AllergyVolume 75, Issue 10 p. 2719-2719 CORRIGENDUMFree Access Correction for: Niers et al. The effects of selected probiotic strains on the development of eczema (the PandA study) This article corrects the following: The effects of selected probiotic strains on the development of eczema (the PandA study) L. Niers, R. Martín, G. Rijkers, F. Sengers, H. Timmerman, N. Van Uden, H. Smidt, J. Kimpen, M. Hoekstra, Volume 64Issue 9Allergy pages: 1349-1358 First Published online: April 9, 2009 First published: 27 October 2020 https://doi.org/10.1111/all.14312AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Correction for: Niers L1,5, Martín R2,6, Rijkers G1,3,4,7,8, Sengers F1,9, Timmerman H3,10, van Uden N1,11, Smidt H2, Kimpen J1,12, Hoekstra M1,13. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy. 2009 Sep;64(9):1349-58. https://doi.org/10.1111/j.1398-9995.2009.02021.x. 1Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, Utrecht, the Netherlands; 2Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands; 3Department of Surgery, University Medical Center, Utrecht, the Netherlands; 4Department of Medical Microbiology and Immunology, Sint Antonius Hospital, Nieuwegein, the Netherlands. Current affiliations: 5Department of Pediatrics, Maxima Medical Center, Veldhoven, The Netherlands; 6Department of Immunity and Allergy, Danone, Paris, France; 7Science Department, University College Roosevelt, Middelburg, the Netherlands; 8Laboratory of Medical Microbiology and Immunology, St. Elisabeth Hospital, Tilburg, the Netherlands; 9GP Practice “Noord”, Tilburg, The Netherlands; 10Live Therapeutics, Boehringer Ingelheim, Alkmaar, The Netherlands; 11Amsterdam University Medical Center, Amsterdam, The Netherlands; 12Global Medical Office, Philips Center, Amsterdam, the Netherlands; 13Department of Pediatrics, DC Clinics, The Hague, the Netherlands. Correspondence: Ger Rijkers, PhD. Science Department, University College Roosevelt, Lange Noordstraat 1, 4331 CB, Middelburg, the Netherlands. Email: g.rijkers@ucr.nl; g.rijkers@etz.nl The authors wish to make a correction concerning the composition of the mixture of probiotic strains used in a previous publication1 and a follow-up study of the same cohort of children.2 In our paper, we have stated that the intervention group (of children) received once daily 3 × 109 colony forming units (CFU) (1 × 109 CFU of each strain: Bifidobacterium bifidum W23, Bifidobacterium lactis W52 (previously classified as Bifidobacterium infantis), and Lactococcus lactis W58) of freeze-dried powder of the probiotic mixture (Ecologic® Panda, supplied by Winclove Bio Industries BV, Amsterdam, the Netherlands). Since our publication, molecular identification techniques have improved greatly, enabling to better distinguish between, in our case, Bifidobacterium strains. It has thus been found that strain Bifidobacterium bifidum W23 is in fact a mixture of two Bifidobacterium strains, namely Bifidobacterium bifidum W23 and Bifidobacterium lactis W51. After confirmation of this finding, the label of the product has been updated and Bifidobacterium lactis W51 has been added to the declaration of Ecologic® PANDA. We would like to stress that the design, execution, results, and conclusions of the original study have not changed. The product itself also has not changed, and the current product is similar to the original study product; only the ingredient declaration has been changed. We believe it is important to communicate this finding because the Ecologic® Panda product is still marketed, and the label gives the composition as indicated above. We apologize for any inconvenience caused. CONFLICT OF INTEREST Dr. Timmerman reports other from Winclove Probiotics, from null, during the conduct of the study; all others have nothing to disclose. REFERENCES 1Niers L, Martín R, Rijkers G, et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy 2009; 64(9): 1349- 1358. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 2Gorissen DM, Rutten NB, Oostermeijer CM, et al. Preventive effects of selected probiotic strains on the development of asthma and allergic rhinitis in childhood. The Panda study. Clin Exp Allergy. 2014; 44(11): 1431- 1433. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Volume75, Issue10October 2020Pages 2719-2719 ReferencesRelatedInformation

