Changes and Clinical Consequences of Smoking Cessation in Patients With COPD: A Prospective Analysis From the CHAIN Cohort.

BACKGROUND: Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD. METHODS: CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. RESULTS: One thousand and eighty-one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV1, 60.2 [20.5]%). During the 2-year follow-up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points. CONCLUSIONS: In this real-life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov.

Cost-effectiveness of combination therapy umeclidinium/vilanterol versus tiotropium in symptomatic COPD Spanish patients.

PURPOSE: Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent. This analysis evaluated the incremental cost-effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective. METHODS: A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) was used. Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council ≥2). Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials). Spanish utility values were derived from a published local observational study. Unitary health care costs (€2015) were obtained from local sources. A 3-year time horizon was selected, and 3% discount was applied to effects and costs. Results were expressed as cost/quality-adjusted life years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) was performed. RESULTS: UMEC/VI produced additional 0.03 QALY and €590 vs TIO, leading to an ICER of €21,475/QALY. According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of €30,000/QALY. CONCLUSION: UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective.

Molecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loading.

High-intensity exercise induces oxidative stress and inflammatory events in muscles. Tumor necrosis factor (TNF)-α may alter muscle protein metabolism or promote muscle regeneration. We hypothesized that a program of noninvasive chronic inspiratory loading of different intensities induces a differential pattern of physiological, molecular, and cellular events within rat diaphragms. Antioxidants and TNF-α blockade may influence those events. In the diaphragm, gastrocnemius, and blood of rats exposed to high-intensity inspiratory threshold loads (2 hour every 24 hours for 14 days), with and without treatment with N-acetyl cysteine or infliximab (anti-TNF-α antibody), inflammatory cells and cytokines, superoxide anion production, myogenesis markers, and muscle structure were explored. In all animals, maximum inspiratory pressure (MIP) and body weight were determined. High-intensity inspiratory loading for 2 weeks caused a decline in MIP and body weight, and in the diaphragm induced a reduction in fast-twitch fiber proportions and sizes, whereas inflammatory cells and cytokine levels, including TNF-α immunohistochemical expression, superoxide anion, internal nuclei counts, and markers of myogenesis were increased. Blockade of TNF-α improved respiratory muscle function and structure, and animal weight, and, in the diaphragm, reduced inflammatory cell numbers and superoxide anion production drastically while inducing larger increases in protein and messenger RNA levels and immunohistochemical expression of TNF-α, internal nuclei, and markers of muscle regeneration. Blunting of TNF-α also induced a reduction in blood inflammatory cytokines and superoxide anion production. We conclude that TNF-α synthesized by inflammatory cells or myofibers could have differential effects on muscle structure and function in response to chronic, noninvasive, high-intensity inspiratory threshold loading.

Vibration response imaging versus perfusion scan in lung cancer surgery evaluation.

OBJECTIVE: Ventilation/perfusion scan is a standard procedure in high-risk surgical patients to predict pulmonary function after surgery. Vibration response imaging is a technique that could be used in these patients. The objective of our study was to compare this imaging technique with the usual scanning technique for predicting postoperative forced expiratory volume. METHODS: We assessed 48 patients with lung cancer who were candidates for lung resection. Forced spirometry, vibration response imaging, and ventilation/perfusion scan were performed in patients before surgery, and spirometry was performed after intervention. RESULTS: We included 48 patients (43 men; mean age, 64 years) undergoing lung cancer surgery (32 lobectomies/16 pneumonectomies). On comparison of both techniques, for pneumonectomy, we found a concordance of 0.84 (95% confidence interval, 0.76-0.92) and Bland-Altman limits of agreement of -0.33 to +0.45, with an average difference of 0.064. By comparing postoperative spirometry with vibration response imaging, we found a concordance of 0.66 (95% confidence interval, 0.38-0.93) and Bland-Altman limits of agreement of -0.60 to +0.33, with an average difference of -0.13. CONCLUSIONS: The 2 techniques presented good concordance values. Vibration response imaging shows non-negligible confidence intervals. Vibration response imaging may be useful in preoperative algorithms in patients before lung cancer surgery.

Spirometry. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR).

Spirometry is the main pulmonary function test and is essential for the evaluation and monitoring of respiratory diseases. Its utility transcends the field of Respiratory Medicine, is becoming increasingly important in primary care and applications have even been described outside the field of respiratory diseases. This document is therefore intended to serve as support for all health professionals who use spirometry, providing recommendations based on the best scientific evidence available. An update of the indications and contraindications of the test is proposed. The document sets out recommendations on the requirements necessary for conventional spirometers and portable office equipment, as well as on spirometer hygiene and quality control measures. Spirometric parameters that must be considered, performance of manoeuvres, criteria for acceptability and repeatability of measurements and their quality control are defined. A proposal is also established for presentation of the results and an evaluation and interpretation is proposed according to information generated in recent years. Finally, lines of adaptation and integration of spirometry in the field of new technologies are considered.

Injury of peripheral muscles in smokers with chronic obstructive pulmonary disease.

