Skip to main content
Download PDF

Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China

Respiratory Research volume 23, Article number: 243 (2022) Cite this article

Abstract

Background

Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits.

Methods

In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared.

Results

CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores.

Conclusions

CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort.

Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017

Introduction

Asthma is a chronic inflammatory disease of the airways. According to onset, triggers, clinical features, airway inflammation, response to treatment, and prognosis, asthma can be divided into different phenotypes, such as early onset asthma, severe asthma, classic asthma or atypical asthma [1, 2]. Asthma is classically characterized by variable episodes of shortness of breath, chest tightness, wheezing and cough. Although breathlessness and wheeze are the more frequent symptoms of asthma, cough can also be most troublesome major complaint [3]. Cough variant asthma (CVA), first described by Corrao and colleagues, presents with cough as a sole presenting symptom associated with normal lung function [4]. Since then, CVA has been recognized as being a common cause of chronic cough [5, 6]. Another less-well recognized type of cough associated with asthma is cough presenting not as the sole symptom but as the predominant persistent symptom of asthma, associated with mild wheezing and/or dyspnea. This type of asthma has been referred to as cough predominant asthma (CPA) in order to distinguish them from CVA [7,8,9]. Similarly, CPA is also recognized as a common cause of chronic cough [9]. In CPA, cough can be persistent even after regular anti-inflammatory treatments are administered and could be an indicator of exacerbation and poor control of asthma [10,11,12,13,14,15,16]. Finally, in contrast to CPA, classical asthma (CA) presents itself predominantly with wheezing and/or dyspnea, with mild cough or no cough symptom.

Asthma is often accompanied by comorbidities such as allergic rhinitis (AR), chronic rhinosinusitis, and gastroesophageal reflux, which are also common causes of chronic cough [5, 17,18,19,20]. However, it is not certain whether these comorbidities are related to cough in asthmatic patients. CVA has been reported to have a similar eosinophilic inflammation and bronchial hyperresponsiveness but higher cough sensitivity compared to CA [21]. For CPA, cough is the predominant symptom, but it was often ignored in current questionnaires of asthma control such as Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) [22, 23]. Furthermore, the differences in clinical features, airway inflammation and cough sensitivity between CVA, CPA and CA have not been studied because there has been no study that has compared these different asthma phenotypes within a single cohort.

In order to fill this knowledge gap, we conducted a prospective, multicenter, CPA Cohort (CPAC) study in 2016 in China in order to elucidate the characteristics of these 3 phenotypes of asthma defined by the presence or absence of cough as a symptom. Within this framework, our objectives were to describe the baseline profiles of CPA versus CVA and CA patients in terms of demographics, symptoms (respiratory and other), co-morbidities, airway inflammation, cough sensitivity and lung function.

Materials and methods

Study design

This was a prospective, multicenter, observational study that was conducted between February 2016 and March 2019, in 20 hospital centers from 11 provinces and municipalities across China (Additional file 1). The study flow chart is presented in Fig. 1. For all patients enrolled into this study, detailed medical history and physical examination were recorded in a standard case report file (Additional file 2), including demographics, respiratory symptoms, concomitant symptoms, comorbidities, smoking history and medications. Relevant questionaires including the asthma control test (ACT), cough symptom score (CSS), cough visual analogue scale (VAS) and Leicester Cough Questionnaire (LCQ) were completed. A total of 633 patients in 10 centers completed the induced sputum test, 842 patients from 16 centers had FeNO measurement and 267 patients from 3 centers underwent capsaicin cough challenge (details in Additional file 1).

Fig. 1
figure 1

Flow chart of the study. #Including demographics, respiratory symptoms, concomitant symptoms, comorbidities, smoking history and medications. CVA: cough variant asthma; CPA: cough predominant asthma; CA: classic asthma FeNO: Fractional exhaled nitric oxide

Full size image

This study was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University and the institutional review boards of each participating center (201604). It has also been registered in the Chinese Clinical Trial Registration Center (ChiCTR-POC-17011646). All participating patients provided written informed consent.

Subjects

Patients aged 14 years old or older were recruited amongst those attending the recruiting centres with a history of wheeze or dyspnea and/or cough and those with a history of chronic cough alone. All patients were diagnosed as asthma by physicians according to the Global Strategy for Asthma Management and Prevention Guidelines (GINA Guidelines, 2016), and the Chinese Guidelines of Diagnosis and Management of Chronic Cough [24, 25]. On the basis of the presence of bronchial hyperresponsiveness [fall in forced expiratory volume in 1 s (FEV1) from baseline of ≥ 20% with increasing doses of inhaled methacholine], or of a positive bronchodilator test (increase in FEV1 ≥ 12% and ≥ 200 mL from baseline), CVA was diagnosed if the patient presented with cough as the sole or main symptom lasting more than 8 weeks without wheeze and dyspnea; CPA was diagnosed if the patient presented with cough as the predominant symptom lasting for more than 8 weeks in addition to transient wheezing and/or dyspnea, and CA was diagnosed if the patient had wheezing and/or dyspnea as the main symptom(s), with or without cough (Table 1 and Additional file 3). Co-morbidities were determined according to history and on previous diagnosis made by other physicians. Patients with an acute asthma attack or an acute upper respiratory tract infection within 8 weeks of recruitment were excluded, as well as those with serious systemic diseases, pregnancy, and breast-feeding.

