Why carry out this study?
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New diagnostic criteria (2018) for asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) were suggested by the Japanese Respiratory Society (JRS). |
This prospective, multicenter, observational cohort study investigated the proportion of COPD patients who meet the JRS ACO diagnostic criteria, and an ongoing follow-up analysis will explore how this changes over a 2-year period. |
What was learned from the study?
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At registration, of 708 COPD patients analyzed, 312 (44.1%) were lacking the necessary data for ACO diagnosis to be conducted, suggesting that some of the examinations/tests required for the diagnosis of ACO are not routine in clinical practice. |
Of the 396 patients with necessary data for diagnosis, 101 (25.5%) met the JRS diagnostic criteria for ACO and 295 (74.5%) were non-ACO. |
Analyses of study data over 2 years will provide relevant information on the ACO symptoms, clinical course, and real-world treatment patterns. |
Digital Features
Introduction
Methods
Study Design
Basic criteria | |
Age ≥ 40 years and chronic airflow obstruction: post-bronchodilator FEV1/FVC < 70% | |
[Characteristics of COPD] One item from 1, 2, and 3 | [Characteristics of asthma] Two items from 1, 2, and 3, or One item from 1, 2, and 3 and at least two items from 4 |
1. Smoking history (10 pack-years or more) or career involving significant air pollution or biomass exposure 2. Presence of low attenuation areas on chest CT demonstrating emphysematous changes 3. Impaired pulmonary diffusing capacity (%DLCO < 80% or %DLCO/VA < 80%) | 1. Variable (diurnally, daily, and seasonally) or paroxysmal respiratory symptoms (cough, sputum, and dyspnea) 2. History of asthma before age 40 years 3. FeNO > 35 ppb 4. (1) Concomitant perennial allergic rhinitis (2) Airway reversibility (change in FEV1 > 12% and > 200 mL) (3) Peripheral blood eosinophils > 5% or > 300/μL (4) High IgE level (total IgE, or IgE specific to perennial inhalant antigens) |
1. To be diagnosed as ACO, one item of the characteristics of COPD plus two items from 1, 2, and 3 or one item from 1, 2, and 3 and at least two items from criterion 4 of the characteristics of asthma are needed 2. If the characteristics of COPD alone are present, it is diagnosed as COPD, and if the characteristics of asthma alone are present, it is diagnosed as asthma (with remodeling) 3. If the characteristics of asthma cannot be confirmed when diagnosing ACO, it is important to monitor for the presence of the characteristics of asthma over time 4. Perennial inhalant antigens include house dust, mites, molds, scales from animals, and feathers, and seasonal inhalant antigens include pollen from trees, plants, and weeds Note 1. Diseases of differential diagnosis (diffuse panbronchiolitis, congenital sinobronchial syndrome, obstructive panbronchiolitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis, lymphangioleiomyomatosis, congestive heart failure, interstitial lung disease, and lung cancer) should be ruled out by standard chest x-rays, etc. Note 2. Respiratory symptoms such as cough, sputum, and dyspnea are variable (diurnally, daily, and seasonally) or paroxysmal in asthma and chronic and continuous in COPD |
