Cough pathogenesis: how the cough reflex develops, why it becomes chronic, and what is cough hypersensitivity

Coughing is a protective reflex that helps remove mucus, germs, foreign particles, smoke, dust, acidic contents, irritating gases, and other potentially harmful stimuli from the airways. Normally, it functions as a safety system: airway receptors recognize a threat, nerve pathways transmit a signal to the brainstem, and the respiratory muscles create a sharp puff of air that expels the irritant. [1]

The pathogenesis of cough is not simply a "throat irritation." It involves the respiratory mucosa, epithelium, mucus, immune cells, mast cells, eosinophils, pain and irritation receptors, the vagus nerve, brainstem, cerebral cortex, larynx, diaphragm, intercostal muscles, and abdominal muscles. [2]

Coughing becomes a problem when the defense mechanism is activated too often, too easily, or without any apparent threat. This is how cough hypersensitivity develops: a person coughs from cold air, talking, laughing, odors, smoke, perfume, household chemicals, or changes in body position, although in a healthy person such stimuli would not trigger a severe cough. [3]

Modern guidelines increasingly consider chronic cough not only as a symptom of asthma, reflux, or rhinitis, but also as a distinct condition associated with increased sensitivity of the cough nerve pathways. This is especially important in refractory and unexplained chronic cough, when conventional treatments for the suspected causes are ineffective. [4]

To understand the treatment, one must first understand the mechanism. One cough is caused by mucus, another by bronchospasm, a third by post-viral nerve sensitization, a fourth by reflux, a fifth by medications, and a sixth by chronic neuropathic hypersensitivity of the cough reflex. [5]

What is involved in the pathogenesis of cough?	The main role
Respiratory tract epithelium	First contact with irritants and infections
Mucus	Captures particles and germs
Cilia of the epithelium	They move mucus towards the exit.
Respiratory tract receptors	Recognize mechanical and chemical irritants
Vagus nerve	Transmits a signal from the respiratory tract to the brain
Brain stem	Coordinates the cough reflex
Cerebral cortex	Participates in the sensation of the urge to cough and partial control
Respiratory muscles	Creates a powerful air flow when coughing

The Normal Cough Reflex: Why It Matters

Physiologically, coughing is necessary for clearing the airways. It helps when normal mucociliary clearance is insufficient: for example, when there is excess mucus, food or saliva gets into the wrong places, or when smoke, dust, or a chemical irritant is inhaled. [6]

Mucociliary clearance is the first line of defense: mucus traps particles, and the cilia of the epithelium move them upward. Coughing is used as a more powerful backup mechanism when a large volume of secretion or an irritant that cannot be removed by the slow movement of the cilia must be quickly removed. [7]

If the cough mechanism is too weak, the airways are less cleared. This occurs in cases of severe muscle weakness, neurological diseases, impaired consciousness, after surgery, with respiratory muscle weakness, and in some elderly patients; then the risk of aspiration, infection, and sputum retention increases. [8]

If the cough mechanism is overactive, another problem arises: coughing ceases to be beneficial and becomes a painful symptom. Frequent coughing irritates the larynx, interferes with sleep, causes chest pain, urinary incontinence, dizziness, social embarrassment, and a significant reduction in quality of life. [9]

Thus, cough has a "double face": it protects the lungs, but when overactivated, it becomes a clinical problem in its own right. Therefore, a modern approach should not simply "suppress any cough," but rather understand when coughing facilitates clearance and when it perpetuates a pathological cycle of irritation and hypersensitivity. [10]

Cough reflex status	What's happening	Possible consequences
Normal cough	Removes irritant or mucus	Respiratory protection
Weakened cough	The secret is difficult to remove	Aspiration, infections, sputum retention
Coughing too often	The reflex is triggered by weak stimuli	Sleep disturbance, pain, fatigue
Chronic hypersensitivity	Nervous pathways become overreactive	Refractory or unexplained cough
Productive cough	Removes phlegm	May be useful for excess secretion.
Dry, irritating cough	Little or no sputum	Often associated with receptor sensitization

Phases of a cough: How the body creates a sharp stream of air

A classic cough consists of three main phases: inhalation, compression, and a sharp exhalation. First, a person inhales to create a volume of air, then the glottis closes, increasing the pressure in the chest, after which the glottis opens sharply and air is expelled at high speed. [11]

