Recurrence of Wheezing Episodes in Children with Respiratory Syncytial Virus and Non-Respiratory Syncytial Virus Bronchiolitis

ORİJİNAL ARAŞTIRMA Recurrence of Wheezing Episodes in Children with Respiratory Syncytial Virus and Non-Respiratory Syncytial Virus Bronchiolitis Özkan KARAMAN, MD, a Burçak TATLI GÜNEŞ, MD, a Zübeyde ERBAYRAKTAR, MD, b Zeynep ARIKAN AYYILDIZ, MD, a Arzu BABAYİĞİT HOCAOĞLU, MD, a Duygu ÖLMEZ, MD, a Nevin UZUNER, MD a a Department of Pediatric Allergy, Dokuz Eylül University Faculty of Medicine, b Molecular Medicine, Dokuz Eylül University Institute of Health Sciences, İzmir Ge liş Ta ri hi/re ce i ved: 10.01.2011 Ka bul Ta ri hi/ac cep ted: 25.05.2011 Ya zış ma Ad re si/cor res pon den ce: Zeynep ARIKAN AYYILDIZ, MD Dokuz Eylul University Faculty of Medicine, Department of Pediatric Allergy, İzmir, TÜRKİYE/TURKEY ztarikan@hotmail.com doi:10.5336/medsci.2011-22557 Cop yright 2011 by Tür ki ye Kli nik le ri ABS TRACT Ob jec ti ve: It has be en shown that many chil dren who ex pe ri en ce res pi ra tory syncyti al vi rus (RSV) in fec ti on in in fancy de ve lop re cur rent whe e zing epi so des and ast hma la ter. Vi - ral ro le in pat ho ge ne sis of ast hma is still a de ba te. We ai med to in ves ti ga te the re cur ren ce of whe e zing epi so des, atopy and se rum cyto ki ne le vels in chil dren en co un te red with RSV in fec ti - on. Ad di ti o nally, we ai med to com pa re the se pa ra me ters in chil dren with non-rsv bronc hi o li - tis. Material and Met hods: The study was con duc ted bet we en Ja nu ary 2006 and No vem ber 2008 in Do kuz Ey lul Uni ver sity hos pi tal. Se venty chil dren aged bet we en 0-36 months who we re diag no sed with acu te bronc hi o li tis for the first ti me we re rec ru i ted for the study. Na sop hary nge - al la va ge flu id was analy zed with poly me ra se cha in re ac ti on (PCR) for RSV an ti gen in all pa ti ents. Se rum im mu nog lo bu lin E, to tal eo si nop hil co unt, in ter le u kin (IL)-4, IL-13 and γ-in ter - fe ron (IFN-γ) le vels we re ob ta i ned at the last exa mi na ti on of the pa ti ents af ter a fol low up pe ri - od of 1-3 ye ars. Re sults: Re cur ren ce of a whe e zing epi so de was ob ser ved in 35% and 53.3% of the pa ti ents in RSV gro up and non-rsv gro up, res pec ti vely (p= 0.064). Me an se rum IFN-γ and IL-4 le vels we re de tec ted to be sig ni fi cantly hig her in non-rsv gro up. No sig ni fi cant re la ti on was de tec ted bet we en re cur ren ce of whe e zing epi so des and to tal eo si nop hil co unt, se rum IgE, IL-4, IL-13, and IFN-γ le vels. Conc lu si on: No dif fe ren ce co uld be de tec ted bet we en RSV and non- RSV bronc hi o li tis re gar ding sub se qu ent whe e zing epi so des. Alt ho ugh se rum IL-4 and IFN-γ le - vels we re hig her in non-rsv bronc hi o li tis gro up, no sig ni fi cant cor re la ti on was ob ser ved bet we en the se pa ra me ters and re cur ren ce of whe e zing epi so des. Key Words: Asthma; bronchiolitis ÖZET Amaç: Süt çocukluğu döneminde respiratuvar sinsityal virus (RSV) infeksiyonu geçiren çocukların daha sonra hışıltı atakları ve astım geçirdikleri gösterilmiştir. Astımın patogenezinde virüslerin rolü halen tartışmalıdır. RSV infeksiyonu ile karşılaşan çocuklarda hışıltı ataklarının tekrarlamasını, atopi ve serum sitokin düzeylerini araştırmayı,ayrıca bu parametreleri RSV-dışı bronşioliti olan çocukların sonuçları ile karşılaştırmayı