American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2015
Clinical TrialImpaired Antibody-mediated Protection and Defective IgA B Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus.
Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. ⋯ This observed specific defect in IgA memory may partly explain the ability of RSV to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone.
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Am. J. Respir. Crit. Care Med. · May 2015
Comparative StudyTargeting PI3K-p110α Suppresses Influenza Viral Infection in Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) and influenza virus infections are major global health issues. Patients with COPD are more susceptible to infection, which exacerbates their condition and increases morbidity and mortality. The mechanisms of increased susceptibility remain poorly understood, and current preventions and treatments have substantial limitations. ⋯ The increased susceptibility of individuals with COPD to influenza likely results from impaired antiviral responses, which are mediated by increased PI3K-p110α activity. This pathway may be targeted therapeutically in COPD, or in healthy individuals, during seasonal or pandemic outbreaks to prevent and/or treat influenza.
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Am. J. Respir. Crit. Care Med. · May 2015
Randomized Controlled Trial Clinical TrialCXCR2 Antagonist MK-7123-A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease.
An antagonist (MK-7123) of the cytokine receptor CXCR2 reduces neutrophil chemotaxis and thus may alleviate airway inflammation in chronic obstructive pulmonary disease (COPD). ⋯ Treatment with MK-7123 50 mg versus placebo led to significant improvement in FEV1 in patients with COPD, suggesting clinically important antiinflammatory effects with CXCR2 antagonism, although dose-related discontinuations were observed because of ANC decreases with MK-7123. Greater response was observed in smokers versus ex-smokers. Clinical trial registered with www.clinicaltrials.gov (NCT 01006616).