Real-World Evidence on the Diagnostic and Clinical Characteristics of Asthma in Japanese Patients with COPD: The ACO Japan Cohort Study

Figures & data

Table 1 Japanese Respiratory Society Diagnostic Criteria for Asthma and COPD Overlap^11,14

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 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 the 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 (post-bronchodilator increases in FEV1 >12% and >200 mL) (3) Peripheral blood eosinophils >5% or >300/μL (4) High IgE level^a (total IgE or IgE specific to perennial inhalant antigens^b)
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, or one 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 (without 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.

Notes: 1. Disease of differential diagnosis (diffuse panbronchiolitis, congenital sinobronchial syndrome, obstructive panbronchiolitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis, lymphangioleiomyomatosis, congestive heart disease, interstitial lung disease, and lung cancer) should be ruled out by standard chest x-rays, etc. 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. Adapted from ref. 11 with permission. ^aDetermined according to the criteria of each study site. ^bSpecific IgE to antigens from dogs, cats, house dust mites (Dermatophagoides pteronyssinus and D. farinae), and fungi (Aspergillus and Candida).

Abbreviations: ACO, asthma–COPD overlap; COPD, chronic obstructive pulmonary disease; CT, computed tomography; D_LCO, diffusion capacity for carbon monoxide; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; Ig, immunoglobulin; V_A, alveolar volume.

Table 2 Proportions of Patients Who Had the Data Necessary for ACO Diagnosis at Least Once During the Study

FAS (N = 708)	At Registration	At 1 Year	At 2 Years
Patients who had data necessary for ACO diagnosis at least once at each time point, n (%)^a	396 (55.9)	478 (67.5)	507 (71.6)
Patients lacking data necessary for ACO diagnosis at each time point, n (%)^a	312 (44.1)	214 (30.2)	160 (22.6)
Not visited at each time point, n (%)^a	N/A	16 (2.3)	41 (5.8)
Patients diagnosed with ACO at least once during the study period	101	118	125
Proportion of patients from the FAS, % (95% CI)^a	14.3 (11.9–17.0)	16.7 (14.1–19.6)	17.7 (15.0–20.6)
Proportion of patients diagnosed with ACO who had data necessary for ACO diagnosis, %^b	25.5	24.7	24.7

Notes: Data are n (%) unless otherwise stated. ^aPercentages were calculated using N = 708. ^bPercentages were calculated using N = 396 (registration), N = 478 (at 1 year), and N = 507 (at 2 years).

Abbreviations: ACO, asthma–chronic obstructive pulmonary disease overlap; CI, confidence interval; FAS, full analysis set; N/A, not applicable.

Table 3 Clinical Characteristics of ACO Patients at Registration Compared with Non-ACO Patients During the 2-Year Follow-Up

