OVERVIEW
An atypical form of asthma in which chronic cough is the sole or predominant symptom and there is airway hyperresponsivenessChronic cough is the sole or predominant symptom and its onset is influenced by a combination of genetic and environmental factorsIdentifying and avoiding possible causes of the disease, along with medication, improves symptoms.
Definition
Cough variant asthma is an atypical form of asthma in which chronic cough is the only or main symptom (excluding cough caused by other diseases), without significant wheezing or shortness of breath, and with airway hyperresponsiveness.
Morbidity
Some studies have shown that cough variant asthma accounts for about one-third of the causes of chronic cough in adults. Cough variant asthma is ultimately diagnosed in approximately 40% of children presenting with chronic cough.
The two peaks of incidence are in boys younger than 15 years of age and in women older than 30 years of age.
Blacks are at higher risk of developing the disease than whites in children.
Causes
Causes
It is currently believed that the development of cough variant asthma is influenced by host and environmental factors.
Genetic factors
Cough variant asthma has a polygenic predisposition and its onset is clustered in families.
Environmental factors
Allergens
House dust mites and fungi are the major indoor airborne allergens, and pollen and grass pollen are common outdoor allergens.
Common medications include biologics, propranolol, neostigmine, aspirin, and ibuprofen.
Foods such as milk, eggs, seafood and flavored food groups are common.
Others include small insect carcasses, cotton and linen fibers, lipstick, lip balm, nail polish, eyebrow strokes, facial oils and hair dyes, organic solvents, various metal ornaments, grain flour, flour, and animal hides.
Infections
Respiratory viral infections are associated with the formation and exacerbation of cough variant asthma, most commonly rhinovirus.
Tobacco exposure, air and environmental pollution
Environmental exposures are strongly associated with the development of asthma.
The most common are gas (especially SO₂), oil smoke, passive smoking, and insecticidal sprays.
Others
Psychosomatic factors
Strong emotions and stress may contribute to the formation and exacerbation of cough variant asthma.
Gastroesophageal reflux
One of the most common causes of cough variant asthma.
Pathogenesis
The pathogenesis of cough variant asthma has not been fully elucidated, but is currently thought to be summarized as airway immune-inflammatory mechanisms, neuromodulatory mechanisms, and their interactions.
Airway immune-inflammatory mechanisms
When allergens enter the body, the immune system is activated, triggering a rapid-onset (increased IgE) allergic reaction and chronic inflammatory response in the airways, mainly mediated by Th2 (an immune cell), which results in contraction of airway smooth muscle, increased mucus secretion, and infiltration of inflammatory cells, leading to the symptoms of cough-variant asthma.
Neuromodulatory mechanisms
The airways are subject to complex autonomic innervation, such as the nonadrenergic noncholinergic (NANC) nervous system. When certain factors imbalance the regulation of the NANC nervous system, it can lead to contraction of airway smooth muscle, causing asthma attacks.
Symptoms
Main Symptoms
Chronic cough is the only or main symptom of cough-variant asthma, usually without wheezing or shortness of breath.
The cough tends to be irritating and dry, and is usually severe.
The cough is predominantly nocturnal.
Colds, odors, fumes, exercise, and cold air tend to trigger or aggravate the cough.
A severe cough may also be accompanied by chest tightness, dyspnea, and wheezing.
Complications
Cough variant asthma can cause the following complications if it is not treated promptly and regularly.
Infection
Chronic infections can occur if the attacks are poorly controlled over a long period of time.
Acute infections may include fever, chills, chills, and weakness.
Bronchiectasis
Repeated infections over a long period of poorly controlled disease can lead to destruction of the supporting structure of the airway wall, causing persistent dilatation of the bronchial wall.
The manifestations are repeated cough, hemoptysis, coughing up a large amount of pus sputum, loss of appetite and emaciation.
Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (COPD) can occur in patients with uncontrolled cough variant asthma who are chronically exposed to cigarettes or air pollution.
It is characterized by chronic cough, coughing up white mucus or plasma foamy sputum, shortness of breath or dyspnea, and in severe cases, wheezing and chest tightness.
Thoracic deformities
Patients with asthma, especially those who start at a young age or have recurrent attacks, may develop thoracic deformities.
Barrel chest (an increase in the anterior and posterior diameter of the chest, which resembles a barrel), chicken chest (chest protruding forward, similar to the chest of an avian), etc. may occur.
