Efficacy and safety of acupoint application for allergic rhinitis: a systematic review and Meta-analysis of randomized controlled trials

doi:10.19852/j.cnki.jtcm.2022.06.003

Abstract

Abstract:

OBJECTIVE: To use evidence-based medicine to explore the efficacy of acupoint application (AA) for allergic rhinitis (AR) at different time points and its safety.

METHODS: We searched 7 databases (PubMed, Cochrane, Embase, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, and China Biology Medicine disc) as well as the international clinical trial registration platform from January 2010 to March 2020 for randomized controlled trials (RCTs) comparing the efficacy of AA versus placebo, Western Medicine or other alternative therapies on AR. Risk of bias was assessed according to the Cochrane handbook, and statistical analysis was performed using RevMan 5.3. Outcomes included the total effective rate, recurrence rate, total nasal symptom score (TNSS), visual analogue scale (VAS), quality of life measured by the Rhinitis Quality of Life Questionnaire (RQLQ) or Short Form-36 (SF-36), adverse events, and biomarkers including immunoglobulin E (IgE), peripheral blood eosinophil count (EOS), interleukin-4 (IL-4), and interferon gamma (INF-γ).

RESULTS: Twenty-eight RCTs involving 3282 participants were included. The short-term and long-term efficacy of AA was significantly better than placebo, including better total effective rate [RR: 3.05, 95%CI (1.84, 5.07), after treatment; RR: 9.29, 95%CI (2.57, 33.66), at 6 months], lower recurrence rate [RR: 0.55, 95%CI (0.45, 0.66), at 6 months; RR: 0.65, 95%CI (0.57, 0.74), at 1 year], lower TNSS [MD: –3.09, 95%CI (–3.58, –2.61), after treatment], and lower RQLQ [MD: –14.79, 95%CI (–21.49, –8.10), after treatment; MD: –11.92, 95%CI (–17.40, –6.45), at 4-6 months]. Compared with Western Medicine, AA had better long-term total effective rate [RR: 1.33, 95%CI (1.05, 1.69), at 3 months; RR: 1.49, 95%CI 1.22 to 1.81, at 1 year) and lower recurrence rate [RR: 0.48, 95%CI (0.39, 0.58), at 6 months; RR: 0.45, 95%CI (0.33, 0.60), at 1 year]. AA had better long-term total effective rate versus acupuncture [RR: 2.06, 95% CI (1.28, 3.31), at 1 year] or oral Chinese medicine [RR: 1.21, 95% CI (1.09, 1.34), ≥ 6 months]. Both AA and Western Medicine can reduce serum levels of IgE, EOS, and IL-4 after treatment. The main adverse event of AA was local skin reaction without systemic side effects.

CONCLUSIONS: The short-term (within one month) and long-term (at 3 months, 6 months and 1 year) efficacy of acupoint application on AR was better than that of placebo. The long-term efficacy of acupoint application was superior to that of Western Medicine (at 3 months, 6 months and 1 year), oral Chinese medicine (at more than 6 months) and acupuncture (at 1 year). AA can reduce serum IgE, EOS, and IL-4 level of AR patients in a short run. Acupoint application is safe, but severe skin reactions can reduce patient compliance.

Key words: rhinitis, allergic, acupoint application, systematic review, Meta-analysis, randomized controlled trial

SHEN Mengxia, SHANG Wenfang, WU Jiangxia, YU Zelin, XUAN Lihua. Efficacy and safety of acupoint application for allergic rhinitis: a systematic review and Meta-analysis of randomized controlled trials[J]. Journal of Traditional Chinese Medicine, 2022, 42(6): 858-868.

