Traditional Chinese Medicine treatment with syndrome differentiation for patients with severe community-acquired pneumonia: a multicenter, randomized, placebo-controlled trial

doi:10.19852/j.cnki.jtcm.2025.06.015

Abstract

Abstract:

OBJECTIVE: To assess the effect of Traditional Chinese Medicine (TCM) treatment with syndrome differentiation in patients with severe community-acquired pneumonia (CAP).

METHODS: A multicenter, randomized, placebo-controlled trial was conducted. Adult patients with severe CAP were randomly allocated to receive conventional medicine treatment (conventional group) or conventional medicine combine with TCM treatment with syndrome differentiation (combination group) underwent a 28-d treatment time. The primary endpoint was treatment failure. Secondary outcomes included time to clinical stability, 28-d mortality, 90-d mortality, length of hospital stay.

RESULTS: A total of 183 patients were included in the intention-to-treat (ITT) population, with 91 allocated to the combination group and 92 to the conventional group. Patients with treatment failure in the combination group (18/91, 19.8%) were lower compared with the conventional group (34/92, 37.0%). Time to clinical stability was shorter in the combination group (11.8 d) than in the conventional group [17.8 d; HR = 2.08, 95% CI (1.38, 3.14); P = 0.001]. The 28-d mortality was lower in the combination group (17.6%) than in the conventional group (31.5%). There was no difference in the length of hospital stay between the two groups (P = 0.901). Adverse events were evenly distributed between the combination and conventional groups (P = 0.837).

CONCLUSION: Among patients with severe CAP, TCM treatment with syndrome differentiation reduced treatment failure, time to clinical stability, and the 28-d mortality and the 90-d mortality among patients admitted to the ward, without an increase in complications.

Key words: community-acquired pneumonia, treatment failure, randomized controlled trial, medicine, Chinese traditional, treatment with syndrome differentiation

LI Jiansheng, WANG Haifeng, ZHANG Kang, XIE Kai, LI Suyun, ZHANG Chenxi, ZHANG Yaqing. Traditional Chinese Medicine treatment with syndrome differentiation for patients with severe community-acquired pneumonia: a multicenter, randomized, placebo-controlled trial[J]. Journal of Traditional Chinese Medicine, 2025, 45(6): 1376-1384.

Figures/Tables 5

References 44.

