2,884
Views
0
CrossRef citations to date
0
Altmetric
Review

Factors and mechanisms contributing to the development of preschool wheezing disorders

, &
Pages 745-760 | Received 29 Oct 2020, Accepted 01 Apr 2021, Published online: 21 Apr 2021

References

  • Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. The group health medical associates. N Engl J Med. 1995;332(3):133–138.
  • Selby A, Munro A, Grimshaw KE, et al. Prevalence estimates and risk factors for early childhood wheeze across Europe: the EuroPrevall birth cohort. Thorax. 2018;73(11):1049–1061.
  • Davies G, Paton JY, Beaton SJ, et al., Children admitted with acute wheeze/asthma during November 1998–2005: a national UK audit. Arch Dis Child. 93(11): 952–958. 2008.
  • Stevens CA, Turner D, Kuehni CE, et al. The economic impact of preschool asthma and wheeze. Eur Respir J. 2003;21(6):1000–1006.
  • Moorman JE, Akinbami LJ, Bailey CM, et al. National surveillance of asthma: United States, 2001–2010. Vital Health Stat.2012;3(35):1–58.
  • Stick SM, Burton PR, Gurrin L, et al. Effects of maternal smoking during pregnancy and a family history of asthma on respiratory function in newborn infants. Lancet. 1996;348(9034):1060–1064.
  • Hanrahan JP, Tager IB, Segal MR, et al. The effect of maternal smoking during pregnancy on early infant lung function. Am Rev Respir Dis. 1992;145(5):1129–1135.
  • Gilliland FD, Li YF, Peters JM. Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med. 2001;163(2):429–436.
  • Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;354(9178):541–545.
  • Henderson AJ, Sherriff A, Northstone K, et al. Pre- and postnatal parental smoking and wheeze in infancy: cross cultural differences. Avon Study of Parents and Children (ALSPAC) study team, European Longitudinal Study of Pregnancy and Childhood (ELSPAC) co-ordinating centre. Eur Respir J. 2001;18(2):323–329.
  • Krishnamoorthy N, Khare A, Oriss TB, et al., Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma. Nat Med. 18(10): 1525–1530. 2012.
  • Grad R, Morgan WJ. Long-term outcomes of early-onset wheeze and asthma. J Allergy Clin Immunol. 2012;130(2):299–307.
  • Beigelman A, Durrani S, Guilbert TW. Should a preschool child with acute episodic wheeze be treated with Oral Corticosteroids? A Pro/Con Debate. J Allergy Clin Immunol Pract. 2016;4(1):27–35.
  • Beigelman A, Ts K, Mauger D, et al. Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing? J Allergy Clin Immunol. 2013;131(6):1518–1525.
  • Oommen A, Lambert PC, Grigg J. Efficacy of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1–5 years: randomised controlled trial. Lancet. 2003 Nov;362(9394):1433–1438.
  • Panickar J, Lakhanpaul M, Lambert PC, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009 Jan;360(4):329–338.
  • Castro-Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: systematic review with meta-analysis. Pediatr Pulmonol. 2016;51(8):868–876.
  • Foster SJ, Cooper MN, Oosterhof S, et al. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018;6(2):97–106.
  • Jartti T, Lehtinen P, Vanto T, et al. Efficacy of prednisolone in children hospitalized for recurrent wheezing. Pediatr Allergy Immunol. 2007;18(4):326–334.
  • Gleeson JG, Loftus BG, Price JF. Placebo controlled trial of systemic corticosteroids in acute childhood asthma. Acta Paediatr Scand. 1990;79(11):1052–1058.
  • Fox GF, Marsh MJ, Milner AD. Treatment of recurrent acute wheezing episodes in infancy with oral salbutamol and prednisolone. Eur J Pediatr. 1996;155(6):512–516.
  • Brodlie M, Gupta A, Rodriguez-Martinez CE, et al. Leukotriene receptor antagonists as maintenance or intermittent treatment in pre-school children with episodic viral wheeze. Paediatr Respir Rev. 2016;17:57–59.
  • Hussein HR, Gupta A, Broughton S, et al. A meta-analysis of montelukast for recurrent wheeze in preschool children. Eur J Pediatr. 2017;176(7):963–969.
  • Nwokoro C, Pandya H, Turner S, et al. Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial. Lancet Respir Med. 2014;2(10):796–803.
