Sage Journals: Discover world-class research

Abstract

Background:

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation.

Objectives:

This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports.

Design:

This is a multicenter and retrospective study.

Methods:

Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected.

Results:

A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C.

Conclusion:

Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

Keywords

chronic obstructive pulmonary disease exacerbation global initiative for chronic obstructive lung disease inhalation therapy mortality

Introduction

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease with high morbidity and mortality, which has become the third leading cause of death.¹ Therefore, treatment and prevention are urgently needed.

The goal of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) program is to produce recommendations for the management of COPD based on the best scientific information available and revise these annually. Until GOLD 2017, the combined assessment tool classified COPD patients into Groups A, B, C, and D based on the COPD assessment test (CAT) or modified Medical Research Council (mMRC) and exacerbation history. For patients in Group A, the initial inhalation therapy recommendation should be a short- or long-acting bronchodilator. For those in Group B, it should be a long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA). Patients in Group C should receive a LAMA and those in Group D should receive a LAMA, LAMA + LABA, or LABA + inhaled corticosteroid (ICS).²

The latest GOLD 2023 report revised the assessment tool and initial inhalation therapy recommendations, after which Groups C and D were merged into Group E. In addition, initial inhalation therapy recommendations for Group A should be a short- or long-acting bronchodilator, while Group B should receive LAMA + LABA and Group E should receive LAMA + LABA or LAMA + LABA + ICS therapy.³ However, further studies are needed to confirm whether the latest combined assessment tool and initial inhalation therapy recommendations are more effective in reducing the risk of future exacerbation and mortality.

Therefore, the purpose of this study was to analyze the future exacerbation and mortality of different inhalation therapies among patients with COPD in various groups according to the GOLD 2017 and GOLD 2023 reports.

Patients and methods

Study participants

This was a multicenter and retrospective study. All subjects were from the outpatient COPD database (Register number: ChiCTR-POC-17010431) which included 12 comprehensive hospitals (Supplemental Table 1). The patients had been diagnosed with COPD between December 2016 and March 2022 according to the GOLD 2017 report: the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) was <0.70 after inhaling a bronchodilator.⁴ Patients with asthma, lung cancer, pneumonia, active tuberculosis, pulmonary fibrosis, and severe heart, liver, or kidney disease were excluded from this study. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.⁵

Data collection

The baseline data including age, sex, body mass index (BMI), smoke history, biofuel exposure history, FEV1 %pred, FEV1/FVC, GOLD grades, CAT scores, mMRC scores, exacerbations, and hospitalizations in the past year and inhalation therapy regimens were collected. All patients were followed up for a duration of 1 year, during which the number of exacerbations, hospitalizations, and mortality was collected.

Study procedures

According to the GOLD 2017 report, the patients were assigned to four groups. Group A, 0 or 1 exacerbation per year and no hospitalizations, CAT scores <10 and mMRC scores of 0–1; Group B, 0 or 1 exacerbation per year and no hospitalizations, CAT scores ⩾10 or mMRC scores ⩾2; Group C, ⩾2 exacerbations or ⩾1 hospitalization per year and CAT scores <10 and mMRC scores of 0–1; Group D, ⩾2 exacerbations or ⩾1 hospitalization per year and CAT scores ⩾10 or mMRC scores ⩾2.² Then, each group was classified into the LAMA, LABA + ICS, LABA + LAMA, and LABA + LAMA + ICS groups based on the inhalation therapy received at their first hospital visit.

According to the GOLD 2023 report, the patients were assigned to three groups. Group A, 0 or 1 exacerbation per year and no hospitalizations, CAT scores <10 and mMRC scores of 0–1; Group B, 0 or 1 exacerbation per year and no hospitalizations, CAT scores ⩾10 or mMRC scores ⩾2; and Group E, ⩾2 exacerbations or ⩾1 hospitalization per year.³ Then, each group was classified into the LAMA, LABA + ICS, LABA + LAMA, and LABA + LAMA + ICS groups based on the inhalation therapy they received at their first hospital visit. Patients with adjusted inhalation therapy were excluded from this study during 1 year of follow-up.

