in recent years , air pollution has been a serious problem in some asian countries .
an 
 important consequence of air pollution is its effect on health , particularly on the 
 respiratory system1 , 2 .
as an assessment of respiratory health , forced expiratory volume in 
 1 second ( fev1 ) is an important measure of the health of older people .
the annual 
 decline in fev1 is an important predictor of morbidity and mortality related to 
 cardiovascular disease3 .
usually , 
 fev1 reaches a maximum in the third decade of life and then decreases gradually 
 with age4 , 5 .
in addition to physiologic factors such as aging , other factors 
 influence the decline in fev1 .
air pollution , as well as respiratory diseases such as asthma and chronic bronchitis , also 
 causes a more rapid decline in fev12 , 7 , 8 . 

respiratory symptoms , including dyspnea , wheezing , coughing , and sputum production , occur as 
 a result of air pollution2 , and reflect 
 airway inflammation9 . however , it is not 
 clear if patients with respiratory symptoms caused by air pollution experience an 
 accelerated decline in fev1 .
because of rapid industrialization in the 1960s in japan , air pollution caused by flue gas 
 emitted from industrial plants became a serious problem10 .
one of the measures , the air 
 pollution control law , was intended to improve the environment .
this law regulated 
 acceptable levels of air pollutants and implemented measures aimed at preventing pollution . 

the acceptable level of sodium dioxide ( so2 ) was stated to be 40 parts per 
 billion ( ppb ) , that of nitrogen dioxide ( no2 ) was 20 ppb ( until 1978 , when it was 
 changed to 40 ppb ) , and the acceptable level of suspended particulate matter ( spm ) was 
 100  g / m .
air environmental conditions improved as evidenced by reports from 
 the air pollution office ( comprising the general environmental air measurement office and 
 motor exhaust measurement office ) . as an example ,
1.concentration of air pollutants in the mizushima district of kurashiki from 1969 to 
 200910 , 11 shows the average annual levels of so2 , no2 and spm recorded in 
 mizushima district from 1969 to 200912 , 13 .
the level of pollutants decreased to 
 below the minimum acceptable level from the mid-1970s .
the other measure , the 
 pollution - related health damage compensation law , protects the cultural lives and health of 
 people .
it compensates officially acknowledged victims with pollution - related illnesses for 
 medical fees and other medical services ( e.g. , medications ) .
concentration of air pollutants in the mizushima district of kurashiki from 1969 to 
 200910 , 11 decades have passed since air pollution was a serious problem in japan .
environmental 
 conditions have improved over time , as has the help and aid for affected individuals .
many 
 studies on air pollution have focused on the immediate or relatively short - term effects on 
 measures of health14,15,16 .
there is a lack of 
 studies in settings in which the environment has improved and a long period of time has 
 elapsed .
our research team has reported several longitudinal studies that targeted 
 officially acknowledged victims with pollution - related illness12 , 13 , 17 .
however , in one of those studies , smokers were excluded 
 to confine observations to the effect of air pollution12 . in our previous report examining the lung function of officially 
 acknowledged victims with pollution - related illness in two geographical areas within japan
those two studies found that the annual change in fev1 
 in non - smokers who were officially acknowledged victims with pollution - related illness was 
 within the normal range .
however , those studies were limited in their application because 
 the effect of smoking was not examined and because factors associated with the annual change 
 of fev1 were not clear .
if the factor associated with a greater decline in 
 fev1 became clear , it could assist in maintaining lung health in countries in 
 which air pollution is present .
the aim of the present study , therefore , was to examine the 
 factors , including cigarette smoking , associated with the annual change in fev1 
 of officially acknowledged victims with pollution - related illness in settings in which the 
 environment has improved and a long period of time has elapsed .
the present study is unique 
 in that the investigation is a longitudinal study of victims in an area in japan in which 
 air pollution was once a serious problem but where , over the years , air quality has 
 improved .
the present study was approved by the ethics review committee of nagasaki university 
 graduate school of biomedical sciences ( nagasaki , japan ) .
this study was undertaken by 
 analyses of retrospective data obtained from annual health surveys conducted with officially 
 acknowledged victims of air pollution - related illnesses from the mizushima district of 
 kurashiki ( okayama prefecture , japan ) between 2000 and 2009 .
this area suffered from air 
 pollution during 19601970 , but the environment improved thereafter . officially acknowledged victims of air pollution - related illnesses were registered after 
 fulfilling two main conditions in the pollution - related health damage special measures law 
 ( 1969 ) and pollution - related health damage compensation law ( 1973 ) .
the first requirement 
 was to register a victim that had been diagnosed to have an air pollution - related illness , 
 such as asthma or chronic bronchitis , by a respiratory physician .
respiratory diseases 
 attributed to air pollution in the pollution - related health damage compensation law were 
 categorized into four groups : asthma , chronic bronchitis , a combination of asthma and 
 chronic bronchitis , or another respiratory disease .
the diagnosis was made based on the 
 results of medical examinations by certified respiratory physicians and official 
 requirements of the law .
chronic bronchitis was diagnosed by the presence of chronic and 
 copious amounts of sputum and a persistent cough .
the second requirement was that individuals had 
 to reside or spend 8  h per day in an area specified as having significant air pollution . 

