American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2018
Randomized Controlled TrialAmikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT): A Prospective, Open-Label, Randomized Study.
Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. ⋯ Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).
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Am. J. Respir. Crit. Care Med. · Dec 2018
Association of Height Growth in Puberty with Lung Function: A Longitudinal Study.
Rationale: Puberty may influence lung function, but the precise role of pubertal height growth in lung development is unclear. Objectives: To examine associations of timing of puberty and peak velocity of pubertal height growth with lung function in adolescence and early adulthood. Methods: Longitudinal analyses of repeat height measurements from age 5 to 20 years for a British birth cohort with 4,772 males and 4,849 females were conducted to characterize height growth trajectories and to derive pubertal age and peak height velocity using the validated SITAR (SuperImposition by Translation and Rotation) model. ⋯ A 1-cm/yr increase in peak velocity was associated with 145-ml (95% CI, 56-234 ml) and 50-ml (95% CI, 2-99 ml) increases in FVC for males and females, respectively. No associations were found with FEV1/FVC. Conclusions: Later onset and greater peak velocity of height growth in puberty are associated with increased FEV1 and FVC in young adults but there was no evidence of dysanapsis of pubertal lung growth.
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Am. J. Respir. Crit. Care Med. · Dec 2018
Increased Extracellular Vesicles Mediate WNT-5A Signaling in Idiopathic Pulmonary Fibrosis.
Rationale: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by lung epithelial cell injury, increased (myo)fibroblast activation, and extracellular matrix deposition. Extracellular vesicles (EVs) regulate intercellular communication by carrying a variety of signaling mediators, including WNT (wingless/integrated) proteins. The relevance of EVs in pulmonary fibrosis and their potential contribution to disease pathogenesis, however, remain unexplored. ⋯ Similarly, EVs from IPF BALF induced phLF proliferation, which was mediated by WNT5A. Conclusions: Increased EVs function as carriers for signaling mediators, such as WNT5A, in IPF and thus contribute to disease pathogenesis. Characterization of EV secretion and composition may lead to novel approaches to diagnose and develop treatments for pulmonary fibrosis.