galactomannan and Cystic-Fibrosis

Aspergillus terreus may colonize the airways of patients with cystic fibrosis (CF). Whether this merits antifungal treatment is still unclear due to heterogeneous reports regarding its pathogenic potential. Although allergic manifestations are documented, invasive aspergillosis (IA) caused by A. terreus has not been described. We present here one case of probable IA caused by A. terreus, highlighting its role as an emerging agent of IA in CF patients. Voriconazole was effective, and the patient was healthy after 12 weeks of treatment. Serial determination of serum galactomannan level and periodic cultures from respiratory specimens may help in monitoring CF patients by identifying such pathogens. Further studies on the fungal species colonizing the CF airways are warranted, especially in India. This case report suggests A. terreus as a potential agent of IA which should not be ignored, particularly in this patient group.

Topics: Antifungal Agents; Aspergillus; Child; Cystic Fibrosis; Drug Monitoring; Galactose; Humans; India; Invasive Pulmonary Aspergillosis; Male; Mannans; Treatment Outcome; Voriconazole

Aspergillus fumigatus frequently colonizes the airways of patients with cystic fibrosis (CF) and may cause various severe infections, such as bronchitis. Serological data, sputum dependent markers and longitudinal data of treated cases of Aspergillus bronchitis were evaluated for further description of this infection. This study, which comprises three substudies, aimed to analyze epidemiological data of Aspergillus in CF and the entity of Aspergillus bronchitis. In a first step, data of the German Cystic Fibrosis Registry were used to evaluate the frequency of Aspergillus colonization in patients with CF (n = 2599). Then a retrospective analysis of 10 cases of Aspergillus bronchitis was performed to evaluate longitudinal data for lung function and clinical presentation parameters: sputum production, cough and physical capacity. Finally, a prospective cohort study (n = 22) was conducted to investigate serological markers for Aspergillus bronchitis: total serum IgE, specific serum IgE, specific serum IgG, as well as sputum galactomannan, real-time PCR detection of Aspergillus DNA in sputum and fungal cultures. Analysis of the German CF registry revealed an Aspergillus colonization rate of 32.5% among the 2599 patients. A retrospective data analysis of 10 treated cases revealed the clinical course of Aspergillus bronchitis, including repeated positive sputum culture findings for A. fumigatus, no antibiotic treatment response, total serum IgE levels <200 kU/l, no observation of new pulmonary infiltrates and appropriate antifungal treatment response. Antifungal treatment durations of 4 ± 1.6 (2-6) weeks significantly reduced cough (P = 0.0067), sputum production (P < 0.0001) and lung function measures (P = 0.0358) but not physical capacity (P = 0.0794). From this retrospective study, a prevalence of 1.6% was calculated. In addition, two cases of Aspergillus bronchitis were identified in the prospective cohort study according to immunological, molecular and microbiological parameters. A prevalence of 9% was assessed. Aspergillus bronchitis appears to occur in a minority of colonized CF patients. Antifungal treatment may reduce respiratory symptoms and restore lung function.

Topics: Adolescent; Adult; Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Biomarkers; Bronchitis; Child; Cystic Fibrosis; DNA, Fungal; Female; Galactose; Germany; Humans; Longitudinal Studies; Male; Mannans; Prevalence; Prospective Studies; Real-Time Polymerase Chain Reaction; Respiratory Function Tests; Retrospective Studies; Serum; Sputum; Young Adult

Aspergillus fumigatus is frequently encountered in sputum samples of patients with cystic fibrosis (CF), which traditionally has been interpreted as saprophytic airway colonization. However, this mere bystander role has been challenged by recent data. There is now evidence that Aspergillus fumigatus accelerates the decline of pulmonary function. (1→3)-β-D-glucan (BDG) and galactomannan (GM) are highly sensitive fungal biomarkers that are used to diagnose invasive fungal disease. However, their diagnostic value in CF patients is largely unknown.. We conducted a retrospective cohort study on 104 CF patients to determine whether serum BDG and GM levels correlate with parameters such as Aspergillus-positive sputum cultures and lung function.. Aspergillus fumigatus was persistently detected in 22 of the 104 CF patients (21%). Mean serum BDG and GM levels in the Aspergillus-positive patients were significantly higher than in those without persistent Aspergillus detection (89 versus 40 pg/ml [p = 0.022] and 0.30 versus 0.15 ODI [p = 0.013], respectively). 27 and 7 patients had elevated BDG (≥ 60 pg/ml) or GM levels (> 0.5 ODI), respectivly. BDG and GM levels showed a significant correlation (p = 0.004). Patients with increased serum concentrations of BDG were more frequently Aspergillus-positive (40.7 versus 14.3%, p = 0.004) and had a significantly lower forced expiratory volume in one second (FEV1) than patients with a normal BDG (61.6 versus 77.1%, p = 0.007). In the multivariate analysis, BDG but not GM or the growth of A. fumigatus, proved to be an independent predictor for the FEV1.. CF patients with persistent Aspergillus detection have elevated BDG and GM levels which ranged between healthy and invasively infected patients. Serum BDG may be superior to GM and fungal culture in predicting an impaired lung function in CF patients.

