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Treatable traits in an English cohort: prevalence and predictors of future decline in lung function and quality of life in COPD

Muhammad Rehan Sarwar, Vanessa Marie McDonald, Michael John Abramson, Eldho Paul, Johnson George
ERJ Open Research 2021 7: 00934-2020; DOI: 10.1183/23120541.00934-2020
Muhammad Rehan Sarwar
1Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia
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Vanessa Marie McDonald
2National Health and Medical Research Council Centre for Research Excellence in Severe Asthma and Centre of Excellence in Treatable Traits, The University of Newcastle, Callaghan, Australia
3The Priority Research Centre for Healthy Lungs, School of Nursing and Midwifery, Callaghan, Australia
4Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, Australia
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Michael John Abramson
5School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
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Eldho Paul
5School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
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Johnson George
1Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia
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  • For correspondence: johnson.george@monash.edu
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  • FIGURE 1
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    FIGURE 1

    Schematic diagram explaining the flow of study participants. ELSA: English Longitudinal Study of Ageing; COPD: chronic obstructive pulmonary disease. #: of the remaining 7452 participants, 3726 were common in both waves yielding a final sample of 3726 participants with 4-year follow-up.

  • FIGURE 2
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    FIGURE 2

    Treatable traits associated with decline in lung function and quality of life (QoL).

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  • TABLE 1

    List of potential treatable traits (TTs) identified from the English Longitudinal Study of Ageing (ELSA) cohort

    TTDiagnostic criteria
    Pulmonary
     Airflow limitationFEV1/FVC <0.7
     Chronic bronchitisPhysician diagnosis/self-report#
     Chronic sputum productionSputum with coughing (≥3 months·year−1)
     BreathlessnessmMRC dyspnoea scale
     Frequent chest infectionsSelf-report
    Extra-pulmonary
     OsteoporosisPhysician diagnosis/self-report
     CVD¶Physician diagnosis/self-report
     ArthritisPhysician diagnosis/self-report
     DiabetesPhysician diagnosis/self-report
     Cancer+Physician diagnosis/self-report
     Psychiatric problems§Physician diagnosis/self-report
     DepressionCES-D scale
     UnderweightBMI <18.5 kg·m−2
     ObesityBMI ≥30 kg·m−2
     SarcopeniaHandgrip strength <27 kg (males) and <16 kg (females)
     Systemic inflammationCRP >3 mg·L−1
     AnaemiaHb <140 g·L−1 (men) or <120 g·L−1 (women)
     DisabilitySelf-reported limitations in basic ADL and IADL
    Behavioural traits/lifestyle-risk factors
     Current smokingInterview/self-report
     Physical inactivityƒInterview/self-report
     Poor family and social supportInterview/self-report

    FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; mMRC: modified Medical Research Council; CVD: cardiovascular disease; CES-D: Centre for Epidemiological Studies-Depression; BMI: body mass index; CRP: C-reactive protein; Hb: haemoglobin; ADL: activities of daily living; IADL: instrumental activities of daily living. #: self-reported by the participants; ¶: including high blood pressure (BP), angina, myocardial infarction, heart attack, high cholesterol, congestive heart failure, stroke and heart murmur or abnormal heart rhythm; +: including cancers of the lung and breast, as well as colorectal cancers, lymphoma, leukaemia and melanoma; §: including hallucinations, anxiety, emotional problems, schizophrenia, psychosis, mood swings and bipolar disorder; ƒ: no mild, moderate or vigorous activity per week.

