Frequencies of pathogenic CFTR variants in Greek cystic fibrosis patients with allergic bronchopulmonary aspergillosis and Aspergillus fumigatus chronic colonization: A retrospective cohort study.

INTRODUCTION: The clinical spectrum of Aspergillus fumigatus diseases in cystic fibrosis (CF) patients, including allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus chronic colonization, has recently gained attention due to its association with the progression of lung disease. Our aim was to examine whether there is a difference on pathogenic variant frequencies of the CFTR gene between CF patients with ABPA and those with A. fumigatus chronic colonization. MATERIAL AND METHODS: Greek CF patients diagnosed with ABPA and/or A. fumigatus chronic colonization were grouped according to their CFTR genotype. Patients with "minimal" CFTR function were defined as carrying a combination of class I or II pathogenic variants, while patients with "residual" function as carrying at least one class III, IV, V or VI pathogenic variant. RESULTS: Fifty-four CF patients were included and all except one were defined as having "minimal" CFTR function. Among the 108 CFTR alleles, 69 (63.9%) of pathogenic variants belonged to class II, and 32 (29.6%) to class I. Five patients had a history of both ABPA and A. fumigatus chronic colonization. No significant difference was detected among patients diagnosed only with ABPA (n = 29) and those who had only a positive history of A. fumigatus chronic colonization (n = 20). The median age of ABPA diagnosis was significantly lower than the median age of A. fumigatus chronic colonization (P = 0.011), while no significant difference was detected on median FEV1% predicted. DISCUSSION: No significant differences were detected in the type of CFTR pathogenic variants among patients with ABPA and those with A. fumigatus colonization. Similar studies should be performed in larger CF populations of different ethnic origin to further confirm our results.

Early-Life Pseudomonas aeruginosa Infection in Cystic Fibrosis and Lung Disease Progression.

Lung disease in cystic fibrosis (CF) starts early, with studies identifying abnormalities on chest computed tomography (CT) scan even in infancy. In this retrospective study, abnormal chest CT was the main outcome; body mass index (BMI) z score and forced expiratory volume percent predicted (FEV1%) predicted at age 6 to 7 years were secondary outcomes. Pseudomonas aeruginosa infection prior to 12 months of age was the main explanatory variable. There was no association between early P aeruginosa infection and abnormal CT after adjustment for CFTR (cystic fibrosis transmembrane conductance regulator) functional mutation class, gender, and other pathogens (odds ratio = 0.30; 95% confidence interval = 0.07-1.35; P = .11). No significant associations were demonstrated for BMI z score and FEV1% predicted. Children with class I-III CFTR mutations had increased risk of abnormal CT findings (odds ratio = 11.67; 95% confidence interval = 1.11-115.06; P = .035) and lower FEV1% predicted (P = .04). In the current era, early-life P aeruginosa infection in CF might not influence the severity of lung disease in school age as much as previously. Larger studies are needed to confirm this finding.

Scedosporium apiospermum complex in cystic fibrosis; should we treat?

Species of the Scedosporium apiospermum complex are the second most frequent filamentous fungi after Aspergillus fumigatus that can be found in cystic fibrosis (CF). Mixed colonisation by S. apiospermum complex and A. fumigatus is also quite common. In this study we summarise all CF patients who were colonised by S. apiospermum complex during their childhood and we present two CF patients who were treated as fungal bronchitis due to S. apiospermum complex. The medical records of 400 CF patients were reviewed in order to identify those with positive respiratory cultures for S. apiospermum complex. Scedosporium apiospermum complex was isolated in 10 CF patients and six of them had more than two positive sputum cultures during the study period. By the time of first isolation, the median age was 14.5 years, the median BMI was 19.41 kg/m2 , the median predicted FEV1 % was 78.65% and six patients had a history of A. fumigatus isolation. Two patients presented symptoms of infection while they were colonised by S. apiospermum complex. A rapid remission of their symptoms was observed only when antifungal therapy was administered. Antifungal treatment should be considered in CF patients who present symptoms of infection not responding to antibacterial therapy and S. apiospermum complex is persistently growing in sputum cultures.

Body composition and lung function in children with cystic fibrosis and meconium ileus.

