allergic diseases are among the most common chronic diseases throughout the world   and the prevalence of atopic diseases in childhood has significantly increased during the past several decades [ 2 , 3 ] .
although there is a general consensus on the importance of a genetic predisposition for atopic diseases , only changes in environmental factors can explain this increase [ 46 ] . there is a strong association between sensitisation and symptoms of allergic diseases although this association is not absolute .
the  allergy march  refers to the natural history of sensitisation to allergens and symptoms of eczema , asthma , and rhinitis , which is characterized by a typical sequence of sensitisation and manifestations of symptoms that appear during a certain age period [ 7 , 8 ] .
food allergy and atopic eczema during the first years of life have been considered risk factors for subsequent asthma and rhinitis caused by indoor and outdoor inhalant allergens [ 5 , 9 , 10 ] .
however , allergy - like symptoms in childhood like wheezing and eczema need not have an atopic background [ 11 , 12 ] .
wheezing episodes in young children are often transient and associated with viral respiratory infections [ 13 , 14 ] .
thus , better predictors of disease development and diagnostic markers for allergic disease are needed to give proper treatment and valuable advice , especially concerning environmental control to parents of young children .
the present study was carried out in order to evaluate the diagnostic performance of phadiatop infant , an in vitro test designed to detect allergen - specific ige antibodies known to be relevant in the development of ige - sensitisation in early childhood .
the study was conducted retrospectively in consecutively included children , below the age of five years and admitted to bkl voksentoppen , rikshospitalet , oslo , during a period of twelve months .
the children were referred from paediatricians and other paediatric departments at hospitals in norway and thus selected for more severe allergic symptoms .
frozen - serum samples from 122 children were analysed and clinical data documented in the patients ' records were compiled for the study .
the study conformed to the principles of helsinki 's declaration and was approved by the local ethics committee .
skin prick test ( spt ) was performed according to standard procedure at the hospital .
glycerinated allergen extract ( soluprick   alk - abello , denmark   and a standard lancet with 1 mm tip and a shoulder ( alk - abello , denmark ) was used .  
histamine chloride 10 mg / ml was used as positive - control and as negative - control glycerol .
the reaction was recorded as 3 + when the reaction was equal to the histamine control , 2 + when half the histamine control , and 4 + when double the histamine control . the panel included egg white , cow 's milk , cod fish , peanut , hazel nut , wheat , house dust mite , cat dander , birch , timothy , cladosporium , and latex .
total and allergen - specific ige antibodies were determined in immunocap   100 ( phadia ab , sweden ) at the hospital laboratory when appropriate according to clinical findings .
serum samples were sent to phadia ab , uppsala , sweden , for determination of specific ige antibodies using immunocap phadiatop , fx5 ( a food mixture of milk , egg white , fish , peanut , wheat , and soy bean ) , and immunocap phadiatop infant using immunocap100 ( phadia ab , uppsala , sweden ) .
phadiatop infant is designed to detect allergen - specific ige antibodies to food and inhalant allergens , relevant in the development of ige - mediated disease in young children .
the following allergens are included in the test : hen 's egg , cow 's milk , peanut , shrimp , cat epithelium and dander , dog dander , house dust mite , common silver birch , timothy , ragweed , and wall pellitory .
the laboratory analyses were performed in a blinded manner and the results of phadiatop and fx5 were sent back to the investigating physician .
atopy was defined as a constitutional disposition to produce ige antibodies to common allergens whether the patients had clinical symptoms or not , as judged by the investigator .
the study was designed to make the diagnosis with best possible available tools ( case history , spt , and allergen - specific ige results ) to evaluate the clinical performance of phadiatop infant . a preliminary diagnosis whether a child was atopic or not was assessed by the investigating physician in retrospect , taking into account clinical history and diagnostic procedures , which includes available spt and allergen - specific ige results , noted in the patient records . in the final diagnosis of the atopic state , the laboratory results from phadiatop and fx5 were also taken into consideration in order to get comparable data of allergen - specific ige sensitisation on all children .
this final diagnosis was used as the reference for calculation of the diagnostic performance of phadiatop infant .
quantitative variables are described in appropriate measures of localisation and dispersion , quantitatively variables presented by counts and percentages .
the diagnostic performance of phadiatop infant was evaluated by calculating sensitivity , specificity , negative and positive predictive values ( npv , ppv ) , respectively , with 95% confidence intervals .
the subgroups divided by age ,   < 2 years and   2 years were compared with regard to the diagnostic performance of phadiatop infant using descriptive statistics .
the demographic characteristics of the children classified according to the final diagnosis of atopy / nonatopy or inconclusive diagnosis are shown in table 1 .
thirty - eight ( 31% ) subjects in the study population were girls and 84 ( 69% ) were boys with a median age of 2.7 years .
of the 122 children , 86 ( 70% ) were atopic , 26 girls and 60 boys , which is a commonly found gender distribution among atopic children at that age .
only 18% of the children presented with wheezing as a single symptom and the majority of these children were nonatopic , 55% below 2 years and 40% above this age , respectively .
eczema as a single symptom was the most prevalent symptom among the children below two years of age ( 49% ) and 63% were classified as atopic . in the older age group of children , eczema and/or wheezing in combination with other allergic symptoms dominated ( 41% ) and
other allergy - like symptoms such as rhinitis , rhinoconjunctivitis , anaphylaxis , and gastrointestinal symptoms were registered in 31 ( 26% ) children , out of whom 22 ( 71% ) were older than 2 years ( data not shown ) .
