Figures
- FIGURE 1
Frequency distribution of age (years), cumulative smoking exposure (pack-years), FEV1/FVC (%), FEV1 (% ref.), diffusing capacity of the lung for carbon monoxide (DLCO) (% ref.) and KLCO (% ref.) in patients (red; n=92) and controls (green; n=197). Dotted vertical lines represent mean values. For further explanations, see text.
- FIGURE 2
Comparison of the main characteristics determined in patients with early COPD (versus controls) in the three cohorts studied here (our own (SPAIN), ECLIPSE and COPDGene). ↓ Indicates reduced in cases, ↑ indicates increased in cases, ∼ indicates similar in patients and controls, and NA means not available in that cohort. Orange, pink and yellow rows indicate, respectively, reproducibility of findings in three out of the three cohorts, two out of two cohorts or two out of three cohorts where this information was available. For further explanations, see text.
- FIGURE 3
Variables associated (p<0.05) with the presence of early COPD in the population studied. Node colour indicates variable category (see legends), node size is proportional to the prevalence of abnormal values of that particular variable and edge (link) width is proportional to p-values (see legends). For further explanations, see text.
Tables
- TABLE 1
Main characteristics of cases and controls
Cases Controls p-value Subjects n 91 107 Demographics Females 35% 50% 0.016 Age years 45.8±3.5 43.3±4.4 <0.001 Height cm 168.7±8.6 168.1±9.0 0.579 Weight kg 80.3±20.5 75.4±15.9 0.043 Body mass index kg·m−2 28.1±6.4 26.6±4.8 0.047 High educational level# 52% 77% <0.001 Active worker (last year) 70% 86% 0.002 Exposure history Cumulative smoking exposure pack-years 31.6±116.3 24.8±13.7 0.001 Current smokers 66% 76% 0.089 Age at smoking initiation years 16.0±2.8 16.6±3.7 0.121 High-risk job¶ 29% 20% 0.129 Family history Maternal asthma 17% 11% 0.221 Maternal bronchitis 16% 8% 0.051 Maternal cardiac disease 31% 17% 0.014 Maternal arterial hypertension 52% 44% 0.282 Maternal cerebrovascular disease 11% 11% 1 Maternal diabetes 18% 17% 0.860 Paternal asthma 13% 6% 0.068 Paternal bronchitis 46% 27% 0.005 Paternal cardiac disease 31% 25% 0.430 Paternal arterial hypertension 43% 37% 0.375 Paternal cerebrovascular disease 18% 9% 0.083 Early-life events Birth <37 weeks 5% 4% 0.754 Birth weight <2.5 kg 4% 6% 0.760 Mother age at delivery years 29.6±7.0 28.3±5.7 0.128 Mother smoked during pregnancy 7% 13% 0.210 Urban residence before the age of 5 65% 74% 0.120 Hospital admission for respiratory disease before 5 years of age 12% 3% 0.009 Symptoms, previous diagnosis and use of healthcare resources mMRC ≥2 29% 6% 0.001 CAT 12.5±6.8 8.6±6.7 <0.001 Ever diagnosed of a respiratory problem 63% 39% 0.001 Ever diagnosed of asthma 30% 9% <0.001 Ever use of respiratory medications 79% 28% <0.001 Oral corticosteroids use in the last 12 months 20% 5% <0.001 Antibiotic use in the last 12 months 31% 21% 0.073 Ever diagnosed of a cardiovascular disease 26% 28% 0.751 Ever use of cardiovascular medications 24% 34% 0.229 Ambulatory (GP) visits due to respiratory reasons 60% 29% <0.001 due to non-respiratory reasons 46% 51% 0.438 Emergency room visits due to respiratory reasons 14% 1% <0.001 due to non-respiratory reasons 27% 37% 0.141 Hospital admissions due to respiratory reasons 11% 1% <0.001 due to non-respiratory reasons 12% 10% 0.686 Physiology FEV1 (pre-bd) % ref. 64.7±20.1 95.3±13.9 <0.001 FVC (pre-bd) % ref. 90.4±18.8 100.3±14.6 <0.001 FEV1/FVC (pre-bd) % 57.2±10.9 