Pericardial abnormalities predict the presence of echocardiographically defined pulmonary arterial hypertension in systemic sclerosis-related interstitial lung disease

OBJECTIVES: To determine the prevalence and significance of pericardial abnormalities in systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: Retrospective study of 41 subjects with SSc-related ILD who underwent evaluation including thoracic high-resolution CT (HRCT) imaging, transthoracic echocardiography (TTE), and pulmonary function testing. HRCT review evaluated the pericardium for the presence of pericardial effusion (PEf), thickness of the anterior pericardial recess (APR) [abnormal defined as > 10 mm], and pericardial thickening as calculated by total pericardial score (TPS) [abnormal defined as > 8 mm]. Pulmonary arterial hypertension (PAH) was defined as a pulmonary artery pressure > 35 mm Hg estimated by TTE. RESULTS: Fifty-nine percent had an abnormal pericardium, 49% had a PEf, 56% had an abnormal APR, and 49% had an abnormal TPS. An abnormal pericardium was more common in men than women. Subjects with and without pericardial abnormalities were otherwise similar with respect to age, SSc classification, autoantibodies, ILD radiographic pattern, and presence of esophageal dilation. Both groups had similar median percentage of predicted total lung capacity, percentage of predicted FVC, percentage of predicted FEV(1), and percentage of predicted diffusion capacity of the lung for carbon monoxide. Subjects with pericardial abnormalities were more likely to have coexistent PAH (35% vs 75%; p = 0.02) and a higher median right ventricular systolic pressure (31 mm Hg vs 44 mm Hg; p = 0.03). Multiple logistic regression revealed that TPS was the best individual predictor of the presence of TTE-defined PAH. CONCLUSIONS: In patients with SSc-related ILD, pericardial abnormalities are commonly seen on HRCT, and their presence is strongly associated with echocardiographically defined PAH, with abnormal TPS as the best individual predictor.     

Right and left ventricular function and pulmonary artery pressure in patients with bronchiectasis

BACKGROUND: Bronchiectasis may have deleterious effects on cardiac function secondary to pulmonary hypertension (PH). This study was designed to assess cardiac function and determine the prevalence of PH in patients with cystic and cylindrical bronchiectasis. METHODS: A cross-sectional study of patients with bronchiectasis diagnosed by CT scan was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between December 2005 and January 2007. Pulmonary function tests were performed, arterial blood gas measurements were made, and cardiac function and systolic pulmonary artery pressure (SPAP) were assessed by echocardiography. RESULTS: Of 94 patients (31% men, n = 29), 62 patients (66%) had cystic bronchiectasis and 32 patients (34%) had cylindrical bronchiectasis. Right ventricular (RV) systolic dysfunction was observed in 12 patients (12.8%), left ventricular (LV) systolic dysfunction was observed in 3 patients (3.3%), and LV diastolic dysfunction was observed in 11 patients (11.7%); all had cystic bronchiectasis. RV dimensions were significantly greater in the cystic bronchiectasis group, and were positively correlated with SPAP (p < 0.0001) and negatively correlated with Pao2 (p < 0.016). Other hemodynamic variables were not different between groups. PH in 31 patients (32.9%) was significantly greater in patients with cystic bronchiectasis compared with cylindrical bronchiectasis (p = 0.04). In cystic bronchiectasis, SPAP was positively correlated with Paco2 (p = 0.001), and inversely correlated with Pao2 (p = 0.03), diffusion capacity of the lung for carbon monoxide percentage (p = 0.02), and FEV1 (p = 0.02). CONCLUSIONS: RV systolic dysfunction and PH were more common than LV systolic dysfunction in bronchiectatic patients. LV diastolic dysfunction was mainly seen in severe PH. We recommend detailed assessment of cardiac function, particularly LV diastolic function, in patients with bronchiectasis.     

Importance of noninvasively measured respiratory muscle overload among the causes of hospital readmission of COPD patients

AIM: To evaluate the influence of respiratory muscle overload and right cardiac overload among the possible risk factors of hospital readmission in a 1-year follow-up of a cohort of patients with moderate-to-severe COPD. METHODS: A total of 112 COPD patients who were admitted consecutively to the hospital for acute exacerbation. At hospital discharge, we evaluated the conventional clinical and functional determinations in addition to the pressure-time index (PTI), which is obtained using the equation PTI = (Pawo/Pimax) x (Ti/Ttot) x 100, where Pawo represents the mean airway pressure measured at the mouth during spontaneous breathing, Pimax is the maximal inspiratory pressure, Ti is the inspiratory time, and Ttot is the total breathing cycle time. A cardiac echo-Doppler examination was carried out when patients were in stable condition and presented clinical signs of right cardiac overload prior to inclusion in the study. RESULTS: Multivariate analysis showed that the use of long-term oxygen therapy (LTOT) and high PTI (> 0.25) were independently related to the risk of hospital readmission. Patients receiving LTOT had higher Paco(2) (p < 0.05), FEV(1) percent predicted (p < 0.05), FVC percent predicted (p < 0.05), and Pao(2) (p < 0.05), and had higher Paco(2) (p < 0.05). An elevated systolic pulmonary arterial pressure (> 40 mm Hg) was also independently related, but only 28 patients had echo-Doppler data that could be used. CONCLUSIONS: At hospital discharge, noninvasively measured respiratory muscle overload as well as the use of LTOT were associated with an increased risk of hospital readmission for exacerbation in patients with moderate-to-severe COPD.     

C-reactive protein levels and survival in patients with moderate to very severe COPD

BACKGROUND: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease. OBJECTIVE: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease. METHODS: In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality. RESULTS: During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival. CONCLUSIONS: In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV(1), IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.     

Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis

STUDY OBJECTIVES: To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension. DESIGN: Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on. SETTING: University hospital. PATIENTS: Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years. MEASUREMENTS AND RESULTS: RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP < 17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP > 17 mm Hg, n = 24) [p < 0.001]; 70.4% in the preserved-Dlco group (percentage of predicted > 40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted < 40%, n = 25) [p < 0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p < 0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2. CONCLUSION: Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.     

Validation of a method to screen for pulmonary hypertension in advanced idiopathic pulmonary fibrosis

BACKGROUND: We have developed a method to screen for pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients, based on a formula to predict mean pulmonary artery pressure (MPAP) from standard lung function measurements. The objective of this study was to validate this method in a separate group of IPF patients. METHODS: Cross-sectional study of 60 IPF patients from two institutions. The accuracy of the MPAP estimation was assessed by examining the correlation between the predicted and measured MPAPs and the magnitude of the estimation error. The discriminatory ability of the method for PH was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: There was strong correlation in the expected direction between the predicted and measured MPAPs (r = 0.72; p < 0.0001). The estimated MPAP was within 5 mm Hg of the measured MPAP 72% of the time. The AUC for predicting PH was 0.85, and did not differ by institution. A formula-predicted MPAP > 21 mm Hg was associated with a sensitivity, specificity, positive predictive value, and negative predictive value of 95%, 58%, 51%, and 96%, respectively, for PH defined as MPAP from right-heart catheterization > 25 mm Hg. CONCLUSIONS: A prediction formula for MPAP using standard lung function measurements can be used to screen for PH in IPF patients.     

