Association of Chinese Herbal Medicines Use with Development of Chronic Obstructive Pulmonary Disease Among Patients with Rheumatoid Arthritis: A Population-Based Cohort Study

Figures & data

Figure 1 Flowchart showing the method of selecting and following study subjects.

Table 1 Characteristics of the Study Subjects

Variables	Total Group	Non-CHMs Users	CHMs Users	P
		N =3360 (%)	N =3360 (%)
Age (years)				0.75
≤50	2743(40.8)	1378(41.0)	1365(40.6)
>50	3977(59.2)	1982(59.0)	1995(59.4)
Mean (SD)	53.8±14.0	53.80±14.3	53.72±13.5	0.81
Sex				0.53
Female	4945(73.6)	2461(73.2)	2484(73.9)
Male	1775(26.4)	899(26.8)	876(26.1)
Monthly income				0.44
Low	2972(44.2)	1504(44.8)	1468(43.7)
Median	3485(51.9)	1733(51.6)	1752(52.1)
High	263(3.9)	123(3.7)	140(4.2)
Residential area				0.84
Urban	3842(57.2)	1933(57.5)	1909(56.8)
Suburban	1043(15.5)	518(15.4)	525(15.6)
Rural	1835(27.3)	909(27.1)	926(27.6)
Medication use				0.50
Yes	5008(74.5)	2492(74.2)	2516(74.9)
No	1712(25.5)	868(25.8)	844(25.1)
Comorbidity
Hypertension	1816(27.0)	902(26.8)	914(27.2)	0.74
Diabetes	850(12.6)	411(12.2)	439(13.1)	0.30
Heart disease	1038(15.4)	499(14.9)	539(16.0)	0.18
Chronic kidney disease	87(1.3)	49(1.5)	38(1.1)	0.24
Cancer	206(3.1)	102(3.0)	104(3.1)	0.89
Alcohol dependence syndrome	14(0.2)	7(0.2)	7(0.2)	0.99
Tobacco use	7(0.1)	5(0.1)	2(0.1)	0.26
Follow-up time (years) (mean, median)	7.84(7.57)	7.85(7.56)	7.84(7.59)

Table 2 Risk of COPD for RA Patients with and Without CHMs Use

Patient Group	N	Events	PYs	Incidence	Crude HR (95% CI)	Adjusted HR* (95% CI)
Non-CHMs users	3360	202	26,380.64	7.66	1.00	1
CHMs users	3360	136	26,352.11	5.16	0.67 (0.54–0.83)	0.68 (0.54–0.84)
CHMs use for 31–365 days	2749	122	20,773.28	5.87	0.77 (0.60–0.94)	0.77 (0.60–0.93)
CHMs use for 366–730 days	346	9	2966.02	3.03	0.40 (0.20–0.77)	0.44 (0.23–0.80)
CHMs use for more than 730 days	265	5	2612.81	1.91	0.25 (0.11–0.63)	0.28 (0.11–0.67)

Notes: *Model adjusted for sex, age, urbanization level, monthly income, medication use and comorbidities.

Figure 2 Cumulative incidence of COPD in RA patients with and without receiving CHMs treatment during the 15-year study period (log-rank test, P< 0.001).

Table 3 Incidence and COPD Risk for RA Patients with and Without CHMs Use, Stratified by Sex and Age

Variables	Non- CHMs Users			CHMs Users			Crude HR (95% CI)	Adjusted HR (95% CI)
	Case	PYs	Incidence	Case	PY	Incidence
Sex
Female	115	19,038.32	6.04	62	19,485.41	3.18	0.53 (0.38–0.71)	0.57^Υ (0.42–0.77)
Male	87	7342.32	11.85	74	6866.71	10.78	0.91 (0.66–1.21)	0.82^Υ (0.60–1.12)
Age (years)
≤50	27	11,230.89	2.40	20	11,182.57	1.79	0.74 (0.42–1.33)	0.74* (0.41–1.32)
>50	175	15,149.74	11.55	116	15,169.54	7.65	0.66 (0.52–0.83)	0.63* (0.50–0.80)

Notes: ^ΥModel adjusted for age, urbanization level, monthly income, medication use and comorbidities. *Model adjusted for sex, urbanization level, monthly income, medication use and comorbidities.

Table 4 Risk of COPD in Relation to the 10 Most Used Single-Herb and Multi-Herb CHMs Products for RA Patients

Chinese Herbal Product	Number of Prescriptions	Crude HR (95% CI)	Adjusted HR* (95% CI)
Single-herb products
Yan Hu Suo	8699	0.45(0.34–0.62)	0.57(0.42–0.70)
Sānɡ Zhī	2119	0.41(0.24–0.70)	0.53(0.32–0.81)
Chuan-Niu-Xi	2186	0.67(0.43–1.04)	0.79(0.47–1.14)
Bei Mu	5221	0.61(0.54–0.96)	0.77(0.56–1.09)
Du-Zhong	5008	0.71(0.50–1.03)	0.72(0.51–1.08)
Dan-Shen	5775	0.52(0.36–0.75)	0.58(0.40–0.84)
Ji-Xue-Teng	4500	0.68(0.35–1.04)	0.69(0.37–1.04)
Huang Qin	5230	0.50(0.35–0.71)	0.59(0.45–0.90)
Hai Piao Xiao	3436	0.57(0.36–0.88)	0.77(0.47–1.15)
Da Huang	4585	0.53(0.35–0.81)	0.74(0.41–1.09)
Multi-herb products
Shu-Jing-Huo-Xue-Tang	9390	0.58(0.44–0.74)	0.64(0.50–0.83)
Jia-Wei-Xiao-Yao-San	8898	0.41(0.29–0.58)	0.65(0.46–0.90)
Shao-Yao-Gan-Cao-Tang	5722	0.72(0.55–0.94)	0.83(0.63–1.10)
Ge-Gen-Tang	5819	0.51(0.37–0.70)	0.65(0.47–0.89)
Dang-Gui-Nian-Tong-Tang	5033	0.63(0.45–0.88)	0.77(0.55–1.07)
Xue-Fu-Zhu-Yu-Tang	4463	0.68(0.50–0.94)	0.76(0.57–1.06)
Du-Huo-Ji-Sheng-Tang	6623	0.56(0.41–0.77)	0.57(0.42–0.77)
Chuan-Xiong-Cha-Tiao-San	4827	0.68(0.47–0.95)	0.73(0.44–1.10)
Zhi-Gan-Cao-Tang	3677	0.71(0.48–1.07)	0.77(0.52–1.12)
Gan-Lu-Yin	4101	0.68(0.41–0.94)	0.75(0.45–1.06)

Notes: *Model adjusted for age, sex, urbanization level, monthly income, medication use and comorbidities.