Table 1 The definition of CVA, CPA and CA
Full size table

Assessment

The details of cough and wheezing VAS scores, cough symptom score (CSS) and Leicester Cough Questionnaire (LCQ) are provided in Additional file 2. In brief, laryngeal sensitivity was assessed by presence of laryngeal symptoms and the ACT was used for evaluating asthma control [22]. Separate cough and wheezing VAS scores were obtained on 100 mm scales on which patients indicated the severity of cough or wheezing, with 0 indicating no cough or wheezing, and 100 indicating the worst cough or wheezing. The cough symptom score (CSS) consists of two questions about the subjective recognition of cough frequency and severity duting the day and night. The scores for each question range from 0 to 5 [26, 27]. Cough-related quality of life was assessed by the Leicester Cough Questionnaire (LCQ), which contains19 items divided into three domains (physical, psychological and social) [28].

Methods

Spirometry and bronchial challenge were performed according to the current ATS/ERS guidelines [29, 30]. The provocative cumulative dose of methacholine causing a 20% fall in FEV1 (PD20-FEV1) less than 2.500 mg was used as a marker for bronchial hyperresponsiveness (BHR) [30]. Sputum was induced and processed as described by the Chinese Guidelines for Diagnosis and Management of Cough (2015) [25]. Briefly, sputum was induced with 3% saline, and sputum was mixed with four times its volume of 0.1% dithiothreitol. The cell smear was stained with hematoxylin–eosin. Differential cell counts were obtained by counting 400 non-squamous cells. FeNO measurements were performed in accordance with the standard procedure as previously described [31]. Cough sensitivity was measured by a single breath inhalation capsaicin test with a compressed air-driven nebulizer controlled by a breath-activated dosimeter. Briefly, doubling concentrations of capsaicin solutions (1.95–1000 μmol/L) were inhaled at 1 min intervals, and coughs were counted in the first 30 s after inhalation. The lowest concentrations of capsaicin (C2) which evoked two coughs were obtained and the level of cough reflex sensitivity (CRS) was presented as the logarithm of C2 (logC2). The lowest concentrations of capsaicin (C5) which evoked five or more coughs were obtained and the level of CRS was presented as the logarithm of C5 (logC5) [25].

Statistical analysis

SPSS 23.0 software was used for analysis. Age, FEV1% pred, body mass index (BMI), cough day and night integral values were expressed as means ± standard deviation. Due to non-normal distributions, the duration of disease, blood eosinophil counts, FeNO values, induced sputum cytology, logC5, cough VAS score, LCQ scores and ACT scores were presented as medians (interquartile range). When the measurement data for two or more groups presented with normal distributions, two independent sample t-tests or one-way analysis of variance (ANOVA) was used. Otherwise, Mann–Whitney U tests or multi-sample Kruskal–Wallis H test for independent samples were performed. The comparison of categorical variables was performed by the χ2 test or Fisher’s exact probability method. We used the Bonferroni correction method for the comparisons in two-group analyses. Two-sided p < 0.05 indicated statistical significance.

Results

Baseline characteristics

A total of 2088 patients with a mean age of 45.4 ± 14.5 years, were enrolled in the study, and were divided into 1041 patients with CPA, 720 with CA and 327 with CVA (Fig. 1 and Table 2). The CVA patients were younger than the CPA and CA patients (all p < 0.05). There were more females in the CVA and CPA patients than that in the CA patients (all p < 0.05). The median duration of disease increased from CVA to CPA to CA patients (p < 0.001), so did for the proportion of smoking (p < 0.001). A total of 549 (26.3%) patients, including 34 CVA, 274 CPA and 241 CA, were treated with inhaled corticosteroids (ICS)/ICS + long-acting Beta2-agonists (LABA) regularly before enrollment in the past 3 months. A total of 1425 (68.2%) patients were not prescribed asthmatic medication, and 114 (5.5%) patients could not report their treatment status (Additional file 4). More CA patients received regular antiasthmatic treatment compared to CPA and CVA patients (p < 0.001). The proportion of patients with dry cough in the CVA patients was higher than that in CPA patients (p < 0.001). As compared with CA patients, more CPA patients presented with cough as the initial symptom (77.1% vs 31.4%, p < 0.001) with a longer time from start of cough to first wheezing or dyspnea (p = 0.013) (Table 2).

Table 2 Clinical characteristics of CVA, CPA and CA
Full size table

Asthma control and cough score

As shown in Table 3, the ACT score in the CPA patients was similar to that in CA patients and both of them were lower when compared to the CVA patients (p < 0.001). CPA patients showed higher cough VAS compared to CA patients (p < 0.001). The daytime CSS of CPA and CVA patients was higher than that of CA patients (p < 0.001). Furthermore, CPA patients had lower LCQ scores than CA patients. There was no significant difference in cough VAS scores between CPA and CVA patients (p = 0.062) (Table 3).

