Are there clinical features of a sensitized cough reflex?
Introduction
Coughing is an important and appropriate response to noxious stimuli. However, in many acute and chronic respiratory disease states, a cough may develop which is troublesome, seems purposeless and is refractory to medication. While most focus has correctly centred on the investigation and treatment of cough as a specific complaint [1], [2] there is increasing recognition that cough patients report a range of additional sensations including an ‘urge to cough’, the feeling of an ‘itch’ or ‘lump’ at the back of the throat, a choking feeling and occasionally chest discomfort and breathlessness. These patients also complain that bouts of coughing are triggered by relatively innocuous stimuli frequently encountered during normal daily routine such as exposure to aerosols, scents and odours, a change in air temperature or when talking or laughing. This airway sensory hyperreactivity (SHR) is often what disturb patients most about their condition and appears to be of sufficient importance to impact on health status [3]. In the development of the two most widely used cough quality of life questionnaires items most frequently perceived as important by cough patients included statements such as; ‘exposure to paint or fumes made me cough’ [4] and ‘I can no longer sing, for example, in church’ [5].
Very little is known regarding the pathophysiology of SHR but in this article we consider the evidence that it may arise as a direct consequence of the neuroinflammatory events considered mechanistically important in cough.
Section snippets
Clinical features of cough
The act of coughing may cause a variety of musculoskeletal (chest wall pain), cardiovascular (syncope) and neurological (headache) symptoms which arise as a consequence of the cough intensity or a direct and profound effect of vagal stimulation. Some of the reasons why patients seek medical attention for cough include insomnia, a feeling of exhaustion, concern of serious underlying illness and self-consciousness from repeated coughing in public [6], [7]. This information tells us more about the
How common is airway sensory hyperreactivity (SHR)?
Millqvist et al. first proposed the term airway sensory hyperreactivity (SHR) to define a syndrome of self-reported odour intolerance combined with heightened sensitivity to inhaled capsaicin [16]. An accurate estimate of the prevalence of SHR in the general population is difficult due to a lack of consistency in its definition. The range of terms commonly used and interchanged includes; airway symptoms from chemicals (ASC) [17], multiple chemical sensitivity (MCS) syndrome [18] and the
Prevalence of SHR in a specialist cough clinic
For the purpose of this brief overview, we have provided some preliminary information on the prevalence and characteristics of airway SHR in patients referred to a specialist cough clinic. As alluded to above we have considered chemical, thermal and mechanical stimuli as the important noxious stimuli that trigger bouts of coughing. We conducted a retrospective review of 135 consecutive patients referred to a specialist cough clinic. We defined airway sensory hyperreactivity (SHR) positive
The cough reflex
The protective (physiological) cough response to a noxious stimulus is likely to be elicited by direct activation of receptors on afferent sensory airway nerves with very little involvement from non-neuronal cells. The precise type of afferent sensory nerve responsible for cough in humans is unknown but there are a number of candidates; rapidly adapting receptors (RARs) located on Aδ-type nerves (chemo and mechanosensitive), small non-myelinated C-fibres (chemosensitive) and a specific sodium
Inflammation, cough reflex sensitization and airway sensory hyperreactivity
Cough reflex sensitization may occur peripherally and/or centrally [54], [55]. As the central processes involved are outside the scope of this review, our intention is to focus on the airway inflammatory events likely to be responsible for the sensitization of cough receptors. Acute and chronic cough are both associated with airway inflammation. Acute viral infection induces lower airway inflammation [56] which may persist long after the infection has resolved [57]. Inflammatory changes
Conclusions
There is an increased appreciation of the range of symptoms that disturb patients with acute and chronic cough. One of the most important, occurring in two-thirds of patients with chronic cough, is the bouts of coughing provoked by relatively innocuous airborne stimuli such as aerosols, scents and cold air. In the last few years, there have been significant advances in the understanding of mechanisms responsible for abnormal sensory responses such as chronic pain and itch. Much of this
References (76)
- et al.
Evaluation of a cough-specific quality-of-life questionnaire
Chest
(2002) - et al.
The treatment of cough. A comprehensive review
Chest
(1991) - et al.
Sick-building syndrome
Lancet
(1997) - et al.
