Cough is a common symptom of respiratory diseases and facilitates the removal of respiratory secretions and harmful factors, but frequent and severe coughing can have a serious impact on the patient’s work, life and social activities. Many patients are misdiagnosed as “chronic bronchitis” or “bronchiectasis” for a long time, and a large number of patients are treated with antibacterial drugs that are ineffective. Many patients have been misdiagnosed as “chronic bronchitis” or “bronchiectasis” for a long time and have been treated ineffectively with a large number of antibacterial drugs, or have undergone various tests repeatedly due to unclear diagnosis, which not only increases patients’ pain but also increases their economic burden.
With the increasing concern about cough, various studies on the causes and treatment of cough have been conducted in Europe and the United States in the past 20 years, which have basically clarified the common causes of chronic cough and have led to the formulation of guidelines for the diagnosis and treatment of cough in recent years. In China, clinical studies on the diagnosis and treatment of cough etiology have also been conducted in recent years, and preliminary results have been obtained. In order to further standardize the diagnosis and treatment of acute and chronic cough in China and strengthen clinical and basic research on cough, the Asthma Group of the Chinese Medical Association’s Respiratory Diseases Branch organized relevant experts and jointly developed the Guidelines for the Diagnosis and Treatment of Cough (draft) with reference to the results of domestic and foreign clinical studies on cough, with a view to providing scientific diagnosis and effective treatment for different types of cough.
I. Classification and causes of cough
Cough is usually classified into 3 categories according to time: acute cough, subacute cough and chronic cough. Acute cough lasts <3 weeks, subacute cough 3-8 weeks, and chronic cough ≥8 weeks.
1. Acute cough: The common cold is the most common cause of acute cough. Other causes include acute bronchitis, acute sinusitis, allergic rhinitis, acute attacks of chronic bronchitis, and bronchial asthma (asthma for short).
2. Subacute cough: The most common causes are post-cold cough (also known as post-infectious cough), bacterial sinusitis, asthma, etc.
3. Chronic cough: Chronic cough has more causes and can usually be divided into two categories: one category is those with clear lesions on initial X-ray chest films, such as pneumonia, tuberculosis and lung cancer. The other category is those who have no obvious abnormalities on X-ray chest films and whose cough is the main or only symptom, which is usually referred to as chronic cough of unknown origin (referred to as chronic cough). The common causes of chronic cough are cough variant asthma (CVA), postnasal drip syndrome (PNDs), eosinophilic bronchitis (E and gastroesophageal reflux cough (GERC), which account for 70% to 95% of chronic cough in respiratory medicine outpatient clinics. Other etiologies are less common but widely involved, such as chronic bronchitis, bronchiectasis, endobronchial tuberculosis, allergic cough (AC), and psychogenic cough.
II. Medical history and auxiliary examination
1. History taking and physical examination: Careful history taking plays an important role in the etiological diagnosis and can narrow down the diagnosis of chronic cough, lead to a preliminary diagnosis for treatment or select relevant examinations according to the clues provided by the present history.
Pay attention to the nature, tone, rhythm and duration of cough, triggering or aggravating factors, postural effects, and concomitant symptoms. Understanding the quantity, color, odor and properties of coughing sputum is of great value for diagnosis. In cases of high sputum volume and purulent sputum, infectious diseases of the respiratory tract should be considered first. The diagnosis of asthma is suggested when the expiratory croup is detected on physical examination, and if the inspiratory croup is detected, central lung cancer or endobronchial tuberculosis should be alerted.
2.Related auxiliary examinations.
(1) Induced sputum examination: it was first used for the diagnosis of bronchial lung cancer, and the positive rate of cancer cell examination can be significantly increased by induced sputum cytology examination, which is even the only diagnostic method for some early lung cancers. Increased eosinophils in cytology is the main indicator for the diagnosis of EB. Sputum induction is often performed by ultrasonic nebulized aspiration of human hypertonic saline.