Table 3 ACT and cough scores in CVA, CPA and CA
Full size table

Accompanying symptoms and comorbidities

The proportion of patients with laryngeal symptoms in CVA and CPA patients were significantly higher than that in CA patients (all p < 0.001). A lower proportion of patients with nasal symptoms and reflux symptoms was observed in the CVA patients as compared with that in CPA and CA patients (all p < 0.05) (Table 4). CA patients had a higher prevalence of comorbidities, including chronic obstructive pulmonary disease (COPD) and bronchiectasis, followed by CPA (p < 0.05). There were more patients with sinusitis among the CA and CPA patients than in the CVA patients (all p < 0.05) (Table 5).

Table 4 Nasal, laryngeal and oesophageal symptoms in CVA, CPA and CA
Full size table
Table 5 Comorbidities in CVA, CPA and CA
Full size table

Lung function and airway inflammation

FEV1, FEV1/FVC (%) and the maximum mid-expiratory flow in % predicted (MMEF% pred) were lowest in CA group, followed by CPA and CVA (all p < 0.05). Forced vital capacity in % predicted (FVC % pred) of CVA patients was significantly higher than that of CPA and CA patients (all p < 0.05) (Table 2). No significant differences were found in eosinophil (Eos %) and neutrophil (Neu %) counts in sputum and FeNO levels between the three groups (Fig. 2).

Fig. 2
figure 2

Airway inflammation in CVA, CPA and CA. A Fractional exhaled nitric oxide (FeNO) in CVA, CPA and CA; B Percentage of eosinophils in sputum in CVA, CPA and CA; C Percentage of neutrophils in sputum in CVA, CPA and CA. CVA: cough variant asthma; CPA: cough predominant asthma; CA: classic asthma

Full size image

Cough sensitivity

A total of 264 patients completed the capsaicin cough challenge test, including 84 CVA, 120 CPA and 60 CA patients. CVA and CPA patients showed similar values of logC5, but lower values than that of the CA patients (1.5, 1.8 vs. 2.5 all p < 0.001) (Fig. 3). For all patients, the cough sensitivity of females was higher than that of males (p < 0.05) (Fig. 3). LogC5 of capsaicin cough sensitivity was positively correlated with LCQ scores (r = 0.416, p < 0.001; n = 183), but eosinophil (r = 0.002, p = 0.510; n = 230) and neutrophil (r = 0.015, p = 0.060; n = 230) counts in induced sputum were not correlated with logC5.

Fig. 3
figure 3

Capsaicin cough sensitivity. A logC5 in CVA, CPA and CA; B logC5 in females and males for total patients (n = 534); C logC2 in females and males for total patients (n = 534). CVA: cough variant asthma; CPA: cough predominant asthma; CA: classic asthma. logC2: the lowest concentrations of capsaicin (C2) which evoked two coughs were obtained and the level of cough reflex sensitivity (CRS) was presented as the logarithm of C2 (logC2); logC5: The lowest concentrations of capsaicin (C5) which evoked five or more coughs were obtained and the level of CRS was presented as the logarithm of C5 (logC5)

Full size image

Discussion

Our study, for the first time, divided asthma into the three phenotypes of CVA, CPA and CA based on the presence and severity of cough in relationship to the presence of other asthmatic symptoms of wheeze and chest tightness and compared the clinical and pathophysiological characteristics. We found that CPA patients had a higher proportion of females, usually presenting initially with cough predominantly. There were no significant differences with regard to comorbidities related with cough, reflux-related symptoms, rhinitis/sinusitis-related symptoms, and sputum eosinophil and neutrophil counts and FeNO levels between CPA and CA. However, the proportion of those with laryngeal symptoms was higher in CPA compared to CA. Cough sensitivity in CPA patients was similar to that in CVA patients, but significantly higher than that in CA patients. In addition, from the asthma severity point of view, both CPA and CA were less well-controlled and had evidence of airflow obstruction compared to CVA. Thus, our study confirms that CVA, CPA and CA phenotypes are distinct in terms of the features of asthma, airflow obstruction and cough severity as well as cough sensitivity.

CPA had a similar female predominance as CVA, as we previously reported [32]. In a worldwide survey of patients attending cough clinics, chronic cough patients were usually found to be middle-aged females who had heightened cough sensitivity compared to males [33].

Cough is one of the most common symptoms reported by asthmatic patients. Although CPA patients showed lower wheezing scores and better lung function, they had higher cough scores and lower LCQ scores than CA, indicating worse quality of life due to cough. Furthermore, there was no significant difference in ACT scores between CPA and CA, indicating that chronic cough caused an impairment of quality of life while ACT scores were not different. This may not be surprising because the ACT does not specifically request information on cough as a symptom of asthma, despite the recognition that cough can be a troublesome as is breathlessness in asthmatic patients [3]. Cough can also be an indicator for exacerbation and poor control [15]. Furthmore, we found that cough remained a prominent symptom in spite of improvement of wheezing in those patients who experienced regular anti-asthma treatment in last 3 months. Therefore, more attention should be paid to cough in the management of asthma.

