Abstract
Background
Cough is a common and troublesome symptom in asthma that can persist despite treatment, but there is no tool to specifically assess cough in asthma patients. We developed the Cough Questionnaire for Asthma (CQA) to evaluate cough severity and its impact in asthma patients.
Methods
We developed an 8-item questionnaire to assess cough severity and its impact, which was later refined to a 6-item version (CQA6). The questionnaire was validated in 289 asthma patients attending a hospital asthma clinic. Internal consistency was assessed using Cronbach’s alpha. Concurrent validity was evaluated through correlations with the 6-item Asthma Control Questionnaire (ACQ6), the Cough Hypersensitivity Questionnaire (CHQ), and both patient and physician cough severity ratings (in a 5-point Liker scale). Repeatability was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analysis of responses obtained 3–6 months later.
Results
CQA6 demonstrated excellent internal consistency (Cronbach’s alpha =0.898) and strong correlations with patient-rated cough control (r=0.769), physician-rated cough control (r=0.692), and ACQ6 scores (r=0.672). CQA6 showed moderate correlation with CHQ scores (r=0.574). In longitudinal assessment, changes in CQA6 scores correlated strongly with changes in patient-assessed cough control (r=0.608) and ACQ6 (r=0.647). The ICC for CQA6 was 0.800 in stable patients, demonstrating good repeatability.
Conclusions
CQA6 is a reliable and valid tool for assessing cough severity and its impact in asthma patients. It will help in the evaluation of cough as an important contributory symptom for asthma management.
Keywords: Cough, asthma, cough questionnaire
Highlight box.
Key findings
• We developed the cough Questionnaire for Asthma (CQA) to evaluate cough severity and its impact in asthma patients. Six-item Cough Questionnaire for Asthma (CQA6) is a reliable and valid tool for assessing cough severity and its impact in asthma patients.
What is known and what is new?
• Currently, asthma control is assessed by two similar patient-reported outcome (PRO) measurement tools: the Asthma Control Questionnaire (ACQ) which evaluates asthma control in the past week and the Asthma Control Test (ACT) that assesses asthma control in the last 4 weeks. However, both questionnaires do not pay particular attention to cough. There are no specific questionnaire evaluating cough severity in patients with asthma.
• The Cronbach’s alpha coefficient of CQA6 was 0.898, which was sufficiently high in internal consistency. CQA6 showed strong correlations with patient’s rating of cough control, 6-item ACQ (ACQ6) score, and physician’s rating of cough control at the first visit, which supported CQA6 being a useful tool to evaluate asthmatic patients’ cough severity in asthma management, and the contribution of cough to level of asthma control.
What is the implication, and what should change now?
• CQA6 should be used to assess cough independently of other asthma symptoms in the management of asthma. The assessment of cough should be incorporated in any assessment tools of asthma control or severity.
Introduction
Cough is a common and troublesome symptom in asthma patients and is often associated with poorer asthma control and occurs during exacerbations (1). Chronic cough associated with a diagnosis of asthma is one of the most common group of patients seen in chronic cough clinics (2). Cough variant asthma, which is asthma presenting solely with cough symptoms (1), is one of the most common causes of chronic cough in cough clinics in East Asian countries (3-5). It is also quite frequent for cough to persist after asthma treatment with inhaled corticosteroids (ICS) or a combination of ICS and long-acting β-agonist (ICS + LABA), despite achieving good asthma control as measured by current asthma control questionnaires (ACQs) that do not contain any assessment of cough (6). However, the systematic evaluation of the impact of cough in patients with asthma and how cough is linked to other symptoms of asthma such as wheeze and breathlessness and to asthma control remains unclear. In addition, there have been very few clinical studies where the effect of ICS alone or ICS + LABA on cough of asthma has been documented (7).
Currently, asthma control is assessed by two similar patient-reported outcome (PRO) measurement tools: the ACQ which evaluates asthma control in the past week (8) and the Asthma Control Test (ACT) that assesses asthma control in the last 4 weeks (9). However, both questionnaires do not pay particular attention to cough. While the ACQ does not mention cough, the ACT asks one question on the severity of a broad collection of asthma symptoms that includes cough (wheezing, cough, shortness of breath, chest tightness or pain) (9). In the item reduction phase of development of the ACQ, the first five listed symptoms were included in the questionnaire, and cough was excluded as it was ranked as the sixth important symptom by 100 asthma clinicians (8). Yet, it is clear that patients with asthma themselves perceive as a major most troublesome symptom of the other asthma symptoms (10-13). In a patient weighting of importance of asthma symptoms study, 58% of the patients were troubled by cough, and daytime cough and breathlessness had a greater impact on these asthmatic patients (12). In addition, recent studies reported that asthma patients with chronic cough had increased exacerbations, health-care utilization, oral steroid exposure, or impaired work productivity and daily activity compared to those asthmatics without a chronic cough (14,15).
