Associations between markers of respiratory morbidity in European children

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1 Eur Respir J 2002; 19: DOI: / Prited i UK all rights reserved Copyright #ERS Jourals Ltd 2002 Europea Respiratory Joural ISSN Associatios betwee markers of respiratory morbidity i Europea childre K.L. Timoe*, J. Schwartz #, J. Nielse }, B. Bruekreef z Associatios betwee markers of respiratory morbidity i Europea childre. K.L. Timoe, J. Schwartz, J. Nielse, B. Bruekreef. #ERS Jourals Ltd ABSTRACT: School-aged childre ofte experiece acute respiratory symptoms. I a multicetre Europea study, the associatio betwee chroic respiratory symptoms (reported i a questioaire), ski-prick test results, ad lug fuctio, ad the occurrece of acute respiratory morbidity, was examied amog childre aged 6 12 yrs with chroic respiratory symptoms. Childre with chroic respiratory symptoms, livig i 10 Europea coutries, were selected from a paret-completed questioaire (=4,307). Atopy was measured with ski-prick tests, ad lug fuctio with spirometry. A total of 1,854 (86% of those i the iitial cohort) childre kept a successful daily diary regardig their respiratory symptoms for 2 3 moths. I multivariate logistic regressio aalyses, childre with asthmatic symptoms, particularly those with doctor-diagosed asthma, had a greater risk of occurrece of lower respiratory symptoms (odds ratio (): 6.12; 95% cofidece iterval (CI): ) tha childre with a dry octural cough as their oly symptom. Atopy, particularly a positive reactio to idoor allerges, was sigificatly associated with occurrece of lower respiratory symptoms. For atopy the was 1.62 (95% CI: ). A reduced level of maximal mid-expiratory flow was associated with a icreased risk of lower respiratory symptoms, cough ad phlegm. The associatios were similar i Scadiavia, Cetral Easter, Wester ad Souther Europe. To coclude, asthmatic symptoms reported i a questioaire, atopic status ad a reduced level of maximal mid-expiratory flow were associated with the occurrece of acute respiratory symptoms, especially those of lower respiratory symptoms. Eur Respir J 2002; 19: *Uit of Evirometal Epidemiology, Natioal Public Health Istitute, Kuopio, Filad. # Harvard School of Public Health, Bosto, MA, USA. } Dept of Occupatioal ad Evirometal Medicie, Uiversity Hospital, Lud, Swede. z Evirometal ad Occupatioal Health Uit, Uiversity of Utrecht, Utrecht, The Netherlads. Correspodece: B. Bruekreef, Istitute for Risk Assessmet Scieces, Evirometal ad Occupatioal Health Group, PO Box 80176, 3508 TD Utrecht, The Netherlads. Fax: b.bruekreef@iras.uu.l Keywords: Atopy, childre, lug fuctio, respiratory symptom Received: October Accepted after revisio October This study was fuded i the framework of the Commissio of the Europea Commuities Eviromet Programme, cotracts EV5V-CT , CIPD-CT ad ERBCIPD- CT K.L. Timoe was supported by grats from The Fiish Ati-Tuberculosis Associatio Foudatio ad The Ida Moti Foudatio. The Fiish, Norwegia ad two Swedish cetres were fuded by grats from the respective Govermets. School-aged childre ofte experiece acute respiratory symptoms. However, few studies have examied the logitudial relatioship betwee host factors, such as atopy ad lug fuctio, ad respiratory morbidity i childre. Amog these are the studies carried out i Southampto, UK [1, 2]. I these studies, childre with either wheeze or cough were followed-up over a year, by daily diaries. The mai coclusio was that, although both atopy ad symptoms of wheeze were associated with respiratory morbidity, a pre-existig doctor-diagosis of asthma was the strogest predictive factor associated with more frequet ad more severe lower respiratory symptom episodes, a greater proportio of symptomatic days, ad a greater overall peak flow variability. Previously, it has bee show amog childre from the 10 Europea coutries that, compared with childre for whom oly dry octural cough was reported i the screeig questioaire, childre with asthmatic symptoms had a greater diural ad day-today variatio i peak expiratory flow (PEF) durig a 2 3 moth follow-up. Moreover, atopy, especially positive reactios to idoor allerges, ad a reduced level of lug fuctio were also predictors of a greater variatio i PEF [3]. Therefore, the aim of the preset study was to ivestigate whether these characteristics would also be associated with occurrece of acute respiratory symptoms durig a 2 3 moth, daily follow-up i this populatio. Study locatios Subjects ad methods The study was carried out withi the framework of the Pollutio Effects o Asthmatic Childre i

