scholarly journals Posaconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

2019 ◽  
Vol 74 (6) ◽  
pp. 1701-1703 ◽  
Author(s):  
J Periselneris ◽  
L Nwankwo ◽  
S Schelenz ◽  
A Shah ◽  
D Armstrong-James
Keyword(s):  
Cystic Fibrosis ◽  
Systemic Corticosteroid ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Drug Level ◽  
Corticosteroid Treatment ◽  
Specific Ige ◽  
Therapeutic Drug ◽  
Serological Response ◽  
Lung Function Decline ◽  
Better Than

Abstract Objectives Allergic bronchopulmonary aspergillosis (ABPA) can accelerate lung function decline in patients with cystic fibrosis (CF). Antifungal medication can be used in addition to systemic corticosteroid treatment. Patients and methods We evaluated Aspergillus-specific IgE and the use of therapeutic drug monitoring of triazoles in a retrospective analysis of 32 patients. Results There was a significant reduction in Aspergillus IgE with posaconazole but not with other triazoles (P = 0.026). Aspergillus IgE levels were inversely correlated with the therapeutic drug level of posaconazole. Conclusions These data suggest that posaconazole is better than comparator azoles at decreasing serological response to Aspergillus and that this response was better with therapeutic levels of posaconazole.

scholarly journals BASOPHILE ACTIVATION TEST FOR THE DIAGNOSTICS OF FUNGAL SENSITIZATION IN THE PATIENTS WITH CYSTIC FIBROSIS

2019 ◽  
Vol 21 (5) ◽  
pp. 919-928
Author(s):  
Ya. I. Kozlova ◽  
E. V. Frolova ◽  
A. E. Uchevatkina ◽  
L. V. Filippova ◽  
O. V. Aak ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stimulation Index ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Basophil Activation Test ◽  
Specific Ige ◽  
Basophil Activation ◽  
Total Ige ◽  
Activation Test ◽  
Fungal Allergens ◽  
Fungal Sensitization

Aspergillus fumigatus colonization in the patients with cystic fibrosis (CF) may cause sensitization against A. fumigatus and/or allergic bronchopulmonary aspergillosis (ABPA), which significantly worsens the course of underlying disease. At the present time, new diagnostic tests are searched for detection of fungal sensitization in these patients. The aim of this work was to evaluate an opportunity of application of basophile activation test with A. fumigatus allergen in vitro using flow cytometry, aiming for identification of fungal sensitization in the CF patients. The study included 190 patients with CF aged 1 to 37 years. All the patients underwent common allergy screening (skin tests with fungal allergens, determination of serum levels of total IgE and specific IgE for the fungal allergens), and mycological examination (microscopy and culture of respiratory substrates). Computed tomography of the chest was performed upon clinical indications. The basophil activation test with the A. fumigatus allergen was performed in 10 CF patients with ABPA, and 10 CF patients without ABPA, in addition to the standard allergological examination. Frequency of sensitization to A. fumigatus in the patients with cystic fibrosis was 27%, the incidence of allergic bronchopulmonary aspergillosis was 5.7%. The number of eosinophils, total IgE and specific IgE levels in CF patients with ABPA were significantly higher than in CF patients without ABPA. In blood of the ABPA patients we have identified 68.5 (52.5-81.5%) of basophilic leukocytes activated by A. fumigatus allergen, with a stimulation index of 17.07 (10.30-27.70). In appropriate comparison group, the stimulation index did not exceed 1.5 (p = 0.000). Direct positive correlation between the levels of specific IgE to A. fumigatus and the number of basophils activated by A. fumigatus allergens was revealed (r = 0.77; р < 0.05). FVC values and the body mass index in CF patients with ABPA were significantly lower when compared with the patients without fungal sensitization. Introduction of the basophil activation test, along with standard techniques, may enable a more differentiated assessment of ABPA development in CF patients. Timely detection of associations between A. fumigatus sensitization and clinical status of CF patients will facilitate early and effective administration of specific therapy.