In view of the increasing evidence that the presence of cough in asthma is associated with worse asthma control and outcomes and of the importance of cough being a most troublesome symptom in patients with asthma, we developed the Cough Questionnaire for Asthma (CQA) in order to assess the impact of cough in patients with asthma because there is no PRO measurement tool to specifically assess cough in asthma. Currently used cough questionnaires such as the Leicester Cough Questionnaire (16) have been developed for assessing patients with a chronic cough defined by a persistent cough that has lasted for more than 8 weeks, which is a pattern of cough that may not be common in patients with mild-moderate asthma. Therefore, we used this newly-developed questionnaire CQA specifically for asthma patients attending an asthma clinic within a general hospital set-up and evaluated its internal consistency, reliability, and concurrent validity.
Methods
Development of the CQA
The CQA was developed as a simple tool for use in both primary and specialist care settings. It was first established in English and this was translated into Mandarin since we first used in the Mandarin-speaking asthma patients attending the University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
The CQA comprises of two parts: Part A measured the impact of cough on life and daily activities and Part B assessed the characteristics of their cough (Appendices 1,2). Part A was conceptually based on the main outcomes for the assessment of patients with chronic cough, such as cough frequency, cough severity, impact on quality of life, and any potential complications of cough. It initially comprised of eight questions related to cough and its impact was assessed over the past week: (I) cough frequency, (II) cough severity; (III) interference with work or daily life; (IV) sleep disturbance; (V) urinary incontinence; (VI) chest pain, and (VII) syncope. These items were chosen based on a literature review and on the opinion of specialist physicians in asthma management. Each question was assessed using a 5-point Likert scale (1-5) with a higher score indicating a greater impact of cough. The CQA score was calculated by totaling each item score.
Part B contained four items that characterizes cough, designed to address clinical features associated with the presence of cough: (I) cough occurring with fever; (II) cough occurring with phlegm; (III) cough occurring with wheeze or chest tightness; and (IV) cough accompanied by throat tightness. Each item was answered with “yes”, “no”, or “not sure”.
Evaluation of the CQA
Adult patients (≥18 years of age) with specialist-diagnosed asthma were consecutively recruited from June 2020 to November 2023. The presence or severity of cough was not an inclusion criterion. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The protocol was approved by the Medical Ethics Committee of the University of Hong Kong-Shenzhen Hospital with the IRB approval number (2020)115. All enrolled patients provided written informed consent prior to study procedure.
Participants completed the 8-item preliminary version of CQA Part A, along with the 6-item ACQ (ACQ6) (17) and Cough Hypersensitivity Questionnaire (CHQ) (18). ACQ6 is a validated measure of asthma control using a 6-item questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment. CHQ is a tool developed using validated methods to assess cough triggers and cough-associated upper airway symptoms with a score ranging from 0 to 22, with a higher score indicating greater likelihood of cough hypersensitivity (18). In addition, both the patients and the physician assessing the patient were required to rate independently using a 5-point Likert scale the severity of cough, with a higher score indicating worse cough (1-5).
Statistical analysis
Data are presented as means ± standard deviation (SD). Internal consistency and reliability were evaluated by calculating Cronbach’s alpha coefficients (19,20) for the initial 8-item version of CQA. Correlations were calculated between each item and the total score (excluding that item). Items with low item-total correlations (Spearman correlation <0.3) were considered candidates for removal. Additionally, items whose removal substantially increased the alpha coefficient were removed. Items with a high ceiling effect (i.e., items with >80% of responses falling into the two lowest categories) were also considered for elimination.
Concurrent validity was assessed by correlating the CQA score with ACQ6, CHQ, and subjective ratings of cough control status by patients and physicians. The correlations of CQA scores with ACQ6 were also examined according to patient-reported cough characteristics in CQA Part B.
We assessed the longitudinal stability of the CQA scores by inviting patients for repeat examination at a second visit within six months of the baseline visit. Repeatability was tested using a Bland-Altman plot and intraclass correlation coefficient (ICC) in subjects with the same patient-rated cough control scores at both visits (assuming comparable cough status). An ICC value of ≥0.61 was deemed satisfactory (21). The limits of agreement were determined as mean ± 1.96 SD of within-subject differences.
