Coughing is a defensive reflex of the body that facilitates the removal of whistle secretions and harmful factors, but frequent and violent coughing has a serious impact on the patient’s work, life and social activities. Clinically, cough is the most common symptom in internal medicine patients, and the causes of cough are numerous and extensive, especially in chronic cough patients with no obvious abnormalities on chest imaging. Many patients are misdiagnosed as “chronic bronchitis” or “bronchiectasis” for a long time and are treated with a large number of antibacterial drugs that are ineffective, or repeatedly undergo various tests due to unclear diagnosis, which not only increases patients’ pain but also aggravates their economic burden.
With the increasing concern about cough, clinical studies on the diagnosis and treatment of cough etiology have been carried out in China 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 to strengthen clinical and basic research on cough, the Asthma Group of the Chinese Medical Association’s Whistling Branch organized relevant experts and formulated the “Draft Guidelines for the Diagnosis and Treatment of Cough” in 2005, taking into account the results of clinical studies on cough at home and abroad. Since the guidelines were formulated, they have provided good guidance for clinical practice in China, and many experts and colleagues have made many valuable suggestions. In order to further improve the guanxi and to reflect the research progress in the diagnosis and treatment of cough at home and abroad, the Asthma Group of the Chinese Medical Association’s Whistling Branch revised the 2005 version of the “Draft Guidelines for the Diagnosis and Treatment of Cough”.
I. Classification of cough
1. Cough is usually classified into three 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.
2. Cough can be further divided into dry cough and wet cough according to their nature.
3. According to the presence or absence of abnormalities in chest X-ray examinations, there are two categories: one category is those with clear lesions on X-ray chest films, such as pneumonia, tuberculosis and bronchopulmonary cancer; the other category is those with no obvious abnormalities on X-ray chest films and cough as the main or only symptom, which is usually referred to as unexplained chronic cough (referred to as chronic cough).
Medical history and auxiliary examination
Careful history taking and physical examination can narrow down the diagnosis of cough, provide clues to the etiology of the diagnosis, and even lead to a preliminary diagnosis and empirical treatment, or select relevant examinations based on the present medical history to clarify the cause.
1. Inquiring into the medical history.
Attention should be paid to the duration, phase, nature, and timbre of the cough, as well as the triggering or aggravating factors, postural effects, and concomitant symptoms. Understanding the quantity, color, odor and properties of sputum is of great value for diagnosis.
Asking about the duration of the cough can determine acute, subacute or chronic cough and narrow the diagnosis. Knowing the chronology of the cough is also suggestive, e.g. post-exercise cough is commonly associated with exercise asthma, and nocturnal cough is most often seen in cough variant asthma (CVA) and heart disease. High sputum volume and purulent sputum should be considered as an infectious disease of the whistle tract. Chronic bronchitis often coughs up white mucus sputum, with winter and spring coughs predominating. Those with blood in sputum or coughing up blood should consider the possibility of tuberculosis, bronchiectasis and lung cancer. Those with a history of allergic diseases and family history should be careful to exclude cough associated with allergic rhinitis and asthma. Heavy smoking and occupational exposure to dust and chemical substances are also important causes of chronic cough. Patients with a history of gastric disease need to rule out gastroesophageal reflux cough (GERC). Those with a history of cardiovascular disease should be aware of cough caused by chronic cardiac insufficiency, etc. Patients with hypertension taking angiotensin-converting enzyme inhibitors (ACEIs) are a common cause of chronic cough.
2. Physical examination.
This includes the nose, pharynx, trachea and lungs, such as the position of the trachea, jugular venous filling, pharyngeal and nasal cavities, and the whistling sounds of both lungs and the presence or absence of croup and popping sounds. If you hear croup in the whistling phase, it suggests bronchial asthma; if you hear croup in the inspiratory phase, you should be alert to central lung cancer or bronchial tuberculosis, and you should also pay attention to whether the heart border is enlarged, whether there are organic murmurs in the valve area and other cardiac signs.
3.Related auxiliary examinations.
(1) Induced sputum examination.
