, and pulmonary function in patients with cystic fibrosis. RESULTS: Mean (+/- SEM) sputum arginase activity was significantly higher in patients admitted for pulmonary exacerbation compared with patients with stable disease (1.032 +/- 0.148 vs. 0.370 +/- 0.091 U/mg protein, p = 0.004). Fourteen days of intravenous antibiotic treatment resulted in significantly decreased sputum arginase activity in all patients (p = 0.0002). However, arginase activity was still significantly (p = 0.0001) higher in CF sputum after treatment for exacerbation compared with induced sputum from healthy control subjects (0.026 +/- 0.006 U/mg protein). Negative correlations were found for sputum arginase activity at admission with FEV1 (r = -0.41, p = 0.01), as well as changes in arginase activity with percent change in FEV1 during antibiotic therapy (r = -0.4, p < 0.01) in CF. Exhaled nitric oxide in CF was positively correlated to FEV1 (r = 0.34, p = 0.007), and in patients admitted for pulmonary exacerbation negatively correlated to sputum arginase activity (r = -0.45, p = 0.03). CONCLUSIONS: These data suggest that increased sputum arginase activity contributes to nitric oxide deficiency in CF lung disease and may be relevant in the pathogenesis of CF airway disease.     

Reduced exercise capacity and stress-induced pulmonary hypertension in patients with scleroderma

OBJECTIVES: We sought to determine the incidence of stress-induced pulmonary artery (PA) systolic hypertension in a referral population of patients with scleroderma, and to examine the relation between stress-induced pulmonary systolic hypertension and exercise capacity in this population. BACKGROUND: Early detection of patients with scleroderma at risk for pulmonary hypertension (PHTN) could lead to more timely intervention and thus reduce morbidity and improve mortality. The change in PA systolic pressure (PASP) with exercise provides a possible tool for such detection. METHODS: Sixty-five patients with scleroderma (9 men and 56 women; mean age 51 +/- 12 years [SD]), normal resting PASP, and normal resting left ventricular function underwent exercise Doppler echocardiography using a standard Bruce protocol. Tricuspid regurgitation velocity was measured before and after exercise. Exercise variables including workload achieved in metabolic equivalents (METS), total exercise time, percentage of target heart rate achieved, and PASP at rest and within 60 s after exercise were recorded. RESULTS: Thirty patients (46%) demonstrated an increase in PASP to > 35 mm Hg plus an estimated right atrial pressure of 5 mm Hg. Postexercise PASP inversely correlated to both the maximum workload achieved (r = - 0.34, p = 0.006) and exercise time (r = - 0.31, p = 0.01). In women, the correlation was more significant (r = - 0.38, p = 0.003). Patients in the lowest quartile of exercise time, with the least cardiac workload achieved, produced the highest postexercise PASP. CONCLUSION: Stress-induced PHTN is common in patients with scleroderma, even when resting PASP is normal. Stress Doppler echocardiography identifies scleroderma patients with an abnormal rise in PASP during exertion. Peak PASP is linearly related to exercise time and maximum workload achieved. Measurement of PASP during exercise may prove to be a useful tool for the identification of future resting PHTN.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea syndrome

The frequency of daytime pulmonary hypertension (PH) in patients with obstructive sleep apnea syndrome (OSAS) has not been well established and its mechanisms are still under debate. We have thus performed right heart catheterization, in addition to standard spirography and arterial blood gas measurements, in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography. Only 9 of the 46 patients (20%) had PH defined by a mean resting pulmonary arterial pressure (Ppa) greater than or equal to 20 mm Hg. Among the patients without resting PH, 14 had exercising PH (defined by a Ppa greater than 30 mm Hg during 40-watt, steady-state exercise). Patients with resting PH differed from the others by a lower daytime PaO2 (60.8 +/- 7.6 versus 76.2 +/- 9.4 mm Hg; p less than 0.001), a higher daytime PaCO2 (44.6 +/- 4.2 versus 38.0 +/- 4.0 mm Hg; p less than 0.001), and lower VC and FEV1 (p less than 0.001). There was no difference between the 2 groups with regard to apnea index (62 +/- 34 versus 65 +/- 40) or the lowest sleep SaO2 (59 +/- 21 versus 66 +/- 18%) or the time spent in apnea. For the group as a whole, there was a good correlation between Ppa and daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), and FEV1 (r = -0.52; p less than 0.001), but there was no significant correlation between Ppa and the apnea index, the lowest sleep SaO2, or the time spent in apnea.(ABSTRACT TRUNCATED AT 250 WORDS)     