During the inhalation phase, the diaphragm and external intercostal muscles increase the volume of the chest cavity. The more air you take in before coughing, the more powerful the subsequent exhalation can be and the more effective the removal of secretions or irritants. [12]

During the compression phase, the larynx closes the glottis, and the expiratory muscles begin to contract against the closed exit. Pressure within the chest cavity rapidly increases, and this accumulated energy is needed for the subsequent explosive expulsion of air. [13]

During the expiratory phase, the glottis opens, the abdominal muscles and internal intercostal muscles contract sharply, and air is expelled at high speed. This flow creates a shear force that helps to tear mucus away from the bronchial wall and expel it upward. [14]

If even one phase is disrupted, coughing becomes ineffective. For example, if the respiratory muscles are weak, the necessary pressure cannot be created; if the larynx is dysfunctional, the opening and closing of the glottis is impaired; and if the sputum is thick, even a strong cough may not clear the bronchi effectively. [15]

Cough phase	What's happening	Why is this necessary?
Inhalation phase	Take a deep breath	Creates air volume for coughing
Compression phase	The glottis is closed, the pressure increases	Accumulates energy
Explosive exhalation	The glottis opens	Quickly removes air and phlegm
Work of the abdominal muscles	Increases pressure	Makes coughing more severe
Function of the larynx	Closes and opens the exit	Controls the force of the ejection
Violation of any phase	The cough becomes weak	The risk of secretion stagnation increases

Cough Receptors: Where the Signal Begins

Coughing begins with the activation of sensory nerve endings in the airways. These are located in the larynx, trachea, large bronchi, small bronchi, and structures of the upper respiratory tract; the larynx is particularly sensitive because it protects the lower respiratory tract from aspiration. [16]

Different receptors respond to different stimuli. Mechanosensitive receptors respond to touch, stretch, mucus, and foreign particles, while chemosensitive nerve endings respond to acid, cold, smoke, capsaicin, inflammatory mediators, adenosine triphosphate, and other chemical irritants. [17]

Two major groups of sensory fibers are important in cough: myelinated A-delta fibers and unmyelinated C-fibers. A-delta fibers conduct signals faster and are particularly important for mechanical protection of the airways, while C-fibers are involved in chemical sensitivity, inflammation, neurogenic response, and hypersensitivity. [18]

Key molecular "sensors" include receptors of the transient receptor potential family, such as transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1, as well as purinergic P2X3 receptors. These channels respond to chemical and inflammatory stimuli and have become important therapeutic targets in chronic cough.[19]

This is why different irritants can trigger similar coughs. Cold air, smoke, strong odors, acid reflux, viral inflammation, and thick mucus all trigger different sensory pathways, but ultimately they all converge on the cough reflex. [20]

Receptor or fiber type	What does it react to?	Clinical significance
Mechanosensitive receptors	Mucus, foreign particles, stretching	Protective cough for sputum and aspiration
A-delta fibers	Fast mechanical signals	A sharp defensive reflex
C-fibers	Chemical irritants and inflammation	Burning sensation, coughing sensation, hypersensitivity
Transient receptor potential vanilloid 1	Capsaicin, acid, heat, inflammation	Cough sensitivity model
Transient receptor potential ankyrin 1	Smoke, cold, chemical irritants	Reaction to odors and pollutants
P2X3 receptors	Adenosine triphosphate in cellular stress	Target for new antitussive drugs

Vagus nerve and brainstem

The main nerve pathway for the cough reflex is the vagus nerve. Sensory signals from the respiratory tract travel along its branches to the brainstem, where the centers integrating respiration, swallowing, protective reflexes, and cough are located. [21]

One of the key processing points is the nucleus of the solitary tract in the medulla oblongata. It receives information from vagal afferents, compares it with the state of the respiratory cycle, and transmits commands further to the respiratory, laryngeal, and muscular centers. [22]

Coughing is not a completely automatic spinal reflex. It is linked to the central respiratory generator, laryngeal motor programs, and higher brain regions, so a person can sometimes delay a cough, intensify it voluntarily, or feel a growing "urge to cough." [23]

The sensation of the urge to cough is an important part of the pathogenesis of chronic cough. Many patients describe not just attacks, but a persistent tickling, scratching, lump, irritation in the larynx, or an inability to refrain from coughing while talking; this indicates the involvement of central sensory processing. [24]

With chronic cough, sensitivity can increase in both the peripheral and central nervous systems. This means that airway receptors become more easily excitable, and the brain begins to react more strongly to signals that would previously have been weak or unnoticeable. [25]

Nervous system level	What does it do?	How does it affect coughing?
Respiratory tract receptors	Recognize the stimulus	They are starting a signal
Vagus nerve	Transmits a signal to the brain	Main afferent pathway
The core of the solitary path	Integrates sensory information	Forms a reflex response
Respiratory centers	Coordinate cough with breathing	Provide the correct rhythm
Laryngeal centers	They close and open the glottis	Create compression and ejection
Cerebral cortex	Participates in urge and partial control	Helps suppress or increase coughing

Inflammation and infection: why cough occurs with a cold

During a viral upper respiratory tract infection, the epithelium becomes inflamed, releases mediators, and becomes more sensitive to cold air, talking, deep inhalation, and normal mucus. Therefore, a cough associated with a cold often persists even after the fever has passed. [26]

Viruses can temporarily increase the sensitivity of cough nerve endings. This post-viral cough is often associated not with an active bacterial infection, but with residual inflammatory and neurosensory hyperreactivity of the airways. [27]

During inflammation, the epithelium releases cytokines, prostaglandins, bradykinin, adenosine triphosphate, and other mediators that lower the threshold for activating cough receptors. Therefore, a stimulus that previously did not trigger a cough begins to trigger an attack. [28]

If the inflammation is accompanied by excess mucus, the cough becomes productive. In this case, it serves a clearing function, and complete suppression of the cough may be undesirable, especially if the mucus is thick, abundant, or difficult to clear. [29]

If the inflammation subsides and there's little sputum, but the cough persists for weeks, the mechanism increasingly becomes neurosensory. This explains why antibiotics usually don't resolve post-viral coughs unless there are signs of a bacterial infection. [30]

Infection stage	What's happening	What kind of cough occurs?
Initial irritation	The virus damages the epithelium	Dry cough, sore throat
Active inflammation	Mediators lower the receptor threshold	Frequent coughing from mild stimuli
Increased mucus	The secret gets bigger	Wet cough
Epithelial restoration	The inflammation goes away gradually.	Residual cough
Postviral sensitization	The nerves remain sensitive	Cough from talking, cold, smells
Bacterial complication	Purulent inflammation or pneumonia	Cough plus systemic signs of illness

Sputum, mucus and mucociliary clearance

Mucus in the respiratory tract serves a protective function: it moistens the surface, traps particles, binds microbes, and helps the immune system function at the interface with the external environment. But when there's too much mucus, it becomes thick or is poorly moved by the cilia, which can worsen coughing. [31]

Mucociliary clearance depends on normal cilia function, proper mucus viscosity, adequate hydration of the airway surface, and the absence of damaging factors such as smoke, chronic inflammation, and certain infections. Impaired mucociliary clearance forces the body to use coughing more frequently as a backup clearance mechanism. [32]

In chronic bronchitis, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, and some post-infectious conditions, sputum becomes a constant driver of coughing. Here, the cough is often productive, occurring in the morning, associated with the accumulation of secretions overnight, and is partially beneficial for clearing the bronchi. [33]

Thick mucus can itself fuel inflammation. It traps microbes and irritants, impairs ventilation of the small bronchi, creates conditions for recurrent infections, and mechanically activates cough receptors. [34]

Therefore, the pathogenesis of a wet cough differs from that of a dry neurogenic cough. With a wet cough, the primary goal is often to improve airway clearance and treat the underlying cause of sputum formation, while with a dry chronic cough, the primary goal is to reduce the hypersensitivity of the cough tract. [35]

The mechanism of sputum	How does coughing occur?
Excess secretion	Mechanically irritates receptors
High viscosity	Mucus is difficult to remove
Disruption of the eyelashes	The secretion is retained in the bronchi
Infection	Increases inflammatory secretion
Smoking	Damages eyelashes and increases mucus
Bronchiectasis	Create a permanent reservoir of mucus
Dehydration of secretions	Makes coughing less effective
Mucostasis	Supports inflammation and infections

Asthma and eosinophilic inflammation

In asthma, cough occurs due to a combination of bronchial inflammation, bronchial hyperreactivity, smooth muscle spasm, increased mucus secretion, and sensitization of cough receptors. In some patients, cough may be the main or even the only noticeable symptom. [36]