24 Comparison of the tolerability of posaconazole versus voriconazole in children with cystic fibrosis

2018 ◽  
Vol 103 (2) ◽  
pp. e2.27-e2 ◽  
Author(s):  
Sian Bentley ◽  
Sukeshi Makhecha ◽  
Siobhan Carr ◽  
Ian Balfour-Lynn ◽  
Jane Davies
Keyword(s):  
Cystic Fibrosis ◽  
Adverse Effects ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Antifungal Prophylaxis ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
List Type ◽  
Retrospective Case ◽  
Clin Microbiol Infect ◽  
Hematopoietic Stem

BackgroundTriazole antifungals (itraconazole and voriconazole), are commonly used for treating isolates of Aspergillus, or in combination with corticosteroids for the empiric treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in children with cystic fibrosis (CF). Posaconazole is a newer triazole that is as effective, but better tolerated than voriconazole and itraconazole in immunocompromised patients1 though there is no published use in CF and it is not licensed in children<18 years old. It is used as a 3rd line agent for Aspergillus or ABPA in our institution.AimOur aim was to evaluate why posaconazole was needed in some children, and to assess its tolerability. Given the difficulty in reaching therapeutic drug levels of triazoles in children with CF2 we also reviewed posaconazole blood levels.MethodA retrospective case note review of all children with CF who had received voriconazole or posaconazole from April 2014 to May 2015 in a tertiary paediatric CF centre with a clinic population of 350 children. Children were identified from pharmacy records and clinical data was collected from case notes and computerised laboratory records. We compared reported adverse effects for both drugs, and for the posaconazole group documented reason for use and blood levels (therapeutic >0.7 mg/L).ResultsVoriconazole was used in 10 children with a median age of 13.5 years (range 12–16), for median 8 weeks. Adverse effects were experienced in 5/10 (50%) of children (photosensitivity – 4; hallucinations and nausea – 1), and 2 children had raised liver functions tests (LFTs). Posaconazole was used in 7 children with a median age of 14 years (range 13–16) for median 37 weeks. No adverse effects were reported but LFTs were raised in 1 child. Posaconazole was commenced in 6/7 (85%) children due to severe photosensitivity with voriconazole. Of these, posaconazole was indicated for concurrent Scedosporium isolates in 2 children, and therapeutic failure with itraconazole in 4 children. Posaconazole levels were consistently therapeutic in 5/7 (71%) children (range 0.7–2.47 mg/L). Levels in 1 child fell to <0.2 mg/L following the introduction of an interacting drug (rifampicin), and a level of 2.47 mg/L was associated with raised LFTs in another, resulting in discontinuation of posaconazole.ConclusionIn this small cohort, posaconazole was better tolerated than voriconazole for the treatment of Aspergillus or ABPA in children with CF, due mainly to the lack of photosensitivity associated with its use. Posaconazole levels attained from our patients indicate that therapeutic levels can be readily obtained in this patient population. Larger studies are needed to support these conclusions.ReferencesDoring M, Blume O, Haufe S, et al. Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in paediatric patients following allogeneic hematopoietic stem cell transplantation. Eur J Clin Microbiol Infect Dis2014;33(4):629–38.Bentley S, Gupta A, Balfour-Lynn IM. Subtherapeutic itraconazole and voriconazole levels in children with cystic fibrosis. J Cyst Fibros2013;12:418–9.

scholarly journals Clinical characteristics of people with cystic fibrosis and frequent fungal infection

2021 ◽  
Author(s):  
Thomas Poore ◽  
Maxene Meier ◽  
Elin Towler ◽  
John Brinton ◽  
Stacey Martiniano ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Fungal Infection ◽  
Clinical Characteristics ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Baseline Period ◽  
Lower Airway ◽  
Potential Contribution ◽  
Lung Function Decline

Background: Individuals with cystic fibrosis (CF) and fungal airway infection may present with fungal bronchitis, allergic bronchopulmonary aspergillosis (ABPA) or may appear unaffected despite fungal detection. We sought to characterize people with CF with frequent detection of fungi from airway samples and determine clinical outcomes. Methods: This retrospective study included individuals with CF with ≥ 4 lower airway cultures over a 2-year baseline period and ≥ 2 years of follow-up. We defined two groups: ≤ 1 positive fungus culture (rare) or ≥ 2 positive cultures during baseline (frequent). Clinical characteristics and outcomes were determined. Results: Between 2004-2016, 294 individuals met inclusion with 62% classified as rare and 38% as frequent fungi during baseline. Median follow-up was 6 years (range 2-9 years). Aspergillus fumigatus was the most common fungal species detected. Individuals with frequent fungi were older (13.7 vs. 11.7 yrs, p = 0.02) and more likely to have Stenotrophomonas maltophilia (35% vs 17%, p < 0.001) at baseline, but did not differ in lung function or ABPA diagnosis. During follow-up, those with frequent fungi were more likely to have chronic P. aeruginosa and S. maltophilia. Individuals with ABPA and frequent fungi had the highest rates of co-infection and co-morbidities, and a trend towards more rapid lung function decline. Discussion: Fungal infection in CF was associated with frequent P. aeruginosa and S. maltophilia co-infection even in those without ABPA. Individuals with frequent fungi and ABPA had worse outcomes, highlighting the potential contribution of fungi to CF pulmonary disease.

Unusual Clustering of Allergic Bronchopulmonary Aspergillosis in Children With Cystic Fibrosis

PEDIATRICS ◽  
1988 ◽  
Vol 82 (6) ◽  
pp. 835-839
Author(s):  
Sabine Maguire ◽  
Patricia Moriarty ◽  
Edward Tempany ◽  
Muiris FitzGerald
Keyword(s):  
Cystic Fibrosis ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Specific Ige ◽  
Skin Tests ◽  
Immediate Hypersensitivity ◽  
Positive Type ◽  
X Ray ◽  
Suppurative Lung Disease ◽  
Peripheral Blood Eosinophilia

Allergic bronchopulmonary aspergillosis has been recognized in association with cystic fibrosis in children since 1965. Since then, however, there have been a paucity of reports of pediatric cystic fibrosis complicated by allergic bronchopulmonary aspergillosis, and, in most cases, these have been diagnosed retrospectively. A cluster of five acute cases seen during a 4-month period in a single cystic fibrosis center with a systemic illness and deterioration in respiratory status are described. In all five patients, reversible bronchoconstriction and infiltrative changes on x-ray films suggested the diagnosis. This was confirmed by the presence of (1) peripheral blood eosinophilia, (2) elevated total IgE and Aspergillus fumigatus-specific IgE, and (3) circulating serum precipitins against A fumigatus in all cases. All children tested had positive type 1 immediate hypersensitivity to skin tests for A fumigatus, in sputum eosinophilia, and Aspergillus cultured from sputum. Only three of five children were previously noted to be atopic and none had severe advanced suppurative lung disease. All children had previously received bronchodilator therapy and appropriate antibiotics. Following treatment with corticosteroids, acute symptoms and radiologic changes resolved for 1 to 5 months. To date, no children have had recurrence of their allergic bronchopulmonary aspergillosis while receiving alternate-day steroid treatment for 6 months.

scholarly journals Recombinant Allergens Combined with Biological Markers in the Diagnosis of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis Patients

2010 ◽  
Vol 17 (9) ◽  
pp. 1330-1336 ◽  
Author(s):  
Hélène Fricker-Hidalgo ◽  
Bérangère Coltey ◽  
Catherine Llerena ◽  
Jean-Charles Renversez ◽  
Renée Grillot ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Retrospective Study ◽  
Biological Markers ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Specific Ige ◽  
Added Value ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Total Ige ◽  
Specific Igg

ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is a frequent complication in cystic fibrosis patients. The diagnosis remains difficult and requires a combination of clinical, radiological, biological, and mycological criteria. The aim of this study was to analyze the added value of two recombinant antigens, rAspf4 and rAspf6, associated with the detection of specific IgG; precipitins; total IgE; and Aspergillus fumigatus in sputum for the diagnosis of ABPA. In a retrospective study, we determined the specific IgE responses to these recombinants in 133 sera of 65 cystic fibrosis patients. We selected an average of five serum samples from each of the 17 patients with ABPA (13 proven and 4 probable ABPA) and from 3 patients with Aspergillus bronchitis and rhinosinusitis. One serum sample for the 45 patients without ABPA was tested. The sensitivity of specific IgE detection against rAspf4 calculated per patient (92.3%) was significantly higher (P < 0.05) than that of rAspf6 (53.8%). When rAspf4 IgE detection was associated with anti-Aspergillus IgG enzyme-linked immunosorbent assay (ELISA) and precipitin detection, the sensitivity rose to 100%. The specificities of rAspf4 and rAspf6 IgE detection were 93.7% and 91.6%, respectively. Other diagnostic criteria had slightly lower specificities (87.5% for anti-Aspergillus IgG ELISA, 89.6% for precipitins, 84.4% for total IgE, and 85.0% for positive A. fumigatus culture in sputum). In conclusion, this retrospective study showed the relevance of rAspf4 IgE detection, in combination with other biological markers (Aspergillus IgG ELISA, precipitins, and total IgE), for improving the biological diagnosis of ABPA.

Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis

2015 ◽  
Vol 47 (1) ◽  
pp. 177-185 ◽  
Author(s):  
Yael Gernez ◽  
Jeffrey Waters ◽  
Bojana Mirković ◽  
Gillian M. Lavelle ◽  
Colleen E. Dunn ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ex Vivo ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Basophil Activation Test ◽  
Surface Expression ◽  
Specific Ige ◽  
Basophil Activation ◽  
Cross Sectional ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

The diagnosis of cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) is clinically challenging, due to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between CF patients with and without ABPA.We conducted a prospective longitudinal study (Stanford cohort) comparing basophil activation test CD203c levels by flow cytometry before and after activation withAspergillus fumigatusallergen extract or recombinantAspf1 in 20 CF patients with ABPA (CF-ABPA) and in two comparison groups: CF patients withA. fumigatuscolonisation (AC) but without ABPA (CF-AC; n=13) and CF patients without either AC or ABPA (CF; n=12). Patients were tested every 6 months and when ill with pulmonary exacerbation. We also conducted cross-sectional validation in a separate patient set (Dublin cohort).Basophil CD203c surface expression reliably discriminated CF-ABPA from CF-AC and CF over time. Ex vivostimulation withA. fumigatusextract or recombinantAspf1 produced similar results within the Stanford (p<0.0001) and the Dublin cohorts. CF-ABPA patients were likelier to have elevated specific IgE toA. fumigatusand were less frequently co-infected withStaphylococcus aureus.Basophil CD203c upregulation is a suitable diagnostic and stable monitoring biomarker of ABPA in CF.

scholarly journals Features of fungal sensitization in patients with asthma and cystic fibrosis: the results of a prospective study

2018 ◽  
Vol 15 (2) ◽  
pp. 11-16
Author(s):  
Y I Kozlova ◽  
E V Frolova ◽  
Y V Borzova ◽  
A V Sobolev ◽  
E V Burygina ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Specific Ige ◽  
Test System ◽  
Candida Spp ◽  
Ige Antibodies ◽  
Fungal Allergens ◽  
Patients At Risk ◽  
Fungal Sensitization

