Obstructive Lung Disease Study Research Articles

Bayesian simultaneous factorization and prediction using multi-omic data

Integrative factorization methods for multi-omic data estimate factors explaining biological variation. Factors can be treated as covariates to predict an outcome and the factorization can be used to impute missing values. However, no available methods provide a comprehensive framework for statistical inference and uncertainty quantification for these tasks. A novel framework, Bayesian Simultaneous Factorization (BSF), is proposed to decompose multi-omics variation into joint and individual structures simultaneously within a probabilistic framework. BSF uses conjugate normal priors and the posterior mode of this model can be estimated by solving a structured nuclear norm-penalized objective that also achieves rank selection and motivates the choice of hyperparameters. BSF is then extended to simultaneously predict a continuous or binary phenotype while estimating latent factors, termed Bayesian Simultaneous Factorization and Prediction (BSFP). BSF and BSFP accommodate concurrent imputation, i.e., imputation during the model-fitting process, and full posterior inference for missing data, including “blockwise” missingness. It is shown via simulation that BSFP is competitive in recovering latent variation structure, and demonstrate the importance of accounting for uncertainty in the estimated factorization within the predictive model. The imputation performance of BSF is examined via simulation under missing-at-random and missing-not-at-random assumptions. Finally, BSFP is used to predict lung function based on the bronchoalveolar lavage metabolome and proteome from a study of HIV-associated obstructive lung disease, revealing multi-omic patterns related to lung function decline and a cluster of patients with obstructive lung disease driven by shared metabolomic and proteomic abundance patterns.

CT trachea surface roughness is associated with chronic obstructive pulmonary disease symptoms

Abstract Background Trachea structural abnormalities occur in patients with chronic obstructive pulmonary disease (COPD), yet there are few methods for quantifying trachea surface topology. Purpose To develop a method to quantify trachea surface roughness on CT imaging and investigate the association with airflow limitation and symptoms in COPD. Materials and Methods Participants from the multicenter prospective Canadian Cohort Obstructive Lung Disease study between 2009 and 2015 underwent CT imaging and analysis. Established CT measurements included: tracheal index (TI), defined as the smallest ratio of coronal-to-sagittal trachea diameter, low attenuation areas below –950 HU, and wall thickness of a theoretical 10-mm airway. Trachea surface roughness shape (SRS) was calculated as the percent fraction of the measurement box filled by the surface mesh. Multivariable regression models were used to determine association for CT measurements with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and Medical Research Council dyspnea scale (MRC)≥3, adjusting for covariates. Results A total of 1253 participants (mean age, 66 ± 10 years; 727 men) from 9 centers were investigated: n = 267 never smokers, n = 369 ever smokers, n = 352 mild COPD, and n = 265 moderate-to-severe COPD. There were no differences between groups for age or race (P < .05). In models including SRS and TI, a 1-standard deviation (SD) increase in SRS was independently associated with a 0.11-SD decrease in FEV1 (β = –0.11; P < .001) and a 0.16-SD decrease in FEV1/FVC (β = –0.16; P < .001); a 1-point increase in SRS was associated with a 13% increased likelihood of MRC ≥ 3 (odds ratio = 1.13; P = .003). In models including SRS, low attenuation areas below –950 HU and wall thickness of a theoretical 10-mm airway, a 1-SD increase in SRS was associated with a 0.21-SD decrease in FEV1 (β = –0.21; P < .001) and a 0.13-SD decrease in FEV1/FVC (β = –0.13; P < .001); a 1-point increase in SRS was associated with a 12% increased likelihood of MRC ≥ 3 (odds ratio = 1.12; P = .006). Conclusion Increased trachea surface shape roughness is independently associated with worse airflow and increased symptom burden in COPD.

Abnormal Exertional Breathlessness on Cardiopulmonary Cycle Exercise Testing in Relation to Self-Reported and Physiological Responses in Chronic Airflow Limitation

Exertional breathlessness is a cardinal symptom of cardiorespiratory disease. How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiological responses in people with chronic airflow limitation (CAL)? An analysis was done of people aged≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output (W), rate of oxygen uptake (V˙o2), and minute ventilation (V˙e) at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated. We included 330 participants (44%women): mean ± SD age, 64 ± 10 years (range, 40-89 years); FEV1/FVC, 57.3%± 8.2%; FEV1, 75.6%± 17.9%predicted. Abnormally low exercise capacity (peak V˙o2< lower limit of normal) was present in 26%. Relative to peak W, V˙o2, and V˙e, abnormally high breathlessness was present in 26%, 25%, and 18%of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiological abnormalities during CPET. Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness.