The proportion of current smokers, COPD and bronchiectasis in CPA was significantly lower than that in CA patients, indicating that smoking, COPD and bronchiectasis could not fully explain the chronic cough of CPA. Rhinitis/sinusitis and gastroesophageal reflux are common causes of chronic cough [5, 34]. Our results showed that CPA patients had similar proportions of sinusitis, rhinitis and gastroesophageal reflux as CA patients. Therefore, the chronic cough in CPA would seem unlikely to be associated with sinusitis, rhinitis and gastroesophageal reflux. In addition, there were no significant differences with regard to the proportion of rhinitis and gastroesophageal reflux between CVA and CA patients, and a lower prevalence of sinusitis and bronchiectasis in CVA patients. It is also worth noting that abnormal laryngeal sensations such as itchy throat, throat clearing and irritation and triggers of cough are common in patients with chronic cough [35, 36], supporting the presence of cough hypersensitivity [36, 37]. Also, the proportion of patients with laryngeal symptoms in CVA and CPA was higher than that in CA patients, which is in line with the higher capsaicin cough sensitivity we report in CVA and CPA patients. Based on the above results, the chronic cough of CPA is underlined by the presence of cough hypersensitivity.

Chronic cough associated with asthma and non-asthmatic eosinophilic bronchitis typically respond well to therapy with corticosteroids, thus leading to the general assumption that the suppression of eosinophilic airway inflammation is the cause of basis for the improvement in cough [38, 39]. However, recent studies have challenged the causal relationship between eosinophilic airway inflammation and cough in asthmatics [40, 41], such as the failure of anti-interleukin (IL)-5 antibody to modify the cough of severe asthma [41], and the possibility for a role of activated mast cells in cough rather than eosinophilic airway inflammation [42, 43]. Similarly, in our cohort, there were no significant differences in the sputum eosinophil and neutrophil counts and FeNO levels among CVA, CPA and CA, which indicates that the measured severity of airway inflammation was not related to cough in asthma. This observation would also indicate that the severity of cough should be used as a measure of asthma control, independent of eosinophilic inflammation.

We found that the cough sensitivity of CPA and CVA was significantly higher than that of CA, supporting a role for the increased cough sensitivity in the pathogenesis of cough in asthma. The mechanism of increased cough sensitivity in asthmatic patients is currently unclear. Cough sensitivity in patients with asthma and COPD has been related to the severity of cough, but not to the degree of airflow obstruction [44]. Cough sensitivity of asthmatic patients could be decreased after inhaled corticosteroids [45]. It was possible that this effect was specific to the provocation agent utilized. In that study, mannitol, targeting on mast cell induced cough, was utilized as the provocative agent [45]. which would be inhibited by steroids. However, cough sensitivity of patients with asthma and COPD sometimes may not decrease after inhaled corticosteroids [44, 46, 47], but responded to anticholinergic treatment [44]. Testing cough sensitivity by capsaicin or citric acid is a direct measure of cough neural sensitivity. Previous studies have shown that patients with CVA had increased cough sensitivity to capsaicin [44, 48, 49]. Moreover, female patients and patients aged > 50 years had higher cough sensitivity to capsaicin than male patients and patients aged < 50 years, respectively [32]. The increased cough sensitivity caused by OVA-sensitized airway inflammation may be related to the expression of the transient receptor potential vanilloid 1 (TRPV1) in lung sensory nerve cells [50]. The overexpression of functional TRPV1 channels in the airway epithelium of patients with refractory asthma may provide a new therapeutic target for such asthma [51]. The mechanism underlying the increased cough sensitivity in CPA needs further study. However, P2X3 antagonist may be beneficial in the cough hypersensitivity of asthma [52].

The current questionnaires used to assess asthma control pay little attention to cough symptoms and their impact on quality of life. ACT and asthma control questionnaire (ACQ) scores are important indicators used to evaluate asthma control levels in the GINA guidelines [24], but they do not include questions relating to cough severity. In the ACT score of the asthma control test, one of the five questions relates to asthma symptoms which are either not defined nor mention cough as one of the symptoms [22]. In the other asthma control questionnaire (ACQ), cough is not asked about separately [23]. Some asthmatic patients have a higher cough frequency but a lower ACQ score [12], which may have resulted because of the lack of emphasis on assessing the severity of cough. The LCQ is widely used to assess the impact of cough on quality of life [53]. In patients with severe asthma, the LCQ score was moderately correlated with the ACQ-6 and asthma quality of life questionnaire (AQLQ) scores [54]. In the current study, we combined the ACT, cough VAS and LCQ scores to obtain a more comprehensive evaluation of asthma control that includes the impact of cough on quality of life.