2 480 K.L. TIMONEN ET AL. Europe (PEACE) project, which looks at the effects of air pollutio o respiratory health of childre. A total of 14 study cetres i 10 coutries took part i this Europea collaboratio. The participatig cetres were, by the locatio of the urba area, Amsterdam (the Netherlads), Kuopio (Filad), Oslo (Norway), Berli ad Hettstedt (Germay), Pisa (Italy), Athes (Greece), Cracow ad Katowice (Polad), Prague ad Teplice (Czech Republic), Budapest (Hugary), Umeå ad Malmö (Swede). I each cetre, the same study protocol was followed [4, 5]. However, i Hettstedt, a differet screeig questioaire was used for selectio of subjects. Therefore, i the preset aalyses, data from 13 study cetres are used, excludig Hettstedt. Study desig I each cetre there were two paels of childre with chroic respiratory symptoms: a urba ad a suburba, or rural, pael. The childre were selected by a screeig questioaire that was completed by the parets of the child. Durig autum 1993 ad witer 1994, the childre were characterized with skiprick tests ad spirometric lug fuctio measuremets. Durig witer , the childre kept, with the help of their parets, a daily diary o respiratory symptoms, ad measured PEF every morig ad eveig for 3 moths [4, 5]. Subjects Of a total of 4,307 childre aged 6 12 yrs eligible to eter the study ad asked to participate, 2,112 (49%) childre were characterized with ski-prick test ad spirometric lug fuctio measuremets. A total of 2,152 childre started keepig the diary o respiratory symptoms ad measurig daily PEF. Of these, 1,854 (86%) childre had valid symptoms ad PEF data o more tha 60% of the days, ad these childre were icluded i the preset aalyses (table 1). A total of 30% of the childre had complete diary data, ad 55% of the childre had data o 80 99% of the days. A detailed descriptio of the paels has bee published previously [3]. Screeig questioaire The screeig questioaire used i the PEACE study has bee described previously [4, 5]. A child was cosidered as eligible to eter the study if there was a positive respose to at least oe of the followig questios: Has your child bee bothered i the past 12 moths by a wheezy chest, apart from colds? Has your child bee bothered i the past 12 moths by a attack of shortess of breath with wheezig? Has your child had dry cough at ight i the past 12 moths, apart from coughig with a cold or chest ifectio? Has a doctor ever said your child had asthma? [4, 5]. Ski-prick tests I all cetres, ski-prick tests were doe usig the ALK ski-prick test allerge pael (ALK Laboratories, Horsholm, Demark). The allerges tested i all cetres were birch (Betula verrucosa) ad timothy grass (Pheleum pratese) polles, cat fur (Felis catus), ad house dust mite (Dermatophagoides pteroyssius) Table 1. Descriptio of the paels i the 13 study cetres i four Europea regios Subjects Females Mea age yrs Atopic Media (25th 75th percetile) proportio of days with symptoms i the diary Lower respiratory symptoms # Upper respiratory symptoms } Cough Phlegm Scadiavia Filad/Kuopio (0 2.0) 29 (14 60) 25 (13 43) 5.3 (0 16) Swede/Umeå (0 7.0) 18 (6.7 37) 11 (2.5 29) 0 (0 8.8) Swede/Malmö (0 3.9) 22 (10 39) 16 (2.1 35) 1.7 (0 8.8) Norway/Oslo (0 9.7) 25 (12 55) 23 (6.7 46) 4.5 (0 16) Cetral Easter Europe Polad/Cracow (0 7.1) 33 (13 66) 23 (9.9 47) 0 (0 11) Polad/Katowice (0 7.8) 26 (12 51) 21 (8.2 39) 10 (1.3 32) Czech Republic/Prague (0 8.2) 28 (14 51) 27 (8.6 49) 7.9 (0 18) Czech Republic/Teplice (0 1.7) 16 (7.9 31) 20 (6.3 35) 0 (0 9.5) Hugary/Budapest (0 3.8) 18 (8.8 34) 21 (9.7 36) 0 (0 5.2) Wester Europe Germay/Berli (0 13) 22 (8.2 42) 19 (3.4 36) 0 (0 5.4) The Netherlads/Amsterdam (0 5.1) 24 (15 55) 25 (13 43) 6.1 (0 23) Souther Europe Italy/Pisa (0 15) 17 (7.4 46) 15 (3.8 32) 6.1 (0 16) Greece/Athes (0 5.2) 17 (5.6 33) 16 (3.5 34) 3.5 (0 19) Data are preseted as percetages uless otherwise stated. # : shortess of breath, wheeze, or attacks of shortess of breath with wheezig; } : sore throat, or ruy or stuffed ose.