amaçladık. Gereç ve Yöntemler: Çalışma Ocak 2006 ile Kasım 2008 arasında Dokuz Eylül Üniversitesi Hastanesinde gerçekleştirildi. İlk kez akut bronşiolit tanısı koyulan 0-36 ay yaş aralığında 70 çocuk çalışmaya alındı. Tüm hastalarda nazofarenjiyal lavaj sıvısı RSV antijeni bakımından polimeraz zincir reaksiyonu (PCR) ile incelendi. Bir ila üç yıllık takip süresinden sonra hastaların son muayenelerinde serum immunoglobulin E, total eozinofil sayısı, interlökin (IL)-4, IL-13 ve interferon-γ (IFN-γ) düzeylerine bakıldı. Bulgular: RSV grubunda ve RSV-dışı grupta hışıltı atağı tekrarı sırasıyla hastaların %35 inde ve %53.3 ünde gözlendi (p= 0.064). Ortalama serum IFN-γ ve IL-4 düzeyleri RSV-dışı grupta belirgin olarak yüksek bulundu. Hışıltı ataklarının tekrarı ile total eozinofil sayısı, serum IgE, IL-4, IL-13 ve IFN-γ düzeyleri arasında önemli bir ilişki saptanmadı. Sonuç: RSV ve RSV-dışı bronşiolit arasında müteakip hışıltı atakları bakımından fark saptanamadı. RSVdışı bronşiolit grubunda serum IL-4 ve IFN-γ düzeyleri daha yüksek olmakla birlikte bu parametrelerle hışıltı ataklarının tekrarı arasında önemli bir korelasyon gözlenmedi. Anah tar Ke li me ler: Astım; bronşiyolit Turkiye Klinikleri J Med Sci 2011;31(6):1507-13 Turkiye Klinikleri J Med Sci 2011;31(6) 1507

Karaman ve ark. cu te bronc hi o li tis (AB) is the most common lo wer res pi ra tory tract in fec ti on se en among in fants and is ca u sed by inf lam ma - ti on of small air ways. Bronc hi o li tis ma ni fests in a typi cal se a so nal pat tern with pe aks du ring win ter and fall. It is one of the prin ci pal ca u ses of hos pi tal ad mis si ons in in fants un der the age of 1 ye ar. 1 Acu - te bronc hi o li tis is ma inly ca u sed by vi ru ses, and res pi ra tory syncyti al vi rus (RSV) ac co unts for 50-90% of the ca ses. 2-4 Ot her vi ru ses such as rhi no vi - ru ses, en te ro vi ru ses, hu man me tap ne u mo vi rus and hu man bo ca vi rus are al so fo und in in fants with this con di ti on. 5-7 It has be en shown that many chil dren who ex pe ri en ce RSV in fec ti on in in fancy de ve lop subse qu ent whe e zing epi so des la ter and the risk for ast hma is in cre a sed in tho se in fants. 8-13 Whe e zing usu ally re-oc curs af ter acu te bronc hi o li tis in 50% of the ca ses. In cre a sed fre qu ency of whe e zing epi - so des and ast hma among the chil dren with bronc hi o li tis his tory co uld not be exp la i ned with only atopy and fa mily his tory. It is still unk nown whether bronc hi o li tis trig gers the im mu ne res - pon se to in vol ve an ast hma tic pro cess la ter or whether RSV in fec ti on in du ces the ast hma tic suscep ti bi lity of the in fants which was presented before. 1 Mast cells, ac ti va ted eo si nop hils and ac ti va ted T-hel per lymphocy tes (Th) are in cre a sed in the air ways of ast hma tic in di vi du als. T-hel per lymphocy tes which pro du ce pro inf lam ma tory cyto ki nes [In ter le u kin (IL)-4, IL-5, IL-13] and che - mo ki nes are in vol ved in this inf lam ma tory pro cess. 1 Res pi ra tory syncyti al vi rus in fec ti on triggers a comp lex im mu ne res pon se. It is pos tu la ted that the ba lan ce bet we en Th1 and Th2 is di rec ted to wards Th2, and with the aid of cyto ki nes in vol - ving in ast hma pat ho ge ne sis, al ler gic inf lam ma ti - on be gins af ter RSV in fec ti on. 14 The aims of this study are (i) to de tect the rela