  • Robertson CF, Price D, Henry R, et al. Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med. 2007;175(4):323–329.
  • Collins SA, Pike KC, Inskip HM, et al. Validation of novel wheeze phenotypes using longitudinal airway function and atopic sensitization data in the first 6 years of life: evidence from the Southampton Women’s survey. Pediatr Pulmonol. 2013;48(7):683–692.
  • Miller EK, Avila PC, Khan YW, et al. Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma. J Allergy Clin Immunol. 2014;2(5):537–543.
  • Krawiec ME, Westcott JY, Chu HW, et al. Persistent wheezing in very young children is associated with lower respiratory inflammation. Am J Respir Crit Care Med. 2001;163(6):1338–1343.
  • Hauk PJ, Krawiec M, Murphy J, et al. Neutrophilic airway inflammation and association with bacterial lipopolysaccharide in children with asthma and wheezing. Pediatr Pulmonol. 2008;43(9):916–923.
  • Marguet C, Jouen-Boedes F, Dean TP, et al. Bronchoalveolar cell profiles in children with asthma, infantile wheeze, chronic cough, or cystic fibrosis. Am J Respir Crit Care Med. 1999;159(5 Pt 1):1533–1540.
  • Bisgaard H, Hermansen MN, Bønnelykke K, et al. Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study. BMJ. 2010;341(oct04 1):c4978.
  • Carlsson CJ, Vissing NH, Sevelsted A, et al., Duration of wheezy episodes in early childhood is independent of the microbial trigger. J Allergy Clin Immunol. 136(5): 1208–14.e145. 2015.
  • Turato G, Barbato A, Baraldo S, et al. Nonatopic children with multitrigger wheezing have airway pathology comparable to atopic asthma. Am J Respir Crit Care Med. 2008;178(5):476–482.
  • Saglani S, Payne DN, Zhu J, et al. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med. 2007;176(9):858–864.
  • Saglani S, Malmström K, Pelkonen AS, et al. Airway remodeling and inflammation in symptomatic infants with reversible airflow obstruction. Am J Respir Crit Care Med. 2005;171(7):722–727.
  • Oommen A, McNally T, Grigg J. Eosinophil activation and preschool viral wheeze. Thorax. 2003;58(10):876–879.
  • Fattouh R, Al-Garawi A, Fattouh M, et al. Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease. Am J Respir Crit Care Med. 2011;183(2):179–188.
  • Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354(19):1985–1997.
  • Murray CS, Woodcock A, Langley SJ, et al. Secondary prevention of asthma by the use of inhaled fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study. Lancet. 2006;368(9537):754–762.
  • Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics. 2009;123(3):e519–25.
  • Guiddir T, Saint-Pierre P, Purenne-Denis E, et al., Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children. J Allergy Clin Immunol. 5(5): 1351–1361.e2. 2017.
  • Fitzpatrick AM, Jackson DJ, Mauger DT, et al., Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 138(6): 1608–18.e12. 2016.
  • Schwerk N, Brinkmann F, Soudah B, et al. Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy. PLoS One. 2011;6(11):e27913.
  • Robinson PFM, Pattaroni C, Cook J, et al., Lower airway microbiota associates with inflammatory phenotype in severe preschool wheeze. J Allergy Clin Immunol. 143(4): 1607–1610.e3. 2019.
  • Hallstrand TS, Hackett TL, Altemeier WA, et al. Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clin Immunol. 2014;151(1):1–15.
  • Holtzman MJ, Byers DE, Alexander-Brett J, et al. The role of airway epithelial cells and innate immune cells in chronic respiratory disease. Nat Rev Immunol. 2014;14(10):686–698.
  • Barbato A, Turato G, Baraldo S, et al. Epithelial damage and angiogenesis in the airways of children with asthma. Am J Respir Crit Care Med. 2006;174(9):975–981.
  • Looi K, Buckley AG, Rigby PJ, et al. Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma. Clin Exp Allergy. 2018;48(5):513–524.
  • Kicic A, Hallstrand TS, Sutanto EN, et al. Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium. Am J Respir Crit Care Med. 2010;181(9):889–898.
  • McDougall CM, Helms PJ, Walsh GM. Airway epithelial cytokine responses in childhood wheeze are independent of atopic status. Respir Med. 2015;109(6):689–700.
