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Dyspnoea and symptom burden in mild–moderate COPD: the Canadian Cohort Obstructive Lung Disease Study

Mathew Cherian, Dennis Jensen, Wan C. Tan, Sara Mursleen, Emma C. Goodall, Gilbert A. Nadeau, Amnah M. Awan, Darcy D. Marciniuk, Brandie L. Walker, Shawn D. Aaron, Denis E. O'Donnell, Kenneth R. Chapman, François Maltais, Paul Hernandez, Don D. Sin, Andrea Benedetti, Jean Bourbeau
ERJ Open Research 2021 7: 00960-2020; DOI: 10.1183/23120541.00960-2020
Mathew Cherian
1Division of Respiratory Medicine, Dept of Medicine, McGill University Health Centre, Montreal, QC, Canada
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Dennis Jensen
2Clinical Exercise and Respiratory Physiology Laboratory, Dept of Kinesiology and Physical Education, Faculty of Education, McGill University, Montréal, QC, Canada
3Research Institute of the McGill University Health Centre, Translational Research in Respiratory Diseases Program and Respiratory Epidemiology and Clinical Research Unit, Montréal, QC, Canada
4Research Centre for Physical Activity and Health, Faculty of Education, McGill University, Montréal, QC, Canada
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Wan C. Tan
5Centre for Heart Lung Innovation, Dept of Medicine, University of British Columbia, Vancouver, BC, Canada
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Sara Mursleen
6GSK, Mississauga, ON, Canada
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Emma C. Goodall
6GSK, Mississauga, ON, Canada
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Gilbert A. Nadeau
6GSK, Mississauga, ON, Canada
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Amnah M. Awan
6GSK, Mississauga, ON, Canada
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Darcy D. Marciniuk
7Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, Canada
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Brandie L. Walker
8Division of Respirology, Dept of Medicine, University of Calgary, Calgary, AB, Canada
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Shawn D. Aaron
9The Ottawa Hospital Research Institute, Ottawa, ON, Canada
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Denis E. O'Donnell
10Dept of Medicine/Physiology, Queens University, Kingston, ON, Canada
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Kenneth R. Chapman
11Asthma and Airway Centre, University Health Network and University of Toronto, Toronto, ON, Canada
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François Maltais
12Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC, Canada
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Paul Hernandez
13Faculty of Medicine, Division of Respirology, Dalhousie University, Halifax, NS, Canada
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Don D. Sin
5Centre for Heart Lung Innovation, Dept of Medicine, University of British Columbia, Vancouver, BC, Canada
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Andrea Benedetti
14Depts of Medicine and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
15Respiratory Epidemiology and Clinical Research Unit, McGill University, Montreal, QC, Canada
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Jean Bourbeau
1Division of Respiratory Medicine, Dept of Medicine, McGill University Health Centre, Montreal, QC, Canada
3Research Institute of the McGill University Health Centre, Translational Research in Respiratory Diseases Program and Respiratory Epidemiology and Clinical Research Unit, Montréal, QC, Canada
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  • For correspondence: jean.bourbeau@mcgill.ca
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  • FIGURE 1
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    FIGURE 1

    Study design and subgroups analysed. #: Current or former smokers were defined as smoking >20 packs in a lifetime, or >1 cigarette·day−1 for ≥1 year. Exacerbation history was limited to the 12 months before Visit 3. The analysis of these data only included people for whom there was Visit 3-specific data. COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s; GOLD: Global Initiative for Chronic Obstructive Lung Disease.

  • FIGURE 2
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    FIGURE 2

    Prevalence and severity of dyspnoea (Medical Research Council (MRC)) (a), and health-related quality of life (COPD Assessment Test (CAT) total score (b); SGRQ total score (c) at baseline. Error bars represent quartiles 1 and 3. Values above the bars in panel (a) represent the mean±sd MRC dyspnoea scores for each group. CAT: COPD Assessment Test; COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; MRC: Medical Research Council; SGRQ: St George's Respiratory Questionnaire. #: significantly different from each other after Tukey adjustment for multiple comparisons (p<0.05).