ti ons hip bet we en re cur ren ce of whe e zing epi so - des in chil dren en co un te red with RSV in fec ti on and atopy as well as se rum cyto ki ne le vels, (ii) to com pa re the se chil dren with tho se did not en co - un ter RSV bronc hi o li tis, (ii i) and to dis cuss the ro - le of cyto ki nes in the eti o pat ho ge ne sis of re cur rent whe e zing. Çocuk Allerjik Hastalıklar MA TE RI AL AND MET HODS This study was con duc ted bet we en Ja nu ary 2006 and No vem ber 2008 in the De part ment of Pe di at rics, Me di cal Fa culty, Do kuz Ey lul Uni ver sity. The study was ap pro ved by the et hics com mit te e of the hos pi - tal. The pa rents of all in fants we re as ked to par ti ci - pa te in the study and ga ve their in for med con sent. Chil dren aged bet we en 0-36 months who we - re di ag no sed with bronc hi o li tis for the first ti me ac cor ding to the his tory obtained from pa rents we - re rec ru i ted for the study. Fol lo wing eva lu a ti on in the De part ment of Pe di at ric Pul mo no logy and Allergy, De part ment of Pe di at ric Emer gency Me di - ci ne or pe di at ric in pa ti ent unit, na sop hary nge al la va ge flu ids we re analy zed with re ver se trans crip - ta se-poly me ra se cha in re ac ti on (RT-PCR) for RSV an ti gen in all pa ti ents. Na sop hary nge al as pi ra tes we re col lec ted with a dis po sab le cat he ter which was in ser ted in the nos tril to the depth of 5-7 cm and drawn back af ter a gent le suc ti on with an injec tor. The spe ci mens we re trans por ted to the la b- o ra tory at ro om tem pe ra tu re. RSV was de tec ted by using an RT-PCR. The pa ti ents we re eva lu a ted bi - an nu ally by the sa me physi ci an. The pa ti ents with a his tory of pre ma tu rity and an acu te bronc hi o li tis epi so de be fo re and pa ti ents with chro nic di se a ses (chro nic lung di se a se, ast hma, cystic fib ro sis, conge ni tal he art de fects) we re exc lu ded. Pa ti ents we re fol lo wed for 1-3 ye ars. Da ta re gar ding gen der, ges ta ti o nal age, birth we ight, expo su re to ci ga ret te smo ke, du ra ti on of bre ast fe e - ding, ma ter nal edu ca ti on le vel, me an monthly fa mily in co me, num ber of fa mily mem bers, pro perti es of the ho u se dwel led in and the pre sen ce of a fe at hery pet and toy at ho me we re no ted. Fa mily his tory for ast hma, al ler gic rhi ni tis and atopy, age at the ti me of bronc hi o li tis were also re cor ded at the first eva lu a ti on. Fre qu ency of whe e zing epi so - des was re cor ded du ring the fol low-up pe ri od follo wing acu te bronc hi o li tis. A blo od samp le was ob ta i ned at the last follow-up visit of each pa ti ent. To tal eo si nop hil co - unt, se rum im mu nog lo bu lin E (IgE), IL-4, IL-13, and in ter fe ron-γ (IFN-γ) le vels we re stu di ed. Inter le u kin-4, IL-13 and IFN-γ le vels we re analy zed 1508 Turkiye Klinikleri J Med Sci 2011;31(6)

