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CMAJ. 2025 Feb 18;197(6):E148–E154. doi: 10.1503/cmaj.241101

Diagnosis and management of chronic rhinosinusitis

Christopher J Chin 1,✉, John R Scott 1, John M Lee 1

• Author information

• Article notes

• Copyright and License information

PMCID: PMC11835454  PMID: 39965812

This article is also available in French. See "Diagnostic et prise en charge de la rhinosinusite chronique".

See the reply "Chronic rhinosinusitis: an underrecognized occupational disease" on page E920.

KEY POINTS

• Patients with chronic rhinosinusitis typically present with long-term nasal congestion, rhinorrhea, facial pressure, and altered sense of smell.

• A definitive diagnosis requires objective findings on endoscopy or computed tomography; sinus radiography is of limited value.

• First-line treatments include the long-term use of topical saline and intranasal corticosteroids.

• Endoscopic sinus surgery is effective but sometimes requires subsequent revision.

• Monoclonal antibody therapies are a treatment option for patients with severe chronic rhinosinusitis with nasal polyps recalcitrant to first-line therapies.

Chronic rhinosinusitis refers to symptomatic inflammation of the nose and paranasal sinuses that has been present for a minimum of 3 months.1 Its true prevalence is difficult to determine because of diagnostic challenges, but estimates range from 2.1%2 to 15%.3 It most commonly affects adults in middle age,3 with females affected slightly more often than males.3,4 Although the condition may be perceived as a minor inconvenience compared with other chronic diseases, it can be associated with impaired sleep,5,6 severe fatigue,7 and depression,8,9 which can interfere substantially with activities of daily living. In Canada, patients lose an average of 20.6 work days per year because of symptoms as well as time off for surgeries and medical appointments related to the condition, leading to substantial economic costs.10–12

Treatment options for patients with chronic rhinosinusitis have recently expanded and improved. We review the evidence related to chronic rhinosinusitis, including the evolving understanding of the condition and treatment modalities (Box 1).

Box 1: Literature review .

We conducted a literature review of PubMed from inception until Nov. 1, 2024. The search terms included “chronic rhinosinusitis,” “sinusitis,” and “CRS,” which we searched in combination with “epidemiology,” “pathophysiology,” and “treatment.” We excluded non-English literature. We emphasized recent clinical practice guidelines and systematic reviews, although we did not restrict article types. We also searched the reference lists of included articles for relevant articles that may have been missed by our search strategy. We focused on treatment guidelines and evidence from 2019 onward.

Note: CRS = chronic rhinosinusitis.

What are the risk factors for chronic rhinosinusitis?

The cause of chronic rhinosinusitis is not yet fully understood. Contributing factors likely include genetic predisposition, microbial pathogens, environmental factors, and allergy, although none of these factors appears to be solely causative. The rate of asthma among people with chronic rhinosinusitis is estimated to be 25%, 5 times higher than in the general public. The unified airway theory proposes that these 2 conditions share many of the same etiological factors, given their similar cellular biology and known triggers.1

What is the pathophysiology of the condition?

Chronic rhinosinusitis is understood to be predominantly an inflammatory condition rather than an infectious process.1,13–15 The underlying pathophysiology likely involves a combination of epithelial barrier insults (e.g., microbes, allergens) and dysregulation of inflammatory pathways (Figure 1). Both the innate and adaptive immune system show dysfunction at the level of the sinus mucosa, leading to goblet cell hyperplasia, impaired mucociliary clearance, and a proinflammatory state.1,14,15

Figure 1:

Open in a new tab

Pathophysiology of chronic rhinosinusitis. Note: IFN = interferon, IL = interleukin, ILC1 = innate lymphoid cell type 1, ILC2 = innate lymphoid cell type 2, ILC3 = innate lymphoid cell type 3, NK = natural killer, Th0 = naive T cell, Th1 = T helper 1 cell, Th2 = T helper 2 cell, Th17 = T helper 17 cell, TNF = tumour necrosis factor, TSLP = thymic stromal lymphopoietin. Created in BioRender and adapted from Xu et al15 with permission from John Wiley and Sons. See Related Content tab for accessible version.

With the advent of targeted therapeutics and increased recognition that certain patients respond better to treatment, chronic rhinosinusitis has increasingly been classsified into endotypes rather than broad phenotypes. The type 2 endotype involves activation of the type 2 inflammatory pathway, whereby T helper 2 cells and type 2 innate lymphoid cells produce the inflammatory cytokines interleukin 4, interleukin 5, and interleukin 13.14–16 In the non–type 2 endotype, both type 1 and type 3 inflammatory pathways have been seen (Figure 1).

How is chronic rhinosinusitis diagnosed?

The diagnostic criteria for chronic rhinosinusitis are sinonasal inflammation persisting for at least 12 weeks with at least 2 symptoms, as well as 1 sign on clinical examination (Table 1).

Table 1:

Diagnostic criteria for chronic rhinosinusitis*

Criterion

Symptom or sign

At least 2 symptoms

Nasal obstruction or congestion

Anterior or posterior nasal drainage

Decreased sense of smell

Facial pressure, pain, or fullness

At least 1 sign

Polyps, edema, or mucopurulence on nasal endoscopy or anterior rhinoscopy

Sinus mucosal thickening on computed tomography

Open in a new tab

*Sinonasal inflammation persisting for more than 12 weeks.

The core symptoms include nasal congestion (synonymous with nasal obstruction), anterior or posterior nasal discharge, an altered sense of smell, and facial pain or pressure.17 Facial discomfort lacks specificity, and some experts believe it should be omitted from diagnostic criteria.1,13

Additional symptoms include ear fullness, cough, headache, fatigue, dental pain, an altered sense of taste, and halitosis.18 These symptoms are individually quite sensitive but not specific.19 Notably, although patients can present with acute rhinosinusitis (i.e., infection on top of their chronically inflamed baseline), they more often appear to have a lingering upper respiratory tract infection.

An overview of the workup and management algorithm is shown in Figure 2. Red-flag signs or symptoms should elicit an urgent referral to an otolaryngologist to rule out more serious pathology, as should failure to respond to standard medical therapy (Table 2). Unilateral symptoms should prompt an expedited referral to rule out other pathologies as chronic rhinosinusitis is typically bilateral in nature.

Figure 2:

Open in a new tab

The workup and diagnostic algorithm for chronic rhinosinusitis (CRS). Note: CT = computed tomography. *Common symptoms include nasal congestion or obstruction, nasal discharge (anterior or posterior), facial pressure, and loss of smell. †Red-flag signs and symptoms are described in Table 2. See Related Content for accessible version.

Table 2:

Important signs or symptoms in rhinosinusitis for which an alternate diagnosis should be considered

Clinical indicator

Potential condition

Proptosis

Neoplasm, acute infection

Paresthesia

Neoplasm, central neurologic disease

Unilateral, persistent, salty, or metallic-tasting rhinorrhea

Cerebrospinal fluid leak

Recurrent or persistent epistaxis

Neoplasm, nasal dryness or irritation

Diplopia

Neoplasm, central neurologic disease, acute infection

Severe pain

Acute infection, neoplasm, migraine, bruxism, tension or cluster headache

Fever

Acute infection

Open in a new tab

Differential diagnosis

The differential diagnosis of chronic rhinosinusitis includes allergic rhinitis, septal deviation, and neoplasms of the sinonasal cavity.

Nasal congestion is often seen with allergic rhinitis, but patients do not typically have facial pressure as they do in chronic rhinosinusitis. Furthermore, the secretions in allergic rhinitis are often clear and thin, in contrast to the thicker mucous seen in chronic rhinosinusitis.20 A deviated septum can lead to nasal obstruction and congestion, but does not typically affect sense of smell or cause substantial nasal discharge. Nasal neoplasm may also cause new onset of facial pressure and nasal obstruction but usually in a unilateral pattern, which should prompt an expedited referral to an otolaryngologist.