内源性硫化氢在慢性阻塞性肺疾病患者中的变化及意义

目的研究内源性硫化氢(H2S)在慢性阻塞性肺疾病(COPD)发病中的作用。方法COPD急性加重组(AECOPD组)27例、稳定期COPD组37例和健康对照组13名,在入选时测定血清H2S和一氧化氮(NO)水平、肺功能、诱导痰细胞分类计数,对AECOPD患者行超声心动图和血气分析。结果(1)血清H2S水平稳定期COPD组[(50·8±2·5)μmol/L]比健康对照组[(39·8±1·6)μmol/L]、AECOPD组[(33·5±2·2)μmol/L]均显著增加(P均<0·01)。(2)AECOPD组吸烟者血清H2S[(28·1±1·3)μmol/L]比非吸烟者[(39·4±3·9)μmol/L,P<0·05]和健康非吸烟者显著降低[(39·8±1·6)μmol/L,P<0·01]。(3)稳定期COPD组不同程度气流阻塞患者血清H2S水平呈线性下降趋势(P<0·05),COPD全球创议(GOLD)Ⅲ期[(45·1±4·1)μmol/L]较Ⅰ期患者[(70·2±6·2)μmol/L]血清H2S水平显著下降(P<0·05)。(4)AECOPD组伴有肺动脉高压患者血清H2S水平显著降低[(26·3±2·2)、(36·2±2·5)μmol/L,P<0·05]。(5)血清H2S与NO、第一秒用力呼气容积占预计值百分比(FEV1占预计值%)、诱导痰淋巴细胞计数、诱导痰巨噬细胞计数均呈正相关(r=0·278~0·533,P均<0·05或0·01),与肺动脉收缩压(PASP)、诱导痰中性粒细胞计数均呈负相关(r=-0·561、-0·422,P=0·011、0·001)。结论内源性H2S可能参与COPD气流阻塞的发病,作为一种无创指标监测疾病严重程度和活动度具有一定意义。     

Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients

The mechanism of sustained awake hypercapnia in the obstructive sleep apnea syndrome (OSA) is unknown. Recent work has implicated coexisting chronic airflow limitation (CAL) as an important contributing factor. We approached this question by studying consecutive patients with both OSA syndrome and severe CAL in detail and comparing those with and without retention of CO2 while awake. Of 28 patients with both severe OSA (mean NREM apnea index = 48 +/- 9, SEM) and severe CAL (mean FEV1 = 1.07 +/- 0.07 L), 14 had persistent awake hypercapnia (mean PaCO2 = 50 +/- 1 mm Hg), and 14 were normocapnic (mean PaCO2 = 40 +/- 1 mm Hg). When separated according to their PaCO2 level, there was no difference in the apnea indices in both non-rapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep, although the hypercapnic group had lower average levels of oxyhemoglobin saturation in both NREM (SaO2 = 77 +/- 2% versus 85 +/- 3%, p less than 0.05) and REM (SaO2 = 60 +/- 4% versus 82 +/- 3%, p less than 0.001) sleep. The mean values for FEV1, VC, lung volumes, and diffusing capacity for CO measured while awake did not differ. The hypercapnic group had lower awake PaO2 levels (p less than 0.001), were heavier (p less than 0.05), had narrower upper airway size on CT scan measurements (p less than 0.01), and gave a history of much heavier alcohol intake (p less than 0.05). Our results demonstrate that some patients with severe OSA and severe CAL can maintain normal awake arterial CO2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

Pulmonary artery pressure in lymphangioleiomyomatosis: an echocardiographic study