Pediatric Allergic Diseases by enz yme-lin ked im mu no sor bent as say (ELI SA) tech ni qu e using com mer ci al kits (Bi o o Sci en ti fic, Aus tin, TX, USA). The lo wer de tec ti on li mits for the se as says we re: 4 pg/ml for IL-4, 30 pg/ml for IL-13 and 10 pg/ ml for IFN-γ. Skin prick tests (SPT) we re per for med fol lo - wing the re com men da ti ons by the Eu ro pe an Aca - demy of Al lergy and Cli ni cal Im mu no logy in each pa ti ent in or der to eva lu a te atopy. 15 A com mer ci al ex tract (Al ler gop har ma, Ger many) was used with the skin prick/punc tu re met hod. A stan dard pa nel of res pi ra tory al ler gens con sis ting of mi tes, grass mix, mold mix, cat and dog dan der, coc kro ach and cer ta in fo od al ler gens (cow s milk, egg whi te, co - co a, ba na na and tu na fish) we re inc lu ded in skin prick test. The SPT was con si de red po si ti ve when the me an di a me ter of the whe al was at le ast 3 mm when re ad af ter 15 mi nu tes. STA TIS TICAL ANALYSIS Da ta we re analy zed with SPSS for Win dows, versi on 15.0. Des crip ti ve sta tis tics we re used to de - mons tra te de mog rap hic cha rac te ris tics. Dif fe ren ces in cli ni cal cha rac te ris tics bet we en pa ti ents with RSV and non-rsv bronc hi o li tis we re analy zed using Chi-squ a re test for ca te go ri cal va ri ab les and Mann Whit ney-u test for nu me ri cal va ri ab les. Karaman et al Krus kal Wal lis test was used for com pa ri son of the gro ups with re cur rent whe e zing epi so des. A p va - lu e of <0.05 was ac cep ted as sta tis ti cally sig ni fi - cant. RE SULTS Of the 212 pa ti ents who met the inc lu si on cri te ri a, 70 pa ti ents (40 chil dren in RSV gro up and 30 in non-rsv gro up) ac cep ted to participate in the study. Forty-one (58.6%) of the se chil dren we re boys. The re was not a sta tis ti cal dif fe ren ce bet we en the RSV and non-rsv gro up by me ans of gen der and ot her de mog rap hic cha rac te ris tics ex cept birth we ights and ad mis si on age (Tab le 1). The me an age of the chil dren at ad mis si on was 6.46 ± 6.78 months (ran ge: 1-33 months) in the RSV gro up whi le it was 9.53 ± 7.55 months (ran ge: 1-30 months) in the non- RSV gro up. The me an ad mis si on age of the RSV gro up was smaller than the non-rsv gro up (p= 0.031). Ot her de mog rap hic cha rac te ris tics of study gro up can be se en in Tab le 1. The fol low-up pe ri od was 18.97 ± 7.95 months (ran ge: 12-42) for the who le study gro up. RSV gro - up was fol lo wed up for a me an pe ri od of 19.7 ± 8.91 months (ran ge: 12-42 months) whi le non-rsv gro - up was fol lo wed up for a me an pe ri od of 18 ± 6.47 months (ran ge: 12-33 months). In RSV gro up, 26 TABLE 1: Demographic characteristics of the study group. RSV group Non-RSV group p Age at admission (month) mean ± SD 6.46 ± 6.78 9.53 ± 7.55 0.031 Sex n (%) Female 17 (42.5) 12 (40) 1 Male 23 (57.5) 18 (60) Way of delivery n (%) Vaginal delivery 11 (27.5) 12 (40) 0.311 CS 29 (72.5) 18 (60) Birth weight (g) mean ± SD 3366 ± 531.28 3075.73 ± 512.96 0.015 Prenatal exposure to cigarette smoke n (%) Yes 9 (22.5) 7 (23.3) 1 No 31 (77.5) 23 (76.7) Family history of atopy n (%) Yes 27 (67.5) 21 (70) 1 No 13 (32.5) 9 (30) Breastfeeding period (month) mean ± SD 11.02 ± 5.59 13. ± 7.38 0.22 Turkiye Klinikleri J Med Sci 2011;31(6) 1509

Karaman ve ark. chil dren (65%) we re fol lo wed up for one ye ar (12-23 months) whi le 12 (30%) we re fol lo wed up for two ye ars (24-35 months) and 2 (5%) we re fol lo - wed up for thre e ye ars (36 months and furt her). In non-rsv gro up, 24 chil dren (80%) we re fol lo wed up for one ye ar whi le six (20%) we re fol lo wed up for two ye ars. Se rum IL-13 le vel was not dif fe rent in non- RSV and RSV gro ups (p= 0.565) (Tab le 2). The se - rum IL-4 le vel was hig her in non-rsv gro up compared to RSV gro up (p= 0.002). The IFN-γ le - vel was al so sig ni fi cantly hig her in non-rsv