A cough with cough as the only or main symptom for more than 8 weeks with no significant abnormalities on chest X-ray is usually referred to as chronic cough of unknown origin, or chronic cough. The diagnosis and treatment of unexplained cough for more than 4 weeks is similar to that of chronic cough. It is frequently seen because of the prolonged cough, which causes pain and distress to the patient. It is not easy to diagnose the cause of this condition and is often simply diagnosed as a condition such as upper respiratory tract infection or acute bronchitis and given antibacterial or antiviral medications. In fact, many coughs are not directly related to bacterial or viral infections, and misuse of antimicrobial or antiviral drugs not only has no therapeutic effect, but also delays the condition and even complicates it, causing unnecessary financial waste and mental burden. Therefore, chronic cough needs to be taken seriously and the cause of the disease needs to be sought for treatment purposes.
Chronic cough involves a variety of etiologies, and with the right diagnosis, most patients can actually obtain a clear etiological diagnosis, and specific treatment based on the etiology can achieve good therapeutic results.
The following is a description of the common causes of chronic cough, etiologic diagnosis and etiologic diagnostic procedures.
I. Common causes of chronic cough
Chronic cough involves a variety of etiologies, not only related to the respiratory system, but also to the nasopharynx and the digestive system. Domestic and international studies have shown that the common causes of chronic cough are postnasal drip syndrome (PNDs), cough variant asthma (CVA), and gastroesophageal reflux (GER). These three etiologies account for approximately 67% to 94% of the total etiology. Eosinophilic bronchitis has also been reported individually as an important cause of chronic cough.
II. Diagnosis of the etiology of chronic cough
1. Diagnosis of postnasal drip syndrome
PNDs are coughs caused by nasopharyngeal diseases that cause more secretions to adhere to the postnasal and laryngopharyngeal areas and even backflow into the vocal cords or trachea. A variety of diseases can cause PNDs, such as allergic rhinitis, sinusitis, and non-allergic rhinitis.
The diagnostic criteria are as follows.
1. Episodic or persistent cough, with coughing predominantly during the day and less often waking up due to coughing after going to sleep;
2. postnasal drip and/or a feeling of mucus adhesion to the posterior pharyngeal wall;
3. History of rhinitis, sinusitis or chronic laryngitis;
4. Mucus adherence and cobblestone-like appearance of the posterior pharyngeal wall;
5. Exclude other common causes of chronic cough;
6. The cough is relieved after targeted treatment (after selecting different treatment plans according to different underlying diseases).
Because PNDs involve a variety of underlying diseases without specific clinical symptoms and signs, the diagnostic criteria are complex, and some patients do not necessarily fully meet these criteria. In recent years, some scholars have directly adopted rhinitis/sinusitis as the etiologic diagnosis of chronic cough without using the term PNDs.
2. Diagnosis of gastroesophageal reflux cough
GER cough is defined as a gastroesophageal reflux disease in which reflux of gastric acid and other gastric contents into the esophagus leads to a cough as the main manifestation.
1. Medical history.
Some patients with GER cough are accompanied by a burning-like sensation behind the sternum, belching, and acid reflux. However, there are many patients who have no reflux symptoms or feeding-related symptoms at all, and cough is their only clinical manifestation. Therefore, GER cough cannot be ruled out in patients with chronic cough without esophageal reflux symptoms.
2. Esophageal pH 24h monitoring.
Esophageal pH 24h monitoring is currently the most effective method for diagnosing GER cough. 32% of patients with GER cough can only be diagnosed by esophageal pH measurement.
By dynamically monitoring the changes in distal and proximal esophageal pH, six parameters such as the number of 24h esophageal pH <4, the longest reflux time, the percentage of esophageal pH <4 to the monitoring time, and finally the Demeester score are obtained. In Europe and America, the Demeester score of lower electrode is usually greater than 14,72 as a criterion to diagnose GERD, and the Demeester score of 24h monitoring of esophageal pH in normal people in China is 12,70. During the examination, the correlation probability (SAP) between reflux and cough symptoms can be obtained by recording reflux and cough symptoms in real time, and the relationship between reflux temporal phase and cough can be clarified.
Esophageal pH 24h monitoring is not diagnostic of non-acidic gastroesophageal reflux. For the diagnosis of non-acidic reflux or biliary reflux, barium swallow examination of the esophagus may be of some value, and confirmation of the diagnosis also depends on the development of bile reflux monitoring and intraesophageal luminal impedance examination methods.
