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Sanjay Sethi,1 Edward Kerwin,2 Henrik Watz,3 Gary T Ferguson,4 Robert M Mroz,5,6 Rosa Segarra,7 Eduard Molins,7 Diana Jarreta,7 Esther Garcia Gil7 1Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA; 2Clinical Research Institute, Medford, OR, USA; 3Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 4Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 5Centrum Medycyny Oddechowej, Białystok, Poland; 6Medical University of Białystok, Białystok, Poland; 7AstraZeneca, Barcelona, Spain Background: AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677).Methods: In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 µg, AB 400 µg, or FF 12 µg, or once-daily TIO 18 µg. Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF). Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective. Normalized area under the curve (AUC)0–3/3 h FEV1 and nighttime and early morning symptoms were also assessed. A subgroup participated in a 24-hour serial spirometry sub-study.Results: A total of 1,594 patients were randomized; 566 entered the sub-study. At week 24, 1-hour post-dose FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P

Rationale: Improvements in FEV1 correlate with patient-related outcomes (PROs) at a population level (Donohue et al. Pulm Pharm Ther. 2018). However, the association of clinically relevant changes in PROs with changes in FEV1 in individual patients have seldom been investigated. Methods: CRYSTAL, a 12-week, prospective, randomised, pragmatic trial, evaluated the effect of indacaterol/glycopyrronium (IND/GLY) or GLY after direct switch from previous treatments in moderate COPD patients. Lung function (FEV1), COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and Transitional Dyspnoea Index (TDI) were evaluated after 12 weeks vs baseline. Results: Of 4324 patients 2774 (64.2%) were classified as responders by TDI, CAT or CCQ with 1365, 826 and 583 patients responding according to 1, 2 or all 3 PROs respectively. In comparison, 3235 patients (74.8%) were considered responders when combining TDI, CAT, CCQ and FEV1 and 1555 patients (36%) responded to PROs only (≥1) but not to FEV1. Out of 1680 responders to FEV1, 1219 (72.6%) patients demonstrated a combined response (FEV1 and ≥ 1 PRO), and 461 (27.4%) showed only a response in FEV1. There was little overlap between responders to TDI, CAT, CCQ and FEV1 (figure). Conclusions: Improvements in lung function do not always translate into improvements in PROs in individual patients. PROs are not interchangeable and hence the definition of treatment success depends on the PRO used.

The association between clinically relevant changes in patient-reported outcomes (PROs) and forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD) has rarely been investigated. Using CRYSTAL, a 12-week open-label study in symptomatic, nonfrequently exacerbating patients with moderate COPD, we assessed at baseline the correlations between several PROs (Baseline Dyspnoea Index, modified Medical Research Council dyspnoea scale, COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ)), and between FEV1 and PROs. Associations between clinically relevant responses in FEV1, CAT, CCQ and Transition Dyspnoea Index (TDI) at week 12 were also assessed. Using data from 4324 patients, a strong correlation was observed between CAT and CCQ (rs=0.793) at baseline, with moderate or weak correlations between other PROs, and no correlation between FEV1 and any PRO. At week 12, 2774 (64.2%) patients were responders regarding TDI, CAT or CCQ, with 583 (13.5%) responding using all three measures. In comparison, 3235 (74.8%) were responders regarding FEV1, TDI, CAT or CCQ, with 307 (7.1%) responding concerning all four parameters. Increases in lung function were accompanied by clinically relevant improvements of PROs in a minority of patients. Our results also suggest that PROs are not interchangeable. Thus, the observed treatment success in a clinical trial may depend on the selected parameters., Assessments of both lung function and various patient-reported outcomes in clinical trials may be necessary for a more complete picture of treatment response in patients with COPD and to guide treatment decisions http://ow.ly/msoz30nmupG

espanolIntroduccion: El manejo odontologico de pacientes medicamente comprometidos requiere un enfoque integral y multidisciplinario. La hipoxemia puede presentarse en pacientes odontologicos con enfermedades respiratorias durante y despues de la intervencion, por lo que se requiere la monitorizacion del porcentaje de saturacion de oxigeno en sangre periferica (%SpO2) para identificar rapidamente aquellos trastornos que precisen intervencion terapeutica. La enfermedad pulmonar obstructiva cronica (EPOC) es una enfermedad que puede permanecer subdiagnosticada en pacientes fumadores asintomaticos, quienes pueden presentar estas alteraciones. Objetivo: Evaluar el %SpO2 durante procedimientos de cirugia bucal en pacientes fumadores. Materiales y metodo: A los pacientes fumadores a quienes se realizaron procedimientos de cirugia bucal en los servicios del Postgrado de Cirugia Bucal de la Facultad de Odontologia de la Universidad Central de Venezuela y aceptaron su inclusion en el estudio se les determino el consumo tabaquico en indice paquetes/ano (p/a) y se les aplico el COPD Assesment Test (CAT), la escala de disnea modified Medical Research Council (mMRC) y la clasificacion de la Global Initiative for Chronic Obstructive Lung Disease (GOLD); tambien se les realizo una espirometria forzada y se registro la %SpO2 mediante un pulsioximetro antes de comenzar el procedimiento quirurgico, al realizar el bloqueo anestesico, un minuto despues de este y al finalizar la sintesis de los tejidos. Los datos fueron analizados utilizando las pruebas t de Student, Chi cuadrado, Mann-Whitney y rho de Spearman. Se considero un contraste estadisticamente significativo si p Resultados: Se incluyeron 33 individuos, distribuidos en dos grupos: G1, n = 16, indice tabaquico > 20 p/a; G2, n = 17, indice tabaquico ≤ 20 p/a. El G1 presento mayor puntuacion CAT (10 vs. 4) y mMRC (2 vs. 0) y una disminucion en los parametros espirometricos %VEF1/CVF 59 vs. 83 %, FEF25-75% 38 vs. 82 l/s (p = 0,001). Todos los pacientes del G1 fueron diagnosticados de EPOC y tuvieron una significante disminucion en el %SpO2 durante los tiempos quirurgicos evaluados (97 vs. 98, 96 vs. 98, 95 vs. 97, 93 vs. 97 %), asi como desaturaciones %SpO2 Conclusiones: Los pacientes fumadores de mas de 20 p/a y con diagnostico de EPOC presentaron disminuciones significativas del %SpO2 durante la realizacion de procedimientos odontologicos independientemente de su duracion total; sin embargo, no se evidenciaron manifestaciones clinicas de hipoxemia. EnglishIntroduction: Hypoxemia commonly arises in dental patients with lung diseases during and after surgery and requires monitoring patients' blood oxygenation to identify life-threatening problems. Chronic Obstructive Lung Disease (COPD) could remain underdiagnosis in smokers without symptoms. Objective: The aim of this study was to evaluate the arterial oxygen saturation (%SpO2) during oral surgery procedures in smoker patients. Materials and methods: The study population consisted in thirty-three smoker patients undergoing oral surgery procedures using local anesthetic at the School of Dentistry in the Central University of Venezuela. A medical history, included information on smoking habits: pack/year, COPD Assessment Test (CAT), modified Medical Research Council (mMRC), all patients were classified by Global Initiative for Chronic Obstructive Lung Disease criteria (GOLD). Oxygen saturation was monitored by pulse oximetry, before the beginning of the surgery, during the anesthetic administration, one minute after and the end of the suture. Data were analyzed using Student's t test, chi-squared, Mann-Whitney test, Spearman's rho test. Results: Subjects were divided in two groups according with the smoking history: group 1, n = 16, > 20 pack/year; group 2, n = 17, ≤ 20 pack/year. Group 1 have higher scores of CAT (10 vs. 4) mMRC (2 vs. 0) and lower spirometric values % FEV1/FVC 59 vs. 83 %, FEF25-75 of 38 vs. 82 lts/s (p = 0,001). All group 1 patients were diagnosis with COPD and lower oxygen saturation during times of surgery (97 vs. 98, 96 vs. 98, 95 vs. 97, 93 vs. 97 %), episodes of %SpO2 90 % (75 vs. 0 %) and times of desaturation below the baseline (3,5 vs. 1). There was not relation between time of surgery and oxygen saturation. Conclusions: Patients with a smoking history > 20 pack-years and COPD diagnosis have episodes of arterial oxygen desaturation during oral surgery procedures and it occurs in the absence of hemodynamic or other physiologic signs of hypoxemia.