Clinical examination

The diagnosis of chronic rhinosinusitis requires objective findings of sinonasal inflammation (Table 1). The phenotypic distinction of whether or not the patient has polyps can guide treatment. Nasal polyps may be suspected on anterior rhinoscopy or computed tomography (CT), but endoscopy by an otolaryngologist is currently considered the gold standard, particularly for detecting smaller polyps.21 Figure 3A shows nasal polyps arising from the middle meatus in the nose. When compared with the nasal turbinates, nasal polyps often have a watery, edematous, translucent quality. Patients with nasal polyps will often have a hyponasal (i.e., stuffy) quality to their voice and frequently sound as one would expect if they were recovering from an upper respiratory tract infection. In contrast, those without polyps more often have thick, mucopurulent secretions on examination (Figure 3B). Given the high rate of association between chronic rhinosinusitis and asthma, screening for lower airway inflammatory disease and chest auscultation are important.

Figure 3:

Open in a new tab

(A) Intraoperative endoscopic view of an inflammatory nasal polyp (NP) in the left nasal cavity, characteristic of chronic rhinosinusitis with nasal polyposis. (B) Intraoperative endoscopic view of purulent discharge (D) in the right nasal cavity, characteristic of chronic rhinosinusitis without nasal polyposis. Note: IT = inferior turbinate, MT = middle turbinate, S = septum.

Rarely, chronic rhinosinusitis can expand beyond the nasal sinuses and start to involve the orbital structures. These patients may present with proptosis, which is usually unilateral and readily apparent. This finding would warrant urgent CT to confirm the diagnosis of complicated rhinosinusitis and help guide treatment (Figure 2).

Investigations

No specific laboratory tests currently exist for the diagnosis of chronic rhinosinusitis. Biomarkers (e.g., serum eosinophil levels) may help with distinguishing the underlying endotype but no markers have yet been found to be useful in predicting treatment response or guiding management.21

The standard imaging modality used in chronic rhinosinusitis is noncontrast CT of the sinuses. Chronic inflammation appears as mucosal thickening or opacification (lack of aeration) of the sinuses on CT. A plain film radiograph of the sinuses lacks sensitivity for diagnosing chronic rhinosinusitis and should not be ordered.17

If a patient presents with symptoms of allergic rhinitis (bilateral clear rhinorrhea, itchy eyes, and sneezing), allergy testing can be helpful to identify and avoid potential triggers.

How is chronic rhinosinusitis managed?

Treatment of chronic rhinosinusitis is focused on reducing inflammatory burden and trying to restore normal mucociliary function. The presence of nasal polyps is relevant but does not change first-line approaches. Table 3 summarizes the standard treatment options.

Table 3:

Standard medical treatment for chronic rhinosinusitis

Treatment

Example agent

Common dosing regimen

Topical saline irrigation

Commercially available sinus rinse or saline mist

1–2 times daily

Topical steroid spray

Mometasone furoate, fluticasone furoate

2 sprays to both nostrils daily for minimum 8 wk

Oral steroids for nasal polyps

Prednisone

30 mg/d for 7 d

Oral antibiotics for acute flares

Amoxicillin–clavulanate

875 mg twice daily for 10 d

Open in a new tab

Pharmacologic treatment

Long-term topical intranasal corticosteroids are the first-line treatment. A Cochrane review of 18 randomized controlled trials (RCTs) compared intranasal steroids to placebo and concluded that intranasal corticosteroids improved patient symptoms, reduced inflammation in the sinonasal mucosa (including the reduction of nasal polyps), and addressed related conditions such as allergic rhinitis.22 Specifically, in 6 studies that reported severity of nasal blockage and rhinorrhea, patients treated with steroids had less severe symptoms (mean difference −0.31, 95% confidence interval [CI] −0.38 to −0.24) than those treated with placebo.22 With regard to polyp size, the relative risk of improvement in size was 1.77 (95% CI 1.06 to 2.95) for patients in the intranasal steroid group, again demonstrating the efficacy of steroids compared with placebo.22 Therefore, it is reasonable to start treatment when chronic rhinosinusitis is clinically suspected based on mild to moderate symptoms. These topical medications are considered safe with minimal systemic absorption. Meta-analyses have shown the risk of biochemical adrenal insufficiency, a feared complication from steroid absorption, to be low (around 0.70%); none of the included studies reported clinical symptoms of adrenal insufficiency (e.g., hypotension, fatigue, irritability).23,24

Topical saline sprays and irrigations are effective adjuvant treatments for chronic rhinosinusitis (both with and without nasal polyps). A systematic review demonstrated that high-volume saline irrigations (squeeze bottle or pot) had greater distribution to the sinus cavities than saline sprays.25 These solutions are typically mixed by the patient by adding a premixed packet (sodium chloride and sodium bicarbonate) to 240 mL of distilled water, which is then used to irrigate the nasal cavity. An RCT found a significant improvement in quality-of-life scores and symptom frequency (absolute risk reduction 0.20, 95% CI 0.02 to 0.38) in the nasal irrigation group, compared with low-volume saline sprays, with a number needed to treat of 5.26 If high-volume irrigations are not well tolerated because of ear pressure or other symptoms, patients should continue to use saline sprays alone. Regardless of the delivery method, irrigation should be done before using an intranasal steroid spray to avoid washing out the medication.

Oral medications

Short bursts of oral steroids such as prednisone can reduce the size of known nasal polyps and provide rapid symptomatic relief, including improved sense of smell.1,13,27 A Cochrane review that included 8 RCTs showed that the benefits of oral steroids were generally limited to a few months.28 Specifically, the mean symptom score after 17 days of treatment was 2.84 standard deviations lower than baseline scores, but just 0.22 standard deviations lower at 3 months, highlighting the short-lived nature of the benefit.28 Judicious use of steroids is recommended, given concerns of long-term adverse effects from systemic absorption.27 The optimal dosage of oral steroids is unknown; a common regimen is provided in Table 3.

Recent guidelines suggest antibiotics should be considered for only acute exacerbations of chronic rhinosinusitis (with and without nasal polyps), while clinicians should remain wary of the patient who presents with fever or severe pain (Table 2).1,27 A 2016 Cochrane review found very little evidence for the efficacy of systemic antibiotics in patients with chronic rhinosinusitis, showing no meaningful improvement compared with placebo treatment.1,29 Adverse effects, concerns over antibiotic stewardship, and the current understanding of chronic rhinosinusitis as an inflammatory process should also discourage antibiotic use. Although long-term, low-dose antibiotics may have some benefit in patients with non-type 2 inflammation, the literature on this topic is still conflicting and no definitive recommendations can be made at this time.1,27

Surgical treatment

Endoscopic sinus surgery is known to be an effective and safe treatment for patients with chronic rhinosinusitis for whom standard medical therapy has not been beneficial. This minimally invasive procedure is done through the nostrils with endoscopes, without external incisions. Inflamed tissue, polyps, and small pieces of bone can be delicately removed to improve the drainage and ventilation of the sinus cavities. Several studies have demonstrated the ability of endoscopic sinus surgery to improve quality of life while reducing the inflammatory burden in the sinuses.30 Perhaps most importantly, surgery facilitates an improved delivery of topical medications to the paranasal sinuses, which is an essential component of long-term management and symptom control.31

However, endoscopic sinus surgery cannot definitively change the underlying pathophysiology of this disease, and patients may require further procedures. Revision rates are estimated to be 10%–30% depending on the length of follow-up.32 One retrospective review found the time between surgeries was 4.39 years, on average.32 Most studies suggest that around 75% of patients will report significantly improved symptoms after endoscopic sinus surgery,33 and patients who undergo revision surgery were found to have a similar improvement in quality-of-life scores as those having primary surgery.34 Risk factors for symptomatic recurrence after surgery include those with severe polyp disease and those with comorbid asthma.32

Monoclonal antibody therapy for chronic rhinosinusitis with polyps

Several monoclonal antibody therapies, also known as biologics, can improve both symptoms and signs among patients with severe chronic rhinosinusitis with polyps. These systemic agents target the type 2 inflammatory pathway.

