Symptom network topological features predict the effectiveness of herbal treatment for pediatric cough

Abstract

Pediatric cough is a heterogeneous condition in terms of symptoms and the underlying disease mechanisms. Symptom phenotypes hold complicated interactions between each other to form an intricate network structure. This study aims to investigate whether the network structure of pediatric cough symptoms is associated with the prognosis and outcome of patients. A total of 384 cases were derived from the electronic medical records of a highly experienced traditional Chinese medicine (TCM) physician. The data were divided into two groups according to the therapeutic effect, namely, an invalid group (group A with 40 cases of poor efficacy) and a valid group (group B with 344 cases of good efficacy). Several well-established analysis methods, namely, statistical test, correlation analysis, and complex network analysis, were used to analyze the data. This study reports that symptom networks of patients with pediatric cough are related to the effectiveness of treatment: a dense network of symptoms is associated with great difficulty in treatment. Interventions with the most different symptoms in the symptom network may have improved therapeutic effects.

Keywords

pediatric cough / complex network / symptoms / traditional Chinese medicine / electronic medical records

References

[1] Gibson PG, Chang AB, Glasgow NJ, Holmes PW, Katelaris P, Kemp AS, Landau LI, Mazzone S, Newcombe P, Van Asperen P, Vertigan AE; CICADA. CICADA: Cough in Children and Adults: Diagnosis and Assessment. Australian cough guidelines summary statement. Med J Aust 2010; 192(5): 265–271

[2] Chang AB, Landau LI, Van Asperen PP, Glasgow NJ, Robertson CF, Marchant JM, Mellis CM; Thoracic Society of Australia and New Zealand. Cough in children: definitions and clinical evaluation. Med J Aust 2006; 184(8): 398–403

[3] Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chest 2006; 129(1 Suppl): 260S–283S

[4] Gilchrist FJ, Carroll WD. Assessing chronic cough in children. Paediatr Child Health 2016; 26(6): 273–275

[5] Feng G, Zheng H, Zheng QZ. Experience of ZHENG Qi-zhong in using Puji Xiaodu Decoction. China J Tradit Chin Med Pharm (Zhonghua Zhong Yi Yao Za Zhi) 2016; 31(7): 2615–2617 (in Chinese)

[6] Wang S, Qiao-Wong JM, Zhao X. Pediatrics in Chinese Medicine: PMPH-USA, 2012

[7] Barabási AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet 2011; 12(1): 56–68

[8] Borsboom D, Cramer AO. Network analysis: an integrative approach to the structure of psychopathology. Annu Rev Clin Psychol 2013; 9: 91–121

[9] Boschloo L, van Borkulo CD, Rhemtulla M, Keyes KM, Borsboom D, Schoevers RA. The network structure of symptoms of the diagnostic and statistical manual of mental disorders. PLoS One 2015; 10(9): e0137621

[10] van Borkulo C, Boschloo L, Borsboom D, Penninx BW, Waldorp LJ, Schoevers RA. Association of symptom network structure with the course of depression. JAMA Psychiatry 2015; 72(12): 1219–1226

[11] van Borkulo C D. NetworkComparisonTest: Statistical comparison of two networks based on three invariance measures. R package version 2.0.1. Retrieved from the website of CRAN-NetworkComparisonTest. 2016

[12] Team RDC. R: a language and environment for statistical computing. Computing 2013; 1: 12–21

[13] Zhou X, Chen S, Liu B, Zhang R, Wang Y, Li P, Guo Y, Zhang H, Gao Z, Yan X. Development of traditional Chinese medicine clinical data warehouse for medical knowledge discovery and decision support. Artif Intell Med 2010; 48(2-3): 139–152

[14] Lu Q. Consensus of experts on standardized diagnosis and treatment of common cold in Chinese children (2013). Chin J Prac Pediatr (Zhongguo Shi Yong Er Ke Za Zhi) 2013; 28(9): 680–681 (in Chinese)

[15] The Subspecialty Group of Respiratory Diseases, The Society of Pediatrics, Chinese Medical Association. Guidelines for the diagnosis and treatment of bronchial asthma in children (2016). Chin J Pediatr (Zhonghua Er Ke Za Zhi) 2016; 54(3): 168–173 (in Chinese)

