Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus.

Purpose: Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management. Methods: The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%. Results: All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%). Conclusion: This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.

Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses.

Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, RORγt, Foxp3, interleukin (IL)-6, -17, -10, and TGF-ß was assessed by RT-qPCR. IL-6, -17, -10, and TGF-ß levels were determined by ELISA. We observed increased STAT3, RORγt, Foxp3, IL-6, and TGF-ß gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, RORγt, IL-6, and TGF-ß gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.

The Mini-Balance Evaluation System Test Can Predict Falls in Clinically Stable Outpatients With COPD: A 12-MO PROSPECTIVE COHORT STUDY.

PURPOSE: This study evaluated the accuracy of the Mini-Balance Evaluation System Test (Mini-BESTest) for predicting falls in patients with chronic obstructive pulmonary disease (COPD) and investigated whether postural balance is a risk factor for falls. METHODS: Postural balance was evaluated by the Mini-BESTest at baseline, and the incidence of falls over a 12-mo period was prospectively measured by a self-reported falls diary and confirmed by telephone calls. A discriminative power analysis was performed using receiver operating characteristic (ROC) curve and logistic regression analysis. RESULTS: Sixty-seven outpatients with COPD (mean age ± SD = 67 ± 9.3 yr) were included. Twenty-five patients (37.3%) experienced ≥1 fall, and 28.2% of the falls resulted in injuries. The Mini-BESTest predicted falls in patients with COPD at the 6- and 12-mo follow-ups with a cut-off score of 22.5 (area under the curve = 0.85 and 0.87) with good sensitivity and specificity (85.7% and 66.7%; 84% and 73.8%, respectively). Higher scores on the Mini-BESTest were associated with a lower risk of falls at 12 mo (OR = 0.50; 95% CI, 0.36-0.70; P < .001). CONCLUSIONS: Postural balance assessed by the Mini-BESTest is a good predictor of falls in patients with COPD. Our results imply that impaired balance contributes to the risk of falling and that balance training and fall prevention programs may be required for this population.

Urbanization is associated with increased asthma morbidity and mortality in Brazil.

INTRODUCTION: Previous cross-sectional studies could establish an association between prevalence of self-reported wheeze and urban-rural environment, but the impact of urbanization on meaningful outcomes of asthma for public health is not established yet. OBJECTIVES: Evaluate the effect of urbanization on asthma burden. METHODS: A time series study of 5,505 Brazilian municipalities. The unit of analysis was the municipality. Two time frames were evaluated: from 1999 to 2001 and from 2009 to 2011. Trends from the first to the second time frame were evaluated. Governmental databases were the source of information. Multivariate binary logistic regression models were used. RESULTS: In the age range from 5 to 24 years old, municipalities with increase in the proportion of individuals living in urban area had lower odds to reduce hospital admission rate from asthma (OR: .93) and lower odds to reduce death rate from asthma (OR: .88). In the age range from 25 to 39 years old, municipalities with increase in the proportion of individuals living in urban area had lower odds to reduce hospital admission rate from asthma (OR: .93) and lower odds to reduce death rate from asthma (OR: .82). Municipalities that increased access to physicians and that supplied inhaled corticosteroids free of charge for asthma since year 2003 had increased odds to reduce hospital admission and death rates from asthma. CONCLUSIONS: Increase in urban population was associated with lower odds to reduce hospital admission and death rates from asthma in children and young adults living in a transition society.

Impaired Pulmonary Function is an Additional Potential Mechanism for the Reduction of Functional Capacity in Clinically Stable Fontan Patients.

