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Background: In patients with COPD, chronic anemia is known as an unfavorable prognostic factor. Whether the association between hemoglobin (Hb) levels and long-term survival is restricted to anemia or extends to higher Hb levels has not yet been systematically assessed., Methods: We determined Hb levels in 309 subjects with COPD and chronic respiratory failure prior to initiation of noninvasive ventilation, accounting for confounders that might affect Hb. Subjects were categorized as anemic (Hb < 12 g/dL in females, Hb < 13 g/dL in males), polycythemic (Hb ≥ 15 g/dL in females, Hb ≥ 17 g/dL in males), or normocythemic. In addition, percentiles of Hb values were analyzed with regard to mortality from any cause., Results: Two-hundred seven subjects (67.0%) showed normal Hb levels, 46 (14.9%) had anemia, and 56 (18.1%) had polycythemia. Polycythemic subjects showed a higher survival rate than anemic (P = .01) and normocythemic subjects (P = .043). In a univariate Cox hazards model, Hb was associated with long-term survival (hazard ratio 0.855; 95% CI 0.783-0.934, P < .001). The 58th percentiles of Hb (14.3 g/dL in females, 15.1 g/dL in males) yielded the highest discriminative value for predicting survival (hazard ratio 0.463, 95% CI 0.324-0.660, P < .001). In the multivariate analysis this cutoff was an independent predictor for survival (hazard ratio 0.627, 95% CI 0.414-0.949, P = .03), in addition to age and body mass index., Conclusions: In subjects with COPD and chronic respiratory failure undergoing treatment with noninvasive ventilation and LTOT, high Hb levels are associated with better long-term survival. The optimal cutoff level for prediction was above the established threshold defining anemia. Thus, predicting survival only on the basis of anemia does not fully utilize the prognostic potential of Hb values in COPD.

Background: For percutaneously tracheostomized patients with prolonged weaning and persisting respiratory failure, the adequate time point for safe decannulation and switch to noninvasive ventilation is an important clinical issue., Objectives: We aimed to evaluate the usefulness of a tracheostomy retainer (TR) and the predictors of successful decannulation., Methods: We studied 166 of 384 patients with prolonged weaning in whom a TR was inserted into a tracheostoma. Patients were analyzed with regard to successful decannulation and characterized by blood gas values, the duration of previous spontaneous breathing, Simplified Acute Physiology Score (SAPS) and laboratory parameters., Results: In 47 patients (28.3%) recannulation was necessary, mostly due to respiratory decompensation and aspiration. Overall, 80.6% of the patients could be liberated from a tracheostomy with the help of a TR. The need for recannulation was associated with a shorter duration of spontaneous breathing within the last 24/48 h (p < 0.01 each), lower arterial oxygen tension (p = 0.025), greater age (p = 0.025), and a higher creatinine level (p = 0.003) and SAPS (p < 0.001). The risk for recannulation was 9.5% when patients breathed spontaneously for 19-24 h within the 24 h prior to decannulation, but 75.0% when patients breathed for only 0-6 h without ventilatory support (p < 0.001). According to ROC analysis, the SAPS best predicted successful decannulation [AUC 0.725 (95% CI: 0.634-0.815), p < 0.001]. Recannulated patients had longer durations of intubation (p = 0.046), tracheostomy (p = 0.003) and hospital stay (p < 0.001)., Conclusion: In percutaneously tracheostomized patients with prolonged weaning, the use of a TR seems to facilitate and improve the weaning process considerably. The duration of spontaneous breathing prior to decannulation, age and oxygenation describe the risk for recannulation in these patients., (Copyright © 2012 S. Karger AG, Basel.)