Results
Study subjects
A total of 289 asthmatic patients (Table 1) were included in the study. The age of the participants was 36.0 (interquartile range, 29, 44) years old; 55.4% were women, 74.4% were non-smokers, 66.1% had atopy, and 68.5% had allergic rhinitis. We also measured fractional level of nitric oxide in exhaled breath (FeNO), blood eosinophil count, and lung function during the first visit. In the study, 85.8% of patients had a blood eosinophil count ≥150/µL, and 85.1% had FeNO levels ≥20 ppb.
Table 1. Baseline characteristics of all participants (N=289).
| Parameters | Value |
|---|---|
| Age (years), mean ± SD | 37.54±11.20 |
| Asthma onset age (years), mean ± SD | 30.60±12.47 |
| Women, n (%) | 160 (55.4) |
| Non-smokers, n (%) | 215 (74.4) |
| BMI (kg/m2), mean ± SD | 23.34±3.58 |
| Asthma severity, n (%) | |
| Mild | 9 (3.1) |
| Moderate | 259 (89.6) |
| Severe | 21 (7.3) |
| Atopy, n (%) | 191 (66.1) |
| FeNO (ppb) (n=275), mean ± SD [range] | 77.22±58.10 [5–300] |
| % subjects with FeNO ≥20 ppb | 85.1 |
| Blood eosinophil count (×106/μL) (n=254), mean ± SD [range] | 0.48±0.38 [0.01–2.42] |
| % subjects with blood eosinophil count ≥150×103/μL | 85.8 |
| Associated comorbidities (17 patients had 2 comorbidities), n (%) | 216 (74.7) |
| Allergic rhinitis | 198 (68.5) |
| Eczema | 11 (3.8) |
| Urticaria | 7 (2.4) |
| Atopic dermatitis | 3 (1.0) |
| GERD | 4 (1.4) |
| Bronchiectasis | 10 (3.5) |
| FEV1% predicted (n=280), mean ± SD | 80.71±17.03 |
| FVC% predicted (n=280), mean ± SD | 94.29±13.32 |
| FEV1/FVC (%), mean ± SD | 72.94±11.10 |
| CQA6 score, mean ± SD | 12.94±5.26 |
| CHQ score, mean ± SD | 5.24±3.47 |
| ACQ6 score, mean ± SD | 1.21±0.92 |
| Patient assessment of cough control (1–5 scale), mean ± SD |
3.10±1.30 |
| Physician assessment of cough control (1–5 scale), mean ± SD | 3.27±1.33 |
| Medication information, n | |
| Low dose ICS | 6 |
| Low dose ICS-LABA as needed | 3 |
| Low dose ICS-LABA | 113 |
| Medium dose ICS-LABA | 156 |
| High dose ICS-LABA | 9 |
| LAMA | 6 |
| LTRA | 6 |
| OCS | 9 |
| Antitussives | 15 |
| Nasal saline | 65 |
| Glucocorticoid nasal spray | 56 |
| Oral antihistamines | 29 |
| Biologic therapy | 4 |
| PPI | 4 |
| Antibiotics | 9 |
ACQ6, 6-item Asthma Control Questionnaire; BMI, body mass index; CHQ, Cough Hypersensitivity Questionnaire; CQA6, 6-item Cough Questionnaire for Asthma; FeNO, fractional nitric oxide level in exhaled breath; FEV1, forced expiratory volume in the first second; FVC, forced expiratory volume; GERD, gastroesophageal reflux disease; ICS, inhaled corticosteroid; ICS-LABA, combination of inhaled corticosteroid and long-acting β-agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; ppb, parts per billion; PPI, proton pump inhibitor; SD, standard deviation.
CQA questionnaire refinement
The Cronbach’s alpha coefficient of the 8-item preliminary version of CQA was 0.868. The item-total correlations ranged from 0.192 to 0.830 (Table 2). Scores for each item are shown in Figure 1, with notably lower scores for urinary incontinence and syncope. Consequently, these two items were removed from analysis. The item-total correlations for these items were 0.192 and 0.345, respectively, and the Cronbach’s alpha increased when either of them was removed. The final CQA was thus revised to a 6-item tool, named CQA6. The Cronbach’s alpha coefficient of CQA6 was 0.898.