Patients
Inclusion criteria | Exclusion criteria |
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1. Patients who provided written informed consent for study participation 2. Patients aged ≥ 40 years 3. Patients with lung function (FEV1/FVC) < 70% after inhalation of a bronchodilator within the past year or at the time of registration 4. Patients who fulfill one of the following criteria: smoking history (≥ 10 pack-years) or equivalent air pollution exposure (including passive smoking) at the time of registration; presence of a low attenuation area showing emphysematous change on chest computed tomography imaging as assessed by the investigator based on the most recent scan within the past year; lung diffusion impairment (defined as %DLCO < 80% or %DLCO/VA < 80%) assessed within the past year 5. Outpatients who were able to regularly visit the study sites in Japan at least once per year | 1. Patients participating in an interventional study within 8 weeks prior to registration 2. Patients who experienced an exacerbation of COPDa or asthmab within the last 8 weeks 3. Patients with a condition that could not be distinguished from COPD or asthma at the time of obtaining consent (diffuse panoramic bronchitis, congenital sinus bronchial syndrome, obstructive panbronchitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis, lymphangiomyomatosis, interstitial lung disease, lung cancer, vocal fold dysfunction, intratracheal tumor, tracheal softening, bronchial tuberculosis, pulmonary thromboembolism, congestive heart failure). However, patients with certain diseases could be registered if remission or stable disease was confirmed by the physician (laryngitis, epiglottitis, airway foreign body, cough induced by a drug such as an angiotensin converting enzyme inhibitor, spontaneous pneumothorax, hyperventilation syndrome, and psychogenic cough) 4. Any patient who could not comply with study procedures or was otherwise determined by the investigator to be ineligible |
Study Endpoints
Statistical Analysis
Results
Participant Characteristics
Full analysis set, N = 708 | ||
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Sex, male, n (%) | 638 (90.1) | |
Age, years, mean (SD) | 73.5 (7.7) | |
BMI, kg/m2, mean (SD) | n = 707 | 22.9 (3.5) |
Smoking status, n (%) | n = 707 | |
Current smoker | 79 (11.2) | |
Never smoker | 12 (1.7) | |
Ex-smoker | 616 (87.1) | |
Smoking history (pack-years), mean (SD) | n = 690 | 56.2 (34.3) |
Duration of COPD, years, mean (SD) | n = 692 | 5.7 (5.2) |
GOLD stage, n (%) | n = 703 | |
I | 197 (28.0) | |
II | 328 (46.7) | |
III | 134 (19.1) | |
IV | 44 (6.3) | |
Post-bronchodilator FEV1/FVC%, mean (SD) | n = 704 | 52.0 (12.7) |
Post-bronchodilator %FEV1 predicted, mean (SD) | n = 703 | 65.1 (22.2) |
FEV1 reversibility (change in FEV1 > 12% and > 200 mL), n (%) | n = 331 | 20 (6.0) |
Complication/comorbidity, n (%) | ||
Asthma (based on physician's diagnosis) | 255 (36.0) | |
Age at onset < 40 years | 24/240 [10.0] | |
Age at onset ≥ 40 years | 216/240 [90.0] | |
Allergic rhinitis | 73 (10.3) | |
Heart failure | 60 (8.5) | |
Diabetes | 89 (12.6) | |