Figures/Tables 6

References 46

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Study ID	Sample size (drop) (E /C)	Age (years, $\bar{x} \pm SD$) (E /C)	Experimental (season /course)	Control	Outcome	Modified Jadad Score
Acupoint application vs placebo (10 studies)
Lin L et al 2019¹⁷	34 /33	E: 34.68±11.93 / C: 38.39±12.79	Marc h-April 19:00-21:00, 2 h, 5 t	Placebo	ER, TNSS, RQLQ, EOS	5
Wang C et al 2019¹⁸	70(5) /70(3)	E: 41.6 / C: 40	Sanfu, 1-2 h, 3 t	Placebo	ER	6
Jiang QY 2018¹⁹	30 /30	E: 32.6 / C: 33.7	NR, 40 min-1 h, 6 t	Placebo	TNSS, IFN-γ, IL-4	6
Huang Q et al 2018²⁰	43 /40	E: 36.65±17.95 / C: 37.3±16.22	Sanfu, 2-6 h, 3 t	Placebo	ER, RQLQ	6
Xu Y et al 2018²¹	44 /42	E: 34.36±15.3 / C: 36.19±16.5	Sanfu, 2-6 h, 3 t	Placebo	ER	5
Hu QM et al 2017²²	38 /40	E: 35±12 / C: 36±9	Sanfu, 2 h, 5 t	Placebo	ER, TNSS, RQLQ, EOS	6
Zhang HL et al 2017²³	161 /81	E: 40±11 / C: 41±12	Sanfu, 2-6 h, 9 t	Placebo	ER, RE, VAS	5
Chen Y 2016²⁴	32 /27	E: 30±6 / C: 30±6	Sanfu, 3 h, 3 t	Placebo	SF-36, IgE, ECP	6
Deng GZ et al 2012²⁵	28 /26	E: 28.36±13.35 / C: 33.19±16.71	Sanfu, 2-6 h, 5 t	Placebo	ER, RQLQ	6
Mi JP Yu ZS 2010²⁶	158 /158	E: 36±12 / C: 36±13	Sanfu, 1-2 h, 9 t	Placebo	ER	4
Acupoint application vs Western Medicine (11 studies)
Liang W et al 2017^a27	40 /42	E: 39.90±12.27 C: 42.45±10.69	Sanfu, 4-6 h, 3 t	Antihistamine /Loratadine	ER, VAS	3
Sun XY 2019²⁸	60 /60	E: 16-40 / C: 16-40	Sanfu, 2-4 h, 9 t	Antihistamine /Loratadine	ER, RE	3
Zhu LJ 2016²⁹	32 /30	E: 42.75±13.04 / C: 40.67±12.70	Sanjiu, 2-4 h, 3 t	Antihistamine /Loratadine	ER, RQLQ, IgE	5
Chen QH 2016³⁰	108 /108	E: 34.9±5.2 / C: 36.6±4.8	Sanfu, 2-6 h, 4 t	Antihistamine /Cetirizine	ER	4
Liu Y 2011³¹	152 /150	E: 8.25±4.32 / C: 8.16±4.13	Sanfu, 3-4 h, 3 t	Antihistamine /Loratadine	ER, RE, IgE	4
Mi JP, Yu ZS 2011³²	49 /44	E: 37.14±13.63 / C: NR	NR, 1-2 h, 9 t	Nasal corticosteroid /Budesonide	ER	4
Xu XF 2011³³	45 /45	E: 30.6 / C: 32.7	Sanfu, 8 h, 3 t	Antihistamine /Loratadine	ER	3
Lin YK et al 2014³⁴	84(12) /84(6)	E: 5-82 / C: 5-82	Sanfu, 2-4 h, 4 t	Nasal corticosteroid / Becl-ometasone dipropionate	ER	4
Shi YJ 2011³⁵	30 /30	E: 20-56 / C: 19-58	NR, 4-6 h, 5-7 t	Antihistamine /Cetirizine	ER	3
Li YJ et al 2018³⁶	58 /57	E: 6.16±2.05 / C: 5.84±1.75	Sanfu, 0.5-1 h, 6 t	Leukotriene antagonist / Montelukast sodium	ER, IL-4, IFN-γ	5
Zhang JJ 2012³⁷	30 /30	E: 10.25±2.56 / C: 11.12±2.12	Sanfu Sanjiu, 2-4 h, 6 t	Immunotherapy / Dust mites drops	ER, IgE, EOS, IL-4, IFN-γ	4
Acupoint application vs acupuncture (3 studies)
Shen J 2014³⁸	28 /30	E: 18-65 / C: 18-65	December to January, 2-4 h, 8 t	Catgut embedding	ER, RE	5
Liang W et al 2017^b27	40 /41	E: 39.90±12.27 / C: 38.49 ±13.16	Sanfu, 4-6 h, 3 t	Needling	ER, VAS	3
Chen XH et al 2011³⁹	58 /58	E: 34.6 / C: 33.2	Sanfu, 3 h, 3 t	Needling	ER	3
Acupoint application vs oral Chinese medicine (4 studies)
Zhou XP et al 2014⁴⁰	40 /40	E: 33.66 ±20.18 / C: 35.92±21.79	Sanfu, 2-4 h, 3 t	Modified Jade Wind-Barrier	ER	3
Zhao MH et al 2012⁴¹	130 /130	E: 27.03±9.05 / C: 29.68±8.51	Sanfu, 2-6 h,3-9 t	Xinqin Granules	ER	3
Li XC 2012⁴²	30 /30	E: 30.87±10.56 / C: 30.40±10.98	2011 August to 2012 March, 8 h,4 t	Xinqin particles	ER	4
Huang L et al 2018⁴³	50 /50	E: 39.8±14.2 / C: 40.4±15.1	Sanfu, 2-6 h, 3 t, 3 y	Sichuan pepper prescription	ER	3

