Bosentan for patients with steroid-resistant pulmonary sarcoidosis: a randomised controlled trial.

BACKGROUND: Sarcoidosis is a disorder of unknown aetiology. Most patients have steroid-responsive disease, but side effects and steroid resistance may necessitate alternative treatments. Endothelin has in-vitro fibrogenic activity and the endothelin system is activated in sarcoidosis. OBJECTIVES: We studied the efficacy and safety of the endothelin receptor antagonist bosentan in sarcoidosis patients. METHODS: In a prospective 12-month, double-blind, 1:1-randomised, placebo-controlled phase II trial, we assessed the effect of bosentan in patients with steroid-resistant sarcoidosis and with impaired exercise capacity and/or resting lung function. Primary endpoints were safety and overall response rate of total lung capacity, diffusion capacity, peak oxygen uptake, 6-minute walking distance and chest computed tomography score. Secondary endpoints included adverse events and quality of life. MAIN RESULTS: Twenty patients were randomised. Three patients discontinued the study medication prematurely. No serious drug-related adverse events occurred. At 12 months no statistically significant differences were observed in the primary endpoints including total lung capacity, diffusion capacity, 6-minute walking distance, peak oxygen uptake, and computed tomography-score. Sixty-three percent of the patients treated with bosentan showed an increase of 10% in at least one of the primary endpoints, compared with 67% in the placebo group (p = 1). CONCLUSIONS: There is no evidence to support efficacy of bosentan as an antifibrotic treatment for patients with steroid-resistant pulmonary sarcoidosis. Bosentan was well tolerated and no drug-related adverse effects were observed within the study population. TRIAL REGISTRATION: ISRCTN registry, ISRCTN73579020.

Diagnosis, Prevention and Treatment of Stable COPD and Acute Exacerbations of COPD: The Swiss Recommendations 2018.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update.

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.

Aspergillus-PCR in bronchoalveolar lavage for detection of invasive pulmonary aspergillosis in immunocompromised patients.

BACKGROUND: Invasive fungal disease (IFD) is a frequent and serious infectious complication in immunocompromised patients. Culture and cytology in bronchoalveolar lavage (BAL) have a high specificity but low sensitivity for the diagnosis of IFD as assessed by histology. Molecular methods are expected to allow a rapid diagnosis of IFD with a high sensitivity. We evaluated the diagnostic accuracy of conventional nested PCR in the bronchoalveolar fluid to diagnose IFD in severely immunocompromised patients. METHODS: Consecutive immunosuppressed patients undergoing bronchoscopy for suspected pulmonary infection in a tertiary care hospital were included. Patients were classified as having "proven", "probable", "possible", and "no" IFD based on definitions of the European Organization for Research and Treatment of Cancer and National Institute of Allergy and Infectious Diseases (EORTC/NIAID) and on clinical grounds. Conventional nested PCR for aspergillus fumigatus, flavus, niger, glaucus, terreus and tomarrii were applied to 2.5 ml bronchoalveolar fluid. RESULTS: A total of 191 patients were included. Mean age was 51 y, 61% were male. There were 129 patients with hematological conditions, 26 solid organ transplant recipients, 24 auto-immune disorders, and 12 HIV. According to the EORTC/NIAID classification, there were 53 patients with potential IFD: 3 (2%) had proven, 8 (4%) probable, 42 (22%) possible and 138 (72%) no IFD. A total of 111 (58%) of the patients - 10 (90.9%) proven or probable IFD, 32 (76.2%) possible IFD and 69 (50%) "no" IFD) were on anti-fungal therapy at the time of bronchoscopy. Conventional nested PCR for Aspergillus was positive in 55 cases (28.8%). According to these results, sensitivity, specificity, PPV and NPV for "proven" IFD was 0%, 71%, 0%, 98%, respectively and "probable" IFD was 36%, 72%, 7%, 95%, respectively. In 53 (28%) cases there was a strong clinical suspicion of IFD in the chest-x-ray and/or chest-CT irrespective of the EORTC/NIAID classification. However, from those, only 15 (28%) had a positive conventional nested PCR. CONCLUSION: In our experience, conventional nested Aspergillus PCR in the BAL seems to be of limited usefulness for detection of invasive fungal disease in immunocompromised patients due to the limited sensitivity and specificity of the method.

Lung resection in hematologic patients with pulmonary invasive fungal disease.

BACKGROUND: Pulmonary invasive fungal disease is a frequent complication in patients with hematologic malignancies. Surgical resection in addition to antifungal therapy is an option for selected cases but often feared because of immunosuppression. METHODS: We analyzed the outcome of 71 patients undergoing lung resection for pulmonary invasive fungal disease. Most patients had leukemia, 44 underwent high-dose chemotherapy, and 18 underwent stem cell transplantation. RESULTS: On the day of surgery, 44 patients were neutropenic, and 41 had a platelet count < 50 × 109/L. Forty-five nonanatomic (atypical) resections and 26 lobectomies were performed. Fungal infection was histologically proven in 53 patients. Reoperation was needed in four patients (bronchial stump dehiscence, persistent air leak, chylothorax, and seroma). Minor complications at the site of surgery occurred in 14 patients. In only two, there was an uncontrolled disseminated fungal infection. Overall, mortality at 30 days was 7% (five of 71). Long-term survival was mainly influenced by the underlying hematologic disease. CONCLUSIONS: Lung resection is a therapeutic option for hematologic patients with pulmonary fungal infection. Despite immunosuppression, the perioperative morbidity and mortality is acceptable, and, therefore, the prognosis is not determined by the surgical intervention.