Topics: Adolescent; Adult; Aspergillus fumigatus; beta-Glucans; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Culture Techniques; Cystic Fibrosis; Female; Forced Expiratory Volume; Galactose; Humans; Male; Mannans; Middle Aged; Multivariate Analysis; Proteoglycans; Pulmonary Aspergillosis; Retrospective Studies; Sputum; Young Adult

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.

Topics: Adult; Allergens; Antibodies, Fungal; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Cystic Fibrosis; Female; Galactose; Humans; Immunoglobulin E; Immunoglobulin G; Male; Mannans; Prospective Studies; Real-Time Polymerase Chain Reaction; Skin Tests; Sputum; Young Adult

Invasive pulmonary aspergillosis is a rare and fatal complication in patients with cystic fibrosis (CF) who lack concomitant risk factors. The few documented cases in children have all resulted in deaths during hospitalisation. We present the case of a 12-year-old boy with CF who was admitted for an exacerbation which was unresponsive to antibiotic therapy. The findings on imaging raised concerns about a possible fungal infection. As a result, voriconazole therapy was started prior to his respiratory deterioration. He was later found to be β-D glucan and Aspergillus Ag galactomannan positive confirming the suspicion for invasive pulmonary aspergillosis. Three months after diagnosis, he was discharged home under stable condition. Voriconazole was continued beyond discharge and resulted in improvement of respiratory symptoms. This underscores the importance of early treatment of pulmonary aspergillosis in patients with CF. Unfortunately, the patient died 6 months after diagnosis from a CF exacerbation.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Bronchoalveolar Lavage; Child; Cystic Fibrosis; Early Diagnosis; Fatal Outcome; Galactose; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Male; Mannans; Pyrimidines; Triazoles; Voriconazole

Cystic fibrosis patients are often colonized by Aspergillus species. Sera from 138 pediatric and adult cystic fibrosis patients were tested for the presence of galactomannan. All serum samples were negative for galactomannan and there was no difference among patients who were chronically, intermittently, and never colonized with Aspergillus.

Topics: Adolescent; Adult; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Child; Cystic Fibrosis; Female; Forced Expiratory Volume; Galactose; Humans; Immunoenzyme Techniques; Lung; Male; Mannans; Middle Aged; Young Adult

Opportunistic fungal infections are life threatening especially for immunosuppressed patients. Early and accurate diagnosis is very important for the prompt initiation of treatment and to reduce unnecessary use of antifungal drugs. In recent years, efforts providing more rapid and more sensitive diagnosis of invasive fungal infections have been increasing. These methods include detection of fungal antigens, specific antibodies, fungal metabolites and DNA in the clinical samples. In this case, we report a seven year-old male patient with cystic fibrosis and diffuse large B-cell lymphoma, who presented with fever, vomiting and chronic cough. Diffuse parenchymal infiltrations and alveolar opacities in the inferior lobe of right lung and focal patchy alveolar infiltrates in different segments in both lungs were seen in thoracal CT scanning. Bronchoalveolar lavage (BAL) sample obtained by bronchoscopy was sent to the mycology laboratory and hypha elements that were compatible with Aspergillus were seen in direct examination. Aspergillus fumigatus was isolated from the culture of BAL sample. Real-time polymerase chain reaction (Rt-PCR), galactomannan (GM = 1.08 ng/ml) and 1,3-ß-D-Glucan (BG > 523 pg/ml) tests in BAL sample yielded positive results, however simultaneously performed PCR, GM (0.13 ng/ml) and BG (< 7 pg/ml) tests in serum sample were found to be negative. Treatment with voriconazole was started and continued for 45 days. The patient was discharged after improvement of his general state. It was concluded that PCR, GM and BG tests performed both in sera and BAL samples might aid to the early diagnosis and treatment of patients with invasive fungal infections in immunosuppressed patients. These data should be supported with further larger scale studies.

Topics: Antifungal Agents; beta-Glucans; Bronchoalveolar Lavage Fluid; Bronchoscopy; Child; Cystic Fibrosis; Galactose; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Lymphoma, Large B-Cell, Diffuse; Male; Mannans; Pyrimidines; Real-Time Polymerase Chain Reaction; Tomography, X-Ray Computed; Triazoles; Voriconazole