1.	Torres A, Cilloniz C, Niederman MS, et al. Pneumonia. Nat Rev Dis Primers 2021; 7: 25. DOI PMID
2.	Ramirez JA, Wiemken TL, Peyrani P, et al. Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality. Clin Infect Dis 2017; 65: 1806-12. DOI PMID
3.	Song JH, Huh K, Chung DR. Community-acquired pneumonia in the Asia-Pacific region. Semin Respir Crit Care Med 2016; 37: 839-54. DOI URL
4.	Ferreira-Coimbra J, Sarda C, Rello J. Burden of community-acquired pneumonia and unmet clinical needs. Adv Ther 2020; 37: 1302-18. DOI PMID
5.	Nair GB, Niederman MS. Updates on community acquired pneumonia management in the ICU. Pharmacol Ther 2021; 217: 107663.
6.	Bartos H, Dzupova O. Severe community-acquired pneumonia in intensive care. Epidemiol Mikrobiol Imunol 2020; 69: 159-63.
7.	Zaragoza R, Vidal-Cortes P, Aguilar G, et al. Update of the treatment of nosocomial pneumonia in the ICU. Crit Care 2020; 24: 383. DOI
8.	Olson G, Davis AM. Diagnosis and treatment of adults with community-acquired pneumonia. Jama 2020; 323: 885-6. DOI PMID
9.	Wang J, Song YL. Advances in severe community-acquired pneumonia. Chin Med J (Engl) 2019; 132: 1891-3.
10.	Sun WZ, Sun GR. General principle of high-quality academic development of Traditional Chinese Medicine: "carrying on the essence, while pursuing innovations". J Tradit Chin Med 2023; 43: 1-2.
11.	Hu Q, Yu T, Li J, Yu Q, Zhu L, Gu Y. End-to-end syndrome differentiation of Yin deficiency and Yang deficiency in Traditional Chinese Medicine. Comput Methods Programs Biomed 2019; 174: 9-15.
12.	Li ZX, Wang XR, Ulloa L, et al. Complementary and alternative medicine on cognitive defects and neuroinflammation after sepsis. J Tradit Chin Med 2024; 44: 408-16. DOI
13.	Ma HD, Deng YR, Tian Z, Lian ZX. Traditional Chinese Medicine and immune regulation. Clin Rev Allergy Immunol 2013; 44: 229-41.
14.	Song Y, Yao C, Yao Y, et al. Xuebijing injection versus placebo for critically ill patients with severe community-acquired pneumonia: a randomized controlled trial. Crit Care Med 2019; 47: e735-43. DOI URL
15.	Cai H, Luo S, Cai X, et al. Effect of Fu Zheng Jie Du formula on outcomes in patients with severe pneumonia receiving prone ventilation: a retrospective cohort study. Front Pharmacol 2024; 15: 1428817.
16.	Wang H, Li J, Yu X, Li SY. Integrated traditional Chinese and conventional medicine in treatment of severe community-acquired pneumonia: study protocol for a randomized placebo-controlled trial. Trials 2018; 19: 620. DOI PMID
17.	Qu JM, Cao B. Guidelines for the diagnosis and treatment of adult community acquired pneumonia in China (2016 edition). Zhonghua Jie He He Hu XI Za Zhi 2016; 39: 241-2.
18.	Li JS, Wang ZW, Li SY. Diagnostic criteria for Traditional Chinese Medicine syndromes of community-acquired pneumonia (2011 edition). Zhong Yi Za Zhi 2011; 52: 2158-9.
19.	Yu XQ, Xie Y, Li JS. Guidelines for Traditional Chinese Medicine in the diagnosis and treatment of community acquired pneumonia (2018 revised edition). Zhong Yi Za Zhi 2019; 60: 350-60.
20.	Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 2015; 313: 677-86. DOI PMID
21.	Halm EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA 1998; 279: 1452-7. DOI URL
22.	Luo X, Xie J, Huang L, Gan WF, Chen M. Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease: a systematic review and Meta-analysis. J Tradit Chin Med 2023; 43: 429-40. DOI
23.	Liu Z, Yan S, Wu J, et al. Acupuncture for chronic severe functional constipation: a randomized trial. Ann Intern Med 2016; 165: 761-9. DOI PMID
24.	Luo Y, Wang CZ, Hesse-Fong J, Lin JG, Yuan CS. Application of Chinese medicine in acute and critical medical conditions. Am J Chin Med 2019; 47: 1223-35. DOI URL
25.	Jiang M, Lu C, Zhang C, et al. syndrome differentiation in modern research of Traditional Chinese Medicine. J Ethnopharmacol 2012; 140: 634-42. DOI PMID
26.	Wang WJ, Zhang T. Integration of Traditional Chinese Medicine and Western medicine in the era of precision medicine. J Integr Med 2017; 15: 1-7.
27.	Zhou LY, Wang YJ, Shi Q. Discuss the unity of opposites between precision medicine and Traditional Chinese Medicine. Zhong Hua Yi Xue Za Zhi 2017; 97: 3281-2.
28.	Liu Y, Zhang C, Li C, Bai C, Shang H. Marked reduction in 28-d mortality among elderly patients with severe community-acquired pneumonia: post hoc analysis of a large randomized controlled trial. Clin Interv Aging 2020; 15: 2109-15.
29.	Qi F, Liang ZX, She DY, Yan GT, Chen LA. A clinical study on the effects and mechanism of Xuebijing injection in severe pneumonia patients. J Tradit Chin Med 2011; 31: 46-9. DOI PMID
30.	Li Y, Tian WM, Wu Q, Zhang R. Combined Traditional and Western Medicine in the treatment of 100 elderly patients suffering from severe pneumonia: an analysis of clinical results. Zhong Guo Wei Zhong Bing Ji Jiu Yi Xue 2011; 23: 44-5.
31.	Menendez R, Torres A. Treatment failure in community-acquired pneumonia. Chest 2007; 132: 1348-55. PMID
32.	Dinh A, Duran C, Ropers J, et al. Factors associated with treatment failure in moderately severe community-acquired pneumonia: a secondary analysis of a randomized clinical trial. JAMA Netw Open 2021; 4: e2129566.
33.	Ceccato A, Cilloniz C, Ranzani OT, et al. Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: a post-hoc exploratory analysis of a randomized controlled trial. PLoS One 2017; 12: e0178022.
34.	Garcia-Vidal C, Carratala J. Early and late treatment failure in community-acquired pneumonia. Semin Respir Crit Care Med 2009; 30: 154-60. DOI PMID
35.	Walden AP, Clarke GM, McKechnie S, et al. Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Crit Care 2014; 18: R58.
36.	Li Y, Guo C, Chen Q, et al. Improvement of pneumonia by curcumin-loaded bionanosystems based on platycodon grandiflorum polysaccharides via calming cytokine storm. Int J Biol Macromol 2022; 202: 691-706. DOI URL
37.	Yang D, Chen C, Zhang Q, Gong J. Network pharmacology predicts targets and pathways of herbal components for the treatment of pneumonia: a review. Medicine (Baltimore) 2025; 104: e41372.
38.	Liang Y, Li Y, Zhang K, et al. Qingfei Jiedu Huatan formula inhibits NLRP 3 inflammasome activation to attenuates inflammation and pyroptosis in severe pneumonia: integrating experimental verification, network pharmacology and transcriptomics. J Ethnopharmacol 2025; 343: 119449. DOI URL
39.	Niu L, Xiao L, Zhang X, et al. Comparative efficacy of Chinese herbal injections for treating severe pneumonia: a systematic review and bayesian network Meta-analysis of randomized controlled trials. Front Pharmacol 2021; 12: 743486. DOI URL
40.	Luo W, Liu Y, Zhang Q, Zhong H, Deng J. Effect of Traditional Chinese Medicine injections on severe pneumonia: a protocol for systematic review and Meta-analysis. Medicine (Baltimore) 2020; 99: e22012. DOI URL
41.	Lodise TP, Anzueto AR, Weber DJ, et al. Assessment of time to clinical response, a proxy for discharge readiness, among hospitalized patients with community-acquired pneumonia who received either ceftaroline fosamil or ceftriaxone in two phase III FOCUS trials. Antimicrob Agents Chemother 2015; 59: 1119-26. DOI PMID
42.	Blasi F, Ostermann H, Racketa J, Medina J, McBride K, Garau J. Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study. Respir Res 2014; 15: 6. DOI URL
43.	Takada K, Matsumoto S, Kojima E, et al. Predictors and impact of time to clinical stability in community-acquired pneumococcal pneumonia. Respir Med 2014; 108: 806-12. DOI PMID
44.	Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015; 385: 1511-8. DOI PMID