3 PREDICTS OF ACUTE RESPIRATY SYMPTOMS 481 [4, 5]. Histamie hydrochloride (10 mg?ml -1 ) ad glycerol (50%) were used as positive ad egative cotrols, respectively. I additio, two local allerges were tested i each cetre: dog epithelial dader ad Cladosporium i Amsterdam, Oslo, Umeå ad Malmö, dog epithelial dader ad mugwort polle i Kuopio, alteraria ad platago i Berli, alteraria ad ragweed i Budapest, alteraria ad parietaria i Pisa, olive ad parietaria i Athes, grass mix polles ad dog epithelial dader i Cracow ad Katowice, ad grass mix polles ad mould mix i Prague ad Teplice. A mea weal diameter of w2 mm was regarded as a positive result [4, 5]. If there was o reactio to the positive cotrol or a reactio w1 mm to the egative cotrol, the results were excluded from the aalyses (=121). Lug fuctio tests The spirometric lug fuctio measuremets were performed accordig to the recommedatios of the Europea Commuity for Coal ad Steel [4 6]. All spirometric results were corrected to body temperature, atmospheric pressure ad saturatio with water vapour. Predicted values based o sex ad height of the subjects were calculated accordig to Zapletal (see [7]). Symptom diaries The childre were followed-up for 2 3 moths durig witer They kept a daily diary o respiratory symptoms with the help of their parets. The followig symptoms were reported: cough, phlegm, ruy or stuffed ose, shortess of breath, wheeze, attack(s) of shortess of breath with wheeze, ad sore throat. I additio, the childre measured their PEF rate every morig ad eveig [4, 5]. Results of PEF measuremets have bee published elsewhere [3]. Defiitios Childre who had suffered from wheezig or attacks of shortess of breath with wheezig durig the previous 12 moths were defied as havig "asthmatic symptoms". Childre who had either these asthmatic symptoms ad/or doctor-diagosed asthma were defied as havig "asthma". Childre who did ot have "asthma", but who had reported dry cough at ight that was ot associated with colds, were defied as havig "cough aloe". "Atopy" was defied as havig at least oe positive reactio i skiprick tests. "Lower respiratory symptom" was defied as beig preset whe the child reported i the diary, o a give day to have at least oe of the followig symptoms: shortess of breath, wheeze, or attacks of shortess of breath with wheeze. "Upper respiratory symptom" was defied as beig preset whe the child reported i the diary to have a sore throat, or a ruy or stuffed ose. To study possible area differeces withi Europe, four regios were defied. The Fiish, Swedish ad Norwegia cetres formed "Scadiavia", the Polish, Czech ad Hugaria cetres formed "Cetral Easter Europe", the Germa ad Dutch cetres formed "Wester Europe", ad the Italia ad Greek cetres formed "Souther Europe". Statistical aalyses For each child, the proportio of the days a symptom was reported to be preset was calculated from the total umber of days o which there was a valid report for that symptom. Days with a missig value for the symptom were excluded from the total umber of days. Multivariate logistic regressio aalyses were performed usig the GENMOD procedure, which allowed for the calculatio of a overor uder-dispersio parameter, ad icorporatio of it i the estimatio of the stadard errors of the variables [8]. I all models, adjustmets were made for sex, age ad study cetre. I additio, whe studyig the effects of chroic respiratory symptoms reported i the screeig questioaire, adjustmets were also made for atopy ad level of lug fuctio as maximal mid-expiratory flow (MMEF) (% from predicted). Similarly, whe studyig the effects of ski-prick test results, the models were also adjusted for chroic symptom status (havig asthma or ot) ad level of lug fuctio. Reactivity to house dust mite, cat ad polle allerges were icluded i the statistical model at the same time, to study the idepedet effects of these allerges. Whe studyig the effects of spirometric lug fuctio, adjustmets were also made for atopy ad chroic symptom status. The results are give as odds ratios () with 95% cofidece itervals (CI). Results The mea SD total umber of follow-up days was amog childre with cough aloe ad amog childre with asthma. A total of 566 (31%) childre had dry octural cough apart from colds as their oly chroic respiratory symptom (table 2). Of the childre 59% with asthma had also had dry octural cough i the past 12 moths. Compared to childre with cough aloe, childre with asthma especially those with both symptoms ad a doctor-diagosis of asthma, more ofte reported all of the acute respiratory symptoms i the diary (table 2). The greatest was observed for lower respiratory symptoms. The differece was lowest i the occurrece of cough. Amog the childre with asthma, the childre with asthmatic symptoms but without a diagosis of asthma, were more likely to experiece acute lower respiratory symptoms tha the childre with a doctor-diagosis of asthma but without asthmatic symptoms. However, both these groups were less likely to have acute respiratory symptoms tha childre with both asthmatic symptoms ad a diagosis of asthma. These differeces betwee the groups were observed i all four regios (table 3).

