American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2014
ReviewMinimal Clinically Important Differences in Pharmacological Trials.
The concept of a minimal clinically important difference (MCID) is well established. Here, we review the evidence base and methods used to define MCIDs as well as their strengths and limitations. Most MCIDs in chronic obstructive pulmonary disease (COPD) are empirically derived estimates applying to populations of patients. ⋯ In a clinical trial setting, many factors, including study duration, withdrawal rate, baseline severity, and Hawthorne effects, can influence the measured treatment effect and determine whether it reaches the MCID. We also address recent challenges presented by clinical trials that compare active treatments and suggest that MCIDs should be used to identify the additional proportion of patients who benefit, for example, when one drug is replaced by another or when a second drug is added to a first. We propose the term "minimum worthwhile incremental advantage" to describe this parameter.
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Am. J. Respir. Crit. Care Med. · Feb 2014
Foxa3 Induces Goblet Cell Metaplasia and Inhibits Innate Antiviral Immunity.
Goblet cell metaplasia accompanies common pulmonary disorders that are prone to recurrent viral infections. Mechanisms regulating both goblet cell metaplasia and susceptibility to viral infection associated with chronic lung diseases are incompletely understood. ⋯ FOXA3 induces goblet cell metaplasia in response to infection or Th2 stimulation. Suppression of IFN signaling by FOXA3 provides a plausible mechanism that may serve to limit ongoing Th1 inflammation during the resolution of acute viral infection; however, inhibition of innate immunity by FOXA3 may contribute to susceptibility to viral infections associated with chronic lung disorders accompanied by chronic goblet cell metaplasia.
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Am. J. Respir. Crit. Care Med. · Feb 2014
The Site and Nature of Airway Obstruction after Lung Transplantation.
The chronic rejection of lung allografts is attributable to progressive small airway obstruction. ⋯ Chronic lung allograft rejection is associated with a progressive form of constrictive bronchiolitis that targets conducting airways while sparing larger airways as well as terminal bronchioles and the alveolar surface.
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Am. J. Respir. Crit. Care Med. · Feb 2014
Comparative StudymiR-199a-5p Silencing Regulates the Unfolded Protein Response in COPD and α1 Antitrypsin Deficiency.
Retention of abnormal α1-antitrypsin (AAT) activates the unfolded protein response in AAT-deficient monocytes. The regulatory role of microRNAs (miRNAs) in unfolded protein responses and chronic obstructive pulmonary disease pathogenesis has not been investigated. ⋯ miR-199a-5p is a key regulator of the unfolded protein response in AAT-deficient monocytes, and epigenetic silencing of its expression regulates this process in chronic obstructive pulmonary disease.
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Am. J. Respir. Crit. Care Med. · Feb 2014
Sleep Disordered Breathing in Hispanic/Latino Individuals of Diverse Backgrounds: The Hispanic Community Health Study/Study of Latinos.
Hispanic/Latino populations have a high prevalence of cardiovascular risk factors and may be at risk for sleep-disordered breathing (SDB). An understanding of SDB among these populations is needed given evidence that SDB increases cardiovascular risk. ⋯ SDB is prevalent in U.S. Latinos but rarely associated with a clinical diagnosis. Associations with diabetes and hypertension suggest a large burden of disease may be attributed to untreated SDB, supporting the development and evaluation of culturally relevant detection and treatment approaches.