BACKGROUND: Exercise-induced hypoxemia is frequent in patients with lymphangioleiomyomatosis (LAM) and could be associated with pulmonary hypertension. The aims of this study were to determine the prevalence of pulmonary hypertension in patients with LAM, to identify physiologic parameters associated with its occurrence, and to evaluate the effect of oxygen on response to exercise. METHODS: Studies were performed in 120 patients. Complete data, including exercise echocardiography, pulmonary function testing, and standard cardiopulmonary exercise testing, were obtained in 95 patients. RESULTS: Resting pulmonary artery pressure (PAP) was 26+/-0.7 mm Hg (mean+/-SEM). Eight patients had pulmonary hypertension (43+/-3 mm Hg), and two patients had right ventricular dilatation. Ninety-five patients exercised (room air, n=64; oxygen, n=31) to a power of 58+/-2 W (49% of predicted) and an estimated peak oxygen uptake of 938+/-30 mL/min (56% of predicted). Sixty-one patients had a decline in arterial oxygen saturation (SaO2)>3%, and 56 patients had an elevation in PAP>40 mm Hg. Peak exercise PAP was negatively correlated with exercise Sao2 (p=0.0005). Multivariate analysis showed that exercise SaO2 was the best predictor of exercise PAP (p=0.012). CONCLUSIONS: Although resting pulmonary hypertension is rare in patients with LAM, a rise in PAP at low exercise levels occurs frequently, in part related to exercise-induced hypoxemia. Optimization of oxygen administration during activities of daily living should be undertaken in patients with LAM to prevent hypoxemia and exercise-induced pulmonary hypertension.     

Prevalence and fate of severe pulmonary hypertension in 559 consecutive patients with severe rheumatic mitral stenosis undergoing mitral balloon valvotomy

BACKGROUND AND AIM OF THE STUDY: The prevalence of severe pulmonary hypertension (PH) in patients with severe mitral stenosis (MS) remains unknown, and the long-term effect of mitral balloon valvotomy (MBV) in large numbers of these patients is not well characterized. METHODS: Details from the prospective MBV database at the authors' institution relating to 559 consecutive patients who had successful MBV were analyzed. Patients were allocated to three groups on the basis of their pulmonary artery systolic pressure (PASP) at cardiac catheterization immediately before MBV: group A (n = 345) had PASP <50 mmHg; group B (n = 183) had PASP 50-79 mmHg; and group C (n = 31) had PASP > or =80 mmHg. Patients were evaluated clinically and echocardiographically at six months after MBV, and annually thereafter for up to 13 years. RESULTS: No mortality was encountered after MBV. Immediately after MBV, the mean PASP was 38.5+/-6.8 mmHg in group A (mild PH), 59.0+/-7.7 mmHg in group B (moderately severe PH), and 97.8+/-17.0 mmHg in group C (severe PH). At follow up (ca. 4 years), Doppler-monitored PASP fell to normal, and was similar in groups A, B and C (29+/-8, 31+/-9, and 29+/-5 mmHg, respectively; p = NS). CONCLUSION: MBV was shown to be safe and effective in treating patients with MS and severe PH. The latter condition regressed to normal levels over 6-12 months after successful MBV.     

Factors that correlate with sleep oxygenation in children with cystic fibrosis

OBJECTIVE: Cystic fibrosis (CF) patients may develop hypoxemia during sleep. Limited information is available on nocturnal oxygen saturation in CF children with less severe lung disease. The aim of this study was to investigate the degree of nocturnal oxygen desaturation and factors that correlate with nocturnal oxygenation in CF children with normal pulmonary function tests (PFTs) or mild to moderate lung disease. METHOD: Awake resting and post-exercise SpO2 were measured by pulse oximetry. Each patient had overnight oximetry monitorization at home. Six minutes walk test (6MWT), Shwachman-Kulczycki (S-K), Brasfield and computed tomography (CT) scores, blood gas analysis and nutritional status of patients were evaluated. RESULTS: Twenty-four patients with a median age of 9.5 years were included. Nocturnal mean SpO2 did not differ according to the severity of lung disease based on PFT. However, lowest SpO2 obtained was lower in children with both mild and moderate lung disease compared to normals (87.4% vs. 91.7%, respectively, p = 0.009). 95.8% of CF children with normal PFT or mild to moderate lung disease had desaturation events during sleep. Nocturnal mean SpO2 correlated with S-K (Spearman's rho = 0.64, p < 0.0001), Brasfield (Spearman's rho = 0.31, p = 0.007) and CT scores (Spearman's rho = -0.67, p < 0.0001) as well as PaO2 (Spearman's rho = 0.28, p = 0.021), SaO2 (Spearman's rho = 0.28, p = 0.023), z-score of weight (Spearman's rho = 0.23, p = 0.20) and height (Spearman's rho = 0.20, p = 0.30), there was no correlation with 6MWT. CONCLUSIONS: In CF children with normal PFT or mild-to-moderate lung disease, nocturnal oxygenation may correlate with S-K, Brasfield and CT scores as well as PaO2, SaO2, z-score of weight and height.     