Atresia Lung Syndrome
Overuse of medication, especially β₂-blockers, can increase bronchospasm and cause the lungs to become “atretic”.
The symptoms include sudden aggravation of wheezing, sitting breathing, cyanosis, accompanied by nervousness, irritability, sweating, and in severe cases, slowing down or even stopping of respiration.
Psychosomatic sleep disorder
May cause anxiety disorder, mood disorder, sleep disorder, etc.
Consultation
Department of Medicine
Respiratory Medicine
Recurrent coughing episodes that are difficult to control are recommended to consult a respiratory medicine department.
Pediatrics
Children with the above symptoms may also be referred to a pediatrician.
Preparation
Preparing for your visit: registering, preparing your documents, and common problems.
Tips
Avoid taking cough suppressants on your own before going to the doctor, as this may affect the doctor’s judgment of the condition.
Chest X-ray or chest CT is often needed, so avoid wearing clothes made of metal, and inform the doctor if you are pregnant or planning to be pregnant.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special signs and symptoms.
Is there fever? What is the highest temperature?
Is there a cough? How long has the cough lasted?
Is there any sputum? What kind of sputum?
How long have the symptoms been present?
Under what circumstances do the symptoms worsen or lessen?
Medical History Checklist
Is there a history of eczema, hives, allergic rhinitis, etc.?
Does anyone in the family have asthma?
Are there allergies to certain foods, medications, mites, pollen, etc.?
Checklist
Test results in the past six months, which can be brought to the doctor’s office
Laboratory tests: blood test, C-reactive protein, specific IgE test, induced sputum cytology
Imaging tests: Chest X-ray, Chest CT scan
Pulmonary function tests: pulmonary ventilation function test, bronchial provocation test, peak expiratory flow rate (PEF) and its variability measurement, bronchodilator test
Medication list
Medication used in the last 3 months, if available in boxes or packages, carry with you to the doctor’s office
Anti-inflammatory drugs: budesonide aerosol, methylprednisolone, montelukast, zalustat
Bronchodilators: salbutamol, terbutaline, aminophylline, ipratropium bromide
Cough suppressants: codeine, dextromethorphan
Diagnosis
Diagnosis is based on
Medical history
A personal or family history of allergic disease.
There are respiratory viral infections, etc.
History of allergen exposure such as dust mites, fungi, pollen, grass pollen, cold air, grain flour, flour, animal fur, etc.
History of exposure to contaminated environments such as gas, fumes, passive smoking, insecticidal sprays, etc.
Clinical manifestations
Chronic cough is the only or main symptom, with frequent attacks at night.
Laboratory Tests
Blood tests
Routine blood tests
Peripheral blood eosinophils can be measured to help determine whether the body is in an allergic state.
There is no need for fasting or water fasting before the test.
Serum Immunology Test
Mainly serum specific IgE test, which is an in vitro test for allergens.
It can clarify whether the patient is in an allergic state, and guide the patient to avoid contact with allergens and carry out specific immunotherapy.
There is no need to fast or abstain from food and water before the test.
Arterial blood gas analysis
It can determine the severity of an acute asthma attack.
In severe asthma attacks, the partial pressure of oxygen decreases significantly while the partial pressure of carbon dioxide increases, and the acid-base balance is disturbed.
There is no need to fast or drink before the test, but after the blood is drawn, it is necessary to press on the eye of the needle for 5 to 10 minutes.
Sputum examination
Basic examination
Sputum eosinophil count can be measured to help determine whether the body is in a state of allergy.
It is recommended to retain the first sputum (natural sputum) in the early morning, first rinse the mouth with water after getting up, then cough out the sputum from the deep part of the trachea with force, put all of them in a clean and dry container, and send the specimen for examination as soon as possible.
Sputum induction and analysis
Before the examination, nebulized inhalation of hypertonic saline induces a strong cough reflex and obtains a specimen of induced sputum; after sputum is coughed out, put all of it into a clean, dry container and send the specimen for examination as soon as possible.
Sputum cell classification and sputum soluble substance testing are feasible to understand the airway secretions. Changes in eosinophils in the induced sputum can be used to assess the severity of cough-variant asthma and to predict the risk of progression to classic asthma.
Lung function tests
It plays a key role in the diagnosis of asthma, in grading the severity of the disease, and in evaluating the effectiveness of treatment.