Background & Aims: In patients with chronic respiratory diseases body mass index (BMI) is a predictor of long-term survival, whereas the prognostic value of body composition, especially fat-free mass index (FFMI), is unknown., Methods: In a prospectively collected cohort of 131 patients (50 females, 81 males; 71% chronic obstructive pulmonary disease, 29% severe restrictive disorders) undergoing home mechanical ventilation (HMV) due to chronic hypercapnic respiratory failure (CHRF), the prognostic value of nutritional composition assessed by bioelectrical impedance analysis was evaluated during a 4-year follow-up and compared to that of BMI, anthropometrics, and functional parameters., Results: After follow-up, 53 patients (40.5%) had died. Regarding all-cause mortality cumulative survival percentages after 1, 2 and 3 years were 89.3, 76.3 and 67.9%, respectively. In univariate analyses, FFMI, BMI, sex, age, leukocyte number, FEV1 and 6-min walking distance were associated with survival (p<0.05). Multivariate analyses using the most significant percentiles identified by univariate analysis revealed FFMI (25th percentile; hazard ratio 0.338 [95% confidence interval: 0.189-0.605]), sex, leukocyte number (50th percentile) and FEV1 (50th percentile) as independent predictors of mortality., Conclusions: In patients with CHRF and HMV, body composition in terms of FFMI was an independent predictor of long-term survival. FFMI was superior to BMI and seems informative in the multidimensional assessment of these patients., (Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The 6-min walk distance (6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease (COPD), but less explored in other chronic respiratory diseases., Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure (CHRF)., Methods: In 424 stable patients with CHRF and non-invasive ventilation (NIV) comprising COPD (n = 197), restrictive diseases (RD; n = 112) and obesity-hypoventilation-syndrome (OHS; n = 115), the prognostic value of 6-MWD for long-term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters., Results: 6-MWD was reduced in patients with COPD (median 280 m; quartiles 204/350 m) and RD (290 m; 204/362 m) compared to OHS (360 m; 275/440 m; p < 0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s (p < 0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median [p < 0.001, hazard ratio (HR) = 3.75, 95% confidence interval (CI): 2.24-6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73-14.10), while in OHS 6-MWD had not any prognostic value., Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long-term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF., ((c) 2007 S. Karger AG, Basel.)

Patients with advanced COPD and acute or chronic respiratory failure are at high risk for death. Beyond pharmacological treatment, supplemental oxygen and mechanical ventilation are major treatment options. This review describes the physiological concepts underlying respiratory failure and its therapy, as well as important treatment outcomes. The rationale for the controlled supply of oxygen in acute hypoxic respiratory failure is undisputed. There is also a clear survival benefit from long-term oxygen therapy in patients withchronic hypoxia, while in mild, nocturnal, or exercise-induced hypoxemia such long-term benefits appear questionable. Furthermore, much evidence supports the use of non-invasive positivepressure ventilation in acute hypercapnic respiratory failure. It application reduces intubation and mortality rates, and the duration of intensive care unit or hospital stays, particularly in the presence of mild to moderate respiratory acidosis. COPD with chronic hypercapnic respiratory failurebecame a major indication for domiciliary mechanical ventilation, based on pathophysiological reasoning and on data regarding symptoms and quality of life. Still, however, its relevance for long-term survival has to be substantiated in prospective controlled studies. Such studies might preferentially recruit patients with repeated hypercapnic decompensation or a high risk for death, while ensuring effective ventilation and the patients' adherence to therapy.

Background: Health-related quality of life (HRQL) is considered as an important outcome parameter in patients with chronic diseases. This study aimed to assess the role of disease-specific HRQL for long-term survival in patients of different diagnoses with chronic hypercapnic respiratory failure (CHRF)., Methods: In a cohort of 231 stable patients (chronic obstructive pulmonary disease (COPD), n = 98; non-COPD (obesity-hypoventilation syndrome, restrictive disorders, neuromuscular disorders), n = 133) with CHRF and current home mechanical ventilation (HMV), HRQL was assessed by the disease-specific Severe Respiratory Insufficiency (SRI) questionnaire and its prognostic value was prospectively evaluated during a follow-up of 2-4 years, using univariate and multivariate regression analysis., Results: HRQL was more impaired in COPD (mean +/- SD SRI-summary score (SRI-SS) 52.5 +/- 15.6) than non-COPD patients (67.6 +/- 16.4; p < 0.001). Overall mortality during 28.9 +/- 8.8 months of follow-up was 19.1% (31.6% in COPD, 9.8% in non-COPD). To identify the overall role of SRI, we first evaluated the total study population. SRI-SS and its subdomains (except attendance symptoms and sleep), as well as body mass index (BMI), leukocyte number and spirometric indices were associated with long-term survival (p < 0.01 each). Of these, SRI-SS, leukocytes and forced expiratory volume in 1 s (FEV1) turned out to be independent predictors (p < 0.05 each). More specifically, in non-COPD patients SRI-SS and most of its subdomains, as well as leukocyte number, were related to survival (p < 0.05), whereas in patients with COPD only BMI and lung function but not SRI were predictive., Conclusion: In patients with CHRF and HMV, the disease-specific SRI was an overall predictor of long-term survival in addition to established risk factors. However, the SRI predominantly beared information regarding long-term survival in non-COPD patients, while in COPD patients objective measures of the disease state were superior. This on one hand highlights the significance of HRQL in the long-term course of patients with CHRF, on the other hand it suggests that the predictive value of HRQL depends on the underlying disease.

