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Objective: To prospectively assess sensitization rates and the development of allergic diseases in a follow-up of a randomized controlled pertussis vaccine trial., Setting: Two-month-old infants were the subject of this double-blind study in 1992 in a collaboration between the Pediatric Clinic and the Primary Care Centers in Linköping., Patients and Intervention: Allergic diseases were evaluated in 667 children, who were randomized to 1 of 4 vaccine groups: a 2-component, a 5-component, or a whole cell pertussis vaccine (all of which were administered with the diphtheria and tetanus toxoids vaccine) and the diphtheria and tetanus toxoids vaccine alone. Allergy development was assessed by questionnaires (n = 667) and skin prick tests (n = 538) at the age of 7 years., Main Outcome Measures: Allergic diseases and skin prick test results at the age of 7 years., Results: The cumulative incidence of allergic diseases was 34.9%, and was similar in the 4 groups (33.3%-37.3%, P =.89), even after adjusting for family history, sex, pets, dampness, environmental smoking at home, and other living conditions. Positive skin prick test results were more prevalent, however, after vaccination with the 2-component acellular vaccine (19.4%) than in the other 3 groups (11.1%-13.5%, adjusted for confounding factors, P =.01). Furthermore, allergic rhinoconjunctivitis was more common in children who were initially immunized with the 2-component pertussis vaccine and received a booster dose with an acellular vaccine compared with those who received no booster vaccination (relative risk, 3.6; 95% confidence interval, 1.1-12.0)., Conclusion: Pertussis vaccination in infancy with any of these vaccines was not associated with allergic manifestations at the age of 7 years, apart from a higher prevalence of positive skin prick test results after an experimental 2-component vaccine, which is no longer in use.

Aim: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children., Methods: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n = 161) and without (n = 296) current wheeze. High BMI was defined as > or = 75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as > or = 95th percentile. Children with a BMI < 75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests., Results: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0-2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0-3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0-4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0-4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness., Conclusion: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.

The hypertonic saline challenge test is the recommended method to assess bronchial hyperresponsiveness in the International Study of Asthma and Allergies in Childhood (ISAAC). The sensitivity of this procedure to assess asthma symptoms, however, has been reported to vary among study centers. The purpose of our study was to evaluate the value of this provocation test in an epidemiological survey in children, and to relate the degree of bronchial hyperresponsiveness to the severity of asthma symptoms. All 11-13-year-old children from 16 randomly selected schools in Linköping, Sweden received a questionnaire regarding respiratory symptoms and allergic disease. Skin prick tests with eight inhalant allergens were performed. In addition, all children with wheeze over the past 12 months (current wheeze) and a random sample of children without current wheeze were invited to perform hypertonic saline provocation tests. A complete data set was available for 170 children, including 50 with and 120 without current wheeze. Bronchial hyperresponsiveness (BHR) was defined as at least 15% decline in FEV1. The degree of BHR was represented by the response/dose ratio, i.e. the fall in FEV1 divided by total dose of inhaled saline. The severity of asthma symptoms was classified by the number of wheezing episodes over the past 12 months. 'Asthma ever' was defined by a combination of symptoms in the questionnaires. Children with 'asthma ever' and current wheeze were considered as having current asthma. Current atopic asthma was defined as current asthma with at least one positive skin prick test. The sensitivity of the procedure to detect 'asthma ever', current asthma and current atopic asthma was 62, 61 and 83%, and the specificity 83, 81 and 60%, respectively. The positive challenge rate was 52, 34, 13 and 7% among current wheezers, previous wheezers, non-wheezers with a history of allergy and healthy children. The degree of bronchial hyperresponsiveness increased with the number of wheezing episodes. Thus, the median and range of the response/dose ratio were 4.8%/ml (2.1-14.8), 2.6%/ml (0.7-8.6) and 1.3%/ml (0.8-2.7), respectively, for children with >/= 4 episodes, 1-3 episodes and no wheezing episodes over the past 12 months (p<0.001). In conclusion, hypertonic saline provocation test is useful as a tool to detect asthma in epidemiological studies in children. The degree of bronchial hyperresponsiveness, as represented by the response/dose ratio, reflects the severity of asthma symptoms.