[16] The Subspecialty Group of Respiratory Diseases, The Society of Pediatrics, Chinese Medical Association. Guidelines for the management of community-acquired pneumonia in children (2013). Chin J Pediatr (Zhonghua Er Ke Za Zhi) 2013; 51(10): 745–749 (in Chinese)

[17] Zhou X, Menche J, Barabási AL, Sharma A. Human symptoms-disease network. Nat Commun 2014; 5(1): 4212

[18] Mann HB, Whitney DR. On a test of whether one of two random variables is stochastically larger than the other. Ann Math Stat 1947; 18(1): 50–60

[19] Maass M, Gieffers J, Krause E, Engel PM, Bartels C, Solbach W. Qgraph: network visualizations of relationships in psychometric data. J Stat Softw 2012; 48(4): 1–18

[20] Barrat A, Barthélemy M, Pastor-Satorras R, Vespignani A. The architecture of complex weighted networks. Proc Natl Acad Sci USA 2004; 101(11): 3747–3752

[21] Watts DJ, Strogatz SH. Collective dynamics of ‘small-world’ networks. Nature 1998; 393(6684): 440

[22] Caldarelli G. Introduction to complex network. AIP Conf Proc 2003; 661: 17–23

[23] Good P. Permutation tests: a practical guide to resampling methods for testing hypotheses. Springer Science & Business Media, 2013

[24] Boccaletti S, Latora V, Moreno Y, Chavez M, Hwang DU. Complex networks: structure and dynamics. Phys Rep 2006; 424(4–5): 175–308

[25] Opsahl T, Agneessens F, Skvoretz J. Node centrality in weighted networks: generalizing degree and shortest paths. Soc Networks 2010; 32(3): 245–251

[26] Bonacich P. Power and centrality: a family of measures. Am J Sociol 1987; 92(5): 1170–1182

[27] Efron B, Tibshirani R J. An introduction to the bootstrap. CRC press, 1994

[28] Jiang M, Lu C, Zhang C, Yang J, Tan Y, Lu A, Chan K. Syndrome differentiation in modern research of traditional Chinese medicine. J Ethnopharmacol 2012; 140(3): 634–642

[29] Miaskowski C, Dodd M, Lee K. Symptom clusters: the new frontier in symptom management research. JNCI Monographs 2004; 2004(32): 17–21

[30] Zhang X, Wang X, Wei W, Zhang X. Analysis on regulation of Wang Xuefeng’s prescriptions on children children chronic cough by data mining technology. Liaoning J Traditi Chin Med (Liaoning Zhong Yi Za Zhi) 2017; 44(9): 1793–1795 (in Chinese)

[31] Zhang QX. Experience of professor NIE Hui-min in treating exogenous cough of children. China J Tradit Chin Med Pharm (Zhonghua Zhong Yi Yao Za Zhi) 2008; 23(4): 335–337 (in Chinese)

[32] Zhou XZ, Zhang RS, Shah J, Rajgor D, Wang YH, Pietrobon R, Liu BY, Chen J, Zhu JG, Gao RL. Patterns of herbal combination for the treatment of insomnia commonly employed by highly experienced Chinese medicine physicians. Chin J Integr Med 2011; 17(9): 655–662

[33] Liu JZ, Huang MX, Liu XY, Chen Y. The data mining analysis of Professor Ni Zhuying’s treatment of pediatric cough disease. World Sci Technol (Shi Jie Ke Xue Ji Shu—Zhong Yi Yao Xian Dai Hua Za Zhi) 2017; 19(9): 1527–1532 (in Chinese)

Acknowledgements

This work was supported by the National Key R&D Program (No. 2004BA721A01Z73) and the National Key Research and Development Project of China (No. 2017YFC1703506).

Compliance with ethics guidelines

Mengxue Huang, Jingjing Wang, Runshun Zhang, Zhuying Ni, Xiaoying Liu, Wenwen Liu, Weilian Kong, Yao Chen, Tiantian Huang, Guihua Li, Dan Wei, Jianzhong Liu, and Xuezhong Zhou declare that they have no conflict of interest. No ethics approval was required because no experiments on humans or animals were carried out.

Electronic Supplementary Material

ƒSupplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-019-0699-3 and is accessible for authorized users.

RIGHTS & PERMISSIONS

2019 Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature