Background
Chronic cough is a common symptom that involves 20%-38% of the patients seeking medical advice in the respiratory clinic [
1,
2], and a medical problem often faced by clinicians. Persistent cough may cause organ injuries as well as psychological and social dysfunction, thereby having a profound adverse impact on quality of life [
3]. With quantitative or semi-quantitative methods, the changes in the health-related quality of life (HRQOL) provoked by cough can be accurately analyzed, which is useful for assessment of cough severity and therapeutic efficacy, and can help to guide clinical practice and research in chronic cough.
Cough symptom score, generic instruments such as the Short form-36 health survey (SF-36), Sickness impact profile and the other respiratory health questionnaires were common tools for the evaluation of HRQOL in chronic cough in early years [
4]. Cough symptom score, although simple and convenient, is not comprehensive while generic instruments are troublesome and time-consuming. Furthermore, lack of scores specific for cough or only several items referring to cough in generic instruments makes it difficult to precisely measure the tiny changes of HRQOL caused by cough. To overcome these shortages, the tools specific for assessments of HRQOL on chronic cough have been designed, including the cough-specific quality-of-life questionnaire [
5], Leicester cough questionnaire (LCQ) [
6] and chronic cough impact questionnaire [
7]. The utilization of these instruments has greatly promoted the studies of quality of life in chronic cough patients.
It has been demonstrated that chronic cough has negative effects on HRQOL of patients in many aspects including physical, psychological and social domains, among which the adverse impact on the psychosocial domain is the most notable and possibly related to gender [
5]. Successful treatments not only relieve the symptoms of cough, but also improve the quality of life [
5,
7,
8]. However, the current data on the HRQOL of chronic cough are only from several western countries. The conclusions extrapolated from these studies might not be suitable for the patients in the other regions of the world because of differences in the geography, ethnic, customs, cultural backgrounds and lifestyle. Therefore, the purpose of the present study was to investigate the changes in HRQOL in Chinese patients with chronic cough.
Results
Validation of repeatability on the Chinese version of LCQ
The intraclass correlation coefficient of LCQ repeatability was 0.94 (95% confidence interval: 0.85-0.98, P = 0.000) for total score, 0.89 (95% confidence interval: 0.73-0.96, P = 0.000) for the physical domain score, 0.93 (95% confidence interval: 0.82-0.97, P = 0.000) for the psychological domain score and 0.92 (95% confidence interval: 0.79-0.97, P = 0.000) for the social domain score respectively.
HRQOL in patients with chronic cough
HRQOL in 110 patients with chronic cough, as represented by scores of SF-36, was significantly poorer than that in 90 healthy volunteers. Among the multi-item scales of SF-36, RE, GH and RP were affected in the most outstanding way (Table
2).
Table 2
Comparison on scores of SF-36 between chronic cough group and healthy control group
PF | 88.9 ± 10.6 | 95.2 ± 6.7 | 5.1 | 0.000 |
RP | 66.3 ± 34.5 | 92.0 ± 25.3 | 5.6 | 0.000 |
RE | 44.5 ± 36.5 | 92.6 ± 21.0 | 11.6 | 0.000 |
VT | 70.8 ± 16.6 | 86.7 ± 10.0 | 8.3 | 0.000 |
MH | 75.8 ± 14.6 | 87.3 ± 9.8 | 6.7 | 0.001 |
SF | 84.9 ± 16.7 | 93.9 ± 9.9 | 4.6 | 0.000 |
BP | 89.5 ± 10.7 | 92.2 ± 10.1 | 1.9 | 0.063 |
GH | 58.8 ± 18.4 | 83.8 ± 13.4 | 10.7 | 0.000 |
PCS | 60.3 ± 5.0 | 66.2 ± 4.3 | 8.8 | 0.000 |
MCS | 57.6 ± 5.6 | 66.0 ± 3.8 | 12.7 | 0.000 |
Differences of HRQOL between different etiologies of chronic cough
The causes of chronic cough in 110 patients were shown in Table
3. Beside the single cause, cough symptoms in 10 patients could be explained by two causes, including 4 cases of cough variant asthma (CVA) plus upper airway cough syndrome (UACS), 4 cases of CVA plus gastroesophageal reflux disease (GERD) and 2 cases of UACS plus GERD. The other causes consisted of one case of environmental factor related cough, 3 cases of angiotensin-converting enzyme inhibitor-induced cough and 7 cases of idiopathic cough. There were no significant differences in HRQOL between the different etiologies of chronic cough, whether measured with LCQ (Table
3) or with SF-36 (Table
4).
