Aspergillus fumigatus colonization in cystic fibrosis: Implications for lung function?

Department of Paediatric Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
Clinical Microbiology and Infection (Impact Factor: 5.77). 11/2010; 17(9):1381-6. DOI: 10.1111/j.1469-0691.2010.03429.x
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Clin Microbiol Infect 2011; 17: 1381–1386
Aspergillus fumigatus is commonly found in the respiratory secretions of patients with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis (ABPA) is associated with deterioration of lung function, the effects of A. fumigatus colonization on lung function in the absence of ABPA are not clear. This study was performed in 259 adults and children with CF, without ABPA. A. fumigatus colonization was defined as positivity of >50% of respiratory cultures in a given year. A cross-sectional analysis was performed to study clinical characteristics associated with A. fumigatus colonization. A retrospective cohort analysis was performed to study the effect of A. fumigatus colonization on lung function observed between 2002 and 2007. Longitudinal data were analysed with a linear mixed model. Sixty-one of 259 patients were at least intermittently colonized with A. fumigatus. An association was found between A. fumigatus colonization and increased age and use of inhaled antibiotics. In the longitudinal analysis, 163 patients were grouped according to duration of colonization. After adjustment for confounders, there was no significant difference in lung function between patients colonized for 0 or 1 year and patients with 2–3 or more than 3 years of colonization (p 0.40 and p 0.64) throughout the study. There was no significant difference in lung function decline between groups. Although colonization with A. fumigatus is more commonly found in patients with more severe lung disease and increased treatment burden, it is not independently associated with lower lung function or more severe lung function decline over a 5-year period.

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    • "The proportion of CF patients with A. fumigatus colonisation in respiratory secretions ranges from 6% to 58% [16]–[18]. A retrospective cohort study involving 259 patients found 61 (24%) were at least intermittently colonized with A. fumigatus between 2002 and 2007 [17]. Culture methods vary substantially between centres, and culture is an insensitive means of determining colonisation [19]. "
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    ABSTRACT: Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative frequencies of these entities have recently been ascertained in a large UK adult CF cohort. We have used this data to estimate the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries reporting CF. National and international CF registry data was accessed and assessed for completeness and age distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those >18 years and compared with notified ABPA cases. Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were >18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases. Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population. ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was <1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.
    PLoS ONE 06/2014; 9(6):e98502. DOI:10.1371/journal.pone.0098502 · 3.23 Impact Factor
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    • "The relationship between host and Af in CF is quite complex [7]. Some CF patients show stable Af colonization (CF-AC), which can last for months to decades with no allergic hypersensitization and uncertain impact on the course of the disease [8] [9] [10]. In others, ABPA occurs, which severely impacts lung function [11]. "
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    ABSTRACT: INTRODUCTION: Fifteen to sixty percent of cystic fibrosis patients harbor Aspergillus fumigatus (Af) in their airways (CF-AC) and some will develop allergic bronchopulmonary aspergillosis (CF-ABPA). Since basophils play a key role in allergy, we hypothesized that they would display alterations in CF-ABPA patients compared to CF-AC or patients without Af colonization (CF). METHODS: Using flow cytometry, we measured CD203c, CD63 and CD123 levels on basophils from CF-ABPA (N=11), CF-AC (N=14), and CF (N=12) patients before and after ex vivo stimulation with Af allergens. RESULTS: Baseline CD203c was increased in basophils from CF-ABPA compared to CF-AC and CF patients. Af extract and recombinant Aspf1 stimulated basophils from CF-ABPA patients to markedly upregulate CD203c, along with modest upregulation of CD63 and a CD123 downward trend. Plasma TARC/CCL17 at baseline and post-stimulation cell supernatant histamine levels were similar in the three groups. CONCLUSIONS: In CF-ABPA, blood basophils are primed and hyperresponsive to Af allergen stimulation.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 05/2012; 11(6). DOI:10.1016/j.jcf.2012.04.008 · 3.48 Impact Factor
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    American Journal of Respiratory and Critical Care Medicine 12/2010; 182(12):1460-1. DOI:10.1164/rccm.201008-1311ED · 13.00 Impact Factor
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