(2) Imaging radiographs can determine the location, extent and morphology of lung lesions, and even their nature, yielding a preliminary diagnosis to guide empirical treatment and correlative testing. X-ray chest radiographs are recommended as a routine examination for chronic cough, and if organic lesions are found, correlative examinations are selected according to lesion characteristics. x-ray chest radiographs without obvious lesions are examined according to the chronic cough diagnostic procedure. Chest CT examination helps to detect anterior and posterior mediastinal lung lesions, small intrapulmonary nodules, enlarged mediastinal lymph nodes and smaller masses in the marginal lung fields. High-resolution CT helps to diagnose early interstitial lung disease and atypical bronchiectasis.
(3) Pulmonary function tests: Ventilation function and bronchodilation tests can help diagnose and identify airway obstructive diseases such as asthma, chronic bronchitis and large airway tumors. Routine lung function is normal, and CVA can be diagnosed by excitation test.
(4) Fiberoptic bronchoscopy (referred to as fiberoptic bronchoscopy): it can effectively diagnose lesions in the tracheal lumen, such as bronchopulmonary cancer, foreign bodies, and endothelia tuberculosis.
(5) Esophageal 24h pH monitoring: It can determine the presence of gastroesophageal reflux (GER), and is the most effective method to diagnose GERC. By dynamically monitoring the change of esophageal pH, six parameters such as the number of times of 24h esophageal pH <4, the longest reflux time, and the percentage of esophageal pH <4 in the monitoring time are obtained, and finally the degree of reflux is expressed by Demeester score. Reflux-related symptoms were recorded in real time during the examination to obtain the correlation probability (SAP) between reflux and cough symptoms, and to clarify the relationship between reflux temporal phase and cough.
(6) Cough sensitivity test: Subjects were made to inhale a certain amount of aerosolized particles of irritants by nebulization to stimulate the corresponding cough receptors and induce cough, and the number of coughs was used as an indicator of cough sensitivity. Capsaicin inhalation is commonly used for cough provocation tests. Increased cough sensitivity is commonly seen in AC, EB, and GERC.
(7) Other tests: Increased eosinophils in peripheral blood tests suggest parasitic infections, allergic diseases. Allergen skin test (SPT) and serum specific IgE assay can help diagnose allergic diseases and determine the type of allergens.
III. Diagnosis and treatment of acute cough
The etiology of acute cough is relatively simple and the most common cause is the common cold. The cough of the common cold is often associated with postnasal drip. A diagnosis of the common cold can be made when a healthy adult has the following four criteria.
(1) Nasal-related symptoms (e.g., runny nose, sneezing, nasal congestion, and postnasal drip), with or without fever.
(2) Tearfulness.
(3) Irritation or discomfort in the throat.
(4) Normal chest physical examination.
Treatment of the common cold: symptomatic treatment is the mainstay, and antibacterial drugs are generally not required.
(1) Decongestants: pseudoephedrine, etc.
(2) Antipyretic drugs: antipyretic and analgesic drugs.
(3) Anti-allergic drugs: first-generation antihistamines.
(4) Anti-cough drugs: central cough suppressants, proprietary Chinese medicines, etc. The first-generation antihistamines + pseudoephedrine are usually used to treat the cough, which can effectively relieve sneezing and nasal congestion. Central cough suppressants, such as dextromethorphan or codeine, are used for obvious cough.
IV. Etiology and treatment of common chronic cough
The etiology of chronic cough is relatively complex, and clarifying the cause is the key to successful treatment. Most chronic coughs are not associated with infection and do not require treatment with antibacterial drugs. When the cause of cough is unknown or infection cannot be excluded, glucocorticoids should be used with caution.
(-) CVA
1. Definition: CVA is a special type of asthma in which cough is the only or main clinical manifestation without obvious symptoms or signs such as wheezing and shortness of breath, but with airway hyperresponsiveness.
