A Study of the Cough Reflex in Idiopathic Pulmonary Fibrosis

Hope-Gill, Benjamin; Hilldrup, Simon; Davies, Christine; Newton, Russell P.; Harrison, N K

doi:10.1164/rccm.200304-597oc

Cited by 186 publications

(160 citation statements)

References 55 publications

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“…This statement is strongly supported [50] and idiopathic pulmonary fibrosis [51]. The cough reflex is also heightened in extra-pulmonary diseases associated with cough such as gastrooesophageal reflux disease [52] and rhinosinusitis [8].…”

Section: The Cough Reflex In Diseasementioning

confidence: 83%

“…As the bronchial epithelium is the first point of contact for noxious stimuli to the airway, these cells are an important source of inflammatory mediators including NGF. Increased neurotrophin levels including NGF have been demonstrated in the airways of patients with pulmonary fibrosis and increased capsaicin cough sensitivity [51]. The high affinity NGF receptor (tyrosine kinase receptor TrKA) is expressed on nociceptors and its activation leads to sensitization of the TRPV1 receptor [73].…”

Section: Inflammation Cough Reflex Sensitisation and Airway Sensory mentioning

confidence: 99%

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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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Section: The Cough Reflex In Diseasementioning

confidence: 83%

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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“…In patients with IPF, cough is one of the most disabling symptoms and is an independent predictor of disease progression [1][2][3]. Cough in IPF is often non-responsive to antitussive therapy [4], and studies on cough are scarce and have unfortunately not yet resulted in effective treatments. Several observations suggest that pirfenidone, an anti-fibrotic drug, might decrease cough [5, 6].…”

mentioning

confidence: 99%

“…Whether this inhibition relates to the antitussive effect of pirfenidone is unclear. In IPF, increased cough reflex sensitivity is thought to be a key mechanism that causes cough [4]. Preliminary studies in guinea pigs show that pirfenidone decreases cough reflex sensitivity [6]; however, its effect on cough reflex sensitivity in patients with IPF is yet unknown.…”

mentioning

confidence: 99%

Effect of Pirfenidone on cough in patients with Idiopathic Pulmonary Fibrosis

et al. 2017

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Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. In patients with IPF, cough is one of the most disabling symptoms and is an independent predictor of disease progression [1][2][3]. Cough in IPF is often non-responsive to antitussive therapy [4], and studies on cough are scarce and have unfortunately not yet resulted in effective treatments. Several observations suggest that pirfenidone, an anti-fibrotic drug, might decrease cough [5, 6]. We aimed to measure objectively the effect of pirfenidone on cough in patients with IPF and substantial cough. In addition, we assessed the effect of pirfenidone on subjective cough and quality of life (QoL) measures.This international, multicentre, prospective, observational study at four sites (The Netherlands, Italy, France and UK) recruited patients between 2013 and 2016. Treatment-naïve IPF patients aged 40-85 years with a forced vital capacity (FVC) ⩾50% and corrected transfer factor of the lung for carbon monoxide (TLCOc) ⩾30%, in whom pirfenidone therapy was about to be initiated according to regular practice, who had daily IPF-related cough for ⩾8 weeks with a cough score of ⩾40 mm on a 0-100 mm visual analogue scale (VAS), were eligible for the present study.Patients underwent baseline 24-h cough recording with the Leicester Cough Monitor (LCM) prior to starting pirfenidone, and after 4 and 12 weeks of treatment. The LCM is a validated ambulatory cough monitoring system [7]. Recordings were centrally analysed with automated cough software as previously described [7]. On the days of cough recording, participants completed the Leicester Cough Questionnaire (LCQ, a cough-specific health status questionnaire), the VAS cough severity, VAS urge-to-cough, King's Brief Interstitial Lung Disease health status questionnaire (K-BILD), the Hospital Anxiety and Depression Scale (HADS) and the seven-item Generalised Anxiety Disorder screener (GAD-7) [8,9].Analyses were performed on the intention-to-treat population. Objective cough frequency data were log transformed. To assess the effect of pirfenidone on cough over time we used a linear mixed model, which accounts for missing data [10]. Sensitivity analyses were performed on the per protocol population with a linear mixed model and paired t-tests. SPSS Statistics version 21.0 and R version 3.2.2 software packages were used for statistical analysis. The study was approved by the ethics committees of all participating centres (clinical trials.gov, NCT02009293). All patients provided written informed consent.Of the 46 patients screened for the study, 43 patients were included. Reasons for exclusion were low TLCOc and/or VAS scores. 38 patients completed 4 weeks of the study, and 31 completed 12 weeks. Reasons for dropout included: cessation of pirfenidone because of adverse events (8), logistic reasons (2), change of proton pomp inhibitor (1) and death (1). The age of the patients was 72±7 (mean±SD); most were men (33, 77%) and former smokers (34, 79%). Baseline cough counts, questionnaire scores and pulmonar...

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“…Thalidomide has been proven to be effective in the treatment of cough [82]. Corticosteroids have also been tested in the treatment of cough [83], but their use is not recommended in light of the results of recent trials mentioned above.…”

Section: Treatment Of Ipf: From 2000 To 2011 and Beyondmentioning

confidence: 99%

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

2013

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During the past decade important progress has been made regarding the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is the most devastating form of idiopathic interstitial pneumonia with a median survival of 3 years. The knowledge gained has been used to design multicentre, randomised, placebo-controlled trials in order to investigate agents with different mechanisms of action. Encouraging results have led to licensing of the first IPF-specific drug, pirfenidone. However, the road to successful treatment is still long. The main aim for the future should be the careful design of clinical trials, by choosing the most clinically meaningful end-point and keeping in mind that combination of various agents may be more effective. This approach has been used in the treatment of lung cancer with which IPF presents many similarities. @ERSpublications Progress toward the treatment of IPF and aims for future clinical trials

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A Study of the Cough Reflex in Idiopathic Pulmonary Fibrosis

Cited by 186 publications

References 55 publications

Are there clinical features of a sensitized cough reflex?

Are there clinical features of a sensitized cough reflex?

Effect of Pirfenidone on cough in patients with Idiopathic Pulmonary Fibrosis

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

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