Objectives Minimal clinically important differences (MCIDs) are used as fixed numbers in the interpretation of clinical trials. Little is known about its dynamics. This study aims to explore the impact of baseline score, study setting, and patient characteristics on health status MCIDs in chronic obstructive pulmonary disease (COPD). Study Design and Setting Baseline and follow-up data on the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and St. George's Respiratory Questionnaire (SGRQ) were retrospectively analyzed from pulmonary rehabilitation (PR) and routine clinical practice (RCP). Anchor- and distribution-based MCID estimates were calculated and tested between settings, gender, age, Global initiative for Obstructive Lung Disease (GOLD) classification, comorbidities, and baseline health status. Results In total, 658 patients were included with 2,299 change score measurements. MCID estimates for improvement and deterioration ranged for all subgroups 0.50–6.30 (CAT), 0.10–0.84 (CCQ), and 0.33–12.86 (SGRQ). Larger MCID estimates for improvement and smaller ones for deterioration were noted in patients with worse baseline health status, females, elderly, GOLD I/II patients, and patients with less comorbidities. Estimates from PR were larger. Conclusion Baseline health status and setting affected MCID estimates of COPD health status questionnaires. Patterns were observed for gender, age, spirometry classification, and comorbidity levels. These outcomes would advocate the need for tailored MCIDs.

Introduction The EQ5D5L, a generic health status measure, is responsive to pulmonary rehabilitation (PR) in those with COPD (1), however responsiveness in other pathologies is not known. As a utility index (UI) it can be used to establish the cost effectiveness of PR programmes, many of which are not uni-pathology. The applicability and outcomes of EQ5D5L in a ‘real life’ multi-pathology PR programme is described. Aim To assess the responsiveness of the EQ5D5L in a UK PR service which includes those with varied respiratory diagnoses. Methods The EQ5D5L UI and visual analogue scale (VAS), Anchor question, COPD Assessment Test (CAT) and either the six-minute or incremental shuttle walk test (6 MWT; ISWT) were completed by patients pre- and post-PR from October 2016 to July 2018. Changes in outcomes are reported as mean ±SD. Paired t-tests were used to test within subject differences and Spearman’s correlation to test for associations. Results 131 patients (mean age 66±16; 76% COPD; FEV160%±22% predicted) completed PR. Following PR, there were significant improvements in CAT (3.1±6.7, p Conclusions These findings show the EQ5D5L is responsive to a ‘real life’ PR programme. The observed improvements are below or at the lower limits of reported minimal important differences (MID) for VAS and UI, 6.5% to 10.1% and 0.037 to 0.109, respectively.1 This may indicate that the MID differs in those with diagnoses other than COPD. The EQ5D5L may be of use as a PR quality indicator and may provide a novel approach to allow PR services to evaluate their cost-effectiveness. Further work to determine the MID and responsiveness in a mixed population is required. Reference Nolan CM, Longworth L, Lord J, Canavan JL, Jones SE, Kon SS, et al. The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and minimum important difference. Thorax 2016;71(6):493–500.

Maaike Giezeman,1,2 Mikael Hasselgren,1 Karin Lisspers,3 Björn Ställberg,3 Scott Montgomery,4–6 Christer Janson,7 Josefin Sundh8 1School of Medical Sciences, Örebro University, Örebro, Sweden; 2Centre for Clinical Research, County Council of Värmland, Karlstad, Sweden; 3Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 4Clinical Epidemiology and Biostatistics, Örebro University, Örebro, Sweden; 5Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 6Department of Epidemiology and Public Health, University College, London, UK; 7Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 8Department of Respiratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden Purpose: The aim of this study was to examine the changing influence over time of comorbid heart disease on symptoms and health status in patients with COPD. Patients and methods: This is a prospective cohort study of 495 COPD patients with a baseline in 2005 and follow-up in 2012. The study population was divided into three groups: patients without heart disease (no-HD), those diagnosed with heart disease during the study period (new-HD) and those with heart disease at baseline (HD). Symptoms were measured using the mMRC. Health status was measured using the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT; only available in 2012). Logistic regression with mMRC ≥2 and linear regression with CCQ and CAT scores in 2012 as dependent variables were performed unadjusted, adjusted for potential confounders, and additionally adjusted for baseline mMRC, respectively, CCQ scores. Results: Mean mMRC worsened from 2005 to 2012 as follows: for the no-HD group from 1.8 (±1.3) to 2.0 (±1.4), (P=0.003), for new-HD from 2.2 (±1.3) to 2.4 (±1.4), (P=0.16), and for HD from 2.2 (±1.3) to 2.5 (±1.4), (P=0.03). In logistic regression adjusted for potential confounding factors, HD (OR 1.71; 95% CI: 1.03–2.86) was associated with mMRC ≥2. Health status worsened from mean CCQ as follows: for no-HD from 1.9 (±1.2) to 2.1 (±1.3) with (P=0.01), for new-HD from 2.3 (±1.5) to 2.6 (±1.6) with (P=0.07), and for HD from 2.4 (±1.1) to 2.5 (±1.2) with (P=0.57). In linear regression adjusted for potential confounders, HD (regression coefficient 0.12; 95% CI: 0.04–5.91) and new-HD (0.15; 0.89–5.92) were associated with higher CAT scores. In CCQ functional state domain, new-HD (0.14; 0.18–1.16) and HD (0.12; 0.04–0.92) were associated with higher scores. After additional correction for baseline mMRC and CCQ, no statistically significant associations were found. Conclusion: Heart disease contributes to lower health status and higher symptom burden in COPD but does not accelerate the worsening over time. Keywords: COPD Assessment Test, CAT, Clinical COPD Questionnaire, CCQ, modified Medical Research Council dyspnea score, mMRC, ischemic heart disease, heart failure

FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo The COPD assessment test (CAT) is a short questionnaire developed to help patients and clinicians to assess the impact of symptoms in routine clinical practice. We aimed to validate and to test the reproducibility of CAT in patients with bronchiectasis and correlate with the severity of dyspnea, aerobic and functional capacity, and physical activity in daily life. This is a cross-sectional study, patients with bronchiectasis underwent spirometry, cardiopulmonary exercise test (CPET), incremental shuttle walk test (ISWT), Saint George`s Respiratory Questionnaire (SGRQ), and received pedometer. CAT was applied twice (CAT-1 and CAT-2, 7 to 10 days apart). The severity of bronchiectasis was assessed by E-FACED and bronchiectasis severity index (BSI). A total of 100 patients were evaluated (48 ± 14 years, 59 women, FVC: 67 ± 22% pred, FEV1: 52 ± 25% pred). According to CAT, 14% patients presented low, 40% medium, 32% high, and 14% very high impact. The higher the CAT, the worse the severity of bronchiectasis, dyspnea, quality of life, performance on the CPET, and smaller the distance walked (DW) on the ISWT and number of steps (NS) per day. There was significant correlation between CAT and SGRQ, E-FACED, BSI, NS, ISWT, oxygen uptake, and workload at CPET. CAT-1 and CAT-2 presented similar values: 21 (13–26) and 19 (13–26), respectively. The CAT is a valid and reproducible instrument in patients with bronchiectasis presenting good correlation with clinical, functional, and quality of life measurements. This easy-to-use, easy-to-understand, quick, and useful tool may play an important role to assess the impact of bronchiectasis on both daily medical practice and clinical trial settings.

Juan José Soler-Cataluña,1,2 Maribel Marzo,3 Pablo Catalán,1 Cristina Miralles,1 Bernardino Alcazar,2,4 Marc Miravitlles2,5 1Pneumology Department, Hospital Arnau de Vilanova, Valencia, Spain; 2CIBER of Respiratory Diseases (CIBERES), Spain; 3Emergency Department, Hospital General de Requena, Valencia, Spain; 4Respiratory Department, Hospital de Alta Resolución de Loja, Granada, Spain; 5Pneumology Department, University Hospital Vall d’Hebron/Vall d’Hebron Research Institute (VHIR), Barcelona, Spain Background: It has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.Objective: Define and subsequently validate “modified” control criteria (MCC) of COPD.Method: Prospective observational study in COPD patients with a 1-year follow-up. Control was defined as the presence of low clinical impact and clinical stability. To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color. Stability was assessed by clinical changes and exacerbations in the last 3 months. The COPD assessment test score and their changes were also evaluated as alternative control criteria. To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established. Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.Results: We included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%. The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%). Similar percentages were found using COPD assessment test scores. The time to the first combined event was significantly greater in controlled patients using MCC criteria (P

The new A-B-C-D Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based on combined symptoms and exacerbation risk assessment. The assumed equivalence between dyspnoea modified Medical Research Council (mMRC) grade ≥2 and COPD Assessment Test (CAT) score ≥ 10 to identify more symptoms has been questioned. Whether the exacerbation risk assessment criteria, old GOLD spirometry staging and frequency of exacerbations, are equivalent has not been examined. We evaluated the extent of agreement between these alternative criteria and whether it improved by redefining the equivalence between mMRC grade and CAT score. CAT scores, mMRC grades of dyspnoea, frequency of exacerbations and spirometry stages were computed in 400 patients with COPD. Receiver operating characteristic curve was analysed to determine the best CAT score to identify more symptoms. CAT scores across mMRC grades and the frequency of exacerbations across spirometry stages showed substantial overlaps. The symptoms criteria gave discordant classification in 88 (22%) patients (kappa 0.62) and the exacerbation risk assessment criteria in 181 (45%) patients (kappa 0.12). A CAT score of ≥10 had 82% sensitivity but 24% specificity to identify mMRC grade ≥ 2, while a score of 17 had 98% specificity but a low sensitivity of 52% and did not improve the agreement. We conclude that symptoms and exacerbation risk assessment criteria of the new GOLD classification yield discordant group categorisations. Lack of any satisfactory equivalence between CAT score and mMRC grades implies that the former cannot be used alone. Using the higher of mMRC ≥ 2 and CAT score ≥ 17 to identify more symptoms would avoid discordant categorisation.

Mariko Morishita-Katsu,1,2 Koichi Nishimura,3 Hiroyuki Taniguchi,1 Tomoki Kimura,1 Yasuhiro Kondoh,1 Kensuke Kataoka,1 Tomoya Ogawa,4 Fumiko Watanabe,4 Shinichi Arizono,5 Osamu Nishiyama,6 Kazuhito Nakayasu,7 Kazuyoshi Imaizumi,8 Yoshinori Hasegawa2 1Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan; 2Division of Respiratory Medicine, Department of Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; 3Department of Pulmonary Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; 4Department of Rehabilitation, Tosei General Hospital, Seto, Japan; 5School of Rehabilitation Sciences, Seirei Christopher University, Hamamatsu, Japan; 6Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, Osakasayama, Japan; 7Data Research Section, Kondo P.P. Inc., Osaka, Japan; 8Department of Respiratory Medicine, Fujita Health University, Nagoya, Japan Background: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a short questionnaire that has facilitated health status measurements in subjects with COPD. However, it remains controversial as to whether the CAT can be used as a suitable substitute for the St George’s Respiratory Questionnaire (SGRQ). This study investigated the reliability and score distributions of the CAT and SGRQ and evaluated which factors contributed to health status for each questionnaire.Methods: A total of 109 consecutive subjects with stable COPD from a single center were enrolled in this study. Each subject completed pulmonary function tests, exercise tests, and the following self-administered questionnaires: the Baseline Dyspnea Index, the Hospital Anxiety and Depression Scale, the CAT, and SGRQ.Results: Internal consistencies of CAT and SGRQ total scores were both excellent (Cronbach’sα coefficients =0.890 and 0.933). Statistically significant correlations were observed between CAT and SGRQ total scores (R=0.668, P