Clinical & Experimental AllergyVolume 44, Issue 11 p. 1431-1433 Letter to the Editor Preventive effects of selected probiotic strains on the development of asthma and allergic rhinitis in childhood. The Panda study D. M. W. Gorissen, Corresponding Author D. M. W. Gorissen Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands Correspondence: Monique Gorissen, Nico Bolkesteinlaan 75, 7416 SE Deventer, Postbus 5001, 7400 GC Deventer, The Netherlands E-mail: [email protected]Search for more papers by this authorN. B. M. M. Rutten, N. B. M. M. Rutten Department of Pediatrics, Sint Antonius Hospital, Nieuwegein, The NetherlandsSearch for more papers by this authorC. M. J. Oostermeijer, C. M. J. Oostermeijer Department of Pediatrics, Deventer Ziekenhuis, Deventer, The NetherlandsSearch for more papers by this authorL. E. M. Niers, L. E. M. Niers Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The NetherlandsSearch for more papers by this authorM. O. Hoekstra, M. O. Hoekstra Department of Pediatrics, University Medical Centre, Groningen, The NetherlandsSearch for more papers by this authorG. T. Rijkers, G. T. Rijkers Department of Sciences, University College Roosevelt Academy, Middelburg, The Netherlands Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The NetherlandsSearch for more papers by this authorC. K. van der Ent, C. K. van der Ent Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The NetherlandsSearch for more papers by this author D. M. W. Gorissen, Corresponding Author D. M. W. Gorissen Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands Correspondence: Monique Gorissen, Nico Bolkesteinlaan 75, 7416 SE Deventer, Postbus 5001, 7400 GC Deventer, The Netherlands E-mail: [email protected]Search for more papers by this authorN. B. M. M. Rutten, N. B. M. M. Rutten Department of Pediatrics, Sint Antonius Hospital, Nieuwegein, The NetherlandsSearch for more papers by this authorC. M. J. Oostermeijer, C. M. J. Oostermeijer Department of Pediatrics, Deventer Ziekenhuis, Deventer, The NetherlandsSearch for more papers by this authorL. E. M. Niers, L. E. M. Niers Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The NetherlandsSearch for more papers by this authorM. O. Hoekstra, M. O. Hoekstra Department of Pediatrics, University Medical Centre, Groningen, The NetherlandsSearch for more papers by this authorG. T. Rijkers, G. T. Rijkers Department of Sciences, University College Roosevelt Academy, Middelburg, The Netherlands Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The NetherlandsSearch for more papers by this authorC. K. van der Ent, C. K. van der Ent Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The NetherlandsSearch for more papers by this author First published: 16 September 2014 https://doi.org/10.1111/cea.12413Citations: 30Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Niers L, Martín R, Rijkers G et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy 2009; 64: 1349–58. 2Asher MI, Keil U, Anderson HR et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995; 8: 483–91. 3Håland G, Carlsen KC, Sandvik L et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med 2006; 355: 1682–9. 4Bousquet J, Khaltaev N, Cruz AA et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update. Allergy 2008; 63(Suppl. 86): 8–160. 5Elazab N, Mendy A, Gasana J, Vieira ER, Quizon A, Forno E. Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics 2013 Sep; 132: e666–76. 6Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003; 361: 1869–71. 7Kalliomaki M, Salminen S, Poussa T, Isolauri E. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol 2007; 119: 1019–21. 8Kuitunen M, Kukkonen K, Juntunen-Backman K et al. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol 2009; 123: 335–41. 9Abrahamsson TR, Jakobsson T, Björkstén B, Oldaeus G, Jenmalm MC. No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy. Pediatr Allergy Immunol 2013; 24: 556–61. 10Wickens K, Stanley TV, Mitchell EA et al. Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization? Clin Exp Allergy 2013; 43: 1048–57. 11West CE, Hammarström ML, Hernell O. Probiotics in primary prevention of allergic disease – follow-up at 8-9 years of age. Allergy 2013; 68: 1015–20. 12Niers LE, Timmerman HM, Rijkers GT et al. Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines. Clin Exp Allergy 2005; 35: 1481–9. 13Niers LE, Hoekstra MO, Timmerman HM et al. Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of neonatal dendritic cells. Clin Exp Immunol 2007; 149: 344–52. 14Yatsunenko T, Rey FE, Manary MJ et al. Human gut microbiome viewed across age and geography. Nature 2012; 486: 222–7. Citing Literature Volume44, Issue11November 2014Pages 1431-1433 ReferencesRelatedInformation

BACKGROUND:One of the IL-17 family members, IL-25, has been implicated with the initiation and amplification of Th2 responses in animal models and has been associated with airway hyper-reactivity. The involvement of IL-25 and also IL-17 in food allergic disease remains to be investigated.FINDINGS:In this study thirty children suspected of peanut allergic disease underwent a double-blind placebo controlled food challenge (DBPCFC) and IL-25 and IL-17 plasma levels were determined before and after challenge. IL-25 was highly elevated only in subgroup of children with a positive DBPCFC outcome. Plasma IL-25 was absent in children with a negative DBPCFC outcome and in healthy controls.CONCLUSIONS:This study shows that IL-25, an IL-17 family member, is highly elevated only in children with a clinical response to peanut. This suggests a role for IL-25 in the pathogenesis of peanut allergy and elevated plasma IL-25 may be a sign of a severe atopic phenotype.

Heat shock protein 60 (hsp60) is a highly conserved stress protein and target of self-reactive T cells in various inflammatory diseases. Not much is known about a possible role in atopic disease. As atopic diseases are considered to be the result of a disturbance in the balance between T helper cells type 2 and regulatory T cells, it is of interest to know whether hsp60 acts as a bystander antigen in atopic disease. Our aim was to investigate whether hsp60 is involved in the chronicity of inflammation of atopic dermatitis (AD). We studied the expression of hsp60 in skin tissue of adults with AD by immunohistochemistry. Peripheral blood mononuclear cells (PBMC) of children with AD were cultured with hsp60 and proliferative responses, cytokine secretion, surface markers, and functional assays were compared to responses of PBMC of healthy controls (HC). Hsp60 was detected more in lesional skin of AD patients compared to nonlesional skin. Furthermore, PBMC of children with AD proliferated more strongly in response to hsp60 compared to HC. hsp60-reactive T cells of atopic children produced high levels of IFNγ and low levels of IL-10. In vitro activation with hsp60 leads to the induction of CD4+CD25bright T cells expressing FOXP3 in both HC as well as in atopic children. However, despite their regulatory phenotype, hsp60-induced CD4+CD25brightCD127−FOXP3+ T cells of AD patients were incapable of suppressing effector T cells in vitro. hsp60 is recognized by proinflammatory (IFNγ high, IL-10 low) T cells in atopic patients and is more present in lesional AD skin. This suggests that hsp60-specific T cell responses contribute to local inflammation in AD.

SummaryBackgroundA novel data‐driven approach was used to identify wheezing phenotypes in pre‐schoolchildren aged 0–8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes.ObjectiveThe objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention.MethodsIn the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with ‘never/infrequent wheeze’ as reference category.ResultsComplete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day‐care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy.Conclusion and Clinical RelevanceWe identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day‐care attendance and breastfeeding, and may be important targets for prevention programmes.