A 2021 Cochrane review demonstrated the efficacy of biologics in the treatment of chronic rhinosinusitis with polyps.35 Therapeutic effects include reduction in nasal congestion, reduction in polyp size, improvement in smell and disease-specific quality-of-life score, and minimization of the need for oral steroids and surgical revisions.35

A 2021 Canadian Consensus Statement, based on a Delphi study, guides the use of biologics in patients with chronic rhinosinusitis. 21 Otolaryngologists must first confirm the presence of polyps by endoscopy to be considered for a trial of therapy. Oral and nasal steroids must not have been effective, and, in most circumstances, patients should have had previous endoscopic sinus surgery, without evidence they might benefit from further surgical revision. Dupilumab, mepolizumab, and omalizumab have been approved for use in Canada. These are administered by injection and are also used in other type 2 inflammatory conditions including asthma and atopic dermatitis.

Ongoing use is required to maintain a therapeutic benefit, and optimal duration of treatment is yet to be determined. Short-term risks of systemic biologic use include arthralgias, rash, and conjunctivitis.36 In a retrospective review of real-world data, fewer than 10% of patients discontinued their biologic because of adverse effects, and most of these effects presented within the first 3 months of therapy.36 A systematic review and meta-analysis found that patients on biologics had an increased risk of developing a rheumatic adverse event (risk ratio 2.53, 95% CI 1.29 to 4.94), compared with those on placebo, usually managed with treatment discontinuation.37 Given that biologics are relatively novel therapies, high-quality, long-term data on adverse effects are not available, and patients should be counselled accordingly. Moreover, the cost of these medications will be prohibitive for many patients. A cost–utility analysis found that treatment with dupilumab cost more than surgery by a factor of 11 per quality-adjusted-life-year.38 Use of biologics should therefore be reserved for the small percentage of patients for whom other treatment options have failed.21

Conclusion

Chronic rhinosinusitis is a common inflammatory condition with serious effects on individual functioning and quality of life. Diagnosis is clinical and depends on subjective symptoms and objective findings on imaging and physical examination. Diagnostic biomarkers may be avilable in the future. First-line treatment involves topical steroid therapy and saline irrigation, with consideration of endoscopic sinus surgery when necessary. Patients with chronic rhinosinusitis with polyps who do not achieve symptomatic relief with standard medical and surgical therapy can now be prescribed biologics, although the long-term effects of these agents are unknown. Future studies should investigate the optimal diagnostic techniques for individual patients based on underlying pathophysiology to better direct treatment and should assess the role of new therapies (Box 2).

Box 2: Unanswered questions .

• Will biomarkers be useful to guide diagnosis and treatment, and if so, which ones?

• How can clinicians identify which treatments will most benefit a patient?

• What is the optimal duration of treatment with biologics?

• What are the long-term adverse effects of biologics in the treatment of chronic rhinosinusitis?

Supplementary Information

241101-review-f1-longdesc.pdf (30KB, pdf)

241101-review-f2-longdesc.pdf (56.2KB, pdf)

Acknowledgement

The authors thank Dr. Ryan Normore for his input and review of the article.

Footnotes

Competing interests: Christopher Chin, John Scott, and John Lee all report honoraria and travel support from Sanofi–Regeneron and GSK, as well as participation on medical advisory boards regarding biologic therapy for the treatment of chronic rhinosinusitis with Sanofi–Regeneron and GSK.

This article has been peer reviewed.

Contributors: Christopher Chin conceived the work. All of the authors contributed to the design of the work, drafted the manuscript, revised it critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

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Associated Data

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Supplementary Materials

241101-review-f1-longdesc.pdf (30KB, pdf)

241101-review-f2-longdesc.pdf (56.2KB, pdf)

Articles from CMAJ : Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

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• What are the risk factors for chronic rhinosinusitis?

• What is the pathophysiology of the condition?

• How is chronic rhinosinusitis diagnosed?

• How is chronic rhinosinusitis managed?

• Conclusion

• Supplementary Information

• Acknowledgement

• Footnotes

• References

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BMC Complement Med Ther. 2025 May 6;25:165. doi: 10.1186/s12906-025-04895-x

Chinese herbal medicines for rhinosinusitis: a text-mining study with comparisons to contemporary research and clinical guidance

Jing Cui 1, Brian H May 1, Wenmin Lin 2,3, Qiulan Luo 2,3, Anthony Lin Zhang 1, Xinfeng Guo 2, Chuanjian Lu 2, Yunying Li 2,3,✉, Charlie C Xue 1,2,✉

• Author information

• Article notes

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PMCID: PMC12054199  PMID: 40329241

Abstract

Background

Rhinosinusitis is an inflammation of the paranasal sinuses and nasal cavity. It is managed with intra-nasal steroids, nasal saline irrigation, oral antibiotics and/or biologics. Chinese herbal medicines (CHMs) have long been used for nasal disorders, including rhinosinusitis, and feature in Chinese clinical guidelines for rhinosinusitis. Systematic reviews suggest some CHM formulations may be beneficial for the management of this condition.

Methods

This text mining study used an established methodology to search a database containing the full texts of more than 1,150 classical and pre-modern Chinese medicine books to identify references to disorders similar to rhinosinusitis, and the CHMs used as interventions. Ten search terms relevant to names of disorders in classical books and the major symptoms of rhinosinusitis were identified. Search results were downloaded, categorised, and analysed descriptively in SPSS®. Qualitative comparisons were made with the modern clinical Chinese medicine literature.

Results

Searches found 436 oral CHM formulae with 3,059 ingredients, 81 nasal or other topical CHMs with 142 ingredients, and 112 single natural products from classical pharmacopoeia used orally and/or topically. The earliest reference to a disorder similar to rhinosinusitis was in a Chinese medical book written approximately 2,000 years ago.

Three oral CHM formulae from the search have been tested in randomised controlled trials and one is included in a clinical guideline. A sample of 13 modern specialist textbooks on Chinese otorhinolaryngology still recommended nine of the oral classical formulae. Three of the seven herbs frequently included in the classical pharmacopoeia are still listed in the official Chinese pharmacopoeia for rhinosinusitis. Nasal formulae found in classical searches differed to those tested in randomised controlled trials, although the most frequent ingredient in the classical formulae was also frequent in modern formulae.

The pharmacological actions of the seven most frequently used herbs included anti-inflammatory, anti-allergic, antioxidant and/or anti-bacterial effects that may have contributed to their observed effects.

Conclusions

Results for classical interventions and the modern clinical literature overlapped for the higher frequency oral formulae and their ingredients, showing evidence of temporal continuity in their use for rhinosinusitis management. Gaps in the clinical and experimental evidence were identified, so there remains scope for further research into these CHMs to develop new interventions for rhinosinusitis.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12906-025-04895-x.

Keywords: Rhinosinusitis, Sinusitis, Chinese medicine, Herbal medicine, Text mining, Drug discovery, Evidence-based medicine, Randomised controlled trials, History of medicine, Biological mechanisms of action

Background

Rhinosinusitis (RS) is an inflammation of the paranasal sinuses and nasal cavity. Its symptoms include nasal blockage, obstruction and/or congestion; and nasal discharge (anterior/posterior nasal drip), with or without facial pain/pressure and/or reduction or loss of smell. RS can be verified by endoscopy or computed tomography (CT) [1–3].

When symptoms have continued for less than four weeks, it is acute RS (ARS). When two or more symptoms persist for 12 weeks or more, it is chronic RS (CRS) [3]. People with CRS can be broadly divided into those with and those without nasal polyps [2, 3]. Another category of RS is fungal [4].

In China, this disorder can be referred to by the traditional name bi yuan, the biomedical name, sinusitis (bi dou yan) and by the most recent biomedical term, rhinosinusitis (bi-bi dou yan). In traditional Chinese medicine (TCM), bi yuan is diagnosed according to the clinical symptoms of nasal blockage, turbid nasal discharge, facial pain and/or pressure and/or headache, and/or reduction in the sense of smell [5]. This clinical diagnosis does not require confirmation by endoscopy and/or computed tomography, although these tests are used in many TCM hospitals in China. In general, bi yuan encompasses disorders that would be biomedically diagnosed as ARS or CRS.

