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      Aspergillus fumigatus Detection and Risk Factors in Patients with COPD–Bronchiectasis Overlap

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          Abstract

          The role of Aspergillus fumigatus in the airways of chronic obstructive pulmonary disease (COPD) patients with bronchiectasis is currently unclear. We searched for a sensitive and noninvasive method for A. fumigatus detection in the sputum of COPD patients and addressed potential risk factors for its presence. Induced sputum samples of 18 COPD patients and 17 COPD patients with bronchiectasis were analyzed for the presence of A. fumigatus by culture, galactomannan detection, and PCR. Of the patients with COPD–bronchiectasis overlap, 23.5% had a positive culture for A. fumigatus versus 10.5% of COPD patients without bronchiectasis ( p = 0.39). The median sputum galactomannan optical density index was significantly higher in patients with COPD and bronchiectasis compared with patients with COPD alone ( p = 0.026) and ranged between the levels of healthy controls and A. fumigatus-colonized cystic fibrosis patients. Both the presence of bronchiectasis and the administration of systemic corticosteroids were associated with sputum galactomannan ( p = 0.0028 and p = 0.0044, respectively) and showed significant interaction ( p interaction = 0.022). PCR for Aspergillus was found to be a less sensitive method, but was critically dependent on the extraction technique. The higher sputum galactomannan levels suggest a more abundant presence of A. fumigatus in the airways of patients with COPD–bronchiectasis overlap compared with patients with COPD without bronchiectasis, particularly when systemic corticosteroids are administered.

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          The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis.

          The relevance of Aspergillus fumigatus in patients with cystic fibrosis (CF) not affected by allergic bronchopulmonary aspergillosis is unclear. Our aim was to determine the effect of persistent infection with A fumigatus on pulmonary exacerbations and lung function in children with CF. This was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children from 1999 to 2006. Persistent A fumigatus infection was defined as the presence of two or more positive sputum or bronchoalveolar cultures for A fumigatus in a given year. The primary outcome measure was the annual number of hospitalizations for pulmonary exacerbations. Two hundred thirty patients with CF were included in the analysis. The FEV(1) of patients persistently infected with A fumigatus was 3.61% (P< or =.0001) lower during the study period compared with uninfected patients. There was a significant interaction between A fumigatus and Pseudomonas aeruginosa on lung function (P=.0006). Patients not infected with either organism had the highest pulmonary function. Persistent A fumigatus infection (relative risk [RR]=1.94, P=.0002) and CF-related diabetes (RR=1.64, P=.028) were associated with an increased risk of pulmonary exacerbations requiring hospitalization, whereas there was no increased risk of pulmonary exacerbations among patients with allergic bronchopulmonary aspergillosis (RR=1.02, P=.94). When adjusted for baseline pulmonary function, none of these variables were associated with a significantly increased risk of pulmonary exacerbations, with only chronic A fumigatus infection trending toward significance (RR=1.40, P=.065). Persistent A fumigatus infection is an independent risk factor for hospital admissions in patients with CF.
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            Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome.

            We describe a large series of patients with chronic obstructive pulmonary disease (COPD) and probable invasive pulmonary aspergillosis (IPA), and the risk factors and incidence of the disease in patients with isolation of Aspergillus from lower respiratory tract samples. From 2000 to 2007, we retrospectively studied all patients admitted with COPD and isolation of Aspergillus (239; 16.3/1000 admissions). Multivariate logistic regression and survival curves were used. Fifty-three patients had probable IPA (3.6 cases of IPA per 1000 COPD admissions). IPA affects at least 22.1% of patients with COPD and isolation of Aspergillus in culture. In 33 of the 53 patients with probable IPA, serum galactomannan was determined; in 14 (42.4%) of these, the result was positive. Five variables were independent predictors of IPA with statistical significance: admission to the intensive-care unit, chronic heart failure, antibiotic treatment received in the 3 months prior to admission, the accumulated dosage of corticosteroids equivalent to >700 mg prednisone received in the 3 months prior to admission, and the similar accumulated dosage of corticosteroids received from admission to the first clinical isolation of Aspergillus. Multivariate analysis gave an area under the curve of 0.925 (95% CI 0.888-0.962; p <0.001). The overall mean survival of the cohort was 64.1% (28.3% for IPA patients and 75.2% for non-IPA patients). The median number of days of survival was 48 (95% CI 33.07-62.92). However, we found statistically significant differences between patients with IPA (29 days; 95% CI 20.59-37.40) and patients without IPA (86 days; 95% CI 61.13-110.86) (log rank, p <0.001).
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              Inflammation: a two-edged sword--the model of bronchiectasis.

              A short-lived, controlled inflammatory response by the host is required to protect against incursions by foreign material into the upper and lower respiratory tract. If this response fails to eliminate the aggressor, inflammation is amplified and becomes chronic in an attempt to rectify the situation. This unsuccessful response is poorly controlled and caused damage to surrounding normal tissue, leading to progressive disease. Hence, inflammation can be helpful or harmful--a two-edged sword. Chronic bronchial sepsis, of which bronchiectasis is an example, and chronic sinusitis display the hallmarks of this 'vicious circle' of host-mediated, inflammatory tissue damage and provide a useful model in man in which to ask questions, the answers to which provide valuable information about the pathogenesis of chronic inflammatory disease of the lung.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 February 2018
                February 2018
                : 19
                : 2
                : 523
                Affiliations
                [1 ]Department of Respiratory Diseases, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium; stephanie.everaerts@ 123456kuleuven.be (S.E.); lieven.dupont@ 123456uzleuven.be (L.J.D.)
                [2 ]Department of Chronic Diseases, Metabolism & Aging, Laboratory of Respiratory Diseases, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium; kristina.vermeersch@ 123456uzleuven.be (K.V.); bart.vanaudenaerde@ 123456kuleuven.be (B.M.V.)
                [3 ]Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium; katrien.lagrou@ 123456uzleuven.be
                [4 ]Department of Microbiology and Immunology, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
                Author notes
                [* ]Correspondence: wim.janssens@ 123456uzleuven.be ; Tel.: +32-1634-6812; Fax: +32-1634-6803
                Author information
                https://orcid.org/0000-0001-8668-1350
                Article
                ijms-19-00523
                10.3390/ijms19020523
                5855745
                29425123
                5d584c1e-8d2a-47e0-be0e-97d94580ed8f
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 January 2018
                : 06 February 2018
                Categories
                Article

                Molecular biology
                sputum galactomannan,aspergillus pcr,aspergillus colonization,corticosteroids

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