Epidemiology of cough in relation to China

Acute cough is one of the most common symptoms in respiratory out patient clinic, the common cause is an acute upper airway infection. Therefore, to some extent, the prevalence of acute upper airway infection can represent the prevalence of acute cough. The prevalence of cough caused by upper airway viral infection fluctuates between 9% and 64% [5]. In patients having sore throat, 50% complain of cough [6].

Despite of the differences of surveyed population and criteria, many surveys on the prevalence of cough revealed a high incidence, which is commonly >10% (Table 1). Barbee et al. carried out a survey on the communities in Arizona and found out the prevalence of chronic cough was 18% [7]. The survey conducted in Italy showed that the incidence of chronic cough was 11.9% [8]. A survey in Switzerland reported that the prevalence of chronic cough in smokers was 3 times higher than non-smokers [9]. In southeast England, 16% of interviewees spent half of their time coughing, 13.2% of them reported productive cough, and over half of them (54%) smoked [10]; A cross-sectional international population survey conducted in 16 European countries involving 18277 interviewees revealed that the prevalence of chronic cough was 33%, and that of nocturnal cough was 30% [11]. However, this study did not differentiate between acute cough and chronic cough, and the high prevalence of nocturnal cough might have resulted from the design of some questions. The first cross-sectional survey on the prevalence of chronic cough was undertaken in West Yorkshire. A total of 36 general practices and nearly 4000 patients were involved in the study. After analyzing the bouts or spasms of coughing at a frequency between once a week and once or more a day in the last 2 months, Ford et al. reported that the prevalence of chronic cough was 12% [12]. A cough survey conducted in 1087 college students in South China revealed a prevalence of 10.9% with 7.6% acute cough and 3.3% chronic cough. No difference was found between male and female. The patients with chronic cough tend to present more likely as the sole or predominant symptom as compared with the patients with acute cough [13]. Since the college students have better health status and life style, we assumed the prevalence of cough could be much higher in the community.

Lai et al. investigated previous diagnosis and management of 558 outpatients with chronic cough in South China, found that the average number of visits for medical service was more than 20 for each patients [18]. More than 80% of the patients were misdiagnosed as "bronchitis, chronic bronchitis or pharyngitis". Antibiotics was given in about 90% of the patients. The results of the latest multicenter survey in China shows the incidence of using antibiotics previously was 69% in patients with chronic cough [19].

Cough is a most common symptom in children as well. Munyard and Bush reported that healthy children coughed 10 times everyday on average, the cough occurs most often in the daytime [20]. About 10%-22% of children aged 5–11 years had chronic cough in the absence of colds [21, 22]. Some surveys demonstrated the prevalence of chronic cough in children 6–12 years of age was between 5% and 10% with a higher incidence in younger children [23, 24]. Chronic cough occurred in 50% of children whose parents smoked [25].

There are few reports on the spectrum of causes of acute cough and subacute cough. It is generally considered that the common cold is the most common cause of acute cough, followed by acute bronchitis. The causes of acute cough include acute exacerbation of chronic respiratory diseases (bronchiectasis, chronic bronchitis and COPD), noxious material and allergen-induced cough. Acute cough occasionally indicates some severe diseases such as pulmonary embolism, pneumonia and congestive heart failure, etc. Postinfectious cough is thought to be the most common cause of subacute cough. Kwon et al. evaluated 184 patients with subacute cough, found that postinfectious cough was in approximately 48% of the cases, followed by postnasal drip syndrome (33%) and cough variant asthma (16%) [26].

Irwin et al. [27] first set up an anatomic-diagnostic protocol for chronic cough in 1981, showed that the common causes of chronic cough were upper airway cough syndrome (UACS, termed as postnasal drip syndrome previously), bronchial asthma and gastroesophageal reflux disease (GERD). Some investigations in Europe and America have similar results on causes of chronic cough [28, 29].

In 1989, Gibson et al. first reported 7 patients with eosinophilic bronchitis (EB), who presented with chronic cough, eosinophilia in induced sputum, normal airway responsiveness, and a good response to corticosteroids [30]. By adding the processing of induced sputum to the diagnostic algorithm of chronic cough, Brigthling et al. found that eosinophilic bronchitis was an important cause of chronic cough in 13% of patients [31]. Others studies from Australia, Korean, and Turkey also showed the proportion of EB to be 7-33% of patients presenting with chronic cough [32‐34], In South China, Lai et al. reported that EB was the most common cause of chronic cough (22%), followed by PNDS (17%), CVA (14%), and GER (12%) [35]. Early studies in North China [36] and East China [37] showed EB was not as common as that in South China. This difference on causes may be due to various diagnosis proceeds. In a latest prospective, multicenters survey on causes of chronic cough in China, EB was identified to be one of the common causes in all regions, ranging from 9.4%-24.2% with a mean proportion of 17.2% [19]. EB has been formally proposed as one of common causes in the guideline on chronic cough by European Respiratory Society (ERS) [38], Chinese Medical Association [39], and American College of Chest Physicians (ACCP) [40]. Therefore, EB as a common cause of chronic cough has been recognized globally.