In conventional medicine, CRS management typically requires intra-nasal steroids, with nasal saline irrigation and/or oral antibiotic therapy during exacerbations, plus allergen avoidance in people with allergies [2, 3]. More recently, biologics have been added [6]. When these approaches don’t sufficiently control symptoms, surgery may be considered [1, 2]. Although these approaches are generally effective, antibiotic resistance remains an issue [7, 8], so there is a need to identify candidates for future product development.

Chinese herbal medicines (CHMs) have long been used for nasal disorders, including RS, and feature in Chinese clinical guidelines [5, 9–11]. Although termed ‘traditional’, modern TCM combines traditional practices with research results, uses modern diagnostic methods, and may combine TCM interventions with conventional biomedicine as ‘integrative Chinese–Western medicine.’ In China, TCM is part of the national healthcare system, with 4,630 Chinese medicine hospitals and 756 integrative Chinese–Western medicine hospitals operating in 2021 [12, 13].

From the perspective of evidence-based medicine, it has been proposed that traditional use that has been well documented could be considered a source of evidence [14], and such evidence could be considered along with the results of clinical and experimental studies as components of a ‘whole evidence’ approach to evaluating TCM interventions [15].

In the field of herbal medicine, systematic investigation of pre-modern texts has been proposed as a bioprospecting strategy in the search for new drugs [16, 17]. Subsequently, several text mining studies have been published based on European [18–20], Korean [21, 22] and Chinese sources [23–28], but none focussed on RS.

This text mining study identifies traditional formulations and their constituent natural product ingredients that have been used for conditions similar to RS during the classical and pre-modern period (until 1949). It then compares these with approaches recommended in contemporary CHM guidelines for RS management and examines the contemporary clinical research into these formulations. The study aimed to investigate the historical use of CHMs for RS and identify prospects for future clinical and experimental studies, which may lead to development of new RS treatments.

The research questions are:

• Which CHM interventions were used in ancient and pre-modern China for nasal disorders similar to RS?

• What are the similarities and differences between ancient CHM interventions, those included in contemporary clinical guidelines, and those tested in modern randomised controlled trials (RCTs)?

• To what extent does the information on CHM in modern specialist textbooks reflect the classical literature and clinical guidelines?

• What are the likely mechanisms of action of the frequently used herbs?

• Are there any gaps in the evidence that could be addressed in future research?

Materials and methods

Classical and pre-modern Chinese medical literature was searched electronically using the Encyclopaedia of Traditional Chinese Medicine (Zhong Hua Yi Dian –ZHYD) 5 th edition. This database contains the full texts of more than 1,150 classical and pre-modern Chinese medical books [29] written between the second century BCE and the mid twentieth century. It is one of the largest collections of such books [30]. Comparisons with other collections of classical books on Chinese medicine found it was representative of the classical and pre-modern medical literature in Chinese [31].

The text mining approach followed a procedure that has been described in detail elsewhere [32]. Terms reportedly used to refer to sinusitis and RS in the pre-modern and ancient Chinese literature were identified from medical dictionaries [33, 34], modern textbooks (Additional file 1) and clinical guidelines [5, 9–11]. Then test searches of ZHYD were conducted of all included books. Terms that did not locate any passages of text relevant to nasal disorders that could have been RS were discarded.

Books and guidelines identified the main names for sinusitis as bi yuan and nao lou. Additional terms related to nao lou included nao shen, nao beng, nao xie, kong nao sha and nao sha (all probable synonyms for ‘sinusitis’). In addition, we included two symptoms from the books and guidelines: zhuo ti (turbid nasal discharge) and bi chu chou qi (foul nasal odour).

We did not include the term bi se, since it could refer to many types of nasal blockage, or bi qiu, since it referred to conditions with clear rather than turbid nasal discharge and is a contemporary term for allergic rhinitis. We also did not include terms related to growths in the nose that could have been polyps (e.g. xi rou, bi zhi). Test searches showed these names alone did not locate good examples of RS. When a citation included one of these excluded terms in addition to the included search terms, it was still included in the data set, since treatments may have been used for multiple nasal disorders.

Search results from all books included in ZHYD were downloaded as semi-structured text. We identified distinct passages of text that referred to one or more of the search terms and included information relevant to symptoms, aetiology, definition of the disorder and/or medical management. These passages were defined as a ‘citation’ and were numbered and entered in a spreadsheet, along with the name of the book in which the citation was located, dynasty and year in which the book was written, description of the disorder, and intervention. Duplicate citations from the same book were identified and excluded. Books written after 1949 were excluded [32].

Citations were read in detail by at least two researchers (WL, JC, and/or BM) and scored yes (= 1) or no (= 0) based on pre-set criteria. Any issues were resolved through discussion between the two researchers, and where necessary with a third person (BM or LQ). If there was no consensus on the meaning of a citation, it was excluded. We did not calculate inter-rater reliability.

When a CHM intervention was mentioned, the formula name (if any) and ingredients were added in separate columns. Formula names were according to the original book. When there was only a list of ingredients the citation was specified as ‘no name’ even when we could infer a likely formula name. In such cases the ingredients were still included in the data sets for herb frequency. When a citation included a formula that had additional ingredients these were regarded as modifications and it was grouped with other formulae with the same name, except when the main ingredients of the base formula were different. In such cases numbers were allocated to the formula name. When there were differences in the name of the same formula (based on the ingredients) such as Cang er san and Cang er zi san (Xanthium powder), these were grouped together as Cang er (zi) san for analysis. Similarly, when the preparation type was different, such as tang (decoction) or san (powder), but the ingredients were the same, these citations were grouped together for analysis. Individual herbs from classical pharmacopoeia were calculated separately.

Codes were allocated to indicate oral CHM, nasal CHM, or other therapies (not included in this paper). We could not reliably distinguish ARS from CRS, because duration of the disorder was not typically included in classical citations. When the description was not consistent with RS signs and symptoms (based on the pre-set criteria), the citation was excluded. Analyses were conducted in SPSS® using descriptive statistics to identify frequencies of search terms, herbal formulae, and their constituent herbs. Cross-tabulations included the source book, year and dynasty during which the book was written and the main disorders or symptoms.

Comparison with contemporary TCM practice was based on the 2012 clinical guideline for TCM, because it included syndrome differentiation plus recommended formulae [5], a convenience sample of 13 modern specialist textbooks on Chinese otorhinolaryngology sourced from libraries in China and Australia and internet searches (Additional file 1), and the official Chinese pharmacopoeia [35]. Comparisons with clinical research were based on two published systematic reviews of CHMs for RS [36, 37] and a recent book with chapters on CHM research [38]. Comparisons were qualitative to identify overlaps and discrepancies in the formula names and formula ingredients between pairs of data sets. All items were considered in comparisons although the results tables focus on the higher frequency items. Ranking based on frequency was used to facilitate comparisons between the formulae and their ingredients in the data sets derived from the classical books and the RCTs. No tests for statistical significance were conducted. Comparisons with the smaller data sets were based on the presence or absence of each item.

Results

ZHYD database searches yielded 1,901 results for the eight search terms. Following duplicate removal and exclusion of irrelevant and unclear passages of text, 678 citations were relevant to RS and included a Chinese medicine (CM) intervention (Fig. 1). Of these, 436 were of oral CHM formulae, 81 were of nasal or other topical CHMs, 112 were single items from classical pharmacopoeia and book sections on materia medica (ben cao) used orally and/or topically, and the remainder (n = 49) referred to acupuncture and related therapies.

Fig. 1.

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Flow diagram of the search and selection process for citations of interventions for disorders similar to rhinosinusitis

The search term bi yuan located 541 citations relevant to RS (79.8% of the total) followed by zhuo ti (148 citations, 21.8%) and nao lou (94 citations, 13.9%) (Table 1).

Table 1.