Study ID	Sample size (drop) (E /C)	Age (years, $\bar{x} \pm SD$) (E /C)	Experimental (season /course)	Control	Outcome	Modified Jadad Score
Acupoint application vs placebo (10 studies)
Lin L et al 2019¹⁷	34 /33	E: 34.68±11.93 / C: 38.39±12.79	Marc h-April 19:00-21:00, 2 h, 5 t	Placebo	ER, TNSS, RQLQ, EOS	5
Wang C et al 2019¹⁸	70(5) /70(3)	E: 41.6 / C: 40	Sanfu, 1-2 h, 3 t	Placebo	ER	6
Jiang QY 2018¹⁹	30 /30	E: 32.6 / C: 33.7	NR, 40 min-1 h, 6 t	Placebo	TNSS, IFN-γ, IL-4	6
Huang Q et al 2018²⁰	43 /40	E: 36.65±17.95 / C: 37.3±16.22	Sanfu, 2-6 h, 3 t	Placebo	ER, RQLQ	6
Xu Y et al 2018²¹	44 /42	E: 34.36±15.3 / C: 36.19±16.5	Sanfu, 2-6 h, 3 t	Placebo	ER	5
Hu QM et al 2017²²	38 /40	E: 35±12 / C: 36±9	Sanfu, 2 h, 5 t	Placebo	ER, TNSS, RQLQ, EOS	6
Zhang HL et al 2017²³	161 /81	E: 40±11 / C: 41±12	Sanfu, 2-6 h, 9 t	Placebo	ER, RE, VAS	5
Chen Y 2016²⁴	32 /27	E: 30±6 / C: 30±6	Sanfu, 3 h, 3 t	Placebo	SF-36, IgE, ECP	6
Deng GZ et al 2012²⁵	28 /26	E: 28.36±13.35 / C: 33.19±16.71	Sanfu, 2-6 h, 5 t	Placebo	ER, RQLQ	6
Mi JP Yu ZS 2010²⁶	158 /158	E: 36±12 / C: 36±13	Sanfu, 1-2 h, 9 t	Placebo	ER	4
Acupoint application vs Western Medicine (11 studies)
Liang W et al 2017^a27	40 /42	E: 39.90±12.27 C: 42.45±10.69	Sanfu, 4-6 h, 3 t	Antihistamine /Loratadine	ER, VAS	3
Sun XY 2019²⁸	60 /60	E: 16-40 / C: 16-40	Sanfu, 2-4 h, 9 t	Antihistamine /Loratadine	ER, RE	3
Zhu LJ 2016²⁹	32 /30	E: 42.75±13.04 / C: 40.67±12.70	Sanjiu, 2-4 h, 3 t	Antihistamine /Loratadine	ER, RQLQ, IgE	5
Chen QH 2016³⁰	108 /108	E: 34.9±5.2 / C: 36.6±4.8	Sanfu, 2-6 h, 4 t	Antihistamine /Cetirizine	ER	4
Liu Y 2011³¹	152 /150	E: 8.25±4.32 / C: 8.16±4.13	Sanfu, 3-4 h, 3 t	Antihistamine /Loratadine	ER, RE, IgE	4
Mi JP, Yu ZS 2011³²	49 /44	E: 37.14±13.63 / C: NR	NR, 1-2 h, 9 t	Nasal corticosteroid /Budesonide	ER	4
Xu XF 2011³³	45 /45	E: 30.6 / C: 32.7	Sanfu, 8 h, 3 t	Antihistamine /Loratadine	ER	3
Lin YK et al 2014³⁴	84(12) /84(6)	E: 5-82 / C: 5-82	Sanfu, 2-4 h, 4 t	Nasal corticosteroid / Becl-ometasone dipropionate	ER	4
Shi YJ 2011³⁵	30 /30	E: 20-56 / C: 19-58	NR, 4-6 h, 5-7 t	Antihistamine /Cetirizine	ER	3
Li YJ et al 2018³⁶	58 /57	E: 6.16±2.05 / C: 5.84±1.75	Sanfu, 0.5-1 h, 6 t	Leukotriene antagonist / Montelukast sodium	ER, IL-4, IFN-γ	5
Zhang JJ 2012³⁷	30 /30	E: 10.25±2.56 / C: 11.12±2.12	Sanfu Sanjiu, 2-4 h, 6 t	Immunotherapy / Dust mites drops	ER, IgE, EOS, IL-4, IFN-γ	4
Acupoint application vs acupuncture (3 studies)
Shen J 2014³⁸	28 /30	E: 18-65 / C: 18-65	December to January, 2-4 h, 8 t	Catgut embedding	ER, RE	5
Liang W et al 2017^b27	40 /41	E: 39.90±12.27 / C: 38.49 ±13.16	Sanfu, 4-6 h, 3 t	Needling	ER, VAS	3
Chen XH et al 2011³⁹	58 /58	E: 34.6 / C: 33.2	Sanfu, 3 h, 3 t	Needling	ER	3
Acupoint application vs oral Chinese medicine (4 studies)
Zhou XP et al 2014⁴⁰	40 /40	E: 33.66 ±20.18 / C: 35.92±21.79	Sanfu, 2-4 h, 3 t	Modified Jade Wind-Barrier	ER	3
Zhao MH et al 2012⁴¹	130 /130	E: 27.03±9.05 / C: 29.68±8.51	Sanfu, 2-6 h,3-9 t	Xinqin Granules	ER	3
Li XC 2012⁴²	30 /30	E: 30.87±10.56 / C: 30.40±10.98	2011 August to 2012 March, 8 h,4 t	Xinqin particles	ER	4
Huang L et al 2018⁴³	50 /50	E: 39.8±14.2 / C: 40.4±15.1	Sanfu, 2-6 h, 3 t, 3 y	Sichuan pepper prescription	ER	3