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study

Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Wellcome Trust.

COPD in Never-Smokers: BOLD Australia Study.

Tobacco smoking is the major risk factor for COPD, and it is common for other risk factors in never-smokers to be overlooked. We examined the prevalence of COPD among never-smokers in Australia and identified associated risk factors. We used data from the Australia Burden of Obstructive Lung Disease (BOLD) study, a cross-section of people aged ≥40 years from six sites. Participants completed interviews and post-bronchodilator spirometry. COPD was primarily defined as an FEV1/FVC ratio <0.70 and secondarily as the ratio less than the lower limit of normal (LLN). The prevalence of COPD in the 1656 never-smokers who completed the study was 10.5% (95% CI: 9.1-12.1%) [ratio<LLN 4.6%]. The likelihood of having COPD increased with advancing age [odds ratio (OR) 4.11 in those 60-69 years and OR 8.73 in those 70 years and older], having attained up to 12 years of education (OR 1.75) compared to those with more than 12 years, having a history of asthma (OR 2.30), childhood hospitalization due to breathing problems before age 10 years (OR 2.50), or having a family history of respiratory diseases (OR 2.70). Being overweight or obese was associated with reduced prevalence of COPD compared with being normal weight. In males and females, advanced age, a history of asthma, and childhood breathing problems before age 10 were factors that elevated the likelihood of COPD. However, in males, additional factors such as a higher body mass index and a family history of respiratory diseases also contributed to increased odds of COPD. COPD was prevalent in this population of never-smokers aged 40 years and over. This finding highlights the significance of risk factors other than smoking in the development of COPD.

Which breathlessness dimensions associate most strongly with fatigue?-The population-based VASCOL study of elderly men.

Breathlessness and fatigue are common symptoms in older people. We aimed to evaluate how different breathlessness dimensions (overall intensity, unpleasantness, sensory descriptors, emotional responses) were associated with fatigue in elderly men. This was a cross-sectional analysis of the population-based VAScular disease and Chronic Obstructive Lung Disease (VASCOL) study of 73-year old men. Breathlessness dimensions were assessed using the Dyspnoea-12 (D-12), Multidimensional Dyspnoea Profile (MDP), and the modified Medical Research Council (mMRC) scale. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Clinically relevant fatigue was defined as FACIT-F≤ 30 units. Scores were compared standardized as z-scores and analysed using linear regression, adjusted for body mass index, smoking, depression, cancer, sleep apnoea, prior cardiac surgery, respiratory and cardiovascular disease. Of 677 participants, 11.7% had clinically relevant fatigue. Higher breathlessness scores were associated with having worse fatigue; for D-12 total, -0.35 ([95% CI] -0.41 to -0.30) and for MDP A1, -0.24 (-0.30 to -0.18). Associations were similar across all the evaluated breathlessness dimensions even when adjusting for the potential confounders. Breathlessness assessed using D-12 and MDP was associated with worse fatigue in elderly men, similarly across different breathlessness dimensions.

A fully automated pipeline for the extraction of pectoralis muscle area from chest computed tomography scans.

Computed tomography (CT)-derived pectoralis muscle area (PMA) measurements are prognostic in people with or at-risk of COPD, but fully automated PMA extraction has yet to be developed. Our objective was to develop and validate a PMA extraction pipeline that can automatically: 1) identify the aortic arch slice; and 2) perform pectoralis segmentation at that slice. CT images from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study were used for pipeline development. Aorta atlases were used to automatically identify the slice containing the aortic arch by group-based registration. A deep learning model was trained to segment the PMA. The pipeline was evaluated in comparison to manual segmentation. An external dataset was used to evaluate generalisability. Model performance was assessed using the Dice-Sorensen coefficient (DSC) and PMA error. In total 90 participants were used for training (age 67.0±9.9 years; forced expiratory volume in 1 s (FEV1) 93±21% predicted; FEV1/forced vital capacity (FVC) 0.69±0.10; 47 men), and 32 for external testing (age 68.6±7.4 years; FEV1 65±17% predicted; FEV1/FVC 0.50±0.09; 16 men). Compared with manual segmentation, the deep learning model achieved a DSC of 0.94±0.02, 0.94±0.01 and 0.90±0.04 on the true aortic arch slice in the train, validation and external test sets, respectively. Automated aortic arch slice detection obtained distance errors of 1.2±1.3 mm and 1.6±1.5 mm on the train and test data, respectively. Fully automated PMA measurements were not different from manual segmentation (p>0.05). PMA measurements were different between people with and without COPD (p=0.01) and correlated with FEV1 % predicted (p<0.05). A fully automated CT PMA extraction pipeline was developed and validated for use in research and clinical practice.

