Recurrent respiratory tract infections (RRTIs) have a negative impact on both children’s health and family wellbeing. Deficiency of ZhengQi used to be an instinct factor driving RRTI in Traditional Chinese Medicine (TCM). Our clinical observations suggest that children with gastrointestinal heat retention syndrome (GHRS) may have a greater risk of catching respiratory tract infections (RTIs). GHRS is a new predisposing factor for RRTI and it is dietary related. This study is aimed to explore association between GHRS and RRTI. A prospective cohort study has been conducted in Beijing, China; children aged 1–18 were enrolled. TCM symptoms, demographic and physiological characteristics were recorded by using semi-structured questionnaire. GHRS was considered as a predisposing factor. Children were followed up for next 12 months. We contacted with their parents using a face-to-face questionnaire survey, via email or phone every 3 months. Episodes of RTIs were recorded in detail. Three hundred thirty four children were enrolled and 307 (91.92 %) followed up for 12 months. The incidence of RTI was 4.32 episodes per child-year (95 % CI 4.03–4.61). 69 (43.13 %) children in the group with GHRS suffered from RRTI; there were 48 (32.65 %) children in group without GHRS. The risk ratio (RR) value of RRTI occurrence was 1.32 (95 % CI 0.91–1.91, P = 0.139), and the attributable risk percent (AR%) was 24.28 %. Dry stool and irritability were positively correlated with RTI episodes, age and BMI were negatively correlated with RTI episodes in a linear regression model. Dry stool (OR = 1.510) was positively correlated with RRTI occurrence, age (OR = 0.889) and BMI (OR = 0.858) were negatively correlated with RRTI occurrence in our logistic regression model. GHRS is associated with RRTI in this cohort. Dry stool was positively associated with RRTI, and BMI was negatively associated with RRTI. Studies with larger sample size and longer follow up are needed to further evaluate this association. Relieving GHRS should be considered when TCM practitioners treat RRTI children, and this may protect children from suffering RTIs. Chinese Clinical Trial Registry Number: ChiCTR-CCH-13003756

Gastrointestinal heat retention syndrome (GHRS) refers to a condition that is associated with increased gastrointestinal heat caused by a metabolic block in energy. It is common in children and is closely related to the occurrence and development of recurrent respiratory tract infection, pneumonia, recurrent functional abdominal pain, etc. However, there are no standardized diagnostic criteria to differentiate the GHRS. Therefore, this study is aimed to establish a diagnostic model for children’s GHRS and explore the possible biological basis by using systems biology to achieve. Furthermore, Delphi method and the clinical data of Lasso analysis were used to screen out the core symptoms. Nineteen core symptoms of GHRS in children were screened including digestive symptoms such as dry stool, poor appetite, vomiting, and some nervous system symptoms such as night restlessness and irritability. Based on the core symptoms, a GHRS diagnosis model was established using the eXtreme Gradient Boosting (XGBoost) method, and the accuracy of internal verification reached 93.03%. Relevant targets of the core symptoms in the Human Phenotype Ontology (HPO) were retrieved, and target interactions were linked through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and core targets were selected after topological analysis using Cytoscape. Relevant biological processes and pathways were analyzed by applying the DAVID and KEGG databases. The enriched biological processes focused on the cell proliferation, differentiation, apoptosis, and mitochondrial metabolism, which were mainly associated with PI3K-AKT, MAPK network pathways, and the Wnt signaling pathway. In conclusion, we established a diagnosis model of GHRS in children based on the core symptoms and provided an objective standard for its clinical diagnosis. And, the Wnt signaling pathway and the estrogen receptor-activated PI3K-AKT and MAPK network pathways may play important roles in the GHRS processing.