To develop an algorithm for estimating EuroQol five-dimensional questionnaire (EQ-5D)-equivalent utilities from the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and evaluate its use in economic evaluations as part of health technology assessments for COPD.Data for the three-level EQ-5D (EQ-5D-3L) and the CAT were obtained from two multinational, phase III clinical trials. Three approaches were explored for estimating EQ-5D-equivalent utilities from the CAT: ordinary least-squares (OLS) regression, multinomial logistic regression, and a combination of the two. Estimated utilities were compared with actual EQ-5D-3L utilities, including treatment effect and the impact of disease severity on health, to evaluate the predictive performance of each algorithm.Root mean squared error and mean absolute error analyses showed that an OLS algorithm performed as well as algorithms developed using more complex modeling structures. The OLS regression included EQ-5D-3L utility weights as dependent variables and CAT items as independent variables. Within-sample validation showed systematic overestimation and underestimation within the range 0.5 ≤ EQ-5D-3L ≤ 0.9 (although all mean absolute errors were ≤0.100), with the smallest difference between estimated and actual values within 0.7EQ-5D-3L ≤ 0.9. The algorithm underestimated utility near full health and overestimated utility less than 0.5. As a consequence, the change from baseline was lower and the confidence intervals were narrower than those observed with actual EQ-5D-3L data.In the absence of EQ-5D data, the OLS regression algorithm may provide an estimate of utility for treatment models, but it is likely to underestimate treatment effects. Therefore, it is recommended that utilities be derived directly from the EQ-5D for the purposes of health technology assessments for COPD treatments in the United Kingdom.

Joon Young Choi,1 Hyoung Kyu Yoon,2 Seoung Ju Park,3 Yong Bum Park,4 Kyeong-Cheol Shin,5 Ju Ock Na,6 Kwang Ha Yoo,7 Ki-Suck Jung,8 Young Kyoon Kim,1 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 5Regional Center for Respiratory Disease, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Background: The chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups.Methods: Data were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups.Results: Of the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups.Conclusion: The present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups. Keywords: chronic obstructive pulmonary disease, chronic bronchitis, COPD assess­ment test

Yoshinosuke Fukuchi,1 Koichiro Tatsumi,2 Hiromasa Inoue,3 Yukinori Sakata,4 Kai Shibata,4 Hideaki Miyagishi,4 Yasuhiro Marukawa,4 Masakazu Ichinose5 1Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, 2Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, 3Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 4Eisai Co., Ltd., Tokyo, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background/aim: Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. Methods: In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270mg) or placebo was administered orally for 52weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate. Results: A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52weeks of the study. Conclusion: The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation. Keywords: lysozyme, COPD exacerbation, forced expiratory volume in 1second, COPD assessment test

Background The COPD Assessment Test (CAT) was developed as a simple instrument to assess health status in patients with COPD. This study aimed to systematically review the determinants of the CAT score, its ability to predict clinical outcomes, and the agreement between CAT (≥ 10) and the modified Medical Research Council scale (mMRC ≥ 2) to categorize patients into the new Global Initiative for Chronic Obstructive Lung Disease classification system. Methods From January 1, 2009, to June 30, 2015, databases were searched for studies using CAT in adults with COPD and in general populations aiming to detect COPD. Two investigators independently screened, selected, and extracted data by using a standardized form. Where appropriate, the results were combined in a random effects meta-analysis. Results Of 453 studies, 17 were included, and eight were used in the meta-analysis. The models to predict the CAT score were able to explain Conclusions CAT may be used as a complementary tool in a patient's clinical assessment to predict COPD exacerbation, health status deterioration, depression, and mortality. The interpretation of this meta-analysis does not support the use of the recommended cutoff points of ≥10 for CAT and ≥2 for mMRC as equivalents for the purpose of assessing patient symptoms.

Background. Research conducted on the quality of life of patients are becoming more common as a valuable complement to data of clinical assessment of the patient and the effectiveness of the therapeutic process. The aim of the study is to assess the quality of life and symptom severity in patients with COPD as well as an attempt to assess the impact of the current status of smoking on quality of life. Material and methods. The study included 97 patients diagnosed with COPD. Resources used: COPD Assessment Test (CAT), The modified Medical Research Council dyspnea scale (mMRC), St. George’s Respiratory Questionnaire for COPD Patients (SGRQ-C) and author’s questionnaire. Results. There is a strong positive correlation between the SGRQ and CAT (r = 0.64, p 0.05 Respondents avowed by smoking status did not differ significantly between each other by comparing the severity of dyspnoea F = 2.95; p > 0.05. Those who never smoked did not obtain significantly better results in the SGRQ than current or former smokers F = 0.20; p > 0.05. Conclusions. Patients included in the study were complaining of poor quality of life and a significant worsening of pulmonary symptoms and signs of disease. The current smoking status does not affect the quality of life in that group.

Aim To develop and do an initial validation of a new simple tool (self-administered questionnaire) that would be sensitive and specific enough to detect early changes in smokers leading to future development of chronic obstructive pulmonary disease (COPD). Methods 224 consecutive participants (50.9% women), with mean ± standard deviation age of 52.3 ± 6.7 years, 37.5 ± 16.7 pack-years smoking history (85.8% active smokers), and no prior diagnosis of COPD were recruited. The MARKO questionnaire was self-administered twice; at the general practitioner's office and after 2-4 weeks at the tertiary care hospital. Participants were assessed for COPD by a pulmonologist after filling in a quality of life (QoL) questionnaires, history-taking, physical examination, lung function test, 6-minute walk test, and laboratory tests. They were divided into four subgroups: “healthy” smokers, symptomatic smokers, and smokers with mild and moderately severe COPD. Results Psychometric analyses indicated that the 18-item questionnaire had a very good internal consistency (Cronbach’s alpha = 0.91) and test-retest reliability for a four week period (ρc = 0.89, 95% confidence interval [CI] 0.85-0.92, Lin’s concordance). A significant correlations of MARKO scores were found with two QoL questionnaires; r = 0.69 (P

Margaret K Pasquale,1 Yihua Xu,1 Christine L Baker,2 Kelly H Zou,3 John G Teeter,4 Andrew M Renda,5 Cralen C Davis,1 Theodore C Lee,6 Joel Bobula2 1Comprehensive Health Insights, Inc., Humana Inc., Louisville, KY, 2Outcomes and Evidence, Global Health & Value, Pfizer Inc., 3Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, Pfizer Inc., New York, NY, 4Global Medical Development, Global Innovative Pharma Business, Pfizer Inc., Groton, CT, 5Retail Strategy& Execution, Humana Inc., Louisville,KY, 6Global Medical Affairs, Global Innovative Pharma Business, Pfizer Inc., New York, NY, USA Background: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs.Methods: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis­eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs.Results: Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P0.10).Conclusion: The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history. Keywords: Global initiative for chronic Obstructive Lung Disease, COPD symptomatology, exacerbations, exacerbation-related cost, survey data