Our study has some limitations. First, medical history and symptom assessment were assessed by questionnaires, which may lead to recall bias. Second, induced sputum tests, FeNO measurements and cough challenges were not conducted in all enrolled patients, this cohort nevertheless represents the largest sample of CVA and CPA patients studied. Third, a small number of patients were found to have concomitant COPD or bronchiectasis, that could have contributed to chronic cough symptoms. Finally, the details of drug name and dose of regular anti-asthma treatment were not collected in the questionnaires. However, we took the effect of treatment into consideration, which was important because inhaled corticosteroids could be effective in controlling asthma symptoms including cough. We divided the patients into groups according to whether they received regular treatment or not in the past 3 months, and found that though there was lower VAS scores in CPA patients with regular treatment, cough still was a prominent symptom, and there was no significant difference in cough VAS scores between those who received regular treatment and those who did not receive regular treatment in CVA, CA patients, indicating that the difference of the proportion of patients who received anti-asthma treatments between CA, CPA/CVA could not explain the presence of cough.

Conclusions

Our analysis supports the concept that CVA, CPA and CA represent distinct phenotypes of asthma when defined according to the presence of cough as a predominant symptom in association with wheeze and/or dyspnea. Asthmatic cough is more likely to be related to cough hypersensitivity rather than to comorbidities and airway inflammation. Our study also highlights the need to include an assessment of the severity of cough which could also be a marker of the severity of asthma independent of eosinophilic inflammation.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CVA:

Cough variant asthma

CPA:

Cough predominant asthma

CA:

Classic asthma

VAS:

Visual analogue scale

LCQ:

Leicester cough questionnaire

ACT:

Asthma control test

FeNO:

Fractional exhaled nitric oxide

FEV1% pred:

The forced vital capacity in percent predicted values

AR:

Allergic rhinitis

CRS:

Cough reflex sensitivity

CPAC:

CPA Cohort

CSS:

Cough symptom score

GINA:

Asthma Management and Prevention Guidelines

BHR:

Bronchial hyperresponsiveness

ICS:

Inhaled corticosteroids

LABA:

Long-acting Beta2-agonists

C5:

The lowest concentrations of capsaicin which evoked five or more coughs

LogC5:

Logarithm of C5

BMI:

Body mass index

ANOVA:

One-way analysis of variance

COPD:

Chronic obstructive pulmonary disease

FVC % pred:

The forced vital capacity in percent predicted values

MMEF % pred:

The maximum mid-expiratory flow in percent predicted values

Eos (%):

Percentage of eosinophils

Neu (%):

The percentage of neutrophils

ACQ:

Asthma control questionnaire

AQLQ:

Asthma quality of life questionnaire

TRPV1:

The transient receptor potential vanilloid 1

References

  1. Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56:219–33.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, Chu HW. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med. 1999;160:1001–8.

    Article  CAS  PubMed  Google Scholar 

  3. Osman LM, McKenzie L, Cairns J, Friend JA, Godden DJ, Legge JS, Douglas JG. Patient weighting of importance of asthma symptoms. Thorax. 2001;56:138–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Corrao WM, Braman SS, Irwin RS. Chronic cough as the sole presenting manifestation of bronchial asthma. N Engl J Med. 1979;300:633–7.

    Article  CAS  PubMed  Google Scholar 

  5. Lai K, Chen R, Lin J, Huang K, Shen H, Kong L, Zhou X, Luo Z, Yang L, Wen F, Zhong N. A prospective, multicenter survey on causes of chronic cough in China. Chest. 2013;143:613–20.

    Article  PubMed  Google Scholar 

  6. Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008;371:1364–74.

    Article  PubMed  Google Scholar 

  7. Niimi A, Matsumoto H, Mishima M. Eosinophilic airway disorders associated with chronic cough. Pulm Pharmacol Ther. 2009;22:114–20.

    Article  CAS  PubMed  Google Scholar 

  8. Lalloo UG, Barnes PJ, Chung KF. Pathophysiology and clinical presentations of cough. J Allergy Clin Immunol. 1996;98:S91-96 (discussion S96-97).

    Article  CAS  PubMed  Google Scholar 

  9. Niimi A, Ohbayashi H, Sagara H, Yamauchi K, Akiyama K, Takahashi K, Inoue H, Wakayama T, Kobayashi H, Hasegawa M, et al. Cough variant and cough-predominant asthma are major causes of persistent cough: a multicenter study in Japan. J Asthma. 2013;50:932–7.

    Article  PubMed  Google Scholar 

  10. Fukumitsu K, Kanemitsu Y, Asano T, Takeda N, Ichikawa H, Yap JMG, Fukuda S, Uemura T, Takakuwa O, Ohkubo H, et al. Tiotropium attenuates refractory cough and capsaicin cough reflex sensitivity in patients with asthma. J Allergy Clin Immunol Pract. 2018;6:1613-1620.e1612.

    Article  PubMed  Google Scholar 

  11. de Marco R, Marcon A, Jarvis D, Accordini S, Almar E, Bugiani M, Carolei A, Cazzoletti L, Corsico A, Gislason D, et al. Prognostic factors of asthma severity: a 9-year international prospective cohort study. J Allergy Clin Immunol. 2006;117:1249–56.

    Article  PubMed  Google Scholar 

  12. Marsden PA, Satia I, Ibrahim B, Woodcock A, Yates L, Donnelly I, Jolly L, Thomson NC, Fowler SJ, Smith JA. Objective cough frequency, airway inflammation, and disease control in asthma. Chest. 2016;149:1460–6.