It was first used for exfoliative cytology diagnosis of bronchial lung cancer. Induced sputum examination with elevated eosinophils is the main indicator for the diagnosis of eosinophilic bronchitis, and the induction of sputum is often performed by ultrasonic nebulized aspiration of hypertonic saline.
(2) Imaging.
X-ray chest radiographs are recommended as a routine examination for chronic cough, and if obvious lesions are found, relevant tests are selected according to the lesion characteristics. X-ray chest radiographs without obvious lesions are examined according to the chronic cough diagnostic procedure (see Chronic cough diagnostic procedure). Chest CT examination helps to detect anterior and posterior mediastinal lung lesions, small intrapulmonary nodules, and enlarged mediastinal lymph nodes, especially lesions not easily detected by chest X-ray, and has important diagnostic value for some rare causes of chronic cough such as bronchial stones and bronchial foreign bodies. High-resolution CT is helpful in diagnosing early interstitial lung disease and atypical bronchiectasis.
(3) Pulmonary function tests.
Ventilation function and bronchodilation test can help diagnose and identify airway obstructive diseases, such as bronchial asthma, chronic obstructive pulmonary disease and large airway tumors. Bronchial excitation test is a key method to diagnose CVA.
(4) Fiberoptic bronchoscopy.
It can effectively diagnose lesions in the tracheal lumen, such as bronchopulmonary cancer, foreign bodies and tuberculosis.
(5) 24h esophageal pH monitoring.
This is the most common and effective method to determine gastroesophageal reflux, but it cannot detect non-acidic reflux. By dynamically monitoring the change of esophageal pH, six parameters such as the number of 24h esophageal pH <4, the longest reflux time, and the percentage of esophageal pH <4 to 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 probability of correlation between reflux and cough symptoms and to determine the relationship between reflux and cough. Non-acidic reflux was monitored using intraesophageal luminal impedance or bilirubin.
(6) Cough sensitivity testing.
The subject is made to inhale a certain amount of irritant aerosol particles by nebulization to stimulate the corresponding cough receptors and induce cough, and the concentration of the inhaled substance is used as an indicator of cough sensitivity. Capsaicin inhalation is commonly used for cough provocation tests. Increased cough sensitivity is commonly seen in allergic cough, post-infectious cough, GERC, etc.
(7) Other tests.
Increased eosinophils in peripheral blood tests suggest parasitic infections and allergic diseases. Allergen skin test and serum specific IgE assay are helpful in diagnosing allergic diseases and determining the type of allergens.
III. Diagnosis and treatment of acute cough
The etiology of acute cough is relatively simple. The common cold and acute tracheobronchitis are the most common diseases of acute cough.
1. Common cold
The clinical manifestations of the common cold are nasal-related symptoms, such as runny nose, sneezing, nasal congestion and postnasal drip flu, throat irritation or discomfort, with or without fever. The cough of the common cold is often associated with postnasal drip.
Treatment is symptomatic, and antibacterial drugs are generally not necessary.
(1) Decongestants: pseudoephedrine hydrochloride (30 – 60 mg/time, 3 times a day), etc.
(2) Anti-allergic drugs: first-generation antihistamines, such as chlorpheniramine maleate (2–4mg/dose, 3 times a day), etc.
(3) antipyretic drugs: antipyretic and analgesic class.
(4) Cough suppressants: for those with severe cough, central or peripheral cough suppressants can be used if necessary.
Clinically, a combination of the above drugs is usually used. First-generation antihistamines + pseudoephedrine are preferred for treatment, which can effectively relieve symptoms such as sneezing and nasal congestion.
2.Acute tracheobronchitis-bronchitis
(1) Definition.
Acute tracheobronchitis is an acute inflammation of the tracheobronchial mucosa caused by biotic or abiotic factors. Viral infection is the most common cause, but often secondary to bacterial infection, cold air, dust and irritating gases can also cause this disease.
(2) Clinical manifestations.
The onset of the disease is often characterized by symptoms of upper whistle infection. Then the cough can gradually increase, with or without coughing sputum, with bacterial infection often cough yellow pus sputum. The cough and sputum usually persist for 2–3 weeks. x-ray examination has no obvious abnormalities or only increased lung texture. On examination, coarse whistling sounds are heard in both lungs, and sometimes wet or dry woven grass can be heard
(3) Diagnosis.
