Published: April 12, 2024

Cough Hypersensitivity Syndrome

Clarifying the pathophysiology, diagnosis, and management of this complex condition and offering insights into emerging therapeutic strategies and the importance of a multidisciplinary approach.

Lyndsay L. Madden, DO, and Kathryn W. Ruckart, MS, CCC-SLP

Woman Holding Throat ThumbnailCough hypersensitivity syndrome (CHS) represents a significant clinical concern characterized by a troublesome cough in response to low-level stimuli that would not typically provoke such a response in healthy individuals. This syndrome encompasses various cough-related disorders, including those previously labeled as idiopathic chronic cough, cough variant asthma, and refractory chronic cough—highlighting the complexity and multifaceted nature of CHS. This article aims to clarify the pathophysiology, diagnosis, and management of this condition, offering insights into emerging therapeutic strategies and the importance of a multidisciplinary approach.

Pathophysiology of Cough Hypersensitivity Syndrome

The pathogenesis of CHS is not fully understood but is believed to involve neural dysregulation at both the peripheral and central levels of the cough reflex pathway. Sensitization of the cough reflex is thought to result from neuroplastic changes within the airway innervation, leading to an exaggerated cough response.1 This sensitization can be triggered by various factors, including viral infections, exposure to environmental irritants, gastroesophageal reflux disease (GERD), and postnasal drip, suggesting a multifactorial etiology.2

Doctor Checking Pediatric ThroatClinical Presentation and Diagnosis

CHS is characterized by a persistent cough lasting more than eight weeks without an identifiable cause after a thorough investigation. Patients often describe a heightened cough sensitivity to stimuli such as cold air, talking, laughter, and odors. The diagnosis of CHS is primarily clinical, based on the characteristic symptoms and the exclusion of other causes of chronic cough. Objective cough reflex sensitivity testing, measuring the cough response to inhaled capsaicin or citric acid, may support the diagnosis but is not routinely performed in clinical practice.3

Management Strategies

The management of CHS is challenging and requires a personalized approach, focusing on both pharmacological and non-pharmacological strategies.

Pharmacological Treatments

    1. Inhaled Corticosteroids (ICS): While ICS are primarily used in asthma, they may be beneficial in CHS by reducing airway inflammation and hypersensitivity.4
    2. Neuromodulators: Given the neural basis of CHS, neuromodulatory agents such as pregabalin, gabapentin, and amitriptyline have been used with varying degrees of success. These medications aim to reduce the hypersensitivity of the cough reflex pathway.5

    Non-pharmacological Treatments

    1. Behavioral cough suppression therapy: Behavioral intervention with a voice and upper airway-specialized speech-language pathologist focusing on cough suppression techniques has emerged as an effective non-pharmacological intervention for CHS.5 Therapeutic interventions include optimization of laryngeal hygiene, psychoeducational counseling, education on the voluntary control of cough, and laryngeal control strategies to suppress cough.6
    2. Diet and lifestyle modifications: Addressing potentially aggravating factors such as GERD and postnasal drip through dietary changes and lifestyle modifications may also provide symptomatic relief.
    3. Superior laryngeal nerve (SLN) blocks: SLN blocks are an emerging and promising therapeutic approach for managing CHS. The SLN, which provides sensory innervation to the larynx, plays a pivotal role in the cough reflex. By targeting this nerve, the SLN block can significantly reduce the sensitivity of the cough reflex, thus alleviating symptoms in patients with CHS.7 

    Emerging Therapies

    Recent research has focused on identifying new therapeutic targets for CHS, including transient receptor potential channel antagonists, P2X3 antagonists, and others that play a crucial role in cough reflex sensitivity. These pathways are currently under investigation and hold potential as future treatments for CHS.8


    CHS represents a complex disorder that challenges both patients and healthcare providers. Understanding the underlying pathophysiology, recognizing the clinical manifestations, and employing a comprehensive management strategy are crucial to improving patient outcomes. Future research into the molecular mechanisms of cough hypersensitivity and the development of targeted therapies may offer new hope for individuals suffering from this debilitating condition.


    1. Morice AH, Millqvist E, Bieksiene K, et al. “ERS guidelines on the diagnosis and treatment of chronic cough in adults and children.” European Respiratory Journal (2020) DOI:13993003.01136-2019.
    2. Song WJ, Chang YS, Faruqi S, Kang MK, Kim JY, Kang MG, Kim S, Jo EJ, Lee SE, Kim MH, Plevkova J, Park HW, Cho SH, Morice AH. Defining Chronic Cough: A Systematic Review of the Epidemiological Literature. Allergy Asthma Immunol Res (2016) DOI: 10.4168/aair.2016.8.2.146.
    3. Ternesten-Hasséus E, Johansson EL, Millqvist E. Cough reduction using capsaicin. Respir Med (2015) DOI: 10.1016/j.rmed.2014.11.001.
    4. Johnstone KJ, Chang AB, Fong KM, Bowman RV, Yang IA. Inhaled corticosteroids for subacute and chronic cough in adults. Cochrane Database Syst Rev (2013) DOI: 10.1002/14651858.CD009305.pub2.
    5. Vertigan AE, Kapela SL, Ryan NM, Birring SS, McElduff P, Gibson PG. Pregabalin and Speech Pathology Combination Therapy for Refractory Chronic Cough: A Randomized Controlled Trial. Chest (2016) DOI: 10.1378/chest.15-1271.
    6. Wright, M. L., Sundar, K. M., Herrick, J. S., & Barkmeier-Kraemer, J. M. Long-term treatment outcomes after behavioral speech therapy for chronic refractory cough. Lung, (2021) DOI: 10.1007/s00408-021-00481-3
    7. Gray AJ, Hoffman MR, Yang ZM, Vandiver B, Purvis J, Morgan JP, Hapner ER, Dominguez L, Tibbetts K, Simpson CB. Indications and Short-Term Outcomes for In-Office Therapeutic Superior Laryngeal Nerve Block. Ann Otol Rhinol Laryngol (2024) DOI: 10.1177/00034894231194384.
    8. Zheng Z, Huang J, Xiang Z, Wu T, Lan X, Xie S, Lin Z, Tang K, Morice A, Li S, Song WJ, Chen R. Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis. E Clinical Medicine (2023) DOI: 10.1016/j.eclinm.2023.102100.         

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