2. Clinical manifestations: The main manifestation is a prickly dry cough, usually more intense, with nighttime cough as its important feature. Cold, cold air, dust and fumes can easily induce or aggravate the cough.
3. Diagnosis: Conventional anti-cold and anti-infection treatment is ineffective, and bronchodilator treatment can effectively relieve cough symptoms, and this point can be used as the basis for diagnosis and differential diagnosis. Pulmonary ventilation function and airway hyperresponsiveness examination are key methods to diagnose CVA.
Diagnostic criteria.
(1) Chronic cough often accompanied by significant nocturnal irritant cough.
(2) Positive bronchial excitation test or diurnal variability of maximal expiratory flow (PEF) >20%.
(3) Effective treatment with bronchodilators and glucocorticoids.
(4) Exclude other causes of chronic cough.
4. Treatment: The principles of CVA treatment are the same as those of asthma treatment. Most patients can be treated with small doses of glucocorticoids plus beta agonists, and oral glucocorticoid therapy is rarely needed. The duration of treatment is not less than 6~8 weeks.
(II) PNDs
1.Definition of NDs is a syndrome in which secretions flow backwards into the postnasal and pharyngeal areas, or even backwards into the vocal cords or trachea due to nasal diseases, resulting in cough as the main manifestation.
2. Clinical manifestations: In addition to cough and sputum, patients with PNDs usually complain of flu dripping from the throat, adherence of oropharyngeal mucus, frequent throat clearing, throat itching discomfort or nasal itching, nasal congestion, runny nose, sneezing, etc. Sometimes patients complain of hoarseness and speech induced cough, but other causes of cough itself also have such complaints. Often the onset is preceded by a history of upper respiratory illness (e.g., cold).
3. Diagnosis: The underlying diseases that cause PNDs include seasonal allergic rhinitis, perennial allergic rhinitis, perennial non-allergic rhinitis, vasodilatory rhinitis, infectious rhinitis, fungal rhinitis, common cold, and paranasal sinusitis. Those with large amounts of sputum are mostly due to chronic sinusitis. Vasodilatory rhinitis is characterized by large amounts of thin, watery nasal secretions sometimes produced in response to changes in temperature.
Imaging signs of chronic sinusitis are mucosal thickening of the paranasal sinuses of more than 6 mm, air-fluid planes, or sinus cavity obscuration. SPT can help in the diagnosis if the cough is seasonal or if the history suggests an association with exposure to specific allergens (e.g., pollen, dust mites). Skin tests for Aspergillus and other fungi and specific IgE testing are feasible when allergic fungal sinusitis is suspected.
Diagnostic criteria.
(1) Episodic or persistent cough with a predominantly daytime cough and less frequent cough after sleep.
(2) Postnasal drip and/or a feeling of mucus adherence to the posterior pharyngeal wall.
(3) History of rhinitis, sinusitis, nasal polyps or chronic pharyngitis.
(4) Examination reveals mucus adherence and cobblestone-like view of the posterior pharyngeal wall.
(5) Relief of cough after targeted treatment.
PNDs involve a variety of underlying diseases, and their diagnosis is mainly based on a combination of history and relevant examinations, so other common causes of chronic cough should be excluded before establishing a diagnosis. In recent years, some scholars have directly adopted rhinitis/sinusitis as the etiological diagnosis of chronic cough without using the terminology of PNDs.
4. Treatment: It depends on the underlying disease that causes PNDs. First-generation antihistamines and decongestants are preferred for PNDs caused by the following etiologies
(1) Non-allergic rhinitis.
(2) Vasodilatory rhinitis.
(3) Year-round rhinitis.
(4) Common cold.
The first generation of antihistamines is represented by chlorpheniramine maleate, and the commonly used decongestant is pseudoephedrine hydrochloride. Most patients develop efficacy within a few days to 2 weeks after initial treatment.
Various antihistamines are effective in the treatment of allergic rhinitis. Second-generation antihistamines without sedative effects are preferred, and commonly used drugs are loratadine or asmizole.
