Where Eastern Medicine Meets Western Medicine: A World Review of the Management of Chronic Cough

ABSTRACT

Purpose

To summarize current Western and Eastern approaches to the evaluation and management of chronic cough, with particular emphasis on etiology‐directed therapy, cough hypersensitivity, behavioral interventions, neuromodulators, procedural treatments, and traditional remedies.

Methods

A literature search of PubMed, Web of Science, CNKI, and Ovid Medline was conducted on February 1, 2024. Adults with chronic cough lasting at least 8 weeks were eligible. Pediatric studies, studies involving immunocompromised patients, smokers or patients with lung cancer, animal studies, and non‐English or non‐Mandarin publications were excluded. Because of substantial heterogeneity in etiologies, interventions, study designs, and outcome measures, findings were synthesized narratively rather than quantitatively. Twenty‐three primary studies were included in the final narrative synthesis.

Results

Chronic cough commonly reflects cough hypersensitivity involving vagal sensory pathways and receptors including TRPV1, TRPA1, and P2X3. Common clinical contributors included upper airway cough syndrome, gastro‐esophageal reflux disease, and cough‐variant asthma. Management was most appropriately organized as a stepwise approach involving identification and treatment of the underlying cause, behavioral cough suppression therapy, and selected pharmacological treatment. Gabapentin and P2X3 antagonists may benefit refractory cough, although adverse effects and limited long‐term data remain important limitations. Superior laryngeal nerve block and antireflux surgery may be considered in carefully selected patients. Acupuncture and selected traditional preparations may provide adjunctive benefit, but the evidence remains heterogeneous and should not replace standard evaluation or treatment.

Conclusion

Chronic cough should be managed using a personalized, stepwise strategy that combines etiology‐directed treatment with interventions targeting cough hypersensitivity. Traditional therapies may have a complementary role, but further well‐designed comparative studies are required.

1. Introduction

Chronic cough, defined as persistent cough lasting ≥ 8 weeks without an identifiable pulmonary etiology, represents a prevalent yet challenging clinical entity, affecting 2%–18% of the global adult population and reaching 10%–20% prevalence in Asia [1, 2]. Epidemiologically, etiologic patterns vary regionally: cough variant asthma (CVA) and upper airway cough syndrome (UACS) predominate in Eastern Asia, with multicenter Chinese data showing CVA (32.6%), UACS (18.6%), eosinophilic bronchitis (17.2%), and atopic cough (13.2%) as leading causes, collectively accounting for 75%–88% of cases; conversely, gastro‐esophageal reflex disease (GERD)‐related cough predominates in Western populations, but is less common in these Asian cohorts at 4.6% [3, 4].

While pulmonary and gastroenterological etiologies often dominate initial evaluations, a considerable proportion of cases may require otolaryngological intervention despite extensive workup [5]. Recent Western advancements in neuromodulators (gabapentin, P2X3 antagonists) and targeted surgical interventions (superior laryngeal nerve blocks, antireflux surgery) have transformed refractory cough management. Concurrently, there is emerging quantitative evidence that traditional Eastern remedies, such as acupuncture and herbal formulations like Tanreqing, offer adjunctive benefit through cytokine modulation and mucus reduction [6]. To our knowledge, no prior review has integrated these disparate paradigms, from etiology‐directed pharmacotherapy and behavioral cough suppression therapy to cross‐cultural complementary approaches and biopsychosocial strategies. This state‐of‐the‐art narrative review hence synthesizes 23 key studies to provide otolaryngologists with a holistic global update, bridging Western and Eastern insights for optimal chronic cough management.

2. Methods

2.1. Search Strategy

This narrative review was informed by a structured literature search across four databases (PubMed, Web of Science, CNKI, Ovid Medline) conducted on February 1, 2024. Search terms included: ((“chronic cough” OR “upper respiratory tract chronic cough” OR “upper airway chronic cough”) AND (“management” OR “therapy” OR “treatment” OR “solution”)).

The broad scope of this review, encompassing heterogeneous interventions (traditional remedies, neuromodulators, surgical techniques), precludes formal systematic review methodology with pooled effect estimation. Instead, this review adopts a narrative approach to integrate cross‐cultural management strategies while providing modality‐level critical appraisal.

2.2. Rationale for Narrative Approach

The broad scope—encompassing heterogeneous interventions from traditional herbal formulations through antireflux surgery, alongside diverse study designs—precludes formal systematic review methodology with unified risk‐of‐bias tools and quantitative synthesis. Instead, this review adopts a narrative approach to integrate cross‐cultural management strategies while providing modality‐level critical appraisal. Key rationales include:

• Intervention heterogeneity: Pooling acupuncture with P2X3 antagonists or Tanreqing with superior laryngeal nerve blocks is methodologically untenable.

• Conceptual integration: Cross‐cultural synthesis exceeds narrow PICO frameworks, requiring evaluative discussion beyond statistical aggregation.

• Practical scope: 23 studies across eight modalities exceeds narrative review capacity for study‐level risk‐of‐bias tables; modality‐level appraisal is provided throughout instead.

A narrative review was the choice of this study for a few reasons. Firstly, the included studies cover diverse aetiologies of chronic cough, spanning from upper airway cough syndrome to neurogenic cough. Each etiology differs fundamentally in pathophysiology (e.g., inflammatory vs. neurogenic mechanisms), disease progression, treatment methodology and responsiveness. Secondly, there is marked variability in the metrics used to quantify treatment outcomes, including cough frequency, severity or even quality of life. While these outcomes are important in measuring treatment effectiveness, they are not directly comparable. Finally, intervention methodologies also differ vastly, spanning from conventional Western methods to traditional Eastern therapies. Pooling data across distinct modalities into a single quantitative conclusion would be clinically misleading. Overall, an attempt at quantitative synthesis would yield non‐generalizable conclusions. Hence, a narrative review is not a methodological compromise, but rather a more appropriate approach to allow for modality‐specific review and clinically meaningful evidence‐based interpretation.

A Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA)‐style flow diagram was adapted to document the identification, screening, eligibility assessment, and inclusion of records despite not pursuing a systematic review in this case. The diagram was used for transparent reporting of the literature‐search process.

2.3. Selection Criteria

Studies included adults (≥ 18 years) with chronic cough diagnosis. Exclusion criteria included: pediatric cases; immunocompromised/smokers/lung cancer patients; animal studies; and non‐English and non‐Mandarin publications. To facilitate interpretation of the heterogeneous literature, each included study was assigned a level of evidence according to the Oxford Centre for Evidence‐Based Medicine framework [7].

3. Results

After initial search (n = 8582), duplicates were removed (n = 4378). Two reviewers independently screened titles/abstracts (excluded n = 3825), then full texts (n = 553 assessed; n = 530 excluded for non‐English/Mandarin, no full text, or acute cough focus). Twenty‐three studies were included in the final review (Figure 1).

Figure 1.

PRISMA flow diagram of study selection for the chronic cough review.

Of the 79 references cited in the manuscript, 23 were classified as primary studies contributing directly to the treatment‐focused narrative synthesis. The remaining references were included for background, mechanistic explanation, guideline context, or secondary evidence synthesis.

4. Discussion

4.1. Physiology of Cough

It is paramount to first delve into the physiology of the cough reflex, and how it is mediated. Cough is fundamentally a protective reflex [8] that prevents aspiration or inhalation of potentially harmful substances [9]. The afferent limb of this reflex pathway involves detection of noxious stimuli that trigger the opening of specific ion channels on the terminals of vagal sensory nerves [10]. Low threshold mechanosensors react to mechanical stimuli such as lung inflation [11]. C‐Fibers compose most of the afferent pathway; to react to chemical stimuli such as bradykinin and capsaicin [12], they express an important class of ionotropic receptors from the transient receptor potential (TRP) family [13]. P2X receptors are also intrinsically linked to the cough reflex [14]; these open in response to specific ligands, such as ATP and capsaicin, and further modulate the afferent cough reflex pathway via nerve fiber sensitization [15]. The efferent limb then involves coordinated contraction of the larynx, respiratory muscles and diaphragm, resulting in a cough [16]. These pathways (Figure 2) highlight potential therapeutic targets for chronic cough modulation.

Figure 2.

Schematic of the cough reflex pathway and key anatomical sites of chronic cough pathophysiology. The figure depicts the afferent and efferent limbs of the cough reflex, highlighting peripheral sensory activation in the nasal mucosa/upper airway, larynx, esophagus, and lower airway. Key receptor targets include TRPV1, TRPA1, and P2X3, which contribute to cough hypersensitivity. Site‐specific interventions are mapped to the relevant pathology, including intranasal therapy and BCST for UACS, PPIs and LARS for reflux‐related cough, inhaled therapy for CVA, and neuromodulators or P2X3 antagonists for neurogenic cough.

It is thus evident that the cough reflex is a multi‐step process; analysis of each step is essential in pinpointing critical receptors and neuronal pathways to alleviate the burden of chronic cough.

