Pneumocystis colonization in asthmatic patients not receiving oral corticosteroid therapy.

Pneumocystis jirovecii can colonize patients with chronic obstructive pulmonary disease. To determine if colonization occurs in asthma patients, sputum samples from 10 patients with mild asthma, who were not receiving oral corticosteroids, were evaluated by a sensitive real-time PCR assay that targets a multicopy gene of P. jirovecii. 2 patients (20%) had Pneumocystis DNA detected; 1 patient had 3 positive samples over an 11-day period. Thus, Pneumocystis colonization occurs in asthma patients, and further studies are warranted to evaluate its role in airways disease. TRIAL REGISTRATION NUMBER: NCT01113034.

A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma.

BACKGROUND: Influenza virus (IFV) infection is associated with increased morbidity and mortality in people with underlying lung disease. Treatment options for IFV are currently limited and antiviral resistance is a growing concern. DAS181, an inhaled antiviral with a unique mechanism of action, has shown promise in early clinical trials involving generally healthy human subjects. This study was undertaken to assess the safety and tolerability of DAS181 in individuals with underlying reactive airway disease. METHODS: This was a randomized, double-blind, placebo-controlled, crossover phase 1 study of DAS181-F02. Dry particle inhaler administration of 10 mg was done on 3 consecutive days in ten adult volunteers with well-controlled asthma. The primary outcome was the frequency of adverse events (AEs), grade 1 or higher that occurred during each study period. RESULTS: There were 280 AEs among ten evaluable subjects (56.8 % active; 43.2 % placebo); 90.7 % were grade 1. No grade 3 or higher AEs occurred. A statistically significant association between exposure to DAS181 and experiencing any AE, a grade 1 AE, or a grade 2 AE was not detected. Overall, the majority of AEs were classified as possibly related (35.7 %), unlikely related (38.9 %), or unrelated (15.4 %) to study drug administration. However, there was a statistically significant association between exposure to DAS181 and experiencing a definitely or probably related AE. Respiratory effects, including dyspnea, dry cough, and chest discomfort related to respirations, accounted for all of the definitely related AEs and one of the most common probably related AEs. CONCLUSIONS: DAS181 was safe in this small study of otherwise healthy subjects with well-controlled asthma. However, the generalizability of these results is limited by the small sample size and generally mild nature of the subjects' asthma at baseline. The increased association of respiratory events classified as probably or definitely related to DAS181 administration suggests caution may need to be employed when administering DAS181 to individuals with less stable reactive airway disease. Further investigation in a controlled setting of the safety and efficacy of DAS181 in a larger population of asthmatic subjects with varying disease activity is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01113034 Trial Registration Date: April 27, 2010.

The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts.

INTRODUCTION: Medical advances have led to an increase in the world's population of immunosuppressed individuals. The most severely immunocompromised patients are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who have other conditions that require immunosuppressive therapies and/or solid organ or stem cell transplants. MATERIALS AND METHODS: Medically attended patients with a positive clinical diagnosis of influenza were recruited prospectively and clinically evaluated. Nasal washes and serum were collected. Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection. RESULTS: Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment. CONCLUSIONS: Immunocompromised patients are at risk for more severe or complicated influenza induced disease, which may be difficult to prevent with existing vaccines and antiviral treatments. Specific issues to consider when managing a severely immunocompromised host include the development of asymptomatic shedding, multi-drug resistance during prolonged antiviral therapy, and the potential high risk of pulmonary involvement. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00533182.