Itraconazole and allergic bronchopulmonary aspergillosis in twin brothers with cystic fibrosis

Mannes, G. P. M.; Heide, S. van der; Aalderen, W. M. C. van; Gerritsen, Jorrit

doi:10.1016/0140-6736(93)90244-b

Cited by 36 publications

(23 citation statements)

References 3 publications

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“…Extended courses of oral corticosteroids are considered first-line treatment for ABPA in asthma, and this is also the case in patients with CF [61][62][63][64][65]. As in asthma, itraconazole add-on therapy has been reported to be clinically beneficial in several uncontrolled studies of ABPA in CF patients [38,[44][45][46][47]. In these studies, reductions in oral steroid dose and stabilisation of lung function have been found.…”

Section: Antifungal Therapy In Abpa and Safsmentioning

confidence: 88%

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

Moss

2013

Eur Respir J

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Severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis encompass two closely related subgroups of patients with severe allergic asthma. Pulmonary disease is due to pronounced host inflammatory responses to noninvasive subclinical endobronchial infection with filamentous fungi, usually Aspergillus fumigatus. These patients usually do not achieve satisfactory disease control with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-acting bronchodilators. Although prolonged systemic corticosteroids are effective, they carry a substantial toxicity profile. Supplementary or alternative therapies have primarily focused on use of antifungal agents including oral triazoles and inhaled amphotericin B. Immunomodulation with omalizumab, a humanised anti-IgE monoclonal antibody, or "pulse" monthly high-dose intravenous corticosteroid, has also been employed. This article considers the experience with these approaches, with emphasis on recent clinical trials. @ERSpublications Treatment of fungal asthma includes glucocorticoids, azoles, amphotericin and anti-IgE. Trial validation is needed.

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Section: Antifungal Therapy In Abpa and Safsmentioning

confidence: 88%

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

Moss

2013

Eur Respir J

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“…Although there is a correlation between the degree of exposure to Aspergillus spores and the development of ABPA, many findings suggest that ABPA is primarily the result of abnormal host immune response to Aspergillus antigens. Given that high incidence rates of ABPA have been reported in a number of families, such an abnormal host response is probably influenced by genetic factors [97,98]. While factors that allow growth of Aspergillus in the airways of ABPA patients remain unclear, bronchial mucus abnormalities have been implicated.…”

Section: Introductionmentioning

confidence: 99%

Fungal allergy in asthma–state of the art and research needs

Denning

Pashley

Hartl

et al. 2014

Clinical & Translational All

306

262

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Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that >6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies.

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“…It is a potential respiratory complication of cystic fibrosis (CF) (1, 7). Recent reports describe successful itraconazole treatment of ABPA in CF patients (4,8,10). This azole derivative is effective against A. fumigatus, including strains isolated from sputum of CF patients (5).…”

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confidence: 99%

Sputum Itraconazole Concentrations in Cystic Fibrosis Patients

Sermet‐Gaudelus

Lesne-Hulin

Lenoir

et al. 2001

Antimicrob Agents Chemother

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Itraconazole diffusion in sputum was studied in 11 cystic fibrosis patients with allergic bronchopulmonary aspergillosis. There was a high interindividual variability in sputum itraconazole concentration and sputum/ serum drug concentration ratio. Three children had sputum drug concentrations before oral administration that were lower than the itraconazole MIC at which 90% of Aspergillus fumigatus strains were inhibited, although their serum drug concentrations were within the therapeutic range.Allergic bronchopulmonary aspergillosis (ABPA) is a disease characterized by lung hypersensitivity due to endobronchial colonization with Aspergillus fumigatus. It is a potential respiratory complication of cystic fibrosis (CF) (1, 7). Recent reports describe successful itraconazole treatment of ABPA in CF patients (4,8,10). This azole derivative is effective against A. fumigatus, including strains isolated from sputum of CF patients (5). It might thus minimize the chronic antigenic stimulation provided by the fungal airway colonization. However, its use remains controversial due to the lack of prospective clinical studies regarding its pharmacokinetics and its sputum diffusion, two characteristics that are often considerably modified in CF. We therefore undertook an evaluation of serum and sputum itraconazole concentrations in CF patients to ascertain whether itraconazole penetration into bronchial secretions was effective.Eleven CF patients with ABPA, 5 to 15 years of age, were enrolled in the study during the usual monitoring of itraconazole treatment. All the patients fulfilled the diagnostic criteria for ABPA as proposed by Ricketti et al. (12). All the patients received itraconazole at 10 mg/kg of body weight once a day in capsules, with or immediately following breakfast and in association with inhaled corticosteroids. None of the patients received drugs which could interfere with the hepatic metabolism of itraconazole or affect the drug bioavailability, such as antacids or H 2 blockers. Assays were performed at the presumed steady state of itraconazole at least 15 days after the beginning of treatment, according to the method described by Woestenborghs et al. (14). Blood and sputum samples were taken simultaneously, before (T0) and 4 h after (T4) oral administration. Salivary samples with less than 20 polymorphonuclear cells per ml were discarded. Sputum was then mixed with liquid nitrogen. A total of 106 specimens (54 in serum, 52 in sputum) were analyzed. More than one sample was obtained from three patients, at a three-month interval. Serum and sputum samples were assayed by high-performance liquid chromatography for itraconazole and its main metabolite, hydroxyitraconazole (OH-itraconazole) (14). All samples were studied twice. Controls were regularly performed.Serum drug concentrations were compared with the manufacturer's recommendations for invasive aspergillosis treatment, i.e., at T0, 250 ng/ml for itraconazole and 1,000 ng/ml for total itraconazole-OH-itraconazole, which represents the active antifungal ...

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Itraconazole and allergic bronchopulmonary aspergillosis in twin brothers with cystic fibrosis

Cited by 36 publications

References 3 publications

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

Fungal allergy in asthma–state of the art and research needs

Sputum Itraconazole Concentrations in Cystic Fibrosis Patients

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