Variable definitions

Exacerbation is a COPD progression that requires antibiotics, oral corticosteroids, or hospitalization.⁶ Frequent exacerbation was defined as at least two exacerbations per year.⁷ A current smoker has had smoking exposure of ⩾10 pack-years, while a former smoker has had ⩾10 pack-years but has not smoked for more than 6 months.⁸ Adjusted inhalation therapy was defined as changing the inhalation therapy drugs or stopping inhalation therapy drugs for more than 3 months during 1 year of follow-up.⁹

Statistical analysis

Continuous variables are expressed as mean ± standard deviation or median and interquartile range (IQR). Continuous variables with a normal distribution and homogeneity of variance were analyzed with analysis of variance; otherwise, non-parametric tests were used. Multiple comparisons of differences between groups were Bonferroni adjusted. The chi-square test or Fisher’s exact test was used to analyze categorical variables. Risk factors for future exacerbation and mortality were identified and their adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using logistic regression analyses. Two sides and a value of p < 0.05 were considered to be statistically significant. SPSS 26.0 (IBM, Armonk, NY, USA) and Free Statistics software version 1.7.1 (Beijing, China) were used for statistical analysis of the data.

Results

The clinical characteristics of the COPD patients

A total of 4623 patients with COPD were enrolled in this study (Figure 1). The mean age was 65.7 ± 9.0 years and the majority were male (85.6%). The patients were assigned to Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), or Group E (47.2%; Table 1).

Figure 1.

Flow chart of this study.

Table 1.

The baseline clinical characteristics of the total COPD patients.

Variables	Total (n = 4623)
Age (years)	65.7 ± 9.0
Sex, n (%)
Male	3958 (85.6)
Female	665 (14.4)
BMI (kg/m²)	22.6 ± 3.5
Smoke history, n (%)
Never smoker	1090 (23.6)
Former smoker	1561 (33.8)
Current smoker	1972 (42.6)
Smoking (pack/year) (median, IQR)	35 (10, 50)
Biofuel exposure, n (%)
Yes	1741 (37.7)
No	2882 (62.3)
FEV1 %pred (mean ± SD)	54.0 ± 20.6
FEV1/FVC (mean ± SD)	48.1 ± 12.4
GOLD grades, n (%)
1	535 (11.6)
2	1915 (41.4)
3	1650 (35.7)
4	523 (11.3)
GOLD groups, n (%)
A	694 (15.0)
B	1747 (37.8)
C	336 (7.3)
D	1846 (39.9)
E	2182 (47.2)
CAT, (mean ± SD)	14.8 ± 6.6
mMRC (median, IQR)	2 (1, 3)
Therapy, n (%)
LAMA	1203 (26.0)
LABA + LAMA	561 (12.1)
LABA + ICS	670 (14.5)
LABA + LAMA + ICS	2189 (47.4)
Exacerbations in the past year (median, IQR)	1 (0, 2)
Exacerbations in the past year, n (%)
Yes	2593 (56.1)
No	2030 (43.9)
Frequent exacerbations, n (%)
Yes	1471 (31.8)
No	3152 (68.2)
Hospitalizations in the past year (median, IQR)	0 (0, 1)
Hospitalizations in the past year, n (%)
Yes	1550 (33.5)
No	3073 (66.5)

BMI, body mass index; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; GOLD, global initiative for chronic obstructive lung disease; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified medical research council.

After 1 year of follow-up, the proportion of patients suffering exacerbation, frequent exacerbation, and hospitalization were 27.7%, 12.5%, and 15.5%, respectively. The mortality was 2.2% (Table 2).

Table 2.

The future exacerbation and mortality in total COPD patients during 1 year of follow-up.