OBJECTIVE:To evaluate the hypoallergenicity of an extensively hydrolysed (EH) casein formula supplemented with Lactobacillus rhamnosus GG (LGG).DESIGN:A prospective, randomised, double-blind, placebo-controlled crossover trial.SETTING:Two study sites in Italy and The Netherlands.STUDY PARTICIPANTS:Children with documented cow's milk allergy were eligible for inclusion in this trial.INTERVENTIONS:After a 7-day period of strict avoidance of cow's milk protein and other suspected food allergens, participants were tested with an EH casein formula with demonstrated hypoallergenicity (control, EHF) and a formula of the same composition with LGG added at 10(8) colony-forming units per gram powder (EHF-LGG) in randomised order in a double-blind placebo-controlled food challenge (DBPCFC). After absence of adverse reactions in the DBPCFC, an open challenge was performed with EHF-LGG, followed by a 7-day home feeding period with the same formula.MAIN OUTCOME MEASURE:Clinical assessment of any adverse reactions to ingestion of study formulae during the DBPCFC.RESULTS:For all participants with confirmed cow's milk allergy (n=31), the DBPCFC and open challenge were classified as negative.CONCLUSION:The EH casein formula supplemented with LGG is hypoallergenic and can be recommended for infants and children allergic to cow's milk who require an alternative to formulae containing intact cow's milk protein.TRIAL REGISTRATION NUMBER:http://ClinicalTrials.gov Identifier: NCT01181297.

Background: To prevent harmful autoimmunity most immune responses to self proteins are controlled by central and peripheral tolerance. T cells specific for a limited set of self-proteins such as human heat shock protein 60 (HSP60) may contribute to peripheral tolerance. It is not known whether HSP60-specific T cells are present at birth and thus may play a role in neonatal tolerance. We studied whether self-HSP60 reactive T cells are present in cord blood, and if so, what phenotype these cells have.Methodology/Principal Findings: Cord blood mononuclear cells (CBMC) of healthy, full term neonates (n = 21), were cultured with HSP60 and Tetanus Toxoid (TT) to study antigen specific proliferation, cytokine secretion and up-regulation of surface markers. The functional capacity of HSP60-induced T cells was determined with in vitro suppression assays. Stimulation of CBMC with HSP60 led to CD4(+) T cell proliferation and the production of various cytokines, most notably IL-10, Interferon-gamma, and IL-6. HSP60-induced T cells expressed FOXP3 and suppressed effector T cell responses in vitro.Conclusion: Self-reactive HSP60 specific T cells are already present at birth. Upon stimulation with self-HSP60 these cells proliferate, produce cytokines and express FOXP3. These cells function as suppressor cells in vitro and thus they may be involved in the regulation of neonatal immune responses.