Hit and citation frequency by search term

Pinyin (translation)

Chinese characters

Hit frequency1

Citations n (%)2,3

bi yuan (sinusitis)

鼻渊

951

541 (79.8)

nao lou (sinusitis, synonym)

脑漏

242

94 (13.9)

nao shen (sinusitis, synonym)

脑渗

51

9 (1.3)

nao beng (sinusitis, synonym)

脑崩

23

5 (0.7)

nao xie (sinusitis, synonym)

脑泻

43

19 (2.8)

(kong) nao sha (sinusitis, synonym)

(控)脑砂/沙

49

7 (1.0)

zhuo ti (turbid nasal discharge)

浊涕

499

148 (21.8)

bi chu chou qi (foul nasal odour)

鼻出臭气

6

3 (0.4)

Totals

1901

678a

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1A hit was an instance of the search term in the database. The numbers are before duplicate removal and screening

2A citation was a distinct passage of text referring to one or more of the search terms. The numbers are after duplicate removal and screening

3Terms not searched included: bi se 鼻塞 (nasal blockage), bi qiu 鼻鼽 (allergic rhinitis), xi rou 瘜肉 (nasal polyp), bi zhi 鼻痔 (nasal polyp), xi rou 息肉 (nasal polyp)

aSome citations were located by two or more search terms

Oral formulae and their constituent ingredients

Of the 436 citations of oral herbal formulae, 105 were of named formulae and 168 formulae were not named. Most formulae (n= 277, 63.5%) were from the Qing dynasty (circa 1645–1911), and 128 formulae (29.4%) were from the Ming dynasty (circa 1369–1644) (Table 2).

Table 2.

Dynastic distribution of citations relating to oral herbal formulae

Dynasty (years)

Number (%) of citations

Tang and 5 Dynasties (618–960) and before

1 (0.2)

Song, Jin & Yuan Dynasties (961–1368)

20 (4.6)

Ming Dynasty (1369–1644)

128 (29.4)

Qing Dynasty (1645–1911)

277 (63.5)

Min Guo/Republic of China (1912–1949)

10 (2.3)

Total

436 (100)

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Comparisons were made between the results of the searches of ZHYD and multiple samples from the modern literature on CHM for RS. The main comparisons are shown in Fig. 2.

Fig. 2.

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Diagram of comparisons between data sets. Abbreviations: CHM Chinese herbal medicine, RCT randomised controlled trial, ZHYD Encyclopaedia of Traditional Chinese Medicine (Zhong Hua Yi Dian)

The most frequent formula name in the ZHYD results was Cang er (zi) san (Xanthium powder) (n = 47), followed by Fang feng san (Saposhnikovia powder) (n = 25). These two formulae were first listed in books written during the Song dynasty (960–1279 CE) (Table 3).

Table 3.

Frequent oral herbal formulae in classical citations by inclusion in guideline, modern textbooks, and clinical trials

Formula namea,b (translation)

Frequency [year range]e

Listed in 2012 guidelinec

Listed in modern textbooks

Tested in RCTs (n)d

Cang er (zi) san (Xanthium powder)

47 [1253–1911]

No

Yes

Yes (2)

Fang feng san (Saposhnikovia powder)

25 [1117–1823]

No

No

No

Xin yi san (Magnolia flower powder)

14 [1565–1930]

No

Yes

No

Fang feng tong sheng san (Ledebouriella powder that sagely unblocks) with additions

13 [1515–1817]

No

No

No

Bu zhong yi qi tang (Tonify the middle and augment the qi decoction)

8 [1665–1893]

No

Yes

No

Qi shou huo xiang wan/tang, Huo xiang tang (aka Huo dan wan)f (Huodan pills)

7 [1665–1831]

No

Yes

Yes (1)

Chuan xiong cha tiao san (Ligusticum chuanxiong powder to be taken with green tea) with additions

5 [1406–1830]

No

Yes

No

Liu wei wan (Six flavour pill)g

4 [1751–1893]

No

Yes

No

Tian luo san (Tianluo Powder)h

4 [1665–1796]

No

No

No

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Abbreviations: aka also known as, RCT randomised controlled trial, SR systematic review

aIncluding modified versions. Four formulae were called Bi yuan fang, but they varied considerably in their ingredients, so were not included in this table

bAll formulae in this table were for bi yuan except for Bu zhong yi qi tang for nao lou, and Tian luo san for kong nao sha. When oral and topical use was mentioned, the citation was included

cChinese Guidelines, 2012[5]

dIn SR 1 Cui J et al. 2022 and/or SR2 Cui J et al. 2023

eYears are based on when the books were written or published. This may be approximate. See [32] for how book years were determined

fThese are all alternative names for the same formula, so they have been grouped together. The most frequent name was Qi shou huo xiang wan (n = 5). The name Huo dan wan did not appear. All had the same ingredients

gThis was not Liu wei di huang wan (Six ingredient pill with rehmannia)

hThe formulae named Bi yuan fang 鼻渊方 (Sinusitis formula, n = 4) are not included due to variability in their ingredients between versions

One low frequency oral formula from the classical citations (Wen fei zhi liu dan, n = 1) was listed in the 2012 clinical guideline (Table 4), nine formulae from the classical citations (including modified versions) were listed in modern textbooks on Chinese otorhinolaryngology (Additional file 2), and three formulae found in the classical search were assessed in RCTs included in the systematic reviews (Table 3, Additional file 3).

Table 4.

Summary of syndrome differentiation and oral herbal formulae from 2012 guideline by inclusion in classical search and clinical trials

Syndrome in 2012 guideline

Oral formula in 2012 guideline (translation)

Formula in classical search

Freq. of the formula used in RCTs of oral CHMa

Wind–heat in the Lung meridian (fei jing feng re)

Yin qiao san (Honeysuckle and forsythia powder), modified

No

0

Stagnant heat in the Gallbladder (dan fu yu re)

Long dan xie gan tang (Gentiana longdancao decoction to drain the liver), modified

No

2

Spleen–Stomach dampness-heat (pi wei shi re)

Gan lu xiao du dan (Sweet dew special pill to eliminate toxin), modified

No

1

Lung qi deficient and cold (fei qi xu han)

Wen fei zhi liu dan (Wenfei Zhiliu Pills), modified

Yes (n = 1)

1

Spleen qi deficient and weak (pi qi xu ruo)

Shen ling bai zhu san (Ginseng, poria, and atractylodes macrocephala powder), modified

No

2

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Abbreviations: CHM Chinese herbal medicine, Freq frequency, RCT randomised controlled trial

aIn the RCTs included in the two systematic reviews, the formula was applied for people with the same syndrome as in the guideline

In the 436 formulae for oral use, there were 3,059 ingredients (mean, 7 ingredients per formula). The most frequently used ingredients were Magnolia spp (xin yi (hua), n = 162), Angelica dahurica (bai zhi, n = 152), Glycyrrhiza spp (gan cao, n = 143), Xanthium sibiricum (cang er (zi), n = 135), and Mentha spp (bo he, n = 135). Most of these herbs were included in multiple books written from the Song dynasty (960–1279 CE) until the early twentieth century (until 1949) (Table 5).

Table 5.

Frequently used ingredients in oral herbal formulae in classical citations by inclusion in clinical trials and modern Chinese pharmacopoeia

Scientific name (main species)a

Herb name

Frequency (rank) in classical citations [year range]b

Frequency (rank) in formulae in SR 1c

Frequency (rank) in formulae in SR 2c

Used for RS in modern Chinese pharmacopoeia (Y/N)

Magnolia spp. flower bud

Xin yi (hua)

162 (1) [1117–1949]

30 (1)

15 (1)

Yesd

Angelica dahurica (Fisch ex Hoffm) Benth et Hook F

Bai zhi

152 (2) [1117–1930]

29 (2)

14 (2)

Yesd

Glycyrrhiza spp

Gan cao

143 (3) [682–1949]

16 (5)

13 (3)

No

Xanthium sibiricum Patr

Cang er (zi)

135 (4) [1253–1930]

26 (3)

12 (4)

Yesd

Mentha haplocalyx Briq

Bo he

135 (4) [1253–1949]

16 (5)

6 (8)

No

Ligusticum chuanxiong Hort

Chuan xiong

134 (6) [1117–1924]

12 (7)

6 (8)

No

Scutellaria baicalensis Georgi

Huang qin

102 (7) [1117–1949]