	Data at Registration			1-Year Data			2-Year Data
	ACO at Registration^a (n = 101)	Non-ACO for 2 Years^b (n = 79)	p-value	ACO at Registration^a (n = 101)	Non-ACO for 2 Years^b (n = 79)	p-value	ACO at Registration^a (n = 101)	Non-ACO for 2 Years^b (n = 79)	p-value
Lung function
Post-BD FEV1				n = 73			n = 56	n = 76
mL, mean (SD)	1850.1 (589.2)	1697.7 (586.4)	0.086	1733.8 (556.8)	1675.2 (592.2)	0.531	1807.3 (575.3)	1740.4 (619.5)	0.528
% predicted, mean (SD)	69.2 (20.6)	66.9 (19.8)	0.45	65.3 (16.9)	66.0 (19.8)	0.828	68.2 (17.7)	68.3 (20.2)	0.977
Post-BD FEV1/FVC				n = 73			n = 56	n = 76
%, mean (SD)	53.3 (9.9)	52.9 (12.0)	0.785	51.9 (9.4)	53.4 (13.4)	0.439	54.0 (10.7)	53.6 (13.4)	0.849
FEV1 change from registration				n = 73			n = 56	n = 76
mL, mean (SD)	N/A	N/A	N/A	−68.8 (365.3)	−22.5 (164.8)	0.324	−92.0 (249.5)	43.4 (208.4)	0.001
Reversibility: improvement rate	n = 61	n = 31		n = 39	n = 29		n = 24	n = 26
%, mean (SD)	6.4 (7.8)	4.5 (6.4)	0.245	7.7 (10.3)	2.2 (8.1)	0.022	6.6 (6.4)	4.5 (4.3)	0.182
ICS^c use				n = 96			n = 90
n (%)	78 (77.2)	19 (24.1)	<0.001	77 (80.2)	25 (31.6)	<0.001	72 (80.0)	27 (34.2)	<0.001
Moderate or severe exacerbation in the past year				n = 98			n = 90
Total exacerbation events, n (event per patient)	17 (0.17)	5 (0.06)	0.055	25 (0.26)	11 (0.14)	0.094	10 (0.11)	6 (0.08)	0.461
Patients who reported exacerbation, n (%)	16 (15.8)	5 (6.3)	0.049	19 (19.4)	6 (7.6)	0.025	8 (8.9)	6 (7.6)	0.761
Questionnaire score
CAT				n = 87	n = 75		n = 74	n = 78
mean (SD)	10.7 (7.8)	9.4 (6.9)	0.242	11.5 (8.6)	7.6 (6.3)	0.001	11.0 (8.2)	9.1 (6.9)	0.127
mMRC				n = 85	n = 85		n = 74	n = 77
mean (SD)	1.0 (1.0)	1.0 (1.1)	0.92	1.0 (1.0)	1.0 (1.0)	0.414	1.1 (1.1)	1.3 (1.0)	0.299
ACQ		n = 78		n = 87	n = 76		n = 72	n = 76
mean (SD)	0.9 (1.0)	0.2 (0.4)	<0.001	0.8 (1.0)	0.3 (0.6)	<0.001	0.7 (1.0)	0.3 (0.5)	0.001
Biomarkers
FeNO	n = 86	n = 72		n = 60	n = 64		n = 42	n = 60
ppb, mean (SD)	47.8 (35.5)	20.5 (9.4)	<0.001	43.5 (38.0)	20.2 (12.1)	<0.001	37.4 (26.7)	18.0 (8.2)	<0.001
Peripheral blood eosinophil count	n = 92	n = 77		n = 63	n = 76		n = 54	n = 75
cells/µL, mean (SD)	392.8 (472.2)	182.4 (126.5)	<0.001	297.2 (311.3)	191.3 (165.9)	0.017	244.8 (197.6)	165.7 (122.4)	0.011
Peripheral blood eosinophil ratio	n = 92	n = 77		n = 63	n = 76		n = 54	n = 75
%, mean (SD)	5.9 (6.0)	3.2 (2.2)	<0.001	4.8 (4.6)	3.3 (2.8)	0.022	4.1 (3.3)	2.9 (2.2)	0.022

Notes: ^aPatients who met the diagnostic criteria for ACO at registration. ^bPatients who did not meet the diagnostic criteria for ACO throughout the 2-year follow-up period. ^cAs monotherapy or any combination.

Abbreviations: ACO, asthma–COPD overlap; ACQ, asthma control questionnaire; BD, bronchodilator; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; ICS, inhaled corticosteroids; mMRC, modified Medical Research Council questionnaire; N/A, not applicable; SD, standard deviation.

Figure 1 Transition of 111 patients with the data necessary to meet the JRS ACO diagnosis criteria between ACO and non-ACO status at registration, 1 year, and 2 years during the study.

Abbreviation: ACO, asthma–chronic obstructive pulmonary disease overlap.

Table 4 Reason for Lack of Data Required for the Diagnosis of ACO at the Time of Registration

Patients Lacking Data for ACO Diagnosis at Registration (n = 312)
The patient was assessed as not having ACO based on clinical features	100 (32.1)
The patient was assessed as having ACO based on clinical features	85 (27.2)
Examinations/tests had already been performed (≥1 year before registration)	47 (15.1)
Other	44 (14.1)
Examinations/tests could not be performed due to the examination/testing system of the study site (eg, reservation is required)	32 (10.3)
Examinations/tests could not be performed due to the patient’s refusal	4 (1.3)

Note: Data are n (%).

Abbreviation: ACO, asthma–chronic obstructive pulmonary disease overlap.

The Japanese Respiratory Society. The JRS Guidelines for the Management of ACO 2018. Tokyo: Medical Review; 2017.

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Mekov E, Nuñez A, Sin DD, et al. Update on asthma-COPD overlap (ACO): a narrative review. Int J Chron Obstruct Pulmon Dis. 2021;16:1783–1799. doi:10.2147/COPD.S312560

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