Role of Laryngeal Afferents in Cough

doi:10.1006/pulp.1996.0040

Pulmonary Pharmacology

Volume 9, Issues 5–6, October 1996, Pages 309-314

https://doi.org/10.1006/pulp.1996.0040 Get rights and content

Abstract

The superior laryngeal nerve (SLN) is the main source of laryngeal afferent activity. A clear respiratory modulation can be noted when recording from the peripheral cut end of this nerve in several mammalian species. This modulation is due to three types of sensory endings: cold, pressure and ‘drive’ receptors. Although respiratory-modulated receptors play an important role in the function of the upper airway, they are not generally viewed as a primary factor in the elicitation of cough. Other more likely candidates for this role are thought to be the so-called ‘irritant’ endings. These are receptors that do not discharge in close association with the breathing cycle, but are usually silent or randomly active in control conditions. However, they are promptly recruited when the laryngeal mucosa is exposed to mechanical and/or chemical irritation. In fact, these receptors respond to well recognized tussigenic stimuli and are therefore thought to provide the triggering mechanisms for the cough reflex from the larynx. Endings with similar characteristics are also found in the most proximal areas of the tracheo-bronchial tree. On the basis of their response to irritants, these receptors are identified under the common denomination of ‘irritant receptors’. However, within this category of endings we find a wide range of distinctive characteristics, be this in terms of responsiveness to water solutions of various osmolarity and composition or to particular responses to substances produced within the body (autacoids) or experimentally administered.

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Cited by (33)

Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough
2016, Clinical Gastroenterology and Hepatology
Citation Excerpt :
Trauma from repeated coughing increases airway sensitivity to less noxious substances. As such, changes in environmental temperature (eg, cold),21 smells and fumes,22 dryness and change in upper airway secretion viscosity,21 and phonation17,18 can sufficiently irritate the nociceptors and chemoreceptors in the vocal folds to activate the cough reflex.23,24 Further supporting the hypothesized role of phonation in idiopathic chronic cough are results from several studies25,26 including 1 randomized trial27 that found that behavioral cough suppressive treatment with speech language pathologists can effectively treat these patients.
Although chronic cough is common, its etiology is often elusive, making patient management a challenge. Gastroesophageal reflux and airway hypersensitivity can cause chronic cough. We explored the relationship between reflux, phonation, and cough in patients with idiopathic chronic cough.
We performed a blinded, cross-sectional study of nonsmoking patients with chronic cough (duration, >8 weeks) refractory to reflux treatment referred to the Digestive Disease Center at Vanderbilt University. All underwent 24-hour acoustic recording concurrently and temporally synchronized with ambulatory pH-impedance monitoring. Cough, phonation, and pH-impedance events were recorded. We evaluated the temporal relationship between cough and phonation or reflux events using Poisson and logistic regression.
Seventeen patients met the inclusion criteria (88% female; 100% white; median age, 63 years [interquartile age range, 52–66 years]; mean body mass index, 30.6 [interquartile range, 27.9–34.0]); there were 2048 analyzable coughing events. The probability of subsequent coughing increased with higher burdens of preceding cough, reflux, or phonation. Within the first 15 minutes after a cough event, the cough event itself was the main trigger of subsequent cough events. After this period, de novo coughing occurred with increases of 1.46-fold in association with reflux alone (95% confidence interval, 1.17–1.82; P < .001) and 1.71-fold in association with the combination of phonation and reflux events.
Antecedent phonation and reflux increased the rate of cough events in patients with idiopathic chronic cough. Reflux events were more strongly associated with increased rate of coughing. Our findings support the concept that airway hypersensitivity is a cause of chronic cough, and that the vocal folds may be an effector in chronic cough ClinicalTrials.gov number: NCT01263626.
Cough
2015, Murray and Nadel's Textbook of Respiratory Medicine: Volume 1,2, Sixth Edition
Laryngospasm in anesthetized children: Fact or fiction?
2015, Praticien en Anesthesie Reanimation
Les complications respiratoires sont fréquentes en anesthésie pédiatrique, et parmi elles, le spectre du laryngospasme reste très redouté. La prévention est fondamentale chez les enfants ayant des facteurs de risque. La symptomatologie associe une ventilation inefficace et une désaturation artérielle en oxygène. Cependant, le diagnostic est bien souvent porté par excès. L’échographie peut permettre d’observer la fermeture des cordes vocales et donc guider les thérapeutiques à mettre en œuvre rapidement afin d’éviter des complications potentiellement létales. Nous proposons de discuter la physiopathologie, les facteurs de risque identifiés, les mesures de prévention et de traitement du laryngospasme chez l’enfant. Nous discutons également l’intérêt de l’échographie dans le diagnostic du laryngospasme.
Pediatric anesthesia is featured by potentially severe respiratory complications, especially laryngospasm considered as one of the most frightening. Laryngospasm produces suddenly ineffective ventilation and oxygen arterial desaturation. Risk factors have been investigated and prevention is critical in patients at risk. The management of laryngospasm follows predetermined guidelines. However, the diagnosis is commonly done in excess. Ultrasound examination could afford new insights into vocal cords closure observation. Thus, differential diagnosis can be ruled out and therapeutics adapted to avoid potentially lethal outcomes. We discuss herein physiopathology, risk factors, prevention and treatments of laryngospasm in pediatric anesthesia.
Effect of airway inflammation on short-latency reflex inhibition to inspiratory loading in human scalene muscles
2012, Respiratory Physiology and Neurobiology
Citation Excerpt :
Although only proprioceptive afferents appear to be critical for the generation of the reflex inhibition (Butler et al., 1995, 1997), and the afferents relevant to reflex modulation might include those from the ventilatory muscles, modulatory inputs may also arise from the upper airway mucosa, the lower airway, or the lung parenchyma. Several brainstem reflexes link airway or pulmonary afferents with motoneurones (e.g. Hering–Breuer reflex (Hering and Breuer, 1868a,b), the J reflex (Gandevia et al., 1998; Paintal, 1970), and the cough reflex (Sant’Ambrogio and Sant’Ambrogio, 1996)). Thus, there are two competing hypotheses for the increased reflex inhibition: (1) chronic systemic inflammation may alter or sensitise respiratory afferent activity or (2) chronic resistive loading may alter the central processing of respiratory afferent activity.
The short-latency reflex inhibition of human inspiratory muscles produced by loading is prolonged in asthma and obstructive sleep apnoea, both diseases involving airway and systemic inflammation. Both diseases also involve repetitive inspiratory loading. Although airway mucosal afferents are not critical components of the normal reflex arc, during airway inflammation, prolongation of the reflex may be caused by altered mucosal afferent sensitivity, or altered central processing of their inputs. We hypothesised that acute viral airway inflammation would replicate the reflex abnormality. The reflex was tested in 9 subjects with a “common cold” during both the acute infection and when well. Surface electrodes recorded electromyographic (EMG) activity bilaterally from scalene muscles. Latencies of the inhibitory response (IR) did not differ significantly (IR peak 67 vs 70 ms (p = 0.12), and IR offset 87 vs 90 ms (p = 0.23), between the inflamed and well conditions, respectively). There was no difference in any measure of the size of the reflex inhibition.
Cough throughout life: Children, adults and the senile
2007, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
These responses were abolished when the superior laryngeal nerves had been cut [23]. As the superior laryngeal nerve is also important in laryngeal function and the cough pathway [28–30], it implies that maturation of the cough reflex would also be influenced. The central cough pathway is intrinsically linked to the brainstem respiratory control network [31].
We review cough from premature birth, mature neonatal life, in childhood and adult life, and in old age. There is a regrettable lack of definitive studies, but many clues in the literature. The cough reflex seems weak in premature infants, but develops with maturity. It is pronounced in childhood, but there seem to be no studies comparing its strength then with that in adulthood. In old age the cough may weaken, as indicated by the prevalence of aspiration pneumonia. These changes are presumably related to the development and degeneration of the afferent and central nervous pathways for cough, which may be reflected in the changes in laryngeal muscle function with age. There is much evidence that age influences the development of the respiratory system in general, and of the immune system which would affect the degree, frequency and clinical issues of cough. Other factors that limit our understanding of the changes in cough with age include the reporting of cough by parents in infants and carers in old age and the use of different diagnostic criteria throughout life. Age-related variation in cough sensitivity seems to be well established, but its quantitation and mechanisms require much further research.
Pharmacological modulation of cough reflex
2006, Advances in Phytomedicine
Citation Excerpt :
Afferent activity may be elicited from the larynx by mechanical and chemical irritants. Most of the sensory traffic from the larynx is conveyed in the superior laryngeal nerves (Fuller and Jackson, 1990; Sant`Ambrogio and Sant`Ambrogio, 1996). Three types of receptors – pressure, drive and cold – take part in a clear respiratory modulation.
The cough reflex is an attack of powerful expiratory efforts produced by active contractions of the expiratory muscles, preceded by deep inspirations.
Cough is a normal physiological defensive reflex responsible for keeping the airways free of obstruction and harmful substances. However, cough is also the most frequent symptom of acute respiratory system diseases and is the most common reason why sick patients visit physicians. The largest diagnostic group associated with chronic cough is asthma or asthma-like syndromes and chronic obstructive pulmonary disease. Furthermore, gastroesophageal reflux, rhinitis/postnasal drip syndrome and unpleasant side effects accompanying the therapy with angiotensin-converting enzyme inhibitors (ACEI) represent other causes of chronic cough. The cough reflex may be elicited by the activation of receptors of non-myelinated nociceptive Aδ-fibers and C-fibers and receptors of myelinated Aδ-fibers distributed throughout the respiratory tract. In recent times as proper cough receptors are thought to be rapidly adapting receptors (RARs) of myelinated fibers, C-fibers and transient receptor potential vanilloid 1 (TRPV1) localize on the non-myelinated fibers.
As the pathological cough (especially its chronic form) has significant impact on patient's quality of life, observed either in physical activity or psychosocial domain, various treatment attitudes are used for different forms of cough (acute, subacute, chronic, productive, nonproductive, psychogenic, asthma-associated, or painful).
Interest of research in this field is accompanied with the fact, that many antitussive drugs (mainly from the opioid group), which have been the antitussives of choice for decades, are limited by their unpleasant and very often adverse reactions.
In this chapter the authors divided the drugs used in the pharmacological treatment of cough into several groups. These include the drugs acting at the level of receptors, the drugs affecting the propagation of cough impulses in afferent nerves, the drugs modulating the central coordination of cough reflex, the drugs acting at the level of efferent nerves, and the drugs affecting the effectors. Efficacy of many antitussive agents is connected with their influence on more than one level of cough reflex.
Another group used in the therapy of cough are mucoactive substances that change the dry, irritant and nonproductive cough into the so-called productive cough with nonirritating expectoration. The last-mentioned group in this chapter is demulcerative and hydrating drugs, which can create a defense layer protecting the mucous membranes from other irritant stimuli.

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^f1: Author for correspondence

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Role of Laryngeal Afferents in Cough