4 482 K.L. TIMONEN ET AL. Table 2. Associatio betwee chroic respiratory symptoms reported i a screeig questioaire, ski-prick test results ad proportio of days with respiratory symptoms preset durig a 2 3-moth follow-up amog childre with chroic respiratory symptoms Subjects Lower respiratory symptoms # Upper respiratory symptoms } Cough Phlegm Days % Days % Days % Days % Chroic respiratory symptom z Cough aloe AS ad/or diagosed asthma ( ) ( ) ( ) ( ) AS ad o diagosed asthma ( ) ( ) ( ) ( ) No AS ad diagosed asthma ( ) ( ) ( ) ( ) AS ad diagosed asthma ( ) ( ) ( ) ( ) Atopy ƒ,## No Yes ( ) ( ) ( ) ( ) PR to house dust mite }} No Yes ( ) ( ) ( ) ( ) PR to cat }} No Yes ( ) ( ) ( ) ( ) PR to timothy or birch polle }} No Yes ( ) ( ) ( ) ( ) : odds ratio; CI: cofidece iterval; AS: asthmatic symptoms; PR: positive reactio. # : shortess of breath, wheeze, or attacks of shortess of breath with wheeze; } : stuffed/ruy ose, sore throat; z : statistical model adjusted for age, sex, atopy, study cetre, ad level of maximal mid-expiratory flow as % from predicted; : durig the past 12 moths wheezig or attacks of shortess of breath with wheezig; ƒ : defied as at least oe positive reactio i ski-prick tests; ## : statistical model adjusted for age, sex, symptom status (havig asthma or ot), study cetre, ad level of maximal mid-expiratory flow as % from predicted; }} : reactivity to house dust mite, cat ad polle at the same time i the statistical model. The model adjusted also for age, sex, symptom status (havig asthma or ot), study cetre, ad level of maximal mid-expiratory flow as % from predicted. The proportio of days with respiratory symptoms, especially with lower respiratory symptoms, rose as the umber of symptoms reported i the screeig questioaire icreased (fig. 1). Atopy was sigificatly associated with a icreased risk of lower respiratory symptoms, but ot with upper respiratory symptoms, cough or phlegm (table 2). Positive reactios to idoor allerges (house dust mite, cat) were idepedetly associated ot oly with lower respiratory symptoms, but also with the occurrece of upper respiratory symptoms ad phlegm. I all four regios, positive reactios to idoor allerges were sigificat predictors of occurrece of lower respiratory symptoms (table 3). The risk of lower respiratory symptoms rose as the umber of positive reactios i the ski-prick test icreased (fig. 2). The relatioship betwee the umber of positive reactios i the ski-prick test ad other symptoms was less strog. I spirometric lug fuctio measuremets, a reduced level of MMEF was most strogly associated with acute respiratory symptoms reported i the diary (table 4). This associatio was observed i all four regios. A low level of forced expiratory volume i oe secod (FEV1)/forced vital capacity (FVC) was also associated with a icreased risk of lower respiratory symptoms ad phlegm. A reduced level of FEV1 was sigificatly associated with a icreased risk of phlegm. There was o clear patter i the associatio betwee FVC ad the risk of acute respiratory symptoms. The level of spirometric lug fuctio was ot associated with upper respiratory symptoms. Discussio I this large epidemiological multicetre study amog Europea childre with chroic respiratory symptoms, chroic respiratory symptoms reported i a screeig questioaire, atopy ad level of spirometric lug fuctio were all idepedetly associated

5 PREDICTS OF ACUTE RESPIRATY SYMPTOMS 483 Table 3. Associatio betwee chroic respiratory symptoms reported i a screeig questioaire, reactivity to house dust mite ad cat allerges i ski-prick tests ad proportio of days with lower respiratory symptoms preset durig a 2 3-moth follow-up amog childre with chroic respiratory symptoms i four Europea regios Scadiavia Cetral Easter Europe Wester Europe Souther Europe % of days % of days % of days % of days Chroic respiratory symptom # Cough aloe AS } ad/or DA ( ) ( ) ( ) ( ) AS ad o DA ( ) ( ) ( ) ( ) No AS ad DA ( ) ( ) ( ) AS ad DA ( ) ( ) ( ) PR to house dust mite z No ( ) ( ) Yes ( ) ( ) ( ) ( ) PR to cat z No Yes ( ) ( ) ( ) ( ) : odds ratio; CI: cofidece iterval; AS: asthmatic symptoms; DA: diagosed asthma; PR: positive reactio. # : statistical model adjusted for age, sex, atopy, study cetre ad level of maximal mid-expiratory flow as % from predicted; } : durig the past 12 moths wheezig or attacks of shortess of breath with wheezig; z : reactivity to house dust mite, cat ad polle at the same time i the statistical model. The model adjusted also for age, sex, symptom status (havig asthma or ot), study cetre, ad level of maximal mid-expiratory flow as % from predicted. a) c) Symptoms b) d) Symptoms Fig. 1. Associatio betwee the umber of chroic respiratory symptoms reported i the screeig questioaire ad occurrece of a) lower respiratory symptoms, b) upper respiratory symptoms, c) cough ad d) phlegm durig a 2 3 moth follow-up. Odds ratios () idicated by the solid horizotal lies at 1.0, ad 95% cofidece itervals (CI) are show.

6 484 K.L. TIMONEN ET AL. a) d) b) d) Reactios Reactios Fig. 2. Associatio betwee the umber of positive reactios i ski-prick tests ad occurrece of a) lower respiratory symptoms, b) upper respiratory symptoms, c) cough ad d) phlegm durig a 2 3 moth follow-up. Odds ratios (), idicated by the horizotal lies at 1.0, ad 95% cofidece itervals (CI) are show. with the proportio of days whe acute respiratory symptoms, especially lower respiratory symptoms, were reported i a daily diary durig a 2 3-moth follow up. A doctor-diagosed asthma with asthmatic symptoms durig the past 12 moths, positive reactios to idoor allerges (house dust mite or cat) ad a reduced level of MMEF were most strogly associated with the occurrece of lower respiratory symptoms. The associatios were similar i Scadiavia, Cetral Easter, Wester ad Souther Europe. The effect estimates i the preset study, however, may be too small. This is because, i the statistical models used, there were always variables for prior symptom status, level of lug fuctio ad reactivity to ski-prick tests. These factors are ot, however, idepedet of each other. Therefore, by havig all of these factors cotrolled for, the effects could have bee uderestimated. Chroic respiratory symptoms reported i the screeig questioaire were associated with the occurrece of acute respiratory symptoms durig the 2 3 moth, daily follow-up, especially the occurrece of lower respiratory symptoms. Compared to childre with cough aloe, childre with asthma experieced lower ad upper respiratory symptoms, ad phlegm more ofte. The differece i reported cough durig the follow-up was ot so clear. Oly childre with both asthmatic symptoms durig the past 12 moths ad doctor-diagosed asthma reported cough more ofte tha childre with cough aloe. I cotrast to the study by PATTEME et al. [2], recet asthmatic symptoms were a better predictor of acute symptoms tha a doctor9s diagosis of asthma. However, childre with both the diagosis ad asthmatic symptoms experieced acute respiratory symptoms most ofte. A similar patter for the occurrece of respiratory symptoms has bee observed i previous studies. PEAT et al. [9] iitially studied a cohort of childre with curret asthma, wheeze oly, or who were ormal. Curret asthma was defied as havig both recet wheeze, assessed by a questioaire, ad brochial hyperresposiveess, assessed by a histamie challege test. Durig the follow-up over a year, most childre (93%) i the group of curret asthma had wheeze, which was clearly more tha amog childre i the wheeze-oly group (52%). However, the latter group demostrated more wheeze tha the childre i the ormal group (18%). Amog 650 childre followed-up prospectively for 2 yrs. Childre for whom curret persistet wheeze was reported at the iitial iterview experieced more lower respiratory illess tha childre without curret persistet wheeze at the iitial iterview [10]. I cotrast, o sigificat differece was foud for upper respiratory illess. CLOUGH et al. [1] studied childre with wheeze or cough oly, ad with or without atopy. The symptom of wheeze was associated with a sigificatly greater severity of acute respiratory symptoms, but ot with a greater proportio of days with lower respiratory

