The state of childhood asthma in young adulthood

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1 Eur Respir J, 1993, 6, Prited I UK - all rights reserved Jourals Ltd 1993 Europea Respiratory Joural ISSN The state of childhood asthma i youg adulthood J. Kokkoe, 0. Lia The state of childhood asthma i youg adulthood. J. Kokkoe, 0. Lia. ERS Jourals Ltd ABSTRACT: We ivestigated whether patiets with childhood asthma had improved whe reachig adulthood. We also evaluated factors which might ifluece the course of the disease. The study icluded a group of 108 asthmatics, diagosed ad moitored throughout childhood at the out-patiets cliics of Oulu Uiversity Cetral Hospital. At the age of 20-2 yrs of age they were evaluated for the cliical state of their disease, veotilatory lug fuctio ad hype.rreactivity of the airways. I the iterval 30 (28%) bad become totally free of symptoms, whilst 2 (22%) coohued to have symptoms weekly, or more ofte. A quarter of the patiets cotiued to use prophybtctic medicatio, hulf still suffered from aijergic rhiitis, ad oe th.ird bad atopic dermatitis. Ski prick tests showed at least oe positive result i 86% of the patiets, most ofte to aimal dadcrs. Vetilatory lug ructio tests showed forced vital capacity (FVC) to be withi ormal limits, but forced expiratory volume i oe secod (FEV 1 )/FVC values less tha -2 so predicted were foud i 18%. Forty eight percet of the asthmatics reacted to methacholie at a dose of 0.8 mg or lower, ad the degree of airway reactivity showed a sigillcat correlatio with the curret attack rate. The compliace to treatmet of asthma was ot adequate, as oe third smoked ad 81 % lacked proper cl1eck-ups. Cocomitat atopic dermatitis, severe early disease ad impaired vetilatory lug fuctio at school age, were observed to be sigificat risk factors for a severe asthma outcome as a youg adult. Eur Respir J., 1993, 6, Dept of Paediatrics, Uiversity of Oulu, Oulu, Filad. Correspodece: J. Kokkoe Dcpt of Paediatrics Uiversity of Oulu SF Outu Filad Keywords: Asthma hyperreactiviry lug fuctio methacholie Received: November Accepted after revisio February Childhood asthma is heterogeeous i severity. There are patiets who have daily wheezig ad cotiuous abormality i lug fuctio, but may patiets experiece symptoms ifrequetly ad oly i special circumstaces. Disability o accout of asthma is also iflueced by such factors as the occurrece of other atopic maifestatios, allerge exposure, social eviromet, smokig habits, type of treatmet, compliace ad age. It is wellkow that may patiets have a remissio i adolescece, but some cotiue to experiece equally severe symptoms i adulthood (1]. Our cliic maitais close cotact with its asthmatic childre up to the age of 16 yrs. For the preset study, a sample of patiets was cajled for re-examiatio at a mea age of 22 yrs (rage 20-2 yrs). We preset the cliical outcome of asthma i these patiets, ad evaluate the factors which iflueced the progosis. Patiets ad methods The series was derived from a set of 131 asthmatic childre, bor betwee , ad referred to the Departmet of Paediatrics before their fifteeth birthday for the diagosis of asthma. They all came from the area for which our uit acts as the primary paediatric hospital. With the permissio of the Ethical Committee of the Medical Faculty of the Uiversity of Oulu, we also checked the register of the Fiish Natioal Isurace Istitutio to fid subjects i that age group who had cotiuously received ati-asthmatic drugs durig childhood, but o other patiets were foud i the area. These 131 patiets comprised 1.% of the total populatio of that age i the regio, ad had bee kept uder close suiveillace, with hospital visits 1-2 times aually, up to their sixteeth birthday. I 1988, 108 of the subjects, 67 males ad 1 females, came for a re-examiatio, which was performed at the age of 20-2 yrs. mea 22 yrs. All had bee persoally examied by oe of the authors (OL) i childhood. All patiets had a typical history of episodic breathlessess ad wheezig ad a relief of symptoms with use of brochodilators. The diagosis had bee established by a positive methacholie challege i 13, by a treadmill exercise ruig test i five ad cliically durig a acute attack i 89, of whom childre bad eeded hospital care i our cliic. Thirty three patiets had had symptoms weekly, 3 mothly, ad 1 less ofte. Forty four patiets had bee usig ati-iflammatory drug therapy, of whom 23 beloged to the most affected group. The cliical data o these patiets are preseted i table 1.

2 658 J. KOKKONEN, 0. LINNA Table 1. - Cliical features of 108 asthmatic childre before 16 yrs of age Follow-up patie~ No follow-up patie~ Male/female 67/1 20/3 Age at oset yrs* 5.5 (0-1).8 (0-13) Atopic/oatopic 90/18 19/ Allergic rhiitis 7 17 Atopic deatitis 53 Hospital care for acute attack 5 Highest attack rate yr >50 33 Ati-iflammatory drug therapy ihaled corticosteroids 22 sodium cromoglycate 22 Rescue medicatio oly 6 19 Vetilatory lug fuctio at yrs** FVC % of predicted 100±16 10±16 FEV/FVC % 82±9 79±8 *: mea ad rage i parethesis; **: mea±so, reliable values available o 79 childre. FVC: forced vital capacity; FEV 1 : forced expiratory volume i oe secod. To test the validity of the lug fuctio ad airway hyperreactivity tests, 29 medical studets from the same birth cohort but without a history of asthma or other atopic diseases were recruited as cotrols. The re-examiatio icluded a cliical history, physical examiatio, simple spirometry, methacholie ihalatio challege, ski prick tests, ad recordig of livig habits. The cliical history of asthma was collected retrospectively from the patiets' records ad by iterview. Ay family history of atopic diseases was recorded, the age at oset, the rate ad factors provokig symptoms. the type of drug therapy, ad the occurrece of other atopic maifestatios at differet periods. The physical examiatio icluded ispectio of the ski, aterior rhioscopy, ad auscultatio of the heart ad lugs. Each patiet made three forced expiratios through a dry wedge spirometer (Vitalograph Ltd, UK) to measure forced vital capacity (FVC), ad forced expiratory volume i oe secod (FEV 1 ). This was followed immediately by a methacholie ihalatio challege, cosistig of successive icreasig doses up to a cumulative dose of 6.5 mg, with the method described by Y AN et al. [2] for histamie challege, usig a sychroized dosireter jet ebulizer, Spira Elektro 2 (Respiratory Care Ceter, Hameelia. Filad). The FVC values were preseted as percetages of predicted ormals [3], ad the FEV 1 values as percetages of FVC. The dose of methacholie causig a fall i the FEV 1 of 20% from the post-salie baselie (PD:zoF'EV 1 ) was calculated by iterpolatio from a curve of FEV 1 versus log dose of methacholie. PD:wfEV 1 values below 0.8 mg were regarded as positive [], as borderlie, ad above 6.5 mg as egative. The ski prick tests were performed at the Dermatological Departmet of the same hospital usig commercial allerges (Soluprick, ALK. Copehage); the cocetratio beig 10 histamie-equivalet pricks (HEP) ml- 1 for ihalats ad 20 w/v for foods, except for egg which was 100 w/v. A wheal reactio equivalet to at least a half of that observed with 10 mg ml ' histamie dihydrochloride plus that elicited by the salie cotrol was regarded as positive. Studet's t-test, X 2 test ad Pearso's correlatio coefficiet were used for statistical aalysis. Results At the time of re-examiatio, 30 out of the 108 patiets (28%) were totally symptom-free without medicatio, 5 (50%) had symptoms ifrequetly, ad the remaiig 2 (22%) had short episodes of symptoms weekly durig the last two years. Three subjects were i complete remissio uder cotiuous therapy with ihaled corticosteroids, but had relapsed if therapy stopped. These patiets were ot classified as symptom-free. Three of the 30 patiets who were symptom-free at r~ examiatio had had wheezig weekly i childhood, seve mothly, ad 20 less ofte. Six of these patiets had used ati-iflammatory drug therapy at some time. I the remaiig 78 subjects, symptoms had become less frequet i 17, more frequet i, ad had remaied uchaged i 50 by the time of the re-examiatio. Twelve of the 17 subjects with less frequet symptoms ad five of the with icreasig attack rate by adulthood had used ati-iflammatory drug therapy durig childhood. Sice leavig the paediatric cliic, 16 patiets had required hospital care for asthma ad 26 (25%) were still receivig prophylactic drug therapy. Twety oe patiets were usig ihaled corticosteroids, 3 sodium cromoglycate, ad 6 slow-release theophyllie. Of those 26 subjects still usig prophylactic drug therapy, 19 had doe so eve i childhood, ad 16 still beloged to the most affected group. Of those usig ati-iflammatory drugs i childhood, 27 had sice stopped but five of them had symptoms weekly. At the time of re-examiatio, 51 subjects were usig oly ~2-agoists as rescue medicatio ad 31 were maagig without ay drug therapy. Fifty five patiets still suffered from allergic rhiitis, ad 35 had atopic dermatitis (table 2). Twety ie patiets smoked, but oe of these beloged to the most severely affected group. Oly 19% of the patiets i the whole group were reportig for regular medical check-ups, ad 17 out of the 2 with frequet symptoms were regulatig their ow medicatio without ay regular check-ups or special examiatios by a physicia. The patiets' FVC showed o differece from the cotrols (102±1 versus 103±16% of predicted), wheteas the FEV/FVC showed sigificat impairmet (83±9 versus 89±5%, p<o.ool). FEV/FVC values less tha 80% were foud i 35 subjects, ad less tha 75% (-2 so) i 19. I 79 subjects, FEV/FVC ratio had bee reliably measured at yrs of age ad showed a liear correlatio to the values obtaied i adulthood (fig. 1 ). Eightee (51%) Qf the 35 subjects who had FEV/FVC ratios below 80% had had equally low values durig childhood.

3 CHILDHOOD ASTifMA IN YOUNG ADULTS 659 Table 2. - The chage of cliical symptoms from Table 3. - Vetllatory lug fuctio ad respose to childhood to adulthood Childhood Adulthood Feature Preset Abset Attack >SO.yr 1 Yes No 75 6 Ati-iflammatory drug therapy Yes No Positive ski test result Yes 90* 82 No 18 7 Allergic rhiitis Yes No Atopic dermatitis Yes No *: four refused i adulthood. 100 * 90 :S :::0 ~ 80.5 u 8 i;!; 70 Cif u FEV,fFVC i childhood % Fig FEV/FVC ratios measured at the age of yrs ad as adults i 79 asthmatics. FEV ; 1 forced expiratory volume i oe secod; FVC: forced vital capacity. Lies extedig from 80% idicate -lso of the predicted mea. Diagoal lie is tbe lie of idetity. methacholie challege accordig to the severity of asthma FEV/FYC <80% PD 20 FEV 1 <0.8 mg Cotrols Symptom ratig category: Symptom Free Ifrequet l-50 yr Frequet >50-yr' $ X 2 value 9.5* 30.7** *: p<o.ol; **: p<o.ool; df2, estimated oly betwee the three symptom rate categories s: ot estimated i two patiets. PD 20 FEV,: provocative dose of methacholie producig a 20% fall i FEY,. For further abbreviatios see leged to table l. Table. - Positive prick test results (=10) Allerge tested Aimal dader (cat, cow, dog, horse) Polles (birch, mugwort, timothy) Fish D. pteroyssius Egg white All egative Not tested Positive % The methacholie ihalatio challege was positive i 51 patiets, borderlie i 30 ad egative i 25. The test was ot carried out o two subjects, oe because of low baselie lug fuctio, ad oe because of refusal. Both FEV/FVC values ad the threshold to methacholie were sigificatly depedet o the severity of the disease (table 3). A sigificat correlatio was also foud betwee the methacholie threshold ad the baselie FEV/FVC ratio (X} 10.6; p<o.ol). Positive ski prick test results were foud i 89 of the 10 patiets tested (table ). Four patiets refused, all of whom had had multiple positive ski test results whe tested i childhood. Cocomitat atopic dermatitis, frequet symptoms at age 7-1 yrs ad a low value i Table 5. - Childhood risk factors for the outcome of asthma, raked accordig to x 2 -value. Childhood factors Frequet symptoms betwee 7-1 yrs Ati-iflammatory drug therapy Atopic dermatitis FEV/FVC <80% at yrs =79 Family history of atopy Age at oset <2 yrs Frequet symptoms below 7 yrs Positive ski test results Need for hospital care Symptom rate category Symptom-free Ifrequet Frequet l-50 yr 1 >50-yr' =30 =5 = * 10.1* 8.9** 6.5** *: p<o.ol; **: p<o.os, df2, estimated betwee the three symptom rate categories. For abbreviatios see leged to table 1.

4 660 J. KOKKONEN,O. LmNA FEV/FVC.i childhood were factors predictig a high attack rate m adulthood, whereas positive family history of atopic disease, positive ski test results, early oset of symptoms ad the eed for hospital care were ot such factors (table 5). Discussio Our results show that a third of asthmatic childre had become totally symptom-free ad oe sixth had symptoms less frequetly, whereas half of the childre had symptoms equally ad oe teth had symptoms more frequetly. The improvemet rate was similar i subjects who used prophylactic ati-iflammatory drug therapy as i those without ay such treatmet. The outcome was best i those with mild disease ad ormal vetilatory lug fuctio i childhood. There are several historical reports o the atural course of childhood asthma [5-10). May of these studies are retrospective, based o questioaires, ad cocerig differet types of materials. Our series represets a selected group of asthmatic childre referred to a Paediatric Out-patiet Uit at a Uiversity Hospital. Sice the total prevalece of asthma i Fiish adolescets bor i the 1960s is about % [), our material comprised ot more tha oe third of all the possible asthmatics i that age group. Sice this is the oly primary paediatric hospital i the area ad o other patiets were registered with the Natioal Health Isurace Istitutio, it ca be assumed that our group icluded all the most severely affected patiets i the regio. Oly a third of our patiets were completely symptomfree i adulthood, which is equal to the figures i the classical studies of Rackema ad Edwards, ad Ryssig from 1952 ad 1959, ad less tha foud i some other previous studies [7, 9, 10). Nevertheless, the follow-up time i our study was shorter tha the 20 yrs followed i some studies [5-10). It is well-kow that although about a half of patiets become symptom-free i adolescece they may suffer from asthma i later life (1, 9, 12]. However, the most affected adult patiets were the same as preseted i childhood. These figures idicate that modem asthma therapy has ot sigificatly iflueced the atural course of asthma. A less favourable course of asthma has bee show to be predicted by such factors as a positive family history of atopic disease, cocomitat allergic rhiitis, or atopic dermatitis, or severe asthma i childhood [9]. Our ow results were oly partly i agreemet with these. Associated atopic dermatitis, frequet symptoms, or a poor lug fuctio at school age ad adolescece, or the eed for prophylactic drug therapy were recogized to be sigificat risk factors for a ufavourable outcome, whereas the early oset, frequet symptoms before school age, the eed for hospital care, ad family history of atopy were ot prove to be risk factors. Severe asthmatic attacks before school age, ofte eedig hospital care, are mostly provoked by respiratory ifectios which later play a mior role. O the other had, other factors, such as allerges ad exercise, that typically cause symptoms at school age, are also sigificat aetiological factors of asthma i adulthood. The FVC values were geerally withi orm.al limits, but. decre~sed ~V/FVC v~lues were foud i may pat1ets, mcludmg those w1th complete remissio of symptoms. I a Melboure follow-up study, ormal lug fuctio was foud i symptorless patiets (13), whereas some other studies have show sigificat decrease i sesitive airflow tests [1, ]. Our ow results are i agreemet with