Table 3
HRQOL comparison of LCQ scale between different causes of chronic cough (n = 110)
UACS | 10 | 14.5 ± 0.7 | 4.6 ± 0.2 | 4.4 ± 0.3 | 5.5 ± 0.3 |
CVA | 54 | 14.2 ± 0.4 | 4.6 ± 0.1 | 4.3 ± 0.1 | 5.3 ± 0.2 |
GERD | 6 | 13.7 ± 0.7 | 3.9 ± 0.5 | 4.5 ± 0.3 | 5.3 ± 0.3 |
NAEB | 10 | 13.7 ± 1.0 | 4.5 ± 0.3 | 4.1 ± 0.4 | 5.2 ± 0.5 |
PVC | 9 | 14.9 ± 1.4 | 4.8 ± 0.3 | 4.6 ± 0.6 | 5.5 ± 0.6 |
Two causes | 10 | 12.8 ± 0.8 | 4.5 ± 0.3 | 3.9 ± 0.3 | 4.4 ± 0.4 |
Others | 11 | 13.9 ± 0.8 | 4.4 ± 0.3 | 4.2 ± 0.3 | 5.4 ± 0.3 |
F value | | 0.57 | 0.61 | 0.44 | 0.99 |
P value | | 0.75 | 0.72 | 0.85 | 0.43 |
Table 4
Comparison on physical and mental component summary of SF-36 between different etiologies (n = 110)
UACS | 10 | 61.9 ± 5.2 | 58.3 ± 6.2 |
CVA | 54 | 60.6 ± 4.7 | 57.8 ± 5.8 |
GERD | 6 | 62.0 ± 5.3 | 57.8 ± 5.0 |
NAEB | 10 | 59.6 ± 4.1 | 55.9 ± 6.3 |
PVC | 9 | 60.5 ± 5.0 | 55.9 ± 5.8 |
Two causes | 10 | 59.7 ± 6.3 | 56.4 ± 5.6 |
Others | 11 | 57.6 ± 5.5 | 57.1 ± 4.4 |
F value | | 0.92 | 0.44 |
P value | | 0.48 | 0.85 |
Differences of HRQOL between males and females with chronic cough
When evaluated by LCQ, no significant difference in HRQOL was found between males and females as a whole, despite that the feelings of embarrassment, frustration and disturbance of sleep were more obvious in women than in men (Table
5).
