Key questions on persistent cough in adults

In our latest CPD module, Professor (Hon.) James Hull, consultant pulmonologist and lead for the chronic cough service at Royal Brompton Hospital in London, answers key questions on persistent cough. Complete the full module on Pulse 365 today

Persistent cough is a common but challenging presentation in primary care, with causes ranging from post-viral symptoms and medication effects to asthma, reflux, upper airway disease and serious underlying pathology. This module provides a practical, evidence-based approach to assessing adults with cough lasting more than eight weeks, explaining how GPs can use a ‘treatable traits’ model to identify contributors, select appropriate investigations and avoid unhelpful empirical treatment.

The module also explores cough hypersensitivity and the role of ACE inhibitors, airway eosinophilia, reflux, rhinosinusitis and laryngeal dysfunction in persistent cough, alongside red flags for lung cancer and other respiratory disease. It highlights commonly overlooked causes, clarifies when imaging and specialist referral are indicated and offers pragmatic advice for managing patients whose cough persists despite initial treatment.

Learning objectives

This module will enhance GPs’ understanding of chronic cough in adults, including:

How to consider and evaluate the cause of chronic cough.
An introduction to the concept of cough hypersensitivity.
The value of using a ‘treatable traits’ model to assess a patient with chronic cough.
When and how to undertake investigations for chronic cough.
Some commonly overlooked issues when assessing chronic cough in primary care.

1. When would you view an adult cough as ‘persistent’, and how does the differential change as the duration increases?

Typically, cough is defined as being acute, subacute and chronic, depending on the duration of symptoms, with acute cough lasting less than three weeks and chronic cough lasting longer than eight weeks.

Acute cough is frequently seen in association with common respiratory tract infections, such as those with viral aetiology. However, there are other causes of acute cough including aspiration (more commonly seen in paediatrics) or certain inflammatory processes, as in forms of interstitial lung disease.

Cough persisting longer than eight weeks should prompt consideration of the presence of lung disease and importantly investigations to rule out a pulmonary disease process, including consideration of neoplasm or interstitial lung disease.

Recently, there has been focus on differentiating chronic cough by response to treatment and other characteristics and thus a variety of terms are used (Table 1).¹

Term	Definition
Acute cough	Cough lasting <3 weeks
Chronic cough	Cough lasting >8 weeks
Refractory chronic cough (RCC)	Cough persists despite addressing treatable traits. May have symptoms suggestive of cough hypersensitivity.
Unexplained chronic cough (UCC)	A term used in clinical trials. Unexplained; no treatable traits but may have symptoms suggestive of cough hypersensitivity.
Cough hypersensitivity syndrome	Disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure. Thought to be mediated by sensitisation of the sensory neuronal pathways controlling cough including the vagus nerve and central nervous system.
Laryngeal hypersensitivity	Neuronal hypersensitivity thought to underlie a range of laryngeal symptoms (including chronic cough, inducible laryngeal obstruction, etc). Thought to be mediated by vagal and central nervous system innervation of laryngeal structures.

Table 1. Terminology for chronic cough as defined in the British Thoracic Society (BTS) clinical statement on chronic cough in adults.¹

A key concept in this area is the emergence of the concept of the cough hypersensitivity syndrome (Table 1). This was introduced in a guideline statement in the European Respiratory Society² and aims to prompt clinicians to view cough as its own ‘disease’ or clinical entity rather than a symptom that arises from an underlying condition.

2. How commonly do ACE inhibitors cause persistent cough? Are there any clues in the nature of the cough that this might be the cause? If ACE inhibitors do cause cough, does this usually come on shortly after initiation, and how long does it take to resolve on stopping the drug?

Angiotensin-converting enzyme (ACE) inhibitors cause cough by blocking the degradation of several pro-tussive peptides in the respiratory tract, principally bradykinin and substance P. Thus, when ACE is inhibited, these mediators accumulate in the upper and lower airways, prompting cough in some individuals.

An evaluation of the published data indicates that ACE inhibitor-induced cough has been reported to be in the range of 5-35%.³ However, in a large cohort (n=27,492) study, a more precise estimate of 4% was reported.⁴ It appears ACE inhibitor-related cough is more common in non-smokers and in some ethnic groups.⁵

The onset of ACE inhibitor-induced cough ranges from within hours of the first dose to several months after the initiation of therapy.³ It is not dose-dependent. Resolution typically occurs within one to four weeks after the cessation of therapy, but cough may linger for up to three months. In any patient with a persistent or recurrent cough, complete cessation of ACE inhibitor treatment, and thus use of an alternative anti-hypertensive or heart failure therapy, is recommended. In this respect, it is also important to note that ACE inhibitor treatment may increase overall cough hypersensitivity and thus may be relevant. in the presence of other causes. Re-introduction of an ACE inhibitor is generally not recommended unless there is a compelling clinical indication to use this class of medication.

3. Some patients with persistent cough seem to start their illness with what sounds like an obvious viral URTI. Yet their cough persists for far longer than we would expect – what might be the explanation in these cases?

The reason cough persists in some individuals following a viral type URTI can often remain unclear. Indeed, despite extensive investigations and treatment trials many people end up with UCC or RCC (see definitions in Table 1 above).

The BTS clinical statement on chronic cough¹ promotes a modern approach to this type of problem, focused on identifying and treating ‘treatable traits’.

A treatable trait describes a cause or contributing mechanism that is:

Identifiable – detectable through history, examination or specific tests.
Clinically relevant – plausibly contributing to symptoms.
Treatable – has a specific intervention (pharmacological or non-pharmacological) that targets it directly.

Treatable traits described in the BTS statement are described below (Table 2).

Treatable trait	Definition	Identifiable factors	Treatment
Smoking	Chronic bronchitis driven by tobacco/nicotine exposure	History of cigarette smoking, productive morning cough; urinary cotinine; exhaled CO	Smoking cessation; nicotine replacement therapy (NRT) to attenuate rebound cough hypersensitivity
Irritant exposure	Ongoing chemical/particulate inhalation perpetuating cough	Occupational history; pets/hobbies; vaping history	Reduce or eliminate exposure
ACE inhibitor use	ACE inhibitors induce cough hypersensitivity regardless of temporal relationship to symptom onset	Medication records; dry cough/throat symptoms	Stop ACE inhibitor in all patients with chronic cough; substitute angiotensin-2 receptor blocker (A2RB) if needed
Airway eosinophilia	T2-high eosinophilic airway inflammation encompassing asthma, cough-variant asthma, and non-asthmatic eosinophilic bronchitis	FeNO >25 ppb; blood eosinophil count (BEC) ≥0.3×10⁹/L; wheeze/breathlessness/nocturnal symptoms	Inhaled corticosteroids (ICS); escalate to high dose ICS. In some cases consider short-course oral prednisolone
Productive cough	Chronic cough with significant sputum production, often due to airways disease or infection	Purulent/thick sputum history; sputum culture and sensitivity; HRCT to exclude bronchiectasis; bronchoscopy if indicated	Airway clearance physiotherapy; mucolytics; antimicrobials; low-dose macrolide.
Chronic rhinosinusitis (CRS)	Upper airway inflammation causing nasal symptoms ≥12 weeks	≥2 symptoms including nasal blockage or discharge ± facial pain/pressure or anosmia	Intranasal steroid spray + saline douching for ≥6 weeks; ENT referral if no improvement at 12 weeks
Inducible laryngeal obstruction (ILO)	Inappropriate laryngeal closure causing dynamic airflow obstruction; previously termed vocal cord dysfunction	History of episodic wheeze, breathlessness, inspiratory stridor, dysphonia; confirmed by functional laryngoscopy	Speech and language therapy (SLT)
Obstructive sleep apnoea (OSA)	OSA may enhance cough hypersensitivity via reflux, rhinitis, and upper airway inflammation	Snoring; excessive daytime sleepiness; obesity; Epworth Sleep Score; formal sleep study	CPAP therapy if OSA confirmed on sleep study; lifestyle advice; weight loss; mandibular advancement device
Gastro-oesophageal reflux disease (GORD)	Physiological or pathological reflux acting as a cough trigger; causation remains controversial	Heartburn (best clinical predictor); oesophageal pH-impedance monitoring; endoscopy; high BMI	PPI only if heartburn present – 4-week trial, discontinue if no response; lifestyle measures (weight loss, dietary modification, head-of-bed elevation); fundoplication only if objective reflux confirmed and typical reflux symptoms – not for cough alone
Obesity	Elevated BMI associated with increased cough prevalence, mediated partly via GORD and OSA	BMI; body habitus	Weight loss strategies
Cough hypersensitivity	Neuronal sensitisation of peripheral and central cough pathways; often the dominant trait in dry/minimally productive refractory chronic cough (RCC)	Dry cough triggered by trivial exposures (cold air, perfumes, talking); cough refractory to treatment of other traits; no positive objective test currently exists	Non-pharmacological cough control therapy (SLT/physiotherapy); low-dose slow-release morphine (5–10 mg BD); gabapentin (100 mg TDS titrating to 600 mg TDS) or pregabalin (25 mg BD titrating to 75 mg BD); P2X3 antagonists (gefapixant – only available privately in the UK).
Anxiety/low mood	Psychological comorbidity frequently coexisting with chronic cough	History; validated screening tools (e.g. HAD score)	Reassurance and explanation; psychological intervention; antidepressants

Table 2. Treatable traits and their assessment in chronic cough as described by the BTS clinical statement on chronic cough in adults.¹

In reality, most clinicians focus on identifying ACE inhibitor-related cough, removing smoking as a potential trigger and then work through three common causes; namely an asthma type process, reflux or sinonasal issues.

4. Persistent cough management seems to diverge to a degree depending on whether the chest is ‘clear’ or not. If not clear, what night we hear, and what are the implications of the findings?

In a patient with chronic cough, clinical examination should focus on identifying positive (and pertinent negative) auscultatory findings that could indicate the presence of underlying pulmonary disease. Examples include reduced air entry or focal wheeze or crackles in structural lung disease, or bilateral end-inspiratory crackles in pulmonary fibrosis (often best heard in the axilla).

Squawks (high pitched musical type sounds) may also point towards a pulmonary interstitial process. It is important to note that many pulmonary disorders won’t be reliably detected or fully ‘ruled’ out by findings on clinical examination and thus if there are clinical features that raise the clinical suspicion of a pulmonary disease, then pulmonary imaging (and ideally CT imaging) and lung function testing is important.

Complete the full module on Pulse 365 and log 2 CPD hours for your appraisal

Professor James Hull is consultant respiratory physician at the Royal Brompton Hospital in London and Honorary Professor at the Institute of Sport, Exercise and Health, University College London

References