22 (4)

11 (5)

No

Saposhnikovia divaricata (Turcz) Schischk

Fang feng

88 (8) [1117–1911]

7 (18)

3 (21)

No

Panax ginseng C A Mey

Ren shen

69 (9) [1117–1911]

0 (NA)

0 (NA)

No

Allium fistulosum L

Cong (bai)

69 (9) [1117–1930]

0 (NA)

0 (NA)

No

Angelica sinensis (Oliv) Diels

Dang gui

64 (11) [1117–1911]

4 (29)

4 (15)

No

Camellia sinensis (L) Kuntze

Cha (ye)

64 (11) [1253–1928]

0 (NA)

0 (NA)

No

Poria cocos Wolf

Fu ling

62 (13) [1132–1945]

10 (9)

7 (6)

No

Schizonepeta tenuifolia Briq

Jing jie

56 (14) [1117–1911]

8 (15)

1 (42)

No

Ophiopogon japonicus (L f) Ker-Gawl

Mai men dong

52 (15) [1117–1883]

0 (NA)

0 (NA)

No

Platycodon grandiflorum (Jacq) A DC

Jie geng

49 (16) [1358–1949]

11 (8)

5 (12)

No

Gardenia jasminoides Elli

Zhi zi

48 (17) [1358–1949]

9 (12)

2 (28)

No

Pinellia ternata (Thunb) Breit (processed)

Ban xia (fa)

45 (18) [1132–1945]

0 (NA)

1 (42)

No

Asarum spp

Xi xin

44 (19) [1266–1924]

5 (26)

3 (21)

Yesd

Gypsum fibrosum

Shi gao

42 (20) [1117–1934]

5 (26)

0 (NA)

No

Zingiber officinale Ros.; fresh/dried

Jiang; sheng/gan

40; 28/12 (21) [1117–1911]

0 (NA)

0 (NA)

No

Atractylodes macrocephala Koidz

Bai zhu

37 (22) [1358–1911]

3 (33)

6 (8)

No

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Abbreviations: RS rhinosinusitis, SR systematic review

aA complete list of the source species for these herbs is available in the Chinese pharmacopoeia [35]. The use of some herbs/ingredients may be restricted in some countries e.g. Asarum spp. Readers are advised to comply with relevant regulations. Herb frequencies include unnamed formulae

bYears are based on when the books were written or published. These may be approximate. See [32] for how book years were determined

cSR 1 is Cui J et al. 2022; SR 2 is Cui J et al. 2023

dFor bi yuan

The comparison between the 22 most frequently used ingredients in classical formulae and ingredients of formulae tested in RCTs was based on one systematic review of oral CHMs for ARS and CRS that included 34 RCTs [36], and one systematic review of CRS following surgery that included 21 RCTs [37]. The first seven herbs from classical formulae, were in the top 10 ingredients in the formulae tested in the RCTs in each systematic review (Table 5). The Chinese pharmacopoeia [35] listed four of the 22 most frequently used ingredients for RS, each for bi yuan.

In the 112 classical pharmacopoeia citations, the most frequent herbs for oral use were Magnolia spp (xin yi (hua), n = 16), Xanthium sibiricum (cang er (zi), n = 14), Angelica dahurica (bai zhi, n = 13) and Piper longum (bi ba, n = 12). Of these, the three most frequent are still listed in the Chinese pharmacopoeia for bi yuan (Table 6).

Table 6.

Frequently mentioned herbs for internal use in classical pharmacopoeia by inclusion in modern Chinese pharmacopoeia

Scientific namea

Herb name (pin yin)

Frequency (rank) in classical citationsb

Used for RS in modern Chinese pharmacopoeia (Y/N)

Magnolia spp. (flower bud)

xin yi (hua)

16 (1)

Yesc

Xanthium sibiricum Patr

cang er (zi)

14 (2)

Yesc

Angelica dahurica (Fisch ex Hoffm) Benth et Hook f

bai zhi

13 (3)

Yesc

Piper longum L

bi ba

12 (4)

No

Luffa cylindrica (L) Roem

si gua/si gua teng (gen)

6 (5)

No

Nelumbo nucifera Gaertn

ou jie

4 (6)

No

Asarum spp.

xi xin

3 (7)

Yesb

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Abbreviations: RS, rhinosinusitis

aA complete list of the source species for these herbs is available in the modern Chinese pharmacopoeia [35]. The use of some herbs/ingredients may be restricted in some countries e.g. Asarum spp, Readers are advised to comply with relevant regulations

bWhen oral and topical use was mentioned, the citation was included

cFor bi yuan

Nasal formulae and their constituent ingredients

Fifty-two classical literature citations mentioned a CHM intervention for nasal application, mainly for bi yuan (n = 29). Most interventions had no name (n = 49). The exception was the powder Liu sheng san (n = 3). It could be sniffed into the nose or mixed with water and blown into the nose. This formula is not used in contemporary CHM [38]. The interventions used 142 ingredients. The most frequent were: Magnolia spp (xin yi (hua), n = 7) and moschus (she xiang, n = 7), followed by Allium fistulosum (cong (bai), n = 6) (Table 7).

Table 7.

Frequently used ingredients in nasal herbal formulae in classical citations by inclusion in clinical trials and modern Chinese pharmacopoeia

Scientific namea

Herb name (pin yin)

Frequency (rank) in classical citations

Frequency (rank) in formulae in RCTs (CRS + ARS)b

Used for RS in modern Chinese pharmacopoeia (Y/N)c

Magnolia spp. (flower bud)

xin yi (hua)

7 (1)

6 (1)

Yesd

moschus

she xiang

7 (1)

0

No

Allium fistulosum L (white section)

cong (bai)

6 (3)

0

No

Ligusticum chuanxiong Hort

chuan xiong

5 (4)

2 (5)

No

realgar

xiong huang

5 (4)

0

No

Luffa cylindrica (L) Roem (vine)

si gua (teng)

4 (6)

0

No

borneol

bing pian

4 (6)

1 (10)

No

Angelica dahurica (Fisch ex Hoffm) Benth et Hook f

bai zhi

3 (8)

4 (2)

Yesd

Pogostemon cablin (Blanco) Benth or Agastache rugosa (Fisch & Mey) O Ktze

huo xiang

3 (8)

0

No

frankincense

ru xiang

3 (8)

0

No

myrrh

mo yao

3 (8)

0

No

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Abbreviations: ARS acute rhinosinusitis, CRS chronic rhinosinusitis, RCT randomised controlled trial, RS rhinosinusitis

aA complete list of the source species for these herbs is available in the Chinese pharmacopoeia [35]. The use of some herbs/ingredients may be restricted in some countries e.g. moschus and realgar. Readers are advised to comply with relevant regulations

bThe book included six RCTs: one of ARS (nasal + oral), four of CRS (nasal), one of CRS (nasal + oral)

cThe Chinese pharmacopoeia does not specify the route of administration

dFor bi yuan (sinusitis)

The comparison with RCTs was based on a systematic review that included six RCTs: one of nasal plus oral CHM for ARS, four of nasal CHMs for CRS, and one of nasal plus oral CHM for ARS [38]. One of the high-frequency CHMs in the nasal formulae from the classical literature, Magnolia spp. (xin yi (hua)), was the highest frequency ingredient (n = 6) in the nasal formulae tested in the RCTs, but the other high-frequency ingredient, moschus (she xiang), was not used in any RCTs. Overall, of the 11 most frequently used ingredients from classical nasal formulae, four were used in one or more RCTs (Table 7). The Chinese pharmacopoeia listed two of the ingredients for RS.

