Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

A CPAnet consensus statement on research priorities for chronic pulmonary aspergillosis: a neglected fungal infection that requires attention.

Chronic pulmonary aspergillosis (CPA) is a severe fungal infection with a high morbidity and mortality, and is usually seen in immunocompetent patients with respiratory disorders. Clinical presentation is nonspecific and often overlaps with the symptoms and the radiological pattern caused by the underlying disease. Clinical management of CPA is further hampered by limited information about the epidemiology, disease dynamics, sensitivity and specificity of different mycological tests, mechanisms of antifungal resistance, efficient treatment and management strategies. In order to contribute to a better understanding and to improve CPA patient management and outcome, we established the Chronic Pulmonary Aspergillosis Network (CPAnet), a self-organized multinational research collaboration. Key research priorities, defined by using a modified Delphi process, include the establishment of a multinational web-based registry, the validation of different diagnostic tests, the establishment of a culture collection from samples of patients with proven CPA and the establishment of a consensus on a treatment outcome definition.

Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives.

Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-Aspergillus activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-Aspergillus agents are needed, along with optimization of currently available treatments.

Aspergillus-specific IgG antibodies for diagnosing chronic pulmonary aspergillosis compared to the reference standard.

OBJECTIVES: To evaluate the performance of Aspergillus-specific IgG antibodies for diagnosing chronic pulmonary aspergillosis (CPA) by using a cohort of patients with histologically proven CPA as a reference standard. METHODS: We collected Aspergillus-specific IgG antibody titres from patients with histologically proven CPA in collaboration with CPAnet study sites in Denmark, Germany, Belgium, India, Moldova, and Pakistan (N = 47). Additionally, sera from diseased and healthy controls were prospectively collected at the Medical Clinic of the Research Center, Borstel, Germany (n = 303). Aspergillus-specific IgG antibody titres were measured by the ImmunoCAP® assay (Phadia 100, Thermo Fisher Scientific, Uppsala, Sweden). An Aspergillus-specific IgG antibody titre ≥50 mgA/L was considered positive. RESULTS: Using patients with histologically proven CPA as the reference standard, the ImmunoCAP® Aspergillus-specific IgG antibody test had a sensitivity and specificity of 85.1% (95% CI: 71.7-93.8%) and 83.6% (95% CI: 78.0-88.3%), respectively. Patients with histologically proven CPA had significantly higher Aspergillus-specific IgG antibody titre with a median of 83.45 mgA/L (interquartile range 38.9-115.5) than all other cohorts (p < 0.001). False-positive test results occurred in one-third of 79 healthy controls. DISCUSSION: Our study results confirm a high sensitivity of the Aspergillus-specific IgG antibody test for the diagnosis of CPA when using patients with histologically proven CPA as a reference standard. However, positive test results should always match radiological findings as false-positive test results limit the interpretation of the test.

CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry.

Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPA Research network (CPAnet) registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. This study's aim was to describe the data collection process and content of CPAnet registry with preliminary clinical data. In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome, and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease, and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising clinical research collaboration.

Pulmonary rehabilitation: course report.

Delegates of an @ERStalk course on pulmonary rehabilitation describe their experiences http://ow.ly/VVp030fGC1x.

Ventilatory disturbances in patients with intrathoracic sarcoidosis - a study from a functional and histological perspective.