    • TABLE 2

      Baseline socio-demographic and clinical characteristics of the cohort

      VariableCOPD (n=406)Non-COPD (n=3320)p-value
      Male gender186 (45.8)1526 (46.0)0.954
      Age years67.0 (59–73)63.0 (57–70)<0.001
      Marital status<0.001
       Single/separated/widowed153 (37.7)938 (28.3)
       Living in a relationship253 (62.3)2382 (71.7)
      Ethnicity
       White395 (97.3)3272 (98.6)0.054
      Socio-economic class<0.001
       Managerial and professional108 (26.6)1209 (36.4)
       Intermediate53 (13.1)467 (14.1)
       Small employers and own-account workers44 (10.8)388 (11.7)
       Lower supervisory and technical50 (12.3)329 (9.9)
       Semi-routine occupations144 (35.5)899 (27.1)
       Other7 (1.7)28 (0.8)
      Self-reported health<0.001
       Excellent36 (8.9)577 (17.4)
       Very good99 (24.4)1140 (34.3)
       Good144 (35.5)1071 (32.3)
       Fair93 (22.9)438 (13.2)
       Poor34 (8.4)94 (2.8)
      Physical activity<0.001
       None25 (6.2)118 (3.6)
       Mild64 (15.8)373 (11.2)
       Moderate236 (58.1)1684 (50.7)
       Vigorous81 (20.0)1145 (34.5)
      Dyspnoea<0.001
       Grade 0172 (42.4)2519 (75.9)
       Grade 1151 (37.2)549 (16.5)
       Grade 234 (8.4)90 (2.7)
       Grade 349 (12.1)162 (4.9)
      Smoking status<0.001
       Never smoker100 (24.6)1346 (40.5)
       Former smoker160 (39.4)1518 (45.7)
       Current smoker146 (36.0)456 (13.7)
      Spirometry measurements
       FEV1 L1.7 (1.1–2.3)2.5 (2.0–3.1)<0.001
       FVC L3.1 (2.3–3.8)3.2 (2.6–4.0)0.001
       PEF L·min−1286.5 (202.8–378.8)385 (307.0–493.0)<0.001
       FEV1 % pred70.2 (49.5–84.6)94.0 (83.5–104.8)<0.001
       FVC % pred92.2 (78.0–107.2)94.4 (83.6–106.0)0.056

      Data are presented as n (%) or median (IQR). p-Values in bold are statistically significant. COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; PEF: peak expiratory flow; IQR: interquartile range (25th to 75th percentile).

      • TABLE 3

        Prevalence of various treatable traits (TTs) at baseline by Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity status

        TTCOPDNon-COPD (n=3320)p-value#
        Mild (n=129)Moderate (n=172)Severe (n=74)Very severe (n=31)Overall (n=406)
        Pulmonary
         Airflow limitation129 (100)172 (100)74 (100)31 (100)406 (100)462 (13.9)<0.001
         Breathlessness61 (47.3)102 (59.3)50 (67.6)16 (51.6)229 (56.4)789 (23.8)<0.001
         Chronic bronchitis4 (3.1)26 (15.1)9 (12.2)4 (12.9)43 (10.6)49 (1.5)<0.001
         Chronic sputum  production29 (22.5)59 (34.3)22 (29.7)10 (32.2)120 (29.6)221 (6.7)<0.001
         Frequent chest infections10 (7.8)24 (14.0)10 (13.5)2 (6.5)46 (11.3)237 (7.1)0.003
        Extra-pulmonary
         Osteoporosis6 (4.7)13 (7.6)9 (12.2)2 (6.5)30 (7.4)149 (4.5)0.010
         CVD23 (17.8)43 (25)18 (24.3)8 (25.8)92 (22.7)742 (22.3)0.747
         Arthritis52 (40.3)76 (44.2)30 (40.5)10 (32.3)168 (41.4)1130 (34)0.003
         Diabetes5 (3.9)14 (8.1)6 (8.1)1 (3.2)26 (6.4)211 (6.4)0.970
         Cancer8 (6.2)15 (8.7)5 (6.8)1 (3.2)29 (7.1)225 (6.8)0.783
         Psychiatric problems11 (8.5)8 (4.7)2 (2.7)0 (0.0)21 (5.2)167 (5.0)0.902
         Depression26 (20.2)51 (29.7)19 (25.7)8 (25.8)104 (25.6)576 (17.3)<0.001
         Underweight1 (0.8)2 (1.2)1 (1.4)1 (3.2)5 (1.2)26 (0.8)0.202
         Obesity36 (27.9)45 (26.2)26 (35.1)8 (25.8)115 (28.3)912 (27.5)0.765
         Sarcopenia6 (4.7)14 (8.1)6 (8.1)2 (6.5)29 (7.1)157 (4.7)0.035
         Systemic inflammation44 (34.1)79 (45.9)35 (47.3)11 (35.5)168 (41.4)985 (29.7)<0.001
         Anaemia8 (6.2)16 (9.3)5 (6.8)2 (6.5)31 (7.6)223 (6.7)0.473
         Disability77 (59.7)131 (76.2)58 (78.4)22 (71.0)288 (70.9)1674 (50.4)<0.001
        Behavioural/lifestyle
         Current smoking33 (25.6)73 (42.4)27 (36.5)13 (41.9)146 (36.0)458 (13.8)<0.001
         Physical inactivity3 (2.3)12 (7.0)10 (13.5)0 (0.0)25 (6.2)118 (3.6)0.010
         Poor family and social  support27 (20.9)37 (21.5)14 (18.9)8 (25.8)86 (21.2)574 (17.3)0.039

