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Summary of clinical practice points
Terminology, epidemiology and impact
Chronic cough (CC) is common, predominantly affecting middle-aged females.
Sufferers experience significantly impaired quality of life (QoL).
Cough is associated with increased healthcare costs.
Recent advances in the diagnosis and management of cough have not yet widely embedded in routine clinical practice in the UK.
Causes of CC
Protocolised investigation and treatment of common comorbidities such as reflux, rhinitis and asthma is not always effective.
A ‘treatable traits’ approach is advocated, to guide personalised treatment.
Cough hypersensitivity is a frequently overlooked treatable trait for many patients and requires specific treatment including antitussives and non-pharmacological treatment.
Clinical assessment
Establish who needs specialist referral or can be initially managed in general practice with a targeted trial of therapy. ‘Red flags’ should prompt urgent referral in line with National Institute for Health and Care Excellence (NICE) guidelines.1
The history should identify possible underlying disease and treatable traits.
All patients with CC should have a chest X-ray (CXR), full blood count (FBC), diagnostic spirometry and fractional exhaled nitric oxide (FeNO) (if available).
CC in a patient with a normal CXR and no response to treatment of known or suspected triggers should be referred on to secondary care.
Treatable traits in cough
Smoking
Smoking cessation will reduce cough as chronic bronchitis resolves. Nicotine suppresses the cough reflex. Nicotine replacement therapy may prevent a rebound in cough hypersensitivity and worsening symptoms.
ACEI treatment
Stop in all patients with CC. Switch to an angiotensin 2 receptor blocker (A2RB) if needed. Improvement may take 4 weeks or more.
Airway disease: productive cough
Productive cough is managed differently to a dry or minimally productive cough.
Look for infection, smoking and airways disease, particularly bronchiectasis.
Optimise airway clearance, treat infection. Consider low-dose macrolide therapy, for example, azithromycin 250 mg three times per week initially, titrating up to 500 mg three times per weekdepending on clinical response (not to be used in chronic dry cough).
Eosinophilic airway disease
In patients with cough and no other features of airway disease, with normal spirometry and low T2 biomarkers, avoid the use of inhaled corticosteroids (ICS) and consider alternative causes.
In patients with other features of airways disease, optimise any traits and manage in line with published disease specific guidance. Consider a 1- month trial of ICS.
Cough with no other symptoms or airflow obstruction and raised T2 biomarkers (FeNO>25 ppb and blood eosinophil count (BEC)≥0.3×109/L). Consider short trial of ICS for 4 weeks,2 for example, budesonide DPI 200 μg two times per day or equivalent.
If response is incomplete, consider add on treatment, for example, double dose of ICS or add a leukotriene receptor antagonist (LTRA),3 for example, montelukast 10 mg nocte. Also consider a short trial of oral corticosteroids (eg, prednisolone 30 mg od for 2 weeks) and consider compliance if markers remain high.
Gastro-oesophageal reflux disease
A difficult area. Physiological levels of reflux can stimulate episodes in CC patients.
Only treat with proton pump inhibitors (PPI’s) if the patient has heartburn or other definitive evidence of acid reflux. For example, lansoprazole 30 mg two times per day or equivalent for 4 weeks. Most patients do not respond.
Fundoplication cannot be recommended for the treatment of cough alone in the absence of more typical reflux symptoms and objective evidence of reflux.
Upper airway symptoms
Symptoms of chronic rhinosinusitis (CRS) should prompt an empirical trial of a nasal steroid.
PPIs are not beneficial for throat symptoms.
Laryngeal dysfunction and hypersensitivity are common in CC.
Obstructive sleep apnoea
Consider obstructive sleep apnoea (OSA) as a potential treatable trait in refractory cough. Continuous positive airway pressure (CPAP) treatment might improve CC if there is objective evidence of OSA on a sleep study.
Obesity
Obesity is associated with CC. Weight loss should be recommended in obese patients and might improve CC.
Complications of CC
Patients who suffer cough syncope should be advised not to drive and contact the Driver Vehicle Licensing Authority (DVLA). See https://www.gov.uk/guidance/neurological-disorders-assessing-fitness-to-drive%23cough-syncope for further guidance.
All patients presenting with CC should be asked if they are experiencing any symptoms of urinary incontinence (UI).
All patients reporting UI should be referred to their local multidisciplinary team (MDT) incontinence service for further specialist input and support.
Management of cough hypersensitivity
Cough hypersensitivity is a treatable trait of many conditions and often the foremost problem in patients with chronic dry/minimally productive cough.
There are currently no tools to positively identify cough hypersensitivity.
Cough hypersensitivity may improve with treatment of other treatable traits, if not the patients has refractory CC (RCC).
In RCC, the most effective treatments are those addressing cough hypersensitivity and include non-pharmacological therapy, low-dose morphine and gabapentin.
Novel therapies are in development with P2x3 antagonists proving most promising.
Delivery of care of CC
Almost all CC can be dealt with in primary or secondary care.
Consider setting up a secondary care cough clinic.
Secondary care organisations should look to providing specialist speech and language therapy and physiotherapy as part of an MDT to support the diagnosis and management of cough and other upper airway disorders.
British Thoracic Society clinical statement on CC in adults
Introduction
CC represents a significant part of everyday practice for practitioners in primary and secondary care. Since the last British Thoracic Society (BTS) guideline on CC in Adults in 2006,4 there has been major progress in the diagnosis, and therapy of this condition but it remains a challenging area with a limited evidence base.5 6 Clinical advances, particularly the recognition of cough hypersensitivity syndrome and the use of appropriate drug and non-pharmacological cough treatment, has not yet embedded in most routine clinical practice in the UK. The objective of this statement is to distill recent progress into practical recommendations to improve the management of this common and frequently misunderstood disease.
Scope
This clinical statement provides practical advice for a wide range of healthcare practitioners in primary and secondary care looking after adult patients with CC. The causes of CC in children differ significantly to adults and has been addressed in a separate BTS guideline.7 8 This statement covers acute cough only briefly as it has been reviewed recently by a NICE guideline.9
Methodology
The Clinical Statement Group (CSG) was jointly chaired by SMP and JAS. Membership was drawn from respiratory medicine, general practice, physiotherapy, speech and language therapy, nursing, ear, nose and throat (ENT) and a trainee. Lay/patient input was received from patient groups linked to the statement authors. The CSG identified key areas requiring Clinical Practice Points. The overall content was developed to reflect the scope approved by the BTS Standards of Care Committee (SOCC) and methodology is described in the clinical statement production manual. Following discussions of broad statement content, individual sections were drafted by group members. A final edited draft was reviewed by the BTS SOCC before posting for public consultation and peer review on the BTS website in November 2022. The revised document was reapproved by the BTS SOCC in June 2023 before final publication.
Terminology, epidemiology and impact of CC
The cough reflex
Cough is a protective reflex, to prevent aspiration of foreign bodies and expectorate secretions. The airways are innervated by sensory neurons, activation of which is carried via the vagus nerve to the brain stem and higher centres (figure 1). Airway nerves sense irritant, noxious or mechanical stimuli through receptors on the nerve terminals (eg, TRPV1 and TRPA1). In health or disease states, stimulation of these receptors may lead to an ‘urge to cough’, associated with a tickle sensation in the throat leading to coughing.10 Receptors such as the ATP gated P2x3 ion channel can also activate airway nerves; ATP may be released by cell damage, inflammation and infection. Activation of cough peripheral nerve endings ultimately feeds into a complex central nervous system (CNS) network regulating the cough response. Within the CNS are important centres for the inhibition of peripheral excitatory inputs. Other anatomical areas innervated by the vagus nerve such as the ear (Arnold’s reflex) and oesophagus may contribute to cough sensitivity.
Neurophysiology of the cough reflex. Coughing is initiated by activation of vagal sensory nerve fibres in response to irritant chemicals (via ion channels such as TRPA1 and TRPV1) and mechanical stimuli that generate action potentials. In patients with RCC, activation of vagal nerves by ATP, through P2x3 ion channels is thought to be important based on the efficacy of novel P2x3 antagonist treatments. ATP is likely released from structural cells e.g. epithelium, through pannexin channels activated by other ion channels such as TRPV4 (J Allergy Clin Immunol. 2016 Jul;138(1):249-261.e12). Vagal nerve fibres important in mediating cough innervate the oropharynx, hypopharynx, larynx and proximal airways. They transmit action potentials to the medulla in the brainstem, where synaptic transmission activates sensory and motor pathways in the central nervous system. Opioids and gabapentinoids are thought to inhibit coughing in the central nervous system through activation of opioid receptors (μ,δ,k) and modulation of Ca2+ channels.
Terminology
Acute cough lasts ≤3 weeks and is usually self-limiting and due to a viral infection. CC lasts >8 weeks. Various terminology11 has been used to describe patients with persistent CC in the literature, commonly used terms in current use are RCC and refractory unexplained CC (table 1). This statement simplifies things. Where cough persists despite addressing comorbidities or where no comorbidities are identified the term RCC is used. RCC should be considered an open multidimensional label, whereby treatment is based on the phenotype of the patient and identified treatable traits will vary or be absent. In many patients, the primary disorder is a hypersensitivity of sensory nerves.
Terminology for chronic cough condition
Epidemiology
The community prevalence of CC is unclear, perhaps as high as 10%.12 13 Both sexes and any age may be affected but the condition appears most prevalent in later middle aged females.14–16 Many sufferers do not access medical services, tolerating symptoms or possibly self-medicating. UK-based primary care studies suggest CC affecting 1.2%–2%15 16 of the population but likely underestimates the prevalence due to coding issues. Factors associated with CC included cigarette smoking, obstructive airways disease, obesity, reflux,17 rhinitis and ACE inhibitor use.15 16 Many patients may have no identified comorbidity.13 15
Impact of CC
The impact on QoL is comparable to other respiratory diseases such as chronic obstructive pulmonary disease (COPD).18 Patients experience numerous unpleasant symptoms; throat discomfort, chest pain, exhaustion, dizziness, syncope and UI.19 Anxiety is common in CC20–22 alongside low mood, more likely if pre-existing depression23), fatigue, physical symptoms, negative illness beliefs and a lack of a clear illness narrative when their condition is unexplained. Concerns around serious underlying illness are common.22 Sufferers report embarrassment and significant social effort directed at managing negative reactions of others to the cough.24 Work absenteeism25 and primary care attendance is frequent.26 Repetitive investigations, trials of treatment and referrals to secondary care increase healthcare costs.15 The ‘over-the-counter’ cough remedy market is significant, around £400m/pa in the UK.
Clinical practice points
CC is common, predominantly affecting middle-aged females.
Sufferers experience significantly impaired QoL.
Cough is associated with increased healthcare costs.
Recent advances in the diagnosis and management of cough have not yet widely embedded in routine clinical practice in the UK.
Causes of CC
Moving beyond the anatomical diagnostic protocol
The usual approach to CC, advocated by consensus panels4 27 28 and informing most routine practice today, is based on the ‘anatomical diagnostic protocol’ developed in the late 1970’s. The approach assumes that cough is ‘caused’ by a well-defined group of comorbidities, particularly the familiar triad of asthma, upper airway disease and reflux. Early case series (no randomised controlled trials, RCTs) suggested a rigorous protocol of investigation and empirical treatment of comorbidities would cure most cases of cough. The anatomical diagnostic protocol has limitations29 30 and most importantly, a significant number of patients (30%–40%) do not get better with treating comorbidities or no obvious comorbidities exist.15 Clinicians often blindly treat possible causes of cough even when not indicated and RCT evidence suggests it is usually ineffective, for example, prescribing PPI’s in the absence of heartburn symptoms.31 Elements of this approach remain valid but need refinement.
Treatable traits and cough
This statement proposes to use the term ‘treatable trait’ to describe conditions that may cause cough. A trait is ‘a therapeutic target identified by phenotypes or endotypes through a validated biomarker’ and amenable to treatment. The biomarker could be any feature that can be objectively measured or evaluated.32 This approach has shown efficacy in airways disease,33 34 is grounded in routine clinical practice and allows an open, multidimensional assessment of the various factors that may be causing CC. Rather than labelling the patient as having ‘reflux cough’ or ‘upper airway cough syndrome’, consider using a general label (CC or RCC) and outlining contributing traits when describing a patient’s presentation, for example, ‘RCC with features of (1) reflux, (2) ACEI use, (3) obesity, (4) cough hypersensitivity, (5) dysphonia…etc. This approach is practical: (a) facilitating a precision medicine approach, treatment is not empiric, rather directed at specifically identified traits and (b) recognising the variable contribution of sometimes multiple common traits (presenting as diverse phenotypes). CC is not simply a symptom of traits such as asthma and reflux, etc, many patients with CC have an underlying hypersensitivity of the cough reflex. This is often overlooked, explaining to some extent why treatment protocols focusing on other comorbidities are sometimes ineffective (figure 2, table 2).
Treatable traits of chronic cough.