3. Other examinations.
Barium meal and gastroscopy have limited diagnostic value for GER cough, with low sensitivity and specificity, and the interrelationship between reflux and cough cannot be determined. When patients are suspected of having local anatomical abnormalities, hiatal hernia, esophageal strictures and ulcers, barium meal examination still has some value.
4. Diagnostic criteria.
(1) Chronic cough;
(2) 24h esophageal pH monitoring Demeester score ≥12, 70 and/or reflux associated with cough symptoms with probability SAP ≥75%;
(3) Exclusion of CVA, EB, allergic rhinitis/sinusitis, 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 financial resources, we recommend that diagnostic treatment be considered for those with the following indications GER cough can be diagnosed by the disappearance or significant relief of cough after anti-reflux treatment.
(1) There is a significant feeding-related cough, such as postprandial cough, feeding cough, etc. ;
(2) Often accompanied by GER symptoms, such as acid reflux, belching, and burning sensation behind the sternum;
(3) Excluding diseases such as CVA, EB, allergic rhinitis/sinusitis, or poor results of treatment according to these diseases.
3.Diagnosis of eosinophilic bronchitis
Eosinophilic bronchitis clinically manifests as chronic dry or morning cough with a little mucous sputum, induced sputum eosinophilia, and effective glucocorticoid therapy, but the patient has no symptoms of reversible airflow obstruction such as shortness of breath and dyspnea. Pulmonary ventilation function and peak expiratory flow rate variability (PEFR) findings were normal, and there was no evidence of airway hyperresponsiveness (AHR). The clinical presentation of patients with eosinophilic bronchitis lacks specificity, and some patients may present with cough-like variant asthma with no abnormal findings on physical examination, and the diagnosis relies mainly on induced sputum cytology.
The 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 AHR, normal PEF inter-day variability;
4, sputum eosinophils ≥ 2, 5%;
5, exclude other eosinophilic diseases;
6, oral or inhaled glucocorticoid therapy is effective.
Clinically, cough as the only symptom or the main symptom for more than 8 weeks with no obvious abnormalities on chest X-ray is called chronic cough of unknown origin, or chronic cough for short. The diagnosis and treatment of unexplained cough for more than 4 weeks is similar to that of chronic cough. It is frequently seen because of the prolonged cough, which causes pain and distress to the patient. It is not easy to diagnose the cause of this disease and is often simply diagnosed as a condition such as upper respiratory tract infection or acute bronchitis and patients are given antibacterial or antiviral medications. In fact, many coughs are not directly related to bacterial or disease infections, and the misuse of antimicrobials or antivirals not only has no therapeutic effect, but also complicates the condition. Therefore, chronic cough needs to be taken seriously and the cause needs to be sought in order to achieve treatment.
Chronic cough involves a variety of etiologies, and with the right diagnosis, most patients can actually obtain a clear etiological diagnosis, and specific treatment based on the etiology can achieve good therapeutic results. Below, we introduce the common causes of chronic cough, etiologic diagnosis and etiologic diagnostic procedures.
I. Common causes of chronic cough
Chronic cough involves a variety of etiologies, not only related to the respiratory system, but also to the nasopharynx and the digestive system. Domestic and international studies have shown that the common causes of chronic cough are postnasal drip syndrome (PNDs), cough variant asthma (CVA), and gastroesophageal reflux (GER). These three etiologies account for approximately 67% to 94% of the total etiology. Eosinophilic bronchitis has also been reported individually as an important cause of chronic cough.
II. Diagnosis of the etiology of chronic cough
1. Diagnosis of postnasal drip syndrome
PNDs are coughs caused by nasopharyngeal diseases that cause more secretions to adhere to the postnasal and laryngopharyngeal areas and even backflow into the vocal cords or trachea. A variety of diseases can cause PNDs, such as allergic rhinitis, sinusitis, and non-allergic rhinitis.
The diagnostic criteria are as follows.
1. Episodic or persistent cough, with coughing predominantly during the day and less often waking up due to coughing after going to sleep;
2. postnasal drip and/or a feeling of mucus adhesion to the posterior pharyngeal wall;
3. History of rhinitis, sinusitis or chronic laryngitis;
4. Mucus adherence and cobblestone-like appearance of the posterior pharyngeal wall;
5. Exclude other common causes of chronic cough;
6. The cough is relieved after targeted treatment (after selecting different treatment plans according to different underlying diseases).
