Desiree Schumann

IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

BackgroundInterferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations?MethodsFive hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months.ResultsThe GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3.ConclusionIFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD.Trial registrationClinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.

Treatment of COPD Exacerbation in Switzerland: Results and Recommendations of the European COPD Audit

Background: The European COPD Audit initiated by the European Respiratory Society (ERS) evaluated the management of hospital admissions due to exacerbation of chronic obstructive pulmonary disease (COPD) in several European countries. Data on the treatment of severe acute exacerbations of COPD (AECOPDs) in Switzerland are scarce. Objectives: In light of the GOLD 2010 guidelines, this work aims to examine the quality of care for AECOPD and to provide specific recommendations for the management of severe AECOPD in Switzerland. Methods: A total of 295 patients requiring hospital admission to 19 Swiss hospitals due to exacerbation of COPD during a predefined 60 days in 2011 were included in the study. We compared the Swiss data to the official GOLD 2010 recommendations and to the results of the other European countries. Results: Approximately 43% of the Swiss patients with severe AECOPD were current smokers at hospital admission, compared to 33% of the patients in other European countries (p < 0.001). In Switzerland and in Europe, spirometry data were not available for most patients at hospital admission (65 and 60%, respectively; p = 0.08). In comparison to other European countries, antibiotics were prescribed 14% less often in Switzerland (p < 0.001). Only 79% of the patients in the Swiss cohort received treatment with a short-acting bronchodilator at admission. Conclusions: Considering the overall high standard of health care in Switzerland, in light of the GOLD 2010 guidelines we are able to make 7 recommendations to improve and standardize the management of severe AECOPD for patients treated in Switzerland.

Multiplex PCR on the Bronchoalveolar Lavage Fluid of Immunocompromised Patients

Characteristic Value Age, y 57.63 14.73 Male sex 306 (58.6) Hospitalization (IQR), d 11 (3; 25) Symptoms and signs Cough 300 (57.5) Dyspnea 124 (23.8) Sputum 118 (22.6) Fever 108 (20.7) Decrease in FEV1 % predicted 59 (11.3) Reasons for immunosuppression Allogenic HSCT 112 (21.5) Lung transplantation 83 (15.9) Other hematologic therapies 79 (15.1) Interstitial lung disease 59 (11.3) Connective tissue disease 52 (10.0) Chemotherapy 37 (7.1) Solid cancer 29 (5.6) HIV/AIDS 25 (4.8) Other conditions 20 (3.8) Renal transplantation 23 (4.4) Autologous HSCT 21 (4.0) Liver transplantation 5 (1.0) Treatment Systemic steroids 271 (51.9) Mycophenolate 154 (29.5) Tacrolimus 109 (20.9) Cyclosporine 75 (14.4) Chemotherapy 72 (13.8) Methotrexate 22 (4.2) Azathioprine 21 (4.0) Highly active antiretroviral agents 17 (3.3) (Continued) Pleural effusion 6 (1.1) Bronchiolitis 5 (0.96) Atelectasis 2 (0.38) Empyema and/or abscess 2 (0.38) Pleural plaques 1 (0.19) Cysts 1 (0.19) Macroscopic bronchoscopy findings No pathologic finding 193 (37.0) Erythema of the mucosa 167 (32.0) Purulent secretion 85 (16.3) Nonpurulent secretion 77 (14.8) Bloody secretion 40 (7.7) Endobronchial tumor 6 (1.1) Others 11 (2.1) Clinical final diagnosis Infection 320 (61.3) Nonpulmonary infection 122 (23.4) Progression of underlying disease 35 (6.7)

Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease

Background The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology‐related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of type I (C1M), type IV (&agr;1 chain, C4M2), and type IV (&agr;3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro‐form of collagen type V (PRO‐C5) were investigated and associated with COPD severity and outcome. Methods In a prospective, observational, multicenter study including 498 patients with COPD Gold Initiative for Chronic Obstructive Lung Disease stage 2 to 4, ECM markers were assessed in serum at stable state, exacerbation, and at follow‐up 4 weeks after exacerbation. Results At stable state, there was a significant inverse association between FEV1 % predicted and C1M, C4Ma3, and Pro‐C5. C1M, C4M2, C4Ma3, and Pro‐C5 were associated with BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index and the modified Medical Research Council (MMRC) score. C1M, C4M2, C4Ma3, and Pro‐C5 were significantly increased from stable state to exacerbation and decreased at follow‐up. Furthermore, the biomarkers were significantly higher during severe exacerbation compared with moderate exacerbation. Multivariate analysis adjusted for BMI, MMRC score, unadjusted Charlson score, and FEV1 %predicted showed a significant influence of C1M, C4Ma3, and C4M2 on time to exacerbation. None of the biomarkers were predictors for mortality. Conclusions Serologically assessed collagen remodeling appears to play a significant role in COPD severity (airflow limitation, dyspnea) and disease outcome (time to exacerbation and prognosis as assessed by the BODE index).

Reactive hyperemia peripheral arterial tonometry as a measure of endothelial dysfunction in COPD

Introduction: Chronic obstructive pulmonary disease is significantly associated with cardiovascular and peripheral vascular disease. The measurement of endothelial dysfunction using reactive hyperemia peripheral arterial tonometry (RH-PAT) is well documented in the field of cardiovascular research. There are no data available for COPD patients. We, therefore, investigated endothelial dysfunction in a cohort of COPD patients using RH-PAT. Methods: A total of 191 subjects with moderate to very severe COPD (n=157), smokers without COPD (n=18) and healthy controls (n=16) were consecutively recruited at a tertiary institution. The reactive hyperemia index (RHI) were associated to lung function, MMRC, BODE index, number of exacerbations, time to exacerbation and death. Results: 57% of the patients with COPD had dysfunctional endothelium compared to 31% of the healthy controls and 33% of the smokers without COPD (p=0.036). Univariate analysis showed a significant difference in RHI between healthy controls and patients with COPD (median 1.94 vs. 1.58; p=0.030), however, this difference disappeared after adjustment for age, BMI, blood pressure and pulse. There was no difference in RHI between patients with COPD and age-matched smokers without COPD (median 1.58 vs. 1.82; p=0.120). RHI did not change significantly whether the patient was in stable state or during an exacerbation (means 2.05 vs 1.91; paired T-Test, p=0.625). There was no association between RHI and body plethysmography lung function, MMRC, BODE, exacerbations or death (p≥0.05). Conclusion: Endothelial dysfunction, as measured by RH-PAT, does not appear to be either a predictor of disease severity or of outcome in COPD.