Table 2. The item-total correlations of CQA.
| Items | Item-total correlation | Cronbach’s α if item deleted |
|---|---|---|
| 1. Cough frequency† | 0.709 | 0.842 |
| 2. Cough severity† | 0.830 | 0.825 |
| 3. Interfered with work/daily life† | 0.807 | 0.829 |
| 4. Interfered with social life/relationship† | 0.796 | 0.831 |
| 5. Disturbed sleep† | 0.737 | 0.839 |
| 6. Urinated involuntarily | 0.345 | 0.876 |
| 7. Chest pain† | 0.451 | 0.868 |
| 8. Fainting/Losing awareness | 0.192 | 0.883 |
†, the final items of CQA6. CQA, Cough Questionnaire for Asthma.
Figure 1.
Distribution of individual scores (between 0 and 5; a higher score indicating a greater impact of cough) of each of the 8 CQA items (C1 to C8) at the first visit of the 289 asthma participants. Each subject’s score is shown. The mean score ± standard deviation for each item is shown both as the actual numbers and as the box value with standard deviation bars. CQA, Cough Questionnaire for Asthma.
The CQA6 score was calculated as the mean of the 6 item scores. The mean CQA score was 12.94±5.26 out of a maximum score of 30 (Table 1). An average of 16.5% of asthmatics that report experiencing ‘most of the time’ and ‘at all times’ the symptoms and effects associated with cough, with 34% reporting ‘seldom’ or ‘sometimes’ and 39.5% no symptom of cough (Figure 2).
Figure 2.
Distribution of the percentage of asthmatic subjects (total number =289) who selected each of the six items in the CQA6 questionnaire. The mean percentage of asthmatic subjects scoring at score 1 to score 5 (y-axis) for each of the six-item responses of the CQA questionnaire (x-axis) is also shown. The scoring scale ranges from bottom (score 1, light green) to top (score 5, dark green). Scoring of CQA: score 1: never; score 2: seldom; score 3: sometimes; score 4: most of the time; score 5: at all times. CQA6, 6-item Cough Questionnaire for Asthma.
CQA6 score showed strong correlations with patients’ ratings of cough control, physicians’ ratings of cough control, and ACQ6 scores (r=0.769, r=0.692, and r=0.672, respectively; all P<0.001). The correlation between CQA6 and CHQ scores was moderate (r=0.574, P<0.001). Neither CQA6 nor CHQ scores correlated with blood eosinophil count, FeNO, forced expiratory volume in the first second (FEV1)% predicted, forced expiratory volume (FVC)% predicted, or FEV1/FVC. ACQ6 showed weak correlations with blood eosinophil count, FeNO, FEV1% predicted, and FEV1/FVC (Table 3).
Table 3. Spearman rank correlations between different questionnaire scores, blood eosinophil count, FeNO, and spirometric parameters at the first visit.
| Items | CQA6 | ACQ6 | CHQ | Prate | Drate | Eos | FeNO | FEV1 | FVC | FEV1/FVC |
|---|---|---|---|---|---|---|---|---|---|---|
| CQA6 | 1 | |||||||||
| ACQ6 | 0.672** | 1 | ||||||||
| CHQ | 0.574** | 0.480** | 1 | |||||||
| Prate | 0.769** | 0.537** | 0.462** | 1 | ||||||
| Drate | 0.692** | 0.491** | 0.372** | 0.767** | 1 | |||||
| Eos | 0.077 | 0.161* | 0.017 | 0.036 | 0.107 | 1 | ||||
| FeNO | −0.015 | 0.162** | −0.050 | −0.029 | 0.063 | 0.502** | 1 | |||
| FEV1 | −0.039 | 0.169** | −0.043 | 0.017 | 0.004 | −0.151* | 0.140* | 1 | ||
| FVC | −0.081 | −0.114 | −0.053 | −0.006 | 0.008 | −0.071 | −0.076 | 0.757** | 1 | |
| FEV1/FVC | 0.020 | 0.166** | −0.026 | 0.036 | 0.000 | 0.174** | 0.128* | 0.711** | 0.204** | 1 |
*, P<0.05; **, P<0.01. ACQ6, 6-item Asthma Control Questionnaire; CHQ, Cough Hypersensitivity Questionnaire; CQA6, 6-item Cough Questionnaire for Asthma; Drate, physician’s rating of cough control; Eos, blood eosinophil count; FeNO, fractional concentration of exhaled nitric oxide; FEV1, forced expiratory volume in the first second; FEV1/FVC, ratio of FEV1 to FVC; FVC, forced vital capacity; Prate, patient’s rating of cough control.