    Article  PubMed  Google Scholar 

  13. Purokivi M, Koskela H, Kontra K. Determinants of asthma control and quality of life in stable asthma: evaluation of two new cough provocation tests. Clin Respir J. 2013;7:253–60.

    Article  PubMed  Google Scholar 

  14. Mincheva R, Ekerljung L, Bjerg A, Axelsson M, Popov TA, Lundback B, Lotvall J. Frequent cough in unsatisfactory controlled asthma–results from the population-based West Sweden Asthma study. Respir Res. 2014;15:79.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kanemitsu Y, Fukumitsu K, Kurokawa R, Takeda N, Suzuki M, Yap J, Nishiyama H, Tajiri T, Fukuda S, Uemura T, et al. Increased capsaicin sensitivity in patients with severe asthma is associated with worse clinical outcome. Am J Respir Crit Care Med. 2020;201:1068–77.

    Article  PubMed  Google Scholar 

  16. Morjaria JB, Rigby AS, Morice AH. Asthma phenotypes: do cough and wheeze predict exacerbations in persistent asthma? Eur Respir J. 2017;50:1701366.

    Article  PubMed  Google Scholar 

  17. Boulet LP. Influence of comorbid conditions on asthma. Eur Respir J. 2009;33:897–906.

    Article  PubMed  Google Scholar 

  18. Price D, Zhang Q, Kocevar VS, Yin DD, Thomas M. Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults. Clin Exp Allergy. 2005;35:282–7.

    Article  CAS  PubMed  Google Scholar 

  19. Bresciani M, Paradis L, Des Roches A, Vernhet H, Vachier I, Godard P, Bousquet J, Chanez P. Rhinosinusitis in severe asthma. J Allergy Clin Immunol. 2001;107:73–80.

    Article  CAS  PubMed  Google Scholar 

  20. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, Calhoun WJ, Castro M, Chung KF, Clark MP, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405–13.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Niimi A. Cough and asthma. Curr Respir Med Rev. 2011;7:47–54.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, Murray JJ, Pendergraft TB. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113:59–65.

    Article  PubMed  Google Scholar 

  23. Juniper EF, O’Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999;14:902–7.

    Article  CAS  PubMed  Google Scholar 

  24. Global strategy for asthma management and prevention (2016 update). 2016.

  25. Asthma Group of Respiratory Medicine Branch of Chinese Medical Association. Guidelines for diagnosis and treatment of cough (2015). Chin J Tuberc Respir Dis. 2016;5.

  26. Hsu JY, Stone RA, Logan-Sinclair RB, Worsdell M, Busst CM, Chung KF. Coughing frequency in patients with persistent cough: assessment using a 24 hour ambulatory recorder. Eur Respir J. 1994;7:1246–53.

    Article  CAS  PubMed  Google Scholar 

  27. Zhan W, Zhang L, Jiang M, Chen M, Yuan X, Sun J, Xu P, Wu F, Zhang C, Luo W, et al. A new simple score of chronic cough: cough evaluation test. BMC Pulm Med. 2020;20:68.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003;58:339–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–73.

    Article  CAS  PubMed  Google Scholar 

  30. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319–38.

    Article  CAS  PubMed  Google Scholar 

  31. American Thoracic Society, European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171:912–30.

    Article  Google Scholar 

  32. Lai K, Long L, Yi F, Tang J, Chen Z, Chen F, Zhou J, Peng W, Zhang L, Li H, et al. Age and sex distribution of Chinese chronic cough patients and their relationship with capsaicin cough sensitivity. Allergy Asthma Immunol Res. 2019;11:871–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Morice AH, Jakes AD, Faruqi S, Birring SS, McGarvey L, Canning B, Smith JA, Parker SM, Chung KF, Lai K, et al. A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J. 2014;44:1149–55.

    Article  PubMed  Google Scholar 

  34. Desai D, Brightling C. Cough due to asthma, cough-variant asthma and non-asthmatic eosinophilic bronchitis. Otolaryngol Clin N Am. 2010;43:123–30, x.

    Article  Google Scholar 

  35. Won HK, Kang SY, Kang Y, An J, Lee JH, Lee SM, Kwon JW, Kim MH, Jo EJ, Lee SE, et al. Cough-related laryngeal sensations and triggers in adults with chronic cough: symptom profile and impact. Allergy Asthma Immunol Res. 2019;11:622–31.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Song WJ, Kim JY, Jo EJ, Lee SE, Kim MH, Yang MS, Kang HR, Park HW, Chang YS, Min KU, Cho SH. Capsaicin cough sensitivity is related to the older female predominant feature in chronic cough patients. Allergy Asthma Immunol Res. 2014;6:401–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Vertigan AE, Gibson PG. Chronic refractory cough as a sensory neuropathy: evidence from a reinterpretation of cough triggers. J Voice. 2011;25:596–601.

    Article  PubMed  Google Scholar 

  38. Niimi A, Amitani R, Suzuki K, Tanaka E, Murayama T, Kuze F. Eosinophilic inflammation in cough variant asthma. Eur Respir J. 1998;11:1064–9.