Background: Although sarcoidosis is commonly considered a restrictive disorder, more recent studies demonstrated opposite results. Objectives: To determine the prevalent functional pattern in patients with intrathoracic sarcoidosis and to assess the role of granulomatous inflammation in determining ventilatory disturbances. Methods: We included 144 consecutive newly diagnosed patients with sarcoidosis, who were evaluated by chest radiography, chest high resolution computer tomography, pulmonary function tests and dyspnea score. Additionally, endobronchial and transbronchial biopsies were performed to a subset of 78 patients. Results: We obtained a wide range of ventilatory abnormalities that characterize airways impairment: FEV1/FVC<70% - in 14 (9.7%) cases, low MMEF25-75 - in 69 (47.9%) patients, increased RV/TLC - in 65 (45.1%) subjects, while the subjects with restrictive defects was observed in a minority of cases - 7 (4.9%). Decreased DLCO was found in 100 (69.4%) individuals, in the majority of cases with mild changes. Patients in whom endobronchial biopsy showed granuloma had worse ventilatory results versus those in whom they have not been detected, with significant differences in FEV1 and MMEF25-75. We found significant correlations between radiological stage and pulmonary function tests. Dyspnea score (mMRC scale) in our cohort reflected lung volumes and DLCO modifications. Conclusion: The dominant functional abnormality in patients with intrathoracic sarcoidosis is obstruction, which affects the entire length of the bronchial tree causing a wide range of airways impairment and altered gas diffusion. These functional disturbances are prevalent from early stages of the disease and have a tendency to coexist with restriction as the disease advances. Granulomatous inflammation seems to have an important role in determining obstructive defect, even from "infra-radiological" stages. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 58-67).

Williams-Beuren syndrome--a rare cause of recurrent hemoptysis.

Williams-Beuren syndrome (WBS) is a rare genetic disease with a distinctive constellation of clinical findings. The disease can be diagnosed clinically by a recognizable pattern of malformations, including cardiovascular malformations, a characteristic facial dysmorphism, as well as neurological and cognitive features. We present the case of a 23-years-old woman repeatedly admitted to Pulmonology Clinic for massive hemoptysis. Diagnosis of Williams-Beuren syndrome was revealed by clinical findings and confirmed by CT-angiography data of cardiovascular malformations and fluorescence in situ hybridization (FISH) genetic test. WBS is a multisystem disorder and usually is recognized by clinician. If clinical impression is not clearly consistent with WBS, FISH remains the most widely used test.

A rare genetic cause of bronchiectasis.

Bronchiectasis, defined as an abnormal and irreversible dilatation of the bronchi, frequently associated with inflammation, is the most common complication of recurrent infections. Effective pulmonary immunity is necessary to prevent chronic bronchial damage due to bacterial infection. Primary immune deficiencies comprise a heterogeneous group of genetically determined disorders that affect development and/or the function of innate or adaptive immunity. In multiple series reported in literature, common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA) and chronic granulomatous disease (CGD) were the most common forms of primary immune deficiencies (PIDs) associated with bronchiectasis (1,15). Despite advances in the molecular knowledge of PIDs during the past two decades, there are many undiagnosed or late diagnosed patients (6,14). We report a case of Bruton's disease late diagnosed, already with bronchiectasis, with an early onset of recurrent respiratory infections.

Summer schools of adult and paediatric respiratory medicine: course report.

ERS hosted summer schools on adult and paediatric respiratory medicine in Lisbon, Portugalhttp://ow.ly/qcas304C5tO.

Interstitial pneumonitis after treatment for hepatitis C virus infection.

Pulmonary toxicity is a rare side effect of interferon treatment with a wide spectrum of lung tissue conditions, including interstitial pneumonitis, pulmonary sarcoidosis, bronchiolitis obliterans organizing pneumonia, pleural effusion, exacerbation of bronchial asthma, reversible pulmonary hypertension and acute respiratory distress syndrome. We report a case of interstitial pneumonitis in a patient treated with pegylated interferon α2-a and ribavirin for chronic hepatitis C virus infection, genotype 1. The case was marked by progression of the respiratory symptoms even after the withdrawn of the pegylated interferon. One-year treatment with systemic corticosteroid ensured a considerable resorption of CT lesions but only a moderate improvement of symptoms and diffusion capacity without a complete recovery.

[Cryptococcosis--a common fungal infection in immunosuppressed patient]. / Criptococoza--infectie fungica frecventa a imunocompromisululi.