Correlations between CQA6 and ACQ6
The correlations of each CQA6 item with the ACQ6 score are shown in Table 4. The correlation coefficients ranged from 0.409 to 0.647 (all P<0.001). The CQA6 item on sleep disturbance showed the strongest correlation with the ACQ6 score (r=0.647), compared to other CQA6 items. The correlations of each ACQ6 item with the CQA6 score are summarized in Table 5. The ACQ6 item ‘awaken at night by symptoms’ showed a strong correlation with the CQA6 score (r=0.629, P<0.001). The correlation between the last ACQ6 item, ‘puffs of short-acting bronchodilator’, and the CQA6 score was weak (r=0.196, P<0.001). The other four ACQ6 items showed moderate correlations with the CQA6 score (Table 5).
Table 4. Spearman correlations between CQA6 items and ACQ6.
| CQA6 items | ACQ6 score |
|---|---|
| Cough frequency | 0.485** |
| Cough severity | 0.580** |
| Interfered work/daily life | 0.564** |
| Interfered social life/relationship | 0.553** |
| Disturbed sleep | 0.647** |
| Chest pain | 0.409** |
**, P<0.01. ACQ6, 6-item Asthma Control Questionnaire; CQA6, 6-item Cough Questionnaire for Asthma.
Table 5. Spearman correlations between ACQ6 items and CQA6.
| ACQ6 items | CQA6 score |
|---|---|
| Awaken at night by symptoms | 0.629** |
| Symptoms when woke up in the morning | 0.552** |
| Limitation of daily activities | 0.575** |
| Short of breath | 0.447** |
| Wheeze | 0.438** |
| Puffs of short-acting bronchodilator | 0.196** |
**, P<0.01. ACQ6, 6-item Asthma Control Questionnaire; CQA6, 6-item Cough Questionnaire for Asthma.
The correlations between CQA6 and ACQ6 scores were compared according to the CQA Part B responses to explore the relationships between cough and asthma control in different clinical contexts. The positive response rate to ‘cough with fever’ was very low (3.5%), and there was a high frequency of ‘not sure’ responses for ‘cough improved with bronchodilator’ (40.5%). The correlation between CQA6 and ACQ6 was comparable regardless of sputum presence. However, it was stronger in patients with ‘cough with shortness of breath’ than in those without (r=0.610 vs. 0.485, Table 6).
Table 6. Spearman correlation between CQA6 and ACQ6 scores according to cough characteristics.
| Parameters | Spearman correlation | |
|---|---|---|
| r | P | |
| Cough with fever | ||
| No (n=274) | 0.675 | <0.001 |
| Yes (n=10) | 0.678 | 0.03 |
| Cough with sputum | ||
| No (n=111) | 0.602 | <0.001 |
| Yes (n=165) | 0.653 | <0.001 |
| Cough with shortness of breath | ||
| No (n=109) | 0.485 | <0.001 |
| Yes (n=157) | 0.610 | <0.001 |
| Cough improved with bronchodilator inhaler | ||
| No (n=18) | 0.760 | <0.001 |
| Yes (n=154) | 0.680 | <0.001 |
| Not sure/not used (n=117) | 0.627 | <0.001 |
ACQ6, 6-item Asthma Control Questionnaire; CQA6, 6-item Cough Questionnaire for Asthma.
Longitudinal response
A total of 123 patients completed the second research visit within six months of the baseline visit. The correlations between the change (Δ) in CQA6 scores and the changes in ACQ6, patient-assessed cough control, and physician-assessed cough control were calculated (Table 7). ΔCQA6 showed strong correlations with both Δ patient’s assessment of cough control and ΔACQ6 (r=0.608 and r=0.647, respectively) and had a moderate correlation with ΔCHQ (r=0.496). Furthermore, the correlations between ΔCHQ and Δ patient’s assessment of cough control with ΔCQA6 were stronger than those with ΔACQ6 (r=0.496, r=0.608, and r=0.378, r=0.507, respectively).