To the Editor: Before puberty, the prevalence of asthma and wheeze is higher in boys than girls.1Almqvist C. Worm M. Leynaert B. Working Group of GA2LEN WP 2.5 GenderImpact of gender on asthma in childhood and adolescence: a GA2LEN review.Allergy. 2008; 63: 47-57PubMed Google Scholar Because of difficulties of diagnosing asthma at early ages,2Martinez F.D. Godfrey S. Wheezing disorders in the preschool child: pathophysiology and management. Martin Dunitz, London and New York2003Crossref Google Scholar it is unknown at what age sex differences in asthma develop. Our main objective was to determine the age of onset of sex differences in asthma risk. Because the mechanisms underlying the observed sex differences in childhood asthma are not yet fully understood,3Postma D.S. Gender differences in asthma development and progression.Gend Med. 2007; 4: S133-S146Abstract Full Text PDF PubMed Scopus (243) Google Scholar we also evaluated the role of atopy and perinatal exposures. In the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort, 4146 pregnant women were recruited from the general population, and their children were followed from birth (1996-1997) to age 8 years.4Brunekreef B. Smit J. de Jongste J. Neijens H. Gerritsen J. Postma D. et al.The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study: design and first results.Pediatr Allergy Immunol. 2002; 13: 55-60Crossref PubMed Scopus (251) Google Scholar Data were collected by questionnaires during pregnancy, at ages 3 months and 1 year, and yearly thereafter. The study population consisted of 3308 children with questionnaire-based data on asthma at age 8 years. Asthmatic wheeze at ages 1 to 7 years was defined as parent-reported wheeze at ages 1, 2, 3, 4, 5, 6, or 7 and asthma at age 8 years. Thus, wheeze at ages 1 to 7 years was only considered to be asthmatic wheeze if children had asthma at age 8 years. Wheeze in children without asthma at age 8 years was considered as transient wheeze. The definition of asthma at age 8 years was based on questionnaire data: at least 1 attack of wheezing and/or 1 episode of dyspnea and/or 1 prescription of inhaled corticosteroids in the past 12 months. Specific IgE was measured at age 8 years in a subgroup of 776 children in which children of mothers with allergy were oversampled.5Scholtens S. Wijga A.H. Seidell J.C. Brunekreef B. de Jongste J.C. Gehring U. et al.Overweight and changes in weight status during childhood in relation to asthma symptoms at 8 years of age.J Allergy Clin Immunol. 2009; 123 (e2): 1312-1318Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar Atopy was defined as a specific IgE concentration of ≥0.70 IU/mL for at least 1 of the following inhalant allergens: house dust mite, cat, dog, birch, grass, and mold. Atopic asthma at age 8 years was defined as asthma with atopy at age 8 years. The relation between sex and the prevalence of asthmatic wheeze was studied longitudinally by using general estimating equations. Sex differences in the incidence (rate of new cases) of asthmatic wheeze were studied by using a Cox proportional hazard analysis (option TIES = discrete of PHREG procedure in SAS; SAS Institute, Inc, Cary, NC). The study population was similar to the total PIAMA population with respect to the characteristics shown in Table I; a significant sex difference was observed only for mean birth weight.Table ICharacteristics of the study populationBoysn (%)Girlsn (%)Region North1698 (30.9)1610 (32.3) Central1698 (43.0)1610 (39.4) West1698 (28.3)1610 (26.2)Low maternal education1691 (21.5)1601 (21.7)Allergic mother†Parents were defined as having allergy if they had hay fever, pet allergy, house dust mite allergy, or asthma ever.1698 (29.0)1610 (28.7)Allergic father†Parents were defined as having allergy if they had hay fever, pet allergy, house dust mite allergy, or asthma ever.1696 (29.8)1609 (31.5)Smoking during pregnancy‡Mother smoked during the first 4 weeks of pregnancy.1678 (15.4)1588 (16.5)Breast-feeding§Any breast-feeding (either exclusive or partial). >16 wk1682 (36.1)1595 (38.2)Older siblings1698 (51.8)1610 (48.8)At 3 mo in the home Smoking mother or father‖Smoking in the home at least once a week.1693 (22.3)1858 (23.2) Cat1697 (33.2)1610 (31.5) Dog1696 (14.9)1609 (14.5) Damp/mold spots¶In living room or child’s bedroom.1662 (9.6)1572 (9.0)First year Attending day care1688 (25.9)1599 (23.7) >4 h/wkMean (SD)Mean (SD)Birth weight (g)3589 (547)3457 (514)∗P < .05.∗ P < .05.† Parents were defined as having allergy if they had hay fever, pet allergy, house dust mite allergy, or asthma ever.‡ Mother smoked during the first 4 weeks of pregnancy.§ Any breast-feeding (either exclusive or partial).‖ Smoking in the home at least once a week.¶ In living room or child’s bedroom. Open table in a new tab At age 8 years, 15.1% of the boys and 10.8% of the girls had asthma (odds ratio [OR], boys vs girls, 1.5; 95% CI, 1.2-1.8). The prevalence of total wheeze decreased strongly with age, in contrast with the prevalence of asthmatic wheeze, which remained fairly stable (Table II).Table IISex differences in the prevalence of total wheeze and asthmatic wheeze∗Wheezing at ages 1 to 7 years was labeled “asthmatic wheeze” only if children had asthma at age 8 years (see Methods). (as opposed to transient wheeze)Age (y)Total wheezeAsthmatic wheeze∗Wheezing at ages 1 to 7 years was labeled “asthmatic wheeze” only if children had asthma at age 8 years (see Methods).NOR†Derived from general estimating equation analysis. (95% CI)OR† (95% CI)GirlsBoysGirls %Boys %Boys vs girlsGirls %Boys %Boys vs girls11543163517.822.71.37 (1.15-1.63)3.76.11.74 (1.25-2.43)21582167314.619.71.43 (1.19-1.72)3.45.71.68 (1.20-2.36)31587166813.916.71.25 (1.04-1.52)4.06.51.72 (1.25-2.37)4156716459.313.71.56 (1.25-1.94)3.86.61.78 (1.30-2.45)5156216447.411.31.60 (1.25-2.03)3.46.72.01 (1.45-2.81)6157116576.78.91.37 (1.06-1.77)3.96.21.63 (1.18-2.24)7152816324.86.61.36 (1.01-1.83)3.05.01.66 (1.16-2.37)∗ Wheezing at ages 1 to 7 years was labeled “asthmatic wheeze” only if children had asthma at age 8 years (see Methods).† Derived from general estimating equation analysis. Open table in a new tab The prevalence of asthmatic wheeze was higher in boys than girls from the first year of life onward (Table II). The sex difference varied little with age (ORs, boys vs girls, ranging 1.6- 2.0; P < .05). The sex difference for total wheeze was smaller, with ORs ranging from 1.3 to 1.6. Boys had a higher incidence of asthmatic wheeze than girls in the first 3 years of life, with an overall incidence ratio for this period of 1.7 (95% CI, 1.3-2.2; Fig 1). In the 4 to 7 years age period, incidence was similar in boys and girls (incidence ratio, 1.1; 95% CI, 0.7-1.7). For total wheeze, the incidence ratio for boys versus girls was 1.3 (95% CI, 1.1-1.5) in the age period 0 to 3 years and 1.1 (95% CI, 0.8-1.4) in the age period 4 to 7 years. Analyses in the subgroup with data on atopy (n = 776) showed that the prevalence of atopy at age 8 years was higher in boys than girls (36.4% vs 24.0%: OR, 1.8; 95% CI, 1.3-2.5). In this subgroup, the prevalence of asthma at age 8 years was higher than in the total study population (19.1% in boys and 14.9% in girls), but the association with sex was similar to the association in the total study population (boys vs girls, OR, 1.4; 95% CI, 0.9-2.0). Sex differences in asthma prevalence were similar in atopic and nonatopic children (no effect modification). In the subgroup, the overall OR for the prevalence of asthmatic wheeze at ages 1 to 7 years in boys versus girls was 1.6 (95% CI, 1.1-2.5). Adjustment for atopy at age 8 years reduced this OR to 1.3 (95% CI, 0.9-2.0). The association between the perinatal risk factors shown in Table I and asthma risk at age 8 years was similar in boys and girls. Sensitivity analyses were conducted, repeating the main analyses with a stricter definition of asthma. In these analyses, atopy was included in the definition of asthma at age 8 years. Thus, wheeze at ages 1 to 7 years was only considered to be asthmatic in children with atopic asthma at age 8 years. Results were similar to those of the main analyses (overall OR for the prevalence of asthmatic wheeze at ages 1-7 years in boys vs girls, 2.0; 95% CI, 1.2-3.2; other results not shown). We used longitudinal data to differentiate at ages 1 to 7 years between asthmatic wheeze (if asthma was present at age 8 years) and transient wheeze (if asthma was absent at age 8 years). Strengths of this longitudinal study are the availability of annual data on wheeze and of data on atopy in a substantial subgroup at age 8 years. There is no gold standard to define asthma, and every questionnaire-based asthma definition, including the PIAMA definition, may result in some misclassification. Potential misclassification is, however, unlikely to differ by sex. Also, sensitivity analyses, using a stricter definition of asthma, showed sex differences very similar to those observed in the main analyses. Atopy was assessed at the age of 8 years, and the directionality of the association between atopy and asthmatic wheeze therefore needs to be interpreted with caution. The follow-up rate was high in the PIAMA study and similar in boys and girls. Stratification showed that oversampling of allergic mothers in the subgroup did not affect sex differences in asthmatic wheeze. The observed sex differences therefore apply to the total study population. The PIAMA population is relatively highly educated compared with the general population, but parental education did not affect the sex differences reported here. We assume therefore that the observed sex differences in the development of asthmatic wheeze are generalizable to the general population. The prevalence of asthmatic wheeze was significantly higher in boys than girls already at the age of 1 year, and this higher prevalence persisted during the first 7 years of life. The incidence of asthmatic wheeze was higher in boys than girls in the first 3 years of life, but not thereafter. The observed sex differences were larger for asthmatic wheeze than for total wheeze, suggesting that sex differences are stronger for asthma than for transient symptoms. Young boys are thought to have smaller airway diameters in proportion to their total lung volume than girls, predisposing them to airway obstruction and wheeze.1Almqvist C. Worm M. Leynaert B. Working Group of GA2LEN WP 2.5 GenderImpact of gender on asthma in childhood and adolescence: a GA2LEN review.Allergy. 2008; 63: 47-57PubMed Google Scholar, 6Becklake M.R. Kauffmann F. Gender differences in airway behaviour over the human life span.Thorax. 1999; 54: 1119-1138Crossref PubMed Scopus (547) Google Scholar Our results suggest that sex differences in asthma may partly be explained by the higher prevalence of atopy in boys and cannot be explained by a stronger effect of perinatal risk factors in boys. Prevalence of asthma in young childrenJournal of Allergy and Clinical ImmunologyVol. 128Issue 2PreviewTo the Editor: Full-Text PDF