Variables	Total (n = 4623)
Exacerbations during 12 months (median, IQR)	0 (0, 1)
Exacerbations, n (%)
Yes	1250 (27.7)
No	3269 (72.3)
Frequent exacerbations, n (%)
Yes	564 (12.5)
No	3955 (87.5)
Hospitalizations during 12 months (median, IQR)	0 (0, 0)
Hospitalizations, n (%)
Yes	700 (15.5)
No	3819 (84.5)
Mortality, n (%)	104 (2.2)

COPD, chronic obstructive pulmonary disease; IQR, interquartile range.

The future exacerbation and mortality of different inhalation therapies in Group A patients

There was a total of 694 patients in Group A who were assigned to LAMA (37.3%), LABA + LAMA (15.9%), LABA + ICS (16.7%), and LABA + LAMA + ICS (30.1%) groups. They were then adjusted for confounding factors including age, sex, BMI, smoke history, biofuel exposure history, FEV1 %pred, CAT scores, mMRC scores, and exacerbation in the past year. There was no significant difference in future exacerbation, frequent exacerbation, hospitalization, and mortality among the LAMA, LABA + LAMA, LABA + ICS, and LABA + LAMA + ICS groups (Table 3 and Supplemental Table 2).

Table 3.

The future exacerbation and mortality of different inhalation therapies during follow-up in Groups A and B patients.

Variables	Group A						Group B
Variables	Total (n = 694)	LAMA (n = 259)	LABA + LAMA (n = 110)	LABA + ICS (n = 116)	LABA + LAMA + ICS (n = 209)	p-Value	Total (n = 1747)	LAMA (n = 432)	LABA + LAMA (n = 202)	LABA + ICS (n = 266)	LABA + LAMA + ICS (n = 847)	p-Value
Exacerbations during 12 months (median, IQR)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 1)	0 (0, 0)	0.821	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.002
Exacerbations, n (%)						0.394						0.007
Yes	136 (19.7)	49 (19.1)	21 (19.3)	26 (22.6)	40 (19.2)		348 (20.2)	98 (23.1)	25 (12.7)	64 (24.2)	161 (19.3)
No	553 (80.3)	208 (80.9)	88 (80.7)	89 (77.4)	168 (80.8)		1372 (79.8)	326 (76.9)	172 (87.3)	200 (75.8)	674 (80.7)
Frequent exacerbations, n (%)						0.557						<0.001
Yes	43 (6.2)	17 (6.6)	6 (5.5)	10 (8.7)	10 (4.8)		127 (7.4)	47 (11.1)	7 (3.6)*,^$	30 (11.4)	43 (5.1)*,^$
No	646 (93.8)	240 (93.4)	103 (94.5)	105 (91.3)	198 (95.2)		1593 (92.6)	377 (88.9)	190 (96.4)	234 (88.6)	792 (94.9)
Hospitalizations during 12 months (median, IQR)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.466	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.180
Hospitalizations, n (%)						0.448						0.215
Yes	77 (11.2)	25 (9.7)	14 (12.8)	10 (8.7)	28 (13.5)		183 (10.6)	49 (11.6)	15 (7.6)	35 (13.3)	84 (10.1)
No	612 (88.8)	232 (90.3)	95 (87.2)	105 (91.3)	180 (86.5)		1537 (89.4)	375 (88.4)	182 (92.4)	229 (86.7)	751 (89.9)
Mortality, n (%)	5 (0.7)	2 (0.8)	1 (0.9)	1 (0.69)	1 (0.5)	1.000	27 (1.5)	8 (1.9)	5 (2.5)	2 (0.8)	12 (1.4)	0.432

The bold p values indicate statistical significance.

Compared with the LAMA group, p < 0.05.

Compared with LABA + ICS group, p < 0.05.

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist.

The future exacerbation and mortality of different inhalation therapies in Group B patients

A total of 1747 patients were in Group B and assigned to either the LAMA (24.7%), LABA + LAMA (11.6%), LABA + ICS (15.2%), or LABA + LAMA + ICS (48.5%) groups. After being adjusted for confounding factors including age, sex, BMI, smoke history, biofuel exposure history, FEV1 %pred, CAT scores, mMRC scores, and exacerbation in the past year, the patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of future exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS (p < 0.05; Table 3 and Supplemental Table 3).

