Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole.

Itraconazole is a new orally active antifungal triazole with impressive activity against Aspergillus spp. Six patients with allergic bronchopulmonary aspergillosis (ABPA), aged 14 to 49 years, were treated with oral itraconazole (200 mg twice daily) for a mean of 3.9 months (range, one to six months; three patients continue on therapy). Two patients received two courses. Three patients had underlying cystic fibrosis, and three had severe asthma; four of the six required continuous high-dose systemic prednisone (mean, 43 mg/day; confidence interval [CI], 23 to 63 mg/day) at the start of therapy. In those treated for two months or longer, the mean total serum IgE level fell from 2,462 U/ml (CI, 752 to 4,202 U/ml) to 502 U/ml (CI, 123 to 880 U/ml) during each course, and the mean daily steroid dosage was decreased to a mean of 24 mg/day (CI, 11 to 37 mg/day). All patients experienced improvement in pulmonary function during the trial, with mean FEV, increasing from 1.43 to 1.77L/sec and mean FVC from 2.3 to 2.9 L in those treated for two months or longer. The mean steady-state serum concentration of itraconazole was 5.1 micrograms/ml (range, 1.8 micrograms/ml to 7.3 micrograms/ml); the patient with the lowest concentrations had the least significant clinical response. Cultures of sputum from two of three patients became negative for A fumigatus during therapy. No adverse clinical effects occurred except loss of libido in one patient. We conclude that oral itraconazole may be an effective adjunctive therapy in ABPA, possibly by clearing the airway of Aspergillus, and that randomized trials of this agent are warranted to better define its usefulness in this disorder.

Pseudomonas hyperimmune globulin passive immunotherapy for pulmonary exacerbations in cystic fibrosis.

We studied the effect of an intravenously administered gamma globulin [Ps-ivIG] enriched fivefold over conventional ivIG for Pseudomonas aeruginosa lipopolysaccharide [PA LPS] antibodies on ten patients with cystic fibrosis [CF] aged 19-32 years during hospitalization for pulmonary deterioration. All were colonized with greater than or equal to 1 PA phenotype resistant to all antibiotics at the time of admission and they received 500 mg/kg Ps-ivIG intravenously as a single dose in addition to conventional treatment, including antibiotics and chest physiotherapy. No adverse effects occurred. Circulating immune complexes and complement levels remained unchanged from baseline. Serum levels of anti-PA LPS IgG, as measured by ELISA for eight PA LPS immunotypes, increased to 244 +/- 65% (mean +/- SE) of baseline levels 1 hour post-infusion (P less than 0.01), remained significantly elevated during a mean hospital stay of 17 days, and returned to near baseline by follow-up 4 weeks after hospital discharge. Plasma half-life and clearance values were similar to those of other subjects receiving conventional ivIG. Sputum PA density declined from 3.0 to 1.2 x 10(8) cfu/mL 1 week post-infusion (P approximately equal to 0.05), and returned to baseline at follow-up. Serum anti-PA opsonic activity increased after infusion (P less than 0.01), but returned to baseline by 72 hours. Clinical scores improved from admission to discharge (P less than 0.005) without decline at follow-up. Forced vital capacity [FVC] and forced expiratory volume in one second [FEV1] increased from admission to discharge (P less than 0.01 and P less than 0.05, respectively) without decline at follow-up. Using autologous historical control data, standard hospital therapy without Ps-ivIG resulted in no improvement in FVC or FEV1, and a subsequent decline in these parameters (P less than 0.05 for each) during a similar follow-up period. This occurred despite the fact that half the patients did not have antibiotic-resistant PA on the control admission. We conclude that Ps-ivIG is a safe adjunctive therapy for pulmonary exacerbations in moderately ill cystic fibrosis patients colonized with resistant PA, and may be associated with both greater and more prolonged improvement in pulmonary function than standard therapy alone.