table 1table 1.time required for certification of exposure to air pollutioncategorychronic bronchitis asthma a ( months)24 12 b ( months)4830c ( months)36 18 category a : subject resided in the designated area before 1973.category b : subject did not reside in the designated area but spent 8  h / day in the 
 designated area.category c : subject resided in the designated area and then relocated , but returned 
 for work in the designated area for 8  h / day .
they 
 were different for each disease and area in which the subject resided or spent time 
 ( including work time ) .
category b : subject did not reside in the designated area but spent 8  h / day in the 
 designated area .
category c : subject resided in the designated area and then relocated , but returned 
 for work in the designated area for 8  h / day .
this was similar to the 
 subjects of a study by tanaka et al.12 , 13 . in 2009 ,
the number of officially 
 acknowledged victims of air pollution - related illness in kurashiki was 1392 .
of these , 774 
 ( 56% ) were 65  years of age in 2009 .
however , 44 individuals were subsequently excluded from this analysis because 
 they had not undergone annual spirometry on 7 occasions .
flow diagram of the study pulmonary function was measured by spirometry ( fudac 70 ; fukuda sangyo inc . ,
chiba , japan ) . 
 officially acknowledged victims of air pollution - related illnesses were required to undergo 
 spirometry once a year .
spirometry was undertaken by trained staff at mizushima kyodo 
 hospital ( okayama , japan ) .
following standardized instructions , spirometry was repeated 
 until 3 reproducible forced expiratory volume - time curve curves had been obtained .
a 
 nose - clip was applied to each subject , and subjects were in the sitting position during 
 tests
. in our analyses , values of forced vital capacity ( fvc ) and fev1 were used , 
 and these are presented in milliliters or as a percentage of the predicted value ( % fvc and 
 % fev1 ) derived from the predicted equations .
smoking habit was divided into two groups : non - smoker or smoker ( including former smokers ) 
 as of the year 2000 .
respiratory symptoms evaluated comprised  breathlessness  ,  wheezing  
 and  cough and sputum production  .
respiratory physicians evaluated the presence and 
 severity of symptoms during medical interviews according to a five - grade system . 

classification of medical management referred to the extent to which an individual required 
 medical care ( e.g. , frequency of medical care and necessity for hospitalization ) .
this 
 parameter was also evaluated according to a five - grade system ( table 2table 2.severity of respiratory symptoms and classification of medical managementgradebreathlessnesswheezecough and sputumproductionmedical managementclassification1too breathless to leave the house , or breathless when 
 dressing or undressingsevere episodes 10 days / month during the last 
 yeardaily cough and sputum , with a large amount of sputum 
 or difficulty clearing sputumrequires hospitalization for exacerbation of symptoms 
 and always requires assistance with activity during daily living2breathless after walking about 50 m or after a few 
 minutes on level groundsevere episodes 5 days / month during the last year , or 
 mild episodes 10 days / month during the last yeardaily cough and sputum , with a moderate amount of 
 sputum or difficulty clearing sputumalways needs medical treatment and hospitalization 
 required for exacerbation of symptoms3breathless when walking on level ground and keeping up 
 with people of the same age , but not breathless when walking at own pacesevere episodes 1 day / month during the last year , or 
 mild episodes 5 days / month during the last yeardaily cough and sputum , but not troublesome during 
 daily lifealways needs medical treatment and sometimes needs 
 hospitalization4breathless when walking up a slight hill or the 
 stairsmild episodes 1 day / month during the last yeardaily cough and sputum for 3 months / yearalways needs to consult a doctor and sometimes needs 
 respiratory medication5breathless only during strenuous exerciseno episodes of wheezingno cough or sputumno need for medical management ) .
the regression 
 coefficient for the annual mean change in fev1 was calculated using simple linear 
 regression analyses .
further , bivariate analyses were conducted to examine the relationship 
 between the annual change in fev1 and other factors .
spearman rank correlation 
 analyses , mann - whitney test , and kruskal - wallis test were included in bivariate analyses . 