    Article  CAS  PubMed  Google Scholar 

  39. Brightling CE, Ward R, Wardlaw AJ, Pavord ID. Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis. Eur Respir J. 2000;15:682–6.

    Article  CAS  PubMed  Google Scholar 

  40. Minoguchi H, Minoguchi K, Tanaka A, Matsuo H, Kihara N, Adachi M. Cough receptor sensitivity to capsaicin does not change after allergen bronchoprovocation in allergic asthma. Thorax. 2003;58:19–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. McGarvey LP, Forsythe P, Heaney LG, MacMahon J, Ennis M. Bronchoalveolar lavage findings in patients with chronic nonproductive cough. Eur Respir J. 1999;13:59–65.

    Article  CAS  PubMed  Google Scholar 

  43. Gibson PG, Zlatic K, Scott J, Sewell W, Woolley K, Saltos N. Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells. J Allergy Clin Immunol. 1998;101:320–6.

    Article  CAS  PubMed  Google Scholar 

  44. Doherty MJ, Mister R, Pearson MG, Calverley PM. Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary disease. Thorax. 2000;55:643–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Koskela HO, Hyvärinen L, Brannan JD, Chan HK, Anderson SD. Coughing during mannitol challenge is associated with asthma. Chest. 2004;125:1985–92.

    Article  PubMed  Google Scholar 

  46. Nieto L, de Diego A, Perpina M, Compte L, Garrigues V, Martinez E, Ponce J. Cough reflex testing with inhaled capsaicin in the study of chronic cough. Respir Med. 2003;97:393–400.

    Article  CAS  PubMed  Google Scholar 

  47. Fujimura M, Hara J, Myou S. Change in bronchial responsiveness and cough reflex sensitivity in patients with cough variant asthma: effect of inhaled corticosteroids. Cough. 2005;1:5.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Cho YS, Lee CK, Yoo B, Moon HB. Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients. J Korean Med Sci. 2002;17:616–20.

    Article  PubMed  PubMed Central  Google Scholar 

  49. De Diego A, Martinez E, Perpina M, Nieto L, Compte L, Macian V, Senent L. Airway inflammation and cough sensitivity in cough-variant asthma. Allergy. 2005;60:1407–11.

    Article  PubMed  Google Scholar 

  50. Zhang G, Lin RL, Wiggers M, Snow DM, Lee LY. Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat. J Physiol. 2008;586:5771–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. McGarvey LP, Butler CA, Stokesberry S, Polley L, McQuaid S, Abdullah H, Ashraf S, McGahon MK, Curtis TM, Arron J, et al. Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma. J Allergy Clin Immunol. 2014;133:704-712.e704.

    Article  CAS  PubMed  Google Scholar 

  52. Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, Ford AP. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020;8:775–85.

    Article  CAS  PubMed  Google Scholar 

  53. Wang K, Birring SS, Taylor K, Fry NK, Hay AD, Moore M, Jin J, Perera R, Farmer A, Little P, et al. Montelukast for postinfectious cough in adults: a double-blind randomised placebo-controlled trial. Lancet Respir Med. 2014;2:35–43.

    Article  CAS  PubMed  Google Scholar 

  54. Natarajan S, Free RC, Bradding P, McGarvey L, Siddiqui S. The relationship between the Leicester cough questionnaire, eosinophilic airway inflammation and asthma patient related outcomes in severe adult asthma. Respir Res. 2017;18:44.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This paper is presented on behalf of the CPA Cohort Study. We thank all the members of each recruiting centre for their dedicated effort, devotion, promptness and care in the recruitment and assessment of the participants in this study.

The members of the CPA Cohort Study Group are as follows: Prof. Ruchong Chen (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Prof. Weijie Guan (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Yanqing Xie (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Prof. Mei Jiang (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Jie Gao (Department of Pulmonary and Critical Care Medicine, Huizhou the Third People’s Hospital, Guangzhou Medical College), Dr. Wen Hua (The Second Hospital Zhejiang University School of Medicine), Dr. Guangyun Cai (The Second Affiliated Hospital of Guangzhou Medical University), Dr. Cuiyi Chen (Dongguan Third People's Hospital), Dr. Mingjuan Zhou (The Second Clinical College of Guangzhou University of Chinese Medicine), Dr. Yanyan Xu (The First People’s Hospital of Yunnan Province), Dr. Minghang Wang (The First Affiliated Hospital of Henan University of Chinese Medicine), Dr. Yimin Guo (Xijing Hospital, Fourth Military Medical University), Dr. Xue Li (The Second Hospital of Hebei Medical Universit), Dr. Lei Liu (West China School of Medicine/West China Hospital of Sichuan University), Dr. Hongmei Yao (Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital), Dr. Hong Wen (Dongguan People’s Hospital), Dr. Jianyou Chen (Qingdao Municipal Hospital), Dr. Xuemei Zhang (Xinqiao Hospital, Third Military Medical University), Dr. Zhiping Zhang (The People’s Hospital of Jiangmen), Dr. Li Yu (Tongji Hospital, School of Medicine, Tongji University), Dr. Dandan Chen (Shenzhen People's Hospital), Dr. Wei Du (Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicin), Dr. Qiaoli Chen (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Hu Li (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Wen Peng (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Liting Zhang (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Jiaman Tang (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Baojuan Liu (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Chen Zhan (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Lianrong Huang (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University), Dr. Xiaomei Chen (State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University) for collecting data and conducting relevant investigations.