Discussion

Classical nomenclature

The term bi yuan indicates a disorder of the nose (bi), with the second character (yuan) suggesting a deep pool or well of water. It appears in the classical book Huang Di Nei Jing Su Wen ‘Huang Di’s Inner Classic – Basic Questions,’ which is considered a product of the Former Han dynasty (circa 206 BCE–24 CE), with additions from the later Han dynasty (circa 25–220 CE) [39, 40]. Chapter 37 (Qi jue lun) states: ‘heat from the Gall bladder [channel] enters the brain causing a burning feeling where the nose meets the forehead, and bi yuan. Bi yuan is continuous turbid discharge.’ This explanation is in accord with the literal meaning of the term bi yuan, and adds that the discharge is turbid, due to heat, and affects the brain. In reference to the external pathogen ‘heat qi’ (re qi), Chapter 74 (Zhe zhen yao da lun) states: ‘if it invades the lung, it [produces] cough and bi yuan’ [41]. This text again notes heat as a causative agent, but that it affects the lung and is associated with cough. The first of these two passages was quoted in multiple included citations. In terms of the aetiology, these two passages are reflected in the names of Chinese medicine syndromes – Stagnant Heat in the Gallbladder (dan fu yu re) and Wind–heat in the Lung Meridian (fei jing feng re) in a modern clinical guideline that includes five syndromes [5].

The term nao lou appeared much later than bi yuan in the literature. It literally means ‘brain leakage’ and appears to paraphrase Chapter 37 above. The earliest use of this term we identified was in the book Chi Shui Xuan Zhu ‘Black Pearl from the Red River’ (circa 1584), which described the symptoms of nao lou as ‘nasal discharge that was clear and/or turbid which lasted many years’ [38]. Notably, in the modern clinical guideline, the syndrome Wind–heat in the Lung Meridian includes white or yellow discharge plus cough among typical symptoms [5].

The book Wai Ke Zheng Zong ‘Orthodox Manual of External Diseases’ (circa 1617) states that nao lou was also called bi yuan [42], and subsequent classical books tended to agree [38]. Of the low-frequency search terms, nao shen was not the name of a disorder, just a term meaning ‘brain leaks’, and the terms nao beng, nao xie and (kong) nao sha (Table 1) appear to have been synonyms for nao lou [38].

From a modern perspective, we cannot be certain that any of the people diagnosed as having these disorders in premodern China would now be diagnosed as having RS. Based on the symptoms of the disorders described in the source books, these disorders were not inconsistent with RS. However, we do not know the prevalence of RS in premodern China and can only assume that it was not a rare disorder. It is also likely that a small proportion of disorders referred to as nao lou or its synonyms referred to leakage/discharge of fluid from the skull through the nose. It is notable that dizziness was a symptom of long-term nao lou [42]. In other cases, allergic rhinitis may have been the disorder, although this is usually included under the term bi qiu, and a wide range of other disorders in which the salient symptom was nasal discharge could have been included within the scope of bi yuan, nao lou and related terms. Nevertheless, a large proportion of the included cases would now likely receive a TCM diagnosis of bi yuan (sinusitis).

Comparisons between classical literature and modern practice

When compared, modern and classical TCM concepts of bi yuan and the interventions used for this disorder show similarities. When the 2012 clinical guideline was used as a reference point, only one of the five recommended oral formulae appeared in the classical search (Table 4). However, when the comparison was broadened to include 13 modern TCM specialist textbooks, that included about 15 different syndrome types and about 60 recommended formulae, nine classical formulae (15%) were still included (Additional file 2). Three of these formulae have been tested in RCTs (Additional file 3).

All the syndromes and oral formulae in the 2012 guideline (Table 4) were also included in one or more of the 13 specialist textbooks (Additional file 2), so the guideline appears to be a subset of modern literature. Overall, the textbook sample provided a broader scope of syndromes and formulae than the guideline and was probably representative of the scope of modern clinical practice.

In terms of evidence base, four of the five oral formulae in the 2012 guideline have been evaluated in one or two RCTs for people with CRS who also had the Chinese medicine syndrome appropriate to the formula (Table 4). Of the 33 named oral formulae tested in the RCTs, 14 (42%) were included in the specialist textbooks (Additional file 3).

When compared, oral formula ingredients that ranked highly in the ZHYD list (ranks 1–7) also ranked highly in the two systematic reviews (ranks 1–8) (Table 5). This suggests that despite the diversity in formula names, formulae tended to be based on similar herbal ingredients. This similarity was likely enhanced by the practice of modifying formulae to add herbs commonly used for RS.

In addition, when classical and modern pharmacopoeia were compared, four of the top seven herbs from the ZHYD list were still listed for bi yuan (sinusitis) in the Chinese pharmacopoeia (Table 6). Notably, three of these were high-frequency items in the RCTs. However, one of the herbs listed in the Chinese pharmacopoeia, xi xin (Asarum spp.), was much less frequently used in the classical formulae (rank 19) and RCTs (ranks 26 and 21) (Table 5). The use of this herb is restricted in many countries due to toxicity concerns.

Data sets were much smaller for nasal formulae than oral formulae. This meant we could not compare formula names because there were few formula names in the ZHYD data, and the 2012 clinical guideline did not include nasal formulae. Four of the 11 nasal formula ingredients (ranked 1–8) were also ingredients in formulae tested in RCTs, and two of these were listed in the Chinese pharmacopoeia (Table 7). A notable difference between classical and modern nasal formulae was the use of strongly aromatic ingredients in the classical formulae, such as moschus (she xiang), allium (cong bai), borneol (bing pian), pogostemon/agastache (huo xiang), frankincense (ru xiang) and myrrh (mo yao), whereas only borneol (bing pian) was used in RCTs. This may be because inhalations were common interventions in classical books, but the RCTs mainly used nasal irrigations.

When the herbs in the three searches of ZHYD were compared, of the top ten in the oral formulae, the herb with the highest ranking, Magnolia spp. (xin yi (hua)) was also the top-ranking herb in nasal formulae and in the classical pharmacopoeia (Additional file 4). Other herbs appearing in all three classical data sets were Angelica dahurica (bai zhi), Mentha haplocalyx (bo he), and Ligusticum chuanxiong (chuan xiong). Xanthium sibiricum (cang er (zi)) ranked highly in the oral formulae and the classical pharmacopoeia but was not present in the classical nasal interventions, although it was used in the RCTs of nasal interventions [38].

Possible mechanisms of action

The seven most frequently used herbs in classical oral formulae that were also frequently used in RCTs each show biological activity relevant to RS in experimental studies that tested their extracts and/or constituent compounds [38]. These activities are summarised below.

Xin yi (hua) is sourced from the flower buds of multiple magnolia species, with Magnolia biondii Pamp. (aka M. fargesii), M. denudata Desr. and M. sprengeri Pamp. being official. It has anti-inflammatory, antihistamine-like and antioxidant effects. Bai zhi, sourced from Angelica dahurica (Fisch ex Hoffm) Benth et Hook f; and A dahurica (Fisch ex Hoffm) Benth et Hook f var formosana (Boiss) Shan et Yuan, has anti-inflammatory, antihistamine-like, anti-microbial, and antioxidant effects. Gan cao, sourced from Glycyrrhiza uralensis Fisch, G. inflata Bat and G. glabra L roots, has anti-inflammatory properties and free radical scavenging activity [38].

Dried fruit from Xanthium sibiricum Patr (aka X. strumarium L) is the source of cang er zi, which has anti-inflammatory, anti-bacterial and antiviral effects, and inhibitory effects on histamine release. Bo he, sourced from the arial parts of Mentha haplocalyx Briq (aka M. canadensis L and M. arvensis L var haplocalyx Briq), has anti-inflammatory and free radical scavenging effects, and inhibitory effects on bacterial growth and histamine production. Chuan Xiong, sourced from Ligusticum chuanxiong Hort (LC) (aka L. wallichii Franch) roots and rhizomes, has anti-inflammatory and free radical scavenging activity. Huang qin, sourced from Scutellaria baicalensis Georgi roots, has anti-inflammatory, anti-allergic, antioxidant, anti-bacterial and anti-fungal effects [38].

In addition to the above seven most frequently used herbs, classical literature searches identified some herbs included frequently in classical pharmacopoeia as interventions for RS that did not appear in the official Chinese pharmacopoeia for this indication (Table 6). Of note is Piper longum L (bi ba), which is also used in foods. It was listed in the most comprehensive of the pre-modern pharmacopoeia, Ben Cao Gang Mu ‘Compendium of Materia Medica’ (circa 1578), for headache and bi yuan, and is still listed for these and other indications in some modern comprehensive pharmacopoeia [43, 44]. Therefore, we searched experimental literature in PubMed to investigate whether this herb has shown activity that may help explain its historical use for RS and related disorders.

