Chest
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Randomized Controlled Trial
Efficacy of roflumilast in the COPD frequent exacerbator phenotype.
COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status. ⋯ Treatment with roflumilast shifts patients from the frequent to the more stable infrequent exacerbator state.
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The study of genetics is providing new and exciting insights into the pathogenesis, diagnosis, and treatment of disease. Both normal sleep and several types of sleep disturbances have been found to have significant genetic influences, as have traits of normal sleep, such as those evident in EEG patterns and the circadian sleep-wake cycle. The circadian sleep-wake cycle is based on a complex feedback loop of genetic transcription over a 24-h cycle. ⋯ Although there is clear evidence of familial aggregation in the obstructive sleep apnea syndrome, no specific gene or locus has been identified for it. Angiotensin-converting enzyme has been proposed as a risk variant, but evidence is weak. Fatal familial insomnia and advanced sleep phase syndrome are sleep disorders with a definite genetic basis.
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The increase in total cross-sectional area in the distal airways of the human lung enhances the mixing of each tidal breath with end-expiratory gas volume by slowing bulk flow and increasing gas diffusion. However, this transition also favors the deposition of airborne particulates in this region because they diffuse 600 times slower than gases. Furthermore, the persistent deposition of toxic airborne particulates stimulates a chronic inflammatory immune cell infiltration and tissue repair and remodeling process that increases the resistance in airways <2 mm in diameter four to 40-fold in COPD. ⋯ However, recent reexamination of this problem based on micro-CT imaging indicates that terminal bronchioles are both narrowed and reduced to 10% of the control values in the centrilobular and 25% in the panlobular emphysematous phenotype of very severe (GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade IV) COPD. These new data indicate that both narrowing and reduction in numbers of terminal bronchioles contribute to the rapid decline in FEV₁ that leads to severe airway obstruction in COPD. Moreover, the observation that terminal bronchiolar loss precedes the onset of emphysematous destruction suggests this destruction begins in the very early stages of COPD.
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COPD is a leading cause of morbidity and mortality worldwide and is now the third leading cause of death in the United States. Acute exacerbations of COPD (AECOPDs) are common events that often lead to hospitalization, and their frequency worsens with disease progression. AECOPDs are associated with worsened quality of life, increased health-care costs, and increased mortality. ⋯ To examine the best available evidence, we restricted this review to include studies that used randomized controlled designs lasting at least 6 months. Pharmacologic interventions discussed include inhaled corticosteroids, long-acting β-agonists, long-acting antimuscarinic agents, macrolide antibiotics, and phosphodiesterase-4 inhibitors. The nonpharmacologic interventions discussed include lung volume reduction surgery, pulmonary rehabilitation, and disease management programs.
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The treatment of stage I and II non-small cell lung cancer (NSCLC) in patients with good or low surgical risk is primarily surgical resection. However, this area is undergoing many changes. With a greater prevalence of CT imaging, many lung cancers are being found that are small or constitute primarily ground-glass opacities. Treatment such as sublobar resection and nonsurgical approaches such as stereotactic body radiotherapy (SBRT) are being explored. With the advent of minimally invasive resections, the criteria to classify a patient as too ill to undergo an anatomic lung resection are being redefined. ⋯ Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC. Lobectomy or greater resection remains the preferred approach to T1b and larger tumors. The use of sublobar resection for T1a tumors and the application of adjuvant radiation therapy in this group are being actively studied in large clinical trials. Every patient should have systematic mediastinal lymph node sampling at the time of curative intent surgical resection, and mediastinal lymphadenectomy can be performed without increased morbidity. Perioperative morbidity and mortality are reduced and long-term survival is improved when surgical resection is performed by a board-certified thoracic surgeon. The use of adjuvant chemotherapy for stage II NSCLC is recommended and has shown benefit. The use of adjuvant radiation or chemotherapy for stage I NSCLC is of unproven benefit. Primary radiation therapy remains the primary curative intent approach for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable. There is growing evidence that SBRT provides greater local control than standard radiation therapy for high-risk and medically inoperable patients with NSCLC. The role of ablative therapies in the treatment of high-risk patients with stage I NSCLC is evolving. Radiofrequency ablation, the most studied of the ablative modalities, has been used effectively in medically inoperable patients with small (< 3 cm) peripheral NSCLC that are clinical stage I.