Association between ambient temperature and lower urinary tract symptoms: a community-based survey

ABSTRACT Purpose The aim of this study was to evaluate the individual change of International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in each patient by temperature conditions. Materials and Methods The severity of lower urinary tract symptoms (LUTS) was explored using the IPSS and OABSS questionnaires that were completed by 2.486 subjects (923 males and 1.563 females) aged 60 years and older. Korea Meteorological Administration data was used to determine daily average temperature and daily temperature difference on the interview dates at each site. Results The mean IPSS and mean age for males was 13.45±8.24 and 75.03±6.20 years, respectively. The mean OABSS and mean age for females was 4.41±3.10 and 73.74±6.03years, respectively. Daily average temperature and daily temperature difference ranged from-3.4-28.3oC and 2.2-16.9oC, respectively. Age was a significantly risk factor for IPSS, OABSS, and QoL (P<0.001, <0.001, and 0.005, respectively). After multiple regression analysis, daily average temperatures did not show a statistically significant change in IPSS and OABSS. Only daily temperature differences were associated with male LUTS. Conclusions While LUTS could be worsened in low temperatures generally, IPSS and OABSS were not affected by daily average temperature conditions. Daily temperature differences may be more influential than daily average temperatures.

environmental stress and ambient temperature change elicited urinary sensations and frequent urination along with increasing heart rate and blood pressure (3,4). However, seasonal changes were not observed in the International Prostate Symptom Score (IPSS), storage symptom score, voiding symptom score, and quality of life (QoL) (5,6). As well, changes in fluid temperature did not significantly change the threshold volume of bladder sensation or increase the incidence of idiopathic detrusor overactivity in urodynamic studies (7). There is no general consensus about the effect of environmental temperature on LUTS associated with BPH and overactive bladder (OAB). Therefore, we focused on ambient temperature as an environmental factor affecting LUTS associated with BPH or OAB, and attempted to explain the temperature difference changes in BPH or OAB severity.
To date, no large cross-sectional surveys have been performed to investigate the association between daily temperature and LUTS. The aim of this study was to investigate this association by community-based survey.

Methodology
This was a cross-sectional study. One investigator conducted face-to-face interviews with all study participants at senior welfare centers in South Korea between August 2010 and November 2012 using the International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) questionnaires. The survey was conducted 36 times in 34 cities within seven major areas of South Korea: Seoul, Gyeonggi, Incheon, Daejeon, Daegu, Gwangju, and Busan ( Figure-2).

Study Area
South Korea is located in the southern portion of the Korean Peninsula, which extends about 1.100km (680mi) from the Asian mainland. The mountainous peninsula is flanked by the Yellow Sea to the west and East Sea to the east. The country, including all its islands, lies between latitudes 33º and 39º N, and longitudes 124º and 130ºE. Its total area is 100.188 square figure 1 -seasonal benign prostatic hyperplasia (international classification of disease code; n40) patient number from 2008 to 2012. L, low daily average temperature (<10ºC), (Jan. to Mar., nov., Dec.); h, high daily average temperature (>20ºC) (Jun. to sept.

Study population
The study used data from a community--based interview survey conducted with 2.486 male (n=923) and female (n=1.563) subjects 60 years of age and older who provided voluntary consent to participate in the questionnaire survey. To enhance the validity of research, exclusion criteria were prior urological surgery; prior treatment for BPH, prostate cancer or OAB; evidence of a neurological condition; history of a malignancy; evidence of urinary tract infection; evidence of psychiatric illness; and evidence of alcohol or substance abuse.

Temperature data collection
In South Korea, the Korea Meteorological Administration maintains a meteorological observational network of 94 stations that measure daily average temperature, daily temperature difference, daily maximum temperature, daily minimum temperature, and daily amount of precipitation (http://www.kma.go.kr). This allowed retrieval of data concerning daily average temperature and daily temperature difference on the interview dates at the specific measurement sites.

QuEsTIOnnAIREs
IPSS Questionnaire: The severity of LUTS associated with BPH for males was measured by use of the IPSS questionnaire, which is based on the American Urological Association symptom index, with one additional question regarding QoL. The Korean version of the IPSS was verified in terms of its relevance and reliability, and it is now the most typical diagnostic instrument for LUTS in Korea.

