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Cough in idiopathic pulmonary fibrosis

Mirjam J.G. van Manen, Surinder S. Birring, Carlo Vancheri, Vincent Cottin, Elisabetta A. Renzoni, Anne-Marie Russell, Marlies S. Wijsenbeek
European Respiratory Review 2016 25: 278-286; DOI: 10.1183/16000617.0090-2015
Mirjam J.G. van Manen
1Dept of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Surinder S. Birring
2Division of Asthma, Allergy and Lung Biology, King's College London, London, UK
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Carlo Vancheri
3Dept of Clinical and Experimental Medicine, Section of Respiratory Disease, University of Catania, Catania, Italy
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Vincent Cottin
4Dept of Respiratory Medicine, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon 1 University, Lyon, France
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Elisabetta A. Renzoni
5Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
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Anne-Marie Russell
5Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
6National Heart and Lung Institute, Imperial College London, London, UK
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Marlies S. Wijsenbeek
1Dept of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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  • For correspondence: m.wijsenbeek-lourens@erasmusmc.nl
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  • FIGURE 1
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    FIGURE 1

    Pathophysiology of cough. TRPV1: transient receptor potential vanilloid 1; TRPA1: transient receptor potential ankyrin 1; RAR: rapidly adapting receptor; SAR: slowly adapting receptor. Reproduced from [17] with permission from the publisher.

  • FIGURE 2
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    FIGURE 2

    Interactions between idiopathic pulmonary fibrosis (IPF), gastro-oesophageal reflux disease (GORD), obstructive sleep apnoea (OSA) and cough. 1: traction leading to a weaker lower oesophageal sphincter tonus [45]; 2: microaspiration inducing epithelial damage [38, 46]; 3: restriction inducing instability of the upper airway [39]; 4: intermitted hypoxaemia promoting profibrotic mechanisms [49]; 5: increased cough reflex sensitivity [22–31]; 6: pressure causing stretch injury and activation of fibrotic mechanisms [31]; 7: microaspiration causing an inflammatory reaction blocking the airway [53]; 8: obstruction increasing trans-diaphragmatic pressure [51, 52]; 9: aspiration directly and acid reflux indirectly stimulate the cough reflex [6, 47]; 10: cough increasing trans-diaphragmatic pressure [47]; 11: less central inhibition and inflammation increasing cough reflex sensitivity [54].

Tables

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  • TABLE 1

    Comorbidities influencing cough in idiopathic pulmonary fibrosis (IPF)

    ComorbidityFrequency in IPF (%)Reference(s)
    GORD21–94[36–38]
    OSA59–88#[38–40]
    Emphysema30–55[41]
    ACE inhibitor use9–15[5, 42]
    Chronic sinusitis/UACS17–34[5, 42, 43]
    Lung cancer4.4–16[41, 44]
    Infection11–20[3]
    • GORD: gastro-oesophageal reflux disease; OSA: obstructive sleep apnoea; ACE: angiotensin converting enzyme; UACS: upper airway cough syndrome. #: with high mean body mass index of 28–32 kg·m−2.

  • TABLE 2

    Cough measurements in idiopathic pulmonary fibrosis (IPF) patients

    Cough measurement toolDescriptionValidation studies and MCIDAdvantagesDisadvantages
    Subjective    
     Visual analogue scale [56]100 mm scale with extremes no cough to worst possible cough severityNot validated in IPFEasy to use
    Repeatable
    Responsive
    Not validated in IPF or chronic cough
     Cough quality-of-life questionnaire [57]28-item cough-specific quality-of-life questionnaire with six domainsValidated in IPF (n=23)
    MCID in IPF: change of five points on a 28–112 scale [57]
    Comprehensive questionnaire
    Reliable
    Valid instrument for assessing impact of cough
    Need more studies in IPF: MCID evaluated with a retrospective anchor scale
     Leicester cough questionnaire [15]19-item self-administered chronic cough quality-of-life questionnaire with three domainsEvaluated in IPF: high correlation found with cough visual analogue scale, cough symptom score and objective cough frequency in IPF [10, 22]
    MCID in chronic cough: 1.3
    High reliability
    Valid instrument for assessing impact of cough
    Ability to detect a response to change
    Need more studies in IPF: MCID evaluated in chronic cough
    Objective
     Cough challenge test [58]Measurement of cough reflex sensitivity by inhalation of nebulised tussive agents (most common citric acid or capsaicin)Not validated in IPF
    No MCID
    Standardised methodology published by ERS [14]
    Useful for testing effect of new cough therapies on cough reflex sensitivity and for obtaining mechanistic insightsDoesn't measure efficacy of therapy or predict response in patients
    Limited availability
     Cough monitor [59]Microphone and recording device measuring cough in a pre-specified time slotValidated cough monitors for chronic cough
    High correlation found with subjective cough measurements [10]
    Measures cough frequency accuratelyCurrently limited to research and trails
    Benefit in routine clinics is not clear
    • MCID: minimal clinically important difference; ERS: European Respiratory Society.

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Vol 25 Issue 141 Table of Contents
European Respiratory Review: 25 (141)
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Cough in idiopathic pulmonary fibrosis
Mirjam J.G. van Manen, Surinder S. Birring, Carlo Vancheri, Vincent Cottin, Elisabetta A. Renzoni, Anne-Marie Russell, Marlies S. Wijsenbeek
European Respiratory Review Sep 2016, 25 (141) 278-286; DOI: 10.1183/16000617.0090-2015

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Cough in idiopathic pulmonary fibrosis
Mirjam J.G. van Manen, Surinder S. Birring, Carlo Vancheri, Vincent Cottin, Elisabetta A. Renzoni, Anne-Marie Russell, Marlies S. Wijsenbeek
European Respiratory Review Sep 2016, 25 (141) 278-286; DOI: 10.1183/16000617.0090-2015
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  • Article
    • Abstract
    • Abstract
    • Introduction
    • Characteristics and demographics of chronic cough
    • Effect on the patient
    • Pathophysiology of chronic cough
    • Pathophysiology of cough in IPF
    • Comorbidities influencing cough
    • Assessment of cough in IPF
    • Treatment of cough in IPF
    • Future trials
    • Conclusion
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  • Interstitial and orphan lung disease
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