Table 7. Spearman correlations between ΔCQA6, ΔACQ6, ΔCHQ and ΔPatients’ assessment of cough control.
| Items | ΔCQA6 | ΔACQ6 | ΔCHQ | ΔPatients’ assessment of cough control |
|---|---|---|---|---|
| ΔCQA6 | 1 | |||
| ΔACQ6 | 0.647** | 1 | ||
| ΔCHQ | 0.496** | 0.378** | 1 | |
| ΔPatients’ assessment of cough control | 0.608** | 0.507** | 0.342** | 1 |
**, P<0.01. Δ: the difference value between V2 score to V1 score. ACQ6, 6-item Asthma Control Questionnaire; CHQ, Cough Hypersensitivity Questionnaire; CQA6, 6-item Cough Questionnaire for Asthma.
Repeatability
Forty-five patients had stable cough between the two visits (with the same patient-rated cough control scores at both visits), and their data were included in the repeatability analysis. The ICC for CQA6 was high (r=0.800, P=0.001). The Bland-Altman plot of CQA6 scores is shown in Figure 3, with a P value of 0.223.
Figure 3.
Bland-Altman plot of CQA6 score repeated in 45 patients that had same cough status at two visits. “----” = mean difference between the two scores, “—” = 95% limits of agreement. P value =0.223. CQA6, 6-item Cough Questionnaire for Asthma; SD, standard deviation.
Discussion
We developed a questionnaire to evaluate the impact of cough in patients with asthma and determined the response characteristics in a group of asthmatic patients attending an asthma clinic unselected by their cough status. The analyses demonstrated internal consistency, concurrent validity, and repeatability of CQA6. Therefore, CQA6 can be used as a simple clinical tool to measure the impact of cough in patients with asthma.
The Cronbach’s alpha coefficient of CQA6 was 0.898, that was sufficiently high in internal consistency. CQA6 showed strong correlations with patient’s rating of cough control, ACQ6 score, and physician’s rating of cough control in first visit, which supported CQA6 being a useful tool to evaluate asthmatic patients’ cough severity in asthma management, and the contribution of cough to level of asthma control. The strength of the correlation between patient’s rating of cough control/physician’s rating of cough control/CHQ and CQA6 were significantly stronger than that with ACQ6. In addition, the correlations between ΔCHQ and ΔPatient’s assessment of cough control with ΔCQA6 were stronger than those with ΔACQ6. These indicate that CQA6 captured cough severity and cough change better than ACQ6. On the other hand, cough-related questionnaires, such as CQA6 and CHQ, were significantly associated with ACQ6 score, conforming to previous study showed cough quality of life correlating well with standard measures of asthma control (22). CQA score did not significantly correlate with blood eosinophil count, FeNO, FEV1% predicted, FVC% predicted, or FEV1/FVC, which are also consistent with previous reports using different cough measures (13,22).
The ICC and Bland-Altman plot of CQA6 score were excellent, showing good repeatability. The longitudinal validity results showed that the CQA6 was responsive to change after treatment: ΔCQA6 had strong correlations with ΔPatient’s assessment of cough control and ΔACQ6 and had moderate correlation with ΔCHQ.
Among the CQA6 items, the item 5 “cough disturbed sleep” showed stronger correlation with ACQ6, and the ACQ6 item “awaken at night by symptoms” showed strong correlations with CQA6 total score, the results consistent with asthma symptoms occurring more often at night (23), and nocturnal cough and sleep quality are useful properties used as markers for asthma control (24).
The CHQ is a questionnaire that records the number of triggers and laryngeal sensations in a structured manner, evaluating cough-associated laryngeal hypersensitivity (18). Our data showed that CHQ was significantly correlated with CQA6, ACQ6, patient’s and physician’s rating of cough control. In the longitudinal evaluation, ΔCHQ correlated with ΔCQA6 and ΔACQ6 significantly too, indicating the asthma patients had features of cough hypersensitivity (25).
In this survey of patients with asthma, we found that cough can be a prominent symptom in up to 17% of asthmatics that report experiencing ‘most of the time’ and ‘at all times’ the symptoms and effects associated with cough, with 34% reporting ‘seldom’ or ‘sometimes’. Thus, cough is affecting up to half of these 289 stable asthmatics attending a hospital asthma clinic in China. Although the CQA questionnaire now confirms the importance of cough in asthma that has been highlighted previously (1,12), this impact of cough in asthma needs to be confirmed by objective counts of cough. This has been reported previously in 24-hour recordings of cough (22,26) but the advent of continuous cough recordings will allow more a more long-term assessment of cough in asthma as has been done in studies of refractory chronic cough (27). Although each score of the 6 items of the CQA6 correlated with the overall ACQ6 score of asthma control, the correlation indicated that the ACQ6 score only accounted for up to 40% of this association. This indicates that the assessment of cough in asthma needs to be done independently of existing asthma control measures.