BACKGROUND:Despite existing effective treatment options, asthma is uncontrolled in a considerable proportion of patients. The aim of this study was to identify determinants of uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study. METHODS:One hundred seventy children using inhaled corticosteroids in the previous 12 months at age 8 were included. Uncontrolled asthma was defined as: ≥3 items present in the past month: (1) day-time or (2) night-time asthma symptoms, (3) limitations in activities, (4) rescue medication use, (5) FEV(1) <0% predicted and (6) unscheduled physician visits because of asthma. Binomial regression was performed to study five groups of determinants representing asthma control: child and parental characteristics, environmental factors, therapy adherence and parental perception towards medication use (Beliefs about Medicines Questionnaire). RESULTS:Seventy seven children (45%) had uncontrolled asthma. Low maternal education (RR 1.6, 95% CI: 1.0-2.4) was associated with uncontrolled asthma. Parental necessity beliefs about medication use to maintain present and future health and parental concerns about potential adverse consequences of medication were also associated with uncontrolled asthma (RR 1.6, 95% CI: 1.1-2.2; and 1.6, 95% CI: 1.0-2.5, respectively). CONCLUSIONS:Environmental factors and therapy adherence were not associated with asthma control. In our cohort, uncontrolled asthma is associated with low maternal education and with strong parental beliefs about medication necessity and higher concern about potential side effects of medication.