Piper longum L fruit contains multiple compounds, including the alkaloids piperine and piperlonguminine, both of which were detected in rat plasma after oral administration, indicating these compounds were absorbed rapidly and cleared slowly over 24 h [45]. Piper longum has shown free radical scavenging activity [46]. In rats, an aqueous extract of its fruits showed low toxicity [47]. A study in rats that tested the dried leaf showed moderate antibacterial activity against Klebsiella pneumoniae, but not against other bacteria included in the screen. Significant anti-inflammatory activity was seen in the carrageenan-induced paw oedema model and other tests [48]. Oral administration of oil extracted from the dried fruit significantly reduced carrageenan-induced paw oedema [49]. Fruit extracts showed anti-inflammatory activity in the same model [47]. Powdered fruits of two varieties of Piper longum showed anti-inflammatory effects in carrageenan-induced paw oedema and formalin-induced paw oedema [50]. In models of Parkinson’s disease, alkaloid extracts (mainly piperine and piperlonguminine) reduced behavioural impairments, increased antioxidant activity, and reduced excessive proinflammatory cytokine release induced by injection of lipopolysaccharide [51, 52]. Overall, these studies showed anti-inflammatory activity in multiple animal models, but none were specific to RS.

Limitations

One limitation of this text mining study is that we used a single source for literature. While this was the largest collection available, it did not include all books written in pre-modern China, so we might have missed some less significant historical publications relevant to RS. Some reports of conditions similar to RS may not have used any of the search terms we identified, even though we used multiple search terms, so these may have been missed.

Although the citations from the classical literature referred to conditions similar to the modern conception of RS, the criteria for similarity were based on classical terminology for which the scope of meaning is likely to have been different to current usage. Therefore, it remains unclear whether a nasal disorder referred to in a classical citation would now be classified as RS. Moreover, we could not reliably distinguish between ARS and CRS. We assume that CRS was more likely in the classical citations since classical books tend to focus on more serious conditions, but this remains an assumption. There were few studies of ARS in the systematic reviews, so comparisons between classical results and clinical trial results were not feasible for ARS.

In the comparisons, we used a sample of modern TCM specialist textbooks based on availability. There was no deliberate selection of books, but as this was not a random sample of all possible books, bias is a possibility.

Analyses were descriptive based on frequency, rank and overlap between data sets. Higher frequency in a data set is an indication of usage or popularity and should not be misconstrued as indicating greater effectiveness of a formula or herbal ingredient for RS management. Similarly, presence or absence of an item in multiple data sets is not a measure of effectiveness.

Our selection of Piper longum for a mini review was based on its frequency alone, and other lower frequency CHMs may have shown stronger evidence.

Evidence gaps

Four of the five oral formulae in the 2012 guideline have been tested in RCTs (Table 4, Additional file 3), but the studies tended to have small sample sizes and be open label, so further, more rigorously designed studies are needed. Moreover, an RCT of the formula Yin Qiao San (Honeysuckle and forsythia powder) for RS was yet to be published and there have been few clinical studies of ARS.

The three most frequent formulae tested in the RCTs appeared in the sample of TCM textbooks but were not included as recommendations in the guideline (Table 4). This may be because these are modern commercially available preparations, whereas the guideline focussed on traditional formulae. Considering the advances in evidence based Chinese medicine over the past 20 years [53], there appears to be scope for TCM guidelines to be updated to include additional oral and nasal formulae based on the findings of clinical research and meta-analyses. This could assist practitioners to base their clinical practice on the best available evidence.

The summary of experimental studies of CHMs frequently used for RS did not find any studies in animal models specific for RS. While the CHMs’ reported benefits in RS could be due to their anti-inflammatory, anti-allergic, antioxidant and/or anti-bacterial effects, further experiments are needed to elucidate the effects of these herbs and their constituents in models directly relevant to RS. Moreover, since the herbs are used clinically as multi-ingredient formulae, their combinations could also be tested.

Conclusions

This text mining study identified references to disorders similar to RS in a Chinese medical book from approximately 2,000 years ago. Results for classical interventions overlapped with findings from two systematic reviews and a sample of 13 specialist textbooks. This showed evidence of temporal continuity in the use of certain orally administered CHMs in RS management. Nevertheless, there is scope for further clinical and experimental research into the frequently cited CHM formulations and their ingredients to inform clinical decision making and their mechanisms of action could be explored in animal models to identify future therapeutics.

Supplementary Information

12906_2025_4895_MOESM1_ESM.docx (32.1KB, docx)

Additional file 1. List of modern specialist textbooks included in the convenience sample.

12906_2025_4895_MOESM2_ESM.docx (54.1KB, docx)

Additional file 2. Summary of syndrome differentiation and oral Chinese herbal medicines from modern specialist textbooks by inclusion in classical search.

12906_2025_4895_MOESM3_ESM.docx (35.2KB, docx)

Additional file 3. List of oral formulae included in the two systematic reviews by inclusion in 2012 guideline, sample of modern textbooks, and classical search.

12906_2025_4895_MOESM4_ESM.docx (31.8KB, docx)

Additional file 4. List of ten most frequent herbs in oral formulae included in the classical search by inclusion in nasal formulae and classical pharmacopoeia.

Acknowledgements

We thank Louise Pobjoy for her comments and editing.

Abbreviations

Aka

Also known as

ARS

Acute rhinosinusitis

CE

Christian era

CHM

Chinese herbal medicine

CM

Chinese medicine

CRS

Chronic rhinosinusitis

CT

Computed tomography

RCT

Randomised controlled trial

RS

Rhinosinusitis

TCM

Traditional Chinese medicine

ZHYD

Zhong Hua Yi Dian

Authors’ contributions

The project was conceptualized by: JC, BHM, WL, ALZ, XG, CL, YL and CCX. Data collection, checking and/or analysis was by: JC, BHM, WL and QL. Methodology was developed by: BHM, WL, JC, ALZ, XG, CJ and CCX. Funding was acquired by: CJ and CCX. The project was administered and/or supervised by: ALZ, XG, CL, CCX and YL. Writing of the original draft was by: JC, BHM and WL, with additional review and editing by QL, ALZ and CCX. All authors reviewed the manuscript.

Funding

The China–Australia International Research Centre for Chinese Medicine (CAIRCCM) – a joint initiative of RMIT University, Australia and Guangdong Provincial Academy of Chinese Medical Sciences, China, and the Foundation for Chinese Medicine and Technology Research of Guangdong Provincial Hospital of Chinese Medicine (2017KT1820, 2016KT1571) provided funding for this project.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Yunying Li, Email: docliyunying@gzucm.edu.cn.

Charlie C. Xue, Email: charlie.xue@rmit.edu.au

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

12906_2025_4895_MOESM1_ESM.docx (32.1KB, docx)

Additional file 1. List of modern specialist textbooks included in the convenience sample.

12906_2025_4895_MOESM2_ESM.docx (54.1KB, docx)

Additional file 2. Summary of syndrome differentiation and oral Chinese herbal medicines from modern specialist textbooks by inclusion in classical search.

12906_2025_4895_MOESM3_ESM.docx (35.2KB, docx)

Additional file 3. List of oral formulae included in the two systematic reviews by inclusion in 2012 guideline, sample of modern textbooks, and classical search.

12906_2025_4895_MOESM4_ESM.docx (31.8KB, docx)

Additional file 4. List of ten most frequent herbs in oral formulae included in the classical search by inclusion in nasal formulae and classical pharmacopoeia.

Data Availability Statement

Data is provided within the manuscript or supplementary information files.

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• Abstract

• Background

• Materials and methods

• Results

• Discussion

• Conclusions

• Supplementary Information

• Acknowledgements

• Abbreviations

• Authors’ contributions

• Funding

• Data availability

• Declarations

• Footnotes

• Contributor Information

• References

• Associated Data

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