American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2019
Randomized Controlled TrialLocal and Systemic Immunity Against RSV Induced by a Novel Intranasal Vaccine: A Randomised, Double- Blind, Placebo-Controlled Trial.
Rationale: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required. Objectives: Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP). ⋯ Palivizumab-like antibodies were consistently induced, but F protein site ∅-specific antibodies were not detected, and virus-specific nasal IgA responses were heterogeneous, with the strongest responses in individuals with lower pre-existing antibody levels. Conclusions: SynGEM is thus the first nonreplicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers. Clinical trials registered with www.clinicaltrials.gov (NCT02958540).
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Am. J. Respir. Crit. Care Med. · Aug 2019
Randomized Controlled TrialTelomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis.
Rationale: Immunosuppression was associated with adverse events for patients with idiopathic pulmonary fibrosis (IPF) in the PANTHER-IPF (Evaluating the Effectiveness of Prednisone, Azathioprine and N-Acetylcysteine in Patients with IPF) clinical trial. The reason why some patients with IPF experience harm is unknown. Objectives: To determine whether age-adjusted leukocyte telomere length (LTL) was associated with the harmful effect of immunosuppression in patients with IPF. ⋯ A propensity-matched University of Texas Southwestern Medical Center IPF cohort showed a similar association between immunosuppression and composite endpoints (death, lung transplantation, or FVC decline) for those with an LTL less than the 10th percentile (hazard ratio, 3.79; 95% confidence interval, 1.73-8.30; P = 0.00085). An interaction was found between immunosuppression and LTL for the combined PANTHER-IPF and ACE-IPF clinical trials (Pinteraction = 0.048), and the University of Texas Southwestern Medical Center IPF cohort (Pinteraction = 0.00049). Conclusions: LTL is a biomarker that may identify patients with IPF at risk for poor outcomes when exposed to immunosuppression.
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Am. J. Respir. Crit. Care Med. · Aug 2019
Randomized Controlled TrialLong-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma.
Rationale: The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy. Objectives: To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes. ⋯ Conclusions: In patients with persistent uncontrolled asthma, azithromycin reduced airway H. influenzae load compared with placebo but did not change total bacterial load. Macrolide resistance increased, reflecting previous studies. These results highlight the need for studies assessing the efficacy of nonantibiotic macrolides as a long-term therapy for patients with persistent uncontrolled asthma.