The role of psycho-social factors in the development of allergy was studied prospectively in 82 infants with a family history of atopy. The family participated in a standardized family test when the children were 18 months old. The ability to adjust to demands of the situation ('adaptability'), and the balance between emotional closeness and distance ('cohesion'), were assessed from videotapes by independent raters. Families rated as functional in both of these aspects were classified as 'functional', otherwise as 'dysfunctional'. The social network, life events, atopic symptoms (based on postal inquiries regarding symptoms answered by the parents, and on physical examinations), psychiatric symptoms, and socio-economic circumstances of the families were evaluated when the children were 18 months and 3 years of age. The children were classified as atopic (asthmatic symptoms or eczema) or as non-atopic. All but two children with atopic disease at 3 years of age had atopic disease before 18 months of age, while 32 of 60 children with atopic disease at 18 months of age had no problems by 3 years of age. An unbalanced family interplay at 18 months was associated with a relative risk (RR) of 1.99 for continuing atopic illness at 3 years of age (1.18 < RR < 3.37, p = 0.01). There was a weak positive confounding effect for smoking (RR reduced by 7%), eczema on three or more localizations (RR reduced by 4.5%), and the amount of cat allergen in household dust (RR reduced by 3%). Recovery from atopic illness between 18 months and 3 years of age was four times as probable in families with functional interaction and a good social supportive network when children were 18 months of age, than in dysfunctional families with a poor social network (74% versus 20% p < 0.01). Children with asthmatic symptoms showed more signs of emotional distress than did healthy children (p = 0.02). Dysfunctional family interaction patterns were more commonly observed in families of children who at 3 years of age still had atopic symptoms, than in children who had recovered. The patterns included expression of emotion and reaction to the needs of others, alternating between total disinterest and over-involvement (p = 0.02), lack of support and rejection of offered support (p = 0.01), a greater number of individual decisions without regard to the other family members (p = 0.04), and indistinct 'generational boundaries' (p = 0.04). We conclude that psychosocial factors, such as family interaction and a supportive social network, play a significant role in the course of atopic illness in early childhood and that measures which enhance family interaction and the social network could influence the course of the disease favorably.

Background: Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD., Methods: The placebo intention-to-treat population of the ETACTM (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean+ SD: 17.2 + 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population., Results: Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P= 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up., Conclusion: We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease.

Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow's milk allergy (CMA). Accepting that none of the hydrolysate-based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85-100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75-100%) tolerated Profylac, and 64% (95% CI: 37-81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctor's supervision. However, the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested.

Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern, Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren (n=2108) aged 10-11 years from Linköping in southern Sweden and Ostersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in Ostersund and in Linköping. A higher prevalence of sensitization to animal dander among children in Ostersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Linköping (adjusted odds ratio 2.1; 95% confidence interval 1.1-4.0) and in Ostersund (adjusted odds ratio 2.0; 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Linköping, whereas current smoking was associated with a decreased risk of sensitization in Ostersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.

The ingestion of food antigens usually results in the induction of oral tolerance, but the clinical and immunologic consequences of brief exposure to cow's milk proteins during the neonatal period are not well-documented. The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed. A group of 129 infants was randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF), or a casein hydrolysate formula (CHF), during the first three days of life. They were then all exclusively breast-fed for a varying period of time and followed for two years. Serum IgG and IgE antibodies to cow's milk proteins and ovalbumin (OVA) were analyzed in blood samples obtained at birth, at 4 days and at 2, 4, 8, 12 and 24 months of age. The levels of IgG antibodies to beta-lactoglobulin (IgG-BLG) and bovine serum albumin (IgG-BSA) were higher in the CMF and the HM groups than in the CHF group for up to two years. This was particularly obvious for IgG-BLG in infants who started weaning before two months. The levels of IgG antibodies to casein (IgG-CAS) were higher in the CMF group, as compared with the CHF group at 8 and 12 months. The levels of IgG antibodies to OVA were similar in all three feeding groups. The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups. Exposure to cow's milk during the first three days of life stimulated IgG antibody production to cow's milk proteins and this was still obvious at 2 years of age, while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow's milk proteins.

