OVERVIEW

What is typical asthma?

Asthma is a chronic respiratory disease that often occurs after exposure to triggers such as allergens, cold air, or exercise. It manifests as recurrent episodes of wheezing, shortness of breath, chest tightness, or coughing, frequently worsening at night and/or in the early morning. Most patients can relieve symptoms on their own or with treatment.

At its core, it is a chronic inflammatory airway disease involving various cells and cellular components. This chronic inflammation is associated with airway hyperresponsiveness, which can lead to narrowed airways and restricted airflow. However, it can be reversed and normalized with treatment^[1].

What is cough-variant asthma?

Cough-variant asthma is a special type of asthma where chronic irritating cough (lasting more than 8 weeks in adults or 4 weeks in children) is the primary or sole clinical manifestation.

It mainly presents as persistent or recurrent coughing, often accompanied by nighttime or early morning coughing episodes. Prolonged antibiotic treatment is ineffective, but bronchodilators can relieve symptoms. Patients often have a personal or family history of allergies^[2].

Since the only or main symptom is chronic irritating cough, it is often misdiagnosed as bronchitis or recurrent upper respiratory infections, leading to delayed treatment.

Can cough-variant asthma develop into typical asthma?

Without medical intervention, about 30%–35% of patients with cough-variant asthma may progress to typical asthma^[2], with an even higher rate in children. Early inhaled corticosteroid treatment can significantly reduce the likelihood of progression.

Which cases of cough-variant asthma are more likely to develop into typical asthma?

Generally, the more severe the airway inflammation, the higher the airway reactivity, the more pronounced the atopy, and the longer the duration of coughing or untreated symptoms, the greater the likelihood of progressing to typical asthma.

SYMPTOMS

What are the typical manifestations of cough variant asthma?

Patients usually have no history of asthma but often have a family history of allergies or allergic diseases, such as allergic rhinitis, eczema, etc. The typical manifestations have the following characteristics:

• Cough often occurs at night, mostly as an irritating dry cough, and may be accompanied by a small amount of white sticky phlegm.
• Persistent and stubborn cough lasting > 8 weeks, often triggered by respiratory irritants (such as smoke), cold air, laughter, deep breathing, or coughing itself.
• No shortness of breath or chest tightness.
• General cough suppressants and antibiotics are ineffective, while bronchodilators (salbutamol, terbutaline) and corticosteroids (prednisone, dexamethasone) can relieve symptoms.

CAUSES

What can cause airway hyperresponsiveness in cough variant asthma?

Airway hyperresponsiveness refers to a state where the airways exhibit an exaggerated response to nonspecific stimuli. Alongside airway inflammation and remodeling, it is one of the key pathological changes in bronchial asthma. As the name suggests, when exposed to certain stimuli such as pollen or cold air, the patient's airways are more sensitive and reactive than those of an average person, leading to a range of symptoms^[3].

How does coughing occur?

Coughing is a protective reflex action of the human body. Typically, the cough reflex effectively clears secretions from the respiratory tract or foreign objects that enter the airways.

After stimuli that trigger coughing are transmitted to the cough center, a series of actions occur, including inhalation, closure of the glottis, rapid contraction of expiratory muscles to generate high pressure in the lungs, sudden opening of the glottis, and explosive expulsion of air to remove substances from the airways.

Stimuli that induce coughing include physical, inflammatory, and psychogenic factors. Mild coughing has little impact on daily life, but severe or persistent coughing can disrupt a patient's daily activities and sleep, necessitating medical evaluation to determine the cause.

How does cough variant asthma develop?

The exact cause of asthma remains unclear. A patient's individual allergic predisposition and external environmental influences are risk factors for the condition, meaning it is related to both internal and external factors—genetic and environmental influences^[3].

