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Characteristics of Chinese patients with cough in primary care centre

Journal of Translational Medicine20119:149

https://doi.org/10.1186/1479-5876-9-149

Received: 15 July 2011

Accepted: 10 September 2011

Published: 10 September 2011

Abstract

Background

Cough is one of the most common respiratory symptoms and is well characterized in specialized cough clinics with high success rates of diagnosis and treatment. However, there is a paucity of data regarding cough in primary care settings. The present study aimed at investigating clinical epidemiology of cough through a national study of two questionnaire surveys sent to primary care physicians in China.

Methods

Approximately 18,000 subjects recruited were having daytime or night symptoms of cough and diagnoses of respiratory disease from February 2005 to April 2006 as Survey 1 and from June 2007 to December 2007 as Survey 2. Patients suffering from respiratory malignancy, hyperthyroidism, hypertension, heart disease, diabetes, severe hypohepatia or renal dysfunction, pregnancy, possible pregnancy or lactation, neutropenia were not eligible. Information regarding demography, history of allergies, symptomatic profile, treatment and curative effects for cough was elicited.

Results

8216 questionnaires were collected in Survey 1 and 9711 in Survey 2. The mean values of ages were 25.7 and 22.3 years old, respectively. Symptoms included expectoration (74% and 76%), wheeze (59% and 74%), breathlessness (22% and 26%), chest pain (9% and 13%) and fever (15% and 18%). About 15% and 23% patients had hypersusceptibility, of whom 6% to 17% had a family history. More than 50% of the cases had histories of allergic rhinitis, asthma, conjunctivitis or atopic dermatitis. Asthma, COPD, and bronchitis were dominant etiologies of cough. Procaterol or the combination of antibiotics and steroids were used as the treatment.

Conclusion

Causes and outcomes of cough differed with ages and time in this particular national study, while successful and precise diagnosis and management of cough in primary care settings need to be further improved in China.

Keywords

Atopic DermatitisAllergic RhinitisChronic CoughBeclomethasone DipropionateAcute Bronchitis

Introduction

Cough is one of the most common respiratory symptoms encountered by clinicians [1], with the reported prevalence varying between 5% and 40% [24]. Cough is also one of the critical factors affecting the quality of life in patients with respiratory diseases. Cough management has massive economic consequences. The first guideline on the management of cough with a significant positive impact was championed in 1998 [5], followed by the publication of other guidelines on chronic cough [69]. The Chinese Medical Association published "Diagnosis and treatment guide (draft) of cough" in 2005 [10], and then the American College of Chest Physicians published evidence-based guidelines for diagnosis and treatment of acute cough, subacute cough, and chronic cough in adults and chronic cough in children in 2006 [1, 6, 11].

Over-the-counter combination cough medication such as cough syrup including traditional Chinese medicine is usually the first choice in China. The majority of people with cough who consulted a health care professional received the diagnosis and was informed that over the counter cough medications could relieve the symptoms. However, there are still a number of those with unclear diagnosis or failure to respond to therapy. The present study aimed at investigating clinical epidemiology of cough through a national study of two questionnaire surveys sent to primary care physicians in China. Approximately 18,000 subjects with daytime or night symptoms of cough and with diagnoses of respiratory disease were recruited for questionnaires from February 2005 to April 2006 as Survey 1 and from June 2007 to December 2007 as Survey 2. It provided further information about the demographic and symptomatic profile in the population and curative effects for cough in Chinese patients with respiratory diseases. This is one of the national projects organized by the Chinese Medical Doctor Association in order to obtain a better understanding of coughs while hoping the results could lead to new ideas and plans to explore in regard to molecular mechanisms and therapies.

Methods

Patients

The present study identified clinical characteristics of patients with cough from a nationwide-based survey conducted by the Chinese Medical Doctor Association. Subjects recruited had daytime or nighttime symptoms of cough and diagnoses of respiratory diseases, from 85 primary care medical centers. The 85 clinics are primary care centers chosen from the north and south of China as representatives in China. One survey started from February 2005 to April 2006 was named Survey 1 and one from June 2007 to December 2007 was named Survey 2. The two surveys were performed at the same 85 clinics. There was no overlap of the two surveys. The reason for calculating using two surveys was to see the improvement of health care and medical care inbetween the two time periods. Patients were provided with written information prior to obtaining oral consent. The study is a questionnaire survey aimed at investigating the clinical epidemiology of the cough for patients when first visiting the primary care center. Information on patient health care data, e.g. numbers, home address, phone number and others, was protected.