Treatable traits in chronic cough
CC as a neuropathic disorder
Increasing evidence supports the concept that dysregulation of the neuronal pathways controlling cough plays a role in patients presenting with CC and especially those with RCC.28 Patients cough in response to trivial exposures to environmental irritants (eg, perfumes, cleaning products), activities not usually evoking cough (eg, talking, laughing) and also without provocation, suggesting a cough hypersensitivity syndrome.10 35 Asthma, reflux and rhinosinusitis are associated with chronic coughing, but this presentation is atypical for these common conditions, suggesting additional processes are operating. Finally, evidence shows heightened experimentally evoked cough responses, increased CNS activity and reduced cough controls in CC patients, alongside clinical trials demonstrating the efficacy of a range of neuromodulating therapies.36–40 There is currently no objective test of cough hypersensitivity; the diagnosis is established by excluding a response to treatment of associated conditions.
Features of cough hypersensitivity are present in many respiratory conditions, not just CC (eg, asthma, COPD, idiopathic pulmonary fibrosis), and can be considered a treatable trait in its own right.32 41–43 In patients presenting with chronic dry cough as their main symptom, it is often the dominant trait. The nature of the neuronal dysregulation underlying cough hypersensitivity may vary. This may explain why in some individuals CC/cough hypersensitivity resolves with treatment of traits such whereas in others it does not. Treatments targeting the mechanisms underpinning cough hypersensitivity are needed.
Clinical practice points
Protocolised investigation and treatment of common comorbidities such as reflux, rhinitis and asthma is not always effective.
A ‘treatable traits’ approach is advocated, to guide personalised treatment.
Cough hypersensitivity is a frequently overlooked treatable trait for many patients and requires specific treatment including antitussives and non-pharmacological treatment.
Clinical assessment
Acute cough
Cough is common in primary care; the practitioner needs to differentiate rare serious disease from what can be safely managed. Most cough is acute (<3 weeks), self-limiting and due to a viral upper respiratory tract infection (URTI) causing a transient cough hypersensitivity.44 COVID-19 should be considered.45 Most cases settle in 7–10 days, but symptoms may persist for several weeks. There is no role for antibiotics (see NICE Cough (acute): antimicrobial prescribing guidance NG120 at online supplemental appendix 1 and accessed here https://www.nice.org.uk/guidance/ng120).9 Bacterial infection may cause acute bronchitis, antibiotics are usually not needed unless systemically very unwell or at high risk of complications.9 Inflammatory markers such as CRP46 and procalcitonin47 may guide decision-making. ‘Delayed’ antibiotic strategies with a postdated prescription for use if symptoms persist are as effective as immediate antibiotics.48 Prediction rules to identify those at highest risk are effective.49 Routine blood tests or CXR are not recommended in the absence of worrying/atypical findings.
Supplemental material
Treatment
Management prioritises reassurance and self-care (honey, OTC remedies).9 50 Evidence for effectiveness of OTC treatments is weak and many medications are likely no better than placebo.51 Careful explanation and ‘safety netting’ is good practice. A number of drugs are ineffective and should be avoided including; bronchodilators52 and inhaled/oral steroids53 54 (unless underlying asthma/COPD), non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines and decongestants,55 mucolytics, codeine56 and montelukast.57
Systematic assessment of the patient with CC
A systematic approach to management of CC is outlined in figure 3 (primary care) and figure 4 (secondary care).
Management of chronic cough in primary care. BEC, blood eosinophil count; COPD, chronic obstructive pulmonary disease; CXR, chest X-ray; FBC, full blood count; ICS, inhaled corticosteroid; ILD, interstitial lung disease; PPI, proton pump inhibitor;; TB, tuberculosis.
Management of chronic cough in secondary care. AFB, acid-fast bacteria; CPAP, continuous positive airway pressure; CXR, chest X-ray; FBC, full blood count; OSA, full blood count; PPI, proton pump inhibitor.
Most patients can be treated in primary care and all patients require a similar basic assessment. The process involves the recognition of serious disease and the systematic elimination and treatment of common traits causing cough. Some causes have an established and uncontroversial link with cough, others are more controversial and treatment may be less effective. Consider if cough hypersensitivity is a trait. Appropriate follow-up should be arranged to assess response to treatment trials.
History and examination
All patients should undergo a face-to-face history and thorough examination including the upper airway and ears. Crackles on auscultation may suggest interstitial lung disease and requires prompt referral. Differentiating serious from non-serious causes of cough can be challenging.58 figure 3 shows red flag features requiring urgent CXR and/or urgent hospital referral. A normal CXR does not exclude lung cancer,59 refer/investigate if there is any concern. Prediction tools can be helpful.60
The history can be quite non-specific.61 Try and identify obvious aggravants such as smoking, ACE inhibitor use, recent viral infection, underlying disease (COPD, etc) and treatable traits. Consider occupation and if the symptoms are work related. Environmental factors such as air pollution may be relevant.62 Ask about the duration of symptoms. The patient should describe the cough in their own words. Clarify that the patient is coughing and not throat clearing (frequently coexists). Productive cough, particularly if sputum is thick or discoloured, suggests possible airways disease or infection. Many patients describe minimally productive (modest amounts of clear/white sputum) or dry cough. Associated symptoms (wheezing, rhinitis, heartburn, etc) suggest an underlying cause. Consider possible symptoms of cough hypersensitivity. Ask about impact on QoL, complications of chronic coughing and effects on mood.22 24 63 64 Several validated tools exist to measure cough frequency65 66 and QoL, but they are largely research tools and their clinical utility is unclear.67
Basic investigations
All patients with CC should have; CXR, Spirometry (and preferably reversibility testing) to look for evidence of underlying airways disease. Sputum culture if infection is suspected. FeNO and BEC to identify eosinophilic/T2 high airway disease that may benefit from inhaled steroid treatment.
When should I refer the patient from primary to secondary care?
Individuals who continue to cough despite treatment, if the diagnosis is unclear or there is suspected underlying disease such as bronchiectasis, interstitial lung disease, TB and heart failure. Red flag symptoms suggestive of malignancy should be referred urgently according to NICE guidelines.1 Patients will usually be seen in a respiratory clinic, but refer appropriately depending on the presentation (eg, refer to ENT service if predominant upper airway symptoms such as nasal obstruction and discharge and voice change).