Context: Psychological comorbidities are prevalent in coal miners with chronic obstructive pulmonary disease (COPD) and contribute to the severity of the disease reducing their health status. Yoga has been shown to alleviate depression and anxiety associated with other chronic diseases but in COPD not been fully investigated. Aim: This study aimed to evaluate the role of yoga on health status, depression, and anxiety in coal miners with COPD. Materials and Methods: This was a randomized trial with two study arms (yoga and control), which enrolled 81 coal miners, ranging from 36 to 60 years with stage II and III stable COPD. Both groups were either on conventional treatment or combination of conventional care with yoga program for 12 weeks. Results: Data were collected through standardized questionnaires; COPD Assessment Test, Beck Depression Inventory and State and Trait Anxiety Inventory at the beginning and the end of the intervention. The yoga group showed statistically significant (P < 0.001) improvements on all scales within the group, all significantly different (P < 0.001) from changes observed in the controls. No significant prepost changes were observed in the control group (P > 0.05). Conclusion: Yoga program led to greater improvement in physical and mental health status than did conventional care. Yoga seems to be a safe, feasible, and effective treatment for patients with COPD. There is a need to conduct more comprehensive, high-quality, evidence-based studies to shed light on the current understanding of the efficacy of yoga in these chronic conditions and identify unanswered questions.

Chronic obstructive pulmonary disease (COPD) is associated with multiple comorbidities, including depression, which carries a higher risk of exacerbation and hospitalization in patients with stable COPD. A newly developed questionnaire, the COPD Assessment Test (CAT), was developed as an alternative to other complex, time-consuming tools for quantifying the symptom burden of COPD in routine practice. It is possible that the correlation between the CAT and depression scales could be useful for early evaluation and management of depression in COPD patients. Thus, we investigated the relationship between the CAT and depression as measured by the Patient Health Questionnaires-9 (PHQ-9). We performed a retrospective observational COPD cohort study. A total of 97 patients were enrolled. The Korean versions of the CAT and PHQ-9 were completed for stable patients. A correlation analysis was performed between the PHQ-9 and CAT scores. Significant depression among the groups based on the 2011 GOLD guidelines occurred only in class Gold B and D patients (40% and 60%, respectively). The frequency of depression was significantly higher in the group with higher CAT scores (20~29 versus ≥30; odds ratio: 5.67 versus 22.66). Significant association was observed between the PHQ-9 and CAT scores (r=0.545 and P

Bioelectrical impedance analysis (BIA) provides a simple method to assess changes in body composition. Raw BIA variables such as phase angle provide direct information on cellular mass and integrity, without the assumptions inherent in estimating body compartments, e.g. fat-free mass (FFM). Phase angle is a strong functional and prognostic marker in many disease states, but data in COPD are lacking. Our aims were to describe the measurement of phase angle in patients with stable COPD and determine the construct and discriminate validity of phase angle by assessing its relationship with established markers of function, disease severity and prognosis.502 outpatients with stable COPD were studied. Phase angle and FFM by BIA, quadriceps strength (QMVC), 4-m gait speed (4MGS), 5 sit-to-stand time (5STS), incremental shuttle walk (ISW), and composite prognostic indices (ADO, iBODE) were measured. Patients were stratified into normal and low phase angle and FFM index.Phase angle correlated positively with FFM and functional outcomes (r = 0.35-0.66, p0.001) and negatively with prognostic indices (r = -0.35 to -0.48, p0.001). In regression models, phase angle was independently associated with ISW, ADO and iBODE whereas FFM was removed. One hundred and seventy patients (33.9% [95% CI, 29.9-38.1]) had a low phase angle. Phenotypic characteristics included lower QMVC, ISW, and 4MGS, higher 5STS, ADO and iBODE scores, and more exacerbations and hospital days in past year. The proportion of patients to have died was significantly higher in patients with low phase angle compared to those with normal phase angle (8.2% versus 3.6%, p = 0.02).Phase angle relates to markers of function, disease severity and prognosis in patients with COPD. As a directly measured variable, phase angle offers more useful information than fat-free mass indices.

Importance Morphine is used as palliative treatment of chronic breathlessness in patients with advanced chronic obstructive pulmonary disease (COPD). Evidence on respiratory adverse effects and health status is scarce and conflicting. Objective To assess the effects of regular, low-dose, oral sustained-release morphine on disease-specific health status (COPD Assessment Test; CAT), respiratory outcomes, and breathlessness in patients with COPD. Interventions Participants were randomly assigned to 10 mg of regular, oral sustained-release morphine or placebo twice daily for 4 weeks, with the possibility to increase to 3 times daily after 1 or 2 weeks. Design, Setting, and Participants The Morphine for Treatment of Dyspnea in Patients With COPD (MORDYC) study was a randomized, double-blind, and placebo-controlled study of a 4-week intervention. Patients were enrolled between November 1, 2016, and January 24, 2019. Participants were recruited in a pulmonary rehabilitation center and 2 general hospitals after completion of a pulmonary rehabilitation program. Outpatients with COPD and moderate to very severe chronic breathlessness (modified Medical Research Council [mMRC] breathlessness grades 2-4) despite optimal pharmacological and nonpharmacological treatment were included. A total of 1380 patients were screened, 916 were ineligible, and 340 declined to participate. Main Outcomes and Measures Primary outcomes were CAT score (higher scores represent worse health status) and arterial partial pressure of carbon dioxide (Paco2). Secondary outcome was breathlessness in the previous 24 hours (numeric rating scale). Data were analyzed by intention to treat. Subgroup analyses in participants with mMRC grades 3 to 4 were performed. Results A total of 111 of 124 included participants were analyzed (mean [SD] age, 65.4 [8.0] years; 60 men [54%]). Difference in CAT score was 2.18 points lower in the morphine group (95% CI, –4.14 to –0.22 points;P = .03). Difference in Paco2was 1.19 mm Hg higher in the morphine group (95% CI, –2.70 to 5.07 mm Hg;P = .55). Breathlessness remained unchanged. Worst breathlessness improved in participants with mMRC grades 3 to 4 (1.33 points lower in the morphine group; 95% CI, –2.50 to –0.16 points;P = .03). Five participants of 54 in the morphine group (9%) and 1 participant of 57 in the placebo group (2%) withdrew because of adverse effects. No morphine-related hospital admissions or deaths occurred. Conclusions and Relevance In this randomized clinical trial, regular, low-dose, oral sustained-release morphine for 4 weeks improved disease-specific health status in patients with COPD without affecting Paco2or causing serious adverse effects. The worst breathlessness improved in participants with mMRC grades 3 to 4. A larger randomized clinical trial with longer follow-up in patients with mMRC grades 3 to 4 is warranted. Trial Registration ClinicalTrials.gov Identifier:NCT02429050

