Chronic cough in children: the etiology and medical history of 420 cases in Shanghai

Chronic cough is one of the most common and frequently-occurring diseases in children. We investigated the etiologies and clinical features of children with chronic cough (CC), in order to improve the diagnostic and treatment of the disease by pediatricians. The clinical data of 420 cases of children, aged 1–14 years old, from 5 hospitals’ Outpatient Department in different regions of Shanghai, who suffered from chronic cough between the period of September 2017 and July 2019 were prospectively analyzed. Children with chronic cough were enrolled to identify the specic cause and clinical information based on a questionnaire survey. All the data were collected and statistically analyzed by Chi-square test to identify the constituent ratio of each cause.


Background
Chronic cough is one of common and frequently-occurring diseases in children. It refers to those who cough for more than 4 weeks [1], cough is the main or only clinical manifestation, and chest lm shows no obvious abnormality. According to the nature of cough, it can be divided into dry cough and wet cough.
A long-term cough without de nite diagnosis and repeated use of antibiotics will cause signi cant impairment to the quality of life, including children's sleep, school attendance and play and parents' experience distress and anxiety [2][3][4].
Therefore, we studied the constituent ratio of various causes of chronic cough in children, analyzed and sorted out their medication history, in order to improve the diagnosis and treatment of non-speci c chronic cough by Page 3/12 pediatricians.

Study population
The Prior to the start of the project, training sessions on research plan and questionnaires will be held. After that, 420 children with chronic cough who met the diagnostic criteria were collected and analyzed statistically.

Selection criteria
The inclusion criteria was:1) a cough of > 4 weeks duration; 2) cough is the main clinical manifestation; 3) aged 1-14 years old; 4) there was no abnormalities in the chest X-ray lm [1].
The exclusion criteria was:1) children had abnormal chest X-ray; 2) had serious systemic diseases; and 3) unwilling/unable to cooperate with researchers to complete the questionnaire.

Survey development
Each of the patients underwent the following procedures for the investigation of the cause of cough: 1) recording of medical history including symptoms and history of ear, nose, throat, respiratory tract, and digestive tract problems; 2) detailed physical examination with the targeted evaluation of throat congestion, follicular hyperplasia, and retropharyngeal postnasal drip; and 3) allergen test, chest X-ray examination, routine blood test, pulmonary function assessment and gastrointestinal dynamic ultrasound in patients with suspicious symptoms or signs.

Methods
The diagnosis of the etiology of all children with non-speci c chronic cough was referenced to the diagnosis and differential diagnosis of chronic cough in children guidelines [1,[5][6][7].
Each of the patients underwent the following procedures for the investigation of the cause of cough: 1) detailed recording of medical history(duration and nature of the cough, associated symptoms, the history of medication, family history of allergic disease or related disease and information about the living environment of the patient); 2) detailed physical examination with particular attention to the heart and lower and upper airways; and 3) allergen test, routine blood test, chest X-ray examination, Pulmonary function assessment, gastrointestinal dynamic ultrasound in patients with suspicious symptoms or signs 2.5 Analyses SPSS 24.0 was used to calculate the incidence rates of the clinical characteristics. The percentage of distribution of causes/medical history of each group was expressed by the percentage of ascertained causes/ medical history of each group to the total number of causes/ medical history of each group. The chisquare (X 2 ) test was used to evaluate the variable. Statistical signi cance was de ned as a two-tailed P-value less than 0.05.

The medication history of children with chronic cough
We collected the medication history of children in the course. The present study shows most children (67.1%) had a history of using antimicrobials. Studies showed using appropriate antibiotics improves cough resolution, especially for the chronic wet cough [12][13][14][15].
175 children (41.7%) had taken Azitromycin in the course. Mycoplasma pneumoniae is extensively regarded as major cause for CVA in clinics [16]. Hodgson David [17]  variety of Chinese patent drug, and Chinese herbal medicine were mostly compound. Although they had certain curative effect in clinic, the mechanism was not clear.

The living environment of children with chronic cough
We found 133 children's family (31.7%) had smokers among the surrounding. Çolak Yunus [24] et al found that smoking is one of the chronic cough risk factors. The prevalence of chronic cough in the current smokers was 8%.
Johannessen Ane [25] et al believed that exposure to environmental tobacco smoke (ETS) is associated with impaired lung function in childhood. ETS might be one of the chronic cough risk factor. 105 children's (25.0%) home were along the street. Fang Zhangfu [26] et al found that the tra c-related air pollution (TRAP) exposures induced cough hypersensitivity and non-allergic eosinophilic in ammation of airways in guineapigs. De Sajal [27] et al found that shopkeepers working in heavily tra cked roadside shops suffer from respiratory morbidity and the risk increases with higher total exposure period. We believe TRAP might be one of the chronic cough risk factor; this is worthy of further investigation.

Conclusion
Among children aged 1-14, the leading 3 causes of chronic cough in Shanghai were PIC, UACS and CVA. The mainly age of onset is 3-6 years. The mainly cough character is wet cough.
By collecting the medical history of children in the course, we found antibiotics are the mainly treatment, often combined with cough medicine and atomization. Azithromycin is the most commonly used antibiotic. More than half of the children used to seek traditional Chinese medicine treatment.