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      Sensitization to Aspergillus fumigatus as a risk factor for bronchiectasis in COPD

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          Abstract

          Background

          Bronchiectasis–chronic obstructive pulmonary disease (COPD) overlap presents a possible clinical phenotype of COPD, but it is unclear why it develops in a subset of patients. We hypothesized that sensitization to Aspergillus fumigatus ( A fum) is associated with bronchiectasis in COPD and occurs more frequently in vitamin D-deficient patients.

          Methods

          This observational study investigated sensitization to A fum in an outpatient clinical cohort of 300 COPD patients and 50 (ex-) smoking controls. Total IgE, A fum-specific IgE against the crude extract and against the recombinant antigens and A fum IgG were measured using ImmunoCAP fluoroenzyme immunoassay. Vitamin D was measured by radioimmunoassay, and computed tomography images of the lungs were scored using the modified Reiff score.

          Results

          Sensitization to A fum occurred in 18% of COPD patients compared to 4% of controls ( P=0.0110). In all, 31 COPD patients (10%) were sensitized to the crude extract and 24 patients (8%) had only IgE against recombinant antigens. A fum IgG levels were significantly higher in the COPD group ( P=0.0473). Within COPD, A fum-sensitized patients were more often male ( P=0.0293) and more often had bronchiectasis ( P=0.0297). Pseudomonas aeruginosa and Serratia marcescens were more prevalent in historical sputum samples of A fum-sensitized COPD patients compared to A fum-non-sensitized COPD patients ( P=0.0436). Vitamin D levels were comparable ( P=0.2057). Multivariate analysis demonstrated that sensitization to recombinant f1 or f3 had a 2.8-fold increased risk for bronchiectasis ( P=0.0030).

          Conclusion

          These results highlight a potential role for sensitization to A fum in COPD-related bronchiectasis.

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          Most cited references 26

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          Chronic obstructive pulmonary disease.

          Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.
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            Inflammation: a two-edged sword--the model of bronchiectasis.

             Jonathan Cole (1985)
            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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              Novel immunologic classification of aspergillosis in adult cystic fibrosis.

              Patients with cystic fibrosis (CF) demonstrate a wide range of hypersensitivity responses to Aspergillus, beyond allergic bronchopulmonary aspergillosis, which require classification. This study integrated 2 new methods of Aspergillus detection-sputum galactomannan (GM) and real-time PCR-alongside established serologic markers, to reclassify aspergillosis in CF. A total of 146 adult patients with CF had serologic tests (ImmunoCap total IgE, specific Aspergillus fumigatus IgE, and specific A fumigatus IgG), sputum real-time Aspergillus PCR, and sputum GM. Patients were classified by using latent class analysis. Both RT-PCR and GM were more sensitive than culture in detecting Aspergillus in sputum (culture 37%, RT-PCR 74%, and GM 46%). Intraassay and interassay reproducibility of PCR and GM was excellent. Latent class analysis of triazole-naive patients identified a nondiseased group and 3 disease classes: class 1 (n = 49, 37.7%) represented patients with or without positive RT-PCR but no immunologic response to A fumigatus and negative GM (nondiseased); class 2 (n = 23, 17.7%) represented patients with positive RT-PCR, elevated total and specific A fumigatus IgE/IgG, and positive GM (serologic allergic bronchopulmonary aspergillosis); class 3 (n = 19, 14.6%) represented patients with or without positive RT-PCR, elevated A fumigatus IgE (not IgG), and negative GM (Aspergillus sensitized); and class 4 (n = 39, 30%) represented patients with positive RT-PCR, elevated A fumigatus IgG (not IgE), and positive GM (Aspergillus bronchitis). Three distinct classes of aspergillosis in CF were identified by latent class analysis by using serologic, RT-PCR, and GM data. This novel classification will facilitate improved phenotyping, pathogenesis studies, and management evaluations. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2017
                31 August 2017
                : 12
                : 2629-2638
                Affiliations
                [1 ]Department of Respiratory Diseases, University Hospitals Leuven
                [2 ]Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, KU Leuven
                [3 ]Department of Laboratory Medicine, University Hospitals Leuven
                [4 ]Department of Microbiology and Immunology, KU Leuven
                [5 ]Department of Radiology, University Hospitals Leuven, Leuven, Belgium
                Author notes
                Correspondence: Wim Janssens, Department of Respiratory Diseases, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium, Tel +32 16 34 6812, Fax +32 16 34 6803, Email wim.janssens@ 123456uzleuven.be
                Article
                copd-12-2629
                10.2147/COPD.S141695
                5587018
                © 2017 Everaerts et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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