There are some limitations in this study. First, this study focused on asthma patients with moderate severity (89.6%) with only 7.3% suffering from severe asthma. Therefore, its validity needs to be ascertained in patients with severe asthma, where the problem of cough may be more important. Second, we determined the CQA6 internal consistency, concurrent validation, repeatability and responsiveness, but we have not determined its minimal important difference because we focused on the refinement and exploration of the questionnaire.
Conclusions
To our knowledge, this is the first study to specifically report a patient-centered evaluation of cough in asthma. CQA6 is a reliable 6-item tool to measure the severity and impact of cough in asthma. Cough is a distinct symptom in asthmatics and affects patients’ quality of life. It should be used to assess cough independently of other asthma symptoms in the management of asthma. Alternatively, its assessment should be incorporated in any assessment tools of asthma control or severity.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The protocol was approved by the Medical Ethics Committee of The University of Hong Kong-Shenzhen Hospital with the IRB approval number (2020)115. All enrolled patients provided written informed consent prior to study procedure.
Footnotes
Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease for the series “Cough Section”. The article has undergone external peer review.
Funding: This study was supported by ‘Sanming Project of Medicine in Shenzhen’ (grant No. SZSM201612096) awarded to the Respiratory and Critical Care Division at The University of Hong Kong-Shenzhen Hospital by the National Health and Family Planning Commission of Shenzhen, China.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-261/coif). The series “Cough Section” was commissioned by the editorial office without any funding or sponsorship. W.J.S. serves as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Journal of Thoracic Disease. K.F.C. serves as an unpaid associate Editor-in-Chief of Journal of Thoracic Disease. M.S.M.I. serves as an unpaid editorial board member of Journal of Thoracic Disease. M.S.M.I. has received consulting fees from AZ and Sanofi; and donation grant support (via institution) from Li Ka Shing Foundation, all unrelated to this work. W.J.S. declares grants from Daewoong Pharmaceutical; consulting fees from GSK and Reckitt Benckiser; and lecture fees from Thermo Fisher/Immunotek, Celltrion, AstraZeneca, GSK, and Organon, all unrelated to this work. He also serves as Chief Editor of ERJ Open Research. K.F.C. declares grants from MRC, EPSRC, NIEHS, GSK, and Merck; lecture fees of Speaking engagements for GSK, Novartis, and AZ; he also served as a member of Advisory Board meeting for GSK, AZ, Novartis, Roche, Merck, Trevi, Rickett-Beckinson, Nocion & Shionogi on asthma, COPD and chronic cough, and Scientific Advisory Board of the Clean Breathing Institute supported by Haleon. The authors have no other conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-261/dss
References
- 1.Lai K, Satia I, Song WJ, et al. Cough and cough hypersensitivity as treatable traits of asthma. Lancet Respir Med 2023;11:650-62. 10.1016/S2213-2600(23)00187-X [DOI] [PubMed] [Google Scholar]
- 2.Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet 2008;371:1364-74. 10.1016/S0140-6736(08)60595-4 [DOI] [PubMed] [Google Scholar]
- 3.Kang SY, Kim GW, Song WJ, et al. Chronic cough in Korean adults: a literature review on common comorbidity. Asia Pac Allergy 2016;6:198-206. 10.5415/apallergy.2016.6.4.198 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lai K, Chen R, Lin J, et al. A prospective, multicenter survey on causes of chronic cough in China. Chest 2013;143:613-20. 10.1378/chest.12-0441 [DOI] [PubMed] [Google Scholar]
- 5.Ishiura Y, Fujimura M, Ogawa H, et al. Prevalence and causes of chronic cough in Japan. Respir Investig 2024;62:442-8. 10.1016/j.resinv.2024.02.017 [DOI] [PubMed] [Google Scholar]
- 6.Adachi M, Hozawa S, Nishikawa M, et al. Asthma control and quality of life in a real-life setting: a cross-sectional study of adult asthma patients in Japan (ACQUIRE-2). J Asthma 2019;56:1016-25. 10.1080/02770903.2018.1514628 [DOI] [PubMed] [Google Scholar]
