https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)60693-6.pdf

Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management

To refine the functional guidelines for operability for lung resection, we prospectively studied 55 consecutive patients with suspected lung malignancy thought to be surgically resectable. Lung function and exercise capacity were measured preoperatively and at 3 and 12 months postoperatively. Preoperative pulmonary scintigraphy was used to calculate the contribution to overall function by the affected lung or lobe and to predict postoperative lung function. Pneumonectomy was performed in 18 patients, lobectomy in 29, and thoracotomy without resection in six. No surgery was attempted in two patients who were considered functionally inoperable. Cardiopulmonary complications developed in 16 patients within 30 days of surgery, including three deaths. The predictions of postoperative function correlated well with the measured values at 3 months. For FEV1, r = 0.51 in pneumonectomy (p less than 0.05) and 0.89 in lobectomy (p less than 0.001). Predicted postoperative FEV1 (FEV1-ppo), diffusing capacity (DLCO), predicted postoperative DLCO (DLCO-ppo) and exercise-induced arterial O2 desaturation (delta SaO2) were predictive of postoperative complications including death and respiratory failure. In patients who underwent pneumonectomy, the best predictor of death was FEV1-ppo. The predictions were enhanced by expressing the value as a percentage of the predicted normal value (% pred) rather than in absolute units. For the entire surgical group a FEV1-ppo greater than or equal to 40% pred was associated with no postoperative mortality (n = 47), whereas a value less than 40% pred was associated with a 50% mortality (n = 6), suggesting that resection is feasible when FEV1-ppo is greater than or equal to 40% pred.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative Assessment as a Predictor of Mortality and Morbidity After Lung Resection

Background Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined. Objective We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function. Methods NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation. Results Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale ( P 1 , symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations ( P  = .002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity ( P  = .009) and dominance of Haemophilus species operational taxonomic units ( P  = .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD. Conclusion NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity.

/pdf/neutrophil-extracellular-traps-are-associated-with-disease-1wq1tz5kmm.pdf

Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease

COPD Readmissions: Addressing COPD in the Era of Value-based Health Care

Background: Current tobacco treatment guidelines have established the efficacy of available interventions, but they do not provide detailed guidance for common implementation questions frequently faced in the clinic. An evidence-based guideline was created that addresses several pharmacotherapy-initiation questions that routinely confront treatment teams.Methods: Individuals with diverse expertise related to smoking cessation were empaneled to prioritize questions and outcomes important to clinicians. An evidence-synthesis team conducted systematic reviews, which informed recommendations to answer the questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in the estimated effects and the strength of recommendations.Results: The guideline panel formulated five strong recommendations and two conditional recommendations regarding pharmacotherapy choices. Strong recommendations include using varenicline rather than a nicotine patch, using varenicline rather than bupropion, using varenicline rather than a nicotine patch in adults with a comorbid psychiatric condition, initiating varenicline in adults even if they are unready to quit, and using controller therapy for an extended treatment duration greater than 12 weeks. Conditional recommendations include combining a nicotine patch with varenicline rather than using varenicline alone and using varenicline rather than electronic cigarettes.Conclusions: Seven recommendations are provided, which represent simple practice changes that are likely to increase the effectiveness of tobacco-dependence pharmacotherapy.

Initiating Pharmacologic Treatment in Tobacco-Dependent Adults. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management.


METHODS
Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified.


RESULTS
Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus.


CONCLUSIONS
Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.

An Official American Thoracic Society/European Respiratory Society Statement: Research Questions in Chronic Obstructive Pulmonary Disease Executive Summary

Alvar Agust

Papers

An Official American Thoracic Society/European Respiratory Society Statement: Research Questions in Chronic Obstructive Pulmonary Disease Executive Summary