To the Editor: In newborns the induction of productive immune responses is generally blunted in comparison with adults, resulting in tolerogenic immune reactivity.1Billingham R.E. Brent L. Medawar P.B. Actively acquired tolerance of foreign cells.Nature. 1953; 172: 603-606Crossref PubMed Scopus (2257) Google Scholar This immune status results in an increased potency to engraft neonatal animals, ineffective vaccination responses in newborns, and reduced occurrence of graft-versus-host disease when cord blood (CB)–derived allografts are used.2Wang J. Zhan P. Ouyang J. Chen B. Zhou R. Yang Y. Unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients: a meta-analysis.Leuk Res. 2010; 34: 1018Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 3Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates.Nat Rev Immunol. 2007; 7: 379Crossref PubMed Scopus (915) Google Scholar We hypothesized that forkhead box protein 3 (FOXP3)–positive regulatory T (Treg) cells are pivotal in this phenomenon because these cells are key players in immune homeostasis.4Bennett C.L. Christie J. Ramsdell F. Brunkow M.E. Ferguson P.J. Whitesell L. et al.The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3.Nat Genet. 2001; 27: 20-21Crossref PubMed Scopus (2676) Google Scholar When comparing the number of FOXP3+ cells in human CB and adult peripheral blood (APB), we found less FOXP3+ cells in CB than APB (Fig 1, A, ex vivo, uncultured cells). However, when naive (CD25−CD45RO−) T cells were activated by plate-bound anti-CD3, significantly more FOXP3+ T cells were induced from CB precursors. Remarkably, we only observed this difference between CB and APB when viable antigen-presenting cells (APCs; T cell–depleted CB or APB mononuclear cell fraction) were included in the culture; replacement with irradiated APCs abrogated the effect, whereas costimulation by soluble anti-CD28 showed a less pronounced difference (Fig 1, A). Induced CB FOXP3+ T cells (sorted as CD4+CD25+CD127low cells) were able to suppress dose dependently the proliferation of both CD4 and CD8 effector T cells when cultured together in different ratios (not shown), confirming the Treg nature of these cells. Thus on the first activation, CB T cells have a tendency to become functional FOXP3+ Treg cells. To substantiate the role of CB APCs in the induction of high percentages of Treg cells, we activated naive T cells in an alloreaction with APCs. Again we observed a higher number of Treg cells when CB T cells were cultured. CB APCs were able to induce higher numbers of Treg cells than APB APCs from both CB and APB precursor T cells (Fig 1, B). Nevertheless, CB T cells always contained higher percentages of Treg cells, indicating a T-cell intrinsic mechanism as well. We investigated the percentages of different APC populations because the APCs used in our previous experiments consisted of a mixture of different cell types. In both APB and CB, we found comparable numbers of conventional dendritic cells (HLA-DR+CD11c+) and plasmacytoid dendritic cells (HLA-DR+CD123+), with slightly more CD14+ monocytes in APB (not shown). When we sorted different subsets as APCs and cultured them with anti-CD3–activated T cells, we observed that all APC subsets induced more Treg cells from CB than from APB precursor cells (Fig 1, C). The augmented Treg cell induction was not correlated with a reduced proliferation of CB T cells, which we showed to be identical in CB and APB by using carboxyfluorescein succinimidyl ester dilution assays (data not shown). Moreover, we found no difference in the kinetics of FOXP3 upregulation when we measured the percentage of FOXP3+ cells daily; both APB and CB showed a peak of FOXP3+ cells around 4 days of culture, after which the percentage of FOXP3+ cells decreased to stable expression at day 6 (Fig 1, D). Both APB and CB cells had a similar stable FOXP3-expressing population compared with the initial peak around day 4; 65% of the FOXP3+ T cells at day 4 remain stable FOXP3-expressing cells during the 8-day culture. The induction of Treg cells in the periphery on activation can be mediated by several factors. Cytokines like TGF-β and IL-2 are known to induce FOXP3,5Lu L. Zhou X. Wang J. Zheng S.G. Horwitz D.A. Characterization of protective human CD4+ CD25+ FOXP3+ regulatory T cells generated with IL-2, TGF-β and retinoic acid.PLoS ONE. 2010; 5: e15150Crossref PubMed Scopus (111) Google Scholar whereas inflammatory cytokines prevent this. To test whether possible differences in secreted mediators, such as cytokines and chemokines, can explain the difference in Treg cell induction, we exchanged culture supernatants between CB and APB every day during the 6-day culture period of naive T cells with APCs and anti-CD3. This approach did not result in altered differences between CB and APB Treg cell induction, making a role for secreted mediators unlikely (not shown). Another factor influencing FOXP3 induction is the strength of the T-cell receptor (TCR) signal and costimulation.6Gottschalk R.A. Corse E. Allison J.P. TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo.J Exp Med. 2010; 207: 1701-1711Crossref PubMed Scopus (211) Google Scholar, 7Semple K. Nguyen A. Yu Y. Wang H. Anasetti C. Yu X.Z. Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling.Blood. 2011; 117: 3096-3103Crossref PubMed Scopus (69) Google Scholar In our settings the TCR signal was standardized by plate-bound anti-CD3, but costimulation is provided by the APCs. High costimulation through CD28 signaling prevents the upregulation of FOXP3. We therefore investigated the role of the CD28 ligands CD80 and CD86 on APCs. We observed no difference in the expression of these molecules. When blocking antibodies toward CD80, CD86, or both were added to the cultures, this did not result in a difference in FOXP3 expression (Fig 2, A). This finding was confirmed by adding increasing concentrations of cytotoxic T lymphocyte–associated antigen 4-immunoglobulin (CTLA4-Ig) to the cultures, blocking both CD80 and CD86, which had no obvious effect (data not shown). Inhibition of downstream signaling pathways of TCR and CD28 on T-cell activation is able to promote FOXP3 induction as well. The phosphoinositide 3-kinase/protein kinase B (PKB) pathway is central in T-cell differentiation.8Haxhinasto S. Mathis D. Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells.J Exp Med. 2008; 205: 565-574Crossref PubMed Scopus (609) Google Scholar Prevention of activation of this pathway by limited costimulation or signaling through inhibitory molecules, such as programmed death 1 (PD-1), promotes FOXP3 upregulation.7Semple K. Nguyen A. Yu Y. Wang H. Anasetti C. Yu X.Z. Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling.Blood. 2011; 117: 3096-3103Crossref PubMed Scopus (69) Google Scholar, 9Francisco L.M. Salinas V.H. Brown K.E. Vanguri V.K. Freeman G.J. Kuchroo V.K. et al.PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.J Exp Med. 2009; 206: 3015-3029Crossref PubMed Scopus (1511) Google Scholar We hypothesized that differential downstream signaling on activation might be pivotal to the high levels of FOXP3 found on day 6 of activation and onward (Fig 1, D). We therefore investigated the role of PD-1 and PKB in the induction of FOXP3 in CB-naive T cells. On activation, CB CD4+ T cells have an increased expression of the PD-1 molecule compared with APB (Fig 2, B). When we blocked the interaction between PD-1 and its ligand PD-L1 by including a blocking mAb to PD-L1 in the culture, a significant reduction in the percentage of FOXP3+ T cells was observed (Fig 2, C), isotype mAb had no effect (not shown). A PD-1–blocking mAb showed comparable results. As a consequence, the phosphorylation status of PKB on activation by different concentrations of anti-CD3 was lower for CB than APB cells (Fig 2, D). Additionally, CB T cells required approximately 10-fold more TCR triggering than APB T cells before an increase in PKB phosphorylation was observed. Shortly after birth, the immune system of the newborn encounters all kinds of neoantigens. The low percentages of Treg cells found ex vivo in CB are not likely to play a major role in maintaining tolerance to these neoantigens. However, we here show that PD-1 signaling in CB T cells facilitates their differentiation into induced functional FOXP3+ Treg cells through a mechanism involving reduced PKB signaling. This phenomenon might well represent a mechanism that is developed to ensure active tolerance in the neonatal immune system.