  • Kicic A, Sutanto EN, Stevens PT, et al. Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma. Am J Respir Crit Care Med. 2006;174(10):1110–1118.
  • Kicic A, Stevens PT, Sutanto EN, et al. Impaired airway epithelial cell responses from children with asthma to rhinoviral infection. Clin Exp Allergy. 2016;46(11):1441–1455. 11.
  • Spann KM, Baturcam E, Schagen J, et al. Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy. Thorax. 2014;69(10):918–925.
  • Turner S, Miller D, Walsh GM, et al. Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze. Pediatr Pulmonol. 2018;53(1):10–16.
  • Bossley CJ, Fleming L, Gupta A, et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. J Allergy Clin Immunol. 2012;129(4):974–982.e13.
  • Saglani S, Mathie SA, Gregory LG, et al. Pathophysiological features of asthma develop in parallel in house dust mite-exposed neonatal mice. Am J Respir Cell Mol Biol. 2009;41(3):281–289.
  • Baraldo S, Turato G, Bazzan E, et al. Noneosinophilic asthma in children: relation with airway remodelling. Eur Respir J. 2011;38(3):575.
  • O’Reilly R, Ullmann N, Irving S, et al. Increased airway smooth muscle in preschool wheezers who have asthma at school age. J Allergy Clin Immunol. 2013;131(4):1024–1032.
  • Regamey N, Ochs M, Hilliard TN, et al. Increased airway smooth muscle mass in children with asthma, cystic fibrosis, and non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2008;177(8):837–843.
  • Ober C, Yao TC. The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev. 2011;242(1):10–30.
  • Larkin EK, Hartert TV. Genes associated with RSV lower respiratory tract infection and asthma: the application of genetic epidemiological methods to understand causality. Future Virol. 2015;10(7):883–897.
  • Halapi E, Gudbjartsson DF, Jonsdottir GM, et al. A sequence variant on 17q21 is associated with age at onset and severity of asthma. Eur J Hum Genet. 2010;18(8):902–908.
  • Sarnowski C, Sugier PE, Granell R, et al. Identification of a new locus at 16q12 associated with time to asthma onset. J Allergy Clin Immunol. 2016;138(4):1071–1080. 10.
  • Bouzigon E, Corda E, Aschard H, et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med. 2008;359(19):1985–1994.
  • Calışkan M, Bochkov YA, Kreiner-Møller E, et al. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med. 2013;368(15):1398–1407.
  • Loss GJ, Depner M, Hose AJ, et al., The early development of wheeze. Environmental determinants and genetic susceptibility at 17q21. Am J Respir Crit Care Med. 193(8): 889–897. 2016.
  • Bønnelykke K, Sleiman P, Nielsen K, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet. 2014;46(1):51–55.
  • Bochkov YA, Watters K, Ashraf S, et al. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci U S A. 2015;112(17):5485–5490.
  • Von Mutius E, Smits HH. Primary prevention of asthma: from risk and protective factors to targeted strategies for prevention. Lancet. 2020;396(10254):854–866. 09.
  • Crump C. Preterm birth and mortality in adulthood: a systematic review. J Perinatol. 2020;40(6):833–843.
  • Gibbons JTD, Wilson AC, Simpson SJ. predicting lung health trajectories for survivors of preterm birth. Front Pediatr. 2020;8:318.
  • Crump C, Sundquist K, Sundquist J. Adult outcomes of preterm birth. Prev Med. 2016;91:400–401. [ 10].
  • Kotecha SJ, Watkins WJ, Paranjothy S, et al. Effect of late preterm birth on longitudinal lung spirometry in school age children and adolescents. Thorax. 2012;67(1):54–61.
  • Been JV, Lugtenberg MJ, Smets E, et al. Preterm birth and childhood wheezing disorders: a systematic review and meta-analysis. PLoS Med. 2014;11(1):e1001596.
  • Wolsk HM, Chawes BL, Litonjua AA, et al. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: a combined analysis of two randomized controlled trials. PLoS One. 2017;12(10):e0186657.
  • Chawes BL, Bønnelykke K, Stokholm J, et al. Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomized clinical trial. JAMA. 2016;315(4):353–361.
  • Gunaratne AW, Makrides M, Collins CT. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood. Cochrane Database Syst Rev. 2015;(7):CD010085.
