Abnormal intraepithelial airway nerves in persistent unexplained cough?

O’Connell, F.; Springall, David R.; Moradoghli-Haftvani, A.; Krausz, T; Price, Daniel L.; Fuller, R W; Polak, J.M.; Pride, N. B.

doi:10.1164/ajrccm.152.6.8520777

Cited by 90 publications

(61 citation statements)

References 19 publications

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“…Neurogenic inflammatory mediators, particularly CGRP, have been implicated in the pathogenesis of chronic cough [12,18]. The present finding of CGRP in the BAL also being related to cough sensitivity in coughers but not in noncoughers is perhaps not surprising.…”

Section: Discussionmentioning

confidence: 49%

“…The present finding of CGRP in the BAL also being related to cough sensitivity in coughers but not in noncoughers is perhaps not surprising. In biopsy specimens, CGRP immunoreactivity has been found to be related to cough sensitivity in adults with chronic cough [18]. This is likely to relate to the plasticity of the peripheral nervous system, with neurotrophins altering the pattern of innervation changes in inflammatory disease, as SP-and CGRP-immunoreactive nerves are sparse in normal human airways [27].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, CGRP has been shown to be important in the mechanism of chronic cough [16,17]. In human studies, increased CGRP but not SP immunoreactive nerves were found in biopsies of adults with chronic cough [18]. These adults also had significantly increased cough sensitivity to capsaicin (i.e.…”

mentioning

confidence: 99%

“…These adults also had significantly increased cough sensitivity to capsaicin (i.e. a reduced threshold to elicit a cough response) [18]. In animal models, gastrooesophageal reflux (GOR) is associated with sensory nerve stimulation [19].…”

mentioning

confidence: 99%

“…Prior studies have used selected populations of adults presenting with cough [13,18], and this may select individuals with an abnormal airway response. In order to avoid this potential bias in the present study, children have been studied presenting for upper gastrointestinal endoscopy where there was no selection bias for coughing [20,21].…”

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confidence: 99%

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

Chang¹,

Gibson²,

Ardill³

et al. 2007

European Respiratory Journal

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Airway neuropeptides, in particular calcitonin gene-related peptide (CGRP), are likely to be important in the pathogenesis of chronic cough. The present authors evaluated the following: 1) the relationship between cough sensitivity and bronchoalveolar lavage (BAL) neuropeptides; and 2) the effect of reflux oesophagitis (RO) on cough, cough sensitivity and BAL neuropeptides in children not selected for cough. It was hypothesised that CGRP would be increased in children with chronic cough and would relate to cough sensitivity.Capsaicin cough sensitivity was performed in children undergoing gastro-duodenal endoscopy. CGRP, substance P and neurokinin A were measured in BAL obtained nonbronchoscopically. Children were defined as ''coughers'' if chronic cough was present.Coughers (n521) had significantly reduced cough sensitivity but were just as likely as noncoughers (n519) to have RO. The median CGRP was significantly higher in coughers with oesophagitis than in noncoughers with oesophagitis. CGRP significantly negatively correlated to cough sensitivity in coughers but not in noncoughers.Elevated calcitonin gene-related peptide, but not substance P or neurokinin A, is only associated with chronic cough in children when oesophagitis coexists. Calcitonin gene-related peptide in bronchoalveolar lavage relates to cough sensitivity and is likely to be important in the pathophysiology of chronic cough.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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

Chang¹,

Gibson²,

Ardill³

et al. 2007

European Respiratory Journal

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Cough, cough receptors, and asthma in children

Chang

1999

Pediatr. Pulmonol.

141

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This review discusses current general concepts on cough and the relationship between cough, cough receptor sensitivity, and asthma in children. It presents models of the relationship between cough and bronchoconstriction, and proposes a new model outlining the relationship between cough receptor sensitivity, airway hyperresponsiveness, and the clinical issues of cough, wheeze, and dyspnea in children with and without asthma. Cough is very common in children, with a prevalence of 15–20%. Those with non‐specific cough (dry cough in the absence of identifiable respiratory illness) are often treated with a variety of drugs, in particular, medications for asthma and gastroesophageal reflux. However, there is little evidence to use these medications for the sole symptom of cough in children. Clinical studies on cough need to be interpreted in light of inherent methodological problems in studying cough. These methodological problems include the nonrepeatable nature of questions on cough, the unreliability of subjective measurements of cough, the lack of objective measurements to quantify cough severity, and the period effect (spontaneous resolution of cough). Although cough can be troublesome, cough serves as an important function for maintaining normal health of the respiratory system. The importance of cough in maintaining respiratory health is reflected in the development of lung atelactasis/collapse from retained secretions and recurrent pneumonia in clinical situations where the cough reflex is ineffective. The cough reflex is complex and still poorly understood. In this article the simplified cough pathway is presented and involves cough receptors, mediators of sensory nerves and the afferent pathway, the vagus nerve, the cough centre, efferent pathway, and cough effectors. Pediatr Pulmonol. 1999; 28: 59–70. © 1999 Wiley‐Liss, Inc.

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Validation of endobronchial biopsy specimens for nerve quantitation by computer-assisted image analysis

et al. 2000

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The aim of this study was to assess the validity of endoscopic bronchial biopsy specimens for the quantitation of nerves. To this end, endobronchial biopsy was simulated ex vivo on surgically resected lung specimens and nerve densities were compared in airway smooth muscle of biopsy and surrounding tissue. Specimens were stained immunohistochemically for the general neural marker protein gene product 9.5 (PGP 9.5) and for vasoactive intestinal peptide (VIP), and nerve densities were quantitated using computer-assisted image analysis. Nerve density for total (PGP 9.5-immunoreactive) nerves was slightly higher in biopsies than in corresponding lung tissue, but this difference did not reach statistical significance (p=0.08). There was also no significant difference in the density of VIP-immunoreactive nerves (p=0.60). These findings support the use of endobronchial biopsy specimens to quantitate nerves in asthma and other airway diseases.

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Abnormal intraepithelial airway nerves in persistent unexplained cough?

Cited by 90 publications

References 19 publications

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

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

Cough, cough receptors, and asthma in children

Validation of endobronchial biopsy specimens for nerve quantitation by computer-assisted image analysis

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