Cough-variant asthma is a condition in which chronic cough is associated with asthmatic inflammation and bronchial hyperreactivity, but wheezing and shortness of breath may be minimal or absent. In such cases, the pathogenesis of cough is associated not only with sputum production but also with increased bronchial sensitivity to exercise, cold air, and irritants. [37]

Non-asthmatic eosinophilic bronchitis may present with a chronic cough without the typical variable airflow obstruction. Eosinophilic inflammation is present, but spirometry may be normal, so diagnosis requires assessment of inflammatory markers or induced sputum where available.[38]

Eosinophils release mediators that irritate the epithelium, increase inflammation, and increase the sensitivity of nerve endings. Therefore, anti-inflammatory therapy targeting eosinophilic inflammation can reduce cough in appropriately selected patients. [39]

Importantly, not every chronic dry cough is asthma. Treating a cough as asthma without confirming the underlying mechanism can miss reflux, upper respiratory cough syndrome, drug-induced cough, bronchiectasis, tumor, interstitial lung disease, or cough hypersensitivity. [40]

Mechanism in asthma and eosinophilic inflammation	How does it affect coughing?
Bronchial hyperreactivity	Cough from cold, stress, irritants
Inflammation of the epithelium	Lowers the receptor threshold
Eosinophils	Support inflammation and sensitization
Bronchospasm	Causes coughing and tightness
Mucus	Enhances the productive component
Night variability	The cough often gets worse at night or in the morning.

Upper respiratory tract, nose and larynx

Coughing can originate not only from the bronchi but also from the upper respiratory tract. The nose, paranasal sinuses, nasopharynx, pharynx, and larynx have sensory innervation, and inflammation or secretion flowing down the back of the throat can support the cough reflex. [41]

The so-called upper respiratory tract cough syndrome includes conditions associated with rhinitis, rhinosinusitis, and postnasal drip. The pathogenesis involves mucosal inflammation, mucus, pharyngeal irritation, altered nasal breathing, and sensitization of laryngeal receptors. [42]

The larynx is a particularly important site for the cough reflex. It protects the lower airways from aspiration, so its receptors are highly sensitive to liquids, particles, acids, odors, cold air, and mechanical irritation. [43]

Chronic cough often develops laryngeal hypersensitivity: a person coughs when talking, laughing, singing, taking a deep breath, or when exposed to strong odors. This does not necessarily indicate a throat infection; it is often a manifestation of sensitization of the laryngeal nerve pathways and the cough reflex. [44]

Therefore, chronic cough therapy sometimes includes not only medications but also speech or physical therapy to suppress cough. These methods focus on controlling the urge to cough, breathing techniques, reducing laryngeal tension, and breaking the habitual cough cycle. [45]

Plot	How can it cause a cough?
Nose	Rhinitis, congestion, mouth breathing
Paranasal sinuses	Inflammation and discharge of secretions
Nasopharynx	Irritation of the posterior wall
Pharynx	A tickling sensation and a mucus sensation
Larynx	Very sensitive defense receptors
Vocal folds	Coughing when talking and using the voice
Upper respiratory nerves	Participate in the sensitization of the cough reflex

Reflux and cough

Reflux can trigger coughing in several ways. Acidic or slightly acidic contents can irritate the esophagus and upper airways, and signals from the esophagus through the nerve arches can enhance the cough reflex even without direct acid entry into the bronchi. [46]

In some patients, coughing is associated with microaspiration, when small amounts of gastric or pharyngeal contents enter the larynx and airways. This can irritate laryngeal receptors, causing a sore throat, hoarseness, nighttime coughing, and a lump in the throat sensation. [47]

However, the relationship between reflux and cough is more complex than it seems. Not every patient with heartburn has a cough caused by reflux, and not every chronic cough without heartburn is "hidden reflux." Therefore, the current approach requires an assessment of clinical signs and caution with long-term empirical treatment without evidence. [48]

Reflux may not be the primary cause, but rather an exacerbator of cough hypersensitivity. Frequent coughing increases intra-abdominal pressure, which can worsen reflux, which in turn further irritates the larynx and fuels further coughing; thus, a vicious cycle is established. [49]

In reflux-associated cough, not only acid but also weakly acidic reflux, gas reflux, pepsin, bile components, esophageal motility disorders, and increased sensitivity of the esophageal-laryngeal nerve pathways are important. [50]

The mechanism of reflux cough	What's happening
Acid irritation	Acid irritates the esophagus or larynx
Microaspiration	Small amounts enter the respiratory tract
Vagal reflex	Esophageal signal increases coughing
Laryngeal hypersensitivity	The larynx responds to weak stimuli
Coughing increases reflux	Intra-abdominal pressure increases
Mild acid reflux	Symptoms are possible even without significant acidity.

