Characterisation of atopic and non-atopic wheeze in 10 year old children Association between Chlamydia pneumoniae antibodies and wheezing in young children and the influence of sex Smoking and the incidence of asthma during adolescence: results of a large cohort study in Germany Heightened bronchial hyperresponsiveness in the absence of heightened atopy in children with current wheezing and low income status Farming environments and childhood atopy, wheeze, lung function, and exhaled nitric oxide. Atopic sensitization and the international variation of asthma symptom prevalence in children. Infant feeding, wheezing, and allergy: a prospective study. Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey The effects of respiratory infections, atopy, and breastfeeding on childhood asthma Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years Moisture damage and childhood asthma: a population-based incident case–control study Season of Birth and Risk of Atopic Disease among Children and Adolescents Dampness and moulds in relation to respiratory and allergic symptoms in children: results from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two) Exposure to Air Pollution from Traffic and Childhood Asthma Until 12 Years of Age Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13.
Background : Wheezing occurs in both atopic and non-atopic children . The characteristics of atopic and non-atopic wheeze in children at 10 years of age were assessed and attempts made to identify whether different mechanisms underlie these states . Methods : Children were seen at birth and at 1 , 2 , 4 and 10 years of age in a whole population birth cohort study ( n = 1456 ; 1373 seen at 10 years ) . Information was collected prospect ively on inherited and early life environmental risk factors for wheezing . Skin prick testing , spirometry , and methacholine bronchial challenge were conducted at 10 years . Wheezing at 10 years of age was considered atopic or non-atopic depending on the results of the skin prick test . Independent significant risk factors for atopic and non-atopic wheeze were determined by logistic regression . Results : Atopic ( 10.9 % ) and non-atopic ( 9.7 % ) wheeze were equally common at 10 years of age . Greater bronchial hyperresponsiveness ( p<0.001 ) and airways obstruction ( p = 0.011 ) occurred in children with atopic wheeze than in those with non-atopic wheeze at 10 years . Children with atopic wheeze more often received treatment ( p<0.001 ) or an asthma diagnosis for their disorder , although current morbidity at 10 years differed little for these states . Maternal asthma and recurrent chest infections at 2 years were independently significant factors for developing non-atopic wheeze . For atopic wheeze , sibling asthma , eczema at 1 year , rhinitis at 4 years , and male sex were independently significant . Conclusions : Non-atopic wheeze is as common as atopic wheeze in children aged 10 years , but treatment is more frequent in those with atopic wheeze . Different risk factor profiles appear relevant to the presence of atopic and non-atopic wheeze at 10 years of age Background : The proposed association between Chlamydia pneumoniae ( Cpn ) infection and  wheezing  needs further clarification . Methods : Serum sample s obtained from 1581 children aged 4 years in a population based cohort were tested for antibodies to Cpn and IgE antibodies to common allergens . Data on environmental factors and disease were collected prospect ively from birth . Results : The occurrence of IgG antibodies to Cpn at 4 years of age was associated with reported wheezing at different ages ; however , these findings were most often not significant . In girls , the occurrence of anti-Cpn IgG was associated with wheezing at the ages of 1 , 2 , and 4 years ( odds ratios ( ORs ) 3.41 ( 95 % confidence interval ( CI ) 1.46 to 7.96 ) , 2.13 ( 95 % CI 1.02 to 4.44 ) , and 2.01 ( 95 % CI 1.14 to 3.54 ) , respectively ) , and even higher ORs were observed for each age category when only high level antibody responses to Cpn were analysed . At the time of blood sampling the association between anti-Cpn IgG and wheezing was restricted to girls without atopic sensitisation ( OR 2.39 ( 95 % CI 1.25 to 4.57 ) . No associations with wheezing were detected in boys , in whom IgE sensitisation was inversely associated with the presence of anti-Cpn IgG ( OR 0.49 ( 95 % CI 0.26 to 0.90 ) . Conclusions : This study suggests an association between evidence of earlier Cpn infection and a history of wheezing in young girls . Infection with Cpn may be an important risk factor for wheezing and possibly for non-atopic asthma , predominantly in girls Background : The association between smoking and asthma or wheeze has been extensively studied in cross sectional studies , but evidence from large prospect i ve cohort studies on the incidence of asthma during adolescence is scarce . Methods : We report data from a cohort study in two German cities , Dresden and Munich . The study population ( n = 2936 ) was first studied in 1995/6 at age 9–11 years as part of phase II of the International Study of Asthma and Allergies in Childhood ( ISAAC II ) and followed up in 2002/3 . At baseline the parents completed a question naire and children underwent clinical examination and blood sampling . At follow up the young adults completed question naires on respiratory health , living , and exposure conditions . Incidence risk ratios ( IRR ) were calculated and adjusted for potential confounders using a modified Poisson regression approach . Results : The adjusted IRR for incident wheeze for active smokers compared with non-smokers was 2.30 ( 95 % confidence interval ( CI ) 1.88 to 2.82 ) . The adjusted IRR was slightly higher for incident wheeze without a cold ( 2.76 , 95 % CI 1.99 to 3.84 ) and the incidence of diagnosed asthma ( 2.56 , 95 % CI 1.55 to 4.21 ) . Analysis of duration and intensity of active smoking indicated dose dependent associations . Stratified analyses showed that the risk of incident wheeze without a cold in atopic smokers increased with decreasing plasma α1-antitrypsin levels at baseline ( 1.64 , 95 % CI 1.22 to 2.20 per interquartile range ) . Conclusions : Active smoking is an important risk factor for the incidence of asthma during adolescence . Relatively lower plasma levels of α1-antitrypsin , although well above currently accepted thresholds , may increase susceptibility to respiratory disease among atopic smokers Background : Although global studies such as the International Study of Asthma and Allergies in Childhood ( ISAAC ) have provided valuable data on the prevalence of asthma in children in Latin America , there is little information on the relationship between asthma symptoms , pulmonary function , bronchial hyperresponsiveness ( BHR ) and atopy in the region . Methods : This study examined the relationship between  self-reported wheezing in the past 12 months , pulmonary function , airway responsiveness and atopy in children from a low income population in a neighbourhood of Santiago , Chile . Two r and om sample s ( 100 each ) of children aged 13–14 years who participated in ISAAC phase I were selected according to whether or not they reported wheezing in the past 12 months .  Spirometry , the methacholine bronchial challenge test and the prick test  were performed in all individuals . Results : Children who reported current wheezing had significantly higher BHR to methacholine compared with those without wheezing ( 71.6 % vs 52.6 % ; p = 0.007 ) and no significant difference was found in forced expiratory volume in 1 s ( 116.7 (12.3)% vs 120.3 ( 14.5 % ) ; p = 0.11 ) . The prevalence of atopy was not significantly different between those children who reported wheezing compared with those who did not ( 44.2 % vs 42.3 % ; p = 0.89 ) . Multiple regression analysis showed that only BHR to methacholine ( OR 2.72 , 95 % CI 1.25 to 4.13 ; p = 0.01 ) and maternal asthma ( OR 3.1 , 95 % CI 1.2 to 8.3 , p = 0.03 ) were significant risk factors for current wheezing . Conclusions : Our results support previous findings suggesting that in adolescents from underprivileged population s , self-reported current wheezing is related to BHR but not to atopy BACKGROUND Previous studies have demonstrated that children raised on farms are protected from asthma and allergies . It is unknown whether the farming effect is solely mediated by atopy or also affects nonatopic wheeze phenotypes . OBJECTIVE We sought to study the farm effect on wheeze phenotypes and objective markers , such as lung function and exhaled nitric oxide , and their interrelation with atopy in children . METHODS The GABRIEL Advanced Studies are cross-sectional , multiphase , population -based surveys of the farm effect on asthma and allergic disease in children aged 6 to 12 years . Detailed data on wheeze , farming exposure , and IgE levels were collected from a r and om sample of 8023 children stratified for farm exposure . Of those , another r and om sub sample of 858 children was invited for spirometry , including bronchodilator tests and exhaled