Endothelial cell activity in chronic obstructive pulmonary disease without severe pulmonary hypertension.

Pulmonary hypertension is common in patients with chronic obstructive pulmonary disease (COPD), but the precise mechanism of vascular impairment in these patients is unknown. We, therefore, decided to investigate whether endothelial cell dysfunction is present in patients with COPD with a wide range of chronic airflow obstruction before the development of severe pulmonary hypertension. Selected plasma markers of endothelial cell activity were studied: nitrate+nitrite (NO-(2)/NO-(3)), thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), soluble selectins (endothelium sES, leukocyte sLS, platelet sPS), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1). Twenty-five patients with COPD (forced expiratory volume in one second/vital capacity [FEV(1)/VC] < 88% predicted) and 29 healthy control subjects were recruited to the study. Among patients nine had a pulmonary artery systolic pressure (PASP) between 15 and 30 mmHg, 13 between 32 and 38 mmHg, 2 had a PASP of 41 and 42 mmHg, respectively. One patient had severe pulmonary hypertension with a PASP of 70 mmHg. The average FEV(1) of patients with COPD was 46 +/- 4% predicted. As compared to control subjects, patients with COPD showed a significant increase in plasma levels of TM and TFPI, indicating that their endothelial cells are still able to produce potent coagulation inhibitors. Levels of NO-(2)/NO-(3) were similar in the two groups of subjects examined, further suggesting preserved endothelial function in patients with COPD. In regard to adhesion molecules, patients with COPD showed a reduction in sLS, sPS, and sPECAM-1, and an increase in sICAM-1. This study shows that endothelial cell activity is largely preserved in patients with COPD without severe pulmonary hypertension, suggesting that these patients, despite quite severe airway obstruction, retain reasonably normal endothelial function until they develop severe pulmonary hypertension.     

Predicting sleep-disordered breathing in patients with cystic fibrosis

STUDY OBJECTIVES: To examine predictors of sleep-disordered breathing in patients with cystic fibrosis (CF) and moderate-to-severe lung disease using a comprehensive evaluation of both sleep and daytime function. DESIGN: Cross-sectional analysis of sleep studies, lung function, respiratory muscle strength, and evening and morning arterial blood gas measurements in patients with stable CF. A questionnaire addressing sleep quality was administered. Forward stepwise regression analysis was used to identify the parameters that best predict sleep-related desaturation, hypercapnia, and respiratory disturbance. SETTING: Sleep investigation unit and lung function laboratory. PATIENTS: Thirty-two patients with CF and FEV(1) < 65% predicted, in stable clinical condition. Patients were aged 27 +/- 8 years (mean +/- 1 SD) with FEV(1) of 36 +/- 10% predicted, evening PaO(2) of 68 +/- 8 mm Hg, and PaCO(2) of 43 +/- 5 mm Hg. RESULTS: Evening PaO(2) (p < 0.0001) and morning PaCO(2) (p < 0.01) were predictive of the average minimum oxyhemoglobin saturation per 30-s epoch of sleep (r(2) = 0.74; p < 0.0001). Evening PaO(2) (p < 0.001) was predictive of the rise in transcutaneous carbon dioxide (TcCO(2)) seen from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep (r(2) = 0.37; p < 0.001). In addition, there was some relationship between expiratory respiratory muscle strength and the REM respiratory disturbance index (r(2) = 0.22; p < 0.01). CONCLUSION: Evening PaO(2) was found to contribute significantly to the ability to predict both sleep-related desaturation and the rise in TcCO(2) from NREM sleep to REM sleep in this subgroup of patients with CF.     

Lung elastic recoil does not correlate with pulmonary hemodynamics in severe emphysema