factors found to be independent variables associated with the annual change in 
 fev1 in bivariate analyses were evaluated stepwise in multiple regression 
 analyses .
significance levels of 10% for bivariate analyses and 5% for multiple regression 
 analyses were adopted . in additional analyses to examine the relationship between annual 
 change in fev1 and percentage predicted fev1 , pearson correlation 
 analyses were carried out with a significance level set at 5% .
characteristics of subjects measured in the year 2000 are shown in table 3table 3.characteristics of the patient cohort as measured in the year 2000characteristicmean  sd or n ( % ) age , years68.8  7.6male gender , n272 ( 37)height , cm153.2  8.5weight , kg56.3  10.1bmi , kg / m23.9  3.7smoking habit , nnon - smoker567 ( 78)smoker163 ( 22)fev1 , ml1546  561% pred fev17  11fvc , ml2559  750% pred fvc9  21fev1 annual change , ml / year29  32disease , nasthma218 ( 30)cb411 ( 56)asthma and cb97 ( 13)others4 ( 1)respiratory symptomsbreathlessness , ngrades 13180 ( 25)grade 4483 ( 66)grade 564 ( 9)wheeze , ngrades 13207 ( 28)grade 4276 ( 38)grade 5247 ( 34)cough and sputum production , ngrades 13373 ( 51)grades 45357 ( 49)medical management classification , ngrades 13192 ( 26)grades 45538 ( 74)bmi : body mass index ; fev1 : forced expiratory volume in one second ; % pred 
 fev1 : percentage of the predicted value of forced expiratory volume in 1 
 second ; fvc : forced vital capacity ; % pred vc : percentage of the predicted value of 
 forced vital capacity ; cb : chronic bronchitis ; other : other conditions such as 
 pulmonary emphysema . there were more females ( 63% ) than males ( 37% ) , and more non - smokers ( 78% ) 
 than smokers ( 22% ) .
categories of respiratory symptoms and classifications of medical 
 management were rationalized into two or three groups .
bmi : body mass index ; fev1 : forced expiratory volume in one second ; % pred 
 fev1 : percentage of the predicted value of forced expiratory volume in 1 
 second ; fvc : forced vital capacity ; % pred vc : percentage of the predicted value of 
 forced vital capacity ; cb : chronic bronchitis ; other : other conditions such as 
 pulmonary emphysema tables 4table 4.correlation coefficients ( r ) and significance levels ( p ) of annual changes in 
 fev1factorrage0.011height0.100*weight0.034*p < 0.1and 5table 5.annual change in fev1 grouped according to subject characteristics by 
 bivariate analysesfactorfev1 ( ml / year)gender*male36  40female25  25smoking habit*non - smoker25  29smoker41  38respiratory disease*asthma23  31cb31  32asthma and cb32  32respiratory symptomsbreathlessness*grades 1320  30grade 431  33grade 533  25wheeze*grades 1322  31grade 429  32grade 533  32cough and sputum*grades 1326  31grades 4531  33medical management classification*grades 1320  30grades 4532  32mean  sd ; * p<0.1 ; fev1 , annual change in fev1 ( ml ) ; cb : 
 chronic bronchitis provide the results of bivariate analyses investigating the relationship 
 between the annual change in fev1 and other factors
. results of bivariate 
 analyses showed that sex , height , weight , smoking habit , respiratory disease , all 
 respiratory symptoms , and classification of medical management were significant factors 
 associated with the annual change in fev1 ( p < 0.1 ) .
the annual change in 
 fev1 in males significantly exceeded that observed in females ( p < 0.05 ) . 

people who had more 
 severe symptoms showed a slower decline than people who had mild symptoms .
in addition , 
 those who required more medical treatment and assistance with activities of daily living had 
 a slower annual decline in fev1 than people who did not require these 
 interventions .
mean  sd ; * p<0.1 ; fev1 , annual change in fev1 ( ml ) ; cb : 
 chronic bronchitis results of multiple regression analyses are shown in table 6table 6.predictors of annual change in fev1factorfev1b95% civifsmoking habit * ( smoker , 0 ; non - smoker , 1)4.220.172.08 to 8.881.157medical management classification * ( grades 13 , 0 ; 
 grades 45 , 1)10.920.1514.15 to 3.561.007gender * ( male , 0 ; female , 1)6.220.092.62 to 12.861.151*p < 0.05 indicates statistical significance .
fev1 , annual change in 
 fev1 ; b , partial regression coefficient ;  , standardized partial 
 regression coefficient ; ci : confidence interval ; vif : variance inflation factor .
the strongest factor related to the annual change in fev1 was 
 smoking habit , followed by classification of medical management , and gender .
there was no 
 multicollinearity according to the variance inflation factor , which means no correlation 
 between these factors .
fev1 , annual change in 
 fev1 ; b , partial regression coefficient ;  , standardized partial 
 regression coefficient ; ci : confidence interval ; vif : variance inflation factor additional analyses revealed a significant weak inverse correlation between the annual 
 change in fev1 and percentage predicted fev1 ( r = 0.26 , p
this finding suggested that subjects with better pulmonary function showed a more 
 rapid decline in fev1 .