  • FIGURE 3
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    FIGURE 3

    Odds ratios of dyspnoea severity for: a) MRC 2 versus MRC 1 and b) MRC ≥3 versus MRC 1. MRC was measured at baseline for comparisons by sex and physician diagnosis of COPD, and at Visit 3 for comparisons by exacerbation history. #: For analysis by exacerbation status, n were as follows: COPD: n=467; mild-COPD (GOLD 1): n=282; moderate-COPD (GOLD 2): n=185. Adjusted OR were obtained by performing multivariate multinomial logistic regression models, adjusted for sex, age, BMI, smoking history, cardiovascular comorbidities, and other respiratory comorbidities. For women versus men comparisons, sex was not included as a covariate. For smokers versus never-smokers, smoking history was not included as a covariate. To estimate the association between exacerbations and MRC, exacerbations were observed in preceding 12 months at Visit 3. BMI: body mass index; COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; MRC: Medical Research Council.

  • FIGURE 4
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    FIGURE 4

    Adjusted β of health-related quality of life for: a) CAT and b) SGRQ. CAT and SGRQ were measured at baseline for comparisons by sex and physician diagnosis of COPD, and at Visit 3 for comparisons by exacerbation history. #: For analysis by exacerbation status, n were as follows: COPD: n=467; mild-COPD (GOLD 1): n=282; moderate-COPD (GOLD 2): n=185. Adjusted β were obtained by performing multivariate linear regression models, adjusted for sex, age, BMI, smoking history, cardiovascular comorbidities and other respiratory comorbidities. For women versus men comparisons, sex was not included as a covariate. For smokers versus never-smokers, smoking history was not included as a covariate. To estimate the association between exacerbations and CAT or SGRQ, exacerbations were observed in preceding 12 months at Visit 3. BMI: body mass index; CAT: COPD Assessment Test; COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; SGRQ: St George's Respiratory Questionnaire.

  • FIGURE 5
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    FIGURE 5

    Dyspnoea severity for people with COPD by: a) sex, b) the presence of a physician diagnosis of COPD, and c) exacerbation frequency. MRC was measured at baseline for comparisons by sex and physician diagnosis of COPD, and at Visit 3 for comparisons by exacerbation history. Values above the bars represent the mean±sd MRC dyspnoea scores for each group. #: Significantly different (p<0.001). p-values were obtained by performing Chi-squared or Fisher's exact test for category variables. For continuous variables, p-values were obtained by t-test (normal distribution) or Mann–Whitney U-test (not normal distribution) for sex and physician diagnosis subgroups. ANOVA (normal distribution) or Kruskal–Wallis test (not normal distribution) were performed for exacerbation subgroups. Analysis of variance subgroup comparisons of mean±sd differences by sex, presence of a physician diagnosis of COPD, and exacerbation frequency were all significant (p<0.001). COPD: chronic obstructive pulmonary disease; MRC: Medical Research Council.

  • FIGURE 6
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    FIGURE 6

    Health-related quality of life severity for people with COPD by: a) and b) sex, c) and d) the presence of a physician diagnosis of COPD, and e) and f) exacerbation frequency. CAT and SGRQ were measured at baseline for comparisons by sex and physician diagnosis of COPD, and at Visit 3 for comparisons by exacerbation history. Error bars represent interquartile range. p-values were obtained by t-test (normal distribution) or Mann–Whitney U-test (not normal distribution) for sex and physician diagnosis subgroups. ANOVA (normal distribution) or Kruskal–Wallis test (not normal distribution) were performed for exacerbation subgroups. Analysis of variance subgroup comparisons of median (interquartile range) differences by sex, presence of a physician diagnosis of COPD, and exacerbation frequency were all significant (p<0.05). CAT: COPD Assessment Test; COPD: chronic obstructive pulmonary disease; HRQoL: health-related quality of life; SGRQ: St George's Respiratory Questionnaire.