Further investigations
CT scan
Chest CT scans should not be ordered routinely. Radiation exposure should be minimised,68 and the relevance of abnormalities picked up when performed routinely is questionable.28 69–71 CT scans should be used to look for evidence of disease when indicated, for example; in chronic productive cough to exclude bronchiectasis,72 to exclude a neoplasm if lung cancer is suspected and/or the patient is in a high risk group (pick up rate 1%–2%),69 haemoptysis and a ‘barking cough’ suggestive of airway collapsibility (dynamic expiratory CT).73
Bronchoscopy
There is no role for routine bronchoscopy for most patients with CC but may be helpful in some circumstances.74 Tracheal abnormalities may be picked up (eg, tracheopathia osteochondroplastica, airway collapsibility and tracheobronchomalacia).74–76 Consider when (a) productive cough and no clear cause, (b) suspicion of airway collapsibility (‘barking’ quality to cough±relevant CT findings), (c) a foreign body and (d) to exclude infection and assess airway secretions when sputum culture is unhelpful/not possible.
Flexible nasendoscopy and laryngoscopy
Flexible nasendoscopy and laryngoscopy allows direct visualisation of the nasal passages and larynx and may be indicated in some patients with CC: (a) symptoms of rhinosinusitis/rhinitis despite treatment, (b) hoarse voice symptoms and (c) where inducible laryngeal obstruction (ILO) is suspected.77
Investigations not indicated in CC
Methacholine/mannitol challenge tests for bronchial hyperreactivity are of limited value in the management of cough. Cough challenges (eg, capsaicin) are research tools and should not be used to diagnose RCC.78 Further research is needed to determine if a cough challenge agent and protocol might discriminate between RCC and other causes of cough.79
Secondary care assessment
Secondary care assessment (figure 4) should: (a) clarify the diagnosis, particularly the recognition of cough hypersensitivity, (b) reassure when no serious disease is present, (c) help patients understand their condition and (d) provide targeted treatment. Clinicians should try and break the often-repetitive cycle of investigations, empirical treatment and worry experienced by these patients. The degree to which patients have been investigated is variable79 so basic tests may be required. Further investigations depend on the individual’s presentation.
Clinical practice points
Establish who needs specialist referral or can be initially managed in general practice with a targeted trial of therapy. ‘Red flags’ should prompt urgent referral in line with NICE guidelines.1
The history should identify possible underlying disease and treatable traits.
All patients with CC should have a CXR, FBC, diagnostic spirometry and FeNO (if available).
CC in a patient with a normal CXR and no response to treatment of known or suspected triggers should be referred on to secondary care.
Treatable traits in cough
Smoking
Smoking cessation improves cough by resolving chronic bronchitis.80 Nicotine withdrawal due to smoking cessation may enhancement cough hypersensitivity,81 hence patients may experience more coughing for a period after quitting. This can be attenuated and quit rates improved by using nicotine replacement. There are a number of interventions that can help smokers quit outlined in NICE guidelines.82
ACE inhibitors
ACE inhibitor medication induces cough hypersensitivity83 and should be discontinued in all patients, regardless of the underlying cause of cough or temporal relationship with symptoms.
Airway disease
If airway disease is suspected, the ‘treatable traits’ approach is advocated; identifying and optimising treatment of pulmonary, extrapulmonary and behavioural traits, well described elsewhere32 33 and in disease-specific guidelines.72 84 85 Optimising airway disease treatment is usually the key to managing cough in these patients. Cough hypersensitivity may be a trait in airway disease and need additional specific treatment. Some relevant traits are described in figure 2 and table 2.
Productive cough
Chronic productive cough is managed differently to a dry or minimally productive cough. The condition is not well understood. Patients suffer adverse health outcomes regardless of co-existent airflow limitation or smoking status.86 Consider early high-resolution computed tomography (HRCT) and sputum culture. Look for bronchiectasis and other airway disease (asthma, COPD), cigarette smoking, environmental exposure (dusts), immune deficiency and possible tracheal abnormalities (eg, tracheopathia osteochondroplastica, airway collapsibility and tracheobronchomalacia). Bronchoscopy may be helpful for some patients.74 An ‘idiopathic productive cough’87 88 phenotype has been described, with persistent airway infection, relatively preserved lung function, neutrophilic airway inflammation and no clear radiological bronchiectasis.
Treatment
There is limited evidence89 so therapy is pragmatic; focus on optimising any underlying condition, treating airway infection, mucolytic therapy (eg, Carbocisteine 750 mg three times a day), and refer to physiotherapy to teach airway clearance techniques.90 Consider a trial of hypertonic saline. There is some evidence to support the use of low dose macrolide treatment91 for patients with productive cough that persists despite these interventions (eg, azithromycin 250 mg three times per week could be used initially with subsequent titration to 500 mg depending on clinical response). Macrolides should only be used for productive CC or where there is underlying airway disease as they are ineffective in patients with a dry/non-productive RCC.92 93 Macrolides should be initiated after assessment in secondary care. Appropriate follow-up and precautions should be taken when commencing macrolide treatment in line with current BTS guidance.94
Eosinophilic airway disease
A common cause of cough and amenable to treatment. Encompasses various labels including ‘classic’ asthma, ‘cough variant asthma’95 and ‘non-asthmatic eosinophilic bronchitis96 and may complicate other airway disease categories (COPD, bronchiectasis). Significant (>3%) sputum eosinophilia is the diagnostic gold standard but is technically challenging and not widely available. FeNO levels and peripheral BEC indirectly estimate airway eosinophilia but this is a difficult area and FeNO is affected by various factors (elevated in allergic rhinitis, atopy and eczema, reduced in smokers, variably affected by viral infections).97BTS,84 NICE,98 ERS99 and Global Initiative for Asthma (GINA) guidelines consider elevated FeNO levels (NICE and ERS specify >40 ppb, GINA a lower level of >20 ppb) supportive of a diagnosis of (T2 high) asthma in an individual with typical symptoms.
The usefulness of these markers in predicting response to ICS in CC is uncertain. A recent meta-analysis noted the response rate to ICS treatment was significantly higher if FeNO was >25 ppb (OR 13.5, sensitivity=77.4%, specificity=81.3%),2 therefore, a FeNO>25 ppb should prompt a trial of ICS. A FeNO<25 ppb is associated with a low rate of ICS response so ICS should be avoided unless there are other factors to suggest eosinophilic airway disease.
A raised BEC (≥0.3×109/L) is supportive of a diagnosis of eosinophilic airway disease but not sensitive or specific enough to make a diagnosis alone84; one study reported a weak correlation with treatment response.100
Treatment
In patients with CC and no other features of airway disease, normal spirometry and low T2 biomarkers avoid the use of ICS and consider alternative causes.