Cryptococcus is a leading mycological cause of morbidity among HIV-infected patients. In many patients, cryptococcosis is the first indication of AIDS. The lung is invariably the portal of entry and initial site of infection for C. neoformans. In immunosuppressed patients all areas of the body can be infected, and central nervous sistem involvement is the most severe complication. Cryptococcosis is an important fungal infection thatshould be considered in the differential diagnosis of the pulmonary infiltrates in the immunosuppressed patient. The purpose of this paper is to review the current knowledge of the management and treatment strategies of cryptococcosis.

[Efficiency of prognostic scores for the assessment of patients with severe influenza pneumonias]. / Eficienta scorurilor prognostice în evaluarea pneumoniilor gripale severe.

AIM: To compare the efficiency of some prognostic scores in patients with severe influenza pneumonias. MATERIALS AND METHODS: The study was performed on a cohort of 75 cases of 2009 AH1N1 influenza associated pneumonias. Clinical and laboratory features at admission were used to calculate retrospectively the following prognostic scores: SCAP (Severe Community Acquired Pneumonia), CAP-PIRO (Community Acquired Pneumonia--Predisposition Infection Reaction, Organ failure), SMRT-CO (Systolic blood pressure, Multilobar infiltrates, Respiration rate, Tachycardia, Confusion, Oxygen), IDSA/ATS (Infectious Diseases Society of America/American Thoracic Society). The scores were used to assess two different outcomes--death and need for invasive mechanical ventilation (IMV). The performance of the prognostic tools were assessed using the area under receiver operating characteristic (AUC), and the sensitivity and specificity for identifying high risk patients for severe course of pneumonia. RESULTS: IMV was applied in 29 (38.7%) of studied cases, in 15 (20%) the diseases had a fatal outcome. Despite the fact that all scores had a very good discriminatory power in predicting both outcomes (AUC > 0,8), some of them have a very low sensitivity, in classes corresponding to sever pneumonias, in predicting mortality (IDSA/ATS-0%; 95% CI, 0-21.8%), as well as the need for IMV (IDSA/ATS-0%; 95% CI, 0-11.9%); SCAP-58.6% (95% CI, 38.9-76.5%); CAP-PIRO-58,6% (95% CI, 38.9-76.5%). CONCLUSIONS: The CAP-PIRO and SMRT-CO scores were found to have the best performances to predict death from influenza associated severe pneumonias and the last, also in predicting the need for IVM. Other analyzed scores underestimate the risk of occurrence of both assessed outcomes.

[Idiopathic pulmonary fibrosis--a case report]. / Fibroza pulmonara idiopatica--caz clinic.

Our understanding of the idiopathic interstitial lung disease (ILD) has undergone dramatic changes in the last decade, mostly in disease classification and diagnostic processes, and the role of high-resolution computed tomography (HRCT) of the chest in assessment of diagnosis and prognosis. The most important change has been the evidence of different histopathologic subgroups that make up the current classification of idiopathic interstitial pneumonias. Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition of uncertain aetiology that should be considered in the differential diagnosis of patients who experience breathlessness, cough and reduced exercise tolerance. The role of high-resolution computed tomography in the diagnosis of interstitial lung disease is increasing as our understanding of its diagnostic accuracy improves. The patient described in the present case was a 59-year-old female who presented with 3 years history of dyspnea on exertion, cough, and low grade fever (thyroidectomy for thyroid malignancy 4 months before current presentation). The findings on HRCT were ground-glass opacities and reticular abnormality with subpleural and lower lung zone predominance. She underwent surgical lung biopsy for differential diagnosis between IPF, nonspecific interstitial pneumonia and thyroid lung metastases. The histological examination showed a pattern of usual interstitial pneumonia (UIP) what is the underlying lesion in IPF.

[Pulmonary epithelioid hemangioendothelioma--a case report]. / Hemangioendoteliom epitelioid pulmonar --prezentare de caz.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare soft tissue tumor of endothelial origin that occurs among young women and typically presents as bilateral multiple nodules, readily mistaken for carcinoma or, as in this case, Wegener's granulomatosis. This is a rare disease, with approximately 50 cases described in the literature. In the present report, we describe a case of PEH in a 39-yr-old woman. Immunohistochemically, the tumor cells were positive for CD34.