        Data are presented as n (%). p-Values in bold are statistically significant. COPD: chronic obstructive pulmonary disease; CVD: cardiovascular disease. #: COPD (overall) versus non-COPD.

        • TABLE 4

          Treatable traits (TTs) associated with decline in forced expiratory volume in 1 s (FEV1)

          TTCOPDNon-COPD
          UnadjustedModel 1#Model 2¶UnadjustedModel 1+Model 2§
          Airflow limitation3.046 (2.825–3.268)2.957 (2.736–3.178)2.976 (2.760–3.193)***1.821 (1.645–1.997)2.046 (1.823–2.268)2.018 (1.798–2.238)***
          Chronic bronchitis−0.243 (−0.387 to −0.100)−0.172 (−0.273 to −0.070)−0.186 (−0.290 to −0.082)***−0.257 (−0.412 to −0.103)−0.097 (−0.213 to 0.019)–
          Chronic sputum production−0.031 (−0.144 to 0.082)––−0.046 (−0.125 to 0.032)––
          Breathlessness−0.304 (−0.416 to −0.192)−0.076 (−0.147 to −0.005)−0.093 (−0.164 to −0.022)*−0.360 (−0.406 to −0.314)−0.112 (−0.146 to −0.078)−0.112 (−0.144 to −0.080)***
          Frequent chest infections−0.043 (−0.188 to 0.103)––−0.063 (−0.131 to 0.006)−0.031 (−0.082 to 0.020)–
          Osteoporosis−0.383 (−0.540 to −0.226)−0.056 (−0.182 to 0.069)–−0.492 (−0.571 to −0.413)−0.039 (−0.037 to 0.115)–
          CVD−0.024 (−0.129 to 0.080)––−0.111 (−0.155 to −0.068)0.012 (−0.018 to 0.042)–
          Arthritis−0.072 (−0.180 to 0.035)––−0.248 (−0.295 to −0.200)0.046 (0.014–0.079)0.039 (0.007–0.071)*
          Diabetes−0.135 (−0.306 to 0.036)––−0.141 (−0.228 to −0.053)−0.078 (−0.142 to −0.015)−0.082 (−0.144 to −0.020)**
          Cancer0.062 (−0.153 to 0.276)––−0.165 (−0.245 to −0.084)−0.006 (−0.067 to 0.055)–
          Psychiatric problems0.196 (−0.028 to 0.420)−0.066 (−0.240 to 0.107)–0.102 (−0.010 to 0.214)0.011 (−0.057 to 0.078)–
          Depression−0.149 (−0.263 to −0.036)0.007 (−0.066 to 0.080)–−0.232 (−0.285 to −0.178)−0.019 (−0.052 to 0.015)–
          Underweight−0.682 (−0.947 to −0.417)−0.207 (−0.370 to −0.043)−0.216 (−0.373 to −0.058)**−0.174 (−0.470 to 0.123)––
          Obesity−0.051 (−0.162 to 0.060)––−0.140 (−0.190 to −0.091)−0.110 (−0.145 to −0.074)−0.104 (−0.139 to −0.069)***
          Sarcopenia−0.402 (−0.537 to −0.267)−0.137 (−0.240 to −0.034)−0.162 (−0.262 to −0.061)**−0.555 (−0.634 to −0.476)−0.120 (−0.177 to −0.063)−0.114 (−0.167 to −0.060)***
          Systemic inflammation−0.061 (−0.171 to 0.050)––−0.272 (−0.323 to −0.221)−0.076 (−0.108 to −0.044)−0.081 (−0.112 to −0.050)***
          Anaemia−0.001 (−0.167 to 0.170)––0.049 (−0.037 to 0.135)––
          Disability−0.244 (−0.344 to −0.143)−0.038 (−0.100 to 0.024)–−0.277 (−0.318 to −0.235)−0.031 (−0.062 to −0.001)−0.036 (−0.064 to −0.009)*
          Current smoking−0.092 (−0.201 to 0.017)−0.218 (−0.294 to −0.142)−0.228 (−0.304 to −0.153)***−0.213 (−0.280 to −0.145)−0.192 (−0.246 to −0.138)−0.202 (−0.254 to −0.150)***
          Physical inactivity−0.273 (−0.448 to −0.097)−0.085 (−0.197 to 0.026)–−0.344 (−0.440 to −0.248)−0.108 (−0.185 to −0.030)−0.096 (−0.169 to −0.023)*
          Poor family and social support0.093 (−0.034 to 0.220)––0.024 (−0.036 to 0.085)––