Cough hypersensitivity

Cough hypersensitivity is a condition in which the cough reflex becomes overly sensitive to common stimuli. Patients often cough from talking, laughing, cold air, perfume, smoke, household chemicals, dust, temperature changes, deep breathing, or even a dry throat.[51]

A modern concept explains chronic cough as a sensory processing disorder: the peripheral nerves of the airways become more easily excitable, while the central brain structures more strongly perceive and amplify signals. Therefore, cough may persist even after the initial inflammation or infection has been treated. [52]

This mechanism is particularly important in refractory chronic cough, when obvious causes have been treated, but the cough persists. A 2025 review emphasizes that such cases are often associated with neuropathic changes in vagal transmission, that is, with disrupted functioning of the cough nerve pathways. [53]

Cough hypersensitivity helps explain why patients may have normal chest x-rays, spirometry, and laboratory tests, but still have a real and severe cough. The problem isn't "imagination," but rather that the cough sensory system is operating at an overdrive. [54]

It is this concept that has led to the development of new treatments: speech therapy to suppress cough, neuromodulators, and drugs that affect P2X3 receptors. These do not treat the infection or mucus, but rather attempt to reduce the pathological excitability of the cough system. [55]

Sign of cough hypersensitivity	How does it manifest itself?
Cough from talking	The larynx and central airways are overly sensitive
Cough from odors	Chemical stimuli trigger a reflex
Cough from cold air	The sensory channels react too easily
Sore throat without phlegm	The urge to cough is associated with nervous sensitization
Normal basic examinations	The problem may be functional neurosensory
Long-term survival after infection	Sensitization outlives the original trigger

Drug-induced cough and the bradykinin pathway

A classic example of drug-induced cough is the cough associated with angiotensin-converting enzyme inhibitors, which are used to treat hypertension, heart failure, and other cardiovascular conditions. This cough is typically dry, persistent, and may develop weeks or months after starting the drug. [56]

The mechanism involves the accumulation of bradykinin, substance P, and other mediators that are normally partially destroyed by angiotensin-converting enzyme. When the enzyme is blocked, these substances can irritate respiratory C-fibers and enhance the cough reflex. [57]

This type of cough is important because it is reversible. If a doctor confirms a connection with the drug and changes it to another class, such as an angiotensin receptor blocker, the cough often gradually improves, although it may take several weeks to resolve. [58]

Not every cough in someone taking an angiotensin-converting enzyme inhibitor is caused by the medication. Infections, asthma, chronic obstructive pulmonary disease, reflux, heart failure, and other causes should be considered, but medication should always be a factor. [59]

This example clearly illustrates the general principle of the pathogenesis of cough: the same symptom can arise not from sputum or from infection, but from biochemical sensitization of nerve endings. [60]

The mechanism of medicinal cough	What's happening
Enzyme blockade	Bradykinin is destroyed more slowly
Accumulation of mediators	C-fibers are irritated
Dry cough	There is usually no sputum
Delayed onset	It may not appear immediately
Reversibility	Decreases after drug discontinuation or replacement
Diagnostic error	A cough can be mistaken for bronchitis or allergies.

Acute, subacute and chronic cough: different pathogenesis

Coughs are typically categorized by duration as acute, subacute, and chronic. In adults, acute coughs last less than 3 weeks, subacute coughs last from 3 to 8 weeks, and chronic coughs last 8 weeks or longer. This classification helps understand the likely mechanism and the extent of investigation. [61]

Acute cough is most often associated with a viral upper respiratory tract infection and temporary inflammatory hypersensitivity. Most cases resolve spontaneously, but it is important to watch for pneumonia, asthma exacerbation, pulmonary embolism, heart failure, or other serious causes. [62]

Subacute cough is often post-infectious. Its pathogenesis is usually associated with epithelial restoration, residual inflammation, airway hyperreactivity, and temporary sensitization of cough receptors following a viral infection. [63]