  • Bisgaard H, Stokholm J, Chawes BL, et al. Fish oil-derived fatty acids in pregnancy and wheeze and Asthma in Offspring. N Engl J Med. 2016;375(26):2530–2539. 12.
  • Lee HS, Barraza-Villarreal A, Hernandez-Vargas H, et al. Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study. Am J Clin Nutr. 2013;98(2):480–487.
  • Zugna D, Galassi C, Annesi-Maesano I, et al. Maternal complications in pregnancy and wheezing in early childhood: a pooled analysis of 14 birth cohorts. Int J Epidemiol. 2015;44(1):199–208.
  • Huang L, Chen Q, Zhao Y, et al. Is elective cesarean section associated with a higher risk of asthma? A meta-analysis. J Asthma. 2015;52(1):16–25.
  • Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–11975.
  • Azad MB, Konya T, Persaud RR, et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG. 2016;123(6):983–993.
  • Almqvist C, Cnattingius S, Lichtenstein P, et al. The impact of birth mode of delivery on childhood asthma and allergic diseases–a sibling study. Clin Exp Allergy. 2012;42(9):1369–1376.
  • Oddy WH, Sly PD, De Klerk NH, et al. Breast feeding and respiratory morbidity in infancy: a birth cohort study. Arch Dis Child. 2003;88(3):224–228.
  • Dogaru CM, Nyffenegger D, Pescatore AM, et al. Breastfeeding and childhood asthma: systematic review and meta-analysis. Am J Epidemiol. 2014;179(10):1153–1167.
  • Tager IB, Ngo L, Hanrahan JP. Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life. Am J Respir Crit Care Med. 1995;152(3):977–983.
  • Hollams EM, De Klerk NH, Holt PG, et al. Persistent effects of maternal smoking during pregnancy on lung function and asthma in adolescents. Am J Respir Crit Care Med. 2014;189(4):401–407.
  • Gilliland FD, Berhane K, McConnell R, et al. Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function. Thorax. 2000;55(4):271–276.
  • Gilliland FD, Berhane K, Li YF, et al. Effects of early onset asthma and in utero exposure to maternal smoking on childhood lung function. Am J Respir Crit Care Med. 2003;167(6):917–924.
  • Young S, Arnott J, O’Keeffe PT, et al. The association between early life lung function and wheezing during the first 2 yrs of life. Eur Respir J. 2000;15(1):151–157.
  • Elliot J, Carroll N, Bosco M, et al. Increased airway responsiveness and decreased alveolar attachment points following in utero smoke exposure in the guinea pig. Am J Respir Crit Care Med. 2001;163(1):140–144.
  • Stevenson MD, Mansbach JM, Mowad E, et al. Prenatal versus postnatal tobacco smoke exposure and intensive care use in children hospitalized with Bronchiolitis. Acad Pediatr. 2016;16(5):446–452.
  • Stein RT, Holberg CJ, Sherrill D, et al. Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson children’s respiratory study. Am J Epidemiol. 1999;149(11):1030–1037.
  • Lannerö E, Wickman M, Pershagen G, et al. Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (BAMSE). Respir Res. 2006;7(1):3.
  • Strachan DP, Cook DG. Health effects of passive smoking. 1. Parental smoking and lower respiratory illness in infancy and early childhood. Thorax. 1997;52(10):905–914.
  • Cook DG, Strachan DP. Health effects of passive smoking. 3. Parental smoking and prevalence of respiratory symptoms and asthma in school age children. Thorax. 1997;52(12):1081–1094.
  • Strachan DP, Cook DG. Health effects of passive smoking. 6. Parental smoking and childhood asthma: longitudinal and case-control studies. Thorax. 1998;53(3):204–212.
  • Sekhon HS, Keller JA, Proskocil BJ, et al. Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung. Association with alpha7 nicotinic acetylcholine receptors. Am J Respir Cell Mol Biol. 2002;26(1):31–41.
  • Wongtrakool C, Wang N, Hyde DM, et al. Prenatal nicotine exposure alters lung function and airway geometry through α7 nicotinic receptors. Am J Respir Cell Mol Biol. 2012;46(5):695–702.
  • Elliot JG, Carroll NG, James AL, et al. Airway alveolar attachment points and exposure to cigarette smoke in utero. Am J Respir Crit Care Med. 2003;167(1):45–49.