4.2. Pathological Basis for Chronic Cough

While cough is a physiological reflex, there are multiple pathological processes that can disrupt these processes. The most common and clinically relevant etiologies are discussed below.

4.2.1. Upper Airway Cough Syndrome (UACS)

UACS, commonly termed postnasal drip syndrome (PNDS), is a common etiology of chronic cough [17]. Patients often present with a nagging cough that may worsen at night or upon awakening, as mucus drips down the throat during sleep [18]. UACS can result from a variety of upper respiratory disorders, including nasal and sinus diseases [19]. There are multiple proposed pathogeneses for UACS. First, sinonasal secretions could stimulate afferent nerves innervating the upper and lower airway when they drip down into these areas, resulting in cough as a defensive reflex [20]. Second, direct stimulation of the nasal mucosa by noxious TRPV1 or TRPA1 agonists, such as capsaicin, histamine and airborne pollutants, could up‐regulate the cough reflex [21]. This is mediated by trigeminal afferent pathways, which make central cough pattern generators more susceptible to upstream vagal afferent input [22]. Finally, long‐term airway inflammation from post‐nasal drip or mechanical stimulation can further cough sensitivity [23]; indeed, patients with UACS often display airway structural changes or remodeling phenomena consistent with long‐term airway inflammation, both in the upper and lower airways [24].

4.3. Gastro‐Esophageal Reflux Disease‐Related Cough (GERC)

GERD is an established contributor to chronic cough, although reported prevalence varies substantially depending on the population studied and the diagnostic definition used; some studies have reported reflux‐related cough in up to 41% of cases, but these estimates are broader than the 4.6% GERD figure reported in multicenter Chinese cohorts [25]. Laryngopharyngeal reflux (LPR), also known as extraesophageal reflux, occurs when acid or non‐acidic reflux reaches the larynx and pharynx, where associated pharyngitis—manifesting as persistent erythema or irritation—may reflect primary LPR pathology, cough‐induced secondary inflammation, or upper airway cough syndrome overlap requiring endoscopic differentiation [26]. There are multiple proposed mechanisms for GERD‐related chronic cough (GERC) [27]. First, acid reflux, the resultant mucous secretion, and micro aspiration can each stimulate afferent airway sensory nociceptors. Second, the esophago‐tracheo‐bronchial reflex theory puts forth that the bronchial cough reflex can also be caused by stimulation of sub‐esophageal mucosal receptors, which release neuropeptide substance P, which then results in the release of inflammatory mediators triggering cough [28]. Finally, esophageal dysmotility in GERD results in longer esophageal acid exposure. This in turn impedes gastric clearance, further causing reflux of gastric acids to damage mucosal walls; these factors exacerbate GERC.

4.4. Cough‐Variant Asthma (CVA)

CVA is another important cause of chronic cough [29]. It is a phenotype of asthma which presents primarily as a persistent, dry cough, without other classic symptoms of asthma [30]. Accordingly, this clinical entity is characterized by eosinophilic inflammation of the entire lower airway [29]. This airway inflammation causes bronchoconstriction, resulting in cough. The responsiveness of the cough of CVA to bronchodilators supports this causal relationship. It has also been shown that CVA is associated with heightened cough reflex sensitivity [31]. However, in CVA, spirometry readings can occasionally be unremarkable [32], with some patients not exhibiting bronchodilator responsiveness [33]. Therefore, challenge testing, such as the methacholine challenge test [34], is frequently utilized to demonstrate airway hypersensitivity, to support the diagnosis of CVA [35].

4.5. Drug‐Induced Chronic Cough

Drug‐induced cough should be considered early in the evaluation of chronic cough, as prompt recognition may prevent unnecessary investigations and ineffective treatment. Cough usually resolves spontaneously within 1‐3 weeks after withdrawal of the causative drug [36]. Common drugs that cause chronic cough include ACE‐Inhibitors (ACEIs), Calcium channel blockers (CCBs), Angiotensin II Receptor Blockers (ARBs) and sitagliptin [37]. There is likely individual susceptibility to drug‐induced cough such as in the case of ACEIs‐induced cough. It may begin days to months after treatment initiation and can occur irrespective of the temporal relationship with drug commencement. Proposed mechanisms include accumulation of bradykinin and substance P, which may sensitize airway sensory nerves and lower the cough threshold [38]. Medication changes should be coordinated with the prescribing clinician, and an angiotensin II receptor blocker may be considered where appropriate. However, the exact mechanisms of how the above drugs lead to cough are still largely unclear [39].

