Calcitonin gene-related peptide relates to cough sensitivity in children with chronic cough

Chang, Anne B.; Gibson, Peter G.; Ardill, J.E.S.; McGarvey, Lorcan

doi:10.1183/09031936.00150006

Cited by 37 publications

(23 citation statements)

References 44 publications

(73 reference statements)

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“…The sensitizing effect of SP on RARs has also been demonstrated in the central nervous system, especially in the nucleus tractus solitarius, which also results in an enhanced cough reflex [38,39]. While airway SP levels or expression in patients with persistent cough are conflicting [10,11,12,13,40,41], we found elevated plasma SP levels in patients with persistent asthmatic and nonasthmatic cough.…”

Section: Discussionmentioning

confidence: 37%

Plasma Substance P Levels in Patients with Persistent Cough

et al. 2011

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Background: Substance P (SP) is involved in the pathogenesis of cough in animal models. However, few studies in humans have been reported and the roles of SP in clinical cough remain obscure. Objectives: To clarify the relevance of plasma levels of SP in patients with persistent cough. Methods: We studied 82 patients with cough persisting for at least 3 weeks and 15 healthy controls. Patients were classified as having asthmatic cough (cough-variant asthma and cough-predominant asthma; n = 61) or nonasthmatic cough (n = 21; postinfectious cough, n = 6; gastroesophageal reflux disease, n = 5; idiopathic cough, n = 5, and others, n = 5). Correlations were evaluated between plasma SP levels as measured with ELISA and methacholine airway hyperresponsiveness (airway sensitivity and airway reactivity), capsaicin cough sensitivity, sputum eosinophil and neutrophil counts, and pulmonary function. Results: Plasma SP levels were significantly elevated in patients with both asthmatic and nonasthmatic cough compared with controls [31.1 pg/ml (range 18.0–52.2) and 30.0 pg/ml (range 15.1–50.3) vs. 15.4 pg/ml (range 11.3–23.7); p = 0.003 and p = 0.038, respectively] but did not differ between the two patient groups (p = 0.90). Plasma SP levels correlated with airway sensitivity (threshold dose of methacholine) in the patients with asthmatic cough (r = –0.37, p = 0.005) but not with airway reactivity, cough sensitivity, FEV₁ values, or sputum eosinophil and neutrophil counts in either group. Conclusions: Increased levels of SP in plasma are associated with persistent cough in humans and might be related to airway sensitivity in asthmatic cough.

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Section: Discussionmentioning

confidence: 37%

Plasma Substance P Levels in Patients with Persistent Cough

et al. 2011

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“…In the same study when lignocaine was instilled topically onto the oesophagus, cough was prevented. We have previously demonstrated that distal oesophageal acid exposure may be associated with increased airway neuropeptide levels, supporting the relationship between acid reflux and airway nerve activation 18 19. Lang et al 20 have shown that in anaesthetised cats, applying acid to the oesophagus was associated with a bronchoconstriction and increased mucus secretion in the airway.…”

Section: Mechanism Of Gord-associated Respiratory and Laryngeal Symptomssupporting

confidence: 57%

Respiratory and laryngeal symptoms secondary to gastro-oesophageal reflux

Rafferty

Mainie

McGarvey

2011

Frontline Gastroenterol

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REVIEW 212Gastro-oesophageal refl ux may cause a range of laryngeal and respiratory symptoms. Mechanisms responsible include the proximal migration of gastric refl uxate beyond the upper oesophageal sphincter causing direct irritation of the larynx and lower airway. Alternatively, refl uxate entering the distal oesophagus alone may stimulate oesophageal sensory nerves and indirectly activate airway refl exes such as cough and bronchospasm. Recognising refl ux as a cause for these extraoesophageal symptoms can be diffi cult as many patients do not have typical oesophageal symptoms (eg, heartburn) and clinical fi ndings on laryngoscopy are not very specifi c. Acid suppression remains an effective treatment in the majority of patients but there is growing appreciation of the need to consider and treat non-acid and volume refl ux. New opinions about the role of existing medical and surgical (laparoscopic techniques) treatment are emerging and a number of novel anti-refl ux treatments are under development.

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“…In an experimental model of itch, tryptase is known to activate the proteinase activated receptor (PAR-2) located on the C-fibre nerve terminal, releasing substance P which in turn sensitises the mast cell to release TNFα which in known to sensitize nociceptor function [64]. Neuropeptides such as substance P and neurokinin A are elevated in the airways of asthmatic patients with cough [65] and airway levels of calcitoningene-related peptide (CGRP) are positively correlated with capsaicin cough reflex sensitivity [66].…”

Section: Inflammation Cough Reflex Sensitisation and Airway Sensory mentioning

confidence: 99%

Are there clinical features of a sensitized cough reflex?

McGarvey

McKeagney²,

Polley

et al. 2009

Pulmonary Pharmacology & Therapeutics

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Key words: sensory hyperresponsiveness, hyperreactivity, cough reflex, receptor AbstractCough reflex hypersensitization is a key feature in patients with troublesome cough. The clinical consequence of this hypersensitive state is typified by bouts of coughing often triggered by low threshold stimuli encountered by the patient during normal daily activities including exposure to aerosols, scents and odours, a change in air temperature and when talking or laughing. These features are often perceived by cough patients to be the most disruptive aspect of their condition and undoubtedly contribute to impaired quality of life.Patients with troublesome cough may describe a range of additional symptoms and sensations including an 'urge to cough' or the feeling of an 'itch' at the back of the throat, or a choking sensation and occasionally chest pain or breathlessness. It is uncertain if these features arise due to the processes responsible for cough reflex sensitisation or as a direct consequence of the underlying cough aetiology. In an attempt to understand the clinical features of a sensitized cough reflex, the spectrum of symptoms typically described by cough patients will be reviewed and possible underlying mechanisms considered. Since an intact cough reflex is crucial to airway protection, anti-tussive treatment that attenuates the hypersensitive cough state rather than abolishing the cough reflex completely would be preferable. Identifying such agents remains a clinical, scientific and pharmacological challenge.

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Calcitonin gene-related peptide relates to cough sensitivity in children with chronic cough

Cited by 37 publications

References 44 publications

Plasma Substance P Levels in Patients with Persistent Cough

Plasma Substance P Levels in Patients with Persistent Cough

Respiratory and laryngeal symptoms secondary to gastro-oesophageal reflux

Are there clinical features of a sensitized cough reflex?

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