gro up compared to RSV gro up (p= 0.003) (Tab le 2). Se - rum IgE le vel and to tal eo si nop hil co unt did not dif fer bet we en the gro ups (p= 0.39, p= 0.121, res - pec ti vely) (Tab le 2). Skin prick test po si ti vity was similar in two gro ups, one pa ti ent in each gro up was sen si ti zed to grass mix. Symptoms of al ler gic rhi ni tis we re no ted in one of the se pa ti ents in the RSV gro up. If the analy sis was ma de ac cor ding to the ye - ars of fol low-up, se rum IL-4 and IFN-γ le vels we - re hig her in non-rsv gro up compared to RSV gro up in the sub sets that we re fol lo wed up for one ye ar (p= 0.04 and p= 0.02, res pec ti vely). Se rum IL- 4 le vel was al so sig ni fi cantly hig her in non-rsv gro up compared to RSV gro up in the sub sets that we re fol lo wed up for two ye ars (p= 0.04). Se rum IL-13 le vel, se rum IgE le vel and to tal eo si nop hil co - Çocuk Allerjik Hastalıklar unt we re not dif fe rent in RSV and non-rsv gro up sub sets fol lo wed up for one and two ye ars. No compa ri son co uld be ma de in the gro ups of chil dren fol lo wed up for thre e ye ars be ca u se in suf fi ci ent num ber of patients. Al ler gic rhi ni tis, ec ze ma and re cur ren ce of whe e zing epi so des we re no ted for each pa ti ent. No pa ti ent was di ag no sed with ec ze ma. Of the pa ti ents in RSV gro up, 65% did not de ve lop any furt her whe e zing. Ho we ver, 30% had whe e zing epi so des fe wer than thre e and 5% de ve lo ped thre e or mo re whe e zing epi so des. Of the pa ti ents in non-rsv gro up, 46.7% did not de ve lop furt her whe e zing. On the ot her hand, 30% had whe e zing epi so des fe - wer than thre e and 23.3% de ve lo ped thre e or mo - re whe e zing epi so des. No dif fe ren ce was no ted bet we en the gro ups for re cur ren ce of whe e zing epi so des (p= 0.064) (Tab le 3). No sig ni fi cant re la ti on was no ted bet we en birth we ight, way of de li very, age at ad mis si on, ma ter nal edu ca ti on le vel, ex po su re to pre na tal or post na tal ci ga ret te smo ke, du ra ti on of bre ast fe e - ding, me an monthly fa mily in co me, pro per ti es of the ho u se dwel led in, num ber of fa mily mem bers and re cur ren ce of whe e zing epi so des (p> 0.05). Recur ren ce of whe e zing epi so des was al so fo und out to be un re la ted to to tal eo si nop hil co unt, se rum IL- 13, se rum IL-4, IFN-γ or se rum IgE le vels (p> 0.05). In addition, no re la ti on was fo und bet we en skin TABLE 2: Laboratory findings of the study group. RSV group Mean ± SD Non-RSV group Mean ± SD p IL-13 (pg/ml) 22.61 ± 34.17 63.68 ± 267.82 0.565 IL-4 (pg/ml) 20.43 ± 45.57 40.77 ± 50.37 0.002 IFN-gama (pg/ml) 90.12 ± 82.3 162.57 ± 98.0 0.003 IgE (IU/mL) 98.8 ± 207.59 267.62 ± 1006.29 0.39 Total eosinophil count (/mm³) 213.22 ± 192.19 240.40 ± 137.40 0.121 TABLE 3: Recurrence of wheezing episodes in RSV positive and non-rsv group. RSV group n (%) Non-RSV group n (%) p No recurrence 26 (65) 14 (46.7) Recurrence of wheezing episode < 3 12 (30) 9 (30) Recurrence of wheezing episode > 3 2 (5) 7 (23.3) Total 40 (100) 30 (100) 0.064 1510 Turkiye Klinikleri J Med Sci 2011;31(6)