this is the first study to investigate the factors associated with the annual change in 
 fev1 in residents previously exposed to air pollution after the environmental 
 conditions had improved and a long time period had elapsed .
multiple regression analyses showed that smoking habit , classification of medical 
 management , and gender were significant factors in order of decreasing effect .
the 
 prediction equation for fev1 is determined mainly by gender20 , 21 but , 
 interestingly , smoking habit exceeded the effects of gender in the present study .
largest 
 decreases in fev1 occurred in smokers , whereas the smallest decreases occurred in 
 non - smokers .
the annual decline in 
 fev1 of the non - smokers was 25  ml / year .
this value falls in the range that has 
 been reported for healthy japanese non - smoking males and females aged > 65  years ( i.e. , 
 31 to 22  ml / year)23,24,25 .
even if people had 
 suffered damage from air pollution at one time , those who were non - smokers demonstrated more 
 preserved lung function over time .
all symptoms were identified to be significant in bivariate analyses , but none of these 
 symptoms were found to be significant in multiple regression analyses .
some studies have 
 suggested that males with a chronic cough or sputum production and females with a chronic 
 cough demonstrate a rapid decline in respiratory function26 , 27 . as a result , 
 respiratory symptoms are usually associated with a decline in fev1 .
conversely , 
 another study found that respiratory symptoms do not necessarily result in a decline in 
 fev128 .
classification of medical management was identified as a specific factor associated with 
 the annual change in fev1 .
presence of a single respiratory symptom did not 
 significantly affect the annual change in fev1 , but the classification of medical 
 management might be a comprehensive index and reflect the overall severity of respiratory 
 disease ( including all respiratory symptoms ) .
interestingly , 
 as classification of medical management and/or respiratory symptoms became more severe , the 
 decline in fev1 became less in the present study . in the understanding potential 
 long - term impacts on function with tiotropium ( uplift ) study , patients with severe chronic 
 obstructive pulmonary disease ( copd ) showed smaller declines in fev1 than those 
 with less severe copd31 .
another study 
 reported that the annual change in fev1 was less in patients with advanced stages 
 of copd32 .
in general , more treatments 
 ( e.g. , bronchodilators or other medication ) are administered as disease severity increases . 
 as a result ,
this phenomenon may 
 explain why the annual decline in fev1 becomes smaller with lower 
 % fev1 ( fig .
another factor that could be associated with the annual change in fev1 is the 
 age of subjects . in the present study ,
in contrast , the mean age of subjects in studies that examined longitudinal changes in 
 pulmonary function ranged from 20 years to 60 years20 , 33 , 34 .
the slope of the prediction equation in those studies was steeper 
 than that in the present study .
however , in studies that involved older subjects , the slope 
 of the prediction equation was less pronounced35 , 
 36
however , the decline may be slowed at an 
 advanced age and then the impact of aging may be slight .
moreover , height was not selected 
 by multiple regression analyses , and is a factor that may also be influenced by aging . 
 however , the most important factor affecting pulmonary function and the decline of 
 fev1 was smoking18 , 19 .
the impact of the factors affecting 
 fev1 might , therefore , be affected by disease progression or aging .
the present study was limited by the fact that it was retrospective and that some 
 information pertaining to participants was incomplete .
for example , details regarding the 
 amount of tobacco smoked by subjects were not available .
furthermore , detailed data 
 pertaining to the medications taken by participants was lacking . the type and dose of 
 medication ( e.g. , bronchodilators or other treatments )
the findings of our study suggest that smoking is the strongest factor affecting the annual 
 change in fev1 in officially acknowledged victims with pollution - related 
 illnesses who now live in environments with improved air conditions . in this population
, 
 current smokers showed a more rapid decline in fev1 than former smokers or 
 non - smokers . in some asian countries in which air pollution
is a serious problem , 
 interventions are required to improve the environment and to reduce the prevalence of 
 smoking to improve the health of citizens .
 [ purpose ] we examined factors affecting annual change in pulmonary function in residents 
 previously exposed to air pollution in an area where pollution has been reduced and a long 
 time period has elapsed . [ 
 subjects and methods ] data of 730 officially acknowledged 
 victims of pollution - related illness from an annual survey during 2000 to 2009 were 
 analyzed . 
 the primary outcome was forced expiratory volume in 1 second ( fev1 ) , 
 along with factors such as age , body composition , smoking habits , respiratory symptoms , 
 and classification of medical management ( an index of the need for treatment ) . 
 multiple 
 regression analyses were used to identify factors associated with the annual change in 
 fev1 . 
 [ results ] three significant factors were identified : smoking habit , 
 classification of medical management , and gender . 
 smoking habits and classification of 
 medical management had stronger effects on the annual change in fev1 than 
 gender . 
 [ conclusion ] with an improved environment , continuation of smoking accelerates the 
 decline in fev1 . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION