pulmicort and Aspergillosis--Allergic-Bronchopulmonary

Nebulized amphotericin B (NAB) has been used in the management of acute stage and exacerbations of allergic bronchopulmonary aspergillosis (ABPA). Whether NAB can prevent exacerbations of ABPA is not known. Herein, we evaluate the efficacy and safety of NAB in subjects with ABPA complicating asthma.. Consecutive subjects of ABPA with recurrent exacerbations were randomized to receive either NAB plus nebulized budesonide (NEB) or NEB alone. The primary outcome was the time-to-first exacerbation of ABPA. The secondary outcomes were the number of subjects with ABPA exacerbations, ACQ7 scores, lung function, IgE levels, and adverse effects of treatment.. Twenty-one subjects (14 men; mean age, 32.3 years) were randomized to either the NAB (n = 12) or the NEB (n = 9) arm. The baseline characteristics were similar in the two groups. The time-to-first exacerbation was similar in the two groups. At one year, the numbers of patients experiencing exacerbation was significantly lower in the NAB arm (1/12 [8.3%] vs. 6/9 [66.7%]; p = 0.016). The other secondary end points were not different between the two groups. There were no major adverse events leading to discontinuation of any of the study drugs. Three patients experienced bronchospasm after first dose of NAB; however, the subsequent doses were well tolerated.. NAB seems to be beneficial in decreasing the frequency of exacerbations in patients with ABPA complicating asthma. Larger trials are required to confirm our study results.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Nebulizers and Vaporizers; Pilot Projects; Vital Capacity

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to

Topics: Adrenal Cortex Hormones; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Budesonide; Cushing Syndrome; Dyspnea; Female; Humans; Iatrogenic Disease; Itraconazole

Topics: Administration, Inhalation; Adolescent; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Child; Cystic Fibrosis; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Respiratory Therapy

A 4-year-old boy with cystic fibrosis developed hypertension, rapid weight gain and a moon face 2 weeks after starting a combined treatment of oral itraconazole and inhaled budesonide for a suspected allergic bronchopulmonary aspergillosis. Adrenal suppression was documented and found to persist 3 months after stopping this combined treatment.. To the best of our knowledge, this is the first time that an iatrogenic Cushing syndrome in a young child with cystic fibrosis after such combined treatment is reported. The inhibition of cytochrome P4503A by intraconazole and a higher glucocorticoid tissue sensitivity is suggested as the underlying mechanism.

Topics: Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Child, Preschool; Comorbidity; Cushing Syndrome; Cystic Fibrosis; Drug Therapy, Combination; Humans; Itraconazole; Male; Time Factors

Topics: Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Bronchodilator Agents; Budesonide; Child; Cystic Fibrosis; Drug Therapy, Combination; Female; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Itraconazole; Male; Pituitary-Adrenal System

Two CF patients developed Cushing's syndrome during administration of inhaled budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug co-administration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchodilator Agents; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Fatal Outcome; Female; Humans; Iatrogenic Disease; Infant, Newborn; Itraconazole; Lung Diseases; Male; Mycobacterium Infections, Nontuberculous

Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo.. This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge.

Topics: Adult; Anti-Inflammatory Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Follow-Up Studies; Humans; Itraconazole; Risk Assessment

Two patients with allergic bronchopulmonary aspergillosis (ABPA) have been treated with a high dose (1600 micrograms daily) of inhaled corticosteroid for 18 months. A beneficial effect with regard to asthmatic symptoms was observed in both patients. During the first 14 months of the observation period no significant changes were observed in lung function parameters. Bronchial histamine challenge showed decreased hyperreactivity. IgE decreased in both patients, while specific IgE and IgG remained the same. After 14 months of treatment one of the patients developed severe, acute exacerbation of the ABPA and was treated with high-dose prednisolone and local steroid. The patient is now fully recovered and has continued on local steroid therapy. The other patient had no episodes of exacerbation and remains stable on this treatment.

Topics: Administration, Topical; Aged; Anti-Inflammatory Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Budesonide; Female; Glucocorticoids; Humans; Immunoglobulin E; Male; Middle Aged; Nebulizers and Vaporizers; Pilot Projects; Pregnenediones; Spirometry