Because PNDs involve a variety of underlying diseases without specific clinical symptoms and signs, the diagnostic criteria are complex, and some patients do not necessarily fully meet these criteria. In recent years, some scholars have directly adopted rhinitis/sinusitis as the etiologic diagnosis of chronic cough without using the term PNDs.
2. Diagnosis of gastroesophageal reflux cough
GER cough is defined as a gastroesophageal reflux disease in which reflux of gastric acid and other gastric contents into the esophagus leads to a cough as the main manifestation.
1. Medical history.
Some patients with GER cough are accompanied by a burning-like sensation behind the sternum, belching, and acid reflux. However, there are many patients who have no reflux symptoms or feeding-related symptoms at all, and cough is their only clinical manifestation. Therefore, GER cough cannot be ruled out in patients with chronic cough without esophageal reflux symptoms.
2. Esophageal pH 24h monitoring.
Esophageal pH 24h monitoring is currently the most effective method for diagnosing GER cough. 32% of patients with GER cough can only be diagnosed by esophageal pH measurement.
By dynamically monitoring the changes in distal and proximal esophageal pH, six parameters such as the number of 24h esophageal pH <4, the longest reflux time, the percentage of esophageal pH <4 to the monitoring time, and finally the Demeester score are obtained. In Europe and America, the Demeester score of lower electrode is usually greater than 14,72 as a criterion to diagnose GERD, and the Demeester score of 24h monitoring of esophageal pH in normal people in China is 12,70. During the examination, the correlation probability (SAP) between reflux and cough symptoms can be obtained by recording reflux and cough symptoms in real time, and the relationship between reflux temporal phase and cough can be clarified. Esophageal pH 24h monitoring is not diagnostic of non-acidic gastroesophageal reflux. For the diagnosis of non-acidic reflux or biliary reflux, barium swallow examination of the esophagus may be of some value, and confirmation of the diagnosis also depends on the development of bile reflux monitoring and intraesophageal luminal impedance examination methods.
3. Other examinations.
Barium meal and gastroscopy have limited diagnostic value for GER cough, with low sensitivity and specificity, and the interrelationship between reflux and cough cannot be determined. When patients are suspected of having local anatomical abnormalities, hiatal hernia, esophageal strictures and ulcers, barium meal examination still has some value.
4. Diagnostic criteria.
(1) Chronic cough;
(2) 24h esophageal pH monitoring Demeester score ≥12, 70 and/or reflux associated with cough symptoms with probability SAP ≥75%;
(3) Exclusion of CVA, EB, allergic rhinitis/sinusitis, 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 financial resources, we recommend that diagnostic treatment be considered for those with the following indications GER cough can be diagnosed by the disappearance or significant relief of cough after anti-reflux treatment.
(1) There is a significant feeding-related cough, such as postprandial cough, feeding cough, etc. ;
(2) Often accompanied by GER symptoms, such as acid reflux, belching, and burning sensation behind the sternum;
(3) Excluding diseases such as CVA, EB, allergic rhinitis/sinusitis, or poor results of treatment according to these diseases.
3.Diagnosis of eosinophilic bronchitis
Eosinophilic bronchitis clinically manifests as chronic dry or morning cough with a little mucous sputum, induced sputum eosinophilia, and effective glucocorticoid therapy, but the patient has no symptoms of reversible airflow obstruction such as shortness of breath and dyspnea. Pulmonary ventilation function and peak expiratory flow rate variability (PEFR) findings were normal, and there was no evidence of airway hyperresponsiveness (AHR).
The clinical presentation of patients with eosinophilic bronchitis lacks specificity, and some patients may present with cough-like variant asthma with no abnormal findings on physical examination, and the diagnosis relies mainly on induced sputum cytology.
The 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 AHR, normal PEF inter-day variability;
4, sputum eosinophils ≥ 2, 5%;
5, exclude other eosinophilic diseases;
6.Oral or inhaled glucocorticoid therapy is effective.
4.Diagnosis of cough variant asthma
CVA is a special type of asthma. Cough is the main or only clinical manifestation of CAV patients without obvious symptoms such as wheezing and shortness of breath, but the airway hyperresponsiveness test is positive. The clinical manifestation is an irritating dry cough, which is more common at night or early in the morning. Irritating odors such as cold air, dust and oil smoke tend to induce or aggravate the cough. The specificity and sensitivity of relying solely on clinical features to diagnose CVA is only 60% to 80%, and pulmonary function tests are the key indicators for diagnosing cough variant asthma. However, it should be noted that factors such as antihistamines, the stimulant used, the method of operation, and the degree of patient cooperation can affect the results of AHR.