OABSS Questionnaire
The severity of LUTS associated with OAB for females was measured by use of the OABSS questionnaire. The OABSS was developed and validated in Japanese populations (9). The OABSS comprises only four questions regarding daytime frequency, nocturia, urgency, and urgency incontinence, and evaluates relevant symptoms from the viewpoint of the patient. Performance of the OABSS is simple and quick, and a good agreement between OABSS items and the corresponding diary variables was found in a clinical trial with anticholinergics (10). The Korean version of the OABSS was verified in terms of its relevance and reliability.

Age
Age is an important factor that has an impact on generation-specific prevalence of BPH and OAB. Therefore, this study queried each participant's date of birth.

Classification of temperature and statistical analyses
Classification of temperature was based on the daily average temperature (low, <10 o C; medium, 10-20 o C; high>20 o C) as previously described (6) and daily temperature difference in tertiles (low, <8 o C; medium 8-10 o C; high>10 o C). To examine the influence of topographical characteristics, the population was divided into two groups: coastal area (Incheon, Busan) and inland area (Seoul, Gyeonggi, Daejeon, Daegu, Gwangju). To examine the relationship between BPH/OAB and age in the population, an analysis of variance (11) and a post hoc analysis were performed to identify any differences in IPSS/OABSS among each age group. Multiple linear regression analysis with IPSS/OABSS as the response variable, and daily average temperature, daily temperature difference, and age as explanatory variables was done. All data are presented as mean and standard deviation (SD). Statistical analysis was performed using SPSS version 21.0 software (IBM, New York, NY, USA) and STATA version 11.2 software (StataCorp LP, Texas, USA). All statistics were two-tailed and P-values <0.05 were considered to be significant.

REsuLTs
The mean IPSS and mean age for the 923 males was 13.45±8.24 and 75.03±6.20 years, respectively. The mean OABSS and mean age for the 1.563 females was 4.41±3.10 and 73.74±6.03 years, respectively (Table-1). Daily average temperature ranged from-3.4 o C to 28.3 o C, with the daily temperature difference ranging from 2.2 o C to 16.9o C (Table-2).
One-way ANOVA analysis was conducted to determine the age-related risk of BPH, OAB, and QoL. The risk of BPH significantly increased with age (12.65±7.96 for those aged 60-69 years and 15.21±8.86 for those over 80 years; P=0.002). The risk of OAB significantly increased with age (3.93±2.82 and 4.90±3.467 for the respective age groups; P<0.001). The risk of QoL increased significantly with age (2.83±1.75 and 3.21±1.53 for the respective age groups; P=0.001) ( Table-3). To evaluate the influence of topographical characteristics, there was no difference of IPSS, QoL, and OABSS between coastal and inland area (Table-4). And also there was no statistical significance for identifying which individual item of IPSS and OABSS was related to the daily average temperature except for QoL item (Table-5).
Figure-3 displays values with 95% confidence intervals after adjustment of age concerning the relationship between temperature factors and IPSS/OABSS. There was a weak negative correlation between IPSS and daily temperature difference. To examine this correlation in more detail, a multiple linear