Pediatric Allergic Diseases test po si ti vity and re cur ren ce of whe e zing epi so des (p> 0.05). DIS CUS SI ON Lo wer res pi ra tory in fec ti ons in in fancy are tho ught to be re la ted to re cur rent whe e zing and ast hma the re af ter. The re are a number of epi de mi o lo gi cal stu di es re gar ding the ro le of res pi ra tory vi ru ses and es pe ci ally RSV in re cur rent whe e zing. 8,10,16-19 In one of the stu di es investigating the ro le of RSV in the de ve lop ment of ast hma, 12 studies we re re vi e wed and increased risk of ast hma and re cur rent whe e - zing af ter RSV in fec ti on was found in the first 36 months, but the re la ti on showed a tendency to dec re a se with age. 18 Hen der son et al. 17 similarly fo - und a re la ti on bet we en RSV bronc hi o li tis be fo re 12 months of age and la ter ast hma, but no re la ti on with atopy. Res pi ra tory syncyti al vi rus bronc hi o li - tis is tho ught to be cha rac te ri zed by an ex cess of type 2 cyto ki nes. 14 Ho we ver, whet her RSV bronc - hi o li tis ca u ses ast hma by de vi a ting sub se qu ent immu ne res pon ses to wards a type 2 cytokines or whet her ast hma and bronc hi o li tis simply ha ve sa - me risk fac tors, with bronc hi o li tis be ing the first pre sen ting ill ness in a child al re ady at risk of de ve - lo ping ast hma as a re sult of im pa i red type 1 im mu - nity is a mat ter of de ba te. Rhi no vi rus-in du ced whe e zing was al so de - mons tra ted as an im por tant risk fac tor for the deve lop ment of ast hma and the risk shows a tendency to per sist with in cre a sing age. 20-22 In a pros pec ti ve study on chil dren from birth to 6 ye - ars of age, Le mans ke et al. 23 conc lu ded that the occur ren ce of rhi no vi rus-as so ci a ted whe e zing du ring in fancy was the most sig ni fi cant risk factor for ast hma and presc ho ol child ho od whe e zing. In stu di es com pa ring the ro le of bronc hi o li tis ca - u sed by RSV and vi ru ses ot her than RSV in re cur - rent whe e zing epi so des, it is shown that in fec ti ons ot her than RSV con fer a subs tan ti ally gre a ter risk of re cur rent whe e zing compared to RSV in fec ti - ons. 24,25 In our study, no sta tis ti cal dif fe ren ce co uld be de tec ted bet we en RSV and non-rsv bronc hi - o li tis re gar ding re cur ren ce of whe e zing epi so des. The vi ral eti o logy of non- RSV ill ness was not de - mons tra ted in our study but it is li kely that most Karaman et al of them we re ca u sed by rhi no vi ru ses or en te ro vi - ru ses. Alt ho ugh sta tis ti cal dif fe ren ce was not shown in our study, it is no ted that re cur ren ce of whe e zing epi so des we re ob ser ved in 53.3% of the non-rsv gro up whi le it was no ted in 35% of the RSV po si ti ve gro up. We think that the num ber of our study gro up, ma jor li mi ta ti on of our study, might have caused this conc lu si on. In ter le u kin-13 de pen dent mec ha nisms are shown to be re la ted with air way eo si nop hi li a and en han ced air way hyper res pon si ve ness du ring rein fec ti on in a mo u se mo del of ne o na tal RSV in fec - ti on. 26 In se ve ral stu di es, it was shown that IL-4, IL-13 and IFN-γ le vels in cre a sed af ter RSV in fec ti - on. 27-29 However no re la ti on was shown bet we en IL-4, IFN-γ le vels and re cur rent whe e zing epi so - des. 30 In our study, IL-13 levels were not dif fe rent in RSV po si ti ve and ne ga ti ve ca ses but IL-4 and IFN-γ le vels we re sig ni fi cantly hig her in the non- RSV gro up. Se rum IL-4 le vels we re hig her in both sub sets of the non-rsv gro up fol lo wed up for one and two ye ars. however this dif fe ren ce did not predict any pa ra me ter in the fol low up. In our pre vi - o us study, we in ves ti ga ted the re la ti ons hip bet we en se rum IL-4, IL-13, IFN-γ le vels and re curren ce of whe e zing epi so des in in fants with acu te bronc hi o li tis, and fo und out a po si ti ve cor re la ti on bet we en se rum IL-13 le vels and the num ber of whe e zing epi so des. 31 We co uld not study the vi ral eti o logy in that study but we sup po sed that RSV had be en the ca u sa ti ve agent in the ma jo rity of ca - ses. In the study of Cas tro et al. 32 206 in fants we re fol lo wed up af ter a se ve re RSV in fec ti on, and IL-2, IL-4, IL-13 and IFN- γ we re stu di ed im me di a tely af ter the in fec ti on, at the age of 2, 4 and 6. The authors fo und that IL-13 ex pres si on was lo wer in the gro up of in fants who de ve lo ped ast hma la ter and de ni ed the ro le of Th2 type im mu ne res pon se in de ve lop ment of ast hma af ter RSV in fec ti on. In current study, we eva lu a ted the re la ti ons hip bet we en IL-13, IL-4, IFN-γ and re cur ren ce of whe e zing epi - so des, but no sig ni fi cant re la ti on was es tab lis hed. Our re sults might have been dif fe rent if we co uld com pa re the ba sal le vels at the ad mis si on of the patient with the le vels at the last follow-up visit. Unfor tu na tely we co uld only study the le vels at the Turkiye Klinikleri J Med Sci 2011;31(6) 1511

Karaman ve ark. last follow-up visit. No re la ti on was no ted bet we - en RSV in fec ti on and atopy and skin test po si ti vity, similar to pre vi o us stu di es. 33 In our study, we in ves ti ga ted the re la ti on bet we en the de mog rap hic fe a tu res and re cur ren ce of whe e zing epi so des. However, no re la ti on was ob ser ved bet we en gen der, ges ta ti o nal age, birth we ight, ex po su re to ci ga ret te smo ke, du ra ti on of bre ast fe e ding, ma ter nal edu ca ti on le vel, fa mily in co me, num ber of fa mily mem bers, pro per ti es of the ho u se dwel led in, pre sen ce of a fe at hery pet at ho me, fa mily his tory of ast hma, al ler gic rhi ni - tis and atopy, age at the ti me of bronc hi o li tis and re cur ren ce of whe e zing epi so des. The li mi ta ti ons of our study might be an exp la na ti on for the se conc lu si ons. First of all, two-thirds of the pa ti ents ful fil ling di ag nos tic cri te ri a co uld not par ti ci pa te in the study. Se condly, the fol low-up pe ri od of one ye ar in so me chil dren may be re gar ded as Çocuk Allerjik Hastalıklar short and the fol low-up pe ri ods are not the sa me. This dif fe ren ce bet we en the fol low-up pe ri ods may li mit the pre sent re sults. Thirdly, we co uld not de ter mi ne the vi ral eti o logy of bronc hi o li tis in non-rsv gro up be ca u se rhi no vi ru ses and ot her res pi ra tory vi ru ses we re not ro u ti nely stu di ed in our hos pi tal du ring the study pe ri od. Un for tu na - tely, we do not ha ve fro zen samp les for furt her rese arch. On the ot her hand, our pa ti ent po pu la ti on con sis ted of pa ti ents with varying se ve rity. As a con se qu en ce, we think that this is su e pre ven ted the study from bi as of se ve re ca ses who we re at the risk of re cur rent whe e zing epi so des. In conc lu si on, our re sults show that both RSV and non RSV bronc hi o li tis ha ve a si mi lar po ten ti - al ro les for re cur ren ce of whe e zing epi so des. 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