Table 5
Gender differences in HRQOL of patients with chronic cough as measure by LCQ (n = 110)
Chest or stomach pains | 5.3 ± 1.7 | 5.5 ± 1.7 | -0.32 | 0.75 |
Phlegm | 4.5 ± 2.3 | 4.6 ± 2.3 | -0.17 | 0.86 |
Tiredness | 5.2 ± 1.6 | 4.7 ± 1.8 | 1.28 | 0.20 |
Controlled by cough | 3.2 ± 1.7 | 3.1 ± 1.8 | 0.44 | 0.66 |
Embarrassment | 4.9 ± 1.6 | 3.7 ± 1.6 | 4.02 | 0.00 |
Anxiety | 4.5 ± 1.9 | 4.2 ± 1.6 | 1.01 | 0.32 |
Interference with job/other daily tasks | 5.2 ± 1.6 | 5.1 ± 1.8 | 0.29 | 0.78 |
Interference with overall enjoyment | 5.4 ± 1.7 | 5.4 ± 1.7 | 0.11 | 0.92 |
Cough by exposure of paints or fumes | 3.8 ± 2.4 | 3.9 ± 2.2 | -0.22 | 0.83 |
Disturbance of sleep | 5.2 ± 1.9 | 4.4 ± 1.9 | 2.16 | 0.03 |
Coughing bouts | 3.1 ± 1.3 | 3.1 ± 1.2 | -0.16 | 0.88 |
Frustration | 5.1 ± 1.7 | 4.5 ± 1.5 | 2.02 | 0.04 |
Feed up | 4.2 ± 1.9 | 4.2 ± 1.6 | 0.05 | 0.96 |
Hoarse voice | 5.5 ± 1.4 | 5.3 ± 1.6 | 0.65 | 0.52 |
Full of energy | 4.8 ± 1.6 | 4.6 ± 1.8 | 0.78 | 0.44 |
Worry about serious diseases | 4.4 ± 1.9 | 4.3 ± 1.7 | 0.49 | 0.63 |
Concerned the others' feelings about your cough | 4.8 ± 2.0 | 5.4 ± 1.6 | -1.70 | 0.09 |
Interrupted conversation or telephone calls | 5.3 ± 1.6 | 4.8 ± 1.5 | 1.68 | 0.10 |
Annoying partner, family or friends | 5.5 ± 1.9 | 5.5 ± 1.7 | -0.08 | 0.94 |
Effects of specific treatment on HRQOL of patients with chronic cough
In 103 patients who got a definite diagnosis for their cough and received the specific treatments, cough resolved completely in 86 patients. Five patients did not respond to the treatment and 12 patients were lost to follow-up and were therefore excluded for the further analysis of the data. As measured with LCQ, the successful treatment of chronic cough obviously improved HRQOL of patients in the physical, psychological and social domains (Table
6). The time intervals between pre- and post-treatment evaluations were 3.9 ± 1.5 (range 2-13) weeks.
Table 6
Changes in HRQOL of patients with chronic cough before and after treatment as measured by LCQ (n = 86)
total score | 14.2 ± 2.7 | 19.5 ± 1.9 | 13.7 | 0.000 |
Physical domain | 4.6 ± 1.0 | 6.3 ± 0.8 | 13.5 | 0.000 |
Psychological domain | 4.3 ± 1.0 | 6.5 ± 0.7 | 17.4 | 0.000 |
Social domain | 5.3 ± 1.2 | 6.7 ± 0.6 | 10.7 | 0.000 |
Relationships between LCQ and SF-36 or cough threshold C5
There was a weak but significant correlation between the total score of LCQ and PCS (r = 0.39, P < 0.0001) or MCS (r = 0.30, P < 0.001) of SF-36 respectively. The median of cough threshold C5 was 3.9 μmol/L (0.49 - 62.5 μmol/L, 95% confidence interval: 8.0-9.3 μmol/L). No significant correlation was found between Log C5 and LCQ (r = 0.134, P = 0.253), PCS (r = -0.092, P = 0.43) or MCS (r = -0.22, P = 0.06) of SF-36.
Discussion
The quality of life is an important outcome parameter in the study of chronic cough. To investigate HRQOL of Chinese patients with chronic cough, we compared the scores of items in SF-36 between patients with chronic cough and healthy volunteers. The reasons for selection of SF-36 were that SF-36 is one of the most common instruments in general health survey, its reliability and validity have been established with extensive application [
16]. Moreover, the measurements by the specific instruments such as LCQ reflect HRQOL in the patients with chronic cough well, but do not accurately represent the health status in healthy volunteers because of lacking cough, which might result in the poor comparability in HRQOL between coughers and non-coughers. Finally, SF-36 has been used for the assessment of the quality of life in the other chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease, and always achieved great success [
17,
18].
