human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    