77.5±5.9 <0.001 FEF25–75% (pre-bd) % 39.5±48.4 81.8±33.9 <0.001 FEV1 (post-bd) % ref. 71.3±20.8 97.7±14.9 <0.001 FVC (post-bd) % ref. 96.5±18.6 98.9±15.0 0.280 FEV1/FVC (post-bd) % 58.5±10.4 79.9±5.3 <0.001 FEF25–75% (post-bd) % 39.1±30.9 92.5±35.5 <0.001 Total lung capacity, % ref. 112.7±17.1 103.1±15.7 <0.001 Residual volume, % ref. 150.6±55.5 113.6±40.9 <0.001 DLCO % ref. 84.16±20.73 91.6±13.51 0.003 KCO % ref. 80.53±19.73 93.25±12.57 <0.001 6MWD test Distance walked m 555±83 570±82 0.152 Dyspnoea at end of test 2.3±2.0 1.5±1.8 0.001 SaO2 at end of test 94.8±4.4 96.3±2.5 0.003 Imaging Presence of CT emphysema (%) 61% 32% <0.001 Biomarkers FeNO ppb 16.9±13.3 17.6±17.0 0.741 Haematocrit % 44.6±3.3 43.5±3.6 0.015 Leukocytes ×109·L−1 8.7 ±2.2 7.8±2.3 0.003 Neutrophils % 60.7±8.1 57.6±9.3 0.005 Lymphocytes % 28.9±6.8 32.4±8.0 <0.001 Eosinophils % 2.5±1.5 2.8±1.9 0.156 Eosinophils >300 cells·µL−1 23% 20% 0.635 Fibrinogen mg·dL−1 390.8±106.3 368.4±81.0 0.084 C-reactive protein >3 mg·/dL−1 (%) 0% 3% 0.327 Results are presented as mean±sd or proportion. p-values <0.05 are highlighted in bold text. mMRC: modified Medical Research Council scale; CAT: COPD Assessment Test; FEV1: forced expiratory volume in 1 s; pre-/post-bd: pre-/post-bronchodilator; % ref.: % of reference value; FVC: forced vital capacity; FEF25–75%: forced expiratory flow at 25–75% of FVC; DLCO: diffusing capacity of the lung for carbon monoxide; KCO: transfer coefficient of the lung for carbon monoxide; 6MWD: 6-min walk test; SaO2: arterial oxygen saturation; CT: computed tomography; FeNO: exhaled nitric oxide fraction. #: High education level includes a Baccalaureate or University degree; ¶: as identified in [12].
- TABLE 2
Main characteristics of patients (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7) and controls (FEV1/FVC≥0.7) included in the ECLIPSE study
Patients Controls p-value Subjects n 119 124 Demographics and exposure history Age years 47.3±2.7 45.7±3.0 <0.001 Males 61% 52% 0.162 Body mass index kg·m−2 26.5±6.9 26.1±4.6 0.650 Cumulative smoking exposure pack-years 34.5±17.0 24.7±11.7 <0.001 Current smokers 38% 23% 0.014 Family history and early-life events Familiar asthma 24% 19% 0.342 Familiar bronchitis 34% 15% 0.001 Familiar emphysema 29% 8% <0.001 Familiar hypertension 49% 48% 1 Symptoms mMRC score ≥2 13% 1% 0.001 Previous treatments and use of healthcare resources Oral Corticosteroid use 2% 0% 0.460 Number of exacerbations 0.7± 0.9 NA Physiology FEV1/FVC (post-bd) % 49.0± 11.8 80.1±4.9 <0.001 FEV1 (post-bd) % ref. 49.0± 18.2 103.9±10.8 <0.001 FVC (post-bd) % ref. 82.5± 22.1 112.8±12.6 <0.001 Total lung capacity % ref. 114.0± 17.5 102.79±11.4 <0.001 6MWD test Distance walked m 425.6±137.7 NA Imaging Presence of CT emphysema n (%) 60% 8% <0.001 Biomarkers Basophils (%) 0.33± 0.23 0.32± 0.24 0.527 Eosinophils (%) 2.6± 2.1 2.55± 1.58 0.464 Haematocrit 0.44±0.04 0.43± 0.04 0.009 Lymphocytes (%) 28.04± 8.61 30.22± 7.11 0.024 Monocytes (%) 5.96± 2.49 5.76± 2.23 0.682 Segmented neutrophils (%) 63.06± 9.52 61.15± 8.29 0.102 Total neutrophils (total ANC) 5.23± 2.2 4.71± 1.95 0.050 Total neutrophils (%) 63.06± 9.52 61.15± 8.29 0.102 White blood cells ×109/L 8.11± 2.49 7.56± 2.37 0.057 Results are presented as mean±sd or proportion. p-values <0.05 are highlighted in bold text. mMRC: modified Medical Research Council scale; post-bd: post-bronchodilator; % ref.: % of reference value; 6MWD: 6-min walk test; CT: computed tomography; ANC: total absolute neutrophil count.
