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/m$^{2}$. 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

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

Background 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. Methods 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. Results 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. Conclusion Normative references for the mBorg/6MWD ratio are presented to assess breathlessness and leg discomfort responses to the 6MWT in COPD

Metabolic profiles among COPD and controls in the CanCOLD population-based cohort

International audienceA high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations

Bronchodilator Responsiveness and Reported Respiratory Symptoms in an Adult Population

<div><p>Background</p><p>The relationship between patient-reported symptoms and objective measures of lung function is poorly understood.</p> <p>Aim</p><p>To determine the association between responsiveness to bronchodilator and respiratory symptoms in random population samples.</p> <p>Methods</p><p>4669 people aged 40 years and older from 8 sites in Canada completed interviewer-administered respiratory questionnaires and performed spirometry before and after administration of 200 ug of inhaled salbutamol. The effect of anthropometric variables, smoking exposure and doctor-diagnosed asthma (DDA) on bronchodilator responsiveness in forced expiratory volume in 1 second (FEV₁) and in forced vital capacity (FVC) were evaluated. Multiple logistic regression was used to test for association between quintiles of increasing changes in FEV₁ and in FVC after bronchodilator and several respiratory symptoms.</p> <p>Results</p><p>Determinants of bronchodilator change in FEV₁ and FVC included age, DDA, smoking, respiratory drug use and female gender [p<0.005 to p<0.0001 ]. In subjects without doctor-diagnosed asthma or COPD, bronchodilator response in FEV₁ was associated with wheezing [p for trend<0.0001], while bronchodilator response for FVC was associated with breathlessness. [p for trend <0.0001].</p> <p>Conclusions</p><p>Bronchodilator responsiveness in FEV₁ or FVC are associated with different respiratory symptoms in the community. Both flow and volume bronchodilator responses are useful parameters which together can be predictive of both wheezing and breathlessness in the general population.</p> </div

Supplementary Material for: A Novel Method of Estimating Small Airway Disease Using Inspiratory-to-Expiratory Computed Tomography

<p><b><i>Background:</i></b> Disease accumulates in the small airways without being detected by conventional measurements. <b><i>Objectives:</i></b> To quantify small airway disease using a novel computed tomography (CT) inspiratory-to-expiratory approach called the disease probability measure (DPM) and to investigate the association with pulmonary function measurements. <b><i>Methods:</i></b> Participants from the population-based CanCOLD study were evaluated using full-inspiration/full-expiration CT and pulmonary function measurements. Full-inspiration and full-expiration CT images were registered, and each voxel was classified as emphysema, gas trapping (GasTrap) related to functional small airway disease, or normal using two classification approaches: parametric response map (PRM) and DPM (VIDA Diagnostics, Inc., Coralville, IA, USA). <b><i>Results:</i></b> The participants included never-smokers (<i>n</i> = 135), at risk (<i>n</i> = 97), Global Initiative for Chronic Obstructive Lung Disease I (GOLD I) (<i>n</i> = 140), and GOLD II chronic obstructive pulmonary disease (<i>n</i> = 96). PRM_GasTrap and DPM_GasTrap measurements were significantly elevated in GOLD II compared to never-smokers (<i>p</i> < 0.01) and at risk (<i>p</i> < 0.01), and for GOLD I compared to at risk (<i>p</i> < 0.05). Gas trapping measurements were significantly elevated in GOLD II compared to GOLD I (<i>p</i> < 0.0001) using the DPM classification only. Overall, DPM classified significantly more voxels as gas trapping than PRM (<i>p</i> < 0.0001); a spatial comparison revealed that the expiratory CT Hounsfield units (HU) for voxels classified as DPM_GasTrap but PRM_Normal (PRM_Normal- DPM_GasTrap = -785 ± 72 HU) were significantly reduced compared to voxels classified normal by both approaches (PRM_Normal-DPM_Normal = -722 ± 89 HU; <i>p</i> < 0.0001). DPM and PRM_GasTrap measurements showed similar, significantly associations with forced expiratory volume in 1 s (FEV₁) (<i>p</i> < 0.01), FEV₁/forced vital capacity (<i>p</i> < 0.0001), residual volume/total lung capacity (<i>p</i> < 0.0001), bronchodilator response (<i>p</i> < 0.0001), and dyspnea (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> CT inspiratory-to-expiratory gas trapping measurements are significantly associated with pulmonary function and symptoms. There are quantitative and spatial differences between PRM and DPM classification that need pathological investigation.</p

Impaired Sleep Quality in COPD Is Associated With Exacerbations: The CanCOLD Cohort Study.

BackgroundCOPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations.MethodsData were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18&nbsp;months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed.ResultsA total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score &gt; 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs&nbsp;5.0 [interquartile range, 2.0-7.0]; P&nbsp;= .01), and they were more likely to have baseline PSQI scores &gt; 5 (50.3%&nbsp;vs&nbsp;37.3%; P&nbsp;= .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95%&nbsp;CI, 1.01-1.18; P&nbsp;= .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95%&nbsp;CI, 1.00-1.21; P&nbsp;= .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95%&nbsp;CI, 1.09-2.03).ConclusionsHigher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18&nbsp;months' prospective follow-up

Impaired Sleep Quality in COPD Is Associated With Exacerbations: The CanCOLD Cohort Study.

BackgroundCOPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations.MethodsData were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed.ResultsA total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score &gt; 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores &gt; 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03).ConclusionsHigher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up