5. Management

The key evidence and limitations of each chronic cough modality have been summarized in Table 1, considering the highest level of evidence available. A summary of evidence‐based treatment options based on underlying etiology of chronic cough has been included in Table 2. We attach a proposed integrated clinical management algorithm for chronic cough as well (Figure 3).

Table 1.

Summary of advantages and disadvantages of treatment modalities for chronic cough.

Category	Treatment	Mechanism/Target	Level of evidence	Limitations
Non‐pharmacological	BCST	Retrains cough reflex via speech therapy	Level 1b [1]	Requires patient adherence; limited accessibility
Traditional remedies	Liquorice/Herbal formulations (e.g., TRQ injection)	Anti‐inflammatory, TRP modulation	Level 1 [40, 41]	Small sample sizes; heterogeneity in formulations
	Acupuncture	Modulates cytokine signaling	Level 2 [42]	High variability in protocols
Pharmacological	PPIs	Acid suppression in GERD/LPR	Level 1 [43]	Effective for GERD cough
	Gabapentin	Central neuromodulation	Level 1 [44]	Pharmacological side effects such as sedation, dizziness; no long‐term data
	P2X3 Antagonists (e.g., Gefapixant)	Blocks ATP‐mediated sensitization	Level 1 [15]	Taste disturbances; limited safety data
Surgical	Superior Laryngeal Nerve Block	Anesthetic/corticosteroid inhibition of afferents	Level 3 [45]	Short‐term data; operator‐dependent
	LARS	Restores LES barrier function	Level 1 [46]	Invasive; requires careful patient selection

Abbreviations: BCST, behavioral cough suppression therapy; GERD, gastro‐esophageal reflux disease; LARS, laparoscopic anti‐reflux surgery; LPR, laryngopharyngeal reflux; RCT, randomized control trial; TRP, transient receptor potential.

Table 2.

Evidence‐based treatment options based on underlying etiology of chronic cough.

Etiology	Therapeutic options
Upper airway cough syndrome	– Treat underlying nasal symptoms: antihistamines, decongestants, intranasal corticosteroids, nasal saline irrigation – PPI
Gastro‐esophageal reflux disease	– Lifestyle/dietary modification – Medical therapy: Antacids, Proton pump inhibitor therapy – Laparoscopic/open anti‑reflux surgery
Cough variant asthma	– Inhaled corticosteroids – Bronchodilators
Neurogenic cough/Refractory chronic cough	– Behavioral cough suppression therapy – Medical therapy: Anti‐tussive, neuromodulators, TPRV1, P2X3 receptor antagonists – Superior laryngeal nerve block
Drug‐induced cough	– Identification and cessation of causative drugs (common drugs: ACEIs, CCBs, ARBs, sitagliptin)

Abbreviations: ACEIs, ACE‐Inhibitors; ARBs, angiotensin II receptor blockers, CCBs, calcium channel blockers; PPI, proton pump inhibitor.

Figure 3.

Proposed integrated clinical management algorithm for chronic cough.

5.1. Non‐Pharmacological Measures

5.1.1. Behavioral Cough Suppression Therapy (BCST)

BCST is by far the most common non‐pharmacological treatment for chronic cough. BCST is an effective standalone measure to improve refractory chronic cough after patients have exhausted empirical medical management [39] while being an inexpensive and safe treatment option. It typically consists of behavioral therapy, speech and language physiotherapy. The components of BCST are detailed in Table 3. Furthermore, Simmons et al. has found that BCST is effective in maintaining reduced cough severity even post‐therapy [47].

Table 3.

Key components in BCST.

Key components	Description
Education	This helps the patient understand the pathophysiology of chronic cough as well as the principles of the subsequent speech and physical therapy. This lays the foundation of BCST by allowing patients to better understand their condition.
Psychoeducation counseling	This manages the patient's stress and anxiety, as well as to divert attention from the need to cough. This allows the patient to gain control over the condition and to be intrinsically motivated.
Cough suppression techniques	Including forced swallow, lip pursing, breathing exercises
Identification and avoidance of triggers	Triggers include mental stress, anxiety, and lack of sleep
Laryngeal hygiene	Includes avoidance of caffeine and alcohol
Throat hydration and laryngeal massage	Helps to moisturize the larynx through increasing water intake and avoiding mouth breathing.

Abbreviation: BCST, behavioral cough suppression therapy.