In patients with other features of airways disease, optimise any traits and manage in line with published disease specific guidance. Consider a 1- month trial of ICS, for example, budesonide DPI 200 μg two times per day or equivalent.
Cough with no other symptoms or airflow obstruction and raised T2 biomarkers (FeNO>25 ppb and BEC≥0.3×109/L). Consider trial of ICS for 4 weeks.2 If response is incomplete, assuming inhaler technique and compliance are adequate, consider escalating treatment, for example, double dose of ICS or add a LTRA3, for example, montelukast 10 mg nocte or equivalent. Also consider trial of oral corticosteroids, for example, prednisolone 30 mg once a day for 2 weeks, and consider poor compliance if markers remain high.
Gastro-oesophageal reflux disease
An area of considerable controversy, gastro-oesophageal reflux has long been associated with CC. Whether it is a major cause or just another aggravant in patients with cough hypersensitivity remains a matter of debate.101 102
Acid reflux
PPIs continue to be prescribed to treat CC, based on uncontrolled observational studies. RCTs of PPIs, generally underpowered and of variable quality, have not demonstrated efficacy.31 103 Reanalysis of pooled data from the studies using 24-hour pH monitoring to characterise reflux, found therapeutic gain was greatest in patients with pathological oesophageal acid exposure.104 PPIs are not likely to benefit most patients with cough and long-term use risks side effects (osteoporosis, infections, kidney disease).105 A small subgroup may respond but evidence is weak. The presence of heartburn is the best indication for PPI treatment but the response rate is still low (28%).106 No measure of reflux or questionnaire in CC patients predicts who will respond to acid suppression.
Non acid reflux
There is much speculation about the roles of micro-aspiration, oesophageal dysmotility and other types of reflux (weakly acid, non-acid, gaseous and laryngopharyngeal).107–109 Microaspiration has been proposed to drive chronic coughing but objective studies utilising biomarkers (pepsin, bile acids) have consistently failed to show elevated levels in CC patients compared with healthy controls. Oesophageal dysmotility is frequently observed110 111 and may reflect a broader autonomic disturbance.112 There are no good quality trials of prokinetic medications and use is limited due to side effects.
Studies evaluating reflux events in CC patients show the number of reflux events is elevated compared with healthy controls but still within normal limits.113 114 Also, irrespective of acidity, reflux precedes cough more frequently than expected by chance alone, in keeping with a generalised propensity for physiological levels of reflux to evoke coughing in CC.113 114 Reflux events extending to the proximal oesophagus are no more likely to evoke coughing than those confined to the distal oesophagus. Reflux reaching the larynx/pharynx and gaseous reflux are challenging to measure reliably, hence conclusions are difficult to draw about their importance. Notably, a recent study of GABAb antagonism (lesogaberan) which reduces relaxations of the lower oesophageal sphincter and therefore reflux of all types, had little effect in patients with RCC; an insignificant reduction in cough frequency of ~25%.115 This would imply that reflux events, regardless of their nature are unlikely an important driver in this patient group.
Treatment
Recommendations are made based on evidence in patients with typical reflux symptoms (eg, heartburn, regurgitation, upper abdominal/chest pain or discomfort).116 The best predictor of treatment response is the presence of heartburn.106 Treatment should not be prescribed to patients with CC in the absence of these symptoms.
Lifestyle measures including weight loss, dietary modification (not eating before bedtime, reduction of acidic, fatty or spicy foods and carbonated drinks) and raising the head of the bed may be valuable.
Trial of twice daily standard dose PPI for 1 month only in patient with heartburn and the dose only increased to control heartburn, for example, Lansoprazole 30 mg two times per day or equivalent. Most effective if taken regularly 30–60 min before meals.117 Discontinue if no effect after 1 month. Rebound heartburn occurs in the first few days after discontinuation and does not necessarily imply long-term treatment is required.
Histamine-2 receptor antagonists taken at bedtime might be beneficial for nocturnal reflux symptoms but evidence is weak.118
Weak evidence for using prokinetic drugs, should not be used routinely for cough and use restricted to specialist services due to potential side effects.119 120
Alginates are frequently used in ENT practice to treat ‘laryngopharyngeal reflux’. The only placebo controlled study is negative121 122 and the findings from an ongoing placebo controlled RCT of alginates in patients with throat symptoms are eagerly awaited.123 There is almost no evidence in cough and no RCTs. Observational studies showing efficacy124 are of limited value given the prominent placebo effects seen with cough treatments. Alginates are well tolerated and effective for typical reflux symptoms such as heartburn so may be prescribed for that. They are not indicated for cough where there are no typical reflux symptoms.
Further investigations, including upper gastrointestinal endoscopy and oesophageal manometry plus either 24 hours oesophageal pH-impedance monitoring or 96 hours wireless oesophageal pH capsule monitoring (BRAVO), should be reserved for patients with refractory reflux symptoms (ie, heartburn, regurgitation) and those requiring high doses of acid suppression to maintain symptom control.116 Gastroenterology/upper GI surgery advice on management should also be sought.
Laparoscopic fundoplication is effective for gastro-oesophageal reflux disease but frequent complications include reflux recurrence, needing further surgery,105 dysphagia (11%), bloating (40%) and flatulence (57%).125 A meta-analysis of the numerous published case series in CC (61 studies, 3869 patients)126 suggested impressive outcomes but should be interpreted cautiously. Studies were of low quality, no RCTs and none using validated cough measures. There is good quality evidence to support fundoplication in patients with ongoing symptoms of heartburn and regurgitation, who have abnormal reflux on oesophageal studies, no significant dysmotility and have not responded to or are intolerant of lifestyle measures and acid suppression treatment. It is reasonable to consider fundoplication for patients in this group who also complain of cough but careful assessment and patient counselling is required.127 Fundoplication cannot be recommended for the treatment of cough alone in the absence of typical reflux symptoms and objective evidence of reflux.
Upper airway symptoms
A frequent diagnostic label in cough with a geographic variation in incidence,128 the ‘upper airway cough syndrome’ encompasses numerous symptoms. Diagnostic criteria have been unclear and diagnosis based on the response to first generation antihistamines, which may have central antitussive effects.129 Upper airway/nasal disease is frequent in CC patients130 131 and other airway disease, making it unclear whether coughing arises from upper or lower airways. Convergence of trigeminal and vagal afferents in central cough pathways132 133 provides a possible mechanistic/neuronal link between upper airway disease and the development of cough hypersensitivity.