• Genetic factors: Many studies indicate that the prevalence of asthma is higher among relatives of asthma patients compared to the general population, with closer relatives showing a higher incidence. The more severe the patient's condition, the higher the prevalence among their relatives. The specific genes associated with asthma have not yet been fully identified^[3].
• Environmental factors: These primarily include certain triggers such as dust mites, pollen, fungi, animal dander, sulfur dioxide, ammonia, and other specific or nonspecific inhalants; infections like bacteria, viruses, protozoa, or parasites; foods such as fish, shrimp, crab, eggs, or milk; medications like propranolol or aspirin; and factors like climate changes, exercise, or pregnancy, all of which may act as asthma triggers.

Which groups are more prone to cough variant asthma?

It can occur at any age, but children have a higher incidence rate, while among adults, it is more common in women^[2].

Does cough variant asthma have seasonal patterns?

Some patients experience seasonal patterns in their episodes, with higher occurrences in spring and autumn, often linked to allergens like pollen in the air, seasonal changes, cold air, and other triggers during these periods^[4].

DIAGNOSIS

What diseases should be considered for cough?

Cough can occur in various diseases involving different parts such as the nose, trachea, lungs, stomach, and esophagus. It can be triggered by infections, inflammation, allergies, reflux, pulmonary congestion, and other causes.

Cough is typically classified by duration: (adults) acute (< 3 weeks), subacute (3–8 weeks), and chronic (> 8 weeks); (children) acute (< 2 weeks), prolonged (2–4 weeks), and chronic (> 4 weeks)^[5].

• Acute cough is most commonly caused by the common cold, but other causes include acute tracheobronchitis, acute sinusitis, allergic rhinitis, acute exacerbation of chronic bronchitis, and bronchial asthma.
• The most common causes of subacute cough are post-infectious cough, bacterial sinusitis, and asthma.
• Chronic cough can be divided into two categories: one with obvious abnormalities on chest X-rays, such as pneumonia, tuberculosis, lung cancer, bronchiectasis, and chronic bronchitis; the other is unexplained chronic cough, where the chest X-ray appears normal, and cough is the primary or sole symptom.

What is chronic cough?

Unexplained chronic cough, commonly referred to as chronic cough, refers to a cough lasting more than 8 weeks (4 weeks in children). It is the main symptom, with no hemoptysis, little or no sputum, normal chest imaging, no history of recurrent respiratory infections, no smoking history (or cessation for 4 weeks), and no exposure to occupational harmful gases or dust.

The most common causes of chronic cough include upper airway cough syndrome (UACS) [also known as postnasal drip syndrome (PNDS)], cough-variant asthma (CVA), gastroesophageal reflux-related cough (GERC), eosinophilic bronchitis (EB), and atopic cough (AC)^[5].

Which department should be visited for cough-variant asthma?

Respiratory medicine.

What tests should be done for cough-variant asthma?

• Bronchial provocation test: Helps diagnose cough-variant asthma (CVA). A negative result largely rules out CVA^[4].
• Bronchodilator test and PEF (peak expiratory flow) diurnal variability monitoring: A positive response to bronchodilator treatment and PEF diurnal variability exceeding 20% suggest CVA^[4].
• Induced sputum cell analysis: This technique obtains lower airway fluid samples. Analyzing sputum cell composition provides insights into cellular changes in respiratory diseases. Eosinophils are detected in all typical asthma patients and in 66.7% of CVA patients^[4].
• Chest imaging: Used for exclusionary diagnosis. CVA typically shows no abnormalities, but patchy shadows may appear if infection is present.

How is cough-variant asthma diagnosed?

• Chronic cough lasting over 8 weeks, often with noticeable nighttime irritative cough, without wheezing or dyspnea, and no history of upper respiratory infection in the past 8 weeks.
• Cough episodes are relieved by bronchodilator treatment (essential diagnostic criterion).
• Airway hyperresponsiveness, confirmed by a positive bronchial provocation test or bronchodilator test, supports the diagnosis.
• Normal chest X-ray findings.
• Increased eosinophils in sputum or blood.
• Exclusion of other causes of chronic cough.

