Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to Aspergillus fumigatus in patients with cystic fibrosis

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

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High Prevalence of Azole-Resistant Aspergillus fumigatus in Adults with Cystic Fibrosis Exposed to Itraconazole

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05077-11 ◽

2011 ◽

Vol 56 (2) ◽

pp. 869-874 ◽

Cited By ~ 120

Author(s):

Pierre-Régis Burgel ◽

Marie-Thérèse Baixench ◽

Michaël Amsellem ◽

Etienne Audureau ◽

Jeanne Chapron ◽

...

Keyword(s):

Cystic Fibrosis ◽

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis ◽

Previous Treatment ◽

University Hospital ◽

Clinical Implications ◽

Content Type ◽

Microdilution Method ◽

Broth Microdilution Method ◽

High Prevalence

ABSTRACTAspergillus fumigatusis the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) orAspergillusbronchitis in CF subjects. We hypothesized thatA. fumigatusisolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection ofA. fumigatus. MICs ofA. fumigatusisolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method.A. fumigatuswas isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. ReducedA. fumigatussusceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in thecyp51Agene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistantA. fumigatusisolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistantA. fumigatusisolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

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80 Value of specific IgE detection against the recombinant antigenic components of Aspergillus fumigatus in the diagnosis of allergic bronchopulmonary aspergillosis in adult patients with cystic fibrosis

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(17)30444-7 ◽

2017 ◽

Vol 16 ◽

pp. S85

Author(s):

D. Hernandez Fernandez de Rojas ◽

G. Anguera de Francisco ◽

S. Pastor Rebenaque ◽

C. Navarro ◽

A. Gomez Perez ◽

...

Keyword(s):

Cystic Fibrosis ◽

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis ◽

Specific Ige ◽

Adult Patients

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Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)

Thorax ◽

10.1136/thx.54.1.44 ◽

1999 ◽

Vol 54 (1) ◽

pp. 44-50 ◽

Cited By ~ 36

Author(s):

M Skov ◽

T Pressler ◽

H E Jensen ◽

N Hoiby ◽

C Koch

Keyword(s):

Cystic Fibrosis ◽

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis ◽

Igg Subclass ◽

Specific Igg ◽

Antibody Pattern

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IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

Allergy ◽

10.1046/j.1398-9995.2003.00310.x ◽

2004 ◽

Vol 59 (2) ◽

pp. 198-203 ◽

Cited By ~ 55

Author(s):

A. P. Knutsen ◽

P. S. Hutcheson ◽

R. G. Slavin ◽

V. P. Kurup

Keyword(s):

Cystic Fibrosis ◽

Aspergillus Fumigatus ◽

Allergic Bronchopulmonary Aspergillosis ◽

Recombinant Allergens ◽

Ige Antibody

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Risk factors for lung disease progression in children with cystic fibrosis

European Respiratory Journal ◽

10.1183/13993003.02509-2017 ◽

2018 ◽

Vol 51 (6) ◽

pp. 1702509 ◽

Cited By ~ 5

Author(s):

Marieke van Horck ◽

Kim van de Kant ◽

Bjorn Winkens ◽

Geertjan Wesseling ◽

Vincent Gulmans ◽

...

Keyword(s):

Risk Factors ◽

Cystic Fibrosis ◽

Lung Disease ◽

Disease Progression ◽

Potential Risk ◽

Allergic Bronchopulmonary Aspergillosis ◽

Pulmonary Exacerbation ◽

Exacerbation Rate ◽

Potential Risk Factors ◽

Pulmonary Exacerbations

To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009–2014).Lung disease progression was expressed as a decline in lung function (forced expiratory volume in 1 s (FEV1) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV1 % pred, best forced vital capacity % pred, genotype, body mass index z-score, pancreatic insufficiency, medication use (proton pump inhibitors (PPIs), prophylactic antibiotics and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis and colonisation with Pseudomonas aeruginosa.The data of 545 children were analysed. PPI use was associated with both annual decline of FEV1 % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV1 % pred at baseline (p=0.007), prophylactic inhaled antibiotic use (p=0.006) and pulmonary exacerbations in the baseline year (p=0.002) were related to pulmonary exacerbations in subsequent years.In a cohort of Dutch children with CF followed for 5 years, we were able to identify several risk factors for future exacerbations. In particular, the association between PPI use and lung disease progression definitely requires further investigation.

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