Background The COPD Assessment Test (CAT) contains eight items (cough, phlegm, chest tightness, breathlessness, limited activities, confidence leaving home, sleeplessness and energy). The current study aimed 1) to better understand the impact of the respiratory and non-respiratory CAT item scores on the CAT total score; and 2) to determine the impact of pulmonary rehabilitation (PR) on CAT items and CAT total score. Methods CAT total score of ≥10 or ≥ 18 points was used to classify patients as highly symptomatic, a decrease of 2 points was considered as clinically relevant improvement. ‘Cough’, ‘phlegm’, ‘chest tightness’, ‘breathlessness’ were defined as respiratory items; ≥3 points on each item was defined as highly symptomatic. Results In total, 497 clinically stable patients (55% male, age 64.0 (57.5–71.0) years, FEV1 46.0 (32.0–63.0)% predicted, CAT total score 22.0 (17.5–26.0) points) were included. 95% had CAT score ≥ 10 points and 75% ≥18 points. Respectively, 45% and 54% of subjects scored high on 3 or 4 of the respiratory CAT items. Following PR, 220 patients (57.7%) reported an improved health status as assessed by CAT total score (− 3.0 (− 7.0–1.0) points). Change in CAT item scores ranged from 0.0 (− 1.0–0.0) to − 1.0 (− 2.0–0.0) points) with best improvements in ‘energy’ (− 1.0 (− 2.0–0.0)points). Conclusions A substantial number of patients classified as highly symptomatic did not report a high level of respiratory symptoms, indicating that non-respiratory symptoms impact on disease classification and treatment algorithm. The impact of PR on CAT item scores varied by individual item. Trial registration Netherlands National Trial Register (NTR3416). Registered 2 May 2012. Electronic supplementary material The online version of this article (10.1186/s12955-018-1034-4) contains supplementary material, which is available to authorized users.

Hideyasu Yamada,1,2 Norihito Hida,2 Nobuyuki Hizawa1 1Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; 2Department of Respiratory Medicine, Hitachinaka General Hospital, Hitachi Ltd, Hitachinaka, Ibaraki, Japan Background: A large body of evidence suggests that long-acting β2-adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) combinations induce a strong synergistic bronchodilatory effect in human isolated airways. Moreover, a recent post hoc analysis demonstrated clinical synergism between LABAs and LAMAs, which induces a synergistic improvement not only in lung function but also in dyspnea in COPD patients. Aim: The aim of this study is to examine the baseline factors related to improvement in lung function or clinical symptoms that results from the administration of LAMA or LAMA/LABA and to compare the differences in improvement in lung function or clinical symptoms between LAMA and LAMA/LABA. Methods: Among 829 patients with COPD who were treated with LAMA or LAMA/LABA in our hospital, 112 patients (aged 40–89 years) matched the criteria. Of these 112 patients, 71 received LAMA (LAMA group) and 41 received LAMA/LABA (LAMA/LABA group) as the initial treatment. Various examination results such as lung function test values, symptom change, and frequency of exacerbations were compared between the two groups. Results: Compared with the monotherapy, the combination therapy significantly improved the FEV1, inspiratory capacity (IC), and total COPD assessment test (CAT) scores. Comparing the improvement in each domain of the CAT produced by the combination therapy with that of the monotherapy, larger improvements were found for the domains of going out and sleeping. The frequency of exacerbations during the 24 weeks was significantly lower in the combination therapy group than in the LAMA monotherapy group (P=0.034). Although no relationship was found between improvement in FEV1 and any pretreatment factors in the LAMA/LABA group, the improvement in the CAT score was strongly related to the baseline CAT score, smoking index, and air trapping index (P-value

The minimal clinically important difference (MCID) quantifies when measured differences can be considered clinically relevant. This study aims to review and triangulate MCIDs of chronic obstructive pulmonary disease (COPD) health status tools.A systematic search in PubMed, EMBASE and Cochrane Library was conducted (Prospero #CRD42015023221). Study details, patient characteristics, MCID methodology and estimates were assessed and extracted by two authors. A triangulated mean was obtained for each tool's MCID, with two-thirds weighting for anchor-based and one-third for distribution-based results. This was then multiplied by a weighted factor based upon the study size and quality rating.Overall, 785 records were reviewed of which 21 studies were included for analysis. MCIDs of 12 tools were presented. General quality and risk of bias were average to good. Triangulated MCIDs for the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St. George's Respiratory Questionnaire (SGRQ) were −2.54, −0.43 and −7.43 for improvement. Too few and/or too diverse studies were present to triangulate MCIDs of other tools.Evidence for the MCID of the CAT and CCQ was strong and triangulation was valid. Currently used MCIDs in clinical practice for the SGRQ (4) and Chronic Respiratory Questionnaire (0.5) did not match the reviewed content, for which the MCIDs were much higher. Using too low MCIDs may lead to an overestimation of the interpretation of treatment effects. MCIDs for deterioration were scarce, which highlights the need for more research.

Context: Patients with chronic obstructive pulmonary disease (COPD) have a high symptom burden and reduced quality of life. There is an increasing attention on palliation for patients with COPD. Recognition of symptoms is a prerequisite for palliation. Objectives: We aim to investigate the extent to which symptoms in patients with COPD are recognized in the documentation of the health professionals, indicated in 'Doctors Symptom Recognition Rate' (DSR), 'Nurses Symptom Recognition Rate' (NSR) or 'Doctors and/or Nurses Symptom Recognition rates '(DNSR) as a team, respectively. Methods: Patients with COPD (n = 40) admitted in two respiratory units, responded within 48 h on two symptom-screening-tools that access quality of life; COPD assessment test (CAT) used for the treatment of COPD and EORTC-QLQ-C15-PAL used for palliation in patients with cancer. Patient-described symptomatology was compared to the symptoms as recognized in the documentation of doctors and/or nurses. Results: There was a significant discrepancy between the symptomatology indicated by patients with COPD on CAT and EORTC-QLQ-C15-PAL, and the degree by which it was recognized in the medical records indicated in DSR or NSR. In 30 out of 44 items DSR or NSR were < 70%. There was a significant difference between DNSR versus DSR or NSR, respectively, in 19 out of 22 items.Conclusion: A team-based symptom recognition DNSR is superior when compared to DSR or NSR. Team-based systematic screening is suggested as a pathway to increase symptom recognition in patients with COPD. Increased rates of symptom recognition may improve symptom alleviation and thus palliation.