The diagnostic criteria for CVA are as follows.
1. Chronic cough, especially if the irritating cough is obvious at night;
2. Positive bronchial excitation test, or positive bronchodilator test, or PEF day-to-day variability >20%;
3. Significant relief of cough after bronchodilator drugs or glucocorticoid therapy;
4. Exclude other causes of induced chronic cough.
III. Diagnostic procedures for the etiology of chronic cough
Based on the fact that stimulation of cough receptors and afferent nerves at different locations can cause cough, Irwin et al. proposed an anatomical diagnostic procedure for chronic cough in 1981, which was modified in 1990 by adding 24-h esophageal pH measurement.
The Irwin diagnostic protocol does not have an induction sputum examination program, and its use is bound to lead to missed diagnoses in this subset of patients. Therefore, we combined the Irwin diagnostic protocol with domestic clinical practice and reformulated a diagnostic procedure for the etiology of chronic cough (see Figure). This procedure is only for the diagnosis of the etiology of chronic cough with no obvious abnormalities on X-ray examination. For patients in primary care hospitals or with limited economic conditions, etiologic diagnostic treatment can be performed based on medical history and cough-related symptoms. If the experimental treatment (1 to 2 weeks) is not effective, then prompt examination and diagnosis should be performed at a hospital in a position to do so to avoid delay.
The following principles must be followed when performing the diagnosis of the etiology of chronic cough.
1. Pay attention to the medical history, including the history of ear, nose and throat, digestive system, occupational exposure and medication history;
2. Select the relevant tests according to the medical history, from simple to complex, with common diseases first, followed by rare diseases;
3. When conditions are not available, diagnostic treatment can be carried out according to clinical specialties, but when treatment is ineffective, timely examination and diagnosis should be carried out at a hospital with conditions to avoid delaying the condition;
4. Determine the cause of cough according to the response to treatment, and then choose to perform relevant examinations when treatment is ineffective.
III. Treatment of chronic cough
After a clear diagnosis, regular treatment is required under the guidance of a doctor.
CVA is a special type of asthma. Cough is the main or only clinical manifestation of CAV patients without obvious symptoms such as wheezing and shortness of breath, but the airway hyperresponsiveness test is positive. The clinical manifestation is an irritating dry cough, which is more common at night or early in the morning. Irritating odors such as cold air, dust and oil smoke tend to induce or aggravate the cough. The specificity and sensitivity of relying solely on clinical features to diagnose CVA is only 60% to 80%, and pulmonary function tests are the key indicators for diagnosing cough variant asthma. However, it should be noted that factors such as antihistamines, the stimulant used, the method of operation, and the degree of patient cooperation can affect the results of AHR.
The diagnostic criteria for CVA are as follows.
1. Chronic cough, especially if the irritating cough is obvious at night;
2. Positive bronchial excitation test, or positive bronchodilator test, or PEF day-to-day variability >20%;
3. Significant relief of cough after bronchodilator drugs or glucocorticoid therapy;
4. Exclude other causes of induced chronic cough.
III. Diagnostic procedures for the etiology of chronic cough
Irwin et al. proposed an anatomical diagnostic procedure for chronic cough in 1981, which was modified in 1990 to include 24-h esophageal pH measurement, based on the fact that stimulation of cough receptors and afferent nerves in different locations can cause cough. Therefore, we combined the Irwin diagnostic protocol with domestic clinical practice and reformulated a diagnostic procedure for the etiology of chronic cough (see Figure). This procedure is only for the diagnosis of the etiology of chronic cough with no obvious abnormalities on x-ray examination. For patients in primary care hospitals or with limited economic conditions, etiologic diagnostic treatment can be performed based on medical history and cough-related symptoms. If the experimental treatment (1 to 2 weeks) is not effective, then prompt examination and diagnosis should be performed at a hospital in a position to do so to avoid delay.
The following principles must be followed when performing the diagnosis of the etiology of chronic cough.
1. Pay attention to the medical history, including the history of ear, nose and throat, digestive system, occupational exposure and medication history;
2. Select the relevant tests according to the medical history, from simple to complex, with common diseases first, followed by rare diseases;
3. When conditions are not available, diagnostic treatment can be carried out according to clinical specialties, but when treatment is ineffective, timely examination and diagnosis should be carried out at a hospital with conditions to avoid delaying the condition;
4. Determine the cause of cough according to the response to treatment, and then choose to conduct relevant examinations when treatment is ineffective.