Objective: Under and overtreatment of asthma may be a serious problem especially in young children, but the evidence is scarce and no longitudinal data are available. Our aim was to investigate whether inhaled medication use in young children was in agreement with asthma symptoms at the age of 2-8 yr.Methods: Data were used from the 'Prevention and Incidence of Asthma and Mite Allergy' birth cohort, consisting of 3963 children born in the Netherlands. Between age 2 and 8 yr, children were followed up using annual postal questionnaires. Age-specific prevalences of asthma symptoms were assessed and compared with reported use of inhaled bronchodilators and/or corticosteroids.Results: The proportion of current wheeze decreased with age. About a third of 'current wheezers' did not use any inhaled medication during the years in which symptoms were reported. At 8 yr, 30% of children with reported 'severe current asthma symptoms' were not using inhaled corticosteroids. On the other hand, up to 50% of children with inhaled corticosteroids for at least 2 yr did not report any wheezing during those 2 yr.Conclusion: The proportion of symptomatic children without appropriate treatment was substantial throughout childhood, even when parents reported prolonged or severe symptoms. Treatment of asymptomatic children with inhaled corticosteroids increased with age and accounted for up to a third of all inhaled steroid use at 8 yr. These findings suggest that under and overtreatment of asthma in children was common.

BACKGROUND & AIMS:Probiotic bacteria are used as food supplement in many different disease settings. The immune modulating capacity of different strains is not always properly tested which might result in a suboptimal choice of strains for clinical use. METHODS:The CD4 T cell responses to 19 different gut derived lactic acid bacteria were tested with different methods to show their diversity in immune modulation and to make a well-founded choice on which strains to use in future clinical trials. After co-culture of PBMC with bacteria, the induction of CD4(+) T cell subsets (regulatory T cells, T helper type (TH)1, TH2 and TH17) was analysed by rtPCR of transcription factor mRNA, intracellular FACS staining of transcription factors and cytokine production. RESULTS:Bacterial strains all have diverse, unique immune modulatory properties. Strains can induce Treg, TH1, TH2 and TH17 cells which can be shown at different levels of T cell activation, and is consistent for most strains tested. For TH1, TH17 and Treg, a positive correlation between the different methods was found. For TH2 cells the correlation was less consistent. CONCLUSIONS:Probiotic bacteria have very different immune modulating capacities. Analysis of transcription factor mRNA is a suitable method for in vitro characterization of strains prior to clinical application.

To the Editor: Recently, Wijga et al1Wijga A. Tabak C. Postma D.S. Kerkhof M. Wieringa M.H. Hoekstra M.O. et al.Sex differences in asthma during the first 8 years of life: the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study.J Allergy Clin Immunol. 2011; 127: 275-277Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar investigated the prevalence and incidence of wheeze with a special emphasis on sex differences. Their short letter contains important information on allergic symptoms of Western young generations. They concluded that the prevalence (incidence) of wheeze in boys was significantly higher than that in girls. The author previously reported the prevalence of asthma by using a standard questionnaire in Japanese children.2Kawada T. Risk factors and prevalence of asthma or atopic dermatitis in young children by a questionnaire survey.J Nippon Med Sch. 2004; 71 (Available at:) (Accessed May 29, 2011): 167-171http://www.jstage.jst.go.jp/article/jnms/71/3/167/_pdfCrossref PubMed Scopus (12) Google Scholar A total of 24,631 children at the ages of 0, 1, 2, and 3 years were surveyed. The parents of the target population completed questionnaires about the symptoms of asthma. Each local government agreed to the study protocol. The Committee on Human Health Survey in Gunma Prefecture approved this study. Informed consent was obtained from all the families of the subjects. The response rate was 70.7% (17,402/24,631). Statistical analysis was performed by using the SPSS 16.0J software package for Windows (SPSS Japan, Inc, Tokyo, Japan). A positive answer to all 6 questions of the American Thoracic Society—Division of Lung Disease (ATS-DLD) questionnaire3Ferris B.G. Epidemiology Standardization Project (American Thoracic Society). II. Recommended respiratory disease questionnaires for use with adults and children in epidemiological research.Am Rev Respir Dis. 1978; 118: 7-53PubMed Google Scholar categorized the subject as having asthma. The 6 questions were quoted in Kawada2Kawada T. Risk factors and prevalence of asthma or atopic dermatitis in young children by a questionnaire survey.J Nippon Med Sch. 2004; 71 (Available at:) (Accessed May 29, 2011): 167-171http://www.jstage.jst.go.jp/article/jnms/71/3/167/_pdfCrossref PubMed Scopus (12) Google Scholar (Table I). By logistic regression analyses, it was found that male gender, increasing age, and family history of asthma significantly contributed to an increase in the risk of asthma. In order to compare his data with the data presented by Wijga et al,1Wijga A. Tabak C. Postma D.S. Kerkhof M. Wieringa M.H. Hoekstra M.O. et al.Sex differences in asthma during the first 8 years of life: the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study.J Allergy Clin Immunol. 2011; 127: 275-277Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar the author newly defined a child as having wheeze when at least 1 of the 6 questions of the ATS-DLD questionnaire was positively answered. The prevalence of wheeze at ages 0, 1, 2, and 3 years was 6.1 (196/3201), 13.5 (329/2445), 17.4 (125/717), and 21.6 (481/2231) in boys, and 4.3 (137/3214), 9.4 (227/2412), 11.2 (85/759), and 14.4 (308/2142) in girls. By using a χ2 test (P < .01), it was found that the prevalence of asthma differed by gender at all ages. Although the trend of wheeze prevalence by age was different from the values presented by Wijga et al (Table II), the prevalence of wheeze in boys was significantly higher than that in girls at all ages. Dissociation might partly be derived from definition, because the prevalence of asthmatic wheeze presented in Table II showed a slightly increasing trend. In addition, Wijga et al speculated that sex differences in asthma might be explained by the higher prevalence of atopy in boys. On this point, there was a related information that the prevalence of atopic dermatitis in boys at ages 0 and 2 was higher than that in girls (P < .01).2Kawada T. Risk factors and prevalence of asthma or atopic dermatitis in young children by a questionnaire survey.J Nippon Med Sch. 2004; 71 (Available at:) (Accessed May 29, 2011): 167-171http://www.jstage.jst.go.jp/article/jnms/71/3/167/_pdfCrossref PubMed Scopus (12) Google Scholar There are relatively fewer studies looking at the prevalence of asthma in young children.4Pearce N. Weiland S. Keil U. Langridge P. Anderson H.R. Strachan D. et al.Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol.Eur Respir J. 1993; 6: 1455-1461PubMed Google Scholar, 5Burr M.L. Limb E.S. Andrae S. Barry D.M. Nagel F. Childhood asthma in four countries: a comparative survey.Int J Epidemiol. 1994; 23: 341-347Crossref PubMed Scopus (100) Google Scholar The standard simple ATS-DLD questionnaire was used to calculate the prevalence of wheeze in the children in this study, and further study is needed to reach a final conclusion. The author thanks all the participants in this study. Sex differences in asthma during the first 8 years of life: The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort studyJournal of Allergy and Clinical ImmunologyVol. 127Issue 1PreviewTo the Editor: Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 128Issue 2PreviewTo the Editor: Full-Text PDF