Isolated small airways obstruction predicts future chronic airflow obstruction: a multinational longitudinal study

BackgroundChronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life.MethodsWe used longitudinal...

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study.

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study.

Dysanapsis is not associated with exertional dyspnoea in healthy male and female never-smokers aged 40 years and older.

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n=100 healthy never-smokers aged≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p<0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609±0.070vs. 0.674±0.082; p<0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p<0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r<0.34; all p>0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea.

Normative Reference Equations for Breathlessness Intensity during Incremental Cardiopulmonary Cycle Exercise Testing.

Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, the interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0-10 category ratio) response in men and women aged ⩾40 years during CPET, in relation to power output (watts), oxygen uptake, and minute ventilation. Methods: Analysis of ostensibly healthy people aged ⩾40 years undergoing symptom-limited incremental cycle CPET (10 W/min) in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study. Participants had smoking histories <5 pack-years and normal lung function and exercise capacity. The probability of each Borg 0-10 category ratio breathlessness intensity rating by power output, oxygen uptake, and minute ventilation (as an absolute or a relative value [percentage of predicted maximum]) was predicted using ordinal multinomial logistic regression. Model performance was evaluated by fit, calibration, and discrimination (C statistic) and externally validated in an independent sample (n = 86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; the mean age was 65 (range, 42-91) years, and the mean body mass index was 26.3 (standard deviation, 3.8) kg/m2. Reference equations were developed for women and men separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (C statistic for men = 0.81-0.92, C statistic for women = 0.81-0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings among individuals or groups and to identify and quantify abnormal breathlessness responses (scores greater than the upper limit of normal) during CPET.

Effectiveness of the integration of a palliative care team in the follow-up of patients with advanced chronic obstructive pulmonary disease: The home obstructive lung disease study

BackgroundAccess to palliative care for patients with end-stage chronic obstructive pulmonary disease (COPD) is still very poor. ObjectivesEvaluate our palliative care program for patients with advanced COPD by assessing whether the referral criteria for advanced COPD patients were adequate in identifying patients in end-of-life care and determine the results of the palliative care team's intervention MethodsThis was a prospective observational study of patients admitted to a multidisciplinary unit for advanced COPD. Data on sociodemographic variables, survival, symptomatology, quality of life, ACP, and health resource utilization were analyzed. ResultsEighty-three patients were included in this study. By the end of the follow-up period, 69 (83%) patients had died, mainly due to respiratory failure (96%). The median duration of survival from the start of follow-up was 4.27 months (95% confidence interval, 1.97–16.07). Most patients (94%) had a dyspnea level of 4. Sixty (72%) patients required opioids for dyspnea control. There were no significant differences in the quality of life of the patients during follow-up. Thirty (43%) patients died at home, 26 (38%) in a palliative care unit, and 13 (19%) in an acute care hospital. ACP was performed for 50 (72%) patients. Forty (57%) patients required palliative sedation during follow-up. Dyspnea was the reason for sedation in 34 (85%) patients. Hospital admissions and emergency room visits decreased significantly (p = 0.01) during follow-up. ConclusionsOur integrated model allows for adequate selection of patients, facilitates symptom control and ACP, reduces resource utilization, and favors death at home.

The modified Borg/6-min walk distance ratio: a method to assess exertional breathlessness and leg discomfort using the 6-min walk test.

The 6-min walk test (6MWT) is widely used to assess exercise capacity across chronic health conditions, but is currently not useful to assess symptoms, as the scores do not account for the 6-min walk distance (6MWD). We aimed to 1) develop normative reference equations for breathlessness and leg discomfort intensity expressed as modified Borg (mBorg)/6MWD ratios; and 2) validate the equations in people with COPD. Analysis of people aged ≥40 years who performed two 6MWTs (on a 20-m course) in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study: a healthy cohort (n=291; mean±sd age 67.5±9.4 years; 54% male) with normal 6MWD and lung function, and a COPD cohort (n=156; age 66.2±9.0 years; 56% male; forced expiratory volume in 1 s (FEV1)/forced vital capacity 56.6±8.2%; FEV1 74.4±18.6% pred). The mBorg score was calculated as the Borg 0-10 category ratio intensity rating of breathlessness or leg discomfort recorded at the end of the 6MWT +1 (range 1-11), to avoid zeros and yield ratios proportional to the symptom score and 6MWD-1. Using data from the healthy cohort, sex-specific normative reference equations for breathlessness and leg discomfort mBorg/6MWD ratios were developed using multivariable linear regression, accounting for age, and body mass or body mass index. In the COPD cohort, abnormal breathlessness and leg discomfort (mBorg/6MWD>upper limit of normal) showed strong concurrent validity with worse airflow limitation, Medical Research Council breathlessness and COPD Assessment Test scores. Normative references for the mBorg/6MWD ratio are presented to assess breathlessness and leg discomfort responses to the 6MWT in COPD.

