NICE NG12 (Suspected Cancer, 2023) mandates a 2WW chest referral for unexplained cough lasting ≥3 weeks in adults aged ≥40 who are current or ex-smokers. Haemoptysis at any age warrants 2WW if unexplained. The 1% PPV threshold used by NICE means that even 1 in 100 patients with these features has lung cancer — the benefit of early detection justifies urgent investigation. A CXR has approximately 70% sensitivity for central lung tumours but misses peripheral and mediastinal pathology — a normal CXR does not exclude cancer in a high-risk patient, and CT chest is required if clinical suspicion persists. TB incidence in the UK is approximately 5–6/100,000 but significantly higher in some urban areas and migrant communities — night sweats + weight loss + chronic cough in a high-risk patient requires TB assessment.

ACE inhibitor cough affects 10–15% of patients in UK populations (higher in South Asian populations — up to 40%) and is the most common drug-induced cough. The mechanism is bradykinin and substance P accumulation in the respiratory mucosa — it is a class effect (all ACEi cause it) and is not dose-related. Stopping the ACE inhibitor resolves the cough within 1–4 weeks in 95% of cases. Failure to resolve after 4 weeks suggests a co-existing diagnosis requiring further investigation. The occupational history is one of the most neglected areas in chronic cough assessment — approximately 15% of adult-onset asthma is occupational in origin and is legally compensatable if identified and reported. The key question is whether cough/wheeze improves on days away from work.

The "big three" causes of chronic cough (UACS, GORD, asthma/CVA) account for up to 90% of cases in non-smoking adults with a normal CXR. Eosinophilic bronchitis is important because it is clinically indistinguishable from CVA without objective testing (spirometry, FeNO, induced sputum) — it responds to ICS but not to bronchodilators. Cough hypersensitivity syndrome is increasingly recognised as the underlying mechanism for many cases of unexplained chronic cough — the cough reflex arch is sensitised (analogous to neuropathic pain), triggered by minimal stimuli. Gabapentinoids (gabapentin, pregabalin) and P2X3 receptor antagonists are emerging treatments targeting this neurogenic component.

FeNO measurement is now the recommended first-line objective test for suspected asthma/CVA in primary care (NICE NG80, 2017) — it identifies eosinophilic airway inflammation with 80% sensitivity and 85% specificity for steroid-responsive disease. A FeNO >40 ppb supports a trial of ICS and predicts response. Normal spirometry is present in up to 30% of patients with cough-variant asthma — a normal spirogram must not be used to exclude CVA. Peak flow variability (diurnal variation >20%) is an alternative diagnostic criterion. The 24-hour ambulatory pH study is the gold standard for GORD-related cough but is invasive and rarely necessary in primary care — an empirical BD PPI trial for 8–12 weeks is both diagnostic and therapeutic.

NICE NG12 has a very low threshold for lung cancer 2WW referral — haemoptysis at any age warrants consideration of 2WW. A normal CXR does not exclude lung cancer and should not be used as a reason to avoid referral in high-risk patients — CT chest has 3-fold higher sensitivity than CXR for peripheral tumours. Specialist cough clinics exist in most large NHS trusts — they provide a multidisciplinary assessment combining respiratory, gastroenterology, ENT, and speech and language therapy expertise alongside objective testing (FeNO, bronchoprovocation, ambulatory pH). They are appropriate for patients who have had an extensive primary care work-up without a clear diagnosis.

Empirical triple therapy (simultaneous UACS + GORD + CVA treatment) is supported by evidence from specialist cough clinics showing that 87% of unexplained chronic cough responds to one or more of these three treatments, and sequential trials would take 6–9 months. Gabapentin's mechanism in CHS is through modulation of sensitised vagal afferent C-fibres in the cough reflex arc — analogous to its mechanism in neuropathic pain. Cough hypersensitivity syndrome should be conceptualised as a neuropathic condition. Gefapixant (a P2X3 receptor antagonist on cough-reflex afferent nerves) is the first novel specific cough therapy — it reduces cough frequency by 45% but causes taste disturbance in 20% of patients. Currently approved by EMA; NICE appraisal pending.

The Gibson et al. Lancet RCT (2009) is the landmark study — physiotherapy-based cough suppression (Lesley Jamieson technique) achieved a 40% reduction in cough severity in patients with chronic refractory cough, comparable to gabapentin but without pharmacological side effects. The mechanism is top-down modulation of the cough reflex — the technique teaches patients to suppress the urge-to-cough sensation (which is mediated by cortical and limbic circuits) rather than simply suppressing the mechanical cough. Coughing itself further traumatises laryngeal mucosa and worsens cough hypersensitivity — breaking the cough-irritation-cough cycle is the therapeutic goal. This intervention is underutilised in primary care and should be considered early in the management pathway, not just as a last resort.

Nasal saline irrigation is underused but evidence-based for UACS — a Cochrane review (2018) confirmed modest but consistent benefit for chronic sinonasal symptoms and cough. Hypertonic (2.7%) saline is more effective than isotonic for mucociliary clearance. Throat clearing is a self-perpetuating habit that worsens cough by repeatedly traumatising vocal fold mucosa — every throat clear causes bilateral vocal fold adduction, which irritates the epithelium and releases substance P, further sensitising the cough reflex. Patients must be explicitly taught to substitute a firm swallow for throat clearing. Cold air-triggered cough is mediated by TRPA1 receptors in sensory nerve endings on the laryngeal mucosa — warming inhaled air by nasal breathing or wearing a scarf significantly reduces this trigger, particularly in CVA and CHS.

The most common reason for failure of empirical treatment for chronic cough is inadequate dosing or delivery technique — PPI once daily instead of twice daily (insufficient for LPR), nasal steroid aimed at the septum (causes nosebleeds and has no therapeutic effect — must aim laterally toward the inner corner of the eye), ICS without spacer (80% of drug impacts oropharynx rather than reaching airways). Before escalating investigation, confirm that treatments have been taken correctly. Rib fractures from severe chronic cough are more common than recognised — an RCT showed that 6% of patients with refractory cough have stress fractures. Urinary incontinence from cough is frequently unreported, particularly in women, and significantly impairs quality of life — it should be actively enquired about and pelvic floor physiotherapy offered.