DIsCussIOn
Temperature has been linked with myocardial infarction (2), ischemic heart disease (12), brain-blood vessel obstruction (13), and respiratory infection (14). For urinary voiding symptoms, it is necessary to consider how ambient temperature changes affect IPSS in medicated patients (4). However, in Japan seasonal changes were found not to be associated with IPSS (6). Also, the report of an average   temperature odds ratio of chronic prostatitis--like symptoms of 0.99 (range 0.98 to 1.00) was indicative of only a weak clinical significance in Korea (5). In this present study, average temperature was not a risk factor for LUTS for adjusted age in multiple regression analysis (P=0.322). Among the variables, only QoL revealed significant association, which was only prominent among male populations. Moreover, the significant level was marginal, which could be interpreted as temporary phenomenon and needs more validation. Concerning urinary storage symptoms, patients without neurological diseases have a heightened perception of cold in the bladder during the ice water test than patients with neurological diseases (15). Storage symptoms, frequency, urgency, and nocturia are considerably affected by seasonal changes (16). However, changes in the temperature of fluid did not significantly change the threshold volume of bladder sensation or increase the incidence of idiopathic detrusor overactivity in urodynamic studies (7). In the present study, the average temperature did not demonstrate a risk of LUTS for adjusted age in multiple regression analysis (P=0.433).
There are several reasons for the varying results. First, several previous studies reported that cold stress induces detrusor overactivity in conscious rats, a finding that occurred with a high temperature change between the treatment group and the control group (△24 o C=room temperature 28oC-low temperature 4ºC) (15,17,18). However, in the present study, the maximum daily temperature difference was 16.9 o C, which was lower than in previous studies. Also, in general, elderly people have shorter exposure times and well-controlled body temperatures in the winter season due to their typically limited physical activity, which could lead to a smaller exposure to extreme temperature changes. Second, the same previous studies measured outcomes during a short exposure time (20-40 min) (15,(17)(18)(19). However, in general, the human body's activity changes with the seasons and gradually adapts to the exposure temperature throughout the season. This phenomenon may account for our finding that the temperature effect on the risk of BPH/ OAB may not affect urinary symptoms in the general population. For instance, in a cold stress-induced detrusor overactivity model, when skin temperature stabilized after 20 min  of low temperature (4±2ºC) exposure and was maintained for the duration of exposure (19), demonstrated that a momentary cold stimulus can act as a trigger for the urinary responses. Also, the results of this model were associated with a sudden decrease in skin temperature (19). This present study also supports previous results that the time-dependent reductions of low temperature stimulated responses represent an adaptive response that is universal in normal healthy humans. Moreover, individual efforts to maintain warmth through the wearing of heavy clothes and heating the environment could diminish the trigger effect of low temperature on LUTS. It has generally been thought that more LUTS patients are associated with BPH/OAB-rela-ted need for hospital examination with regard to their urinary symptoms in low temperature circumstances. However, the present results indicate that this does not mean that the urinary severity of patients in low temperature environments is higher than high temperature exposure.
The guideline by the Japanese Urological Association recommends one of the conservative treatments that males with LUTS avoid exposing the lower body to cold temperature (20). However, the American Urological Association and European Association of Urology have not provided high-quality and reliable evidence about the influence of ambient temperature on LUTS (21,22). Only the American Urological Association guideline on the management of BPH recommended future study of life style interventions (21). The present data address this recommendation. There are several limitations to this study. In view of the imprecision of some geographical data, coupled with the fact that we used spatially-derived ambient temperature as a surrogate for personal temperature, the risk estimates presented here are clearly misclassified. Thus, our results may underestimate the true risk of LUTS associated with exposure to temperature in this population. However, as in most epidemiological surveys, there will be some errors in exposure classification. In this study, which was performed as a large-scale research project that covered seven major areas of South Korea, the collected data were judged to be sufficiently homogeneous. As a result, the misclassification of this study would most likely be non-differential with regard to temperature status. This would tend to bias the regression parameter toward null. Second, this study does not include the detailed biological data of each population, which means we could not determine clinical BPH or OAB. This is mainly due to the nature of this cross-sectional survey.
Topographical characteristics were taken into consideration with regard to variations in LUTS severity among areas. Since coastal and inland communities are evenly distributed in interview surveys areas 36 times in 34 cities in seven major areas of South Korea, there is no difference of IPSS, QoL, and OABSS between coastal and inland area. Thus, the topographical difference is also thought to be unrelated.
Lastly, we could not describe the longitudinal data to consider potential seasonal varia-tion effects. The variance of daily temperature could not substitute for seasonal variation. Hence, this type of cross sectional study has to be repeated by seasonal sequence.

COnCLusIOns
Our findings did not demonstrate an increased clinically significant risk of BPH or OAB severity in connection with daily average temperature. Only daily temperature differences were associated with male LUTS. Daily temperature differences may be more influential than daily average temperatures. A large prospective study set will be needed to validate this association in the future.