nitric oxide measurements . RESULTS We found effects of exposure to farming environments on the prevalence and degree of atopy , on the prevalence of transient wheeze ( adjusted odds ratio , 0.78 ; 95 % CI , 0.64 - 0.96 ) , and on the prevalence of current wheeze among nonatopic subjects ( adjusted odds ratio , 0.45 ; 95 % CI , 0.32 - 0.63 ) . There was no farm effect on lung function and exhaled nitric oxide levels in the general study population . CONCLUSIONS Children living on farms are protected against wheeze independently of atopy . This farm effect is not attributable to improved airway size and lung mechanics . These findings imply as yet unknown protective mechanisms . They might include alterations of immune response and susceptibility to triggers of wheeze , such as viral infections RATIONALE Atopic sensitization has long been known to be related to asthma in children , but its role in determining asthma prevalence remains to be eluci date d further . OBJECTIVES To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma . METHODS Cross-sectional studies of r and om sample s of 8- to 12-year-old children ( n = 1,000 per center ) were performed according to the st and ardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood ( ISAAC ) . Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions , from rural Africa to urban Europe . Data were collected by parental question naires ( n = 54,439 ) , skin prick tests ( n = 31,759 ) , and measurements of allergen-specific IgE levels in serum ( n = 8,951 ) . Economic development was assessed by gross national income per capita ( GNI ) . MEASUREMENTS AND MAIN RESULTS The prevalence of current wheeze ( i.e. , during the past year ) ranged from 0.8 % in Pichincha ( Ecuador ) to 25.6 % in Uruguaiana ( Brazil ) . The fraction of current wheeze attributable to atopic sensitization ranged from 0 % in Ankara ( Turkey ) to 93.8 % in Guangzhou ( China ) . There were no correlations between prevalence rates of current wheeze and atopic sensitization , and only weak correlations of both with GNI . However , the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI ( Spearman rank-order coefficient rho = 0.50 , P = 0.006 , and rho = 0.74 , P < 0.0001 , respectively ) . In addition , the strength of the association between current wheeze and skin test reactivity , assessed by odds ratios , increased with GNI ( rho = 0.47 , P = 0.01 ) . CONCLUSIONS The link between atopic sensitization and asthma symptoms in children differs strongly between population s and increases with economic development The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease . A r and omised controlled trial examined the effects of withholding cows ' milk protein during the first three months of life and replacing cows ' milk with soya milk . The children were followed up to the age of 7 years . Withholding cows ' milk did not reduce the incidence of allergy or wheezing . Children who had ever been breast fed had a lower incidence of wheeze than those who had not ( 59 % and 74 % respectively ) . The effect persisted to age 7 years in the non-atopics only , the risk of wheeze being halved in the breast fed children after allowing for employment status , sex passive smoking , and overcrowding . Allergic disease was not associated with exposure to tobacco smoke , house dust mite antigen , or cats . Breast feeding may confer long term protection against respiratory infection The association between  breastfeeding and wheezing , lung function and atopy  was evaluated in the International Study of Asthma and Allergy in Childhood ( ISAAC ) Phase II . Cross-sectional studies were performed in 27 centres in 20 countries . Information on disease and exposure factors was collected by parental question naires . Data from 54,000 r and omly selected school children ( aged 8–12 yrs , 31,759 with skin prick testing ) and a stratified sub sample ( n = 4,888 ) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function . R and om effect models for meta- analysis were applied to calculate combined odds ratios ( ORs ) . Any breastfeeding was associated with less wheeze both in affluent ( adjusted OR ( ORadj ) 0.87 , 95 % confidence interval ( CI ) 0.78–0.97 ) and nonaffluent countries ( ORadj 0.80 , 95 % CI 0.68–0.94 ) . Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries ( ORadj 0.69 , 95 % CI 0.53–0.90 ) . Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries . In contrast , breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only ( mean ratio 1.11 , 95 % CI 1.02–1.20 ) . Breastfeeding is associated with protection against nonatopic wheeze , which becomes particularly evident in nonaffluent countries . Overall , breastfeeding was not related to any measure of allergy . These findings may explain some of the controversy regarding breastfeeding , since the direction of the association with breastfeeding depends on the predominating wheeze phenotype ( e.g. atopic , nonatopic ) BACKGROUND A farming environment protects against development of  asthma , hay fever , and atopic sensitisation in children . We aim ed to establish whether increased exposure to microbial compounds has to occur early in life to affect maturation of the immune system and thereby reduces risk for development of allergic diseases . METHODS We did a cross-sectional survey in rural areas of Austria , Germany , and Switzerl and . 2618 ( 75 % ) of 3504 parents of 6 - 13-year-old children completed a st and ardised question naire on asthma , hay fever , and atopic eczema . Children from farming families , and a r and om sample of non-farmers ' children , who gave consent for blood sample s to be obtained for measurements of specific serum IgE antibodies to common allergens were invited to participate ( n=901 ) . FINDINGS Exposure of children younger than 1 year , compared with those aged 1 - 5 years , to stables and consumption of farm milk was associated with lower frequencies of asthma ( 1 % [ 3/218 ] vs 11 % [ 15/138 ] ) , hay fever ( 3 % [ 7 ] vs 13 % [ 18 ] ) , and atopic sensitisation ( 12 % [ 27 ] vs 29 % [ 40 ] ) . Protection against development of asthma was independent from effect on atopic sensitisation . Continual long-term exposure to stables until age 5 years was associated with the lowest frequencies of asthma ( 0.8 % [ 1/122 ] ) , hay fever ( 0.8 % [ 1 ] ) , and atopic sensitisation ( 8.2 % [ 10 ] ) . INTERPRETATION Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma , hay fever , and atopic sensitisation The objectives of the present study were to quantify the association of atopy and respiratory infections with asthma , and exclusive breastfeeding with  respiratory illness , atopy and asthma in children . A cohort study of 2,602 children enrolled prior to birth and followed prospect ively , provided data on respiratory illness , the method of feeding in the first year of life , as reported on a prospect i ve diary card , and current asthma at the age of 6 yrs ( defined as doctor-diagnosed asthma with wheeze in the last year or cough without a cold , and currently taking either preventer or reliever asthma medication ) , as reported by parental question naire .  Atopy  was defined by a positive skin-prick test assessed at the age of 6 yrs . Wheezing lower respiratory illness ( LRI ) in the first year of life , particularly multiple episodes of wheezing LRI , increased the risk for current asthma in both nonatopic ( odds ratio ( OR ) 4.10 , p⪕0.0005 ) and atopic children ( OR 9.00 , p⪕0.0005 ) , but did not increase the risk for atopy . In contrast , up to three upper respiratory tract infections demonstrated a negative association and four or more a positive risk for current asthma in unadjusted ( p=0.006 ) and adjusted ( p=0.057 ) analysis . Following adjustment , exclusive breastfeeding for < 4 months was associated with an increased risk for current asthma ( OR 1.36 , 95 % confidence interval 1.00–1.85 , p=0.047 ) . Wheezing lower respiratory illness in the first year of life and atopy are independently associated with increased risk for current asthma at the age of 6 yrs , suggesting that their effects are mediated via different causal pathways and that these risk factors are multiplicative when they operate concomitantly within individual children . Exclusive breastfeeding protects against asthma via effects on both these pathways , as well as through other as yet undefined mechanisms The role of repeated infections early in life in the development of childhood asthma and allergies has not been clarified . The aim of this study was to investigate the effect of repeated episodes of fever and antibiotic treatments during the first years of life on the prevalence of asthma , bronchial hyperresponsiveness ( BHR ) , and atopy at school age in a representative population . R and om sample s of schoolchildren aged 5 - 7 yrs ( n=7,545 ) and 9 - 11 yrs ( n=7,498 ) were studied using the International Study of Asthma and Allergies in Childhood ( ISAAC ) phase II protocol . To assess the prevalence of disease and early childhood exposures , parental question naires were administered ( response rates 82.2 % and 85.3 % , respectively ) . In addition , children underwent skin prick tests , hypertonic saline challenge and blood sampling for the measurement of serum immunoglobulin (Ig)E. Repeated episodes of fever and antibiotic treatment in early life were strongly associated with the prevalence of asthma ( odds ratio (OR)=7.95 ; 95 % confidence interval ( CI ) 6.02 - 10.50 ) and current wheeze at school age . Within asthmatic children the number of fever episodes and antibiotic courses were strongly inversely related to the prevalence of atopy ( OR=0.25 ; 95 % CI 0.11 - 0.54 for skin test reactivity ) and BHR ( OR=0.31 ; 95 % CI 0.10 - 0.92 ) . Furthermore , asthmatic children with recurrent early childhood infections were at a lower risk of being symptomatic at school age . When considering atopic and nonatopic asthmatic children separately , the highest risk of asthma with repeated early childhood infections was found for nonatopic asthma ( OR=24.29 ; 95 % Cl 11.86 - 49.76 ) . These findings suggest that a subgroup of children with a triggering or inducing of asthmatic symptoms through repeated early childhood infections exists within the " asthma syndrome " which has a better prognosis and is less related to the atopic phenotype BACKGROUND The relation between lower respiratory tract illnesses in early life caused by the respiratory syncytial virus ( RSV ) and the subsequent development of wheezing and atopy in childhood is not well understood . We studied this relation in children who had lower respiratory tract illnesses that occurred before 3 years of age . METHODS Children were enrolled at birth and cases of lower respiratory tract illness were ascertained by a physician . Viral tests were done for specimens collected at the time of the illness . Children were classified into five groups according to type and cause of lower respiratory tract illness . Children were then followed prospect ively up to age 13 , and we measured frequency of wheezing , pulmonary function , and atopic status ( allergy skin-prick tests , serum IgE concentrations ) . FINDINGS RSV lower respiratory tract illnesses were associated with an increased risk of infrequent wheeze ( odds ratio 3.2 [ 95 % CI 2.0 - 5.0 ] , p < 0.001 ) , and an increased risk of frequent wheeze ( 4.3 [ 2.2 - 8.7 ] , p < or = 0.001 ) by age 6 . Risk decreased markedly with age and was not significant by age 13 . There was no association between RSV lower respiratory tract illnesses and subsequent atopic status . RSV lower respiratory tract illnesses were associated with significantly lower measurements of forced expiratory volume ( 2.11 [ 2.05 - 2.15 ] , p < or = 0.001 ) when compared with those of children with no lower respiratory tract illnesses , but there was no difference in forced expiratory volume after inhalation of salbutamol . INTERPRETATION RSV lower respiratory tract illnesses in early childhood are an independent risk factor for the subsequent development of wheezing up to age 11 years but not at age 13 . This association is not caused by an increased risk of allergic sensitisation Most previous studies on the association between moisture damage and asthma have been cross-sectional and relied on self-reported exposure and health . The present authors studied the association by carrying out careful home inspections among new , clinical ly determined cases of asthma and controls . New cases of asthma aged 12–84 months ( n = 121 ) were recruited prospect ively and matched for year of birth , sex and living area with two r and omly selected population controls ( n = 241 ) . Trained engineers visited all homes . Both cases and controls had lived ≥75 % of their lifetime or the past 2 yrs in their current home . Risk of asthma increased with severity of moisture damage and presence of visible mould in the main living quarters but not in other areas of the house . Cases more often had damage in their bedroom . Associations were comparable for atopic and nonatopic asthma and for children aged > 30 months or ≤30 months . The present results , using st and ardised assessment of exposure and asthma , suggest that moisture damage and mould growth in the main living quarters are associated with the development of asthma in early childhood Background . Season of birth ( SOB ) has been regarded as a risk factor for atopy . The aim of this study was to explore the relationship between season of birth ( SOB ) and later development of atopic disease in children and adolescents . Methods . A total of 1,007 r and omly selected