What diseases can cough-variant asthma be confused with?

Cough-variant asthma should be differentiated from the following conditions^[4]:

• Atopic cough: Patients often have a history of allergies or allergen exposure but no airway hyperresponsiveness. Bronchodilators are ineffective. A bronchial provocation test can help differentiate.
• Eosinophilic bronchitis: Patients mainly exhibit chronic irritative cough with increased eosinophils in sputum but no airway hyperresponsiveness. A bronchial provocation test can distinguish it.
• Post-infectious cough: Patients typically have a dry, irritative cough with small amounts of white sticky sputum and a recent upper respiratory infection history. Airway hyperresponsiveness may be transient. Symptoms are self-limiting and resolve within 3–8 weeks. Differentiation relies on infection history and induced sputum cell analysis.
• Postnasal drip syndrome: Often secondary to rhinitis, acute sinusitis, or nasal polyps, with a sensation of postnasal drip. Cough is triggered by throat irritation from dripping secretions. Sinus CT can aid differentiation.

Additionally, it should be distinguished from rhinitis, sinusitis, gastroesophageal reflux syndrome, airway tumors (or foreign bodies), etc. A detailed medical history, medication review, sinus CT, 24-hour esophageal pH monitoring, and bronchoscopy may be necessary for differentiation^[4].

TREATMENT

How to Treat Cough Variant Asthma?

The key to treating cough variant asthma (CVA) lies in accurate diagnosis. Its treatment principles are largely the same as those for typical asthma, focusing primarily on anti-inflammatory therapy supplemented by bronchodilator treatment. Inhaled corticosteroids and β2-agonists are the first-line medications^[4].

Corticosteroids are the most effective drugs for controlling airway inflammation. Anti-inflammatory therapy can reverse airway inflammation and prevent coughing episodes, making it the most important and fundamental treatment for CVA. After diagnosis, inhaled corticosteroids should be initiated as soon as possible to reduce the risk of CVA progressing to typical asthma. Commonly used drugs include prednisone and dexamethasone.

In addition to inhaled corticosteroids, leukotriene receptor antagonists (LTRAs) can be combined to further alleviate cough symptoms, reduce airway inflammation, and promote lung function recovery. These drugs have minimal side effects and rare adverse reactions, though patients with liver dysfunction may experience nausea, vomiting, or jaundice^[4].

β2-agonists are bronchodilators that effectively relieve cough symptoms by expanding the airways but do not reduce airway hyperresponsiveness. Common drugs include salbutamol, terbutaline, and salmeterol. They act on β2 receptors on airway smooth muscle and mast cells, relaxing smooth muscles, reducing degranulation and mediator release from mast cells and eosinophils, decreasing microvascular permeability, and enhancing ciliary movement in airway epithelium to alleviate asthma symptoms. Common side effects include arrhythmia, muscle tremors, and an increased risk of acidosis^[4].

What Should Be Noted in the Medication for Cough Variant Asthma?

Inhalation is the preferred route of administration, as it delivers medication directly to the airways, requiring smaller doses and acting quickly. Like typical asthma, CVA is prone to recurrence, making treatment during stable periods crucial.

Additionally, patient education is essential to ensure a thorough understanding of the disease, adherence to regular medication, and cooperation with treatment for optimal outcomes.

Strengthening immune function and avoiding triggers as much as possible can help prevent CVA recurrence.

Does the Treatment Approach Remain the Same if CVA Progresses to Typical Asthma?

CVA and typical asthma share the same underlying pathology, so the basic treatment principles are identical. While minimizing exposure to risk factors, the focus remains on managing chronic airway inflammation and relieving bronchospasm, with regular follow-ups to adjust treatment under medical supervision.

Can Cough Variant Asthma Be Cured?

CVA is difficult to cure. Like chronic conditions such as hypertension and diabetes, asthma involves chronic non-specific airway inflammation that can be well-controlled but not eradicated. Standardized treatment is necessary to achieve symptom control and maintain normal daily life.

