Figures
- 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
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
- TABLE 1
Comorbidities influencing cough in idiopathic pulmonary fibrosis (IPF)
Comorbidity Frequency in IPF (%) Reference(s) GORD 21–94 [36–38] OSA 59–88# [38–40] Emphysema 30–55 [41] ACE inhibitor use 9–15 [5, 42] Chronic sinusitis/UACS 17–34 [5, 42, 43] Lung cancer 4.4–16 [41, 44] Infection 11–20 [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 tool Description Validation studies and MCID Advantages Disadvantages Subjective Visual analogue scale [56] 100 mm scale with extremes no cough to worst possible cough severity Not validated in IPF Easy to use
Repeatable
ResponsiveNot validated in IPF or chronic cough Cough quality-of-life questionnaire [57] 28-item cough-specific quality-of-life questionnaire with six domains Validated 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 coughNeed 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 domains Evaluated 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: 1.3High reliability
Valid instrument for assessing impact of cough
Ability to detect a response to changeNeed 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 insights Doesn't measure efficacy of therapy or predict response in patients
Limited availabilityCough monitor [59] Microphone and recording device measuring cough in a pre-specified time slot Validated cough monitors for chronic cough
High correlation found with subjective cough measurements [10]Measures cough frequency accurately Currently limited to research and trails
Benefit in routine clinics is not clearMCID: minimal clinically important difference; ERS: European Respiratory Society.