  • Collins MH, Moessinger AC, Kleinerman J, et al. Fetal lung hypoplasia associated with maternal smoking: a morphometric analysis. Pediatr Res. 1985;19(4):408–412.
  • Wongtrakool C, Grooms K, Bijli KM, et al. Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism. PLoS One. 2014;9(10):e109602.
  • Maritz GS, Woolward K. Effect of maternal nicotine exposure on neonatal lung elastic tissue and possible consequences. S Afr Med J. 1992;81(10):517–519.
  • Fu XW, Wood K, Spindel ER. Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium. Am J Respir Cell Mol Biol. 2011;44(2):222–229.
  • Rona RJ, Gulliford MC, Chinn S. Effects of prematurity and intrauterine growth on respiratory health and lung function in childhood. BMJ. 1993;306(6881):817–820.
  • Urs R, Kotecha S, Hall GL, et al. Persistent and progressive long-term lung disease in survivors of preterm birth. Paediatr Respir Rev. 2018;28:87–94.
  • Wongtrakool C, Grooms K, Xd P, et al. In utero nicotine exposure promotes M2 activation in neonatal mouse alveolar macrophages. Pediatr Res. 2012;72(2):147–153.
  • Devereux G, Barker RN, Seaton A. Antenatal determinants of neonatal immune responses to allergens. Clin Exp Allergy. 2002;32(1):43–50.
  • Noakes PS, Hale J, Thomas R, et al. Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses. Eur Respir J. 2006;28(4):721–729.
  • Hinz D, Bauer M, Röder S, et al. Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year. Allergy. 2012;67(3):380–389.
  • Spindel ER, McEvoy CT. The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease. Implications for dangers of E-cigarettes. Am J Respir Crit Care Med. 2016;193(5):486–494.
  • Cook DG, Strachan DP. Health effects of passive smoking-10: summary of effects of parental smoking on the respiratory health of children and implications for research. Thorax. 1999;54(4):357–366.
  • Li S, Williams G, Jalaludin B, et al. Panel studies of air pollution on children’s lung function and respiratory symptoms: a literature review. J Asthma. 2012;49(9):895–910.
  • Rojas-Martinez R, Perez-Padilla R, Olaiz-Fernandez G, et al. Lung function growth in children with long-term exposure to air pollutants in Mexico city. Am J Respir Crit Care Med. 2007;176(4):377–384.
  • Gauderman WJ, Avol E, Gilliland F, et al. The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med. 2004;351(11):1057–1067.
  • Rice MB, Rifas-Shiman SL, Litonjua AA, et al. Lifetime exposure to ambient pollution and lung function in children. Am J Respir Crit Care Med. 2016;193(8):881–888.
  • Andersen ZJ, Loft S, Ketzel M, et al. Ambient air pollution triggers wheezing symptoms in infants. Thorax. 2008;63(8):710–716.
  • Mölter A, Simpson A, Berdel D, et al. A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project. Eur Respir J. 2015;45(3):610–624.
  • Khreis H, Kelly C, Tate J, et al. Exposure to traffic-related air pollution and risk of development of childhood asthma: a systematic review and meta-analysis. Environ Int. 2017;100:1–31.
  • Holst GJ, Pedersen CB, Thygesen M, et al. Air pollution and family related determinants of asthma onset and persistent wheezing in children: nationwide case-control study. BMJ. 2020;370:m2791.
  • Norbäck D, Lu C, Zhang Y, et al. Sources of indoor particulate matter (PM) and outdoor air pollution in China in relation to asthma, wheeze, rhinitis and eczema among pre-school children: synergistic effects between antibiotics use and PM(10) and second hand smoke. Environ Int. 2019;125:252–260.
  • Heinzerling AP, Guarnieri MJ, Mann JK, et al. Lung function in woodsmoke-exposed guatemalan children following a chimney stove intervention. Thorax. 2016;71(5):421–428.
  • Morales E, Garcia-Esteban R, De La Cruz OA, et al. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age. Thorax. 2015;70(1):64–73.
  • Hsu HH, Chiu YH, Coull BA, et al. Prenatal particulate air pollution and asthma onset in urban children. Identifying sensitive windows and sex differences. Am J Respir Crit Care Med. 2015;192(9):1052–1059.