Purpose This study was conducted to assess the validity of parental reported use of inhaled corticosteroids (ICS) in children.Methods ICS users were identified within the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and the PIAMA pharmacy sub-cohort which is nested within the PIAMA study. Complete medication histories were available for the first 8 years of life for children within the PIAMA pharmacy sub-cohort. Parental reported ICS use was measured by using data from questionnaires. ICS use in the pharmacy records was determined by using the Anatomical Therapeutic Chemical (ATC) codes. The proportion of overall agreement and kappa statistics with their corresponding 95% confidence intervals were calculated to quantify agreement between self-reported medication use and pharmacy prescription data.Results At all ages overall agreement was very high (>97%) and Cohen's kappa's ranged from 0.80 to 0.88 which also reflects excellent agreement between parental reported use of ICS and pharmacy prescription data.Conclusions Our finding suggests that parental report of medication use is a reliable source of data to asses ICS use in children. The questionnaire-based medication data collected within the PIAMA study can be used to study asthma medication use in a large group of children. Copyright (C) 2010 John Wiley & Sons, Ltd.

SummaryBackground T cell responses involved in peanut allergy are poorly understood.Objective To investigate T cell responses towards major peanut allergens in peanut‐allergic (PA) subjects compared with peanut‐sensitized (PS) non‐allergic children and non‐atopic (NA) controls.Methods Eighteen PA children, seven non‐allergic PS children and 11 NA adults were included. Peripheral blood mononuclear cells were stimulated with a crude peanut extract (CPE). Short‐term T cell lines were generated and subsequently stimulated with CPE and purified Ara h 1, Ara h 2, Ara h 3 and Ara h 6. The proliferation and production of IL‐13, IFN‐γ, IL‐10 and TNF‐α were analysed.Results Proliferation to CPE and major allergens was enhanced in PA subjects. The primary response to CPE was comparable with PS subjects, with increased production of IL‐13 and IFN‐γ compared with NA. Production of IL‐10 was not observed. In short‐term T cell lines, the response to CPE was stronger in PA than in PS and NA subjects. Only PA children had a detectable response to major peanut allergens, characterized by IL‐13 production. The response was the highest after Ara h 3 stimulation, and the lowest after Ara h 2 stimulation. No significant correlation was observed between peanut‐specific IgE levels and T cell responses to CPE.Conclusion T cell responses to CPE in PA and PS children were characterized by Th1 and Th2 cytokines. Only PA children showed enhanced Th2 responses to Ara h 1, Ara h 3 and Ara h 6. Cite this as: A. E. Flinterman, S. G. M. A. Pasmans, C. F. den Hartog Jager, M. O. Hoekstra, C. A. F. M. Bruijnzeel‐Koomen, E. F. Knol and E. van Hoffen, Clinical & Experimental Allergy, 2010 (40) 590–597.

Background Exposure to environmental tobacco smoke (ETS) is known to increase the risk of respiratory tract infections (RTI). Some children, however, may be more susceptible to the harmful effects of ETS than others. We examined whether early atopic status (defined by elevated neonatal total IgE (tIgE) or symptoms of atopic dermatitis) modified the association between ETS exposure and RTI. Methods The data of 2863 children from the Prevention and Incidence of Asthma and Mite Allergy birth cohort were collected to the age of 4 years. Neonatal tIgE was collected from a subset of 914 children, and clinical information by yearly parental questionnaires. The effect of pre- and/or postnatal ETS exposure, early atopic status and interaction between these factors was studied for various RTI. Results Children with elevated tIgE or atopic dermatitis and prenatal ETS exposure have a strongly increased risk of frequent RTI (aOR 6.18 (95% CI 1.45 to 26.34) and 5.69 (2.01 to 16.04), respectively; interaction p=0.006 and p=0.14, respectively) compared to non-atopic children without prenatal ETS exposure. Similar results were seen for lower RTI and otitis. This effect was less evident for postnatal ETS. Conclusion Early atopic status enhances the risk of RTI in children with prenatal ETS exposure. This suggests that host factors modify the association between ETS and RTI.