Central factors negatively affect the functional capacity of Fontan patients (FP), but "non-cardiac" factors, such as pulmonary function, may contribute to their exercise intolerance. We studied the pulmonary function in asymptomatic FP and its correlations with their functional capacity. Pulmonary function and cardiopulmonary exercise tests were performed in a prospective study of 27 FP and 27 healthy controls (HC). Cardiovascular magnetic resonance was used to evaluate the Fontan circulation. The mean age at tests, the mean age at surgery, and the median follow-up time of FP were 20(±6), 8(±3), and 11(8-17) years, respectively. Dominant ventricle ejection fraction was within normal range. The mean of peak VO2 expressed in absolute values (L/min), the relative values to body weight (mL/kg/min), and their predicted values were lower in FP compared with HC: 1.69 (±0.56) vs 2.81 (±0.77) L/min; 29.9 (±6.1) vs 41.5 (±9.3) mL/kg/min p < 0.001 and predicted VO2 Peak [71% (±14) vs 100% (±20) p < 0.001]. The absolute and predicted values of the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), inspiratory capacity (IC), total lung capacity (TLC), diffusion capacity of carbon monoxide of the lung (DLCO), maximum inspiratory pressure (MIP), and sniff nasal inspiratory pressure (SNIP) were also significantly lower in the Fontan population compared to HC. An increased risk of restrictive ventilatory pattern was found in patients with postural deviations (OD:10.0, IC:1.02-97.5, p = 0.042). There was a strong correlation between pulmonary function and absolute peak VO2 [FVC (r = 0.86, p < 0.001); FEV1 (r = 0.83, p < 0.001); IC (r = 0.84, p < 0.001); TLC (r = 0.79, p < 0.001); and DLCO (r = 0.72, p < 0.001). The strength of the inspiratory muscles in absolute and predicted values was also reduced in FP [-79(±28) vs -109(±44) cmH2O (p = 0.004) and 67(±26) vs 89(±36) % (p = 0.016)]. Thus, we concluded that the pulmonary function was impaired in clinically stable Fontan patients and the static and dynamic lung volumes were significantly reduced compared with HC. We also demonstrated a strong correlation between absolute Peak VO2 with the FVC, FEV1, TLC, and DLCO measured by complete pulmonary test.

The Role of Exercise in a Weight-Loss Program on Clinical Control in Obese Adults with Asthma. A Randomized Controlled Trial.

RATIONALE: Clinical control is difficult to achieve in obese patients with asthma. Bariatric surgery has been recommended for weight loss and to improve asthma control; however, the benefits of nonsurgical interventions have been poorly investigated. OBJECTIVES: To examine the effect of exercise training in a weight-loss program on asthma control, quality of life, inflammatory biomarkers, and lung function. METHODS: Fifty-five obese patients with asthma were randomly assigned to either a weight-loss program plus exercise (WL + E group, n = 28) or a weight-loss program plus sham (WL + S group, n = 27), where the weight-loss program included nutrition (caloric restriction) and psychological therapies. The WL + E group incorporated aerobic and resistance muscle training, whereas the WL + S group incorporated breathing and stretching exercises. MEASUREMENTS AND MAIN RESULTS: The primary outcome was clinical improvement in asthma control over 3 months. Secondary outcomes included quality of life, lung function, body composition, aerobic capacity, muscle strength, and inflammatory/antiinflammatory biomarkers. After 3 months, 51 patients were analyzed. Compared with the WL + S group, the WL + E group demonstrated improved clinical control scores (median [25th to 75th percentile], -0.7 [-1.3 to -0.3] vs. -0.3 [-0.9 to 0.4]; P = 0.01) and greater weight loss (mean ± SD, -6.8% ± 3.5 vs. -3.1% ± 2.6; P < 0.001) and aerobic capacity (median [25th to 75th percentile], 3.0 [2.4 to 4.0] vs. 0.9 [-0.3 to 1.3] ml O2 × kg-1 × min-1; P < 0.001). These improvements in the WL + E group were also accompanied by improvements in lung function, antiinflammatory biomarkers, and vitamin D levels, as well as reductions in airway and systemic inflammation. CONCLUSIONS: Adding exercise to a short-term weight-loss program should be considered as a useful strategy for achieving clinical control of asthma in obese patients. Clinical trial registered with www.clinicaltrials.gov (NCT 02188940).

The effects of exercise training in a weight loss lifestyle intervention on asthma control, quality of life and psychosocial symptoms in adult obese asthmatics: protocol of a randomized controlled trial.

BACKGROUND: Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown. METHODS/DESIGN: This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m(2)) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups. DISCUSSION: This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms. TRIAL REGISTRATION: NCT02188940.