Mainly based on clinical manifestations, we should pay attention to differentiate from influenza, pneumonia, tuberculosis, whooping cough, acute tonsillitis and other diseases.
(4) Treatment.
The principle of treatment is mainly symptomatic treatment. For severe dry cough, appropriate cough suppressants can be applied, and sputum medicine can be used when coughing with sputum that cannot be easily coughed out. If there is bacterial infection, such as purulent sputum or increased peripheral blood leukocytes, antibacterial drugs can be selected according to the pathogen of the infection and the results of drug sensitivity tests. Oral antimicrobial drugs such as macrolides and β-lactams can be used until positive results of pathogenic bacteria are obtained. Bronchodilator drugs can be used when bronchospasm is present.
IV. Diagnosis and treatment of subacute cough
The most common cause of subacute cough is post-infectious cough, followed by upper airway cough syndrome and CVA. In the management of subacute cough, it is important to first clarify whether the cough is secondary to a previous whistling infection and to treat it empirically. If treatment is ineffective, other etiologies are then considered and the diagnosis and treatment are made with reference to the chronic cough diagnostic procedure.
When the cough persists after the acute phase of the whistle infection has disappeared. In addition to whistling viruses, other pathogens such as bacteria, mycoplasma and chlamydia may cause post-infectious cough, of which cough caused by a cold is the most common, also known as “post-cold cough”. Post-infectious cough is usually characterized by an irritating dry cough or a small amount of white mucus sputum that usually lasts for 3 – 8 weeks and is not abnormal on x-ray chest examination.
Post-infectious cough is self-limiting and mostly resolves on its own. Antibiotics are usually not necessary, but treatment with macrolide antibiotics is effective for post-infectious cough caused by Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis. Short-term application of cough suppressants and antihistamines plus decongestants may be indicated in some patients with significant cough symptoms. Ipratropium bromide may be effective in some patients.
V. Diagnosis and treatment of common causes of chronic cough
Common causes of chronic cough include CVA, UACS [also known as postnasaldripsyndrome (PNDS)], EB, and GERC, which account for 70% to 95% of the causes of chronic cough in outpatient whistling medicine. Other etiologies are less common but are widely involved and are associated not only with diseases of the whistle system, but also with diseases of other systems. Most chronic coughs are not associated with infections and do not require treatment with antibacterial drugs. Use oral or intravenous glucocorticoids with caution when the cause of the cough is unknown or when infection cannot be excluded.
1. UACS/PNDS
(1) Definition.
A syndrome in which nasal disease causes secretions to flow backwards behind the nose and throat, directly or indirectly stimulating cough receptors, resulting in a cough as the main manifestation is called PNDS. Since it is not possible to identify the cause of cough receptors in the upper whistle tract, the 2006 American Cough Diagnosis and Treatment Guidelines recommend replacing PNDS with UACS.
UACS is one of the most common causes of chronic cough. In addition to nasal diseases, UACS is often associated with diseases of the pharynx, such as allergic or non-allergic pharyngitis, laryngitis, pharyngeal neoplasia, and chronic tonsillitis.
(2) Clinical manifestations.
Symptoms: In addition to cough and sputum, it may manifest as nasal congestion, increased nasal discharge, frequent throat clearing, adherence of mucus in the back of the throat, and postnasal drip of influenza. Allergic rhinitis manifests as nasal itching, sneezing, running snot, itchy eyes, etc. Rhino-sinusitis manifests as mucopurulent or purulent snot, and may be associated with pain (facial pain, toothache, headache) and olfactory disturbance. Allergic pharyngitis is characterized by pharyngeal itching and paroxysmal irritating cough. Non-allergic pharyngitis is often characterized by sore throat, foreign body sensation or burning sensation in the pharynx. Inflammation of the larynx and neoplastic organisms are usually accompanied by hoarseness.
Signs: In allergic rhinitis, the nasal mucosa is mainly pale or edematous, and clear or mucous snot is seen in the nasal passages and nasal floor. In non-allergic rhinitis, the nasal mucosa is mostly characterized by mucosal hypertrophy or congestion-like changes, and in some patients, the mucosa of the oropharynx can be seen to have pebble-like changes or mucopurulent secretions attached to the posterior pharyngeal wall.