Outcome	Length of follow up	No. of Studies	No. of Parti-cipants	Statistical method	Effect estimate with 95% CI	I² value (%)	P value	GRADE level
Total effective rate
AA vs Placebo		7	742	RR (M-H, random)	3.05 (1.84, 5.07)	82	< 0.0001	Low
AA vs Placebo	3 months	2	383	RR (M-H, random)	10.52 (1.07, 102.97)	67	< 0.00001	Very low
AA vs Placebo	6 months	2	558	RR (M-H, random)	9.29 (2.57, 33.66)	84	0.0007	Low
AA vs Placebo	1 year	1	242	RR (M-H, random)	73.45 (10.47, 515.49)	-	< 0.0001	Moderate
AA vs Western Medicine	≤ 1 month	11	1350	RR (M-H, random)	1.02 (0.89, 1.18)	80	0.74	Very low
AA vs Western Medicine	3 months	1	93	RR (M-H, random)	1.33 (1.05, 1.69)	-	0.02	Low
AA vs Western Medicine	1 year	2	306	RR (M-H, fixed)	1.49 (1.22, 1.81)	0	< 0.0001	Low
AA vs Acupuncture		3	255	RR (M-H, random)	0.61 (0.35, 1.06)	94	0.08	Very low
AA vs Acupuncture	1 year	1	116	RR (M-H, random)	2.06 (1.28, 3.31)	-	0.003	Low
AA vs Oral Chinese medicine	≤ 1 month	2	320	RR (M-H, fixed)	1.07 (0.96, 1.20)	0	0.22	Very low
AA vs Oral Chinese medicine	≥ 6 months	3	440	RR (M-H, fixed)	1.21 (1.09, 1.34)	0	0.0003	Low
RQLQ
AA vs Placebo		4	282	MD (IV, random)	-14.79 (-21.49, -8.10) (-21.49, -8.10)	63	< 0.0001	Low
AA vs Placebo	4-6 months	2	137	MD (IV, fixed)	-11.92 (-17.40, -6.45)	0	< 0.0001	Moderate
AA vs Placebo	8 months	1	83	MD (IV, fixed)	-9.97 (-20.43, 0.49)	-	0.06	Moderate
AA vs Western Medicine		1	62	MD (IV, fixed)	-7.13 (-13.46, -0.80)	-	0.03	Low
TNSS
AA vs Placebo		2	145	MD (IV, fixed)	-3.09 (-3.58, -2.61)	0	< 0.00001	Low
AA vs Placebo (sneezing)		1	60	MD (IV, fixed)	-0.43 (-0.75, -0.12)	-	0.006	Low
AA vs Placebo (rhinorrhea)		1	60	MD (IV, fixed)	-0.53 (-0.93, -0.13)	-	0.009	Low
AA vs Placebo (nasal itching)		1	60	MD (IV, fixed)	0.37 (-0.08, 0.81)	-	0.1	Low
AA vs Placebo (nasal congestion)		1	60	MD (IV, fixed)	-0.57 (-1.01, -0.13)	-	0.01	Low
Recurrence rate
AA vs Western Medicine	6 months	2	422	RR (M-H, fixed)	0.48 (0.39, 0.58)	50	< 0.00001	Low
AA vs Western Medicine	1 year	1	120	RR (M-H, fixed)	0.45 (0.33, 0.60)	-	< 0.00001	Low
AA vs Acupuncture	1 month	1	58	RR (M-H, fixed)	3.21 (0.71, 14.63)	-	0.13	Very low
AA vs Placebo	6 months	1	242	RR (M-H, fixed)	0.55 (0.45, 0.66)	-	< 0.00001	Moderate
AA vs Placebo	1 year	1	242	RR (M-H, fixed)	0.65 (0.57, 0.74)	-	< 0.00001	Moderate
VAS
AA vs Placebo		1	242	MD (IV, random)	-1.58 (-2.11, -1.05)	-	< 0.00001	Low
AA vs Placebo	6 months	1	242	MD (IV, random)	-2.32 (-2.91, -1.73)	-	< 0.00001	Low
AA vs Placebo	1 year	1	242	MD (IV, random)	-2.34 (-2.93, -1.75)	-	< 0.00001	Low
AA vs Acupuncture		1	81	MD (IV, fixed)	6.79 (4.59, 8.99)	-	< 0.00001	Very low
AA vs Acupuncture	6 months	1	81	MD (IV, fixed)	1.82 (-0.39, 4.03)	-	0.11	Very low
AA vs Western Medicine		1	82	MD (IV, fixed)	8.40 (6.49, 10.31)	-	< 0.00001	Very low
AA vs Western Medicine	6 months	1	82	MD (IV, fixed)	-2.40 (-4.48, -0.32)	-	0.02	Very low
IgE
AA vs Placebo		1	59	MD (IV, fixed)	-2.00 (-137.77, 133.77)	-	0.98	Low
AA vs Western Medicine		3	424	SMD (IV, random)	-18.50 (-25.84, -11.15)	100	< 0.00001	Very low
EOS
AA vs Placebo		1	78	MD (IV, fixed)	-1.49 (-2.74, -0.24)	-	0.02	Low
AA vs Western Medicine		1	60	MD (IV, fixed)	2.42 (1.67, 3.17)	-	< 0.00001	Very low
IL-4
AA vs Western Medicine		2	175	SMD (IV, fixed)	0.63 (0.33, 0.94)	9	< 0.0001	Low
IFN-γ
AA vs Western Medicine		2	175	SMD (IV, fixed)	-0.03 (-0.33, 0.27)	0	0.84	Low