Evaluation Scores

Physicians were invited to complete and follow up the cough questionnaires and were then completed by the referred patients who had been in primary care settings during the first time. After then, they were continuously followed up for an additional 14 days, in order to audit social and demographic factors as well as qualitative measures of responses to treatment. The physicians filled out the questionnaires. Sections of open questions were asked, including demographic details, symptoms, history of the cough, hypersusceptibility patterns, and treatment outcomes. Hypersusceptibility was defined as a cough condition of abnormal susceptibility to stimuli that are entirely innocuous in the normal individual. Cough severity was assessed on a scale of 0 (no cough) to 3(severe cough) and recorded on a daily record. Effectiveness was evaluated as cured (symptom score decreased to 0), markedly improved (symptom score decreased ≥ 4), improved (Symptom score decreased ≥ 2), or no effect (unchanged or aggravated). Adverse events were elicited at each visit by enquiring about the side effects of therapy recorded from a symptom checklist.

Statistics

Data were analyzed by the two-sided test and p value less than 0.05 was considered significant. Non-parametric statistics rank sum test was used for the analysis of recovery percentage. The quota target was used and described by statisticians, including the computation arithmetic mean value, the standard deviation, the median, the minimum value, the maximum value. The example number was calculated and the percentage of corresponding was classified with the identification target. Data was analyzed using the SAS 9.1.2 program by Health Statistics Laboratory of Chinese Center for Disease Control and Prevention.

Results

Of 18000 questionnaires, 8216 were received by the end of April, 2006, and 9711 by the end of Dec 2007, respectively. There were 4655 males and 3561 females with a mean age of 25.7 (standard deviation 24, range 1-98 years) in Survey 1 with 8216 patients. Of them, 46% were less than 10 years old (Table 1 and Table 2). There were 5331 males and 4010 females with a mean age of 22.3 years (standard deviation 22 years) in Survey 2 with 9711 patients, among whom the age of 425 patients were not recorded.
Table 1

Characteristic of the subjects in Survey 1

Age

Male

Female

Total

Years

Cases

Percentage

Cases

Percentage

Cases

Percentage

0-10

2102

45.2%

1710

48.0%

3812

46.4%

11-20

249

5.3%

196

5.5%

445

5.4%

21-30

279

6.0%

281

7.9%

560

6.8%

31-40

519

11.1%

397

11.1%

916

11.2%

41-50

492

10.6%

299

8.4%

791

9.6%

51-60

382

8.2%

239

6.7%

621

7.6%

61-70

321

6.9%

151

4.2%

472

5.7%

71-80

212

4.6%

107

3.0%

319

3.9%

81-90

99

2.1%

181

5.1%

280

3.4%

Total

4655

100%

3561

100%

8216

100%

Table 2

Characteristic of the subjects in Survey 2

Age

Male

Female

Total

 

