Clinically, a person with cough as the only or main symptom for more than 8 weeks and 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. 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 a predominantly daytime cough and less frequent awakening from coughing after going to sleep.
2. postnasal drip and/or a feeling of mucus adherence to the posterior pharyngeal wall.
3. a history of rhinitis, sinusitis or chronic pharyngitis
4. mucus adherence and cobblestone-like appearance of the posterior pharyngeal wall.
5. exclusion of other common causes of chronic cough.
6. relief of cough after targeted treatment (after selecting different treatment regimens according to different underlying diseases).
Because PNDs involve a variety of underlying diseases without specific clinical signs and symptoms, 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 etiological 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 also 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 24 h monitoring.
Esophageal pH 24 h 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 24-h esophageal pH <4, the longest reflux time, and the percentage of esophageal pH <4 in the monitoring time are obtained, and finally the Demeester score is derived. In Europe and the United States, the Demeester score of the lower electrode is usually greater than 14.72 as a criterion for the diagnosis of GERD, and the Demeester score of 24h monitoring of esophageal pH in normal people in China is 12.70. During the examination, the reflux and cough symptoms are recorded in real time, and the correlation probability (SAP) between reflux and cough symptoms can be obtained to clarify the relationship between reflux temporal phase and cough.
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, etc.
(iv) 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.
(i) There is a significant feeding-related cough, such as postprandial cough and feeding cough.
② Often accompanied by GERD symptoms, such as acid reflux, belching and retrosternal burning sensation.
(iii) Excluding diseases such as CVA, EB, allergic rhinitis/sinusitis, or poorly treated as these diseases.
(iii) Diagnosis of eosinophilic bronchitis
Eosinophilic bronchitis clinically presents 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).
Patients with eosinophilic bronchitis lack characteristic clinical manifestations, and some patients may present with cough-like variant asthma with no abnormal findings on physical examination, and the diagnosis mainly relies 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 radiograph.
3, normal pulmonary ventilation, negative AHR and normal PEF inter-day variability.
4, sputum eosinophils ≥ 2. 5%.
5, exclude other eosinophilic diseases.
6, oral or inhaled glucocorticoid therapy is effective.
Clinically, a person with cough as the only symptom or main symptom for more than 8 weeks and no obvious abnormalities on chest X-ray is usually referred to as 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 a predominantly daytime cough and less frequent awakening from coughing after going to sleep.
2. postnasal drip and/or a feeling of mucus adherence to the posterior pharyngeal wall.
3. a history of rhinitis, sinusitis or chronic pharyngitis
4. mucus adherence and cobblestone-like appearance of the posterior pharyngeal wall.
5. exclusion of other common causes of chronic cough.
6. relief of cough after targeted treatment (after selecting different treatment regimens according to different underlying diseases).
Because PNDs involve a variety of underlying diseases without specific clinical signs and symptoms, 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 etiological 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 24 h monitoring.
Esophageal pH 24 h 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 24-h esophageal pH <4, the longest reflux time, and the percentage of esophageal pH <4 in the monitoring time are obtained, and finally the Demeester score is derived. In Europe and the United States, the Demeester score of the lower electrode is usually greater than 14.72 as a criterion for the diagnosis of GERD, and the Demeester score of 24h monitoring of esophageal pH in normal people in China is 12.70. During the examination, the reflux and cough symptoms are recorded in real time, and the correlation probability (SAP) between reflux and cough symptoms can be obtained to clarify the relationship between reflux temporal phase and cough.
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, etc.
(iv) 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.
(i) There is a significant feeding-related cough, such as postprandial cough and feeding cough.
② Often accompanied by GERD symptoms, such as acid reflux, belching and retrosternal burning sensation.
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 presents as chronic dry cough or morning cough with a little mucous sputum, induced sputum eosinophilia, and effective glucocorticoid therapy, but the patient does not have reversible airflow obstruction symptoms 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).
Patients with eosinophilic bronchitis lack characteristic clinical manifestations, and some patients may present with cough-like variant asthma with no abnormal findings on physical examination, and the diagnosis mainly relies 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 radiograph.
3, normal pulmonary ventilation, negative AHR and 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 irritating cough is evident at night
2, positive bronchial provocation test, or positive bronchodilator test, or PEF day-to-day variability >20%.
3. significant relief of cough after bronchodilator drugs, 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 with the addition of 24-h esophageal pH measurement.
The Irwin diagnostic protocol does not include an induction sputum test, and its use is bound to lead to missed diagnoses in this subset of patients. Therefore, a new diagnostic procedure for the etiology of chronic cough was developed by combining the Irwin diagnostic protocol with domestic clinical practice (see Figure). This procedure is only used for the etiological diagnosis of chronic cough with no obvious abnormalities on X-ray examination. For patients in primary care or with limited economic conditions, aetiological diagnostic treatment can be performed based on medical history and cough-related symptoms. If experimental treatment (1 to 2 weeks) is ineffective, 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 chronic cough etiology.
① Emphasize 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 history, from simple to complex, with common diseases first, followed by rare diseases.
③ When conditions are not available, diagnostic treatment can be performed according to clinical features? but when treatment is ineffective, timely examination and diagnosis should be performed at a hospital in a condition 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 irritating cough is evident at night
2, positive bronchial provocation test, or positive bronchodilator test, or PEF day-to-day variability >20%.
3. significant relief of cough after bronchodilator drugs, 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 with the addition of 24-h esophageal pH measurement.
The Irwin diagnostic protocol does not include an induction sputum test, and its use is bound to lead to missed diagnoses in this subset of patients. Therefore, a new diagnostic procedure for the etiology of chronic cough was developed by combining the Irwin diagnostic protocol with domestic clinical practice (see Figure). This procedure is only used for the etiological diagnosis of chronic cough with no obvious abnormalities on X-ray examination. For patients in primary care or with limited economic conditions, aetiological diagnostic treatment can be performed based on medical history and cough-related symptoms. If experimental treatment (1 to 2 weeks) is ineffective, 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 chronic cough etiology.
① Emphasize 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 history, from simple to complex, with common diseases first, followed by rare diseases.
③ When conditions are not available, diagnostic treatment can be performed according to clinical features? but when treatment is ineffective, timely examination and diagnosis should be performed at a hospital in a condition 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.