Early changes of cardiac structure and function in COPD patients with mild hypoxemia

BACKGROUND: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD patients with severe hypoxemia, little is known about these changes in patients with normoxia and mild hypoxemia. STUDY OBJECTIVES: To assess the structural and functional cardiac changes in COPD patients with normal Pa(O2) and without signs of RV failure. METHODS: In 25 clinically stable COPD patients (FEV1, 1.23 +/- 0.51 L/s; Pa(O2), 82 +/- 10 mm Hg [mean +/- SD]) and 26 age-matched control subjects, the RV and left ventricular (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP) was estimated from right pulmonary artery distensibility. RESULTS: RV mass divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 +/- 0.18 g/mL in the COPD group and 0.41 +/- 0.09 g/mL in the control group (p < 0.01). LV and RV ejection fractions were 62 +/- 14% and 53 +/- 12% in the COPD patients, and 68 +/- 11% and 53 +/- 7% in the control subjects, respectively. PAP estimated from right pulmonary artery distensibility was not elevated in the COPD group. CONCLUSION: From these results, we conclude that concentric RV hypertrophy is the earliest sign of RV pressure overload in patients with COPD. This structural adaptation of the heart does not alter RV and LV systolic function.     

Development and validation of a survey-based COPD severity score

OBJECTIVE: To develop a comprehensive disease-specific COPD severity instrument for survey-based epidemiologic research. STUDY DESIGN AND SETTING: Using a population-based sample of 383 US adults with self-reported physician-diagnosed COPD, we developed a disease-specific COPD severity instrument. The severity score was based on structured telephone interview responses and included five overall aspects of COPD severity: respiratory symptoms, systemic corticosteroid use, other COPD medication use, previous hospitalization or intubation, and home oxygen use. We evaluated concurrent validity by examining the association between the COPD severity score and three health status domains: pulmonary function, physical health-related quality of life (HRQL), and physical disability. Pulmonary function was available for a subgroup of the sample (FEV1, n = 49; peak expiratory flow rate [PEFR], n = 93). RESULTS: The COPD severity score had high internal consistency reliability (Cronbach alpha = 0.80). Among the 49 subjects with FEV1 data, higher COPD severity scores were associated with poorer percentage of predicted FEV1 (r = - 0.40, p = 0.005). In the 93 subjects with available PEFR measurements, greater COPD severity was also related to worse percentage of predicted PEFR (r = - 0.35, p < 0.001). Higher COPD severity scores were strongly associated with poorer physical HRQL (r = - 0.58, p < 0.0001) and greater restricted activity attributed to a respiratory condition (r = 0.59, p < 0.0001). Higher COPD severity scores were also associated with a greater risk of difficulty with activities of daily living (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.8 to 3.0) and inability to work (OR, 4.2; 95% CI, 3.0 to 5.8). CONCLUSION: The COPD severity score is a reliable and valid measure of disease severity, making it a useful research tool. The severity score, which does not require pulmonary function measurement, can be used as a study outcome or to adjust for disease severity.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Updated evaluation of the cost-effectiveness of lung volume reduction surgery

BACKGROUND: The National Emphysema Treatment Trial, a randomized clinical trial of lung volume reduction surgery (LVRS) vs medical therapy for severe emphysema, included a prospective economic analysis. We present an updated analysis of cost-effectiveness with 1-year additional follow-up data. METHODS: Following pulmonary rehabilitation, 1,218 patients at 17 medical centers were randomized to receive LVRS or continued medical treatment. The cost-effectiveness of LVRS vs medical therapy was calculated over the duration of the trial (January 1998 to December 2003) and estimated at 10 years using modeling based on observed trends in survival, cost, and quality of life. RESULTS: The cost-effectiveness of LVRS vs medical therapy was $140,000 per quality-adjusted life-year (QALY) gained (95% confidence interval, $40,155 to $239,359) at 5 years, and was projected to be $54,000 per QALY gained at 10 years. In subgroup analysis, the cost-effectiveness of LVRS in patients with upper-lobe emphysema and low exercise capacity was $77,000 per QALY gained at 5 years, and was projected to be $48,000 per QALY at 10 years. Compared to the initial results, the updated results are similar for the overall cohort but vary substantially for the subgroups. CONCLUSIONS: LVRS is costly relative to other health-care programs during the time horizon when costs and outcomes are known. The extended follow-up period offers more certainty regarding the long-term value and economic impact of this procedure.     

Tiotropium and simplified detection of dynamic hyperinflation

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.     