Cases

Percentage

Cases

Percentage

Cases

Percentage

0-10

2439

45.5%

2252

55.8%

4691

50.5%

11-20

812

15.2%

539

13.4%

1351

14.5%

21-30

216

4.2%

175

4.2%

391

4.2%

31-40

426

8.1%

269

6.6%

695

7.5%

41-50

535

9.9%

249

6.2%

784

8.4%

51-60

361

6.7%

208

5.1%

569

6.1%

61-70

297

5.5%

154

3.8%

451

4.9%

71-80

201

3.8%

132

3.2%

333

3.6%

81-90

14

0.2%

7

0.1%

21

0.2%

Total

5301

100%

3985

100%

9286

100.0%

The cough was reported to be productive in 6256 of 8216 patients (76%) with complaint of wheeze 59%, breathlessness 22%, chest pain 9% and fever 18% in Survey 1, while cough (74%), wheeze (74%), breathlessness (26%), chest pain (13%) and fever (15%) were noticed in Survey 2. Of 8216 patients in Survey 1, 1919 (23%) had hypersusceptibility and 1359 (17%) had a family history of hypersusceptibility. Of 9177 patients in Survey 2, 1444 (15%) had hypersusceptibility and 621 (6%) had a family history of hypersusceptibility. More than 50% of cases had a history of allergic rhinitis, asthma, allergic conjunctivitis or atopic dermatitis (Table 3). Inclusion subjects were given a diagnosis, mainly including COPD and asthma. Table 4 described the details of diagnosis. Tubercular pleurisy, stomatitis, acute pharyngitis, hypertension of pulmonary artery or fewer were listed in the section of others.
Table 3

History of diseases in subjects with cough

Disease

Survey 1

Survey 2

 

Cases

Percentage

Cases

Percentage

Allergic rhinitis

1359

16.5%

1972

20.3%

Asthma

3202

39.0%

6236

64.2%

Allergic conjunctivitis

88

1.1%

227

2.3%

Atopic dermatitis

120

1.5%

104

1.1%

Table 4

Diagnosis of inclusion subjects

Diagnosis

Survey 1

Survey 2

 

Cases

Percentage

Cases

Percentage

Influenza

2

0.02%

1

0.01%

Rhinitis

28

0.34%

30

0.31%

Bronchial hyperreactivity

19

0.23%

0

0.00%

COPD & Asthma

90

1.10%

0

0.00%

Chronic bronchitis

124

1.51%

105

1.08%

Pneumonia

290

3.53%

87

0.90%

Allergic cough

334

4.07%

301

3.10%

Asthmatoid bronchitis

341

4.15%

292

3.01%

Common cold

394

4.80%

31

0.32%

Chronic cough

520

6.33%

249

2.56%

Acute bronchitis

932

11.34%

1000

10.30%

Asthma (except CVA)

1799

21.89%

4521

46.56%

COPD

1303

15.86%

1135

11.69%

Cough variant asthma(CVA)

1723

20.97%

1563

16.10%

others

317

3.86%

400

4.08%

Total

8216

100.00%

9711

100.00%

Patients were treated with Procaterol, of whom 1098 in Survey 1 and 1046 in Survey 2 also had a combination of drugs, including expectorant (Ambroxol, Bromhexine, Carbocisteine), methylxanthines (Aminophylline, Theophylline), antihistamines (Cetirizine, Ketotifen, Cyprohentadine, Loratadine, Chlorphenamine, Tranilast), leukotriene modifiers (Montelukast), beta2 agonists (Salbutamol), inhaled long-acting beta2 agonists, Sametrol/Fluticasone, Formoferol/Budesonide, anticholinergics (Ipratropine). Combined drugs also included cough syrup (e.g. graifenesin, methylephedrine, chlorphenamine syrup, dextromethorphan hydrobromide with chlorpheniramine maleate, or pseudoe phedrine hydiochloride solution), Asmeton, Chinese traditional medicine, inhaled steroids (e.g. budesonide, fluticasone, and beclomethasone dipropionate), systemic steroids (e.g. methylprednisolone, prednisone, and dexamethasone), anti-virus (Ribavirin), or antibiotics(e.g. macrocyclic lactone, quinolone, cephalosporin, benzylpenicillin, and others), as shown Table 5.
Table 5

Treatments of inclusion subjects

Treatment

Survey 1

Survey 2

  

Cases

Percentage

Cases

Percentage

Expectorant

194

2.36%

1

0.01%

Methylxanthines

126

1.53%

39

0.40%

Antihistamines

197

2.40%

48

0.49%

Leukotriene modifiers

104

1.27%

151

1.55%

SABAS

43

0.52%

184

1.89%

LABA

34

0.41%

53

0.55%

Anticholinergics

36

0.44%

2

0.02%

Combination Drugs

82

1.00%

1

0.01%

Chinese traditional medicine

169

2.06%

14

0.14%

Inhaled steroids

180

2.19%

225

2.32%

Systemic Corticosteroids

45

0.55%

22

0.23%

Anti-virus

6

0.07%

0

0.00%

 