Pei-Ju Chen,1 Kuang-Yao Yang,2,3 Wann-Cherng Perng,4 Kuan-Chia Lin,5,6 Kwua-Yun Wang7 1School of Nursing, National Yang-Ming University, Taipei, Taiwan, Republic of China; 2Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 3Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 4Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 5Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China; 6Communty Medicine Research Center, Preventive Medicine Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China; 7Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan, Republic ofChina Purpose: Chronic obstructive pulmonary disease (COPD) impacts health-related quality of life in men more than in women. In patients with dyspnea, frailty is more likely to develop and aggravate disability. Despite this, few studies have addressed frailty in men with COPD. The present study investigated the effects of dyspnea and its related factors on frailty in men with COPD. Patients and methods: This cross-sectional observational study selected 125 participants by voluntary sampling at the thoracic outpatient clinics of two medical centers in Taiwan. The modified Medical Research Council questionnaire was used as the basis to classify dyspnea. Data were collected using questionnaires and analyzed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corporation., Armonk, NY, USA). Results: There were 85.90% and 26.70% patients with COPD assessed in the unfit stage among the dyspnea and non-dyspnea groups, respectively. Additionally, the number of medication use and the COPD Assessment Test (CAT) scores were correlated with the period from fitness to unfitness among the dyspnea group and non-dyspnea group. Conclusion: COPD with dyspnea was more common in the unfit stages. The total number of medication use and CAT scores were significantly related to frailty. Keywords: chronic obstructive, dyspnea, frail elderly, men, pulmonary disease

Esra Ertan Yazar,1 Tevfik Özlü,2 Muzaffer Sarıaydın,3 Mahşuk Taylan,4 Aydanur Ekici,5 Derya Aydın,6 Ä°brahim Güven Coşgun,7 Nagihan Durmuş Koçak8 On behalf of the COHOV Study Group 1Department of Pulmonology, Yedikule Chest Disease and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey; 2Department of Pulmonology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey; 3Department of Pulmonology, School of Medicine, Afyon Kocatepe University, Afyon, Turkey; 4Department of Pulmonology, School of Medicine, Dicle University, Diyarbakır, Turkey; 5Department of Pulmonology, School of Medicine, Kırıkkale University, Kırıkkale, Turkey; 6Department of Pulmonology, Balıkesir Chest Disease Government Hospital, Balıkesir, Turkey; 7Department of Pulmonology, Afyonkarahisar Government Hospital, Afyonkarahisar, Turkey; 8Department of Pulmonology, Sureyyapasa Chest Disease and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey Background: Domiciliary noninvasive ventilation (NIV) use in stable hypercarbic COPD is becoming increasingly widespread. However, treatment compliance criteria and factors related to compliance remain to be defined. Methods: This research was designed as a prospective, cross-sectional, multicenter real-life study. Chronic hypercapnic COPD patients who were using domiciliary NIV for at least 1 year and being followed up in 19 centers across Turkey were included in the study. The patients who used NIV regularly, night or daytime and ≥5 hours/d, were classified as “high-compliance group,” and patients who used NIV irregularly and

BACKGROUNDPatients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5.METHODSWe performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were stratified according to blood eosinophil count (>= 150 per cubic millimeter at screening or >= 300 per cubic millimeter during the previous year). In METREO, all patients had a blood eosinophil count of at least 150 per cubic millimeter at screening or at least 300 per cubic millimeter during the previous year. The primary end point was the annual rate of moderate or severe exacerbations. Safety was also assessed.RESULTSIn METREX, the mean annual rate of moderate or severe exacerbations in the modified intention-to-treat population with an eosinophilic phenotype (462 patients) was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group (rate ratio, 0.82; 95% confidence interval [CI], 0.68 to 0.98; adjusted P = 0.04); no significant between-group differences were found in the overall modified intention-to-treat population (836 patients) (rate ratio, 0.98; 95% CI, 0.85 to 1.12; adjusted P>0.99). In METREO, the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100-mg mepolizumab group, 1.27 per year in the 300-mg mepolizumab group, and 1.49 per year in the placebo group. The rate ratios for exacerbations in the 100-mg and 300-mg mepolizumab groups versus the placebo group were 0.80 (95% CI, 0.65 to 0.98; adjusted P = 0.07) and 0.86 (95% CI, 0.70 to 1.05; adjusted P = 0.14), respectively. A greater effect of mepolizumab, as compared with placebo, on the annual rate of moderate or severe exacerbations was found among patients with higher blood eosinophil counts at screening. The safety profile of mepolizumab was similar to that of placebo.CONCLUSIONSMepolizumab at a dose of 100 mg was associated with a lower annual rate of moderate or severe exacerbations than placebo among patients with COPD and an eosinophilic phenotype. This finding suggests that eosinophilic airway inflammation contributes to COPD exacerbations.

Peter Kardos,1 Ingo Mokros,2 Rüdiger Sauer,3,4 Claus F Vogelmeier5,6 1Group Practice and Centre for Allergy, Respiratory, and Sleep Medicine, at Maingau Red Cross Hospital, Frankfurt am Main, Germany; 2AstraZeneca GmbH, Unternehmensbereich Medizin, Wedel, Germany; 3Group Practice with Respiratory, Allergy and Sleep Unite, Lung Center, Ulm, Germany; 4Health Center Clinic Blaubeuren, Blaubeuren, Germany; 5Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Marburg, Germany; 6German Center for Lung Research (DZL), Giessen, Germany Purpose: DINO and DACOTA were prospective, noninterventional studies assessing the health status and quality of life of patients with COPD newly treated with roflumilast 500 µg once-daily add-on therapy.Patients and methods: Patients were evaluated over 6 months. Clinical COPD questionnaire (CCQ) and COPD assessment test (CAT) scores were recorded at baseline and after 3 and 6 months. In DACOTA, post-bronchodilator FEV1 was recorded at each time point.Results: Of 5,462 and 3,645 patients recruited into DINO and DACOTA, respectively, 3,274 patients in DINO and 916 patients in DACOTA completed the 6-month visit. Almost all patients had severe or very severe airway obstruction; mean baseline CCQ total score was 3.9 in DINO and 3.7 in DACOTA. Overall, 33.8% of patients in DACOTA and 30.6% in DINO discontinued treatment prematurely. Significant and clinically relevant improvements in CCQ total scores were observed in both studies (mean change from baseline of 1.36 in DINO and 0.91 in DACOTA at Month 6 [all P