Muscle injury has clinical relevance in diseased individuals because it is associated with muscle dysfunction in terms of decreased strength and/or endurance. This study was aimed at answering three questions: whether the presence of chronic obstructive pulmonary disease (COPD) is associated with peripheral muscle injury; whether muscle injury is associated with some of the relevant functional impairment in the muscles; and whether muscle injury can be solely justified by deconditioning. Twenty-one male COPD patients were eligible for the study. Seven healthy volunteers recruited from the general population were included as controls. Function of the quadriceps muscle was assessed through specific single-leg exercise (strength and endurance). Cellular (light microscopy) and subcellular (electron microscopy) techniques were used to evaluate muscle injury on biopsies from the vastus lateralis muscle. Signs of injury were found in muscles from both control and COPD patients, not only in cases showing severe airflow obstruction but also in the mild or moderate stages of the disease. Current smoking and presence of COPD were significantly associated with increased injury of the muscle as assessed by light and electron microscopy techniques. The authors conclude that peripheral muscle injury is evident in mild, moderate, and severe stages of COPD even in the absence of respiratory failure, hypercapnia, chronic steroid treatment, low body weight, or some coexisting disease. These findings support the theory that systemic factors with deleterious effect are acting on peripheral muscles of smokers with COPD, increasing the susceptibility of the muscle fibers to membrane and sarcomere injury.

Consensus document on the overlap phenotype COPD-asthma in COPD.

INTRODUCTION: Although asthma and COPD are different pathologies, many patients share characteristics from both entities. These cases can have different evolutions and responses to treatment. Nevertheless, the evidence available is limited, and it is necessary to evaluate whether they represent a differential phenotype and provide recommendations about diagnosis and treatment, in addition to identifying possible gaps in our understanding of asthma and COPD. METHODS: A nation-wide consensus of experts in COPD in two stages: 1) during an initial meeting, the topics to be dealt with were established and a first draft of statements was elaborated with a structured "brainstorming" method; 2) consensus was reached with two rounds of e-mails, using a Likert-type scale. RESULTS: Consensus was reached about the existence of a differential clinical phenotype known as"Overlap Phenotype COPD-Asthma", whose diagnosis is made when 2 major criteria and 2 minor criteria are met. The major criteria include very positive bronchodilator test (increase in FEV(1) ≥ 15% and ≥ 400ml), eosinophilia in sputum and personal history of asthma. Minor criteria include high total IgE, personal history of atopy and positive bronchodilator test (increase in FEV(1) ≥ 12% and ≥ 200ml) on two or more occasions. The early use of individually-adjusted inhaled corticosteroids is recommended, and caution must be taken with their abrupt withdrawal. Meanwhile, in severe cases the use of triple therapy should be evaluated. Finally, there is an obvious lack of specific studies about the natural history and the treatment of these patients. CONCLUSIONS: It is necessary to expand our knowledge about this phenotype in order to establish adequate guidelines and recommendations for its diagnosis and treatment.

Cigarette smoke-induced oxidative stress: A role in chronic obstructive pulmonary disease skeletal muscle dysfunction.

RATIONALE: Inflammation and oxidative stress contribute to muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). Oxidants contained in cigarette smoke (CS) induce adverse effects on tissues through oxidative phenomena. OBJECTIVES: To explore oxidative stress and inflammation in quadriceps of human smokers and in diaphragm and limb muscles of guinea pigs chronically exposed to CS. METHODS: Muscle function, protein oxidation and nitration, antioxidants, oxidized proteins, inflammation, creatine kinase activity, and lung and muscle structures were investigated in vastus lateralis of smokers, patients with COPD, and healthy control subjects and in diaphragm and gastrocnemius of CS-exposed guinea pigs at 3, 4, and 6 months. MEASUREMENTS AND MAIN RESULTS: Compared with control subjects, quadriceps muscle force was mildly but significantly reduced in smokers; protein oxidation levels were increased in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed animals; glycolytic enzymes, creatine kinase, carbonic anydrase-3, and contractile proteins were significantly more carbonylated in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed guinea pigs. Chronic CS exposure induced no significant rise in muscle inflammation in either smokers or rodents. Muscle creatine kinase activity was reduced only in patients with COPD and in both diaphragm and gastrocnemius of CS-exposed animals. Guinea pigs developed bronchiolar abnormalities at 4 months of exposure and thereafter. CONCLUSIONS: CS exerts direct oxidative modifications on muscle proteins, without inducing any significant rise in muscle inflammation. The oxidative damage to muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle loss and dysfunction in smokers and patients with COPD.

Evaluation of the utility of vibration response imaging device and Operation Planning Software in the assessment of patients before lung resection surgery.

BACKGROUND AND OBJECTIVES: A variety of methods have been used to evaluate patients with lung cancer to define a patient cohort at high risk for postoperative mortality and respiratory complications associated with lung resection surgery. Our aim was to evaluate the utility of vibration response imaging (VRI(XP)) Operation Planning Software (O-Plan) in assessing suitability for surgical resection and for the prediction of postoperative forced expiratory volume in 1s (ppoFEV(1)). METHODS: A total of 58 subjects with lung cancer underwent evaluation prior to lung resection surgery and postoperative lung function after surgery. RESULTS: Preoperative pulmonary function tests and quantitative breath sound measurements by VRI were performed in all patients to estimate postoperative lung function. In addition, 20 patients underwent perfusion scan prior to surgery. VRI(XP) O-Plan predictions (12 pneumonectomies and 46 lobectomies) showed good correlation and concordance (Lin's coefficient) with postoperative FEV(1) (l) (r=0.865, Lin's coefficient 0.858) and FEV(1) (%) (r=0.877, Lin's coefficient 0.861) 4-6 weeks after surgery. Predicted and postoperative measured FEV(1) showed no significant differences (p>0.05). Average lung function predicted postoperative values were similar for perfusion and VRI(XP) O-Plan calculations with a correlation of 0.74 and concordance of 0.700. CONCLUSIONS: VRI(XP) O-Plan has shown high accuracy in predicting postoperative FEV(1) after lung resection surgery. Given its simplicity of operation and the non-invasive nature of VRI(XP) and O-Plan, it could be a good alternative to perfusion scan in pre-surgery assessment.