Predictors of survival in COPD patients with chronic hypercapnic respiratory failure receiving noninvasive home ventilation

BACKGROUND: Patients with COPD and chronic hypercapnic respiratory failure (CHRF) are at high risk, and noninvasive ventilation at home is increasingly being used. Knowledge of prognostic parameters under these conditions is limited but may be clinically helpful and highlight the role of noninvasive ventilation. METHODS: In 188 patients with COPD (mean +/- SD FEV1, 31.0 +/- 9.6% of predicted; PaCo2, 56.3 +/- 9.4 mm Hg) discharged from the hospital receiving NIV between July 1994 and July 2004, the prognostic value of body mass index (BMI), lung function, laboratory parameters, and blood gas levels was assessed by univariate and multivariate Cox regression analyses. Moreover, the impact of changes in risk factors on mortality assessed 6.7 +/- 2.8 months after the initiation of noninvasive ventilation was evaluated. RESULTS: Overall, the mortality rate during follow-up (duration, 32.2 +/- 24.3 months) was 44.7%, with 1-year, 2-year, and 5-year survival rates of 84.0%, 65.3%, and 26.4%. Deaths resulted predominantly from respiratory causes (73.8%). Univariate regression analyses revealed age, BMI, hemoglobin, FEV1, specific airway resistance, residual volume (RV)/total lung capacity (TLC), pH, and base excess (BE) to be associated with prognosis (p < 0.01 each), whereas multivariate analysis identified only age, BMI, RV/TLC, and BE as independent predictors (p < 0.05). In patients at risk (BMI < 25 km/m2, RV/TLC >or= 73%, or BE >or= 9 mmol/L), changes in these predictors were also associated with survival. CONCLUSIONS: In patients with COPD and CHRF, nutritional status, hyperinflation, and BE, which turned out to be reliable and consistent markers in CHRF, were independent prognostic factors for mortality. These data favor a multidimensional approach in these patients, including the use of noninvasive ventilation.     

Angiogenesis in chronic lung disease

Chronic lung diseases like COPD, severe progressive pulmonary hypertension (PH), and interstitial lung diseases all have a lung vascular disease component. Cellular and molecular mechanisms of pulmonary vascular remodeling have been experimentally explored in many animal models, and it is now clear that microvessels are involved. In emphysema patients, there is a loss of lung microvessels, and in many forms of severe PH there is obliteration of precapillary arterioles by angioproliferation. Thus, COPD/emphysema and severe angioproliferative PH are on the opposite ends of a spectrum of vascular biology responses. Animal experiments have provided insight regarding some of the initiating events that shape the various forms of pulmonary vascular remodeling. In pulmonary fibrosis and in the postinjury phase of acute lung injury, the angiogenic/angiostatic balance is also affected. This review will therefore discuss angiogenesis in several chronic lung diseases and will speculate on how altered vascular homeostasis may contribute to lung disease development.     

Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients

BACKGROUND: Pulmonary involvement is the leading cause of systemic sclerosis (SSc)-related deaths. A simple test to evaluate exercise capacity is the 6-min walk test (6MWT), and the walk distance is used as a primary outcome in clinical trials. Hemoglobin desaturation during a 6MWT is predictive of mortality in patients with primary pulmonary hypertension. Our objectives were to evaluate the walk distance and resting oxygen saturation - oxygen saturation after the 6-min period (DeltaSat) during the 6MWT in patients with SSc, and to establish correlations between the 6MWT results and other clinical variables. METHODS: We analyzed 110 SSc patients. DeltaSat was defined as a fall of end-of-test saturation >or= 4%. Clinical and demographic data were collected. All the patients were submitted to chest radiographs and high-resolution CT (HRCT) and underwent pulmonary function testing and echocardiography, and the presence of autoantibodies was determined. RESULTS: The variables associated with a walk distance < 400 m (p < 0.05) were age, dyspnea index, fibrosis on radiography, pulmonary arterial systolic pressure (PASP) >or= 30 mm Hg, and desaturation. The variables associated with DeltaSat (p < 0.05) were age, positive anti-Scl-70 autoantibody, dyspnea index, fibrosis on radiography, FVC < 80% of predicted, PASP >or= 30 mm Hg, and ground-glass or reticular opacities on HRCT. In the multivariate logistic regression analysis, three variables were significant when tested with walk distance: age, race, and dyspnea index; four variables were significant when tested with DeltaSat: age, dyspnea index, positive anti-Scl-70 autoantibody, and FVC < 80% of predicted. CONCLUSIONS: Desaturation during a 6MWT provides additional information regarding severity of disease in scleroderma patients with pulmonary manifestations.     

Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis

BACKGROUND: Pulmonary hypertension (PH) is commonly seen in patients with idiopathic pulmonary fibrosis (IPF). We sought to examine the relationship between pulmonary function tests (PFTs), including the percentage of predicted FVC (FVC%), percentage of predicted total lung capacity, percentage of predicted diffusing capacity of the lung for carbon monoxide (Dlco%), the composite physiologic index (CPI), and PH. The ability of FVC%, Dlco%, and FVC%/Dlco% ratio to predict underlying PH was assessed. METHODS: Retrospective review of IPF patients seen at a tertiary referral center over an 8-year interval in whom both PFT and right-heart catheterization data were available. RESULTS: The study cohort consisted of 118 patients, of whom 48 patients (40.7%) had PH. There was no correlation between measures of lung volumes or the CPI with underlying PH. There was a modest association between Dlco% and PH, with Dlco% < 30 having a twofold-higher prevalence of PH (56.4%) compared to Dlco% >/= 30 (28.6%). Cardiac dysfunction might have played a small role, since 16.1% of the patients had an associated elevated pulmonary capillary wedge pressure. There was a trend to a higher prevalence and greater severity of PH in those patients with FVC% > 70 compared to the group with FVC% < 40. CONCLUSION: PH is common in patients with IPF. There is a poor correlation between lung function measures and PH, suggesting that factors other than fibrosis may play a role in the etiology. The unexpected high prevalence and severity of PH in patients with well-maintained lung function have implications for the prognosis and management of the disease.     

Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia

STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well. METHODS: A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender. RESULTS: At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, P(I(max)), P(E(max)), and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pa(O2) affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients. CONCLUSION: In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.     

Systemic inflammation and COPD: the Framingham Heart Study

BACKGROUND: The current paradigm for the pathogenesis of COPD includes an ultimately maladaptive local inflammatory response to environmental stimuli. We examined the hypothesis that systemic inflammatory biomarkers are associated with impaired lung function, particularly among those with extensive cigarette smoking. METHODS: Using data from the Framingham Heart Study, we examined cross-sectional associations of systemic inflammatory biomarkers (CD40 ligand [CD40L], intercellular adhesion molecule [ICAM]-1, interleukin [IL]-6, monocyte chemoattractant protein-1, P-selectin, and myeloperoxidase, in addition to C-reactive protein) to impaired lung function. RESULTS: IL-6 was consistently associated with impaired lung function; a 1-SD higher concentration of IL-6 was associated with a 41-mL lower FEV(1) (95% confidence interval [CI], - 61 to - 20) and a borderline 15% higher odds of COPD (odds ratio, 1.15; 95% CI, 0.99 to 1.34). Additionally, P-selectin was associated with lower FEV(1) levels; after adjusting for the other biomarkers, a 1-SD higher concentration of P-selectin predicted an FEV(1) that was on average 19 mL lower (95% CI, - 37 to 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function/biomarker association; the relations of ICAM-1 to FEV(1), and ICAM and CD40L to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40L and COPD appeared greater in individuals with more extensive smoking histories. CONCLUSIONS: Among participants in the Framingham Heart Study, systemic inflammation was associated with lower levels of pulmonary function. Further research into the role of systemic inflammation in the development of pulmonary dysfunction is merited.     