Nasal disease
In association with global airways inflammation and cough should preferably be referred to as CRS. In adults, CRS is a symptom-based diagnosis defined as the presence of two or more symptoms for ≥12 weeks, one of which should be either nasal blockage or nasal discharge (anterior or posterior), with or without facial pain/pressure or reduction or loss of smell.134 It can be difficult to discriminate between allergic rhinitis, non-allergic rhinitis and CRS. Allergic rhinitis symptoms include rhinorrhoea (anterior or posterior), nasal congestion, nasal itching, itchy eyes and sneezing. Radiological investigations may be useful and guided by nasal symptoms. Incidental sinus changes may be present in up to one-third of CT scans135 and two-thirds of MRI scans.136
‘Post nasal drip’ (PND) can be a symptom of underlying CRS and accompany persistent throat symptoms. There is doubt about the relationship with CC.137 Only a minority of patients with demonstrable post nasal secretions, secondary to infective CRS, report cough as a symptom.138 When PND was mimicked by inserting hyperviscous solution into the nasal cavities of CRS patients and controls, coughing was not evoked.139
Throat symptoms
Many patients report persistent throat symptoms despite a normal otolaryngology examination; a feeling of a lump in throat (globus), dysphonia, throat mucus or ‘phlegm’, ‘catarrh’ or mucus entering the throat from the nose, throat clearing, throat discomfort, irritation, tickling and choking. These symptoms often coexist with CC and may represent a unifying underlying condition.140 141 Attributed to underlying gastro-oesophageal reflux in the otolaryngology literature for many years,142 143 ‘laryngopharyngeal reflux’ has remained a popular label to group these symptoms together, despite the lack of evidence supporting this mechanism and lack of effect of reflux treatment.144 Clinicians should explore other potential causes of chronic throat symptoms that have received little attention in the face of the reflux aetiology theory. Psychological distress,145 obesity,146 life events,147 148 snoring, upper airway dryness, hormonal changes and laryngeal hypersensitivity have all been associated with chronic throat and voice symptoms.149 Laryngeal hypersensitivity could be a common mechanism.150
‘Red flag’ symptoms suggestive of malignancy/demonstrable pathology are persistent dysphonia (every word of every sentence, not chronicity) or progressive dysphagia±localised pain; risk being greatest in smokers >45 years. Functional symptoms are more intermittent in nature.
ILO is defined as ‘inappropriate laryngeal closure at the glottic and/or supraglottic level, which leads to dynamic airflow obstruction and causes breathing difficulties’. Previously referred to as ‘vocal cord dysfunction’. It may manifest as cough, wheeze, breathlessness and voice disturbance. Symptoms may be episodic, usually inspiratory and associated with certain triggers. ILO can coexist with a number of conditions including asthma and CC. In a tertiary RCC population, ILO is a common finding151 152 often associated with voice disturbance and breathing pattern disorder and may be a manifestation of laryngeal hypersensitivity.153 Diagnosis is confirmed by functional laryngoscopy154 and treatment is by speech and language therapy intervention.
Treatment
Evidence is limited, only uncontrolled case series suggest that nasal steroids improves cough symptoms.155 156 For cough patients who report symptoms of CRS, treatment should include an intranasal steroid spray with saline irrigation/rinses for a minimum of 6 weeks, for example, mometasone furoate nasal steroid spray 100 μg two times per day, following the saline douching, reduced to 100 μg once daily thereafter. Antibiotics should be avoided. Secondary care referral should be considered if the nasal symptoms are not improved after 12 weeks of therapy.
A recent large UK multicentre RCT (Trial Of Proton-Pump Inhibitors in Throat Symptoms) found that lansoprazole 30 mg two times per day conferred no benefit over placebo.157 PPIs should not be used to treat upper airway symptoms.
Consider treatment of laryngeal hypersensitivity (see management of cough hypersensitivity)
Obstructive sleep apnoea
The prevalence of OSA in the CC population may be significant (reportedly 39%–68%158 159) and CC is common in sleep clinic populations.160 161 CPAP therapy improved cough related QoL in uncontrolled studies.160 A single-centre RCT comparing CPAP with sham treatment showed a significant improvement in cough-related QoL but unfortunately did not record any objective cough counting data.162 OSA may enhance cough hypersensitivity via associated gastro-oesophageal reflux, rhinitis,163 164 upper respiratory tract irritation and consequent inflammation.160 162 Patients with cough may have obvious risk factors for OSA (snoring, excessive daytime sleepiness, obesity) but may not be sleepy and other more common causes of cough should be considered. OSA should be considered a possible treatable trait when assessing patients with CC.
Treatment
If OSA is suspected, patients should undergo a sleep study and if appropriate a trial of CPAP. The success rate of CPAP therapy for CC is unknown and patients may struggle to tolerate therapy unless there is a marked and obvious improvement, which may be difficult to achieve in patients who aren’t sleepy. Larger multicentre trials using objective cough recording are required to better assess the impact of intervention.
Obesity
A number of studies have suggested a link between obesity and CC.165 166 Obesity was more common in patients attending specialist care for CC (24.3% vs 19% in controls).167 Large population studies offer conflicting results,17 168most compelling is the Copenhagen General Population Study,169 7.4% of obese individuals had a CC, compared with 4.2% in the non-obese group. The prevalence of cough increased with increasing body mass index. The main mediator of increased risk appeared to be gastro-oesophageal reflux disease. A study of patients seen in secondary care with CC suggested a higher incidence of reflux in obese patients and better response of cough to PPI treatment.170 Another possible mechanistic link is OSA (as outlined above) and possibly type two diabetes.166 The role of weight loss as a treatment for CC has not been studied directly although weight loss improves OSA and gastro-oesophageal reflux.166 It is not unreasonable to consider obesity as a potential treatable trait in patients with CC and recommend weight loss strategies as part of a treatment plan.
Clinical practice points
Smoking
Smoking cessation will reduce cough as chronic bronchitis resolves. Nicotine suppresses the cough reflex. Nicotine replacement therapy may prevent a rebound in cough hypersensitivity and worsening symptoms.
ACEI treatment
Stop in all patients with CC. Switch to an A2RB if needed. Improvement may take 4 weeks or more.
Airway disease: productive cough
Productive cough is managed differently to a dry or minimally productive cough.
Look for infection, smoking and airways disease, particularly bronchiectasis.
Optimise airway clearance, treat infection. Consider low-dose macrolide therapy, for example, Azithromycin 250 mg three times per week initially, titrating up to 500 mg three times per weekdepending on clinical response (not to be used in chronic dry cough).
Eosinophilic airway disease
In patients with cough and no other features of airway disease, with normal spirometry and low T2 biomarkers, avoid the use of ICS and consider alternative causes.
In patients with other features of airways disease, optimise any traits and manage in line with published disease specific guidance. Consider a 1- month trial of ICS.
Cough with no other symptoms or airflow obstruction and raised T2 biomarkers (FeNO>25 ppb and BEC≥0.3×109/L). Consider short trial of ICS for 4 weeks,2 for example, budesonide DPI 200 μg two times per day or equivalent.
If response is incomplete, consider add on treatment, for example, double dose of ICS or add a LTRA,3 for example, montelukast 10 mg nocte. Also consider a short trial of oral corticosteroids (eg, prednisolone 30 mg once daily for 2 weeks) and consider compliance if markers remain high.
Gastro-oesophageal reflux disease
A difficult area. Physiological levels of reflux can stimulate episodes in CC patients.
Only treat with PPIs if patient has heartburn or other definitive evidence of acid reflux, for example, lansoprazole 30 mg bd or equivalent for 4 weeks. Most patients do not respond.
Fundoplication cannot be recommended for the treatment of cough alone in the absence of more typical reflux symptoms and objective evidence of reflux.
Upper airway symptoms
Symptoms of CRS should prompt an empirical trial of a nasal steroid.
PPIs are not beneficial for throat symptoms.
Laryngeal dysfunction and hypersensitivity are common in CC.
Obstructive sleep apnoea
Consider OSA as a potential treatable trait in refractory cough. CPAP treatment might improve CC if there is objective evidence of OSA on a sleep study.
Obesity
Obesity is associated with CC. Weight loss should be recommended in obese patients and might improve CC.
Complications of cough
Urinary incontinence
CC can contribute to the development of stress UI. Predominantly affecting females and often under reported due to embarrassment, many patients go untreated. UI is associated with worse QoL and may impact on psychological health.64 The impact of specific interventions for UI is unknown and the focus is usually on treating the cough. Specific interventions, including the input of a nurse specialist and pelvic health physiotherapy, to aid continence may also be beneficial.171 A trial looking at the impact of the antitussive, gefapixant, in females with UI is ongoing.172
Cough syncope
Cough syncope is a relatively uncommon63 but consequences can be severe, particularly the potential for serious motor vehicle accidents. Increased intrathoracic pressure during coughing reduces cerebral blood flow173 via cardioinhibitory baroreflex activation, peripheral vasodilatation and impaired responses to hypotension174–177 resulting in syncope. The diagnosis is usually clear from the history and the focus is on (a) diagnosing and treating the cause of the cough and (b) ensuring the patient is informed about restrictions on driving. There may be a number of specific conditions associated with cough syncope that should be considered.63 In the UK, the DVLA provides clear rules regarding driving after cough syncope. A patient who has suffered even a single episode of cough syncope, regardless of cause, should be advised not to drive and that they must inform the DVLA of their condition. https://www.gov.uk/guidance/neurological-disorders-assessing-fitness-to-drive%23cough-syncope for further information.178
Clinical practice points
Patients who suffer cough syncope should be advised not to drive and contact the DVLA. See https://www.gov.uk/guidance/neurological-disorders-assessing-fitness-to-drive%23cough-syncope for further guidance.
All patients presenting with CC should be asked if they are experiencing any symptoms of UI.
All patients reporting UI should be referred to their local MDT incontinence service for further specialist input and support.
Management of cough hypersentivity
For patients with RCC, neuromodulating treatments targeting cough hypersensitivity are needed. Unfortunately, at present, no treatments are licensed, but novel therapies are in development and non-pharmacological techniques have been found to have efficacy. Some unlicensed neuromodulator therapies are also beneficial. Cough treatments are likely to work via complex mechanisms and significant placebo effects are common.179
Non-pharmacological treatment
A complex intervention,180 developed by speech and language therapists but also delivered by physiotherapists, based on techniques that actively suppress coughing. There are two RCTs and a number of observational studies showing efficacy.181–185 The PSALTI study showed a 40% reduction in cough frequency and improved QoL compared with sham therapy. Most patients respond186 but the long-term effect is unknown. Can be complimentary to pharmacological treatment187 and allow a reduction of pharmacological treatment. It is best delivered by therapists experienced in managing CC. Not widely available, this statement urges all secondary care organisations to look at ways of providing this therapy, preferably as part of an ‘upper airway service’ also diagnosing and treating ILO. Group therapy can be a cost-effective way of delivering treatment.188
Pharmacological treatment
Less evidence supports the use of pharmacological therapies for RCC and few studies have used validated endpoints. Initiation should usually be in secondary care only.
Opioids
Low-dose slow-release morphine sulphate 5–10 mg two times per day has been shown in an RCT to improve cough specific QoL,40 and in patients reporting a clinical response, 24 hours cough frequency was reduced by 71% over placebo.189 The main side effect is constipation, managed with laxatives or the addition of oral naloxone. Around 50% of patients report benefit usually within about 5 days.130 Once daily dosing may be sufficient if cough symptoms are mainly troublesome during waking hours or overnight. Symptoms quickly return if treatment stops, so long-term use is required to maintain effects. Tolerance does not seem to occur and doses above 10 mg bd should not be needed. Concerns remain about abuse/addiction potential and patients should be carefully monitored.
Codeine has frequently been used as an antitussive. It is a weak opiate with variable and unpredictable metabolism into active components including morphine.190 Clinical trials show it is ineffective in treating acute cough due to URTI56 191 and in patients with COPD.192 It is unlikely to be a reliable antitussive and should not be used.
Gabapentinoids
Gabapentin improved cough-specific QoL in a single RCT.193 A second study assessed the effects of pregabalin versus placebo as an adjunct to non-pharmacological therapy, but found the effects confined to improvements in cough severity and QoL without a change in cough frequency.187 Gabapentinoids have beneficial effects on anxiety and therefore improvements in mood may have contributed to the apparent benefit or changes in symptom perception or cough intensity. Side effects are common, wide ranging and can be difficult for patients to tolerate. Escalating the dose slowly may help minimise these and maximal doses may not be needed to afford some improvement in cough. Gabapentin and pregabalin are classed as controlled medicines in the UK due to the potential for misuse and addiction.
Gabapentin should be started at a low dose, for example, gabapentin 100 mg three times a day and then titrated up to a maximum dose of 600 mg three times a day depending on clinical effects and side effects.
Pregabalin 25 mg two times per day initially and increase in increments to 75 mg two times per day.
Patients should be reassessed during does titration and therapy stopped if there are significant side effects or inadequate response to treatment.
Other neuromodulator therapies
A single study of low dose amitriptyline (10 mg once daily) reported significantly improved cough over a combination of codeine/guaifenesin in a randomised trial of patients with CC.194 Clinical experience, however, suggests more limited value. Baclofen has also been reported to have comparable effects to gabapentin in one trial but causes significant somnolence, dizziness and seizures on sudden withdrawal.195
Novel therapies
Significant effort has been invested in the development of novel therapies for RCC in recent years, following the first report of the positive effects of a P2x3 antagonist196 Subsequent studies have confirmed efficacy of gefapixant in RCC39 197 198; however, disturbances in taste are a common side effect. More selective P2x3 antagonists are effective with less taste disturbance.199–202 There are currently ongoing clinical trials of camlipixant but the development of eliapixant and sivopixant has been halted. Placebo effects in more recent trials have made demonstrating treatment effects more challenging. The potential effects of P2x3 antagonists outside of RCC is largely unexplored apart from one study in idiopathic pulmonary fibrosis which gave borderline results.203 Licensing of gefapixant in the USA has been held up by the FDA, but the drug is currently used in Japan and recently been approved for use in refractory cough by regulatory authorities in the EU.204
Other promising agents currently being investigated include a TRPM8 (menthol receptor) agonist205 and mixed findings for neurokinin one receptor antagonists.206 207 There have been negative trials of several TRP receptor antagonists208–210 and a negative trial of a nicotinic receptor antagonist.211 The dual-acting ƙ opioid receptor agonist/µ opioid receptor antagonist nalbuphine has demonstrated impressive effects on IPF cough in phase 2 studies, further clinical trials are awaited including for RCC.212
Clinical practice points
Cough hypersensitivity is a treatable trait of many conditions and often the foremost problem in patients with chronic dry/minimally productive cough.
There are currently no tools to positively identify cough hypersensitivity.
Cough hypersensitivity may improve with treatment of other treatable traits, if not the patients has RCC.
In RCC, the most effective treatments are those addressing cough hypersensitivity and include non-pharmacological therapy, low-dose morphine and gabapentin.
Novel therapies are in development with P2x3 antagonists proving most promising.
Delivery of care for CC
Delivering care for patients with CC
The healthcare systems across the UK are largely similar but local healthcare needs and how they are met vary considerably. Clinical assessment of cough does not require particularly specialised procedures or equipment and is focused on a thorough and systematic clinical assessment. Cough can almost always be dealt with quite adequately in general practice or a secondary care. There are a small and increasing number of tertiary cough clinics in the UK, often with a research focus, which have evolved ad hoc.
Increasingly secondary care organisations have merged, and consultants work in large teams. This allows subspecialisation and development of special interests such as cough clinics. Work is simply redirected from general clinics to a cough clinic, there should not be any resource implications here and a special ‘business case’ should not be needed. A cough clinic offers advantages; the development of expertise and confidence in managing this difficult condition develops a better understanding of cough phenotypes/treatable traits, particularly the recognition of cough hypersensitivity. This allows a focus on treatments aimed at reducing cough hypersensitivity and draws a line under repetitive investigations and empirical treatment trials. Recruitment into clinical trials of novel antitussives can be beneficial for patients when other measures have not been helpful. Trainees attending a cough clinic will get focused training in this area.
Care for patients with CC is multidisciplinary. Specialist nurse input is beneficial and the role should be developed.171 Access to specialist speech and language therapy and physiotherapy is essential for delivering non-pharmacological cough control therapy alongside the assessment and treatment of ILO and breathing pattern disorder. Speech and language therapy services, particularly voice therapy, have been delivering ‘vocal hygiene’ and similar therapy for cough to ENT clinics for some time so local expertise may already exist. Speech and language therapy provision is likely to become a vital component of all respiratory MDTs over time, not just tertiary services. Workforce planning within organisations should reflect this, but access to funding to deliver this within the UK remains challenging. Delivering this effective treatment should be economically beneficial over time by delivering effective therapy and minimising repetitive healthcare use by sufferers. The Royal College of Speech and Language Therapists have now formally identified the role of speech and language therapy in upper airway disorders within adult respiratory services and the RCSLT 2021 position paper recommends, as a minimum care standard, equitable patient access to appropriately trained staff for those individuals suffering with CC. The RCSLT position paper and this document should be used to support service development.213
Clinical practice points
Almost all CC can be dealt with in primary or secondary care.
Consider setting up a secondary care cough clinic.
Secondary care organisations should look to providing specialist speech and language therapy and physiotherapy as part of an MDT to support the diagnosis and management of cough and other upper airway disorders.
Research
As evident in this document, high-quality evidence for the current clinical management of patients with CC is scant, and therefore, numerous opportunities exist to advance knowledge in this field. The development of validated tools to assess cough provides the ability to better evaluate therapies targeting treatable traits and, perhaps more importantly, identify predictors of treatment response that could guide therapy and improve the patient experience.
The development of P2x3 antagonists as the first novel, effective therapies for RCC has the potential to substantially improve the care of patients with RCC, assuming licensing of these treatments becomes widespread. However, treatments using other mechanisms to address cough hypersensitivity are required, as 25%–30% of patients in clinical trials did not gain clinical meaningful improvements and the trials did not include those with less severe RCC. Care would also be improved by the optimisation/standardisation of non-pharmacological treatment. Including only the most effective components would likely facilitate more extensive adoption.
Finally, currently the diagnosis of RCC is a diagnosis of exclusion. This inevitably produces difficulty in establishing this diagnosis, the expense associated with investigations/treatment trials and prolongs the time to reach this diagnosis for patients. A better understanding of the mechanisms underlying cough hypersensitivity and the identification of biomarkers capable of positively identifying this trait has the potential to transform the management of CC for patients and clinicians and should also be a focus of future research efforts.
Ethics statements
Patient consent for publication
References
Footnotes
Twitter @drsmparker, @jemhaines, @MancRespDoc
SMP and JAS contributed equally.
Contributors SMP and JAS were joint chairs of the clinical statement group. All authors (SMP, JAS, SSB, SC-M, KG-J, JH, SH, LPM, PM, MJM, AM, JO'H and MT) contributed to the development of the statement.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Disclaimer A Clinical Statement reflects the expert views of a group of specialists who are well versed in the topic concerned, and who carefully examine the available evidence in relation to their own clinical practice. A Clinical Statement does not involve a formal evidence review and is not developed in accordance with clinical practice guideline methodology. Clinical Statements are not intended as legal documents or a primary source of detailed technical information. Readers are encouraged to consider the information presented and reach their own conclusions.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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