Relationship between self-reported odor intolerance and sensitivity to inhaled capsaicin: proposed definition of airway sensory hyperreactivity and estimation of its prevalence
Chest
(2006) - et al.
Cough in hot pepper workers
Chest
(1991) Anatomy and neurophysiology of the cough reflex: ACCP evidence-based clinical practice guidelines
Chest
(2006)- et al.
Production of reflex cough by brainstem respiratory networks
Pulm Pharmacol Ther
(2004) Short- and long-term reproducibility of capsaicin cough challenge testing
Pulm Pharmacol Ther
(2003)- et al.
Interregulation of proton-gated Na(+) channel 3 and cystic fibrosis transmembrane conductance regulator
J Biol Chem
(2006) - et al.
Acid-sensitive vagal sensory pathways and cough
Pulm Pharmacol Ther
(2007)
Capsaicin cough sensitivity increases during upper respiratory infection
Respir Med
Plasticity of peripheral mechanisms of cough
Respir Physiol Neurobiol
Plasticity of central mechanisms for cough
Pulm Pharmacol Ther
Phosphoinositide-3-kinase and mitogen activated protein kinase signaling pathways mediate acute NGF sensitization of TRPV1
Mol Cell Neurosci
The diagnosis and management of chronic cough
Eur Respir J
Recommendations for the management of cough in adults
Thorax
Impact of chronic cough on quality of life
Arch Intern Med
Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ)
Thorax
Cough. A comprehensive review
Arch Intern Med
Evaluation and outcome of patients with chronic non-productive cough using a comprehensive diagnostic protocol
Thorax
Enhanced cough response to hyperpnea with cold air challenge in chronic cough patients showing increased cough sensitivity to inhaled capsaicin
Allergy
High prevalence of asthma in cross country skiers
BMJ
TRPM8 mechanism of autonomic nerve response to cold in respiratory airway
Mol Pain
The capsaicin receptor: a heat-activated ion channel in the pain pathway
Nature
Mirth-triggered asthma: is laughter really the best medicine?
Pediatr Pulmonol
Laughter-associated asthma
J Asthma
Respiratory dynamics during laughter
J Appl Physiol
Sensory hyperreactivity – a possible mechanism underlying cough and asthma-like symptoms
Allergy
Relationship of airway symptoms from chemicals to capsaicin cough sensitivity in atopic subjects
Clin Exp Allergy
Multiple chemical sensitivities: summary and directions for future investigators
Occup Med
Prevalence and nature of allergy and chemical sensitivity in a general population
Arch Environ Health
Prevalence of people reporting sensitivities to chemicals in a population-based survey
Am J Epidemiol
Prevalence and risk factors for self-reported odour intolerance: the Skovde population-based study
Int Arch Occup Environ Health
Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures
Arch Environ Health
Respiratory symptoms among glass bottle workers – cough and airways irritancy syndrome?
Occup Med (Lond)
Irritant-induced chronic cough: irritant-induced TRPpathy
Lung
Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms
Allergy
Quality of life and capsaicin sensitivity in patients with airway symptoms induced by chemicals and scents: a longitudinal study
Environ Health Perspect
Cited by (80)
Standardized Behavioral Treatment Improves Chronic Cough
2023, Journal of VoiceWAO-ARIA consensus on chronic cough – Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19
2022, World Allergy Organization JournalWAO-ARIA consensus on chronic cough – Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways
2021, World Allergy Organization JournalPatient-Reported Burden of Chronic Cough in a Managed Care Organization
2021, Journal of Allergy and Clinical Immunology: In PracticeGlobal Physiology and Pathophysiology of Cough: Part 1: Cough Phenomenology – CHEST Guideline and Expert Panel Report
2021, ChestCitation Excerpt :But the cough may persist long after the initiating insult has resolved, and this chronicity is a source of considerable morbidity. Physicians experienced in the management of chronic cough are readily aware of how troubled their patients are by spasms of cough provoked by everyday activities including talking or laughing and changes in ambient air temperature or exposure to aerosols or perfumes.19-21 Many patients also describe abnormal sensations such as a persisting itch or tickle in the throat or the feeling of a “lump” in the back of the throat.22
Laryngopharyngeal Reflux and Atypical Gastroesophageal Reflux Disease
2020, Gastrointestinal Endoscopy Clinics of North America