Chronic cough in adults is more often associated with asthma, non-asthmatic eosinophilic bronchitis, upper respiratory cough syndrome, reflux, smoking, chronic obstructive pulmonary disease, bronchiectasis, angiotensin-converting enzyme inhibitors, or cough hypersensitivity.[64]

In children, chronic cough has a different diagnostic logic. CHEST guidelines emphasize the use of pediatric algorithms in children, and wet chronic cough especially requires evaluation for persistent bacterial bronchitis, bronchiectasis, and other causes different from those in adults. [65]

Duration	Frequent mechanism	What is important
Less than 3 weeks	Viral infection, irritation	Eliminate dangerous signs
3-8 weeks	Post-infectious sensitization	Not to be confused with a bacterial infection without reason
8 weeks and more in adults	Chronic diseases and hypersensitivity	A systematic search for causes is needed.
Chronic wet cough in children	Often an infectious-secretory mechanism	A children's algorithm is needed
Refractory cough	Neuropathic hypersensitivity	Consider special treatments
Unexplained cough	The cause was not found after examination.	Assess cough hypersensitivity

Modern therapeutic targets in the pathogenesis of cough

Understanding the pathogenesis of cough has changed the approach to treatment. If the cough is caused by sputum, methods for clearing the airways and treating the cause of mucus formation are needed; if by inflammation, anti-inflammatory therapy; if by reflux, addressing the reflux mechanism; if by hypersensitivity, methods for reducing sensory excitability. [66]

One of the important modern targets is P2X3 receptors. When damaged or inflamed, cells release adenosine triphosphate, which activates P2X3 receptors on sensory nerves and enhances the cough signal; therefore, P2X3 antagonists have become a new approach to treating chronic cough. [67]

Gefapixant, a P2X3 receptor antagonist, reduced cough frequency in patients with refractory or unexplained chronic cough in the COUGH-1 and COUGH-2 studies, but often caused taste disturbances. It is licensed in the European Union, the United Kingdom, and Japan, but the Food and Drug Administration has withheld approval in the United States due to insufficient evidence of efficacy.[68][69]

Neuromodulators, such as gabapentin, pregabalin, or low doses of certain antidepressants, are used in selected patients with refractory chronic cough when a neuropathic mechanism is suspected. Their use requires caution due to drowsiness, dizziness, interactions, and the need for an individual benefit-risk assessment. [70]

Non-pharmacological cough suppression therapy through speech and respiratory rehabilitation targets the central and behavioral components of the reflex. It teaches recognition of the urge to cough, the use of alternative breathing maneuvers, reduction of laryngeal irritation, and the interruption of the "urge-cough-more irritation" cycle. [71]

Treatment target	What mechanism corrects
Anti-inflammatory therapy	Eosinophilic inflammation, asthma, bronchitis
Mucoactive approaches	Thick sputum and poor clearance
Treatment of rhinitis and rhinosinusitis	Upper respiratory cough syndrome
Reflux control	Esophageal-laryngeal and aspiration mechanisms
Discontinuation of angiotensin-converting enzyme inhibitor	Bradykinin sensitization
Neuromodulators	Neuropathic cough hypersensitivity
P2X3 antagonists	Purinergic sensory transmission
Speech therapy	Central control and laryngeal hypersensitivity

Why can't all coughs be treated the same way?

Cough is a common symptom of various mechanisms, so there is no universal treatment for all cases. A drug that reduces a dry neurogenic cough may be ineffective against sputum; an asthma remedy will not resolve a drug-induced cough; and reflux treatment will not help if the cough is caused by bronchiectasis. [72]

It is especially important to distinguish a cough with sputum from a dry, persistent cough. A wet cough often reflects the need to clear the airways, while a dry, chronic cough is more often associated with irritation, inflammation, or sensitization of the nerve pathways. [73]

Centrally acting cough suppressants may reduce symptoms but should not be used as a substitute for diagnosis if there is blood in the sputum, weight loss, shortness of breath, chest pain, prolonged fever, recurrent pneumonia, smoking with a change in cough pattern, or suspicion of serious lung disease.[74]

On the other hand, a long-standing dry cough with normal examinations cannot be treated indefinitely with antibiotics or expectorants. If the mechanism is related to cough hypersensitivity, other approaches are needed: explanation of the neurosensory nature, trigger control, speech therapy, neuromodulators, or specialized medications. [75]