Tables

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  • TABLE 1

    Demographics and baseline characteristics

    COPDNon-COPDp-value#COPDNon-COPDp-value¶
    Mild (GOLD 1)Moderate (GOLD 2)SmokersNever-smokers
    Subjects n659784397262449335
    Age years67.2±10.165.9±9.60.01968.0±9.8§,f65.9±10.3f65.6±9.4§66.3±9.80.008
    Male404 (61.3)412 (52.6)<0.001259 (65.2)145 (55.3)262 (58.4)150 (44.8)<0.001
    BMI27.2±4.827.8±5.20.12226.9±4.4§27.6±5.228.1±5.2§27.4±5.20.017
    Never-smokers190 (28.8)335 (42.7)<0.001132 (33.2)§58 (22.1)§0335 (100.0)<0.001
    Former smokers352 (53.4)346 (44.1)<0.001212 (53.4)§140 (53.4)f346 (77.1)§,f0<0.001
    Current smokers117 (17.8)103 (13.1)0.01553 (13.4)§,f64 (24.4)f103 (22.9)§0<0.001
    GOLD1397 (60.2)0–397 (100.0)000–
    GOLD2262 (39.8)0–0262 (100.0)00–
    Self-reported physician-diagnosed asthma202 (30.7)124 (15.8)<0.00193 (23.4)§109 (41.6)§,f76 (16.9)f48 (14.3)§<0.001
    Any respiratory medication prescription+215 (32.6)85 (10.8)<0.00181 (20.4)§,f134 (51.1)§,f54 (12.0)f31 (9.3)§<0.001
    Emphysema score1.8±3.10.5±1.3<0.0011.4±2.5§2.3±3.7§0.7±1.5§0.2±0.7§<0.001
    RV/TLC %42±9.637.5±8.2<0.00139.2±8.7f46.3±9.4§,f37.4±8.0f37.6±8.5§<0.001
    Chronic bronchitis112 (17.0)99 (12.6)0.001944 (11.1)¶¶68 (26.0)f,##,¶¶69 (15.4)##30 (9.0)f<0.001

    Data are presented as n, mean±sd or n (%), unless otherwise stated. BMI: body mass index; COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; ICS: inhaled corticosteroids; LABA: long-acting β2-agonist; LAMA: long-acting muscarinic antagonist; RV/TLC: residual volume/total lung capacity; SABA: short-acting β2-agonist; SAMA: short-acting muscarinic antagonist. #: p-values were obtained by performing Chi-squared or Fisher's exact test for category variables, and t-test (normal distribution) or Mann–Whitney U tests (non-normal distribution) for continuous variables. ¶: p-values were obtained by performing Chi-squared or Fisher's exact tests for category variables, and analysis of variance (normal distribution) or Kruskal–Wallis test (not normal distribution) for continuous variables. +: Respiratory medicines included were: SAMA/SABA; LABA±SAMA/SABA; LAMA±SAMA/SABA; LAMA+LABA±SAMA/SABA; ICS±SAMA/SABA; LABA+ICS±SAMA/SABA; LAMA+ICS±SAMA/SABA; LAMA+LABA+ICS±SAMA/SABA. §, f, ##, ¶¶: Values with the same symbol are significantly different from each other after Tukey adjustment for multiple comparisons (p<0.05). Bold indicates statistical significance.

    • TABLE 2

      Dyspnoea severity and health related quality of life by sex, COPD physician diagnosis status, and exacerbation frequency for people with mild (GOLD 1) or moderate (GOLD 2) COPD