Outcome	Length of follow up	No. of Studies	No. of Parti-cipants	Statistical method	Effect estimate with 95% CI	I² value (%)	P value	GRADE level
Total effective rate
AA vs Placebo		7	742	RR (M-H, random)	3.05 (1.84, 5.07)	82	< 0.0001	Low
AA vs Placebo	3 months	2	383	RR (M-H, random)	10.52 (1.07, 102.97)	67	< 0.00001	Very low
AA vs Placebo	6 months	2	558	RR (M-H, random)	9.29 (2.57, 33.66)	84	0.0007	Low
AA vs Placebo	1 year	1	242	RR (M-H, random)	73.45 (10.47, 515.49)	-	< 0.0001	Moderate
AA vs Western Medicine	≤ 1 month	11	1350	RR (M-H, random)	1.02 (0.89, 1.18)	80	0.74	Very low
AA vs Western Medicine	3 months	1	93	RR (M-H, random)	1.33 (1.05, 1.69)	-	0.02	Low
AA vs Western Medicine	1 year	2	306	RR (M-H, fixed)	1.49 (1.22, 1.81)	0	< 0.0001	Low
AA vs Acupuncture		3	255	RR (M-H, random)	0.61 (0.35, 1.06)	94	0.08	Very low
AA vs Acupuncture	1 year	1	116	RR (M-H, random)	2.06 (1.28, 3.31)	-	0.003	Low
AA vs Oral Chinese medicine	≤ 1 month	2	320	RR (M-H, fixed)	1.07 (0.96, 1.20)	0	0.22	Very low
AA vs Oral Chinese medicine	≥ 6 months	3	440	RR (M-H, fixed)	1.21 (1.09, 1.34)	0	0.0003	Low
RQLQ
AA vs Placebo		4	282	MD (IV, random)	-14.79 (-21.49, -8.10) (-21.49, -8.10)	63	< 0.0001	Low
AA vs Placebo	4-6 months	2	137	MD (IV, fixed)	-11.92 (-17.40, -6.45)	0	< 0.0001	Moderate
AA vs Placebo	8 months	1	83	MD (IV, fixed)	-9.97 (-20.43, 0.49)	-	0.06	Moderate
AA vs Western Medicine		1	62	MD (IV, fixed)	-7.13 (-13.46, -0.80)	-	0.03	Low
TNSS
AA vs Placebo		2	145	MD (IV, fixed)	-3.09 (-3.58, -2.61)	0	< 0.00001	Low
AA vs Placebo (sneezing)		1	60	MD (IV, fixed)	-0.43 (-0.75, -0.12)	-	0.006	Low
AA vs Placebo (rhinorrhea)		1	60	MD (IV, fixed)	-0.53 (-0.93, -0.13)	-	0.009	Low
AA vs Placebo (nasal itching)		1	60	MD (IV, fixed)	0.37 (-0.08, 0.81)	-	0.1	Low
AA vs Placebo (nasal congestion)		1	60	MD (IV, fixed)	-0.57 (-1.01, -0.13)	-	0.01	Low
Recurrence rate
AA vs Western Medicine	6 months	2	422	RR (M-H, fixed)	0.48 (0.39, 0.58)	50	< 0.00001	Low
AA vs Western Medicine	1 year	1	120	RR (M-H, fixed)	0.45 (0.33, 0.60)	-	< 0.00001	Low
AA vs Acupuncture	1 month	1	58	RR (M-H, fixed)	3.21 (0.71, 14.63)	-	0.13	Very low
AA vs Placebo	6 months	1	242	RR (M-H, fixed)	0.55 (0.45, 0.66)	-	< 0.00001	Moderate
AA vs Placebo	1 year	1	242	RR (M-H, fixed)	0.65 (0.57, 0.74)	-	< 0.00001	Moderate
VAS
AA vs Placebo		1	242	MD (IV, random)	-1.58 (-2.11, -1.05)	-	< 0.00001	Low
AA vs Placebo	6 months	1	242	MD (IV, random)	-2.32 (-2.91, -1.73)	-	< 0.00001	Low
AA vs Placebo	1 year	1	242	MD (IV, random)	-2.34 (-2.93, -1.75)	-	< 0.00001	Low
AA vs Acupuncture		1	81	MD (IV, fixed)	6.79 (4.59, 8.99)	-	< 0.00001	Very low
AA vs Acupuncture	6 months	1	81	MD (IV, fixed)	1.82 (-0.39, 4.03)	-	0.11	Very low
AA vs Western Medicine		1	82	MD (IV, fixed)	8.40 (6.49, 10.31)	-	< 0.00001	Very low
AA vs Western Medicine	6 months	1	82	MD (IV, fixed)	-2.40 (-4.48, -0.32)	-	0.02	Very low
IgE
AA vs Placebo		1	59	MD (IV, fixed)	-2.00 (-137.77, 133.77)	-	0.98	Low
AA vs Western Medicine		3	424	SMD (IV, random)	-18.50 (-25.84, -11.15)	100	< 0.00001	Very low
EOS
AA vs Placebo		1	78	MD (IV, fixed)	-1.49 (-2.74, -0.24)	-	0.02	Low
AA vs Western Medicine		1	60	MD (IV, fixed)	2.42 (1.67, 3.17)	-	< 0.00001	Very low
IL-4
AA vs Western Medicine		2	175	SMD (IV, fixed)	0.63 (0.33, 0.94)	9	< 0.0001	Low
IFN-γ
AA vs Western Medicine		2	175	SMD (IV, fixed)	-0.03 (-0.33, 0.27)	0	0.84	Low