Ventilation Function Tests
Decreased 1-second forceful expiratory volume (FEV₁), FEV₁ as a percentage of predicted value (FEV₁%pred), 1-second rate (FEV₁/FVC%), mid-maximal expiratory flow rate (MMFR), and peak expiratory flow rate (PEF).
FEV₁/FVC% <70% or FEV₁% <80% were used as the most important indicators of airflow limitation.
Bronchial provocation test
It is used to measure airway responsiveness.
Commonly used inhalation stimulants are acetylmethacholine and histamine.
Positive diagnostic criteria: FEV₁ decreased ≥20%, the judgment result is positive, suggesting the existence of airway hyperresponsiveness.
Positive bronchial provocation test is the most important condition for the diagnosis of the disease.
It is indicated for patients with non-asthmatic exacerbations and FEV₁ above 70% of the normal expected value.
Bronchodilator test
Used to determine airway reversibility.
Commonly used inhaled bronchodilators are albuterol and terbutaline.
Positive diagnostic criteria: an increase in FEV₁ of 12% or more from the pre-medication level and an increase in its absolute value of 200 mL or more.
Measurement of peak expiratory flow rate (PEF) and its rate of variability
A mean daily variability of PEF >10% or a mean weekly variability of PEF >20% suggests the presence of reversible changes in the airway.
The examination helps in diagnosis and evaluation of the condition.
Imaging
Chest X-ray
Lung lesions can be visualized to aid in diagnosis.
It may show increased translucency of both lungs, presenting as hyperinflation, etc.
Precautions
Remove any metal objects, such as metal necklaces, during the examination.
Keep still for a certain period of time during the examination. Children need to be assisted during the examination.
CT examination
The associated lesions of the bronchial tubes can be observed to assist in the diagnosis.
Characteristic manifestations such as bronchial wall thickening and mucus obstruction can be seen.
Precautions
Fasting is not required before the examination, and you can eat and drink normally.
Remove any metal objects, such as metal necklaces, during the examination.
Children or critically ill patients need to be accompanied.
Skin prick test
Helps to determine the type of allergen and guide the patient to avoid exposure to the allergen as much as possible, as well as specific immunotherapy.
A positive test indicates that the patient is allergic to the allergen.
Precautions
Since the skin prick test is an in vivo test, it is important to ensure that a healthcare professional is present during the test and 30 minutes after the test to prevent accidents.
It needs to be performed in a hospital with resuscitation facilities.
Exhaled breath nitric oxide (FeNO) test
assesses the level of airway inflammation and disease control and can also be used to determine response to inhaled hormone therapy.
FeNO reacts to the level of airway inflammation in the T2 pathway; elevated levels may indicate asthma, but low levels do not exclude asthma.
Diagnostic Criteria
Cough variant asthma can be diagnosed by the presence of clinical signs and any one of the objective tests for variable airflow limitation, except for cough caused by other diseases. It should be noted that a positive bronchial provocation test is important for the diagnosis of cough variant asthma, but there are false-positive and false-negative possibilities, which need to be combined with the effectiveness of anti-asthma treatment to confirm the diagnosis.
Clinical manifestations
Chronic cough is the only or main symptom, without wheezing, shortness of breath and other typical asthma symptoms.
Objective tests for variable airflow limitation
Positive bronchodilator test.
Positive bronchial provocation test.
Mean daily PEF diurnal variation >10% or PEF weekly variation >20%.
Differential diagnosis
Eosinophilic bronchitis
Similarities: both have similar cough symptoms.
Differences: eosinophilic bronchiolitis has no airway hyperresponsiveness and can be differentiated by bronchial provocation test.
Bronchial tuberculosis
Similarities: both have similar coughing symptoms.
Difference: Bronchial tuberculosis may also have symptoms of tuberculosis toxicity such as low afternoon fever, night sweats, malaise, emaciation, etc. It can be differentiated by tuberculin test, conjugated antibody test, gamma-interferon release test and bronchoscopy.
Bronchopulmonary carcinoma
Similarity: both have similar cough symptoms.
Differences: Bronchopulmonary cancer often has long-term smoking history, early bronchopulmonary cancer has insidious onset and atypical symptoms. In middle and late stage, it may manifest as irritating dry cough, blood in sputum, chest pain, emaciation and other symptoms, or the nature of the original cough changes, which can be differentiated by imaging examination, bronchoscopy and pathological examination.
Chronic bronchitis
Similarities: Both have similar cough symptoms.
Differences: Chronic bronchitis often has a history of smoking and is accompanied by coughing and wheezing, with an onset of illness lasting 3 months per year, for 2 or more consecutive years, with effective anti-infective treatment, and can be differentiated by pulmonary function tests.
Bronchiectasis
Similarities: Both have similar coughing symptoms.
Differences: bronchiectasis may also have symptoms such as coughing up pus and hemoptysis, and can be differentiated by imaging tests such as chest CT.
Medicinal Cough
Similarities: Both have similar cough symptoms.
Difference: Drug induced cough may disappear after stopping medication.
Treatment
Treatment goal: to achieve overall asthma control, both to achieve current symptom control and to reduce risk factors for poor prognosis.
Treatment principle: The treatment principle of cough variant asthma is the same as that of typical asthma, mainly adopting medication, but also trying to choose immunotherapy and so on according to the condition.
General treatment
Determine and avoid the possible causes of the disease
Treat respiratory infections.
Avoid or reduce exposure to possible allergens such as dust mites, pollen, paint, tobacco, etc.
Avoid allergenic medications and foods.
Avoid factors that may trigger a cough attack
Take rest and avoid excessive exercise.
Reasonable adjustment of emotions, avoiding nervousness, agitation, etc.
Pay attention to prevent cold and keep warm.
Gastroesophageal reflux should be treated actively.
Medications
Bronchodilator drugs
β₂ agonists
Effects: Can relax the airway smooth muscle, reduce the permeability of microvessels, increase the swing of airway epithelial cilia, etc., to relieve symptoms.
Commonly used drugs: salbutamol, terbutaline, salmeterol, formoterol, procaterol, bambuterol, etc.
Adverse effects: common skeletal muscle tremor, hypokalemia, cardiac arrhythmia.
Precautions: Long-term, single application of β₂ agonists can appear clinical resistance phenomenon, so should be avoided.
Theophyllines
Drug effect: can act directly on the bronchial smooth muscle, with the role of diastolic bronchial smooth muscle.
Commonly used drugs: Dosophylline, dihydroxypropyl theophylline, aminophylline.
Adverse effects: nausea, vomiting, cardiac arrhythmia, hypotension.
Precautions: Its blood concentration must be monitored during use to avoid adverse reactions.
Anticholinergic drugs
Effects: By reducing vagal tone and bronchial relaxation, and β₂ agonists have synergistic and complementary effects.
Commonly used drugs: ipratropium bromide and tiotropium bromide.
Adverse reactions: mainly dry mouth, bitter taste sensation, occasionally dry cough and throat discomfort.
Precautions: When nebulized inhalation, avoid the drug entering the eye; use with caution in patients with glaucoma and prostatic hyperplasia.
Anti-inflammatory drugs
Glucocorticoid
Effects: Glucocorticosteroids are the most effective anti-anaphylactic inflammatory drugs, which can effectively relieve symptoms.
Commonly used drugs: prednisone, prednisolone or methylprednisolone, hydrocortisone succinate, beclomethasone propionate, budesonide, fluticasone propionate and so on.
Route of administration: inhalation, oral and intravenous administration, etc. Inhalation is the preferred route.
Adverse effects: Inhaled glucocorticosteroids may cause hoarseness, pharyngeal discomfort and candida infections; long-term oral or intravenous application of glucocorticosteroids may cause osteoporosis, hypertension, diabetes mellitus and obesity.
Precautions: Patients with tuberculosis, parasitic infections, osteoporosis, glaucoma, diabetes mellitus, severe depression, or peptic ulcer should be cautious when given systemic glucocorticoid therapy and should be followed closely.
Leukotriene modifier
Drug effects: strong anti-inflammatory effect, can reduce cough symptoms, improve the quality of life.
Indications: Especially suitable for people with allergic rhinitis.
Commonly used drugs: zalustat, montelukast, etc.
Adverse effects: Psychiatric symptoms may occur.
Precautions: Generally less commonly used alone. Because its anti-inflammatory effect is not as good as glucocorticoids, it needs to be used in combination with glucocorticoids.
Antihistamines
Drug effects: has an anti-allergic effect, but the role in the treatment of bronchial asthma is weaker.