Auxiliary examinations: imaging of chronic sinusitis shows thickening of the sinus mucosa and the presence of fluid planes in the sinuses. When the cough is seasonal or suggests exposure to specific allergens (e.g., pollen, dust mites), allergen testing is helpful for diagnosis.
(3) Diagnosis.
UACS/PNDS involves a variety of underlying diseases such as nose, sinuses, pharynx, and larynx, and the symptoms and signs vary widely and many are non-specific. It is difficult to make a definitive diagnosis simply by history and physical examination, and a definitive diagnosis can only be made when treatment for the underlying disease can effectively relieve the cough, and attention should be paid to the presence of combined lower airway disease, GERC, and other compound causes.
(4) Treatment.
Depending on the underlying disease causing UACS/PNDS.
(6) Diagnostic procedures for the etiology of chronic cough
The etiologic diagnosis of chronic cough should be based on the following principles.
(1) Pay attention to the medical history, including the history of otorhinolaryngological and digestive system diseases.
(2) Select relevant tests according to the medical history, from simple to complex.
(3) Common diseases should be examined first, followed by rare diseases.
(4) Diagnosis and treatment should be performed simultaneously or sequentially.
If examination conditions are not available, diagnostic treatment can be performed according to clinical features and the cause of the cough can be determined according to the response to treatment, and relevant tests can be selected when treatment is ineffective. When treatment is partially effective but does not provide complete relief, compound causes should be excluded.
The diagnostic process of chronic cough etiology, in the following steps.
1. History taking and physical examination: The diagnosis is narrowed by history taking. Sometimes the history can directly suggest the corresponding cause, such as a history of smoking, exposure to environmental irritants, or being on ACEI-type medications. A history of specific occupational exposure should be noted for the possibility of occupational cough.
2. X-ray chest examination: It is recommended as a routine examination for patients with chronic cough. for those with obvious lesions on the X-ray chest, further examination can be selected according to the morphology and nature of the lesions. for those without obvious lesions on the X-ray chest, if there is smoking, exposure to environmental irritants or taking ACEI, quit smoking, remove from exposure to irritants or stop taking the medication and observe for 4 weeks. If the cough remains unrelieved or if there are no predisposing factors as described above, proceed to the next step in the diagnostic procedure.
3. Pulmonary function tests: First, ventilation function tests are performed. If there is clear obstructive ventilation dysfunction (FEV170% normal expected value), bronchodilatation test is performed to determine the reversibility of airway obstruction; if FEV170% normal expected value, bronchial excitation test can be performed to detect the presence of airway hyperresponsiveness. 24h peak flow velocity variability measurement is helpful for the diagnosis and Identification. Normal ventilation function and negative bronchial excitation test should be performed to diagnose EB by induced sputum cytology.
4. History of the presence of postnasal drip or frequent throat clearing can be treated first as UACS/PNDS with a combination of first-generation antihistamines and decongestants.
For allergic rhinitis, topical glucocorticoids can be used nasally. If the symptoms do not improve in 1 – 2 weeks of treatment, sinus CT or nasopharyngoscopy can be performed.
5. If the above tests are not abnormal, or if the patient has reflux-related symptoms, 24h esophageal pH monitoring can be considered. If pH monitoring is not available and is highly suspected, empirical treatment can be performed.
6. For suspected allergic cough, allergen skin test, serum IgE and cough sensitivity testing are feasible.
7. If the diagnosis cannot be confirmed by the above tests, or if the cough continues after the test treatment, high-resolution CT, fiberoptic bronchoscopy and cardiac examinations should be considered to exclude rare intra- and extra-pulmonary diseases such as bronchiectasis, interstitial lung disease, bronchial tuberculosis, bronchial tumors, bronchial foreign bodies and left heart insufficiency.
8. The diagnosis of the cause of cough can be established only after the cough is relieved by corresponding treatment, and some patients may have multiple causes at the same time. If the patient’s cough is only partially relieved after treatment, consideration should be given to whether other etiologies are combined at the same time.