Item	Subgroup	No. of Studies	No. of Participants	Risk ratio with 95% CI	I²	P value
AA vs placebo on the total effective rate after treatment
Application season	Sanfu	6	675	2.53 (1.65, 3.86)	77%	<0.0001
	Non-sanfu	1	67	30.09 (4.35, 207.89)	-	0.0006
Times of application	<5	3	301	2.62 (1.33, 5.19)	73%	0.006
	≥5	4	441	4.51 (1.59, 12.73)	89%	0.005
AA vs Western Medicine on the total effective rate after treatment
Controlled intervention	AA vs Antihistamines	6	842	0.99 (0.78, 1.26)	87%	0.97
	AA vs Glucocorticoids	2	243	0.99 (0.89, 1.10)	1%	0.93
	AA vs Antihistamines plus Glucocorticoids	1	90	0.80 (0.66, 0.98)	-	0.03
	AA vs Leukotriene antagonists	1	115	1.17 (0.86, 1.59)	-	0.31
	AA vs Immunotherapy	1	60	1.25 (0.93, 1.69)	-	0.14
Age	Children	3	477	1.27 (1.14, 1.42)	0%	<0.001
	Adults	8	873	0.95 (0.80, 1.12)	82%	0.53
Application season	Sanfu	7	1075	1.00 (0.82, 1.23)	87%	0.98
(two studies NR)	Sanjiu	1	62	1.05 (0.84, 1.33)	-	0.65
	Sanfu plus Sanjiu	1	60	1.25 (0.93, 1.69)	-	0.14
Times of application	<5	6	902	0.93 (0.75, 1.17)	87%	0.55
	≥5	5	448	1.11 (0.93, 1.32)	65%	0.26

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