5.2. Pharmacological Measures

5.2.1. Traditional Medications

Traditional medications can be valuable treatment options for chronic cough, leveraging centuries‐old practices from various cultures. Persian traditional medicine often utilizes herbal remedies, such as thyme and liquorice, which have natural anti‐inflammatory and soothing properties to relieve cough. In a randomized double‐blind study by Ghaemi et al involving 70 patients with chronic cough, there was a significant decrease in cough severity score after consuming liquorice three times daily for 2 weeks (1.2 ± 0.93 vs. 1.8 ± 1.03, p < 0.001) [40]. In Korean traditional medicine similarly employs herbal combinations like Wolbigachul–Tang and Maekmoondong‐tang. These formulations are believed to enhance lung function and reduce phlegm by reducing irritation in the lungs with their antioxidant and anti‐inflammatory effects [48]. There is an ongoing clinical trial by Kim et al. to determine their effectiveness [49]. Simple remedies such as sips of water can also be beneficial, as they help keep the throat moist and clear irritants that may trigger coughing. In a case report by Tariq et al. of a patient with chronic cough associated with GERD who had failed both conventional medical therapy and surgical management, their chronic cough was only amenable to taking frequent sips of water to clear their pharyngeal secretions [50]. It must be acknowledged that current data stems from small single‐centre RCTs/meta‐analyses; these may suffer formulation heterogeneity, short follow‐up, and potential publication bias. However, these traditional treatments, rooted in holistic approaches, offer alternative or complementary options for managing chronic cough, often with fewer side effects than modern pharmaceuticals.

Acupuncture, a cornerstone of traditional Chinese medicine, has also shown promise in treating chronic cough. A meta‐analysis by Lee et al. involving 30 randomized controlled trials with 2835 participants found that when acupuncture‐related therapies were combined with conventional treatments, such as customized medication and lifestyle advice, significant improvements were observed in cough severity (simplified cough score median = −0.85, 95% CI − 1.25 to −0.45, I ² = 86%), quality of life, and the total effective rate [42]. Its benefits are attributed to potential roles in modulating cytokine signaling and interleukin production [51]. These findings suggest that acupuncture may serve as a valuable complementary approach to managing chronic cough, particularly for patients seeking alternatives to pharmacological interventions.

Another traditional treatment, the Tanreqing (TRQ) injection, has been studied for its impact on mucus hyperproduction and cough in bronchiectasis patients. A meta‐analysis by Zhang et al., which included 20 randomized controlled trials involving 1544 patients, showed that TRQ significantly reduced mucus hypersecretion, decreased the cough and phlegm duration, and reduced symptom scores (cough symptom scores MD = −1.48, 95% CI (−2.63, −0.34), p = 0.01) [41]. TRQ injections are made of a combination of 5 traditional Chinese herbs and have been shown to have immunomodulatory effects such as decreasing levels of TNF‐α, IL‐1β, IL‐6, and IL‐8 [52]. This could potentially downregulate the signaling pathways of MAPK/NF‐κB, resulting in reduced mucus hypersecretion and thus reduced cough trigger. These results highlight TRQ's potential as a treatment for cough and related symptom management in bronchiectasis, offering a traditional yet evidence‐based option for patients.

5.3. Antitussives

Antitussives are a diverse group of drugs that aim to prevent or relieve chronic cough, primarily by inhibiting central neuronal pathways involved in cough hypersensitivity [53].

Dextromethorphan is a frequently prescribed over‐the‐counter treatment for cough. As a d‐isomer of levorphanol methylether, Dextromethorphan binds to a series of receptors, such as N‐methyl‐d‐aspartate (NMDA) glutamate receptors [54], altering the threshold for cough initiation [55]. A study by Matthys et al further showed that it had comparable efficiency to dihydrocodeine, noscapine and codeine [56]. Despite the wide usage of dextromethorphan in the management of cough, further adequately powered studies would be beneficial in better establishing its significance in the management of chronic cough.

Overall, in a cohort study by Zhang et al, it was found that anti‐tussive could only offer transient respite for patients with chronic cough [53]. The authors suggested several hypotheses to explain these results. Firstly, these neuromodulators do not target the underlying etiologies. Secondly, there might be desensitization to antitussives after the initial response. As antitussives have shown to be insufficient as a standalone treatment for refractory chronic cough, future studies should be done to evaluate its efficacy as a complementary treatment when paired together with other treatment methods instead.

6. Proton pump inhibitor (PPI)

PPIs are a common etiology‐specific treatment for chronic cough, especially in the context of postnasal drip (PND), GERD and LPR [57]. Proposed mechanisms through which PPIs improve chronic cough include reducing esophageal acid reflux and reducing gastric volume in the context of GERD and LPR, or via the possible antihistaminergic effects of drying up nasal secretions in PND‐induced chronic cough [58]. In a randomized, double‐blinded, control trial by Pawar et al involving 47 participants taking PPI (rabeprazole 20 mg) twice daily 30 min before meals for 90 days, the test group showed greater improvement than the placebo group in terms of frequency of PND at Day 90 as measured on VAS (p = 0.0180) and symptoms of chronic cough (p = 0.024) [43].

In a meta‐analysis by Floria et al., it was shown that extending the duration of PPIs past the usual treatment duration of 6–8 weeks did not correlate with better outcomes, suggesting that alternate agents must be considered in such cases of refractory chronic cough [59]. Moreover, the usage of PPIs is limited to specific etiologies of chronic cough ‐ an empiric trial of PPIs in chronic cough is not recommended based on current guidelines [60].

6.1. Neuromodulators

Neuromodulators, such as gabapentin and amitriptyline, have also been shown to be beneficial in the treatment of chronic cough [61]. As explained earlier, chronic cough involves the central sensitization of the afferent cough receptor pathway. The neurological pathways involved in this sensitization share similarities with those activated in chronic neuropathic pain syndromes, for which neuromodulators are well‐established therapies [44, 62]. A study by Van de Kerkhove et al demonstrated that gabapentin could reduce cough, especially in patients with higher scores for pre‐treatment cough severity and previous airway infections prior to the cough [63]. Ryan et al further conducted a randomized, double‐blinded trial involving 62 patients, which showed that gabapentin was more effective than placebo in improving refractory chronic cough [44]. Such studies have led to the American College of Chest Physicians recommending such therapies in guidelines for the management of chronic, refractory cough [64]. However, neuromodulators are known to have numerous adverse effects. Gabapentin can lead to somnolence, giddiness and lethargy, while amitriptyline can lead to dry mouth, constipation and postural giddiness; these limit the tolerability of and adherence to such agents. It is thus recommended that these agents be prescribed at their lowest effective doses, for which frequent reassessment by the clinician is required [65].

6.2. TRPV1, P2X3 Receptor Antagonists

Capsaicin, the active compound found in chili peppers, has emerged as a potential treatment for chronic cough. In a crossover randomized controlled trial by Ternesten‐Hasséus et al. involving 46 patients, oral capsaicin was found to be well‐tolerated and clinically effective [66]. The study revealed that the mean capsaicin inhalation concentration needed to trigger two to five coughs is significantly higher after usage of capsaicin compared to baseline (p < 0.05 and p < 0.03, respectively). While capsaicin did not significantly reduce overall cough frequency, subgroup analysis showed that low coughers (≤ 400 coughs within 24 h) experienced significantly better outcomes with capsaicin compared to placebo. Leicester Cough Questionnaire scores also improved across all categories (p < 0.01 for total score), indicating enhanced quality of life. The therapeutic effect of capsaicin is attributed to its ability to desensitize receptors such as TRPV1 involved in the cough reflex, thereby reducing hypersensitivity [67]. Further therapies leaning onto impeding this receptor offers a promising multimodal approach to managing chronic cough.

TPRV1 receptor antagonists and P2X3 receptor antagonists have also been explored as a treatment option for chronic cough refractory to other medications or those with a possible neurogenic etiology. In a retrospective analysis of 201 patients with sensory neuropathic cough by Hoseli et al, 63.7% had a reduction in cough symptoms with ≥ 75% resolution in symptoms in 30.8% of patients [68]. In terms of side effects, 78.3% reported no complications. In one randomized double‐blinded clinical trial involving 21 patients with refractory chronic cough by Khalid et al., it was noticed that TRPV1 antagonists improved the cough reflex sensitivity to capsaicin but not the frequency of coughing (p = 0.51) [69].

Similarly, P2X3 receptor antagonists work similarly along the neurologic cough pathway to reduce coughing [70]. In a meta‐analysis of 11 trials including 1350 patients with refractory cough by Ramadan et al., it was noted that P2X3 antagonists decreased 24‐h cough frequency significantly (median = −4.99, 95% CI [−7.15 to −2.82], p < 0.01) with limited side effect profile in the short‐term [15]. However, the most‐studied agent, Gefapixant, commonly results in taste‐related adverse events, which has led to some patients stopping this therapy. While these disturbances typically resolve after cessation of therapy, they may persist in the minority of cases [71]. Overall, while there are high quality randomized control trials that show modest effect sizes (−4.99 coughs/24 h) with large placebo responses, these two antagonists also lack long term safety data [72]. Furthermore, in some trials, the magnitude of benefit of these agents is modest, with large placebo responses observed. Such findings cast doubt on the clinical significance and cost‐effectiveness of these agents; that the FDA and EMA have not licensed these medications is revealing [73]. Long‐term P2X3 use requires extended trials assessing tachyphylaxis, taste disturbance reversibility (resolves post‐cessation in most), and post‐marketing registries for durability in real‐world refractory cough hypersensitivity post‐neuromodulator failure [71]. Nevertheless, especially given the limited efficacy or applicability of existing pharmacological therapies for chronic cough, these targeted treatments remain new exciting avenues that should be further studied.