The future exacerbation and mortality of different inhalation therapies in Group C patients

A total of 336 patients were in Group C and assigned to the LAMA (29.5%), LABA + LAMA (14.9%), LABA + ICS (21.4%), and LABA + LAMA + ICS (34.2%) groups. After being adjusted for confounding factors including age, sex, BMI, smoke history, biofuel exposure history, FEV1 %pred, CAT scores, mMRC scores, and exacerbation in the past year, there was no significant difference in future exacerbation, frequent exacerbation, hospitalization, and mortality among the LAMA, LABA + LAMA, LABA + ICS, and LABA + LAMA + ICS groups (Table 4 and Supplemental Table 4).

Table 4.

The future exacerbation and mortality of different inhalation therapies during follow-up in Groups C and D patients.

Variables	Group C						Group D
Variables	Total (n = 336)	LAMA (n = 99)	LABA + LAMA (n = 50)	LABA + ICS (n = 72)	LABA + LAMA + ICS (n = 115)	p-Value	Total (n = 1846)	LAMA (n = 413)	LABA + LAMA (n = 199)	LABA + ICS (n = 216)	LABA + LAMA + ICS (n = 1018)	p-Value
Exacerbations during 12 months (median, IQR)	0 (0, 1)	0 (0, 1)	0 (0, 1)	0 (0, 1)	0 (0, 1)	0.593	0 (0, 1)	0 (0, 2)	0 (0, 1)*^$	0 (0, 2)	0 (0, 1)*^$	<0.001
Exacerbations, n (%)						0.526						<0.001
Yes	119 (35.7)	36 (36.7)	22 (44.0)	24 (34.3)	37 (32.2)		647 (36.4)	171 (43.2)	59 (31.1)	90 (42.9)	327 (33.3)
No	214 (64.3)	62 (63.3)	28 (56.0)	46 (65.7)	78 (67.8)		1130 (63.6)	225 (56.8)	131 (68.9)	120 (57.1)	654 (66.7)
Frequent exacerbations, n (%)						0.796						<0.001
Yes	54 (16.2)	16 (16.3)	10 (20.0)	12 (17.1)	16 (13.9)		340 (19.1)	105 (26.5)	19 (10.0)*^$	54 (25.7)	162 (16.5)*^$
No	279 (83.8)	82 (83.7)	40 (80.0)	58 (82.9)	99 (86.1)		1437 (80.9)	291 (73.5)	171 (90.0)	156 (74.3)	819 (83.5)
Hospitalizations during 12 months (median, IQR)	0 (0, 0)	0 (0, 0)	0 (0, 0.8)	0 (0, 0)	0 (0, 0)	0.532	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.885
Hospitalizations, n (%)						0.634						0.785
Yes	72 (21.6)	20 (20.4)	13 (26.0)	12 (17.1)	27 (23.5)		368 (20.7)	75 (18.9)	40 (21.1)	43 (20.5)	310 (21.4)
No	261 (78.4)	78 (79.6)	37 (74.0)	58 (82.9)	88 (76.5)		1409 (79.3)	321 (81.1)	150 (78.9)	167 (79.5)	771 (78.6)
Mortality, n (%)	3 (0.9)	1 (1.0)	0 (0.0)	2 (2.8)	0 (0.0)	0.229	69 (3.7)	17 (4.1)	9 (4.5)	6 (2.8)	37 (3.6)	0.780

The bold p values indicate statistical significance.

Compared with the LAMA group, p < 0.05.

Compared with LABA + ICS group, p < 0.05.

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting β2-Agonist; LAMA, long-acting muscarinic antagonist.

The future exacerbation and mortality of different inhalation therapies in Group D patients

A total of 1846 patients were in Group D and assigned to the LAMA (22.4%), LABA + LAMA (10.8%), LABA + ICS (11.7%), and LABA + LAMA + ICS (55.1%) groups. Afterward, patients were adjusted for confounding factors including age, sex, BMI, smoke history, biofuel exposure history, FEV1 %pred, CAT scores, mMRC scores, and exacerbation in the past year. The patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of future exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS (p < 0.05; Table 4 and Supplemental Table 5).

