What is cough and what should be measured?

Fontana, Giovanni; Widdicombe, J. G.

doi:10.1016/j.pupt.2006.11.009

Cited by 74 publications

(55 citation statements)

References 29 publications

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“…In addition, similar drug concentrations have been shown previously to be selective in in vivo preparations (4,15,20,23,36,42,54,61), i.e., agonist and antagonist concentrations have been shown to be capable of activating or blocking the corresponding receptors in the absence of effects on other types of receptors or other nonspecific effects. Mechanical stimulation of the tracheobronchial tree is usually followed by a sequence of rhythmic expulsive cough efforts (11,16,17,24,35,42,44,46). In agreement with our previous findings (16,17,42,44,46), repeated stimuli are required to trigger a cough epoch that appears with a variable latency and outlasts the stimulation period.…”

Section: Discussionsupporting

confidence: 89%

Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

Mutolo¹,

Bongianni

Cinelli

et al. 2010

Journal of Applied Physiology

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Mutolo D, Bongianni F, Cinelli E, Pantaleo T. Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit. J Appl Physiol 109: 1002-1010, 2010. First published July 22, 2010 doi:10.1152/japplphysiol.00406.2010.-We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. These findings led us to suggest that the cVRG region, and possibly other neural substrates involved in cough regulation, may be sites of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30 -50 nl) of some antitussive drugs into the cVRG of pentobarbital-anesthetized, spontaneously breathing rabbits. [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO) and baclofen at the lower concentrations (0.5 mM and 0.1 mM, respectively) decreased cough number, peak abdominal activity, and peak tracheal pressure and increased cough-related total cycle duration (TT). At the higher concentrations (5 mM and 1 mM, respectively), both drugs abolished the cough reflex. DAMGO and baclofen also affected baseline respiratory activity. Both drugs reduced peak abdominal activity, while only DAMGO increased TT, owing to increases in expiratory time. The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. The NK 2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the cVRG is a site of action of some antitussive agents and support the hypothesis that several neural substrates involved in cough regulation may share this characteristic.control of breathing; -opioid receptors; GABAB receptors; neurokinin receptors; expiratory activity -ol]-enkephalin (DAMGO), the GABA B receptor agonist baclofen, the neurokinin-1 (NK 1 ) receptor antagonist CP-99,994, and the NK 2 receptor antagonist MEN 10376. We also proposed (42) that several neural substrates involved in the regulation of cough (12,16,17,31,44,46,48,56,57) may be sites of action of antitussive drugs. In agreement with our previous suggestion and preliminary results (17, 42, 44) as well as the proposal by Bolser and colleagues (12, 49), the responsive sites may comprise, in particular, the caudal part of the ventral respiratory column (2), i.e., the so-called caudal ventral respiratory group (cVRG), where bulbospinal expiratory neurons are concentrated (6,30,63).Several morphological and electrophysiological lines of evidence indicate that cVRG expiratory neurons are probably not involved in respiratory rhythmogenesis since very likely they do not have medullary axon collaterals (6,14,30,41,63). However, microinjections of the broad-spectrum excitato...

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Section: Discussionsupporting

confidence: 89%

Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

Mutolo¹,

Bongianni

Cinelli

et al. 2010

Journal of Applied Physiology

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“…The distinction between cough and the expiration reflex is important. Different neural mechanisms underlie the two reflexes (3), which have different physiological and pharmacological properties, as well as different functions (23,31; for further references, see also Ref. 57).…”

Section: Methodsmentioning

confidence: 99%

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit

Mutolo¹,

Bongianni²,

Cinelli³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii (NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30 -50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits. [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO) and baclofen decreased baseline respiratory frequency because of increases in the inspiratory time only at the higher concentration employed (5 mM and 1 mM, respectively). DAMGO (0.5 mM) and baclofen (0.1 mM) significantly decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration. At the higher concentrations, these agents suppressed the cough reflex. The effects of these two drugs were counteracted by specific antagonists (10 mM naloxone and 25 mM CGP-35348, respectively). The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) abolished cough responses, whereas the NK2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the caudal NTS is a site of action of some centrally acting drugs and a likely component of a neural system involved in cough regulation. A crucial role of substance P release in the mediation of reflex cough is also suggested.-opioid receptors; GABAB receptors; neurokinin receptors; control of breathing; airway defensive reflexes PREVIOUS STUDIES LED TO THE conclusion that some antitussive drugs act centrally since they inhibit cough when administered by intravertebral arterial or intracerebroventricular route in guinea pigs and cats (7,8). These drugs comprise the opioid receptor agonist codeine, the -opioid receptor agonist morphine, the neurokinin-1 (NK 1 ) receptor antagonist (ϩ)(2R,3R)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994), the NK 2 receptor antagonist {(ϩ)-N-methyl-[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-di-dichlorophenyl) butyl]benzamide} (SR48968), and the GABA B receptor agonist baclofen. A prominent central antitussive effect has been proven for the selective -opioid receptor agonist [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO) by using intracerebroventricular administration in the rat (30). However, the central responsive structures and the mechanism of action of these drugs remain to be investigated.It is widely agreed that tracheobronchial rapidly adapting receptors (RARs) are involved in cough mediation, while the role of bronchopulmonary C-fibers and A␦-nociceptive pulmonary afferent fibers in this reflex is controversial (see e.g., 36, 49, 62; for further references, also see Ref. 43). We have ...

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“…Ambulatory sound recording systems are increasingly used to measure coughing objectively, but there is no agreement about the best method for quantifying the recorded events. Indeed, many studies to date have failed to describe how cough is defined or quantified [7]. The European guidelines for the assessment of cough state: ''there is little to commend any particular method of quantifying cough over any other'' [8].…”

mentioning

confidence: 99%

“…In disease, prolonged series of explosive phases tend to occur ( fig. 2), either after a single breath or with several breaths interspersed; these are often referred to as cough ''epochs'', ''peals'', ''bouts'' or ''attacks'' [7]. Consequently, coughing is commonly quantified by counting either explosive phases or epochs.…”

mentioning

confidence: 99%

How to quantify coughing: correlations with quality of life in chronic cough

Kelsall¹,

Decalmer²,

Webster³

et al. 2008

European Respiratory Journal

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Different methods are used for quantifying coughing in sound recordings, but as yet no method has been shown to be more valid than any other. In the present study, the relationships between three different units of cough were examined and their ability to predict subjective ratings of cough and cough-related quality of life were evaluated.In total, 70 subjects (mean¡SD age 55¡11.7 yrs, 51 (73%) females) with chronic unexplained cough (median duration 4.8 yrs, interquartile range 2.5-10.1 yrs) performed fully ambulatory 24-h sound recordings, which were manually counted by trained observers and quantified by 1) explosive phases, 2) cough seconds and 3) cough epochs. Subjects also completed cough visual analogue scales (VAS) and the Leicester Cough Questionnaire (LCQ).All units of cough were strongly correlated; explosive phases and cough seconds correlated slightly more strongly than cough seconds with cough epochs or explosive phases with cough epochs. LCQ scores correlated moderately with explosive phases and seconds; epochs correlated slightly less well. Cough VAS scores showed a similar pattern.Explosive phases and seconds are interchangeable units of cough, moderately related to subjective measures and cough-related quality of life; epochs are a less satisfactory alternative.

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What is cough and what should be measured?

Cited by 74 publications

References 29 publications

Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit

How to quantify coughing: correlations with quality of life in chronic cough

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