Yi Li,1,2 Jing Feng,3,4 Yuechuan Li,2 Wei Jia,2 Hongyu Qian2 1Graduate School, Tianjin Medical University, 2Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, 3Respiratory Department, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Neuropharmacology Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA Background: The benefit of pulmonary rehabilitation (PR) for patients with COPD diminishes over time. We investigated a new strategy involving home-visit and phone contact and compared this to usual care in maintenance of PR benefits.Methods: A total of 172 stable COPD patients receiving 8-week PR program were recruited for this prospective study. Patients were allocated into usual care group (UC) and PR maintenance group (PRMG) randomly. Patients in PRMG participated in maintenance strategy at home under supervision through home-visit and phone contact. The 6-minute walking test (6MWT), COPD assessment test (CAT), and modified Medical Research Council scale (mMRC) scores were evaluated every 3 months.Results: Of the total, 151 patients completed 8-week PR program with satisfactory PR results (p

Background Chronic obstructive pulmonary disease (COPD) is a global public health problem. It is the third-leading cause of death in the world, the fourth leading cause of death in Kazakhstan, and is strongly associated with smoking. Smoking cessation reduces the severity of respiratory symptoms and COPD exacerbations. Heated tobacco products, such as HeatSticks heated by the iQOS device, a smoke-free electronic device, may serve as less risky alternatives to conventional combustible cigarettes. Objective The purpose of this study is to evaluate frequency of exacerbations, respiratory symptoms, physical exercise intolerance, and abnormal lung functions, as well as other parameters and comorbidities among men and women aged 40-59 residing in Almaty, Kazakhstan, who use iQOS with HeatSticks compared to smokers of conventional cigarettes. Methods This is a 5-year single-center cohort observational study. It includes two cohorts of participants consisting of men and women aged 40-59 residing in the city of Almaty, Kazakhstan: (1) smokers of combustible cigarettes (control group) and (2) users of iQOS with HeatSticks (exposure group). The study has baseline and periodic (ie, annual) comprehensive clinical assessments, as well as continuous COPD case-finding activities and registration of acute respiratory exacerbations over the course of the 5-year observation period. Study measures include spirometry, chest computed tomography, electrocardiography, physical exams, laboratory testing of serum for biomarkers of inflammation and metabolic syndrome, anthropometry, and the 6-minute walk test. Information about COPD symptoms will be collected using the COPD Assessment Test. Results Participant recruitment began December 2017, and enrollment is expected to last until late summer 2018. Conclusions This is the first cohort observational study in Kazakhstan to assess differences in lung function between users of the heated tobacco product, iQOS with HeatSticks, and smokers of conventional combustible cigarettes. The study results will add to knowledge on whether switching from combustible cigarettes to iQOS with HeatSticks affects respiratory symptoms and diseases, including the development and progression of COPD. Trial registration ClinicalTrials.gov NCT03383601; https://clinicaltrials.gov/ct2/show/NCT03383601 (Archived by WebCite at http://www.webcitation.org/72BYoAKxa). International registered report identifier (irrid) PRR1-10.2196/10006.

Heidi B Bringsvor,1,2 Knut Skaug,1 Eva Langeland,3 Bjørg Frøysland Oftedal,2 Jörg Assmus,4 Doris Gundersen,1 Richard H Osborne,5 Signe Berit Bentsen2 1Department of Research and Innovation, Helse Fonna HF, Haugesund, 2Department of Quality and Health Technology, University of Stavanger, Stavanger, 3Department of Nursing, Western Norway University of Applied Sciences, 4Center for Clinical Research, Haukeland University Hospital, Bergen, Norway; 5Health Systems Improvement Unit, School of Health and Social Development, Centre For Population Health Research, Deakin University, Burwood, Victoria, Australia Purpose: Self-management is crucial for effective COPD management. This study aimed at identifying associations between self-management and sociodemographic characteristics, clinical characteristics, and symptom burden in people with COPD. Patients and methods: In this cross-sectional study with 225 participants diagnosed with COPD grades II–IV, multiple linear regression analysis was conducted, using sociodemographic and clinical characteristics and symptom burden (COPD Assessment Test) as the independent variables and the eight self-management domains of the Health Education Impact Questionnaire (heiQ) as the outcome variables. Results: Higher symptom burden was significantly associated with worse scores in all self-management domains (p

Nurdan Kokturk,1 Mehmet Polatli,2 I Kivilcim Oguzulgen,1 Sarfraz Saleemi,3 Mohammed Al Ghobain,4 Javed Khan,5 Adam Doble,6 Luqman Tariq,7 Fayaz Aziz,7 Abdelkader El Hasnaoui7 1Department of Pulmonary Medicine, School of Medicine, Gazi University, Besevler, Turkey; 2Department of Pulmonary Medicine, School of Medicine, Adnan Menderes University, Aydin, Turkey; 3Section of Pulmonary Medicine, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 4Department of Medicine, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 5Department of Medicine, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 6Foxymed, Paris, France; 7GlaxoSmithKline, Dubai, UAE Background: COPD affects millions of people worldwide. Poor treatment adherence contributes to increased symptom severity, morbidity and mortality. This study was designed to investigate adherence to COPD treatment in Turkey and Saudi Arabia. Methods: An observational, cross-sectional study in adult COPD patients in Turkey and Saudi Arabia. Through physician-led interviews, data were collected on sociodemographics and disease history, including the impact of COPD on health status using the COPD Assessment Test (CAT); quality of life, using the EuroQol Five-Dimension questionnaire (EQ-5D); and anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). Treatment adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS-8). Multivariate logistic regression analysis examined the predictors of non-adherence and the impact of adherence on symptom severity. Results: Four hundred and five COPD patients participated: 199 in Turkey and 206 in Saudi Arabia. Overall, 49.2% reported low adherence (MMAS-8 15) compared to 58.4% reporting medium/high adherence (p=0.0008). Patients with low adherence reported a lower mean 3-level EQ-5D utility value (0.54±0.35) compared to those with medium/high adherence (0.64±0.30; p10 was associated with lower adherence (OR 2.50 [95% CI: 1.43–4.39] and 2.43 [95% CI: 1.39–4.25], respectively; p=0.0008). Being a high school/college graduate was associated with better adherence compared with no high school (OR 0.57 [95% CI: 0.33–0.98] and 0.38 [95% CI: 0.15–1.00], respectively; p=0.0310). After adjusting for age, gender, and country, a significant association between treatment adherence (MMAS-8 score ≥6) and lower disease impact (CAT ≤15) was observed (OR 0.56 [95% CI: 0.33–0.95]; p=0.0314). Conclusion: Adherence to COPD treatment is poor in Turkey and Saudi Arabia. Non-adherence to treatment is associated with higher disease impact and reduced quality of life. Depression, age, and level of education were independent determinants of adherence. Keywords: COPD, non-adherence, 8-item Morisky Medication Adherence Scale, MMAS-8, EuroQol Five-Dimension questionnaire, EQ-5D, COPD Assessment Test, CAT, Turkey, Saudi Arabia