Nasal inhalation glucocorticoids are the drug of choice for allergic rhinitis, usually beclomethasone propionate (50 μg/dose per nostril) or equivalent doses of other inhaled glucocorticoids once or twice daily. Sodium cromoglycate inhalation also has a good preventive effect on allergic rhinitis, applied at a dose of 20 mg/dose 3-4 times daily. Improving the environment and avoiding allergenic stimuli are effective measures to control allergic rhinitis. Allergen immunotherapy may be effective, but has a long onset of action.
Antibacterial drug therapy is the main drug for acute bacterial sinusitis, and nasal inhalation of glucocorticoids and decongestants may be used to reduce inflammation when the effect is poor or the secretion is high.
For the treatment of chronic sinusitis, the following primary treatment regimen is recommended: application of antibacterial drugs effective against gram-positive, gram-negative and anaerobic bacteria for 3 weeks; oral first-generation antihistamines and decongestants for 3 weeks; nasal decongestants for 1 week; and nasal inhaled glucocorticoids for 3 months. Negative pressure drainage, puncture drainage or surgery is feasible when internal treatment is not effective.
(C) EB
1. Definition: A non-asthmatic bronchitis characterized by airway eosinophil infiltration, which is an important cause of chronic cough.
2. Clinical manifestations: The main symptom is chronic irritant cough, which is often the only clinical symptom, usually dry, occasionally with a little mucous sputum, and can be coughing during the day or at night. Some patients are sensitive to fumes, dust, odors or cold air, which are often triggering factors for coughing. Patients do not have symptoms such as shortness of breath or dyspnea. Pulmonary ventilation function and peak expiratory flow rate variability (PEFR) are normal, and there is no evidence of airway hyperresponsiveness.
3. Diagnosis: The clinical manifestations of EB lacked characteristic features, and some of them were similar to CVA, with no abnormal findings on physical examination, and the diagnosis mainly relied on induced sputum cytology. Specific criteria are as follows.
(1) Chronic cough, mostly irritating dry cough, or with a small amount of mucous sputum.
(2) Normal x-ray chest film.
(3) Normal pulmonary ventilation function, negative airway hyperresponsiveness test, and normal PEF inter-day variability.
(4) Sputum cytology with eosinophil ratio ≥0.03.
(5) Exclude other eosinophilic diseases. Oral or inhaled glucocorticoids are effective.
4. Treatment: EB responds well to glucocorticoid therapy and the cough disappears or is significantly reduced after treatment. Bronchodilator treatment is ineffective.
Usually treated with inhaled glucocorticoids, beclomethasone dipropionate (250-500 μg each time) or equivalent doses of other glucocorticoids, applied twice daily for more than 4 weeks. Dry powder inhalers are recommended. Initial treatment can be combined with prednisone orally at 10-20 mg per day for 3-7 d.
(iv) GERC
1.Definition: GERC is a common cause of chronic cough due to reflux of gastric acid and other gastric contents into the esophagus, resulting in a prominent clinical manifestation of cough.
2. Clinical manifestations: Typical reflux symptoms are burning sensation behind the sternum, acid reflux, belching, chest tightness, etc. GER patients with trace aspiration are more likely to have cough symptoms and throat symptoms in the early stage. There are also many patients with GERC who have no clinical symptoms of reflux, and cough is their only clinical manifestation. The cough mostly occurs in the daytime and in the upright position, with a dry cough or a small amount of white mucous sputum.
3. Diagnosis: Patients with cough accompanied by reflux-related symptoms or cough after eating are of some significance in suggesting the diagnosis. 24h esophageal pH monitoring is currently the most effective method for diagnosing GERC by dynamically monitoring the changes in distal and proximal esophageal pH, and the results are expressed as Demeester’s score, SAP (see Annex 3 for details of the operation method).
Barium meal examination and gastroscopy have limited diagnostic value for GERC, and the correlation between reflux and cough cannot be determined.