Indications: can be used for people with allergic rhinitis.
Commonly used drugs: ketotifen, loratadine, astemizole, trinitrotol and so on.
Adverse reactions: dizziness, drowsiness, hypotension, cardiac arrhythmia, gastrointestinal reactions.
Allergen-specific immunotherapy (desensitization therapy)
Indications
For asthma patients with clear allergens and poor control despite strict environmental control and medication.
Principle of treatment
The allergen extract is given to the patient by injection and oral administration. By continuously increasing the dose to stimulate the immune system and induce the body’s immune tolerance, the final result is to reduce the symptoms of the allergic reaction, or make the symptoms occur less or even not occur, so as to achieve the purpose of desensitization.
Treatment Methods
Including subcutaneous injection immunotherapy, sublingual immunotherapy, the latter is only available for dust mite allergy in China.
Adverse reactions
Injection site or sublingual may have injection site itching, redness, swelling, hard nodules, etc. Local or generalized urticaria, asthma attacks, gastrointestinal reactions (e.g., abdominal pain, diarrhea), etc. may also occur.
Prognosis
Cure
Some patients with mild disease and clear allergens may experience gradual relief of symptoms after detachment from the allergens.
In most patients, symptoms can be controlled with treatment, but may recur after stopping medication and require long-term treatment.
Some patients will develop typical asthma.
Harmful
Causes complications
If the treatment is not timely and standardized, it can cause infections, bronchiectasis, chronic obstructive pulmonary disease and other complications.
Affects life
Prolonged coughing can affect normal sleep and life.
Symptoms persisting for a long time can have depression, anxiety, fear, personality changes, etc. Often, there is a decrease in social adaptability, self-confidence, and a decrease in socialization.
Daily routine
Daily management
Remove allergens
Avoid foods associated with asthma attacks, such as fish, shrimp, crab, eggs and milk.
Avoid medications associated with asthma attacks, such as propranolol, neostigmine, aspirin, etc.
Remove yourself from work environments that are prone to powders, dust, and odors, such as flour milling, animal fur handling, painters, and insecticide spraying.
Dietary management
Eat a light diet (less oil, less salt, less sugar), avoid spicy and stimulating foods such as chili, pepper, coffee, curry, etc. Avoid eating hard, cold and fried foods.
Maintain a balanced nutrition and eat more foods rich in vitamins and fiber, such as vegetables and fruits.
Certain food additives, such as tartaric yellow and nitrite, can trigger asthma attacks and should be avoided.
Emotional management
Avoid emotional tension and excitement.
Read books, listen to music, drink tea, etc. to regulate your emotions.
Exercise management
Avoid strenuous exercise.
After the disease is controlled and stabilized, moderate aerobic exercise such as walking, jogging, swimming, etc. can be carried out under the guidance of the doctor.
Replenish water in time during exercise.
Follow-up and review
Regular use of medication and regular follow-up examinations are crucial to the treatment of cough variant asthma.
If medication is not effective in relieving cough symptoms, it is recommended that you seek medical attention.
Lung function tests may be required.
Prevention
Nutrition during pregnancy
Eating foods rich in vitamin D and vitamin E during the mother’s pregnancy may reduce the risk of childhood morbidity.
Avoid exposure to allergens
Allergic individuals should avoid exposure to possible allergens.
Avoid foods associated with asthma attacks, such as fish, shrimp, crab, eggs, and milk.
Avoid medications associated with asthma attacks, such as propranolol, neostigmine, and aspirin.
Remove yourself from work environments that are prone to powders, dust, and odors, such as flour milling, animal fur handling, painters, and pesticide spraying.
Avoid contact with house dust mites, fungi and other indoor allergens, maintain environmental hygiene in the living room, sunlight bedding and open windows for ventilation.
Avoid contact with outdoor allergens such as pollen, grass pollen, etc. Reduce going out in spring and fall, and wear a mask when you must go out.
Others
Pay attention to prevent cold and keep warm: cold and respiratory viral infections can easily trigger asthma, seasonal changes in time to add or subtract clothing, to avoid low-temperature stimulation, and do not blow the fan and air conditioning for a long time in summer.
Weight loss: Overweight people should lose weight appropriately to keep their weight within a reasonable range.
Timely vaccination against influenza, pneumonia and new coronavirus when asthma is well controlled.