eighty - three of the children ( 68% ) reported at least one first degree relative , with about the same proportion for the atopic as for the nonatopic children , 71% and 61% , respectively ( data not shown ) .
the diagnostic performance characteristics of phadiatop infant in this study population with a prevalence of 70% are presented in table 2 .
the sensitivity calculated for the whole group of children was 98% ( 95% ci : 92100% ) and the specificity 89% ( 95% ci : 7497% ) .  
the ppv and npv values were 95% ( 95% ci : 8999% ) and 94% ( 95% ci : 8099% ) , respectively .
the diagnostic performance of the test was found to be similar when the children were separated in the two age groups , below or above two years , but due to small numbers of children in the separated age groups , the calculated values are not presented .
symptoms of allergic disease in young children are generally unspecific and the diagnosis without objective tests could be an arbitrary process .
the paediatric section of the european academy of allergy and clinical immunology has recently published a position paper with recommendations on allergy testing in children to improve the identification of allergy and quality of care .
an earlier published study has shown that 76 out of 147 children could not be classified as having an ige - mediated disease or not , based on case history and physical examination alone .
similar results were found in a recently published study , where measurements of ige - antibodies , added to case history and physical examinations , highly improved the discrimination between ige- and non - ige - mediated diseases in young children .
the results from our study confirm these findings and suggest that phadiatop infant could be a useful tool for discrimination between atopy / non - atopy .
a positive phadiatop infant test should however be followed by allergen - specific antibody testing to a selected panel to identify the offending allergen(s ) [ 19 , 20 ] .
the test seems to be at least as useful among the youngest children , below two years , as among children at 24 years of age .
the youngest child in the study was 6 months , which confirms findings from other publications that allergen - specific ige - antibodies can be detected early in life [ 17 , 18 , 21 ] .
these findings support the value of testing children with allergy - like symptoms at an early age .
family history has been considered an important risk factor for atopy and has been widely used for prediction of allergy and allergic diseases .
the results from our study are in good agreement with the notion that allergy / atopy is extremely commonly found . on the other hand ,
the fact that 30% of the atopic children did not have a family history of allergy agrees with investigators claiming that a great portion of newly diagnosed allergics / atopics do not have a family history of allergy / atopy .
thus it could be stated that family history is no longer practical in predicting allergic disease .
this study population represents a selected cohort as voksentoppen is a hospital having referred patients with allergy - like symptoms and allergic diseases from general paediatricians in the whole country , often of a more severe character .
however , other studies have shown that phadiatop infant could be applied in populations with a lower prevalence of atopy , still demonstrating good performance characteristics [ 17 , 18 , 21 ] .
the clinical appearance of allergy in our study is in agreement with the concept of the allergy march and supports what has been reported earlier from other studies [ 7 , 8 ] .
thus , eczema was not common in the nonatopic group of children and only one of the 31 children with eczema was classified as nonatopic . the progression from eczema to other allergic problems
eighty - six percent of the children with eczema and wheezing in combination with other symptoms were found in the older age group and as many as 82% were classified as atopic .
the majority of children , all ages , presenting with wheezing were nonatopic ( 73% ) .
many infants and children who wheeze have transient conditions associated with diminished airway function and do not have an increased risk of asthma later in life .
however , children with persistent wheezing , starting during the first years of life , and with an atopic heredity , should be considered being at risk for asthma later during childhood [ 11 , 22 , 23 ] .
therefore , an early diagnosis of ige sensitisation may be important for the choice of treatment to wheezing toddlers .
children with allergic symptoms usually present at a general paediatrician who needs to discriminate which patients have to be sent to an allergist for further evaluation .
rule - out tests with a high discriminating potential are suggested to have a gateway function to fulfil this differentiation and an important role to prevent the march of allergic children from the first to secondary level of care .
the present study shows that phadiatop infant has a diagnostic performance with a high sensitivity and specificity .
thus , the test could be recommended as a complement to the clinical information in the differential diagnosis on ige - mediated disease in young children with allergy - like symptoms .
furthermore , the test could be useful in assisting primary care physicians in selecting atopic children at an early stage for further intervention or referral to an allergist .
an early correct diagnosis will thus allow for better management and a possibility to delay or even prevent the onset of asthma in children with eczema and the avoidance of further deterioration of lung function in children with asthma [ 16 , 25 ] .
 
 background and objective . 
 allergy - like symptoms such as wheezing and eczema are common in young children and an early diagnosis is important to initiate correct management . the objective of this study was to evaluate the diagnostic performance of phadiatop infant , an in vitro test for determination of early sensitisation to food and inhalant allergens . 
 patients and methods . 
 the study was conducted , retrospectively , using frozen sera from 122 children ( median age 2.7 years ) admitted to the hospital with suspected allergic symptoms . 
 the doctor 's diagnosis atopic / nonatopic was based on routinely used procedures such as clinical evaluation , spt , total and allergen - specific ige antibodies . 
 the performance of phadiatop infant was evaluated in a blinded manner against this diagnosis . 
 results . 
 eighty - four of the 86 children classified as atopic showed a positive phadiatop infant test . 
 thirty - six were classified as nonatopic , 32 of who had a negative test . with a prevalence of atopy of 70% in this population , this gives a sensitivity of 98% , a specificity of 89% , and a positive and negative predictive value of 95% and 94% , respectively . 
 conclusion . 
 the results from the present study suggest that phadiatop infant could be recommended as a complement to the clinical information in the differential diagnosis on ige - mediated disease in young children with allergy - like symptoms . 
1. Introduction
2. Patients and Methods
3. Results
4. Discussion