          Data are presented as β (95% CI). Values in bold are statistically significant. COPD: chronic obstructive pulmonary disease; CVD: cardiovascular disease; CI: confidence interval. #: adjusted for sex, age, marital status, socioeconomic class and TTs (p<0.1) from the univariate analyses; ¶: adjusted for sex, age and TTs (p<0.1) from the multivariate analyses; +: adjusted for sex, age, marital status, ethnicity, socioeconomic class and TTs (p<0.1) from the univariate analyses; §: adjusted for sex, age, marital status, ethnicity, socioeconomic class and TTs (p<0.1) from the multivariate analyses. *: p<0.05; **: p<0.01; ***: p<0.001.

          • TABLE 5

            Treatable traits (TTs) associated with decline in quality of life (QoL)

            TTCOPDNon-COPD
            UnadjustedModel 1#Model 2¶UnadjustedModel 1+Model 2§
            Airflow limitation−3.63 (−8.17 to 0.91)––−4.02 (−5.77 to −2.28)−0.366 (−1.95 to 1.21)–
            Chronic bronchitis−3.28 (−5.46 to −1.09)−2.81 (−4.67 to −0.95)−2.87 (−4.65 to −1.08)**−4.09 (−6.24 to −1.95)−0.68 (−2.39 to 1.03)–
            Chronic sputum production−2.10 (−3.49 to −0.72)−0.96 (−2.35 to 0.43)–−3.96 (−4.93 to −2.99)−0.88 (−1.79 to 0.03)−0.96 (−1.86 to −0.06)*
            Breathlessness−3.64 (−4.91 to −2.38)−0.76 (−2.03 to 0.50)–−4.53 (−5.11 to −3.95)−1.76 (−2.30 to −1.22)−1.76 (−2.29 to −1.23)***
            Frequent chest infections−2.10 (−4.43 to 0.23)−1.25 (−3.13 to 0.63)–−0.71 (−1.53 to 0.10)−0.19 (−0.94 to 0.55)–
            Osteoporosis−0.83 (−2.86 to 1.20)––−2.85 (−3.95 to −1.74)−1.58 (−2.63 to −0.52)−1.57 (−2.62 to −0.52)**
            CVD−2.62 (−3.93 to −1.31)−1.34 (−2.60 to −0.08)−1.69 (−2.90 to −0.48)**−2.03 (−2.51 to −1.56)−1.16 (−1.57 to −0.76)−1.17 (−1.57 to −0.77)***
            Arthritis−3.52 (−4.80 to −2.23)−1.41 (−2.67 to −0.15)−1.52 (−2.76 to −0.28)*−3.05 (−3.55 to −2.56)−1.28 (−1.71 to −0.84)−1.28 (−1.72 to −0.85)***
            Diabetes−3.56 (−5.42 to −1.69)−1.40 (−3.17 to 0.37)–−2.56 (−3.50 to −1.62)−0.81 (−1.64 to 0.03)−0.81 (−1.64 to 0.02)
            Cancer−1.40 (−4.26 to 1.47)––−0.22 (−1.21 to 0.77)––
            Psychiatric problems−0.68 (−3.23 to 1.88)––−0.15 (−1.12 to 0.83)––
            Depression−7.88 (−9.38 to −6.38)−7.08 (−8.73 to −5.44)−7.19 (−8.81 to −5.57)***−8.70 (−9.38 to −8.01)−5.87 (−6.54 to −5.20)−5.82 (−6.48 to −5.15)***
            Underweight−0.71 (−3.51 to 2.10)––0.62 (−3.49 to 4.74)––
            Obesity−0.27 (−1.70 to 1.16)––−1.95 (−2.51 to −1.40)−0.58 (−1.09 to −0.07)−0.51 (−1.01 to −0.02)*