  • Deng Q, Lu C, Li Y, et al. Exposure to outdoor air pollution during trimesters of pregnancy and childhood asthma, allergic rhinitis, and eczema. Environ Res. 10 2016;150: 119–127.
  • Kerkhof M, Postma DS, Brunekreef B, et al. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma. Thorax. 2010;65(8):690–697.
  • MacIntyre EA, Brauer M, Melén E, et al. GSTP1 and TNF Gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) study. Environ Health Perspect. 2014;122(4):418–424.
  • Gref A, Merid SK, Gruzieva O, et al. Genome-Wide interaction analysis of air pollution exposure and childhood Asthma with functional follow-up. Am J Respir Crit Care Med. 2017;195(10):1373–1383.
  • Esposito S, Tenconi R, Lelii M, et al. Possible molecular mechanisms linking air pollution and asthma in children. BMC Pulm Med. 2014;14(1):31.
  • Wang B, Chen H, Chan YL, et al. Why do intrauterine exposure to air pollution and cigarette smoke increase the risk of Asthma? Front Cell Dev Biol. 2020;8:38.
  • Sly PD, Boner AL, Björksten B, et al. Early identification of atopy in the prediction of persistent asthma in children. Lancet. 2008;372(9643):1100–1106.
  • Lloyd CM, Saglani S. Development of allergic immunity in early life. Immunol Rev. 2017;278(1):101–115.
  • Jackson DJ, Gangnon RE, Evans MD, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178(7):667–672.
  • Illi S, Von Mutius E, Lau S, et al. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet. 2006;368(9537):763–770.
  • Lynch SV, Wood RA, Boushey H, et al., Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. J Allergy Clin Immunol. 134(3): 593–601.e12. 2014.
  • Stern DA, Guerra S, Halonen M, et al. Low IFN-gamma production in the first year of life as a predictor of wheeze during childhood. J Allergy Clin Immunol. 2007;120(4):835–841.
  • Singh AM, Moore PE, Gern JE, et al. Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. Am J Respir Crit Care Med. 2007;175(2):108–119.
  • Henderson J, Hilliard TN, Sherriff A, et al. Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: a longitudinal birth cohort study. Pediatr Allergy Immunol. 2005;16(5):386–392.
  • Wu P, Dupont WD, Griffin MR, et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am J Respir Crit Care Med. 2008;178(11):1123–1129.
  • Thomsen SF, Van Der Sluis S, Stensballe LG, et al. Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study. Am J Respir Crit Care Med. 2009;179(12):1091–1097.
  • Brunwasser SM, Snyder BM, Driscoll AJ, et al. Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis. Lancet Respir Med. 2020;8(8):795–806.
  • Scheltema NM, Nibbelke EE, Pouw J, et al. Respiratory syncytial virus prevention and asthma in healthy preterm infants: a randomised controlled trial. Lancet Respir Med. 2018;6(4):257–264.
  • Mochizuki H, Kusuda S, Okada K, et al. Palivizumab prophylaxis in preterm infants and subsequent recurrent wheezing. Six-year follow-up study. Am J Respir Crit Care Med. 2017;196(1):29–38.
  • Simoes EA, Groothuis JR, Carbonell-Estrany X, et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr. 2007;151(1):34–42. 42.e1.
  • Culley FJ, Pollott J, Openshaw PJM. Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood. J Exp Med. 2002;196(10):1381–1386.
  • Korppi M, Kotaniemi-Syrjänen A, Waris M, et al. Rhinovirus-associated wheezing in infancy: comparison with respiratory syncytial virus bronchiolitis. Pediatr Infect Dis J. 2004;23(11):995–999.
  • Jartti T, Gern JE. Rhinovirus-associated wheeze during infancy and asthma development. Curr Respir Med Rev. 2011;7(3):160–166.
  • Lemanske Jr. RF, Jackson DJ, Gangnon RE, et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. 2005;116(3):571–577.
  • Van Der Gugten AC, Van Der Zalm MM, Uiterwaal CS, et al. Human rhinovirus and wheezing: short and long-term associations in children. Pediatr Infect Dis J. 2013;32(8):827–833.
  • Jackson DJ, Evans MD, Gangnon RE, et al., Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life. Am J Respir Crit Care Med. 185(3): 281–285. 2012.
