Cough is an essential defence mechanism [1]. However, chronic cough is a significant cause of morbidity, seriously impairing quality of life [2]. Previously, chronic cough was considered a consequence of various diseases, such as asthma/eosinophilic bronchitis, rhinitis and gastro-oesophageal acid reflux disease [3,4]. Recent evidence, however, suggests that chronic cough is a clinical syndrome with distinct intrinsic pathophysiology characterised by neuronal hypersensitivity [5][6][7]. Here, we estimated the worldwide epidemiological burden of chronic cough irrespective of putative diagnosis in general adult populations using a comprehensive systematic literature review.We searched the literature for prevalence of chronic cough in community-based adult populations using Pubmed and Embase databases according to the recommendations of the PRISMA statement [8]. The search terms were "cough AND (epidemiology OR epidemiologic OR epidemiological OR prevalence OR

Genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP; SLC10A1) and ileal apical sodium-dependent bile acid transporter (ASBT; SLC10A2), which greatly contribute to bile acid homeostasis, were extensively explored in the Korean population and functional variants of NTCP were compared among Asian populations. From direct DNA sequencing, six SNPs were identified in the SLC10A1 gene and 14 SNPs in the SLC10A2 gene. Three of seven coding variants were non-synonymous SNPs: two variants from SLC10A1 (A64T, S267F) and one from SLC10A2 (A171S). No linkage was analysed in the SLC10A1 gene because of low frequencies of genetic variants, and the SLC10A2 gene was composed of two separated linkage disequilibrium blocks contrary to the white population. The stably transfected NTCP-A64T variant showed significantly decreased uptakes of taurocholate and rosuvastatin compared with wild-type NTCP. The decreased taurocholate uptake and increased rosuvastatin uptake were shown in the NTCP-S267F variant. The allele frequencies of these functional variants were 1.0% and 3.1%, respectively, in a Korean population. However, NTCP-A64T was not found in Chinese and Vietnamese subjects. The frequency distribution of NTCP-S267F in Koreans was significantly lower than those in Chinese and Vietnamese populations. Our data suggest that NTCP-A64T and -S267F variants cause substrate-dependent functional change in vitro, and show ethnic difference in their allelic frequencies among Asian populations although the clinical relevance of these variants is remained to be evaluated.

PurposeRecent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics.MethodsA systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions.ResultsA total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough ≥3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough ≥8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I2=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity.ConclusionsThis study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required.

BackgroundThe epidemiology of cough in the elderly population has not been studied comprehensively. The present study aimed to investigate the epidemiology of cough in a community elderly population, particularly in relation with their comorbidity.MethodsA cross-sectional analysis was performed using a baseline dataset from the Korean Longitudinal Study on Health and Aging, a community-based elderly population cohort study. Three types of cough (frequent cough, chronic persistent cough, and nocturnal cough) were defined using questionnaires. Comorbidity was examined using a structured questionnaire. Health-related quality of life was assessed using the Short Form 36 questionnaire.ResultsThe prevalence was 9.3% for frequent cough, 4.6% for chronic persistent cough, and 7.3% for nocturnal cough. In multivariate logistic regression analyses, smoking, asthma and allergic rhinitis were found to be risk factors for cough in the elderly. Interestingly, among comorbidities, constipation and uncontrolled diabetes mellitus (HbA1c ≥ 8%) were also found to have positive associations with elderly cough. In the Short Form 36 scores, chronic persistent cough was independently related to impairment of quality of life, predominantly in the mental component.ConclusionsCough has a high prevalence and is detrimental to quality of life in the elderly. Associations with smoking, asthma and rhinitis confirmed previous findings in younger populations. Previously unrecognised relationships with constipation and uncontrolled diabetes mellitus suggested the multi-faceted nature of cough in the elderly.