American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2014
ReviewNew Therapeutic Targets in Idiopathic Pulmonary Fibrosis: Aiming to Rein in Runaway Wound Healing Responses.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease, with a median survival as short as 3 years from the time of diagnosis and no pharmacological therapies yet approved by the U. S. Food and Drug Administration. ⋯ The rationales for most of these therapeutic candidates are based on the current paradigm of IPF pathogenesis, in which recurrent injury to the alveolar epithelium is believed to drive aberrant wound healing responses, resulting in fibrosis rather than repair. Here we discuss drugs in recently completed or currently ongoing phase II and III IPF clinical trials in the context of their putative mechanisms of action and the aberrant repair processes they are believed to target: innate immune activation and polarization, fibroblast accumulation and myofibroblast differentiation, or extracellular matrix deposition and stiffening. Placed in this context, the positive results of recently completed trials of pirfenidone and nintedanib, and results that will come from ongoing trials of other agents, should provide valuable insights into the still-enigmatic pathogenesis of this disease, in addition to providing benefits to patients with IPF.
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Am. J. Respir. Crit. Care Med. · Oct 2014
Ambient Air Pollution Exposure and Incident Adult Asthma in a Nationwide Cohort of US Women.
Limited prior data suggest an association between traffic-related air pollution and incident asthma in adults. No published studies assess the effect of long-term exposures to particulate matter less than 2.5 μm in diameter (PM2.5) on adult incident asthma. ⋯ Results suggest that PM2.5 exposure increases the risk of developing asthma and that PM2.5 and NO2 increase the risk of developing wheeze, the cardinal symptom of asthma, in adult women.
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Am. J. Respir. Crit. Care Med. · Oct 2014
Comparative Study Clinical TrialNovel Tests for Diagnosis of Invasive Aspergillosis in Patients with Underlying Respiratory Diseases.
Invasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases. ⋯ Probable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of β-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316).
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Am. J. Respir. Crit. Care Med. · Oct 2014
The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause that leads to respiratory failure and death within 5 years of diagnosis. Overt respiratory infection and immunosuppression carry a high morbidity and mortality, and polymorphisms in genes related to epithelial integrity and host defense predispose to IPF. ⋯ IPF is characterized by an increased bacterial burden in BAL that predicts decline in lung function and death. Trials of antimicrobial therapy are needed to determine if microbial burden is pathogenic in the disease.
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Am. J. Respir. Crit. Care Med. · Oct 2014
Seeking Worldwide Professional Consensus on the Principles of End-of-life Care for the Critically Ill: The Welpicus Study.
Great differences in end-of-life practices in treating the critically ill around the world warrant agreement regarding the major ethical principles. This analysis determines the extent of worldwide consensus for end-of-life practices, delineates where there is and is not consensus, and analyzes reasons for lack of consensus. Critical care societies worldwide were invited to participate. ⋯ Consensus was obtained for 77 of 81 (95%) statements. Worldwide consensus could be developed for the majority of definitions and statements about end-of-life practices. Statements achieving consensus provide standards of practice for end-of-life care; statements without consensus identify important areas for future research.