these fmdigs. O the other had, it is evidet that a more sigificat deterioratio i lug fuctio is maifested oly after a log duratio of active disease [13]. A sigificat correlatio was foud betwee the symptom rate ad the lug fuctio, o oe had, ad the degree of airway hyperreactivity o the other. A correlatio betwee lug fuctio ad the respose to methacholie has also bee detected i other studies [13], although sigificat hyperreactivity is ofte preset without ay decrease i basal lug fuctio [16]. The threshold dose for methacholie of 0.8 mg or lower had bee thought to support the diagosis of asthma (]. I our series, the provocative dose of methacholie was, however, higher i may curret a~thmatics. O the other had, all the cotrols had their PDwfEV 1 values higher tha 6.5 mg. Therefore, i cliical ad epidemiological studies may cases of asthma are missed if the cut-off value of 0.8 mg or lower are used, whereas ot sigificat risk for false positive reactios exists if higher cutoff values are used i youg adults. We coclude from our results, that moder treatmet ca chage the cliical picture of asthma by suppressig symptoms or reducig hospital admissios. However, sice the 1950s, the proportio of those reachig complete cliical remissio has remaied uchaged, ad most patiets retai brochial hyperreactivity ad abormalities of vetilatory lug fuctio. Therefore, active ati-iflammatory drug therapy, educatio ad regular check-ups should be cotiued beyod the paediatric age. Refereces l. Marti AJ, McLea LA, Ladau LI, Phela PD. - The atural history of childhood asthma to adult life. Br Med J 1980; 1: Ya K, Salome C, Woolcock A. - Rapid method for measuremet of brochial resposiveess. Thorax 1983; 38: Viljae A. - Referece values for spirometric, pulmoary diffusig capacity ad body plethysmographic studies. Scad J Cli Lab Ivest 1982; 2 (Suppl. 9): Woolcock AJ. - Expressio of results of airway hyperresposiveess. I: Hargreave E, Woolcock AJ, eds. Airway Resposiveess: Measuremet ad Iterpretatio. Otario, Astra, 1985; pp Rackema FM, Edwards MC. - Asthma i childre: a follow-up study of 688 patiets after a iterval of twety years. N Egl J Med 1952; 26: ad Ryssig E. - Cotiued follow-up ivestigatio cocerig the fate of 298 asthmatic childre. Acta Paediatr 1959; 8:

5 CHILDHOOD ASTHMA IN YOUNG ADULTS Barr LW, Loga GB. - Progosis of childre havig asthma. Pediatrics 196; 3: Buffum WP, Settipae GA. - Progosis of asthma i childhood. Am J Dis Child 1966; 2: Blair H. - Natural history of childhood asthma. Arch Dis Child 1977; 52: Josso JA, Boe J, Berli E. - The log-term progosis of childhood asthma i a predomiatly rural Swedish couty. Acta Paediatr Scad 1987; 76: 95(} Haahtela T, Heiskala M, Suoiemi I. - Allergic disorders ad immediate ski test reactivity i Fiish adolescets. Allergy 1980; 35: 3~ Kelly WJW, Hudso I, Phela PD, Pai MCF, Olisky A. - Childhood asthma i adult life: a further study at 28 years of age. Br Med J 1987; 29: Kelly WJW, Hudso I, Rave J, et al. - Childhood asthma ad adult fuctio. Am Rev Respir Dis 1988; 138: Cooper DM, Cutz E, Leviso H. - Occult pulmoary abormalities i asymptomatic asthmatic childre. Chest 1977; 71: Kerrebij KF, Fioo1e AC, Betveld RDW. - Lug fuctio i asthmatic childre after a year or more without symptoms or treatmet. Br Med J 1978; 1: Lia 0. - Ifluece of baselie lug fuctio o exercise-iduced respose i childhood asthma. Acta Paediatr Scad I 990; 79: