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

Skov, Marianne; Pressler, Tacjana; Jensen, H. E.; Høiby, Niels; Koch, Christian

doi:10.1136/thx.54.1.44

Cited by 51 publications

(28 citation statements)

References 20 publications

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“…Anti-Aspergillus IgG levels are directly related to carriage of the microbe, while anti-Aspergillus IgA levels are inversely related to carriage (270). A positive correlation between fungal carriage and antifungal IgG antibodies is supported by a more recent study (299). These data seem to support a prominent role of IgA in protection in normal individuals, and they indicate that in CF patients, some host defense factor is compromised that dysregulates the humoral response, causing the production of unprotective antibodies.…”

Section: Emerging Pathogens Affecting Cystic Fibrosis Patientsmentioning

confidence: 76%

Lung Infections Associated with Cystic Fibrosis

2002

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While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host

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Section: Emerging Pathogens Affecting Cystic Fibrosis Patientsmentioning

confidence: 76%

Lung Infections Associated with Cystic Fibrosis

2002

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“…81 Although previous works detected no association between ABPA and P. aeruginosa colonisation. 82 Nikolaizik et al reported a positive correlation between the two entities, suggesting that P. aeruginosa colonisation favours the process of A. fumigatus sensitisation. 83 The causal relationship between Aspergillus sensitisation and Pseudomonas colonisation has motivated great discussion over the years as it is difficult to disentangle the influences of the Pseudomonas from that of Aspergillus.…”

Section: Abpamentioning

confidence: 99%

Cystic fibrosis, atopy, asthma and ABPA

Antunes

Fernandes

Borrego

et al. 2010

Allergologia et Immunopathologia

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The role of atopy on cystic fibrosis (CF) progression remains unclear but evidence suggests that it may influence the appearance of co-morbid conditions such as CF asthma or allergic bronchopulmonary aspergillosis (ABPA). Recognising asthma in patients with CF is not always easy but the identification of atopic markers favours the diagnosis. Physicians should be aware of this fact in order to achieve a better control of respiratory symptoms in patients with CF. Bronchial mucosa inflammation and abnormal mucus predispose to mould colonisation. These patients are at higher risk of allergic sensitisation, especially when atopic susceptibility is present. In the particular case of A. fumigatus, allergic sensitisation precedes ABPA development, which occurs in up to 10% of CF patients. Progression of lung function deterioration is most strikingly pronounced in patients with ABPA. Therefore, sensitisation with A. fumigatus should be regularly tested in patients with CF, especially those at higher risk. Recombinant allergens constitute an important advance in differentiating Aspergillus sensitisation from ABPA itself.

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“…After withdrawal of itraconazole treatment, all the patients were closely controlled with specific IgG subclass antibodies to A. fumigatus [24] in order to follow the activity of ABPA. In patients with increasing specific IgG subclass antibodies and clinical signs of exacerbation in ABPA, itraconazole treatment was restarted after withdrawal of budesonide.…”

Section: Follow-upmentioning

confidence: 99%

Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

Skov¹,

Main²,

Sillesen³

et al. 2002

Eur Respir J

132

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A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide.An adrenocorticotrophic hormone (ACTH) test (250 µg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls.Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2–10 months after itraconazole treatment had been discontinued.Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.

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

Cited by 51 publications

References 20 publications

Lung Infections Associated with Cystic Fibrosis

Lung Infections Associated with Cystic Fibrosis

Cystic fibrosis, atopy, asthma and ABPA

Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

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