The aim of this study was to explore whether history of meconium ileus (MI) at birth in children and adolescents with cystic fibrosis (CF) adversely affects body composition and lung function in later life. Data of children and adolescents with CF who underwent spirometry and DXA as part of their routine care were analyzed. Associations between MI (explanatory variable) and areal bone mineral density (total body less head-TBLH aBMD), lean tissue mass (LTM), and fat mass (FM) (outcomes) were assessed using general linear models. Potential relationships of TBLH aBMD, LTM, and FM with FEV1 (additional outcome) were also explored. One hundred and one subjects with CF (mean age 14 ± 3 years) were included, 19 (18.8%) of whom had history of MI. Negative associations were demonstrated between history of MI and FEV1 (P = 0.04), TBLH aBMD (P = 0.03), and FM (P < 0.01) but not between history of MI and LTM (P = 0.07) after adjustment for other variables. Lung function was positively associated with TBLH aBMD (P < 0.01) and LTM (P = 0.02) but not with FM (P = 0.20). CONCLUSION: Among children and adolescents with CF, those with history of MI have lower bone mineral density, FM, and lung function. What is Known: • Among children and adolescents with cystic fibrosis, those with history of meconium ileus in the neonatal period are at risk of having lower body mass index percentile and FEV 1 percent predicted. What is New: • Children and adolescents with cystic fibrosis and history of meconium ileus have decreased bone mineral density and fat mass compared to patients without such history. • Lower lung function in children with MI coexists with suboptimal bone mineral density.

The role of basophil activation test in allergic bronchopulmonary aspergillosis and Aspergillus fumigatus sensitization in cystic fibrosis patients.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus sensitization (AFS) are quite often observed in cystic fibrosis (CF) patients. The aim of this study was to evaluate the use of basophil activation test (BAT) in these manifestations of hypersensitivity reactions. METHODS: BAT (CD63 and CD203c) was performed for 56 CF patients (17 ABPA, 24 AFS and 15 non-AFS). A receiver operating characteristic (ROC) curve analysis and a survival analysis were performed. RESULTS: Both markers significantly contributed in ABPA diagnosis (P value<0.001 for both). Twelve AFS patients fulfilled the criteria for ABPA diagnosis during the follow-up period. The median time to ABPA diagnosis was 9months for patients whose values were over the best cutoffs (P value<0.001 for both). CONCLUSIONS: BAT could be considered as an additional criterion for ABPA diagnosis in CF as well as a potential marker for the monitoring of patients with AFS.

Candida albicans chronic colonisation in cystic fibrosis may be associated with inhaled antibiotics.

Candida albicans is increasingly recognised as a coloniser of the respiratory tract in cystic fibrosis (CF) patients. Yet, the potential role, if any, of the micro-organism in the progress of the disease remains unclear. In this study, we investigated the association between inhaled antibiotics and C. albicans chronic colonisation in patients with CF. A cohort of 121 CF patients born from 1988 to 1996 was, respectively, studied. The medical records of each patient were reviewed from the first time they attended the CF Centre until the occurrence of C. albicans chronic colonisation or their last visit for the year 2010. Chronic colonisation was defined as the presence of C. albicans in more than 50% of cultures in a given year. A number of possible confounders were included in the multivariate logistic regression analysis to identify an independent association between inhaled antibiotics and C. albicans chronic colonisation. Fifty-four (44.6%) of the 121 patients enrolled in the study developed chronic colonisation by the micro-organism. Multivariate logistic regression analysis determined the independent effect of inhaled antibiotic treatment on the odds of chronic colonisation (OR 1.112, 95% CI [1.007-1.229], P = 0.036). Candida albicans chronic colonisation may be associated with the duration of inhaled antibiotic treatment.

Inhaled corticosteroids and Aspergillus fumigatus isolation in cystic fibrosis.

Aspergillus fumigatus isolation in cultures from respiratory specimens of patients with cystic fibrosis (CF) is quite common; however, the role of A. fumigatus as a pathogen and whether its presence is associated with progression of pulmonary disease remain unclear. We investigated the association between inhaled corticosteroids and the recovery of A. fumigatus by performing a retrospective cohort study of CF patients born between 1988 and 1996. The patients' medical records from their first visit to the CF Center until December 2010 were reviewed. Outcomes were the occurrence of A. fumigatus first isolation, chronic colonization, or the last visit at the CF Center. A number of possible confounders were included in the multivariate logistic regression analysis in order to identify an independent association between inhaled corticosteroids and colonization status. A total of 121 patients were included in the study. Thirty-nine patients (32.2%) had at least one positive culture and 14 (11.6%) developed chronic colonization. Multivariate logistic regression analysis was used to determine the independent effect of inhaled corticosteroids on the odds of first isolation (odds ratio [OR], 1.165; 95% confidence interval [CI], 1.015-1.337; P = 0.029) and chronic colonization (OR, 1.180; 95% CI, 1.029-1.353; P = 0.018). In conclusion, A. fumigatus first isolation and chronic colonization are associated with the duration of inhaled corticosteroid treatment.