α1-Antitrypsin deficiency and chronic respiratory disorders

α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments

Water pipe smoking and its association with cigarette and cannabis use in young adults in Switzerland

Background: Water pipe is a traditional method of tobacco use, which is epidemically spreading throughout Europe. There are scarce data about the use of water pipe and its relation to other addictive behaviors among young adults in Western countries. Objectives: It was our aim to identify the sociodemographic characteristics of water pipe users in Switzerland and to describe concurrent cigarette and cannabis smoking habits. Methods: Young adults aged 16-30 years were evaluated based on a 16-item standardized questionnaire on tobacco consumption and exhaled carbon monoxide. Current water pipe smoking was defined as water pipe use at least once within the last 4 weeks; regular water pipe smoking was defined as water pipe use at least once a week during the last 52 weeks. Results: Out of 353 volunteers, a total of 204 subjects (mean age 21 ± 3.5 years, 113 males) met the inclusion criteria for the study. A total of 78% (n = 160), 30.0% (n = 55) and 3.9% (n = 8) reported ever, current and regular water pipe smoking, respectively. Males smoked more often than females: 2.8 sessions/year (interquartile range 1.1-8) versus 2 sessions/year (interquartile range 0-4; p = 0.022). The major risk factor for ever smoking water pipe was cigarette smoking (odds ratio 6.22, 95% confidence interval 2.33-16.62), followed by cannabis consumption (odds ratio 1.44, 95% confidence interval 1.29-1.62). Ever water pipe smoking was more common among current cannabis users (100 vs. 0%; p > 0.0001) and related to higher exhaled carbon monoxide values (6.0 ± 9.0 vs. 2.1 ± 4.6 ppm; p > 0.001). Conclusion: Water pipe smoking is common among young adults and strongly associated with cigarette smoking and cannabis consumption

Longitudinal Measurement of Serum Vascular Endothelial Growth Factor in Patients with Chronic Obstructive Pulmonary Disease

Impaired vascular endothelial growth factor (VEGF) signaling causes emphysema in animal models. In chronic obstructive pulmonary disease (COPD) patients, alterations in VEGF tissue expression have been observed. We hypothesize that circulating VEGF may be a biomarker to phenotype COPD patients.; The aim of this study was to investigate VEGF serum levels in stable and exacerbated COPD.; VEGF serum levels as well as parameters of short- and long-term outcome were assessed and analyzed in two COPD cohorts [PROMISE, n = 117; ProCOLD (PC), n = 191].; VEGF serum levels at stable COPD were neither related to forced expiratory volume in 1 s nor to the Modified Medical Research Council dyspnea score, 6-min walking distance or BODE index. There was no association between single VEGF levels and COPD exacerbation frequency or mortality at 1 and 2 years of follow-up. In PC an increase in VEGF over time (ΔVEGF) was associated with the exacerbation frequency as well as the 1- and 2-year hospitalization rate (p = 0.046, 0.009 and 0.006, respectively). Furthermore, in PC ΔVEGF was associated with 1- and 2-year survival (p = 0.009 and 0.041, respectively).; Single serum VEGF levels, at stable and exacerbated COPD, were not associated with clinically significant outcomes in COPD. Conversely, the VEGF course seems related to COPD prognosis

Vasoactive Intestinal Peptide for Diagnosing Exacerbation in Chronic Obstructive Pulmonary Disease