The future exacerbation and mortality of different inhalation therapies in Group E patients

A total of 2182 patients in Group E and assigned to LAMA (23.5%), LABA + LAMA (11.4%), LABA + ICS (13.2%), and LABA + LAMA + ICS (51.9%) groups. After adjusting for confounding factors including age, sex, BMI, smoke history, biofuel exposure history, FEV1 %pred, CAT scores, mMRC scores, and exacerbation in the past year. The patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of future exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS (p < 0.05; Table 5 and Supplemental Table 6).

Table 5.

The future exacerbation and mortality of different inhalation therapies during follow-up in Groups E and (A + C) patients.

Variables	Group E						Group (A+C)
Variables	Total (n = 2182)	LAMA (n = 512)	LABA + LAMA (n = 249)	LABA + ICS (n = 288)	LABA + LAMA + ICS (n = 1133)	p-Value	Total (n = 1030)	LAMA (n = 358)	LABA + LAMA (n = 160)	LABA + ICS (n = 188)	LABA + LAMA + ICS (n = 324)	p-Value
Exacerbations during 12 months (median, IQR)	0 (0, 1)	0 (0, 1)	0 (0, 1)*,^$	0 (0, 1)	0 (0, 1)*,^$	<0.001	0 (0, 0)	0 (0, 0)	0 (0, 1)	0 (0, 1)	0 (0, 0)	0.682
Exacerbations, n (%)						0.003						0.752
Yes	766 (36.3)	207 (41.9)	81 (33.8)	114 (40.7)	364 (33.2)		255 (25.0)	85 (23.9)	43 (27.0)	50 (27.0)	77 (23.8)
No	1344 (63.7)	287 (58.1)	159 (66.2)	166 (59.3)	732 (66.8)		767 (75.0)	270 (76.1)	116 (73.0)	135 (73.0)	246 (76.2)
Frequent exacerbations, n (%)						<0.001						0.552
Yes	394 (1).7	121 (24.5)	29 (12.1)*,^$	66 (23.6)	178 (16.2)*,^$		97 (9.5)	33 (9.3)	16 (10.1)	22 (11.9)	26 (8.0)
No	1716 (81.3)	373 (75.5)	211 (87.9)	214 (76.4)	918 (83.8)		925 (90.5)	322 (90.7)	143 (89.9)	163 (88.1)	297 (92.0)
Hospitalizations during 12 months (median, IQR)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.680	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.198
Hospitalizations, n (%)						0.648						0.222
Yes	440 (20.9)	95 (19.2)	53 (22.1)	55 (19.6)	237 (21.6)		149 (14.6)	45 (12.7)	27 (17.0)	22 (11.9)	55 (17.0)
No	1670 (79.1)	399 (80.8)	187 (77.9)	225 (80.4)	859 (78.4)		873 (85.4)	210 (87.3)	132 (83.0)	163 (88.1)	268 (83)
Mortality, n (%)	72 (3.3)	18 (3.5)	9 (3.6)	8 (2.8)	37 (3.3)	0.940	8 (0.8)	3 (0.8)	1 (0.6)	3 (1.6)	1 (0.3)	0.419

The bold p values indicate statistical significance.

Compared with the LAMA group, p < 0.05

Compared with LABA + ICS group, p < 0.05.

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting β2-Agonist; LAMA, long-acting muscarinic antagonist.

The future exacerbation and mortality of different inhalation therapies in Group (A + C) patients

A total of 1030 patients were in Group (A + C) and assigned to the LAMA (34.8%), LABA + LAMA (15.5%), LABA + ICS (18.3%), and LABA + LAMA + ICS (31.4%) groups. After being adjusted for confounding factors including age, sex, BMI, smoke history, biofuel exposure history, FEV1 %pred, CAT scores, mMRC scores, and exacerbation in the past year, there was no significant difference in future exacerbation, frequent exacerbation, hospitalization, and mortality among the LAMA, LABA + LAMA, LABA + ICS, and LABA + LAMA + ICS groups (Table 5 and Supplemental Table 7).