Macrocyclic lactone

88

1.07%

5

0.05%

 

Quinolone

51

0.62%

0

0.00%

Antibiotics

Cephalosporin

267

3.25%

243

2.50%

 

Benzylpenicillin

45

0.55%

31

0.32%

 

others

12

0.15%

72

0.74%

Others drugs (unknown)

414

5.04%

19

0.20%

The daily cough diary showed a rapid and highly significant reduction in the cough score (Table 6 and Table 7). Of them, 83% in Survey 1 and 92% in Survey 2 had no symptom during the daytime after 14 days of treatment, while 82% in Survey 1 and 94% in Survey 2 had no symptom during the night. There was a significant difference between before and after the treatments (p < 0.05 or 0.01, respectively). No patient dropped out because of severe adverse events.
Table 6

Daytime cough symptom assessment

Days

Cases in survey 1

Cases in survey 2

 

No symptom

Mild cough

Moderate cough

Severe cough

No symptom

Mild cough

Moderate cough

Severe cough

0

34

807

3146

3926

12

182

2561

6463

1

35

701

2978

3617

7

206

2475

5764

2

87

910

3493

2903

69

557

3337

4568

3

218

1291

4075

1890

227

1016

4371

3156

4

366

1671

4495

846

145

1426

6034

673

5

521

2070

4326

413

309

2390

5394

173

6

805

2692

3682

183

633

3342

4229

65

7

1151

3482

2896

76

1326

3777

3473

42

8

1449

4035

1756

41

890

4810

1614

29

9

1895

4250

1077

24

1438

5065

647

26

10

2382

4199

605

13

2240

4401

251

20

11

3166

3075

304

5

3058

3617

102

19

12

4370

2655

123

7

4758

1859

48

19

13

5280

1799

62

4

5056

966

33

19

14

6083

1388

46

5

5540

704

33

19

Table 7

Night cough symptom assessment

Days

Cases in survey 1

Cases in survey 2

 

No symptom

Mild cough

Moderate cough

Severe cough

No symptom

Mild cough

Moderate cough

Severe cough

0

149

819

2939

3942

43

239

2471

6441

1

80

818

2632

3756

39

272

2424

5690

2

167

944

2967

3165

88

615

2830

4971

3

318

1190

3382

2349

236

1110

4274

3132

4

466

1512

3944

1310

171

1467

5455

1159

5

640

1800

4126

637

339

2198

5420

296

6

895

2223

3826

287

555

3124

4483

92

7

1276

2780

3272

133

1379

3777

3423

39

8

1513

3180

2373

68

978

4664

1747

23

9

1809

3655

1605

28

1395

4759

1091

19

10

2151

3944

936

14

2048

4518

392

15

11

2704

3809

495

4

3096

3591

132

15

12

3711

3077

214

1

4651

1983

48

17

13

4778

2121

87

1

5030

998

28

17

14

5903

1417

48

0

5716

531

24

18

Discussion

Cough is an important defensive reflex of the respiratory tract to clean up and protect the upper airway, while also being the commonest symptom for which patients seek medical advice. Causes and outcomes of cough differ with age and its presentation and other related symptoms vary with time (e.g. seasonality) and habits (e.g. smoking, occupation, body weight, use of drug etc.). Children below 10 years may have more episodes of bronchiolitis and asthma, which is the reason why their prevalence is high among both surveys in the present, while the adults suffer more from pneumonia and other chronic conditions. One of the common causes is chronic upper airway cough syndrome, previously referred to as postnasal drip syndrome, secondary to rhinosinus diseases, common cold, asthma, gastroesophageal reflux disease, bronchitis (e.g. acute bronchitis, chronic bronchitis, acute exacerbation of chronic bronchitis, or nonasthmatic eosinophilic bronchitis), bronchiectasis, post infectious cough, or others [12]. Thus, it is unexpectedly challenging for clinicians to define the etiology and pathogenesis of coughs in addition to selecting the optimal treatment in primary care settings. According to our knowledge, the present study incorporates the largest population sample yet to study the clinical epidemiology of coughs, which in turn can provide an overall figure indicating personal feelings, signs and clinical indications of coughs in primary care settings.