Vasoactive intestinal peptide (VIP) is the most abundant neuropeptide in the lung. VIP has been linked to pulmonary arterial hypertension and hypoxia.; We aimed to assess circulating VIP levels at exacerbation and at stable chronic obstructive pulmonary disease (COPD) and to evaluate the diagnostic performance in a well-characterized cohort of COPD patients.; The nested cohort study included patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV. Patients were examined at stable state and at acute exacerbation of COPD (AE-COPD), and dedicated serum was collected at both conditions. Serum VIP levels were determined by enzyme-linked immunosorbent assay. Diagnostic accuracy was analyzed by receiver operating characteristic curve and area under the curve (AUC).; Patients with acute exacerbation (n = 120) and stable COPD (n = 163) had similar characteristics at baseline. Serum VIP levels did not correlate with oxygen saturation at rest (p = 0.722) or at exercise (p = 0.168). Serum VIP levels were significantly higher at AE-COPD (130.25 pg/ml, 95% CI 112.19-151.83) as compared to stable COPD (40.07 pg/ml, 95% CI 37.13-43.96, p < 0.001). The association of increased serum VIP with AE-COPD remained significant after propensity score matching (p < 0.001). Analysis of the Youden index indicated the optimal serum VIP cutoff value as 56.6 pg/ml. The probability of AE-COPD was very low if serum VIP was ≤35 pg/ml (sensitivity >90%) and very high if serum VIP was ≥88 pg/ml (specificity >90%). Serum VIP levels presented a robust performance to diagnose AE-COPD (AUC 0.849, 95% CI 0.779-0.899).; Increased serum VIP levels are associated with AE-COPD

Associations between dietary patterns and post-bronchodilation lung function in the SAPALDIA cohort

Background: Chronic obstructive pulmonary disease (COPD) is not restricted to smokers. Dietary habits may contribute to the disease occurrence. Epidemiological studies point to a protective effect of fruit and vegetable intake against COPD. Objective: To investigate the associations between dietary patterns and parameters of lung function related to COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Methods: Data were included from the second follow-up assessment of the SAPALDIA cohort in 2010-2011 using a food frequency questionnaire. Principal component factor analysis was used to derive dietary patterns, whose association with FEV1, FEV1/FVC, FEF2575, and COPD was investigated by applying multivariate regression analyses. Results: After adjustment for potential confounders, the “prudent dietary pattern” characterised by the predominant food groups vegetables, fruits, water, tea and coffee, fish, and nuts was positively associated with FEV1 (increase of 40 mL per SD, p < 0.001). Also for factor 3 (“high-carbohydrate diet”), we found a significant positive association with FEV1 (with an increase per SD of 36 mL, p = 0.006). Conclusions: The main results are consistent with a protective effect of a diet rich in fruits, vegetables, fish, and nuts against age-related chronic respiratory disease. If confirmed in prospective cohorts, our results may guide nutritional counselling towards respiratory health promotion

Endothelin-1 precursor peptides correlate with severity of disease and outcome in patients with community acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>Circulating levels of endothelin-1 are increased in sepsis and correlate with severity of disease. A rapid and easy immunoassay has been developed to measure the more stable ET-1 precursor peptides proET-1. The objective of this study was to assess the diagnostic and prognostic value of proET-1 in a prospective cohort of mainly septic patients with community-acquired pneumonia.</p> <p>Methods</p> <p>We evaluated 281 consecutive patients with community acquired pneumonia. Serum proET-1 plasma levels were measured using a new sandwich immunoassay.</p> <p>Results</p> <p>ProET-1 levels exhibited a gradual increase depending on the clinical severity of pneumonia as assessed by the pneumonia severity index (PSI) and the CURB65 scores (p < 0.001 and p < 0.01). The diagnostic accuracy to predict bacteraemia of procalcitonin (AUC 0.84 [95% 0.74–0.93]) was superior than C-reactive protein (AUC 0.67 [95%CI 0.56–0.78]) and leukocyte count (AUC 0.66 [95%CI 0.55–0.78]) and in the range of proET-1(AUC of 0.77 [95%CI 0.67–0.86]). ProET-1 levels on admission were increased in patients with adverse medical outcomes including death and need for ICU admission. ROC curve analysis to predict the risk for mortality showed a prognostic accuracy of proET-1 (AUC 0.64 [95%CI 0.53–0.74]), which was higher than C-reactive protein (AUC 0.51 [95%CI 0.41–0.61]) and leukocyte count (AUC 0.55 [95%CI 0.44–0.65]) and within the range of the clinical severity scores (PSI AUC 0.69 [95%CI 0.61–0.76] and CURB65 0.67 [95%CI 0.57–0.77]) and procalcitonin (AUC 0.59 [95% 0.51–0.67]). ProET-1 determination improved significantly the prognostic accuracy of the CURB65 score (AUC of the combined model 0.69 [95%CI 0.59–0.79]). In a multivariate logistic regression model, only proET1 and the clinical severity scores were independent predictors for death and for the need for ICU admission.</p> <p>Conclusion</p> <p>In community-acquired pneumonia, ET-1 precursor peptides correlate with disease severity and are independent predictors for mortality and ICU admission. If confirmed in future studies, proET-1 levels may become another helpful tool for risk stratification and management of patients with community-acquired pneumonia.</p> <p>Trial registration</p> <p>ISRCTN04176397</p

Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]

INTRODUCTION: Pro-adrenomedullin (proADM) is helpful for individual risk assessment and outcome prediction in sepsis. A major cause of sepsis is community-acquired pneumonia (CAP). The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in CAP. METHODS: Data from 302 patients admitted to the emergency department with CAP were included in a prospective observational study. Procalcitonin, C-reactive protein levels, leukocyte count, clinical variables and the pneumonia severity index (PSI) were measured. ProADM levels were measured with a new sandwich immunoassay for mid regional ProADM (MR-proADM, Brahms AG, Hennigsdorf/Berlin, Germany). RESULTS: ProADM levels, in contrast to C-reactive protein and leukocyte count, increased with increasing severity of CAP, classified according to the PSI score (ANOVA, p < 0.001). In patients who died during follow-up, proADM levels on admission were significantly higher compared to levels in survivors (2.1 (1.5 to 3.0) versus 1.0 (0.6 to 1.6) nmol/l, p < 0.001). In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for proADM was 0.76 (95% confidence interval (CI) 0.71–0.81), which was significantly higher compared to procalcitonin (p = 0.004), C-reactive protein (p < 0.001) and total leukocyte count (p = 0.001) and similar to the AUC of the PSI (0.73, p = 0.54). A clinical model including the PSI and proADM increased the prognostic accuracy to predict failure compared to a model relying on the PSI alone (AUC, 0.77 (0.70 to 0.84), p = 0.03). CONCLUSION: ProADM, as a novel biomarker, is a useful tool for the risk stratification of patients with CAP

External Validation of the Revised Pretransplant Assessment of Mortality Score in Allogeneic Hematopoietic Cell Transplantation: A Cohort Study

Pretransplant risk scores such as the revised Pretransplant Assessment of Mortality (rPAM) score help to predict outcome of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Since the rPAM has not been validated externally in a heterogeneous patient population with different diseases, we aimed to validate the rPAM score in a real-world cohort of allo-HCT patients. A total of 429 patients were included receiving their first allo-HCT from 2008 to 2015. The predictive capacity of the rPAM score for 4-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) after allo-HCT was evaluated. Moreover, we evaluated the impact of the rPAM score for OS and used uni- and multivariable analyses to identify patient- and transplant-related predictors for OS. In rPAM score categories of 30, the OS probability at 4 years differed significantly with 61%, 36%, 26%, and 10%, respectively (P < 0.0001). In contrast to CIR, the NRM increased significantly in patients with higher rPAM scores (P < 0.001). Regarding the OS, the rPAM score had an area under the receiver operating characteristics curve of 0.676 (95% confidence interval [CI], 0.625-0.727) at 4 years. In the multivariable analysis, the rPAM score was associated with OS-independently of conditioning regimens (adjusted hazard ratio per 1-unit increase, 1.10; 95% CI, 1.06-1.10; P < 0.001). Additionally, forced expiratory volume in 1 second and the disease risk index were the components of the rPAM significantly associated with outcome. In our large real-world cohort with extended follow-up, the rPAM score was validated as an independent predictor of OS in patients with hematologic disorders undergoing allo-HCT