Characteristic		Combination group (n = 91)	Conventional group (n = 92)	P value
Age (mean±SD, years)		64.6±14.8	62.9±15.6	0.439^b
18-60 [n (%)]		26 (28.6)	31 (33.7)	0.280^c
>60 [n (%)]		65 (71.4)	61 (66.3)	0.280^c
Male [n (%)]		62 (68.1)	68 (73.9)	0.389^c
Body mass index [median (IQR), kg/m²]		22.85 (19.86, 25.62)	22.84 (20.24, 25.06)	0.778^d
TCM syndrome differentiation [n (%)]	phlegm-heat obstruction in the lung	54 (59.3)	54 (58.7)	0.929^c
	pulmonary stagnation of phlegm	35 (38.5)	35 (38.0)	0.954^c
	pathogenic heat trapped in the pericardium	2 (2.2)	3 (3.3)	0.659^c
Clinical signs [median (IQR)]	Temperature (℃)	37.00 (36.70, 38.10)	37.20 (36.63, 38.28)	0.973^d
	Respiratory rate (breaths/min)	23.0 (20.0, 29.0)	24.0 (20.0, 29.8)	0.509^d
	Heart rate (beats/min)	98.0 (82.0, 110.0)	97.5 (84.0, 110.0)	0.492^d
	Systolic blood pressure (mm Hg)	124.0 (114.0, 135.0)	128.0 (115.0, 137.8)	0.398^d
Comorbidities [n (%)]	Hypertension	33 (36.3)	38 (41.3)	0.484^c
	Cerebrovascular disease	24 (24.7)	26 (27.6)	0.775^c
	Diabetes mellitus	23 (25.9)	21 (23.0)	0.698^c
	Coronary artery disease	21 (22.4)	22 (24.1)	0.894^c
	Chronic pulmonary disease	15 (16.5)	17 (18.5)	0.722^c
Serum levels [median (IQR)]	Creatinine (μmol/L)	64.15 (44.15, 81.35)	71.00 (56.95, 92.70)	0.074^d
	Platelets (× 10⁹/L)	213.00 (132.50, 279.75)	188.00 (120.25, 258.50)	0.376^d
	White blood cell count (× 10⁹/L)	10.17 (7.47, 13.60)	10.16 (6.70, 15.17)	0.92^d
	PaO₂/FiO₂ (mm Hg)	182.95 (135.78, 270.50)	187.50 (145.03, 254.75)	0.685^d
Severity criteria	ICU admission [n (%)]	40 (44.0)	50 (54.3)	0.160^c
	SOFA score [median (IQR)]	4.0 (2.0, 6.0)	4.5 (2.25, 6.0)	0.423^d
	PSI score (mean±SD)	107.9±35.2	106.4±42.5	0.992^b
Risk class [n (%)]^a	Ⅰ-Ⅲ	35 (38.4)	34 (37.0)	0.992^c
	Ⅳ	34 (37.4)	35 (38.0)
	Ⅴ	22 (24.2)	23 (25.0)