Background. To estimate the frequency of fungal sensitization and allergic bronchopulmonary aspergillosis in patients with asthma or cystic fibrosis. Methods. The study included 205 patients with asthma and 190 patients with cystic fibrosis. For detection of fungal sensitization specific IgE antibodies in the blood serum with «AllergoELISA-specific IgE» test system and biotinylated fungal allergens were determined. Mycological examination included microscopy and cultural study of respiratory biomaterials. According to the indications, a CAT scan of the chest was performed. Results. The incidence of fungal sensitization in patients with asthma was 35,6%, CI [29,1%; 42,6%], in patients with cystic fibrosis - 56,8% [49,5%; 64%]. In patients with severe asthma the main fungal allergens were Alternaria spp. (70%) and Aspergillus spp. (60%); in patients with cystic fibrosis: Candida spp. - 73%, Alternaria spp. - 34%, Aspergillus spp. - 27%. The incidence of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma was 5,3%, in patients with cystic fibrosis - 5,7%. Conclusion Early detection of ABPA in patients with asthma and cystic fibrosis is very important as it changes the therapeutic measures of patients’ management and prevents progression of bronchiectasis and respiratory failure. Determination of specific Aspergillus spp. IgE antibodies in vitro is a necessary stage of diagnosis of ABPA in patients at risk.

scholarly journals New Commercially Available IgG Kits and Time-Resolved Fluorometric IgE Assay for Diagnosis of Allergic Bronchopulmonary Aspergillosis in Patients with Cystic Fibrosis

2015 ◽  
Vol 23 (3) ◽  
pp. 196-203 ◽  
Author(s):  
Coralie Barrera ◽  
Bénédicte Richaud-Thiriez ◽  
Steffi Rocchi ◽  
Bénédicte Rognon ◽  
Sandrine Roussel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Aspergillus Fumigatus ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Specific Ige ◽  
Enzyme Linked Immunosorbent Assay ◽  
Time Resolved ◽  
Content Type ◽  
Elisa Kit ◽  
Fungal Allergens ◽  
Specific Igg

ABSTRACTAllergic bronchopulmonary aspergillosis (ABPA) is difficult to diagnose; diagnosis relies on clinical, radiological, pathological, and serological criteria. Our aim was to assess the performance of two new commercially available kits and a new in-house assay: anAspergillus fumigatusenzyme-linked immunosorbent assay (ELISA) IgG kit (Bordier Affinity Products), anAspergillusWestern blotting IgG kit (LDBio Diagnostics), and a new in-house time-resolved fluorometric IgE assay (dissociation-enhanced lanthanide fluorescent immunoassay, or DELFIA) using recombinant proteins from anAspergillussp. recently developed by our laboratory for ABPA diagnosis in a retrospective study that included 26 cystic fibrosis patients.Aspergillus fumigatus-specific IgG levels measured by a commercial ELISA kit were in accordance with the level of precipitins currently used in our lab. The ELISA kit could accelerate and help standardize ABPA diagnosis.Aspergillus fumigatus-specific IgE levels measured by ImmunoCAP (Phadia) withA. fumigatusM3 antigen and by DELFIA with a purified protein extract ofA. fumigatuswere significantly correlated (P< 10−6). The results with recombinant antigens glucose-6-phosphate isomerase and mannitol-1-phosphate dehydrogenase were encouraging but must be confirmed with sera from more patients. The DELFIA is an effective tool that can detect specific IgE against more fungal allergens than can be detected with other commercially available tests.

scholarly journals Neurologic Adverse Events Associated with Voriconazole Therapy: Report of Two Pediatric Cases

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Sevliya Öcal Demir ◽  
Serkan Atici ◽  
Gülşen Akkoç ◽  
Nurhayat Yakut ◽  
Nilay Baş İkizoğlu ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Side Effects ◽  
Adverse Events ◽  
Pediatric Patients ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Therapeutic Drug ◽  
Color Sensation ◽  
First Case ◽  
Current Report ◽  
Visual Disturbances

Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients.

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