6.3. Surgical Interventions

For disabling chronic cough, refractory to optimized pharmacological and behavioral therapy, interventional and surgical options that directly target the neural or mechanical drivers of cough hypersensitivity may be considered in highly selected patients. However, the studies that support these procedures comprise predominantly retrospective series and non‑randomized data; long‑term durability and safety of these procedures remain incompletely defined.

6.4. Superior Laryngeal Nerve Blocks

Superior laryngeal nerve block has emerged as a promising option for patients with otherwise unexplained or neurogenic chronic cough who remain symptomatic despite guideline‑based medical and behavioral therapy. Nerve blocks in this region typically take the form of a mixture between a local anesthetic such as lidocaine or bupivacaine, and a corticosteroid [74]. The internal branch superior laryngeal nerve is involved in the cough reflex arc and hypersensitivity of the nerve to trigger chronic cough without any obvious etiology – labeled as neurogenic cough [75]. In a retrospective study by Gray et al. involving 209 patients with chronic cough, there was a notable improvement in cough severity index post‐procedure (25.2 ± 11.2 to 19.0 ± 12.8; p < 0.001), with improvements showing as soon as 2 weeks [45]. In a longitudinal follow up study by Dhillon et al, patients who had undergone superior laryngeal nerve blocks maintained good symptom for control for up to 10 months post‐procedure (W = 2, z = −4.659, p < 0.05) [76]. While theoretical risks of bleeding, infection and damage to surrounding structures are to be considered, superior laryngeal nerve block remains relatively risk free; documented adverse reactions by Gray et al. were limited to ecchymosis and temporary tongue paresthesia [45]. However, both studies were uncontrolled and subject to selection and recall bias; moreover, neither study defined optimal dosing intervals.

6.5. Antireflux Surgery

In patients with objectively confirmed GERD and chronic cough refractory to optimized PPI therapy and lifestyle modification, laparoscopic anti‑reflux surgery (LARS) may be considered as a second‑line option. LARS reduces the amount of gastric acid that refluxes to the larynx, hence treating chronic cough by reducing laryngeal irritation by gastric acids. Standard surgical approaches include laparoscopic Nissen or partial fundoplication, often combined with hiatal hernia repair; newer options such as magnetic sphincter augmentation and Collis gastroplasty are used in selected anatomical scenarios, but have more limited cough‑specific data. The surgical intervention for esophageal manifestations of GERD refractory to medical management has been shown to have great success, boasting a 85%–93% curative rate; however, extra‑esophageal manifestations such as cough tend to respond less consistently [77]. In a series of 420 patients with extra‑esophageal GERD manifestations, Weltz et al. reported that 80.8% experienced improvement in chronic cough over a mean follow‑up of 18.9 ± 16.6 months after LARS, based on patient‑reported quality‑of‑life surveys. A meta‑analysis of 503 patients undergoing laparoscopic fundoplication for refractory GERD‑related cough found a pooled cough ‘cure’ rate of 61% (95% CI 52%–70%), with a further proportion achieving partial improvement rather than complete resolution. These figures highlight that while surgery can meaningfully reduce cough burden in many patients, it does not guarantee complete remission; careful counseling regarding expectations is thus essential [78]. This is congruent with a meta‐analysis done by Liu et al involving 503 patients who underwent laparoscopic fundoplication for refractory gastro‐esophageal reflux‐related cough, with a cure rate of 61% (95% CI: 52%–70%) [46]. However, LARS is associated with procedure‑specific risks, including dysphagia, gas‑bloat syndrome, wrap failure and the potential need for re‑operation. These risks must be weighed against the severity of cough and degree of reflux documented on pH‑impedance and manometry [78]. Current guidelines therefore recommend that anti‑reflux surgery for chronic cough be undertaken only after multidisciplinary evaluation, comprehensive reflux work‑up and shared decision‑making with patients who fully understand the trade‑offs [79].