- TABLE 3
Main characteristics of patients (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7) and controls (FEV1/FVC≥0.7) included in the COPDGene study
Patients Controls p-value Subjects n 205 560 Demographics and exposure history Age years 47.8±1.5 47.5±1.5 0.007 Females 50% 51% 0.178 Body mass index kg·m−2 28.4±7.0 29.4±6.4 0.051 Cumulative smoking exposure pack-years 38.2±15.0 32.6±16.4 <0.001 Current smokers 76% 71% 0.154 High educational level# 47% 58% 0.011 Active worker (last year) 33% 50% <0.001 Family history and early-life events Maternal asthma 14% 11% 0.438 Maternal bronchitis 16% 16% 0.997 Maternal emphysema 23% 16% 0.045 Paternal asthma 7% 4% 0.285 Paternal bronchitis 8% 10% 0.765 Paternal emphysema 26% 17% 0.024 Mother smoked during pregnancy 52% 47% 0.261 Symptoms mMRC score 1.9±1.5 0.8±1.2 <0.001 Previous treatments and use of healthcare resources Oral corticosteroid use 4% 1% 0.015 Number of ambulatory (GP) visits due to respiratory reasons (exacerbations) 0.44±1.02 0.11±0.44 <0.001 Number of hospital admissions due to respiratory reasons (exacerbations) 0.20±0.71 0.03±0.21 <0.001 Physiology FEV1/FVC (post-bd) % 59±12 79±1 <0.001 FEV1 (post-bd) % ref. 66±22 92±14 <0.001 FVC (post-bd) % ref. 87±19 92±14 <0.001 6MWD test Distance walked m 435.4±114.3 476.2±103.2 <0.001 Shortness of breath at end of test 76% 51% <0.001 Imaging Presence of CT emphysema n (%) 29% 9% <0.001 Results are presented as mean±sd or proportion. P-values <0.05 are highlighted in bold text. mMRC: modified Medical Research Council scale; post-bd: post-bronchodilator; % ref.: % of reference value; 6MWD: 6-min walk test; CT: computed tomography. #: High education level includes a Baccalaureate or University degree.
- TABLE 4
Independent clinical characteristics associated with the presence of early chronic obstructive pulmonary disease (COPD) identified by multiple regression logistic analysis (by odds ratio value)
OR (95% CI) p-value Hospital admission for respiratory disease before the age of 5 years 9.292 (2.57–36.10) <0.001 Emergency room visits due to respiratory reasons 9.160 (1.43–180.74) <0.05 mMRC ≥2 2.336 (1.36–4.14) <0.01 Packs-years 1.030 (1.00–1.06) <0.05 KCO % ref. 0.950 (0.92–0.98) <0.001 Active worker 0.391 (0.16–0.99) <0.05 mMRC: modified Medical Research Council scale; KCO: transfer coefficient of the lung for carbon monoxide; % ref.: % of reference value.
Supplementary Material
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Supplementary material 00047-2020.supplement