4. Diagnostic criteria.
(1) Chronic cough, mainly daytime cough.
(2) 24h esophageal pH monitoring Demeester score ≥12.70, and/or SAP ≥75%.
(3) Exclusion of CVA, EB, PNDs and other diseases.
(4) Significant reduction or disappearance of cough after anti-reflux treatment.
For patients with chronic cough in units without esophageal pH monitoring or with limited economic conditions, diagnostic therapy may be considered for those with the following indications
(1) The patient has a significant feeding-related cough, such as postprandial cough and feeding cough.
(2) Patients with GER symptoms, such as acid reflux, belching, and retrosternal burning sensation.
(3) Exclusion of diseases such as CVA, EB, PNDs, etc., or poor results of treatment according to these diseases. The cough disappears or is significantly relieved after anti-reflux treatment, and GERC can be clinically diagnosed.
5. Treatment.
(1) Lifestyle adjustment: lose weight, eat less and more often, avoid oversaturated bedtime meals, avoid acidic and oily foods and beverages, avoid coffee and smoking. High pillow position, elevate the head of the bed.
(2) acid control drugs: often choose proton pump inhibitors (such as omeprazole or other similar drugs) or H2 receptor antagonists (ranitidine or other similar drugs).
(3) Gastric stimulants: such as domperidone, etc.
(4) Any patient with underlying gastroduodenal disease (chronic gastritis, gastric ulcer, duodenitis or ulcer) with H. pylori infection should be treated accordingly.
(5) The duration of medical treatment should be more than 3 months, usually 2 to 4 weeks to show the effect. In a small number of patients with severe reflux who fail medical treatment, anti-reflux surgery can be considered.
V. Other chronic coughs
Etiology and diagnosis and treatment
(I) Chronic bronchitis
Definition: as cough and sputum for more than 2 consecutive years, accumulating or persisting for at least 3 months each year, and excluding other causes of chronic cough. ChB is the most common cause of chronic cough, yet it accounts for only a minority of patients with chronic cough seen in outpatient clinics. It is important to note that many patients with chronic cough of other etiologies are often misdiagnosed as ChB in clinical practice.
(ii) Bronchiectasis
Non-reversible bronchial dilatation and luminal deformation due to destruction of the airway wall caused by chronic inflammation, with the main lesion sites being the subsegmental bronchi. The clinical manifestations are cough, coughing up pus sputum and even hemoptysis. The diagnosis is not difficult for those with a typical medical history, while mild bronchiectasis without a typical medical history is easily misdiagnosed. x-ray chest changes (e.g., curly hair-like) are suggestive of the diagnosis, and when bronchiectasis is suspected, the best diagnostic method is high-resolution CT of the chest.
(iii) Allergic cough (AC)
1. Definition: Some patients with chronic cough with some atopic factors and effective treatment with antihistamines and glucocorticoids but cannot be diagnosed with asthma, allergic rhinitis or EB define this type of cough as AC. its relationship with allergic pharyngitis, EB and post-cold cough and its similarities and differences need to be further clarified.
2. Clinical manifestations: irritating dry cough, mostly paroxysmal, daytime or nighttime cough, easily induced by fumes, dust, cold air, speech, etc., often accompanied by itching of the throat. Ventilation function is normal, and the percentage of eosinophils in induced sputum cytology is not high.
3. Diagnostic criteria: There are no accepted criteria, and the following criteria are for reference.
(1) Chronic cough.
(2) Normal pulmonary ventilation function and negative airway hyperresponsiveness test.
(3) One of the following indications: (1) history of allergen exposure; (2) positive SPT; (3) increased serum total IgE or specific IgE; (4) increased cough sensitivity.
(4) Exclude other causes of chronic cough such as CVA, EB, and PNDs.
(5) Effective treatment with antihistamines and/or glucocorticoids.
It should be noted that the latest guidelines have changed PNDs to upper airway cough syndrome.