Subjects recruited in the present study had daytime or night symptoms of cough and diagnoses of respiratory disease, of whom about half were children. The accompanied symptoms included expectoration, fever, chest pain, usually indicative of the respiratory infection, wheezing, and breathlessness, which was usually accompanied with COPD and asthma. The two common diseases were COPD and asthma including cough variant asthma. Breathlessness and cough may be the clinical indicators of COPD or asthma exacerbations [13], while acute bronchitis should not be diagnosed until the common cold, asthma, and an acute exacerbation of chronic bronchitis have been ruled out [14]. However, it was often over-diagnosed, leading to the abuse of antibiotics. About 10% of patients were diagnosed as acute bronchitis in the Surveys, which was a lower percentage than that of COPD and asthma. Nasal disease was an important risk factor of cough, especially of chronic cough. It would be more valuable for the therapeutic strategies to further distinguish acute and chronic cough, rhinitis and other nasal disease if the proportion was large enough.

Hypersusceptibility has been suggested as one of major challenging factors in cough. We found that more than half of the patients with cough had a history of allergic rhinitis, asthma, allergic conjunctivitis or atopic dermatitis. About 15% to 23% patients had hyper-susceptibility, while 6% to 17% had a family history of hyper-susceptibility. More patients had a history of asthma in Survey 2 (64%) than in Survey 1 (39%). Allergic rhinitis is a common cause of postnasal drip and coughs, with a high prevalence in patients with asthma [15]. Patients with allergic rhinitis should be identified and clarified in the future study, in order to evaluate the significance and difference of allergic diseases in cough.

Procaterol was used as the treatment of patients, although the symptom of acute cough was sometimes automatically cured [16]. Responses to the used treatment were rapid and efficient, evidenced by the fact that 83% and 92% of patients in Surveys 1 and 2, respectively, had no daytime symptoms and 82% and 94% had no night symptoms after 14 days of treatment. Although our data showed that Procaterol could improve the symptom of cough in patients with respiratory diseases, we do not know the exact effects of the drug as our study was not a randomized controlled trial. Antibiotics were hardly effective for chronic cough and acute cough caused by the common cold, acute bronchitis, asthma, mild exacerbations of chronic bronchitis related to smoking, or environmental irritants [17, 18]. However, the application of antibiotics could be beneficial for upper airway cough syndrome resulted from bacterial sinusitis, and infection in the lower respiratory tract (whooping cough), if given early. The prescription rate of antibiotics was about 4-6% in patients with cough, which was considered as acceptable according to the conditions of the patients studied. Inhaled steroids were used in about 2% of patients, while systemic corticosteroids in 0.6%.

However, a number of limitations in the present study should be improved in future studies. For example, such cross-sectional studies should be followed up longitudinally, results based on self-reports should be compared with clinical information, including physical examinations, imaging and biochemical analyses. More diagnoses should be included in the questionnaire form, including pneumonia, common cold, acute bronchitis, and chronic bronchitis, even though it may be difficult to confirm those diagnoses. More attention on etiology and pathogenesis of cough should be considered as well as further education on cough management should be delivered to physicians working in primary care settings.

Conclusion

In conclusion, cough causes a high level of morbidity in the community, annually resulting in massive health economy consequences. Demography and symptomatology seem to be similar to that reported in specialist hospital centers, but successful and precise diagnosis and treatment of cough was not as satisfactory. Management of cough in primary care needs to be improved in China.

Declarations

Acknowledgements

The study was sponsored by the Chinese Medical Doctor Association and Zhejiang Otsuka Pharmaceutical Co. Ltd, China.

Conflict statement

The authors declare that they have no competing interests.

Authors’ Affiliations

(1)
Department of Pulmonary Medicine, Fudan University Zhongshan Hospital, Shanghai, China
(2)
Biomedical Research Center, Fudan University Zhongshan Hospital, Shanghai, China

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Copyright

© Hong et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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