The best result is achieved not by suppressing the cough at any cost, but by a precise understanding of the underlying mechanism: inflammatory, secretory, reflux, medicinal, infectious, bronchial, upper respiratory, neurogenic or mixed. [76]

Error	Why is this a problem?
Treat any cough with an antibiotic	Most acute cases are viral.
Suppress a wet cough without evaluation	It may impair bronchial cleansing.
Consider any dry cough as an allergy	You may miss reflux, medication, asthma, or hypersensitivity
Treating reflux without symptoms for a long time	Risk of futile therapy
Do not check medications	Angiotensin-converting enzyme inhibitors are often forgotten
Do not take into account the larynx	Laryngeal hypersensitivity often supports coughing.
Ignoring quality of life	Chronic cough can be an independent disease.
Do not separate adults and children	Children have other common causes and algorithms

FAQ

Is cough a symptom or a separate disease? Cough can be a symptom of infection, asthma, reflux, sputum, medication effects, or lung disease, but chronic refractory cough is increasingly being considered as an independent condition associated with cough hypersensitivity. [77]

Why can a cough linger for weeks after a cold? After a viral infection, the epithelium and nerve endings of the respiratory tract remain sensitive, so a cough can persist due to post-viral sensitization even after the fever and runny nose have disappeared. [78]

Why does coughing get worse with odors, cold, and talking? This is typical of cough hypersensitivity: the sensory nerves of the larynx and airways react to mild irritants as if they were dangerous. [79]

Why can reflux cause a cough without heartburn? Reflux can trigger a cough through vagal reflexes, laryngeal irritation, or microaspiration, so in some patients, the cough is associated with more than just classic heartburn. [80]

Why do angiotensin-converting enzyme inhibitors cause cough? These drugs can lead to a buildup of bradykinin and substance P, which irritate the sensory C-fibers of the airways and enhance the cough reflex. [81]

Should a wet cough always be suppressed? No. If a cough produces mucus, it can serve a useful clearing function, so it's important to treat the cause of the excess secretion and improve airway clearance, rather than simply blocking the reflex. [82]

What are P2X3 receptors? These are purinergic receptors on sensory nerves that are activated by adenosine triphosphate during inflammation or tissue damage and can enhance the cough signal. [83]

Why is gefapixant not equally available everywhere? Gefapixant has been licensed in several regions, including the European Union, the United Kingdom, and Japan, but the US Food and Drug Administration has not approved it due to questions about the evidence of effectiveness, although the refusal was not related to safety. [84] [85]

Why might speech therapy be prescribed for chronic cough? This therapy doesn't "treat the voice," but rather teaches how to control the urge to cough, reduce laryngeal tension, and break the neurobehavioral cycle of chronic cough. [86]

Why is chronic cough assessed differently in children than in adults? Children have different common causes, different danger signs, and different algorithms; for example, a chronic wet cough in a child requires separate assessment for bacterial and structural causes. [87]

Key points from experts

Alyn H. Morice, professor of respiratory medicine at Hull York Medical School and lead author of the European Respiratory Society guidelines, established the concept of cough hypersensitivity as an explanation for why adults with chronic cough overreact to cold air, odors, smoke, and other mild stimuli. [88]

Richard S. Irwin, MD, a key contributor to the American College of Chest Physicians cough guidelines, emphasized in a 2025 review that documented refractory or unexplained chronic cough is often associated with neuropathic changes in vagal transmission, not just with an "undertreated infection." [89]

Jacky A. Smith, Professor of Respiratory Medicine, University of Manchester. Her work and current reviews highlight that chronic cough involves not only peripheral receptors but also central processing of the cough urge, so neurosensory and behavioral treatments have a biological basis. [90]

Lorcan P. McGarvey, Professor of Respiratory Medicine, Queen's University Belfast. In the COUGH-1 and COUGH-2 studies, his group showed that P2X3 receptor blockade with gefapixant can reduce cough frequency in patients with refractory or unexplained chronic cough, although taste disturbances remain an important limitation. [91]

Anne B. Chang, professor of pediatric respiratory medicine and lead author of the CHEST guidelines for cough in children, emphasizes that childhood chronic cough cannot be automatically assessed using adult guidelines: in children, it is especially important to use age-specific algorithms and separately address chronic wet cough. [92]