Although TCM is widely used in the treatment of bronchiectasis in China, a system of syndrome differentiation using evidence-based medicine has not been established (16). Since syndrome diagnosis is key to TCM therapy, there is an urgent need for TCM researchers to perform more epidemiological studies of high methodological quality on syndrome distribution in bronchiectasis patients. To our knowledge, this is the first study to investigate TCM syndrome distribution in bronchiectasis patients using real-world data. RWS offer insights into the interactions between patient characteristics, preferences, lifestyles, and treatment outcomes that are often excluded from double-blind clinical randomized controlled trials (RCTs) (23). This type of study also offers the opportunity to explore how these interactions differ between therapies and treatment modalities and to evaluate important clinical outcomes, such as bronchiectasis exacerbations, that can be underpowered in RCTs owing to their short duration and their pre-selection of idealized patients in whom negative outcomes are often relatively infrequent (24).
Through comprehensive summary, the results of the present study demonstrate that the four most common Shi syndromes among bronchiectasis patients, in decreasing order of frequency, were Tan_Re_Yong_Fei, Tan_Zhuo_Zu_Fei, Gan_Huo_Fan_Fei, and Feng_Re_Fan_Fei. Frequency analyses showed all four Shi syndromes were present with > 5.0% frequency. These results suggest that the four Shi syndromes are the most common in bronchiectasis. Similarly, the Xu syndrome of Fei_Yin_Xu was identified in a significant proportion of bronchiectasis patients. Additionally, frequency analyses, factor analyses, cluster analyses, and association rule analyses for different syndrome elements demonstrated that the predominant elements in the pathogenesis of bronchiectasis were Huo, Tan, Yin_Xu, and Feng, representing the four elements phlegm, fire, Yin-deficiency, and wind, respectively. The main disease locations were Fei (lung) and Gan (liver), indicating that bronchiectasis can be attributed to functional disorders of the lungs and liver. However, it should be pointed out that the “liver” in TCM refers not only to the anatomical organ but also to a complex system which includes a series of functions which modern medicine ascribes to the metabolic system, central nervous system, endocrine system, blood system, digestive system, and others (25).
According to TCM theory, bronchiectasis arises from the invasion of evils (i.e., wind, heat, and dampness, which conceptually resemble pathogenic infection in western medicine) (26). Our results indicate that bronchiectasis can be divided into five overlapping categories based on TCM syndromes. In the first type of bronchiectasis cases, bronchiectasis may lead to retention of body fluids in all meridians and collaterals, leading to the production of sputum, which clinically manifests as Tan_Zhuo_Zu_Fei (phlegm-turbidity obstructing the lung) (27). In the second type of cases, the accumulation of phlegm and heat readily results in bronchial necrosis (27). This type of bronchiectasis is the end result of a pathological process involving a vicious circle of inflammation, recurrent infection, and bronchial wall damage caused by phlegm and heat (28). This phlegm-heat obstructing the lung has been associated with exaggerated inflammatory responses secondary to airway destruction (28). In the third type of cases, bronchiectasis is the result of stagnated wind evils, particularly in patients with frailty (27). In these cases, wind and heat (the pathogenetic causes) stagnate in the lungs; this usually occurs in the early stage of bronchiectasis (26). In the fourth type of cases, liver-fire invading the lung syndrome appears in cases of bronchiectasis with hemoptysis, which is consistent with the traditional understanding (7).In the fifth type of cases, prolonged courses of bronchiectasis, coupled with evil stagnation and frailty, can render a substantial loss of primordial Yin (29).According to TCM theory, a deficiency of bodily fluid in the respiratory system, especially in the mucous epithelium, is the mechanism behind the Yin-deficiency in the lung syndrome (29). Therefore, these patients presented with Yin-deficiency in the lung syndrome. In the present study, Yin-deficiency syndrome is the most common Xu TCM syndrome with bronchiectasis patients, suggesting the importance of nourishing Yin and moisturizing the lungs(30).
In terms of distribution of the TCM syndrome in bronchiectasis, the detected frequency of phlegm-heat syndrome was significantly higher than that of other syndromes, indicating that phlegm-heat is a major contraindication in the treatment of bronchiectasis. The frequency of Yin-deficiency was also significantly higher than the other three syndromes (phlegm turbidity, liver-fire, and wind-heat). It can therefore be inferred that Yin-deficiency has a wide distribution as a fundamental syndrome pattern with a high frequency of occurrence in bronchiectasis patients, especially in the elderly, frail, and patients with long illness durations.
Identification of the aforementioned five syndrome categories suggests that they form the core pathogenesis of bronchiectasis and should thus be the fundamental diagnostic elements taken into account during differentiation of bronchiectasis. It follows that, when formulating a prescription to treat bronchiectasis, the five strategies that should be considered depending on the presenting syndrome pattern are removing sputum and clearing heat, resolving phlegm turbidity, clearing away liver-fire, and nourishing Yin. Furthermore, the target organs of treatment should be the lung and liver (as defined by TCM).
This study achieved three primary results of significance. First, this study identified the distribution of TCM syndromes in patients with bronchiectasis using objective parameters from real-world datasets. This method may help reduce bias and may also encourage more practitioners to use this syndrome differentiation approach. Second, results from this study can guide clinical trials in evaluating the efficacy of TCM treatments for bronchiectasis. Once the most common TCM syndromes of bronchiectasis are identified, further interventional research can investigate the efficacy and safety of TCM treatments for bronchiectasis based on the specific syndromes identified. Third, since this study established that wind-heat syndromes usually occur in the early stage of bronchiectasis, effective treatment can be targeted to this population to slow down the progression of the disease, ultimately reducing the burden for both patients and the medical system caused by advanced complications.
There are some limitations of this study. First, selection bias may exist because the present study was based on a RWS design. All data were derived from participants in hospitals in five cities using a relatively small sample, and therefore may not be representative of the distribution of TCM syndromes in bronchiectasis patients in the rest of China. Additional multi-center studies with larger samples are required to verify the conclusions of the present study. Second, the different causes, severity, and stages of bronchiectasis in the original sample population were unclear because we did not subdivide the data. Third, the associations between TCM syndromes and modern medicine indicators were not explored in this work. Future research should focus in greater depth on the objective evidence of TCM syndromes in bronchiectasis patients.