      Subjects nMRCMRC 1MRC 2MRC ≥3CAT total scoreSGRQ total score
      Dyspnoea and HRQoL by sex
       Mild COPD (GOLD 1)397
        Men2591.3±0.5190 (73.4)63 (24.3)6 (2.3)4.0 (2.0–7.0)6.8 (2.3–12.4)
        Women1381.6±0.668 (49.3)62 (44.9)8 (5.8)5.0 (3.0–9.0)8.0 (2.7–17.1)
        p-value<0.001<0.001<0.0010.0730.0490.039
       Moderate COPD (GOLD 2)262
        Men1451.6±0.769 (47.6)61 (42.1)15 (10.3)7.0 (4.0–12.5)14.6 (5.2–28.5)
        Women1171.9±0.840 (34.2)60 (51.3)17 (14.5)9.0 (5.0–15.0)21.0 (9.3–31.4)
        p-value0.0260.0290.1370.3040.0280.023
      Dyspnoea and HRQoL by COPD diagnosis
       Mild COPD (GOLD 1)397
        Diagnosed COPD661.6±0.628 (42.4)35 (53.0)3 (4.5)7.0 (5.0–12.0)13.9 (7.1–20.0)
        Undiagnosed COPD3311.3±0.6230 (69.5)90 (27.2)11 (3.3)4.0 (2.0–7.0)6.2 (2.0–12.4)
        p-value<0.001<0.001<0.0010.712<0.001<0.001
       Moderate COPD (GOLD 2)262
        Diagnosed COPD972.0±0.827 (27.8)51 (52.6)19 (19.6)12.0 (7.0–17.0)24.9 (14.9–34.9)
        Undiagnosed COPD1651.6±0.782 (49.7)70 (42.4)13 (7.9)6.0 (3.0–10.0)11.7 (4.5–25.2)
        p-value<0.001<0.0010.1110.005<0.001<0.001
      Dyspnoea and HRQoL by exacerbation frequency#
       Mild COPD (GOLD 1)282
        02271.3±0.5163 (71.8)59 (26.0)5 (2.2)4.0 (2.0–7.0)5.1 (1.6–12.3)
        1391.6±0.823 (59.0)9 (23.1)7 (17.9)7.0 (3.0–11.0)12.6 (6.8–21.5)
        ≥2161.8±0.76 (37.5)8 (50.0)2 (12.5)8.5 (3.5–15.0)20.7 (8.4–35.6)
        Overall p-value0.0020.0070.094<0.001<0.001<0.001
       Moderate COPD (GOLD 2)185
        01281.5±0.675 (58.6)44 (34.4)9 (7.0)6.5 (3.0–11.0)11.5 (3.6–24.3)
        1351.9±0.813 (37.1)15 (42.9)7 (20.0)11.0 (6.0–17.0)24.0 (15.3–35.4)
        ≥2221.8±0.78 (36.4)11 (50.0)3 (13.6)9.5 (5.0–18.0)32.5 (12.5–42.8)
        Overall p-value<0.0110.0240.3000.0660.002<0.001

      Data are presented as n, mean±sd, median (interquartile range) or n (%), unless otherwise stated. CAT: COPD Assessment Test; COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; HRQoL: health-related quality of life; MRC: Medical Research Council; SGRQ: St George's Respiratory Questionnaire. MRC was measured at baseline for comparisons by sex and physician diagnosis of COPD, and at Visit 3 for comparisons by exacerbation history. #: Number of exacerbations in the 12 months preceding Visit 3. p-values were obtained by performing Chi-squared or Fisher's exact test for category variables, and t-test (normal distribution) or Mann Whitney U test (not normal distribution) for continuous variables. Bold indicates statistical significance.

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      Dyspnoea and symptom burden in mild–moderate COPD: the Canadian Cohort Obstructive Lung Disease Study
      Mathew Cherian, Dennis Jensen, Wan C. Tan, Sara Mursleen, Emma C. Goodall, Gilbert A. Nadeau, Amnah M. Awan, Darcy D. Marciniuk, Brandie L. Walker, Shawn D. Aaron, Denis E. O'Donnell, Kenneth R. Chapman, François Maltais, Paul Hernandez, Don D. Sin, Andrea Benedetti, Jean Bourbeau
      ERJ Open Research Apr 2021, 7 (2) 00960-2020; DOI: 10.1183/23120541.00960-2020

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      Dyspnoea and symptom burden in mild–moderate COPD: the Canadian Cohort Obstructive Lung Disease Study
      Mathew Cherian, Dennis Jensen, Wan C. Tan, Sara Mursleen, Emma C. Goodall, Gilbert A. Nadeau, Amnah M. Awan, Darcy D. Marciniuk, Brandie L. Walker, Shawn D. Aaron, Denis E. O'Donnell, Kenneth R. Chapman, François Maltais, Paul Hernandez, Don D. Sin, Andrea Benedetti, Jean Bourbeau
      ERJ Open Research Apr 2021, 7 (2) 00960-2020; DOI: 10.1183/23120541.00960-2020
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