6.5.1. Integration of Traditional and Western Therapies

While traditional and Western therapies converge on shared cough pathways, current evidence supports an integrative, stepwise rather than mutually exclusive model. From a mechanistic standpoint, traditional and Western therapies for chronic cough converge on several shared physiological targets, including modulation of vagal afferent sensitivity, attenuation of airway and mucosal inflammation, and reduction of laryngopharyngeal irritation from reflux.

However, their exact biological targets may differ acupuncture and herbal formulations such as liquorice‐based preparations or Tanreqing appear to act predominantly through cytokine modulation, anti‐inflammatory effects, and possible neuromodulator pathways, whereas Western approaches such as proton pump inhibitors, gabapentin, and P2X3 antagonists more directly target acid exposure or neuronal hypersensitivity. Therefore, traditional therapies should be positioned primarily as adjuncts, to supplement rather than replace for evidence‐based standard care.

Traditional and Western therapies should be integrated through a stepwise, phenotype‐directed approach rather than used as competing alternatives. Initial assessment should identify treatable causes, including upper airway cough syndrome, asthma or eosinophilic airway disease, gastro‐esophageal reflux disease, and medication‐related cough. Conventional etiology‐directed treatment should remain the foundation of management.

BCST may be introduced early for patients with cough hypersensitivity, laryngeal symptoms, or persistent cough despite initial treatment. It provides a low‐risk option incorporating education, trigger avoidance, breathing retraining, cough‐suppression techniques, and laryngeal hygiene. For refractory cough, gabapentin may be considered after counseling regarding adverse effects and regular reassessment.

In patients with UACS‐predominant cough, acupuncture may be considered as an adjunct to etiology‐directed management and behavioral cough suppression therapy, particularly in those seeking non‐pharmacological treatment or demonstrating partial response to first‐line measures. Again, it should not, based on current evidence, be framed as a substitute for standard evaluation or as a formal second‐line intervention after proton pump inhibitor failure, since PPI therapy is relevant in selected reflux‐related.

For refractory neurogenic or cough‐hypersensitivity phenotypes, gabapentin remains the better‐established neuromodulator option because it is supported by guideline‐cited randomized data, whereas capsaicin‐based desensitization should be framed as a complementary or investigational sensory‐modulating strategy rather than a standard alternative to gabapentin. A pragmatic sequence would therefore involve optimization of behavioral therapy and cause‐directed treatment first, followed by gabapentin in appropriate refractory cases, with capsaicin considered selectively where available and clinically appropriate.

Traditional therapies should be used as adjuncts rather than replacements for standard care. For herbal formulations such as Tanreqing, current evidence is insufficient to define specific contraindications, pharmacokinetic interactions, or synergistic effects when combined with P2X3 antagonists. Accordingly, any such combination should be described as investigational, and clinicians should remain cautious regarding additive adverse effects, tolerability, and confounding attribution of benefit in the absence of direct comparative or interaction studies.

7. Conclusion

In conclusion, the treatment of chronic cough is diverse, spanning from pharmacological treatments that target specific etiologies such as GERD and PND, to pharmacological interventions that directly impede the cough reflex, to biopsychosocial rewiring, to surgery in select populations refractory to other management. A focused history to localize specific etiologies is paramount in pinpointing efficacious treatment options for specific pathologies such as UACS and GERD. Nonetheless, identifying the etiology of chronic cough often can be challenging. There are multiple symptom‐focused treatment options for such cases, ranging from pharmacological neuromodulators, to non‐pharmacological BCST, to procedural nerve blocks, allowing the clinician to offer tailored options for this prevalent and debilitating condition based on specific patients' needs. Finally, emerging evidence suggests that traditional therapies may be useful adjuncts to Western therapies in the management of chronic cough.

Author Contributions

Thomas Zheng Jie Teng: Conceived the study, contributed to the design and implementation of the research, data analysis, interpreted the results, took the lead in writing the manuscript. Zhi Xuan Koh: data analysis, interpreted the results, took the lead in writing the manuscript. Kavimalar Ravi: Data analysis of results and writing of the manuscript. Justin Yi Shen Lim: Data analysis of results and writing of the manuscript. Jin Wayne Kyler Ong: Data analysis of results and writing of the manuscript. Christina Hui Lee Ng: Conceived the study, supervised the project, provided critical feedback that helped share the direction, analysis and writing of the manuscript.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Teng T. Z. J., Koh Z. X., Lim J. Y. S., Ravi K., Ong J. W. K., and Ng C. H. L., “Where Eastern Medicine Meets Western Medicine: A World Review of the Management of Chronic Cough,” World Journal of Otorhinolaryngology ‐ Head and Neck Surgery 0 (2026): 1‐13. 10.1002/wjo2.70185.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.