Funding

The study was funded by the Clinical Research Foundation of GMU (2017-160) and the Key-Area Research and Development Program of Guangdong Province (2019B020227006). We also thank the Daiichi Sankyo Company as a sponsor of this study. However, they did not play a role in the study design, conducting, data analysis and manuscript preparing.

Author information

Author notes

  1. Jianmeng Zhou and Fang Yi contributed equally to this study and were listed as co-first authors

  2. Kian Fan Chung and Nanshan Zhong are senior authors

Authors and Affiliations

  1. Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Rd., Guangzhou, 510120, China

    Jianmeng Zhou, Fang Yi, Jiayu Pan, Wei Luo, Nanshan Zhong & Kefang Lai

  2. Department of Pulmonary and Critical Care Medicine, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, China

    Feng Wu

  3. The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    Pusheng Xu

  4. Dongguan Third People’s Hospital, Dongguan, China

    Meihua Chen

  5. The Second Hospital Zhejiang University School of Medicine, Hangzhou, China

    Huahao Shen

  6. The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China

    Lin Lin

  7. The First People’s Hospital of Yunnan Province, Kunming, China

    Yunhui Zhang

  8. The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China

    Suyun Li

  9. Xijing Hospital, Fourth Military Medical University, Xi’an, China

    Changgui Wu

  10. The Second Hospital of Hebei Medical University, Shijiazhuang, China

    Yadong Yuan

  11. West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China

    Gang Wang

  12. Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital, Guiyang, China

    Xianwei Ye

  13. Dongguan People’s Hospital, Dongguan, China

    Ping Zhang

  14. Qingdao Municipal Hospital, Qingdao, China

    Huaping Tang

  15. Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China

    Qianli Ma

  16. The People’s Hospital of Jiangmen, Jiangmen, China

    Lanqing Huang

  17. Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China

    Zhongmin Qiu

  18. The Second People’s Hospital of Shenzhen, Shenzhen, China

    Haiyan Deng

  19. Shenzhen People’s Hospital, Shenzhen, China

    Chen Qiu

  20. Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Guochao Shi

  21. National Heart and Lung Institute, Imperial College London, & Royal Brompton and Harefield Foundation NHS Trust, London, UK

    Kian Fan Chung

Authors
  1. Jianmeng Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fang Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pusheng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meihua Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huahao Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yunhui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Suyun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Changgui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yadong Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xianwei Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Huaping Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Qianli Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Lanqing Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Zhongmin Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Haiyan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Chen Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Guochao Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Jiayu Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Wei Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Kian Fan Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Nanshan Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Kefang Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the CPA Cohort Study Group

  • Ruchong Chen
  • , Weijie Guan
  • , Yanqing Xie
  • , Mei Jiang
  • , Jie Gao
  • , Wen Hua
  • , Guangyun Cai
  • , Cuiyi Chen
  • , Mingjuan Zhou
  • , Yanyan Xu
  • , Minghang Wang
  • , Yimin Guo
  • , Xue Li
  • , Lei Liu
  • , Hongmei Yao
  • , Hong Wen
  • , Jianyou Chen
  • , Xuemei Zhang
  • , Zhiping Zhang
  • , Li Yu
  • , Dandan Chen
  • , Wei Du
  • , Qiaoli Chen
  • , Hu Li
  • , Wen Peng
  • , Liting Zhang
  • , Jiaman Tang
  • , Baojuan Liu
  • , Chen Zhan
  • , Lianrong Huang
  •  & Xiaomei Chen

Contributions

KL designed the study, interpreted the data and takes responsibility for the integrity of the data and the accuracy of the analysis, wrote, and revised the manuscript. NZ and KFC revised the manuscript. JZ performed the analysis and wrote the first draft of the manuscript. JZ, FY, FW, HS, PX, MC, LL, YZ, SL, CW, YY, GW, XY, PZ, HT, QM, LH, ZQ, HD, CQ, GS, JP collected the clinical data, performed the analysis. WL, being responsible for induced sputum test. KL, KFC, FY had made substantial contributions to collecting the clinical data and revising the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kefang Lai.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University and the institutional review boards of each participating center (201604). It has also been registered in the Chinese Clinical Trial Registration Center (ChiCTR-POC-17011646). All participating patients provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

List of all clinical centers participating in the study.

Additional file 2.

Case Report Form of the study.

Additional file 3.

Questions for indicating diagnosis of CVA, CPA and CA from questionnaire.

Additional file 4.

Comparison of clinical characteristics among CVA, CPA and CA patients with regular and without regular treatment.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, J., Yi, F., Wu, F. et al. Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China. Respir Res 23, 243 (2022). https://doi.org/10.1186/s12931-022-02104-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12931-022-02104-8

Keywords

Respiratory Research

ISSN: 1465-993X

Contact us