- 7.Holmes J, Heaney LG, McGarvey LPA. Objective and Subjective Measurement of Cough in Asthma: A Systematic Review of the Literature. Lung 2022;200:169-78. 10.1007/s00408-022-00527-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Juniper EF, O'Byrne PM, Guyatt GH, et al. Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999;14:902-7. 10.1034/j.1399-3003.1999.14d29.x [DOI] [PubMed] [Google Scholar]
- 9.Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol 2004;113:59-65. 10.1016/j.jaci.2003.09.008 [DOI] [PubMed] [Google Scholar]
- 10.Song WJ, Won HK, Lee SY, et al. Patients' experiences of asthma exacerbation and management: a qualitative study of severe asthma. ERJ Open Res 2021;7:00528-2020 . 10.1183/23120541.00528-2020 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Holmes J, O'Neill V, McGarvey LP, et al. Adverse perception of cough in patients with severe asthma: a discrete choice experiment. ERJ Open Res 2023;9:00442-2022 . 10.1183/23120541.00442-2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Osman LM, McKenzie L, Cairns J, et al. Patient weighting of importance of asthma symptoms. Thorax 2001;56:138-42. 10.1136/thorax.56.2.138 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lee HY, Lee Y, Lee JH, et al. Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma. Lung 2024;202:405-14. 10.1007/s00408-024-00710-5 [DOI] [PubMed] [Google Scholar]
- 14.Deng SJ, Wang J, Liu L, et al. Chronic cough in asthma is associated with increased airway inflammation, more comorbidities, and worse clinical outcomes. Allergy Asthma Proc 2022;43:209-19. 10.2500/aap.2022.43.220022 [DOI] [PubMed] [Google Scholar]
- 15.Lee HY, Lee Y, Lee SE, et al. Relationships Between Chronic Cough and Asthma Control and Quality of Life in Patients With Severe Asthma: A 6-Month Longitudinal Analysis. J Allergy Clin Immunol Pract 2025;13:533-541.e3. 10.1016/j.jaip.2025.01.006 [DOI] [PubMed] [Google Scholar]
- 16.Birring SS, Prudon B, Carr AJ, et al. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax 2003;58:339-43. 10.1136/thorax.58.4.339 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Juniper EF, Bousquet J, Abetz L, et al. Identifying 'well-controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. Respir Med 2006;100:616-21. 10.1016/j.rmed.2005.08.012 [DOI] [PubMed] [Google Scholar]
- 18.Hirons B, Cho PSP, Krägeloh C, et al. The development of the Cough Hypersensitivity Questionnaire for chronic cough. ERJ Open Res 2024;10:00468-2024 . 10.1183/23120541.00468-2024 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Kite M, Whitley BE. Principles of research in behavioral science. 3rd edition. Routledge; 2012. [Google Scholar]
- 20.Robinson J. Triandis' theory of interpersonal behaviour in understanding software piracy behaviour in the South African context. University of the Witwatersrand Johannesburg; 2010. [Google Scholar]
- 21.Weir JP. Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res 2005;19:231-40. 10.1519/15184.1 [DOI] [PubMed] [Google Scholar]
- 22.Marsden PA, Satia I, Ibrahim B, et al. Objective Cough Frequency, Airway Inflammation, and Disease Control in Asthma. Chest 2016;149:1460-6. 10.1016/j.chest.2016.02.676 [DOI] [PubMed] [Google Scholar]
- 23.Turner-Warwick M. Nocturnal asthma: a study in general practice. J R Coll Gen Pract 1989;39:239-43. [PMC free article] [PubMed] [Google Scholar]
- 24.Tinschert P, Rassouli F, Barata F, et al. Nocturnal Cough and Sleep Quality to Assess Asthma Control and Predict Attacks. J Asthma Allergy 2020;13:669-78. 10.2147/JAA.S278155 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Chung KF, McGarvey L, Mazzone SB. Chronic cough as a neuropathic disorder. Lancet Respir Med 2013;1:414-22. 10.1016/S2213-2600(13)70043-2 [DOI] [PubMed] [Google Scholar]
- 26.Hsu JY, Stone RA, Logan-Sinclair RB, et al. Coughing frequency in patients with persistent cough: assessment using a 24 hour ambulatory recorder. Eur Respir J 1994;7:1246-53. 10.1183/09031936.94.07071246 [DOI] [PubMed] [Google Scholar]
- 27.Chung KF, Chaccour C, Jover L, et al. Longitudinal Cough Frequency Monitoring in Persistent Coughers: Daily Variability and Predictability. Lung 2024;202:561-8. 10.1007/s00408-024-00734-x [DOI] [PMC free article] [PubMed] [Google Scholar]