American journal of respiratory and critical care medicine
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Theophylline (dimethylxanthine) has been used to treat airway diseases for more than 80 years. It was originally used as a bronchodilator, but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have antiinflammatory effects in asthma and chronic obstructive pulmonary disease (COPD) at lower concentrations. ⋯ Theophylline is now usually used as an add-on therapy in patients with asthma not well controlled on inhaled corticosteroids with or without long-acting β2-agonists and in patients with COPD with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting, and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism. In the future, low-dose theophylline may be useful in reversing corticosteroid resistance in COPD and severe asthma.
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Am. J. Respir. Crit. Care Med. · Oct 2013
ReviewUpdate in tuberculosis and nontuberculous mycobacterial disease 2012.
In 2012, new publications in the Journal described both the predictive value of the new IFN-γ release assays for diagnosis of latent tuberculosis (TB), but also provided evidence that these new tests cannot be interpreted simply as positive or negative, as initially hoped. Surgical masks can reduce transmission of TB infection, but other measures such as state-wide implementation of targeted testing and treatment of latent TB or active case finding require substantial and sustained effort to successfully reduce TB morbidity and mortality. A quasiexperimental study revealed that a package of social interventions could substantially reduce risk of TB disease in heavily exposed (and infected) children in the preantibiotic era. ⋯ Studies of nontuberculous mycobacteria (NTM) described a rapid rise in the prevalence and spatial clustering of NTM in the United States over the past decade. Although risk factors for pulmonary NTM such as advanced age and low BMI are known, the mechanisms underlying infection and disease remain mysterious. Four studies of therapy of NTM disease highlighted the pressing need for well-designed international randomized controlled trials to improve our management of NTM disease.
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Am. J. Respir. Crit. Care Med. · Oct 2013
ReviewModern Pharmacotherapy of Lung Disease: Targeted Therapy for Non-Small Cell Lung Cancer.
The treatment of advanced non-small cell lung cancer has been with systemic chemotherapy and usually consists of a platinum doublet chemotherapy. The identification of somatic driver mutations has resulted in new drugs that target these mutations. This report discusses the two most important new targeted therapy drugs for the treatment of advanced non-small cell lung cancer that have these driver mutations.
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Am. J. Respir. Crit. Care Med. · Oct 2013
Defining Phenotypic Causes of Obstructive Sleep Apnea: Identification of Novel Therapeutic Targets.
The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized. ⋯ This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.
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Am. J. Respir. Crit. Care Med. · Oct 2013
Systemic sRAGE is a Biomarker of Emphysema and Associated with AGER Genetic Variants in COPD Patients.
Emphysema in chronic obstructive pulmonary disease (COPD) can be characterized by high-resolution chest computed tomography (HRCT); however, the repeated use of HRCT is limited because of concerns regarding radiation exposure and cost. ⋯ Lower circulating sRAGE levels are associated with emphysema severity and genetic polymorphisms in the AGER locus are associated with systemic sRAGE levels. Clinical trial registered with www.clinicaltrials.gov (NCT 00413205 and NCT 00292552).