Respiratory medication at registration, n (%) | ||
ICS (as monotherapy or any combinations) | 298 (42.1) | |
ICS monotherapy | 12 (1.7) | |
LAMA monotherapy | 81 (11.4) | |
LABA monotherapy | 40 (5.6) | |
LAMA and LABAa | 271 (38.3) | |
ICS and LABAa | 99 (14.0) | |
ICS and LAMA | 7 (1.0) | |
ICS, LAMA, and LABAa | 180 (25.4) |
Primary Outcome: Proportion of ACO Patients at Registration
Analysis According to Each ACO Diagnostic Criterion at Registration
Characteristic, n (%) | Met ACO criteria (n = 101) | Did not meet ACO criteria (n = 295) | |||
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Patients who underwent evaluationa | Patients who met the criterionb | Patients who underwent evaluationa | Patients who met the criterionb | ||
Characteristics of COPD | 1. Smoking history (10 pack-years or more) or career involving significant air pollution or biomass exposure | 101 (100.0) | 98 (97.0) | 295 (100.0) | 292 (99.0) |
2. Presence of low attenuation areas on chest CT demonstrating emphysematous changes | 80 (79.2) | 64 (80.0) | 231 (78.3) | 201 (87.0) | |
3. Impaired pulmonary diffusing capacity (%DLCO < 80% or %DLCO/VA < 80%) | 53 (52.5) | 31 (58.5) | 130 (44.1) | 99 (76.2) | |
Characteristics of asthma | 1. Variable (diurnally, daily, and seasonally) or paroxysmal respiratory symptoms (cough, sputum, and dyspnea) | 98 (97.0) | 84 (85.7) | 292 (99.0) | 42 (14.4) |
2. History of asthma before age 40 years | 99 (98.0) | 27 (27.3) | 294 (99.7) | 1 (0.3) | |
3. FeNO > 35 ppb | 86 (85.1) | 59 (68.6) | 269 (91.2) | 16 (5.9) | |
4. Applies to the following two or more items | 77 (76.2) | 59 (76.6) | 200 (67.8) | 29 (14.5) | |
(1) Concomitant perennial allergic rhinitis | 101 (100.0) | 37 (36.6) | 295 (100.0) | 20 (6.8) | |
(2) Airway reversibility (change in FEV1 > 12% and > 200 mL) | 61 (60.4) | 8 (13.1) | 178 (60.3) | 6 (3.4) | |
(3) Peripheral blood eosinophils > 5% or > 300/μL | 92 (91.1) | 49 (53.3) | 278 (94.2) | 47 (16.9) | |
(4) High IgE level (total IgE, or IgE specific to perennial inhalant antigens) | 64 (63.4) | 56 (87.5) | 128 (43.4) | 75 (58.6) |
Comparison of Patient Characteristics, Biomarkers, and Lung Function Between ACO and Non-ACO Patients at Registration
Patients with the data necessary for ACO diagnosis | p value | |||
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All (n = 396) | ACO (n = 101) | Non-ACO (n = 295) | (ACO vs non-ACO) | |
Sex, male, n (%) | 353 (89.1) | 90 (89.1) | 263 (89.2) | 0.990 |
Age, years, mean (SD) | 73.2 (8.0) | 71.5 (9.6) | 73.8 (7.3) | 0.025 |
BMI, kg/m2, mean (SD) | 23.0 (3.4) | 23.0 (3.1) | 23.0 (3.5) | 0.869 |
Smoking status, n (%) | ||||
Current smoker | 42 (10.6) | 6 (5.9) | 36 (12.2) | 0.108 |
Never smoker | 4 (1.0) | 2 (2.0) | 2 (0.7) | |
Ex-smoker | 350 (88.4) | 93 (92.1) | 257 (87.1) | |
Smoking history (pack-years) | n = 392 | n = 99 | n = 293 | |
Mean (SD) | 55.1 (35.8) | 57.7 (40.7) | 54.2 (34.1) | 0.441 |
Duration of COPD, years | n = 390 | n = 99 | n = 291 | |
Mean (SD) | 5.3 (5.4) | 5.3 (4.6) | 5.3 (5.7) | 0.997 |
GOLD stage, n (%) | ||||
I | 125 (31.6) | 30 (29.7) | 95 (32.2) | 0.207 |
II | 194 (49.0) | 54 (53.5) | 140 (47.5) | |
III | 59 (14.9) | 16 (15.8) | 43 (14.6) | |
IV | 18 (4.5) | 1 (1.0) | 17 (5.8) | |
Complication/comorbidity, n (%) | ||||
Asthma (based on physician’s diagnosis) | 177 (44.7) | 68 (67.3) | 109 (36.9) | < 0.001 |
Age at onset < 40 years | n = 175 | n = 67 | n = 108 | |
24 (13.7) | 23 (34.3) | 1 (0.9) | < 0.001 | |
Age at onset ≥ 40 years | n = 175 | n = 67 | n = 108 | |
151 (86.3) | 44 (65.7) | 107 (99.1) | < 0.001 | |
Allergic rhinitis | 57 (14.4) | 37 (36.6) | 20 (6.8) | < 0.001 |
Heart failure | 45 (11.4) | 3 (3.0) | 42 (14.2) | 0.002 |
Diabetes | 58 (14.6) | 15 (14.9) | 43 (14.6) | 0.946 |
Respiratory medication at baseline, n (%) | n = 396 | n = 98 | n = 289 | |
ICS (monotherapy or any combinations) | 180 (45.5) | 75 (76.5) | 105 (36.3) | < 0.001 |
ICS monotherapy | 4 (1.0) | 3 (3.1) | 1 (0.3) | 0.052 |
LAMA monotherapy | 44 (11.1) | 10 (10.2) | 34 (11.8) | 0.674 |
LABA monotherapy | 20 (5.1) | 1 (1.0) | 19 (6.6) | 0.032 |
LAMA and LABAa | 138 (34.8) | 11 (11.2) | 127 (43.9) | < 0.001 |
ICS and LABAa | 65 (16.4) | 22 (22.4) | 43 (14.9) | 0.083 |
ICS and LAMA | 4 (1.0) | 2 (2.0) | 2 (0.7) | 0.267 |
ICS, LAMA, and LABAa | 107 (27.0) | 48 (49.0) | 59 (20.4) | < 0.001 |
Symptoms based on interview | ||||
Presence of variable symptoms, n (%) | 96 (24.2) | 67 (66.3) | 29 (9.8) | < 0.001 |
Presence of paroxysmal symptoms, n (%) | n = 387 | n = 95 | n = 292 | < 0.001 |
90 (23.3) | 57 (60.0) | 33 (11.3) | ||
Questionnaire | ||||
CAT | n = 395 | n = 101 | n = 294 | |
Mean (SD) | 10.3 (7.0) | 10.7 (7.8) | 10.1 (6.7) | 0.492 |
mMRC | n = 395 | n = 101 | n = 294 | |
Mean (SD) | 1.0 (1.0) | 1.0 (1.0) | 1.1 (1.0) | 0.523 |
ACQ | n = 394 | n = 101 | n = 293 | |
Mean (SD) | 0.5 (0.8) | 0.9 (1.0) | 0.4 (0.6) | < 0.001 |
Patients with the data necessary for ACO diagnosis | p value | |||
---|---|---|---|---|
All (n = 396) | ACO (n = 101) | Non-ACO (n = 295) | (ACO vs non-ACO) | |
Biomarkers | ||||
FeNO, ppb | n = 355 | n = 86 | n = 269 | |
Mean (SD) | 27.4 (23.5) | 47.8 (35.5) | 20.9 (12.5) | < 0.001 |
Median | 22.0 | 41.5 | 20.0 | |
FeNO > 35 ppb, n (%) | 75 (21.1) | 59 (68.6) | 16 (5.9) | < 0.001 |
Peripheral eosinophils absolute count, cells/μL | n = 370 | n = 92 | n = 278 | |
Mean (SD) | 241.1 (277.9) | 392.8 (472.2) | 190.9 (139.4) | < 0.001 |
Median | 176.0 | 289.5 | 160.5 | |
Eosinophil ratio, % | n = 370 | n = 92 | n = 278 | |
Mean (SD) | 3.8 (3.8) | 5.9 (6.0) | 3.1 (2.3) | < 0.001 |
Total IgE, IU/mL | n = 278 | n = 75 | n = 203 | |
Mean (SD) | 415.1 (837.9) | 833.2 (1330.2) | 260.6 (475.1) | < 0.001 |
Median | 133.5 | 398.0 | 92.0 | |
Presence of ≥ 1 positive allergen detected in the specific IgE exam, n (%) | n = 147 | n = 39 | n = 108 | |
64 (43.5) | 24 (61.5) | 40 (37.0) | 0.008 | |
Lung function | ||||
Post-bronchodilator FEV1/FVC%, mean (SD) | 53.1 (12.0) | 53.3 (9.9) | 53.0 (12.7) | 0.545 |
Post-bronchodilator %FEV1 predicted, mean (SD) | 68.1 (21.7) | 69.2 (20.6) | 67.7 (22.1) | 0.792 |
FEV1 reversibility (change in FEV1 > 12% and > 200 mL) | n = 239 | n = 61 | n = 178 | |
Yes, n (%) | 14 (5.9) | 8 (13.1) | 6 (3.4) | 0.010 |
Presence of emphysema on CT, n (%) | n = 311 | n = 80 | n = 231 | |
265 (85.2) | 64 (80.0) | 201 (87.0) | 0.128 | |
%DLCO < 80% or %DLCO/VA < 80%, n (%) | n = 183 | n = 53 | n = 130 | |
130 (71.0) | 31 (58.5) | 99 (76.2) | 0.017 |