In the US or Europe, GERD is a common cause of chronic cough, however, GERD is found to be only a minor cause of chronic cough in Asia: 2% in Japan [41] and 4.6% in China [19]. The lower incidence of GERD-related cough might be related to the lower incidence of GERD in Asia as compared with the US or Europe [42]. In contrast to typical Western life style, the Asian dietary consists of high content of fiber, grains and vegetables. A diet rich in fiber has been reported to decrease the risk of cough [43].

Atopic cough (AC) was defined first by Fujimura in Japan as a bronchodilator-resistant dry cough associated with sputum eosinophilia or an atopic predisposition [44, 45], and was reported being a common cause of chronic cough in Japan. AC reported in Japan overlap with EB in fact. The definition of AC in China is different from that of Japan since the patients with eosinophilia in induced sputum were excluded in China. Although the concept of AC remains controversial and is not widely accepted,many patients with atopic predisposition are seen in our clinics, and the cough can be relieved by corticosteroids or antihistamine therapy. Two regional surveys in Guangzhou and Shenyang, a Southern and a Northern region of China respectively, show a proportion of approximately 12% AC in patients with chronic cough [35, 46]. Recently, a prospective, multicenter survey in China found that AC was identified in 13.2% of patients with chronic cough [19].

Idiopathic cough (or unexplained cough) would not be considered until a thorough diagnostic and treatment approach for the common causes of cough have been completed and uncommon causes are adequately evaluated [47]. The incidence of idiopathic cough is not uncommon in some studies [48, 49]. In China, the unexplained cough accounted for 8.4% of the cases in a latest multicenter survey [19]. It is still unclear whether some unexplained cough (idiopathic cough) represents a single entity or includes certain undiscovered causes of chronic cough. Those idiopathic cough are more common in middle age women and perimenopause women, characteristiced by being hypersensitive to smoke, dust, cold air and other stimulants, increased cough sensitivity, no causes could be identified in spite of many investigation. Recently, a new single discrete clinical entity termed as ’cough hypersensitivity syndrome’ was introduced. It was postulated that the new term would focus on the problem on the cough symptomatology and lead to a better understanding of the mechanisms of cough sensitization [50, 51].

Although epidemiological surveys in the community show a high incidence of chronic bronchitis, the hospital-based studies on the etiology of chronic cough have shown that the proportion of these patients is only 4%-7% [27, 28] (Table 2).

Angiotensin converting enzyme inhibitor (ACEI)-induced cough should be noted predictively in the elderly. Because the incidence of cardiovascular disease is associated with age, elderly people are might expected to have ACEI-induced cough more frequently [55].

The common causes of chronic cough in children vary according to different age groups [56]. Acute respiratory infection and protracted bacterial bronchitis are the most common causes for infant and early children [57]. Allergy and asthma become predominant causes during the school years [58]. Foreign body aspiration is much more common in infant than adults. Gastroesophageal reflux during infancy is a physiological phenomenon with an occurrence rate of 40% to 65%, reaching a peak in infants of 1 to 4 months, and this eases after age of 1 year. It is debatable whether GERD is a common cause of chronic cough in children. Chang et al. found a low incidence of GERD related to chronic cough in children [24]. However, a high incidence of GERD related chronic cough was reported in another study [58]. There are few reports concerning the incidence of EB in children with chronic cough. In China, the epidemiological surveys concerning chronic cough in children are lacking. Zhao et al. analyzed the causes of chronic solitary cough in 50 children aged 6–12 years, finding that 20 were PNDs 17 CVA, 5 postinfectious cough, 4 psychogenic cough, 1 primary gastroesophageal reflux disease and 2 EB [59].

Cold air, cigarette smoking, allergens, environmental pollutants, various noxious substances, poor diet habit and female gender may contribute to cough.

Chronic cough can lead to physiological disorder, psychological stress and disrupt social life. Complications induced by cough involve the respiratory, cardiovascular, digestive, genitourinary, musculoskeletal and nervous systems. An increasing prevalence of complications is in line with an aggravating and prolonged cough [79]. Thoracoabdominal pain caused by the damage of muscle fibers, as well as hoarseness due to vocal cords damage, are common in clinic. Many women with chronic cough experience urinary incontinence [80]. In China, Yang et.al reported that chronic cough seriously interfered with the patient's quality of life, which shows no gender difference. However, women have urinary incontinence with a proportion of about 50% [81].

Chronic cough impact seriously quality of life on physiological, psychological and social aspects. Questionnaires are used to comprehensively assess impact of cough on quality of life, such as Cough-Specific Quality of Life Questionnaire (CQLQ) [82], Leicester Cough Questionnaire(LCQ) [83] and Chronic Cough Impact Questionnaire (CCIQ) [84]. In addition to physiological complications, patients with chronic cough experience psychological imbalance and social predicament. Patients suffer from embarrassing emotion caused by prolonging cough, they feel anxious about the cough and prejudices from others, which may aggravate their psychological condition [82]. Among patients with chronic cough in New York, 53% of them experience depression, indicating that depression is a common incidental symptom [85]. Psychological symptoms are often relieved with inmprovement of chronic cough [84]. A survey in Guangzhou showed that patients with an average duration of 4 years of cough are also troubled with mental and social problems, one-half of patients feel embarrassed and annoyed, and greater than one-quarter feel upset and even depressed [86].