subjects , 7 to 17 years of age , who were living in urban Copenhagen , Denmark were studied . All participants were interviewed about respiratory symptoms and possible risk factors for atopic disease . Skin test reactivity , serum total immunoglobulin E ( IgE ) , and airway responsiveness were measured using st and ard techniques . Results . The overall risk of atopy , as judged by skin test reactivity and serum total IgE , was the same regardless of SOB . On the contrary , asthma was more common in subjects born in the autumn compared with subjects born during the remaining part of the year ( 12.4 % vs. 5.6 % ) , OR = 2.40 , 95 % CI ( 1.56–3.94 ) , p < 0.001 . This was observed both for atopic asthma OR = 2.41 , 95 % CI ( 1.25–4.64 ) , p = 0.007 , non-atopic asthma , OR = 2.35 , 95 % CI ( 1.14–4.83 ) , p = 0.02 , and house dust mite ( HDM ) sensitive airway hyperresponsiveness , OR = 3.00 , 95 % CI ( 1.44–6.24 ) , p = 0.002 . Rhinitis and pollen allergy were not significantly related to SOB . Conclusions . Atopy itself is independent of season of birth , whereas asthma is more prevalent among subjects born during the autumn . Regarding asthma , these results suggest that the first months of life enclose a period of particular vulnerability towards environmental risk factors , especially exposure to aeroallergens like HDM Many studies report that damp housing conditions are associated with respiratory symptoms . Less is known about mechanisms and possible effect modifiers . Studies of dampness in relation to allergic sensitization and eczema  are scarce Background : There are limited prospect i ve data on long-term exposure to air pollution and effects on  childhood respiratory morbidity .  We investigated the development of asthma and related symptoms longitudinally over the first 12 years of life in relation to air pollution from road traffic . Methods : The Swedish birth cohort BAMSE ( Children , Allergy , Milieu , Stockholm , Epidemiological Survey ) includes 4089 children who were followed up with repeated question naires and blood sample s for up to 12 years of age . Residential , daycare , and school addresses , time-activity patterns , emission data bases , and dispersion models were used to estimate individual exposure to particulate matter with aerodynamic diameter < 10 & mgr;m ( PM10 ) and nitrogen oxides ( NOx ) from traffic . Results : Overall , the data suggested possible associations between exposure to air pollution during the first year of life and  asthma and wheezing  in children up to 12 years of age . Asthma risks seemed to be particularly increased in children age 8 to 12 years ; the overall odds ratio was 2.0 ( 95 % confidence interval = 1.1–3.5 ) , and for nonallergic asthma , the odds ratio was 3.8 ( 0.9–16.2 ) for a 5th to 95th percentile increase in time-weighted average exposure to PM10 ( corresponding to 7.2 µg/m3 ) . Results were similar using exposure to traffic-NOx . Conclusions : We found modest positive associations between air pollution exposure from traffic during infancy and  asthma  in children during the first 12 years of life , with stronger effects suggested for nonallergic asthma We have prospect ively studied  wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus ( RSV ) bronchiolitis in infancy and 93 matched control subjects . Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified . Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects .  Wheezing disorder and clinical allergy were estimated using a question naire .  Skin prick tests  were performed and  serum IgE antibodies  measured .  Spirometry  was undertaken at rest , after dry air challenge , and after beta2-agonist inhalation . The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects , 43 % versus 8 % for asthma/recurrent wheezing and 39 % versus 15 % for allergic rhinoconjunctivitis . Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects , judged by skin prick tests ( 50 % versus 28 % ; p = 0.022 ) , or by serum IgE antibodies ( 45 % versus 26 % ; p = 0.038 ) . Compared with the control subjects , the RSV group showed mild airway obstruction both at rest and after bronchodilation , and had slightly more reactive airways . RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence
Background The study of non-atopic asthma/wheeze in children separately from atopic asthma is relatively recent .
Studies have focused on single risk factors and had inconsistent findings .
Objective To review evidence on factors associated with non-atopic asthma/wheeze in children and adolescents .