The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study

BackgroundSpirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.MethodsUsing data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN).ResultsAlmost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease.ConclusionSpirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.

Reference values for six-minute walk distance and six-minute walk work in Caucasian adults

RationaleThe six-minute walk test (6MWT) is a practical and simple field-based test to assess physical capacity. Several reference equations for six-minute walking distance (6MWD, m) exist, but have a number of limitations that decrease their clinical utility. In addition, no reference equations exist for the 6MWT-derived outcome six-minute walk work (6MWORK, kg.m). ObjectivesTo establish new reference equations for 6MWD and 6MWORK on a 20 m course using data from the population-based Canadian Cohort Obstructive Lung Disease study. Methods and MeasurementsA total of 335 participants without obstructive or restrictive pulmonary function, with normal self-reported health status, normal exercise capacity, and <30 pack years cigarette smoking history were selected to create a representative sample of Canadian adults aged ≥40 years. All participants performed two 6MWTs. Reference equations were derived using multiple regression analyses. Main ResultsOn average, 6MWD and 6MWORK were 541±98 m and 41.3 ± 11.2 kg.m, respectively. All outcomes were significantly greater in males than females. Sex-specific reference equations were derived from the results of 6MWD and 6MWORK with an explained variance of 24 to 35%. ConclusionsThis study established reference equations for 6MWD and 6MWORK on a 20 m course in Caucasian males and females aged ≥40 years with normal pulmonary function, self-reported health status and exercise capacity. These newly derived reference equations add value to the assessment of functional capacity in clinical practice.

Quantitative CT Lung Imaging and Machine Learning Improves Prediction of Emergency Room Visits and Hospitalizations in COPD.

Predicting increased risk of future healthcare utilization in chronic obstructive pulmonary disease (COPD) patients is an important goal for improving patient management. Our objective was to determine the importance of computed tomography (CT) lung imaging measurements relative to other demographic and clinical measurements for predicting future health services use with machine learning in COPD. In this retrospective study, lung function measurements and chest CT images were acquired from Canadian Cohort of Obstructive Lung Disease study participants from 2010 to 2017 (https://clinicaltrials.gov, NCT00920348). Up to two follow-up visits (1.5- and 3-year follow-up) were performed and participants were asked for details related to healthcare utilization. Healthcare utilization was defined as any COPD hospitalization or emergency room visit due to respiratory problems in the 12 months prior to the follow-up visits. CT analysis was performed (VIDA Diagnostics Inc.); a total of 108 CT quantitative emphysema, airway and vascular measurements were investigated. A hybrid feature selection method with support vector machine classifier was used to predict healthcare utilization. Performance was determined using accuracy, F1-measure and area under the receiver operating characteristic curve (AUC) and Matthews's correlation coefficient (MC). Of the 527 COPD participants evaluated, 179 (35%) used healthcare services at follow-up. There were no significant differences between the participants with or without healthcare utilization at follow-up for age (p=0.50), sex (p=0.44), BMI (p=0.05) or pack-years (p=0.76). The accuracy for predicting subsequent healthcare utilization was 80% ± 3% (F1-measure=74%, AUC=0.80, MC=0.6) when all measurements were considered, 76% ± 6% (F1-measure=72%, AUC=0.77, MC=0.55) for CT measurements alone and 65% ± 5% (F1-measure=60%, AUC=0.67, MC=0.34) for demographic and lung function measurements alone. The combination of CT lung imaging and conventional measurements leads to greater prediction accuracy of subsequent health services use than conventional measurements alone, and may provide needed prognostic information for patients suffering from COPD.

Associations in Perceived Health and Persistent Breathlessness: A Cross-Sectional Study.

Persistent breathlessness is debilitating and increases in prevalence with advanced age and at end of life. This study aimed to evaluate any relationship between self-reported global impressions of change (GIC) in perceived health and breathlessness in older men. Cross-sectional study of 73-year-old Swedish men in the VAScular and Chronic Obstructive Lung disease study. A postal survey included items on perceived changes in health and breathlessness (GIC scales) and breathlessness (assessed using the modified Medical Research Council [mMRC] breathlessness scale, Dyspnea-12 and Multidimensional Dyspnea Scale) since age 65. Of 801 respondents, breathlessness (mMRC ≥2) was reported by 17.9%, worsening breathlessness by 29.1%, and worsening perceived health by 51.3%. Worsening breathlessness was strongly correlated with worsening perceived health (Pearson's correlation coefficient of 0.68 [p < 0.001] and Kendall's τ of 0.56 [p < 0.001]) and associated with more limited function (47.2% vs. 29.7%; p < 0.0001) and increased rates of anxiety/depression. The strong correlation between perceived changes in health and persistent breathlessness helps delineate a more comprehensive picture of the challenges faced by older adults living with this disabling symptom.

Factors Associated with Attrition in a Longitudinal Cohort of Older Adults in the Community.

Retaining participants in longitudinal studies increases their power. We undertook this study in a population-based longitudinal cohort of adults with COPD to determine the factors associated with increased cohort attrition. In the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, 1561 adults > 40 years old were randomly recruited from 9 urban sites. Participants completed in-person visits at 18-month intervals and also were followed up every 3 months over the phone or by email. The cohort retention for the study and the reasons for attrition were analyzed. Hazard ratios and robust standard errors were calculated using Cox regression methods to explore the associations between participants who remained in the study and those who did not. The median follow-up (years) of the study is 9.0 years. The overall mean retention was 77%. Reasons for attrition (23%) were: dropout by participant (39%), loss of contact (27%), investigator-initiated withdrawal (15%), deaths (9%), serious disease (9%), and relocation (2%). Factors independently associated with attrition were lower educational attainment, higher pack-year tobacco consumption, diagnosed cardiovascular disease, and a higher Hospital Anxiety and Depression Scale score: adjusted hazard ratios (95% confidence interval) were 1.43(1.11, 1.85); 1.01(1.00, 1.01); 1.44(1.13, 1.83); 1.06(1.02, 1.10) respectively. Identification and awareness of risk factors for attrition could direct targeted retention strategies in longitudinal studies. Moreover, the identification of patient characteristics associated with study dropout could address any potential bias introduced by differential dropouts.

Physical Activity and Symptom Burden in COPD: The Canadian Obstructive Lung Disease Study.

The relationship between symptom burden and physical activity (PA) in chronic obstructive pulmonary disease (COPD) remains poorly understood with limited data on undiagnosed individuals and those with mild to moderate disease. The primary objective was to evaluate the relationship between symptom burden and moderate-to-vigorous intensity PA (MVPA) in individuals from a random population-based sampling mirroring the population at large. Baseline participants of the Canadian Cohort Obstructive Lung Disease (n=1558) were selected for this cross-sectional sub-study. Participants with mild COPD (n=406) and moderate COPD (n=331), healthy individuals (n=347), and those at risk of developing COPD (n=474) were included. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to estimate MVPA in terms of energy expenditure. High symptom burden was classified using the COPD Assessment Test ([CAT] ≥10). Significant associations were demonstrated between high symptom burden and lower MVPA levels in the overall COPD sample (β=-717.09; 95% confidence interval [CI]=-1079.78, -354.40; p<0.001) and in the moderate COPD subgroup (β=-694.1; 95% CI=-1206.54, -181.66; p=0.006). A total of 72% of the participants with COPD were previously undiagnosed. The undiagnosed participants had significantly higher MVPA than those with physician diagnosed COPD (β=-592.41 95% CI=-953.11, -231.71; p=0.001). MVPA was found to be inversely related to symptom burden in a large general population sample that included newly diagnosed individuals, most with mild to moderate COPD. Assessment of symptom burden may help identify patients with lower MVPA, especially for moderate COPD and for relatively inactive individuals with mild COPD.

Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study

Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters. The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 μg salbutamol) and post-bronchodilator (ie, after administration of 200 μg salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis. 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction. Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline. National Heart and Lung Institute and Wellcome Trust. For the Dutch, Estonian, French, Icelandic, Malay, Marathi, Norwegian, Portuguese, Swedish and Urdu translations of the abstract see Supplementary Materials section.