Asthma control entails two aspects: first, effectively managing symptoms like cough, wheezing, and chest tightness to minimize or prevent attacks; second, preventing acute exacerbations, improving lung function, and enhancing long-term prognosis.

Achieving these goals requires consistent treatment, regular follow-ups, and adjustments to the treatment plan under medical guidance. Patients must avoid irregular medication use or self-discontinuation, which can worsen the condition^[4].

Can Antibiotics Be Used for Airway Inflammation in CVA?

Asthma involves "chronic non-specific inflammation" of the airways, which differs from infections caused by bacteria or viruses. Instead, it is mediated by various cells and cellular components. Therefore, antibiotics targeting bacteria are ineffective, and corticosteroids are necessary to control airway inflammation.

Is Hormone Therapy Safe for CVA?

Many worry about side effects like weight gain, acne, hyperglycemia, or osteonecrosis with corticosteroids. However, inhaled corticosteroids (ICS) are recommended for airway inflammation in asthma, acting directly on the airways. Compared to systemic use, ICS rarely cause systemic complications and are clinically safe, even for pregnant women. Common local side effects include throat discomfort, hoarseness, and fungal infections, which can largely be avoided with proper inhalation techniques.

Fear of ICS side effects may lead to uncontrolled asthma attacks, necessitating higher systemic steroid doses—resulting in more adverse effects. This trade-off is counterproductive.

DIET & LIFESTYLE

What are the precautions for using inhalation devices in cough variant asthma?

• Different inhalation devices have different usage methods.
• Slow, forceful inhalation and breath-holding after inhalation are crucial.
• If not performed correctly, it may significantly reduce the dose of medication reaching the lower respiratory tract and lungs, thereby affecting clinical efficacy.
• Additionally, to minimize the side effects of inhaled corticosteroids, it is important to rinse the throat thoroughly and promptly after use to remove residual medication.

Is cough syrup effective for severe cough variant asthma?

Most Western cough syrups contain ingredients like codeine or ephedrine, which have central cough-suppressing effects. While they may partially relieve coughing, cough variant asthma is fundamentally caused by chronic airway inflammation and hyperresponsiveness. Symptomatic treatment with cough suppressants alone often fails to address the root cause and may delay proper diagnosis and treatment. Therefore, cough suppressants are not recommended—targeting the underlying cause is essential.

What lifestyle precautions should be taken for cough variant asthma?

• Adjust clothing according to weather changes to avoid colds that may trigger coughing and worsen asthma symptoms.
• Those prone to allergies should avoid pollen, dust mites, paint, and other irritants to prevent respiratory tract irritation.
• Avoid crowded or poorly ventilated areas; wear a mask if necessary.
• Learn the correct usage of inhalation devices, as methods vary by device—consult the manufacturer for specifics.

What dietary precautions should be taken for cough variant asthma?

Maintain a light, easily digestible diet with adequate vitamins and protein, such as fish, soy products, and fresh fruits and vegetables, to strengthen immunity.
Quit smoking and alcohol to avoid irritating the respiratory tract and worsening symptoms.

Individuals allergic to certain foods (e.g., eggs, peanuts, milk) should avoid them^[4].

PREVENTION

How to Prevent Cough Variant Asthma Attacks?

• During seasonal transitions or sudden temperature changes, parents should keep their children warm to avoid catching colds.
• It is recommended to undergo allergen testing at a hospital to identify and avoid allergens.
• Avoid consuming foods that may trigger allergic reactions, such as foreign proteins (eggs, milk), seafood, and cold drinks.
• Avoid keeping pets or flowers at home, and do not use carpets to minimize exposure to pollen, dust mites, cooking fumes, and paint.
• Do not let children sleep with long-haired stuffed toys.
• Maintain a clean and hygienic living environment with regular ventilation.
• Use dehumidifiers and air purifiers in bathrooms and basements, and replace filters regularly.
• Frequently air out bedding and quilts.