7 PREDICTS OF ACUTE RESPIRATY SYMPTOMS 485 Table 4. Associatio betwee spirometric lug fuctio ad proportio of days with respiratory symptoms preset durig a 2 3-moth follow-up amog childre with chroic respiratory symptoms. Odds ratios () ad 95% cofidece itervals (CI) adjusted for age, sex, study cetre, atopy, ad symptom status (havig asthma or ot) Subjects Lower respiratory symptoms # Upper respiratory Cough Phlegm symptoms } Days % (CI) Days % (CI) Days % (CI) Days % (CI) FVC % from predicted w ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) v ( ) ( ) ( ) ( ) FEV1 % from predicted w ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) v ( ) ( ) ( ) ( ) MMEF % from predicted w ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) v ( ) ( ) ( ) ( ) FEV1/FVC % w ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) v ( ) ( ) ( ) ( ) FVC: forced vital capacity; FEV1: forced expiratory volume i oe secod; MMEF: maximal mid-expiratory flow. # : shortess of breath, wheeze, or attacks of shortess of breath with wheeze; } : stuffed/ruy ose, sore throat. tract symptoms, compared with cough as observed i the preset study. Furthermore, ulike this study o iteractio betwee atopy ad wheeze was show. I the subject selectio phase of the study, oe-half of the childre asked, agreed to participate. This is a little less tha i the follow-up study of PATTEME et al. [2] i which the respose was 62%. It is possible that childre, who had had more respiratory symptoms, would have bee more likely to participate i the study. However, this selectio would have led to more symptomatic childre i all groups. Therefore, it is ulikely that the iitial selectio of subjects would have led to overestimatio of the effects. I additio, if childre with less severe chroic respiratory symptoms, e.g. cough aloe, were less motivated to fill i the diary whe free of symptoms, the proportio of days with acute respiratory symptoms would have bee overestimated. This would lead to atteuatio i the differece betwee childre with asthma ad with cough aloe. I the preset study, this is ot likely. A child had to havew60% of the days with valid data to be icluded i the aalyses. Moreover, there was o differece i the total umber of reportig days betwee childre havig asthma ad childre with cough aloe. Atopy, ad especially a positive reactio to house dust mite ad cat were sigificatly associated with the occurrece of lower respiratory symptoms. These results are supported by previous studies. I their study amog childre with cough or wheeze, CLOUGH et al. [1] demostrated that whe cotrollig for the symptom of wheeze, atopy was associated with a sigificatly greater proportio of days with symptoms tha the absece of atopy, durig a follow-up over a year. HENDERSON et al. [11] examied correlates of recet wheezig episodes i a case-cotrol study amog childre. I that study, sesitizatio to house dust mite was cosistetly associated with recurret wheezig episodes, with a of 5.2 (95% CI: ), whereas o evidece that polle allergy cotributed sigificatly to susceptibility to recurret wheezig episodes was provided. Previously, it has bee stated that sesitivity to house dust mite ad to cat dader is closely associated

8 486 K.L. TIMONEN ET AL. with curret asthma i childre, whereas grass sesitivity is ot a sigificat idepedet risk factor for asthma [12]. This was further supported by the preset study. These results cofirm the importat role idoor allerges play i the occurrece of asthmatic symptoms. However, sice this study was cofied to the witer time, whe childre were little exposed to polle, a role for polle i the occurrece of acute respiratory symptoms caot be ruled out. There was o clear patter i the associatio betwee the level of FVC ad the occurrece of acute respiratory symptoms. A reduced level i FEV1 was positively associated with the occurrece of respiratory symptoms, but was sigificat oly with the occurrece of phlegm. A low level of FEV1/FVC was sigificatly associated with lower respiratory symptoms as well as phlegm. Coversely, a reduced level of MMEF was sigificatly associated with lower respiratory symptoms, cough ad phlegm. This fidig together