Background: Mouth occlusion pressure measurement is widely used for assessment of respiratory muscle function, particularly in patients with respiratory failure. However, its predictive value for long-term survival remains largely unexplored., Methods: In 464 patients with chronic hypercapnic respiratory failure (CHRF) due to various underlying disorders and receiving non-invasive ventilation (NIV), maximal inspiratory mouth pressure (PI(max)), mouth occlusion pressure at 100 ms during quiet breathing (P(0.1)) and the ratio P(0.1)/PI(max) were assessed prior to and after treatment including NIV. Baseline data and changes at follow-up were used to evaluate their predictive value for long-term survival., Results: Overall, median (quartiles) P(0.1) was 177.0 (109.2;287.0) %pred, PI(max) 35.0 (24.0;47.0) %pred, and P(0.1)/PI(max) 564.0 (275.7;1082.3) %pred. In multivariate analyses, P(0.1) was related to airflow obstruction, lung hyperinflation, haemoglobin (Hb) and leukocytes, and PI(max) to airflow obstruction and hyperinflation (p<0.05 each). All-cause mortality during follow-up (median 31.6 months) was 31.5%. Survival was associated with age, body-mass index (BMI), lung function, leukocytes, Hb, PI(max), P(0.1) and P(0.1)/PI(max) (p<0.01 each, univariate). Among these multivariate Cox regression identified age, BMI, FEV(1), leukocytes and P(0.1)/PI(max) as independent predictors (p<0.05 each). Furthermore, the decrease of P(0.1)/PI(max) at follow-up was associated with improved survival in patients with high baseline P(0.1)/PI(max) (>50th or 75th percentile; p<0.05)., Conclusions: In patients with CHRF and current NIV therapy, P(0.1)/PI(max) was an independent predictor of long-term survival, in addition to previously established risk factors. Moreover, a decrease in P(0.1)/PI(max) after treatment including NIV was associated with an improved survival in patients with high baseline P(0.1)/PI(max) values.

Background: Natriuretic peptides are considered as reliable indicators of left-heart failure (HF) and are useful for differential diagnosis of dyspnoea., Aim: We evaluated the clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic hypercapnic respiratory failure (CHRF)., Methods: In 60 patients with CHRF, plasma concentrations of NT-proBNP were assessed at baseline and after treatment including non-invasive ventilation (NIV). The relationship of NT-proBNP to disease severity and its predictive value for survival were evaluated up to 4 years., Results: NT-proBNP levels were markedly elevated in patients with CHRF (n=60; geometric mean (SD) 546.4 (4.9) pg/mL; p<0.001) compared to healthy controls (n=182; 49.0 (2.2) pg/mL). After excluding patients with concomitant HF or renal impairment, levels were still increased (n=43; 393.2 (3.8) pg/mL; p<0.001). According to multivariate regression, hypoxia and exacerbation independently determined NT-proBNP levels (p<0.05 each). After initiation of NIV, blood gases and lung function improved and NT-proBNP decreased (-31.3 (0.3)%; p<0.001). During 22.5 (2.2) months follow-up, NT-proBNP was not significantly associated with survival in the total population, however, the subgroup of patients with levels >722 pg/mL (67th percentile) and no adherence to NIV displayed poor prognosis (hazard ratio=0.21; 95%-CI=0.022-0.580; p=0.0091)., Conclusions: NT-proBNP was highly elevated in patients with CHRF and correlated with the degree of respiratory impairment and exacerbation. Correspondingly, treatment including NIV led to reduction of NT-proBNP. These data indicate a potential role of NT-proBNP in assessing disease severity, treatment efficacy and prognosis in CHRF.

Background and Objectives: Non-invasive positive pressure ventilation (NPPV) is an established treatment in restrictive thoracic disorders (RTD) with chronic hypercapnic respiratory failure. The aim of this study was to identify predictors of long-term survival for patients on NPPV therapy., Methods: In a 10-year retrospective cohort of patients with RTD and chronic hypercapnic respiratory failure, survival and the predictive value of nocturnal and daytime blood gases, lung function and laboratory data measured before initiation of NPPV were assessed. The impact of ventilator settings and daily use of NPPV on survival were also evaluated. Patients were re-admitted every 6 months for follow-up assessment., Results: The study recruited 77 patients; 18 died during the study period and three ceased NPPV. Respiratory failure caused eight of the nine respiratory deaths (88.9%). One-, 2- and 5-year survival rates were 92.5%, 81.0% and 59.0%, respectively. In univariate analyses, higher night-time PaCO(2), base excess (night- and daytime) and lower Hb at baseline were associated with significantly worse survival (P < 0.05). Multivariate Cox regression analysis revealed night-time PaCO(2) as an independent predictor of survival (P = 0.042). The small differences in daily duration of use of NPPV and ventilator settings were not significantly related to survival. At follow up, significant improvements were observed for blood gases, lung and respiratory muscle function, as well as a decrease in Hb level (P < 0.01 each)., Conclusions: Base excess, Hb and particularly nocturnal PaCO(2) are relevant prognostic factors for survival in RTD and should be considered in assessing patients receiving NPPV.

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.

Objective: To investigate the effects of respiratory muscle training (RMT) in patients with restrictive thoracic disorders and intermittent noninvasive positive-pressure ventilation (NPPV)., Design: Prospective randomized controlled trial., Setting: Home-based RMT, with assessment in a primary care pulmonary center., Participants: Thirty patients with restrictive thoracic disorders; 28 patients completed the trial., Intervention: Three months of RMT by isocapnic hyperpnea or sham training., Main Outcome Measures: Respiratory muscle strength and endurance, lung function, exercise performance, and health-related quality of life (HRQOL)., Results: After RMT, maximal inspiratory mouth pressure was increased (27.6%+/-36.5%, P=.013). In patients who could perform cycle ergometer testing (n=17), peak oxygen consumption (2.24+/-3.39mLxkg(-1).min(-1) vs -1.71+/-2.54mLxkg(-1).min(-1), P=.014) and maximal work rate (9.4+/-14.8W vs -5.1+/-10.8W, P=.043) increased relative to a control group. Similar differences occurred regarding changes of HRQOL (physical performance, 3.3+/-11.4 score vs -6.6+/-9.0 score; P=.012) and time of ventilator use (-0.6+/-1.2h/d vs 0.4+/-0.5h/d, P=.010). Lung volumes, 12-second maximum voluntary ventilation, 6-minute walking distance, and blood gases were unchanged., Conclusions: In patients with restrictive thoracic disorders and NPPV, RMT improved inspiratory muscle strength. Exercise performance and HRQOL were improved when the 2 groups were compared. RMT was practicable and safe despite severe respiratory impairment. Further evaluation, including different training intensities and modalities, seems warranted.

Background: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information. Objective: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD. Methods: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves. Results: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk. Conclusion: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Patients with COPD who require prolonged weaning from invasive mechanical ventilation show poor long-term survival. Whether non-invasive home mechanical ventilation (HMV) has a beneficial effect after prolonged weaning has not yet been clearly determined. Methods: Patients with COPD who required prolonged weaning and were admitted to a specialized weaning centre between January 2002 and February 2008 were enrolled in the study. Long-term survival and prognostic factors, including the role of non-invasive HMV, were evaluated. Results: Of 117 patients (87 men, 30 women; mean age 69.5 ± 9.5 years) included in the study, weaning from invasive ventilation was achieved in 82 patients (70.1%). Successful weaning was associated with better survival 1 year after discharge from hospital (hazard ratio (HR) 2.24, 95% CI: 1.16-4.31; P = 0.016). Among the 82 patients who were successfully weaned, non-invasive HMV was initiated in 39 (47.6%) due to persistent chronic ventilatory failure. Initiation of HMV was associated with a higher rate of survival to 1 year as compared with patients who did not receive ventilatory support (84.2% vs 54.3%; HR 3.68, 95% CI: 1.43-9.43; P = 0.007). In addition, younger age and higher PaO2, haemoglobin concentration and haematocrit at discharge were associated with better survival. In an adjusted multivariate analysis, initiation of non-invasive HMV after successful weaning remained an independent prognostic factor for survival to 1 year (HR 3.63, 95% CI: 1.23-10.75; P = 0.019). Conclusions: These findings suggest that based on the potential for improvement in long-term survival, non-invasive HMV should be considered in patients with severe COPD and persistent chronic hypercapnic respiratory failure after prolonged weaning. [ABSTRACT FROM AUTHOR]