Discussion

Combined COPD assessment is an important tool to evaluate COPD patients in the GOLD reports and recommended initial inhalation therapy. This was different from the ‘ABCD’ groups based on the GOLD 2017 report where Groups C and D were merged into Group E to highlight the clinical relevance of exacerbation in the GOLD 2023 report. In addition, the initial inhalation therapy recommendations had changed and highlighted the important status of LABA + LAMA in Groups B and E based on the GOLD 2023 report. In fact, further studies are needed to validate the latest proposal. In this study, we are the first to analyze the future exacerbation and mortality of different inhalation therapies in various groups according to the GOLD 2017 and GOLD 2023 reports to validate whether the latest proposal is appropriate.

Although the initial inhalation therapy recommendation for patients in Group A should be a short- or a long-acting bronchodilator according to the GOLD 2023 report, mono-LAMA has in fact become the preferred initial therapy for patients in Group A among clinical practices.¹⁰ A previous study confirmed that 97% of patients in Group A received a LAMA as the initial inhalation therapy.¹¹ In this study, we found that the future exacerbation and mortality showed no significant difference between the different inhalation therapies in Group A. In addition, we found that the patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation compared to patients treated with LAMA or LABA + ICS in Groups B, D, and E. It is considered that ICS could increase the risk of pneumonia in COPD patients. Therefore, this implied that mono-LAMA should be recommended for patients in Group A, while LABA + LAMA should be recommended for patients in Groups B and E as the initial inhalation therapy. In other words, our findings support the updated GOLD 2023 report.

In fact, the number of patients in Group C was relatively small and had poor stability during follow-up.¹² In addition, we found that the future exacerbation and mortality showed no significant difference between different inhalation therapies in Group C. It is implied that mono-LAMA should be recommended for patients in Group C instead of LABA + LAMA. Considering the future exacerbation and mortality showed no significant difference between the different inhalation therapies in Group A. Therefore, we combined Groups A with C into a single group to analyze the outcomes. We found that the future exacerbation and mortality also showed no significant difference between different inhalation therapies after combining Groups A with C. Although several studies have confirmed that LABA + LAMA or LABA + LAMA + ICS were superior to LAMA or LABA + ICS in reducing future exacerbation and improving pulmonary function in COPD patients,^13
–17 these studies only focused on total patients with COPD rather than determining drug effectiveness according to the GOLD groups. In addition, studies showed that the treatment with LABA + LAMA or LABA + LAMA + ICS was better than LAMA at improving symptoms and reducing the risk of exacerbation in more symptomatic COPD patients (including Groups B and D).^18–19 However, our previous study found that there were no significant differences in exacerbation, hospitalization, and mortality during the follow-up among different inhalation therapies on less symptomatic COPD patients.²⁰ This study also confirmed that the patients in Groups A and C treated with LABA + LAMA or LABA + LAMA + ICS did not achieve better outcomes than patients treated with LAMA or LABA + ICS. Therefore, merging Groups C and D into Group E and recommending LABA + LAMA or LABA + LAMA + ICS as the initial inhalation therapy must be considered. However, merging Groups A and C into a single group (A + C) and recommending mono-LAMA as an initial inhalation therapy is also worth considering.

This study has some limitations. First, this is a retrospective study, meaning that randomized controlled trials are needed in the future. Finally, some studies have shown that the real-world prescriptions of initial inhalation therapy for COPD patients were not consistent with GOLD reports and the causes including pulmonary function, poor familiarity with recommendations, low self-efficacy, and time constraints might have an influence on the future exacerbation and mortality.^20–21

Conclusion

Patients in Group A should recommended a mono-LAMA, while patients in Groups B and E should recommended a LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is also worth considering merging Groups A and C into a single group and recommending a mono-LAMA as the initial inhalation therapy.

Supplemental Material

sj-docx-1-tar-10.1177_17534666231213715 – Supplemental material for The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports

Supplemental material, sj-docx-1-tar-10.1177_17534666231213715 for The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports by Qing Song, Wei Cheng, Cong Liu, Xueshan Li, Ling Lin, Yating Peng, Yuqin Zeng, Rong Yi, Yi Liu, Xin Li, Yan Chen, Shan Cai and Ping Chen in Therapeutic Advances in Respiratory Disease

Footnotes

Acknowledgements

We would like to thank the staff of the hospitals for their cooperation in collecting the study data.

Declarations

ORCID iD

Ping Chen

Supplemental material

Supplemental material for this article is available online.

References

GBD Chronic Respiratory Disease Collaborators. Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med 2020; 8: 585–596.

GOLD Executive Committee, Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2017 REPORT), https://goldcopd.org/ (2017, accessed November 2016).

GOLD Executive Committee, Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2023 REPORT), https://goldcopd.org/ (2023, accessed 16 November 2022).

Vogelmeier

Criner

Martinez

, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 2017; 195: 557–582.

von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453–1457.

Alcázar-Navarrete

Jamart

Sánchez-Covisa

, et al. Clinical characteristics, treatment persistence, and outcomes among patients With COPD treated with single- or multiple-inhaler triple therapy: a retrospective analysis in Spain. Chest 2022; 162: 1017–1029.

Le Rouzic

Roche

Cortot

, et al. Defining the ‘Frequent Exacerbator’ Phenotype in COPD: a hypothesis-free approach. Chest 2018; 153: 1106–1115.

Song

Zhao

Zeng

, et al. The characteristics of airflow limitation and future exacerbations in different GOLD Groups of COPD Patients. Int J Chron Obstruct Pulmon Dis 2021; 16: 1401–1412.

Covvey

Mullen

Ryan

, et al. A comparison of medication adherence/persistence for asthma and chronic obstructive pulmonary disease in the United Kingdom. Int J Clin Pract 2014; 68: 1200–1208.

10.

Ninane

Corhay

Germonpré

, et al. Inhaled treatment of COPD: a Delphi consensus statement. Int J Chron Obstruct Pulmon Dis 2017; 12: 793–801.

11.

Zeng

Cai

Chen

, et al. Current status of the treatment of COPD in China: a multicenter prospective observational study. Int J Chron Obstruct Pulmon Dis 2020; 15: 3227–3237.

12.

Soriano

Hahsler

Soriano

, et al. Temporal transitions in COPD severity stages within the GOLD 2017 classification system. Respir Med 2018; 142: 81–85.

13.

Rodrigo

Price

Anzueto

, et al. LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis 2017; 12: 907–922.

14.

Horita

Goto

Shibata

, et al. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev 2017; 2: CD012066.

15.

Calverley

PMA

Hoz

Xue

, et al. COPD maintenance therapy with tiotropium/olodaterol compared with tiotropium: an analysis in the absence of additional ICS therapy. COPD 2020; 17: 477–484.

16.

Anzueto

Kostikas

Mezzi

, et al. Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study. Respir Res 2018; 19: 121.

17.

Rabe

Martinez

Singh

, et al. Improvements in lung function with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler versus dual therapies in patients with COPD: a sub-study of the ETHOS trial. Ther Adv Respir Dis 2021; 15: 17534666211034329.

18.

Sethi

Kerwin

Watz

, et al. AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD. Int J Chron Obstruct Pulmon Dis 2019; 14: 667–682.

19.

Cheng

Duan

Zhou

, et al. Real-world effectiveness of inhalation therapy among patients with symptomatic COPD in China: a multicenter prospective study. Front Pharmacol 2021; 12: 753653.

20.

Song

Lin

Zhou

, et al. The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study. Ann Med 2023; 55: 1317–1324.

21.

Perez

Wisnivesky

Lurslurchachai

, et al. Barriers to adherence to COPD guidelines among primary care providers. Respir Med 2012; 106: 374–381.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.05 MB