Characteristic		Combination group (n = 91)	Conventional group (n = 92)	P value
Age (mean±SD, years)		64.6±14.8	62.9±15.6	0.439^b
18-60 [n (%)]		26 (28.6)	31 (33.7)	0.280^c
>60 [n (%)]		65 (71.4)	61 (66.3)	0.280^c
Male [n (%)]		62 (68.1)	68 (73.9)	0.389^c
Body mass index [median (IQR), kg/m²]		22.85 (19.86, 25.62)	22.84 (20.24, 25.06)	0.778^d
TCM syndrome differentiation [n (%)]	phlegm-heat obstruction in the lung	54 (59.3)	54 (58.7)	0.929^c
	pulmonary stagnation of phlegm	35 (38.5)	35 (38.0)	0.954^c
	pathogenic heat trapped in the pericardium	2 (2.2)	3 (3.3)	0.659^c
Clinical signs [median (IQR)]	Temperature (℃)	37.00 (36.70, 38.10)	37.20 (36.63, 38.28)	0.973^d
	Respiratory rate (breaths/min)	23.0 (20.0, 29.0)	24.0 (20.0, 29.8)	0.509^d
	Heart rate (beats/min)	98.0 (82.0, 110.0)	97.5 (84.0, 110.0)	0.492^d
	Systolic blood pressure (mm Hg)	124.0 (114.0, 135.0)	128.0 (115.0, 137.8)	0.398^d
Comorbidities [n (%)]	Hypertension	33 (36.3)	38 (41.3)	0.484^c
	Cerebrovascular disease	24 (24.7)	26 (27.6)	0.775^c
	Diabetes mellitus	23 (25.9)	21 (23.0)	0.698^c
	Coronary artery disease	21 (22.4)	22 (24.1)	0.894^c
	Chronic pulmonary disease	15 (16.5)	17 (18.5)	0.722^c
Serum levels [median (IQR)]	Creatinine (μmol/L)	64.15 (44.15, 81.35)	71.00 (56.95, 92.70)	0.074^d
	Platelets (× 10⁹/L)	213.00 (132.50, 279.75)	188.00 (120.25, 258.50)	0.376^d
	White blood cell count (× 10⁹/L)	10.17 (7.47, 13.60)	10.16 (6.70, 15.17)	0.92^d
	PaO₂/FiO₂ (mm Hg)	182.95 (135.78, 270.50)	187.50 (145.03, 254.75)	0.685^d
Severity criteria	ICU admission [n (%)]	40 (44.0)	50 (54.3)	0.160^c
	SOFA score [median (IQR)]	4.0 (2.0, 6.0)	4.5 (2.25, 6.0)	0.423^d
	PSI score (mean±SD)	107.9±35.2	106.4±42.5	0.992^b
Risk class [n (%)]^a	Ⅰ-Ⅲ	35 (38.4)	34 (37.0)	0.992^c
	Ⅳ	34 (37.4)	35 (38.0)
	Ⅴ	22 (24.2)	23 (25.0)