Unexplained pulmonary hypertension in elderly patients

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) preferentially affects young women. However, a subset of patients with IPAH is elderly. Our objective was to compare elderly (age >/= 65 years) vs younger persons with unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH. METHODS: Clinical, echocardiographic, hemodynamic, and survival data were collected on consecutive patients with suspected IPAH after evaluation in a large tertiary center PH clinic. RESULTS: Of 197 patients (mean age +/- SD, 52 +/- 16 years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 +/- 20.3 mm Hg vs 86.9 +/- 18.8 mm Hg, respectively; p = 0.21), and severity of right ventricular enlargement and dysfunction. Elderly patients had higher pulmonary capillary wedge pressure (PCWP) [15.3 +/- 7.3 mm Hg vs 11.1 +/- 5.3 mm Hg; p < 0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and more cardiovascular disease. Among those patients with normal PCWP, elderly patients had worse survival than young patients (p = 0.007). Among those patients with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better survival (p = 0.02). CONCLUSIONS: Elderly patients with clinically suspected IPAH often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to define the proper diagnostic strategy and the safety and efficacy of pulmonary vasodilators in elderly patients with unexplained PH are needed.     

A 1-year prospective study of the infectious etiology in patients hospitalized with acute exacerbations of COPD

INTRODUCTION: Infection is a major cause of acute exacerbations of COPD (AECOPDs). We aimed to study the infectious etiology related to AECOPD. METHODS: Patients admitted to an acute care hospital in Hong Kong with an AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Sputum samples, nasopharyngeal aspirate (NPA) samples, and paired serology specimens were collected. Spirometry was performed with patients in the stable phase 2 to 3 months after hospital discharge. RESULTS: There were 643 episodes of AECOPD among 373 patients. Their mean age was 75.3 years (SD, 7.9 years) with 307 male patients. The mean FEV(1) was 40.4% predicted (SD, 18.7% predicted), and the mean FEV(1)/FVC ratio was 58.4% (SD, 16.0%). Among sputum samples from the 530 episodes of AECOPD hospital admissions that were saved, 13.0%, 6.0%, and 5.5%, respectively, had positive growth of Haemophilus influenzae, Pseudomonas aeruginosa, and Streptococcus pneumoniae. Among the 505 hospital admissions with patients who had NPA samples saved, 5.7%, 2.3%, 0.8%, and 0.8%, respectively, had influenza A, respiratory syncytial virus (RSV), influenza B, and parainfluenza 3 isolated from viral cultures. Paired serology test results revealed a fourfold rise in viral titers in 5.2%, 2.2%, and 1.4% of patients, respectively, for influenza A, RSV, and influenza B. Very severe airflow obstruction (stable-state spirometry) was associated with a higher chance of a positive sputum culture (FEV(1) >/= 30% predicted, 28.2%; FEV(1) < 30% predicted, 40.4%; p = 0.006). CONCLUSION: H influenzae and influenza A were the most common etiologic agents in patients who were hospitalized with AECOPDs. More severe airflow obstruction was associated with a higher chance of a positive sputum culture finding.     

Improvement of pulmonary hypertension after liver transplantation.

Pulmonary hypertension at the end stage of chronic liver disease is not an uncommon situation. This association termed portopulmonary hypertension raises the question of the feasibility of performing orthotopic liver transplantation (OLT). In the case reported herein, there was a favorable outcome after OLT, even though the mean pulmonary artery pressure (MPAP) before transplantation was increased to 45 mm Hg. Before OLT, the cardiac index (CI) was considerably elevated (7.69 L/min/m2), giving evidence of a marked hyperdynamic circulatory state. The CI decreased significantly after OLT (3.38 L/min/m2), and this produced a significant decrease in the MPAP. Our observation suggests that portopulmonary hypertension due to a marked increase in the CI can be managed successfully by OLT.