The results showed that the quality of life in patients with chronic cough deteriorated significantly when compared with healthy volunteers. The scores of patients with chronic cough were lower in 7 testing multi-item scales of SF-36 except for physical pain than those of healthy volunteers. Among the affected domains, the decrease in the scores of RE, GH and RP related to emotional problems was more obvious. These observations were in accordance with previous reports on HRQOL in patients with chronic cough [
5‐
8,
19].
There was comparable HRQOL among the patients in spite of causes of chronic cough, which confirmed the findings of French and Canonica who had observed that HRQOL in the chronic coughers was unrelated to the causes of cough [
8,
20]. The impact of cough on quality of life was to a large extent dependent upon the frequency and intensity of cough [
5]. Our previous study has also shown that the cough severity was not significantly different among different causes of chronic cough [
21]. Although the pathogenesis of chronic cough is associated with the cause, airway inflammation and increased sensory nerve sensitivity in the airway is a common pathway and may play an important role [
22,
23]. Therefore, it is reasonable that different causes eliciting chough result in the similar cough severity and HRQOL in the cohort of patients.
Gender is one possible factor determining the quality of life of patients with chronic cough. Most studies have demonstrated that women accounted for the majority of patients with chronic cough seeking medical care, with the ratio of 1:1.2-3.6 between males and females [
24,
25]. It seems that negative HRQOL caused by cough was more conspicuous in women than in men, and might be attributed to the predominance of females in the patients with chronic cough [
26]. In contrast, the present study showed that only several adverse events including embarrassment, frustration and sleep disorder were more apparent in women than men as measured with LCQ, and did not confirm the gender difference in overall HRQOL of patients with chronic cough. The selecting bias of patients should not be an explanation since we recruited the patients consecutively. It is likely that in previous studies reporting gender differences in HRQOL, female patients were coughing more frequently than men, and in this study, coughing bouts were identical in men and women.
Another possibility is that the quality of life in the patients with chronic cough visiting hospital was affected in a similar level regardless of gender. Women with chronic cough were more likely to see a doctor than men because of embarrassment and the other psychosocial issues provoked by cough-related urinary incontinence [
26]. However, it only explains more females in patients with chronic cough seeking medical advice. When a man went to hospital due to his cough, it meant that his HRQOL was decreased to a level comparable with females, thereby not leading to the significant differences in HRQOL between men and women.
When cough resolved with successful treatment specific for the cause, the quality of life in the patients could be significantly improved as judged by total score and domain scores in LCQ, which is in accordance with the previous study [
5]. Therefore, HRQOL assessments of chronic cough, as a precise and quantitative measurement, could be applied in monitoring of cough severity, evaluation of treatment efficacy and verification of new therapeutic regimen.
Birring and Kalpaklioglu have found that there was a negative correlation between LCQ and the other tools such as cough symptom score and visual analogue scale respectively [
6,
27]. Recently, Kelsal has demonstrated that a correlation existed between LCQ and cough frequency recording [
28]. Our study has shown that there was a weak but significant correlation between LCQ and SF-36. The similar relationship was verified between SF-36 and a Dutch version of LCQ [
29]. These evidences suggest that LCQ, like the other cough-specific instruments, could accurately measure the HRQOL changes in patients with chronic cough. As indicated by our data, the Chinese version of LCQ is helpful for evaluation of the health status in Chinese patients with chronic cough.
There was no obvious correlation between LCQ and capsaicin cough threshold, which was similar to the results reported by Birring [
6] and Chang [
30]. It may be due to the different implications of HRQOL and capsaicin cough sensitivity in assessment of cough severity. Capsaicin cough threshold mainly represents the susceptibility of cough while HRQOL reflects the perception of multidimensional damage caused by cough. Therefore, HRQOL and capsaicin cough threshold may measure different aspects of the severity of cough and can be complemented by each other.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
WM was in charge of collection of cases and writing the manuscript, LY was in charge of collection, process, and statistical analysis of data and took part in review of the manuscript, YW, XL and HL took part in the collection of cases and review of the manuscript, ZQ was in charge of design and coordination of the program, review and correction of the manuscript. All authors read and approved the final manuscript.