Outcome	Intention-to-treat populations				Per-protocol populations
Outcome	Combination group (n = 91)	Conventional group (n = 92)	Between-group different (95% CI)	P value	Combination group (n = 83)	Conventional group (n = 87)	Between-group different (95% CI)	P value
Treatment failure [n (%)]^a	18 (19.8)	34 (37.0)	0.17 (0.04, 0.30)	0.010	14 (16.9)	31 (36.5)	0.19 (0.04, 0.32)	0.006^c
28d mortality [n (%)]	16 (17.6)	29 (31.5)	0.14 (0.02, 0.26)	0.029	13 (15.7)	27 (31.0)	0.15 (0.03, 0.27)	0.018^c
90-d mortality [n (%)]	21 (23.1)	31 (33.7)	0.11 (－0.02, 0.24)	0.111	18 (21.7)	29 (33.3)	0.12 (－0.02, 0.25)	0.090^c
Time to clinical stability (mean±SD, days)^b	11.8±1.1	17.8±1.2		0.001	9.6±0.8	17.9±1.2		0.001^d
Clinical stability [n (%)]	61 (67.0)	37 (40.2)	0.27 (0.13, 0.41)	0.001	59 (71.1)	36 (41.1)	0.30 (0.15, 0.44)	0.001^c
Length of hospital stay [median (IQR), days]	17.0 (10.0, 23.0)	16.0 (10.2, 25.0)	0 (－3.00, 3.00)	0.901	17.0 (10.0, 22.0)	16.0 (11.0, 26.0)	－2.00 (－5.00, 1.00)	0.231^e

Outcome	Intention-to-treat populations				Per-protocol populations
Outcome	Combination group (n = 91)	Conventional group (n = 92)	Between-group different (95% CI)	P value	Combination group (n = 83)	Conventional group (n = 87)	Between-group different (95% CI)	P value
Treatment failure [n (%)]^a	18 (19.8)	34 (37.0)	0.17 (0.04, 0.30)	0.010	14 (16.9)	31 (36.5)	0.19 (0.04, 0.32)	0.006^c
28d mortality [n (%)]	16 (17.6)	29 (31.5)	0.14 (0.02, 0.26)	0.029	13 (15.7)	27 (31.0)	0.15 (0.03, 0.27)	0.018^c
90-d mortality [n (%)]	21 (23.1)	31 (33.7)	0.11 (－0.02, 0.24)	0.111	18 (21.7)	29 (33.3)	0.12 (－0.02, 0.25)	0.090^c
Time to clinical stability (mean±SD, days)^b	11.8±1.1	17.8±1.2		0.001	9.6±0.8	17.9±1.2		0.001^d
Clinical stability [n (%)]	61 (67.0)	37 (40.2)	0.27 (0.13, 0.41)	0.001	59 (71.1)	36 (41.1)	0.30 (0.15, 0.44)	0.001^c
Length of hospital stay [median (IQR), days]	17.0 (10.0, 23.0)	16.0 (10.2, 25.0)	0 (－3.00, 3.00)	0.901	17.0 (10.0, 22.0)	16.0 (11.0, 26.0)	－2.00 (－5.00, 1.00)	0.231^e

Outcome	Intention-to-treat populations				Per-protocol populations
Outcome	Unadjusted OR or HR (95% CI)	P value^c	Adjusted OR or HR (95% CI)^d	P value^c	Unadjusted OR or HR (95% CI)	P value^c	Adjusted OR or HR (95% CI)^d	P value^c
Treatment failure^a	0.42 (0.22, 0.82)	0.011	0.43 (0.21, 0.88)	0.021	0.37 (0.18, 0.76)	0.007	0.41 (0.19, 0.89)	0.025
28-d mortality	0.46 (0.23, 0.93)	0.030	0.52 (0.24, 1.09)	0.083	0.38 (0.18, 0.812)	0.012	0.45 (0.20, 1.01)	0.051
90-d mortality	0.59 (0.31, 1.13)	0.113	0.63 (0.31, 1.28)	0.196	0.56 (0.28, 1.12)	0.101	0.67 (0.31, 1.44)	0.306
Time to clinical stability^b	2.08 (1.38, 3.14)	0.001	2.29 (1.50, 3.50)	0.001	2.55 (1.67, 3.90)	0.001	2.43 (1.58, 3.73)	0.001
Clinical stability	0.33 (0.18, 0.61)	0.001	0.27 (0.13, 0.55)	0.001	0.29 (0.15, 0.54)	0.001	0.25 (0.12, 0.53)	0.001
Length of hospital stay	0.67 (0.36, 1.25)	0.209	0.87 (0.47, 1.66)	0.673	0.69 (0.35, 1.35)	0.277	0.97 (0.47, 1.99)	0.924

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