with the previous results, i which a reduced level of MMEF was closely associated with asthmatic symptoms, positive reactios to idoor allerges, ad a greater PEF variability, supports MMEF as a sesitive parameter of airway obstructio [13]. MMEF is effort idepedet ad measures flow predomiatly i the peripheral airways, whereas FEV1 measures airflow predomiatly i the cetral airway. Therefore, MMEF might be reduced while asymptomatic or i a earlier stage tha FEV1. It is oteworthy that i additio to the level of lug fuctio, positive reactios to house dust mite ad cat, ad a doctor-diagosis of asthma with symptoms i the past 12 moths were also strogly associated with phlegm i this study. Phlegm is ot a classical asthmatic symptom, but clearly i this study, it respods to the same risk factors as more traditioal symptoms like wheezig. The preset multicetre study is the first focused o associatios betwee chroic respiratory symptoms, ski test results ad lug fuctio, ad acute respiratory morbidity i differet Europea regios. I all four regios, the associatios betwee chroic respiratory symptoms, atopy, lug fuctio ad acute respiratory morbidity were similar amog symptomatic childre. To coclude, asthmatic symptoms (reported i a questioaire), atopy (especially a positive reactio to house dust mite ad cat), ad a reduced level of maximal mid-expiratory flow were associated with the occurrece of acute respiratory symptoms specifically lower respiratory symptoms, durig the 2 3-moth follow-up. Refereces 1. Clough JB, Williams JD, Holgate ST. Effect of atopy o the atural history of symptoms, peak expiratory flow ad brochial resposiveess i 7- ad 8-year-old childre with cough ad wheeze. A 12-moth logitudial study. Am Rev Respir Dis 1991; 143: Pattemore PK, Lampe FC, Smith S, Clough JB, Holgate ST, Johsto SL. Asthma survey items as predictors of respiratory problems i childre 2 yrs later: a logitudial study. Eur Respir J 1999; 14: Timoe KL, Nielse J, Schwartz J, et al. Chroic respiratory symptoms, ski test results ad lug fuctio as predictors of peak flow variability. Am J Respir Crit Care Med 1997; 156: Aoymous. Effects of short-term chages i urba air pollutio o the respiratory health of childre with chroic respiratory symptoms. I: Bruekreef B, ed. Study procedures for collaborative study fuded by the Commissio of the Europea Commuities i the framework of the "ENVIRONMENT" RDT Programme. Wageige Agricultural Uiversity, Roemer W, Hoek G, Bruekreef B, et al. Effect of short-term chages i urba air pollutio o the respiratory health of childre with chroic respiratory symptoms: the PEACE project: Itroductio. Eur Respir Rev 1998; 8: Quajer PH, Tammelig GJ, Cotes JE, Pederse OF, Pesli R, Yerault JC. Lug volumes ad forced vetilatory flows. Report Workig Party, Stadardizatio of lug fuctio tests, Europea Commuity for Coal ad Steel, Official statemet of the Europea Respiratory Society. Eur Respir J 1993; 6: Suppl. 16, Quajer PH, Stocks J, Polgar G, Wise M, Karlberg J, Borsboom G. Compilatio of referece values for lug fuctio measuremets i childre. Eur Respir J 1989; 2: Suppl. 4, 184s 261s. 8. SAS Istitute Ic. I: SAS7 Techical Report P-243, SAS/STAT7 Software: The GENMOD Procedure, Release Caty, NC, US SAS Istitute Ic., 1993; p Peat JK, Toelle BG, Salome CM, Woolcock AJ. Predictive ature of brochial resposiveess ad respiratory symptoms i a oe year cohort study of Sydey schoolchildre. Eur Respir J 1993; 6: Weiss ST, Tager IB, Speizer FE, Roser B. Persistet wheeze. Its relatio to respiratory illess, cigarette smokig, ad level of pulmoary fuctio i a populatio sample of childre. Am Rev Respir Dis 1980; 122: Hederso FW, Hery MM, Ivis SS, et al. Correlates of recurret wheezig i school-age childre. Am J Respir Crit Care Med 1995; 151: Sears MR, Herbiso GP, Holdaway MD, Hewitt CJ, Flaery EM, Silva PA. The relative risks of sesitivity to grass polle, house dust mite ad cat dader i the developmet of childhood asthma. Cli Exp Allergy 1988; 19: Lebecque P, Kiakulada P, Coates AL. Spirometry i the asthmatic child: is FEF25 75 a more sesitive test tha FEV1/FVC? Pediatr Pulmool 1993; 16: