What is the pathophysiological mechanism of cough?

Whether it’s a tickle in your throat or a full-blown coughing fit, this powerful reflex is all about protecting your lungs. But what's really going on behind the scenes?

🔬 Step-by-step: The Cough Reflex Arc

1️⃣ Irritant or trigger detected

• Cough begins when sensory nerve endings in the respiratory tract are stimulated.
• These include mechanoreceptors (responding to mechanical stimuli like dust, food particles, or foreign bodies) and chemoreceptors (responding to chemical irritants like smoke, acid reflux, or infection-related inflammation).
• Most are located in the larynx, trachea, and carina, but also in the pharynx, external auditory canal, pleura, pericardium, and diaphragm.

2️⃣ Afferent signal via the vagus nerve

• Once activated, the sensory signal travels via the vagus nerve (cranial nerve X) to the cough centre in the medulla oblongata of the brainstem.
• The cough centre integrates information and decides whether to initiate the cough reflex.

3️⃣ Processing in the brainstem

• The cough centre coordinates a complex motor response involving respiratory muscles and upper airway structures.

4️⃣ Efferent signal – time to act!

The response involves a series of highly coordinated events:

• Deep inspiration – to fill the lungs with air.
• Closure of the glottis – traps the air inside, allowing pressure to build.
• Contraction of expiratory muscles – particularly the intercostals and abdominal muscles, sharply increasing intrathoracic pressure.
• Sudden glottal opening – releases the air forcefully, often at speeds >100 km/h 🌪️
• → This high-speed airflow expels mucus, pathogens, or foreign particles from the airways.

🩺 Why do people cough excessively?

➡️ In chronic cough, the reflex arc becomes hypersensitive – even minor stimuli can activate it. This may be due to:

• Inflammation of the airways (e.g. post-viral cough, asthma)
• Upregulation of cough receptors (neuropathic changes)
• GORD, where acid irritates the distal oesophagus or larynx
• Medications, like ACE inhibitors, which can increase bradykinin and substance P, triggering the reflex

🔄 Summary

✅ Cough is a neurally mediated reflex arc designed to protect the airway

✅ It involves sensory detection, central processing, and motor execution

✅ In disease, the reflex can become dysregulated or overactive

🔬 What about C fibres?

C fibres are slow-conducting, unmyelinated chemoreceptive afferent nerves located in the airway epithelium, especially in the lower respiratory tract.

They’re activated by a wide range of chemical mediators, including:

• Prostaglandins
• Bradykinin
• Substance P
• Capsaicin (chilli compound!)
• Acid (from reflux)
• Environmental irritants (smoke, pollutants, etc.)

🧠 C fibres and the cough reflex

Once stimulated, C fibres: ➡️ Send signals via the vagus nerve to the nucleus tractus solitarius in the brainstem

➡️ Trigger a cough reflex, often with a different character compared to mechanically triggered coughs:

Often described as dry, persistent, and irritating

Common in chronic cough, post-viral cough, asthma, GORD, and ACE inhibitor-induced cough

🌶️ Did you know?

Capsaicin cough challenge tests use this mechanism!

In research, capsaicin (the “hot” in chilli) is used to stimulate C fibres and assess cough reflex sensitivity.

In chronic refractory cough, C fibre hypersensitivity is a major focus of treatment (e.g. neuromodulators like gabapentin).

📚 Clinical link:

🩺 If a patient has a dry, chronic cough with no clear mechanical cause (normal CXR, no infection), C fibre hypersensitivity may be to blame.

🧠 This is called the “cough hypersensitivity syndrome”, now recognised as a distinct clinical entity.