            Sarcopenia−3.35 (−5.16 to −1.54)−1.32 (−3.49 to 0.84)–−4.24 (−5.24 to −3.24)−1.32 (−2.26 to −0.38)−1.34 (−2.28 to −0.41)**
            Systemic inflammation−0.93 (−2.43 to 0.57)––−1.13 (−1.69 to −0.57)0.11 (−0.34 to 0.56)–
            Anaemia−3.15 (−5.55 to −0.75)−2.61 (−4.42 to −0.79)−3.28 (−5.06 to −1.49)***−1.42 (−2.27 to −0.57)−0.88 (−1.56 to −0.20)−0.90 (−1.57 to −0.23)**
            Disability−3.81 (−4.95 to −2.67)−2.30 (−3.59 to −1.01)−2.83 (−4.06 to −1.60)***−4.15 (−4.62 to −3.68)−0.82 (−1.25 to −0.39)−0.80 (−1.22 to −0.37)***
            Current smoking−1.44 (−2.82 to −0.05)−1.31 (−2.66 to 0.04)−1.12 (−2.40 to 0.17)−2.69 (−3.52 to −1.85)−1.92 (−2.70 to −1.14)−1.90 (−2.67 to −1.13)***
            Physical inactivity−3.47 (−5.48 to −1.46)1.35 (−0.68 to 3.37)–−4.90 (−6.14 to −3.67)−1.43 (−2.55 to −0.32)−1.41 (−2.50 to −0.31)*
            Poor family and social support−5.44 (−7.05 to −3.83)−5.25 (−6.82 to −3.68)−5.12 (−6.65 to −3.59)***−5.58 (−6.29 to −4.88)−3.59 (−4.22 to −2.96)−3.57 (−4.19 to −2.95)***

            Data are presented as β (95% CI). Values in bold are statistically significant. COPD: chronic obstructive pulmonary disease; CVD: cardiovascular disease; CI: confidence interval. #: adjusted for age, marital status, socioeconomic class and TTs (p<0.1) from the univariate analyses; ¶: adjusted for socioeconomic class and TTs (p<0.1) from the multivariate analyses; +: adjusted for age, marital status, socioeconomic class and TTs (p<0.1) from the univariate analyses; §: adjusted for age, socioeconomic class and TTs (p<0.1) from the multivariate analyses. *: p<0.05; **: p<0.01; ***: p<0.001.

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            Treatable traits in an English cohort: prevalence and predictors of future decline in lung function and quality of life in COPD
            Muhammad Rehan Sarwar, Vanessa Marie McDonald, Michael John Abramson, Eldho Paul, Johnson George
            ERJ Open Research Apr 2021, 7 (2) 00934-2020; DOI: 10.1183/23120541.00934-2020

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            Treatable traits in an English cohort: prevalence and predictors of future decline in lung function and quality of life in COPD
            Muhammad Rehan Sarwar, Vanessa Marie McDonald, Michael John Abramson, Eldho Paul, Johnson George
            ERJ Open Research Apr 2021, 7 (2) 00934-2020; DOI: 10.1183/23120541.00934-2020
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