Regulation of cough by neuronal Na+–K+ ATPases

Canning, Brendan J.; Farmer, David G.S.

doi:10.1016/j.coph.2015.05.002

Cited by 3 publications

(3 citation statements)

References 75 publications

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“…Importantly, gastrointestinal symptoms demonstrated an association with cough rather than smoking, cancer stage, location, treatment and COPD. Recent research in the non-cancer setting has elucidated central nervous system circuitry and pathways common to cough and the gastrointestinal tract leading to a more comprehensive understanding of cough neurochemistry and higher order control of coughing 26,27 . As a result, new potential targets for antitussive therapies have been identified that may be relevant to patients with lung cancer 28,29 .…”

Section: Discussionmentioning

confidence: 99%

Cough in Patients With Lung Cancer

Harle

Blackhall

Molassiotis

et al. 2019

Chest

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Background: Cough is common in patients with lung cancer and current antitussive treatments are suboptimal. There is little published data describing cough in patients with lung cancer or work assessing clinical associations; the aim of the current is study is to fill that gap. Methods: Longitudinal prospective observational single-cohort study over 60 days. Patients were assessed through self-reported validated scales and, in a subsample, ambulatory cough monitoring, at study entry (day 0), day 30 and day 60. Results: At study entry, 177 patients were included and 153 provided data at day 60. The median duration of cough was 52 weeks (IQR 8.5-260). Cough was described as severe enough to warrant treatment in 62% of the patients. Depending on the scale used, performance status was associated with both cough severity and cough impact (p<0.001) at study entry, while higher cough severity at study entry was associated with female sex (p=0.02), asthma (p=0.035), and reflux disease (p<0.001); cough impact at study entry was additionally associated with experiencing nausea (p=0.018). Cancer characteristics (i.e. cancer stage, histology) were not associated with cough severity nor cough impact; neither was smoking or COPD. Conclusions: This is the first study to describe characteristics of cough in patients with lung cancer and identify clinical associations that may be relevant for its treatment. Our data suggest that cough is a frequent and distressing symptom, and an unmet clinical need. Its associationwith gastro-intestinal symptoms in this study may improve our understanding of pathophysiology and therapeutic options for cough occurring in patients with lung cancer.

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Section: Discussionmentioning

confidence: 99%

Cough in Patients With Lung Cancer

Harle

Blackhall

Molassiotis

et al. 2019

Chest

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“…The effect may be related to blockade of acid-sensing ion channels [ 18 , 43 ], blockade of voltage-gated ion channels [ 17 ], modulation of N-methyl- d -aspartate-type glutamate receptor channels [ 44 ] that may also be relevant to cough suppression [ 13 ], or neuronal sodium pump inhibition [ 16 – 18 ]. Drugs known to interact with sodium pumps dose-dependently suppress cough in guinea pigs and in patients [ 15 , 45 , 46 ]. However, many are nonselective, limiting their utility due to significant off-target effects.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial

Balasubramanian

Holbrook²,

Canning³

et al. 2023

ERJ Open Res

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BackgroundCough is the most reported symptom in the US, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway.Research QuestionWe sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough.Study Design and MethodsThis was a randomized, placebo-controlled, parallel design pilot trial of individuals with chronic refractory cough. The effects of six weeks of zinc acetateversusplacebo on quality of life and symptoms as measured by the Cough Quality of Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), Cough Visual Analog Score (C-VAS), and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome.ResultsA total of 34 participants, 17 in each group, were enrolled and randomized. Participants were primarily White females with moderate-severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS, and GACC scores, but the treatment effects of zinc acetateversusplacebo were small with confidence intervals that did not include the MCIDs.InterpretationWe observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.

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“…Also, the hypothalamic arcuate nucleus is known to regulate feeding behavior and appetite [20]. The α3 subunit is also expressed in all vagal afferent neurons [21]. The spinal trigeminal motor nucleus, which integrates sensory input from the dental and craniofacial regions and feeds into the hypothalamus, modulates vagal responses and is strongly positive for α3 Na, K-ATPase, at least in mice fetuses [9,22].…”

Section: Diagnoses and Interventionsmentioning

confidence: 99%

Alternating Hemiplegia of Childhood: gastrointestinal manifestations and correlation with neurological impairments

Pratt

Uchitel

McGreal

et al. 2020

Orphanet J Rare Dis

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Background: Alternating Hemiplegia of Childhood (AHC) is caused by mutations of the ATP1A3 gene which is expressed in brain areas that include structures controling autonomic, gastrointestinal, gut motility and GABAergic functions. We aimed to investigate, in a cohort of 44 consecutive AHC patients, two hypotheses: 1) AHC patients frequently manifest gastrointestinal, particularly motility, problems. 2) These problems are often severe and their severity correlates with neurological impairments. Results: 41/44 (93%) exhibited gastrointestinal symptoms requiring medical attention. For these 41 patients, symptoms included constipation (66%), swallowing problems (63%), vomiting (63%), anorexia (46%), diarrhea (44%), nausea (37%), and abdominal pain (22%). Symptoms indicative of dysmotility occurred in 33 (80%). The most common diagnoses were oropharyngeal dysphagia (63%) and gastroesophageal reflux (63%). 16 (39%) required gastrostomy and two fundoplication. Severity of gastrointestinal symptoms correlated with non-paroxysmal neurological disability index, Gross Motor Function Classification System scores, and with the presence/absence of non-gastrointestinal autonomic dysfunction (p = 0.031, 0.043, Spearman correlations and 0.0166 Cramer's V, respectively) but not with the paroxysmal disability index (p = 0.408). Conclusions: Most AHC patients have gastrointestinal problems. These are usually severe, most commonly are indicative of dysmotility, often require surgical therapies, and their severity correlates with that of non-paroxysmal CNS manifestations. Our findings should help in management-anticipatory guidance of AHC patients. Furthermore, they are consistent with current understandings of the pathophysiology of AHC and of gastrointestinal dysmotility, both of which involve autonomic and GABAergic dysfunction.

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Regulation of cough by neuronal Na+–K+ ATPases

Cited by 3 publications

References 75 publications

Cough in Patients With Lung Cancer

Cough in Patients With Lung Cancer

Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial

Alternating Hemiplegia of Childhood: gastrointestinal manifestations and correlation with neurological impairments

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