BACKGROUND: It has been postulated that right ventricular (RV) function may improve after lung volume reduction surgery (LVRS) for severe emphysema due to improvement in lung elastic recoil. Improved lung elastic recoil after LVRS is hypothesized to "tether" open extraalveolar vessels, thereby leading to a decrease in pulmonary vascular resistance (PVR) and improved RV function. Whether a relationship exists between static elastic lung recoil and pulmonary hemodynamics in severe emphysema, however, is unknown. METHODS: We prospectively studied 67 patients with severe emphysema (32 women; mean age, 65.3+/-6.6 years [SD]; mean FEV1, 0.79+/-0.25 L) who had hyperinflation (total lung capacity [TLC], 122.5+/-12.3% of predicted) and gas trapping (residual volume, 209.1+/-41.1% of predicted), and were referred to the National Emphysema Treatment Trial. Lung elastic recoil was measured both at TLC (coefficient of retraction [CR]) and at functional reserve capacity (CR at functional residual capacity [CRfrc]) in each patient. RESULTS: CR and CRfrc values were 1.3+/-0.6 cm H2O/L and 0.61+/-0.5 cm H2O/L, respectively. Hemodynamic measurements revealed a pulmonary artery (PA) systolic pressure of 35.9+/-8.9 mm Hg, mean PA pressure of 24.8+/-5.6 mm Hg, and PVR of 174+/-102 dyne*s*cm(-5). No significant correlations were found between CR and PVR (R=-0.046, p=0.71), PA systolic pressure (R=0.005, p=0.97), or mean PA pressure (R=-0.028, p=0.82). Additionally, no significant correlations were found between CRfrc and PVR (R=-0.002, p=0.99), PA systolic pressure (R=-0.062, p=0.62), or mean PA pressure (R=-0.041, p=0.74). CONCLUSIONS: We conclude there is no correlation between lung elastic recoil and pulmonary hemodynamics in severe emphysema, suggesting that elastic lung recoil is not an important determinant of secondary pulmonary hypertension in this group. Registered with www. clinicaltrials.gov, #NCT00000606.     

Rheumatic mitral valve stenosis is associated with impaired flow-mediated dilatation

Isolated pulmonary hypertension with clinical implication is rare in rheumatoid arthritis. We sought to study the prevalence of pulmonary arterial hypertension in an unselected population of 45 patients with rheumatoid arthritis (classified according to the ARA criteria) without cardiac disease and corresponding age and sex matched controls by Doppler echocardiography. The pulmonary artery systolic pressure was higher in patients with Rheumatoid Arthritis (27.49+/-12.66 mm Hg) than in controls (20.40+/-8.88) (p=0.003). Incidence of pulmonary artery systolic pressure>30 mm Hg suggesting pulmonary hypertension was significantly higher in patients with RA (26.7% versus 4.5% in controls; p=0.03) and 20% of patients had pulmonary hypertension without lung disease or cardiac disease evident on pulmonary function testing, and echocardiogram respectively. There was also a strong correlation between the pulmonary artery pressure and the disease duration (r=0.68, p<0.0001) suggesting a subclinical involvement of the pulmonary vasculature with disease progression and may be relevant to the high incidence of cardiovascular deaths observed in patients with Rheumatoid Arthritis.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics.

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.     

Vascular and cardiac reactivity in pulmonary hypertension due to chronic obstructive lung disease: assessment with various oxygen concentrations.

The aim of the present work was to evaluate vasoreactivity in patients with pulmonary hypertension related to chronic obstructive lung disease. This was done by comparing haemodynamic data recorded while patients were breathing room air, and hypoxic and hyperoxic mixtures. We estimated the role of vasoconstriction in determining the level of pulmonary hypertension. This study included 26 patients with moderate pulmonary hypertension mean pulmonary arterial pressure (MPAP) = 27.3 +/- 1.2 mmHg) secondary to chronic obstructive lung disease (COLD), forced expiratory volume in one second (FEV1) = 0.95 +/- 0.13 l; arterial oxygen tension (PaO2) = 8.7 +/- 0.25 kPa). After insertion of a thermodilution catheter in the pulmonary artery and a cannula in the femoral artery, mixtures containing 15, 21, 30 and 100% oxygen were randomly administered for 20 min each. As fractional inspiratory oxygen (FIO2) increased, MPAP decreased relatively less than cardiac index. Cardiac output was at its highest during room air breathing and the hypoxic mixture did not lead to a further increase. Unlike normal subjects, in whom adjustment of cardiac output is achieved by heart rate alone, haemodynamic regulation in these patients also involved stroke volume. Variations in MPAP and cardiac index were strongly correlated with arterial oxygen saturation (SaO2). The greatest variations were noted in the patients with the highest pulmonary hypertension. Under normoxic and hyperoxic condition the relationship between pulmonary artery driving pressure and cardiac index was linear and its slope steeper in patients having the highest pulmonary hypertension at steady-state.(ABSTRACT TRUNCATED AT 250 WORDS)