  • Kusel MM, De Klerk NH, Kebadze T, et al. Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol. 2007;119(5):1105–1110.
  • Moffatt MF, Kabesch M, Liang L, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448(7152):470–473.
  • Papadopoulos NG, Stanciu LA, Papi A, et al. A defective type 1 response to rhinovirus in atopic asthma. Thorax. 2002;57(4):328–332.
  • Holt PG, Strickland DH, Hales BJ, et al. Defective respiratory tract immune surveillance in asthma: a primary causal factor in disease onset and progression. Chest. 2014;145(2):370–378.
  • De Schutter I, Dreesman A, Soetens O, et al. In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis. BMC. Pediatr. 2012;12(1):83.
  • Bacharier LB, Guilbert TW, Mauger DT, et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial. JAMA. 2015;314(19):2034–2044.
  • Stokholm J, Chawes BL, Vissing NH, et al. Azithromycin for episodes with asthma-like symptoms in young children aged 1–3 years: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2016;4(1):19–26.
  • Mandhane PJ, P PZDS, Yn A, et al. Treatment of preschool children presenting to the emergency department with wheeze with azithromycin: a placebo-controlled randomized trial. PLoS One. 2017;12(8):e0182411.
  • Bush A. Azithromycin is the answer in paediatric respiratory medicine, but what was the question? Paediatr Respir Rev. 2020;34:67–74.
  • Teo SM, Mok D, Pham K, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17(5):704–715.
  • Teo SM, Tang HHF, Mok D, et al., Airway microbiota dynamics uncover a critical window for interplay of pathogenic bacteria and Allergy in childhood respiratory disease. Cell Host Microbe. 24(3): 341–352. 2018.
  • Bosch AATM, Waa DSP, Van Houten MA, et al. Maturation of the infant respiratory microbiota, environmental drivers, and health consequences. A prospective cohort study. Am J Respir Crit Care Med. 2017;196(12):1582–1590.
  • Bisgaard H, Hermansen MN, Buchvald F, et al. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med. 2007;357(15):1487–1495.
  • Brealey JC, Sly PD, Young PR, et al. Viral bacterial co-infection of the respiratory tract during early childhood. FEMS Microbiol Lett. 2015;362(10):10.
  • Genuneit J. Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis. Pediatr Allergy Immunol. 2012;23(6):509–518.
  • Von Mutius E, Vercelli D. Farm living: effects on childhood asthma and allergy. Nat Rev Immunol. 2010;10(12):861–868.
  • Alfvén T, Braun-Fahrländer C, Brunekreef B, et al. Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle–the PARSIFAL study. Allergy. 2006;61(4):414–421.
  • Genuneit J, Büchele G, Waser M, et al. The GABRIEL advanced surveys: study design, participation and evaluation of bias. Paediatr Perinat Epidemiol. 2011;25(5):436–447.
  • Ege MJ, Mayer M, Normand A-C, et al. Exposure to environmental microorganisms and childhood Asthma. N Engl J Med. 2011;364(8):701–709.
  • Ober C, Sperling AI, Von Mutius E, et al. Immune development and environment: lessons from Amish and Hutterite children. Curr Opin Immunol. 2017;48:51–60.
  • Stein MM, Hrusch CL, Gozdz J, et al., Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N Engl J Med. 375(5): 411–421. 2016.
  • Eder W, Klimecki W, Yu L, et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol. 2004;113(3):482–488.
  • Saglani S, Gregory LG, Manghera AK, et al. Inception of early-life allergen-induced airway hyperresponsiveness is reliant on IL-13. Sci Immunol. 2018;3(27):27.
  • Rossi GA, Pohunek P, Feleszko W, et al. Viral infections and wheezing-asthma inception in childhood: is there a role for immunomodulation by oral bacterial lysates? Clin Transl Allergy. 2020;10(1):17.
  • Russell SL, Gold MJ, Hartmann M, et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 2012;13(5):440–447.
  • Thorburn AN, McKenzie CI, Shen S, et al. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat Commun. 2015;6(1):7320.
  • McKenzie C, Tan J, Macia L, et al. The nutrition-gut microbiome-physiology axis and allergic diseases. Immunol Rev. 2017;278(1):277–295.
  • Olin A, Henckel E, Chen Y, et al. Stereotypic immune system development in newborn Children. Cell. 2018;174(5):1277–1292.