American journal of respiratory and critical care medicine
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FEV1, measured using spirometry, provides a straightforward, widely available, and inexpensive global measurement of airflow limitation and lung function. For decades, FEV1 has remained the main intermediate endpoint used in research studies and for the development of new chronic obstructive pulmonary disease (COPD) therapies. Not surprisingly, treatments that acutely improve FEV1 dominate as COPD therapies. ⋯ In individual patients and in COPD cohort studies, thoracic imaging using X-ray computed tomography, and magnetic resonance imaging (conventional (1)H as well as hyperpolarized noble gases such as (129)Xe, (3)He, and inhaled O2 and (19)F) can be used to directly visualize the structural and functional consequences of COPD and thus provide a clearer picture of COPD mechanisms, disease progression, and response to therapy. We briefly describe pulmonary imaging methods that provide a way to visualize and quantify, with high spatial and temporal resolution, regional ventilation abnormalities, gas trapping, emphysema, and airway remodeling in COPD. Finally, we discuss the implications of recent imaging findings and their impact on future biomarker and therapy research aimed at improving COPD outcomes.
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Am. J. Respir. Crit. Care Med. · Jul 2014
Randomized Controlled TrialThe Effect of Inhaled Interferon-beta on Worsening of Asthma Symptoms Caused by Viral Infections: a Randomised Trial.
Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores antiviral activity. ⋯ Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-β is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the need for further, adequately powered, trials in this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).
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Am. J. Respir. Crit. Care Med. · Jul 2014
Wnt Co-receptor Lrp5 is a Driver of Idiopathic Pulmonary Fibrosis.
Wnt/β-catenin signaling has been implicated in lung fibrosis, but how this occurs and whether expression changes in Wnt pathway components predict disease progression is unknown. ⋯ We show that the Wnt coreceptor, Lrp5, is a genetic driver of lung fibrosis in mice and a marker of disease progression and severity in humans with IPF. Evidence that TGF-β signaling can override a loss in Lrp5 has implications for patient selection and timing of Wnt pathway inhibitors in lung fibrosis.