In search of potential new indoor allergen sources, all mites in dust from homes of 55 asthmatic children living in three climatic regions in Sweden were counted and identified by light microscope. Antibodies of the IgE class against three house-dust mites and three storage mites were measured in corresponding serum samples. Mites were found in all but two homes from the northernmost area, where levels also were lower than in the other regions. The highest mite densities were most often found in bedrooms (50%) and living rooms (40%). Mite density was increased in homes with high humidity and was higher in bungalows than in flats. House-dust mites predominated in the south and storage mites in the east central area, particularly in kitchens and bathrooms. Mite-density and IgE-antibody levels against house-dust mites were significantly associated. The same association applied to storage mites. Other species numbered around 100 mites/g dust in some homes. Microscopy helps to identify potentially important mites. Analysing home dust only for house-dust mites will underestimate mite exposure. Storage mites may be as relevant to sensitivity as house-dust mites. As other species occasionally were found in high numbers, their relevance should also be assessed.

Background: Higher prevalences of allergic diseases and IgE antibodies to inhalant allergens have been reported for persons living in urban areas than for persons living in rural areas., Methods: Associations between cumulative incidences of allergic diseases in 1878 children aged 13-14 years and their place of residence (urban, semiurban, or rural) from birth were assessed by questionnaire (ISAAC), in order to find out whether there is a period of increased sensitivity to external influences during the first few years of life. Family history and exposure to pets, tobacco smoke, and damp were considered in multiple regression., Results: There was a significantly higher prevalence of allergic diseases with urban residence than with rural residence during the first 2 years of life (e.g., for bronchial asthma, relative risk (RR) for the first year 2.1, 95% CI 1.2-3.7). An increased risk was still found after multiple regression (RR=1.7). Semiurban residence was associated with an intermediate cumulative incidence of allergic diseases. Maternal smoking during pregnancy was associated with asthma (RR=1.4, 95% CI 1.0-2.0)., Conclusions: The findings support a period of increased susceptibility during the first years of life. Whether rural lifestyle protects against allergy or whether urban pollutants contribute to allergy has to be elucidated [corrected].

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively)., (Copyright 1999 Academic Press.)

Background: Pertussis toxin (PT) stimulates IgE production in animals, and pertussis vaccination and whooping cough may have similar effects in man., Methods: We analyzed IgE responses to PT (PT-IgE) in sera from children primarily immunized with three doses of either an acellular 2- or 5-component vaccine, or a whole-cell (Wc) pertussis vaccine, and in children after whooping cough. The study comprised 50 children with both atopic disease and positive skin prick test, 99 nonatopic controls, and 40 children with verified pertussis., Results: Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5 years. At 7 months, PT-IgE was more common after vaccination with acellular (24%) than with the Wc vaccine (3%, P = 0.02). PT-IgE was also more common (P = 0.001) after vaccination in children classified as atopic (36%) than in the control group (10%). Thirty percent of the children with pertussis had PT-IgE, more often so in atopic than nonatopic children (P = 0.02)., Conclusions: Transient production of PT-IgE seems to be common after primary pertussis immunization with acellular vaccines, and after whooping cough, particularly in atopic subjects.

Background: Pertussis vaccination in infancy has been suggested to increase the risk for development of asthma and allergy., Objective: To assess sensitization rates and development of atopic diseases in a prospective randomized controlled trial of pertussis vaccine., Patients and Methods: A total of 669 children were randomized to 1 of 4 vaccine groups (2-component acellular pertussis, 5-component acellular pertussis, whole-cell pertussis vaccines, and placebo [diphtheria and tetanus toxoids]). Diphtheria and tetanus toxoids were also given to the children in the pertussis vaccine groups. The children were evaluated by means of questionnaires at age 2 months, 7 months, and 2 1/2 years; skin prick tests at age 7 months and 2 1/2 years; and blinded clinical investigation at age 2 1/2 years. The families were contacted at regular intervals to assess possible adverse effects after the vaccinations and symptoms of whooping cough., Results: The cumulative incidence of atopic diseases was 30% and incidence rates were similar in the 4 groups after adjusting for family history. Exposure to environmental tobacco smoke and home dampness did not confound these results. The frequency of adverse effects did not differ appreciably between atopic and nonatopic children, with the exception that a nodule at the vaccination site was more frequent after whole-cell pertussis vaccination in the nonatopic children. Among 47 children with proven pertussis, atopic disease appeared in 19 (40%). Of these 47 children, 9 (19%) developed asthma, as compared with 58 (9%) noninfected children (P=.03)., Conclusions: We found no support for a drastic increase in allergic manifestations after pertussis vaccination. There was a positive association between whooping cough and asthma by 2 1/2 years of age. There seems to be little reason to withhold pertussis vaccination from infants, irrespective of family history of allergy.

The major allergen of Dermatophagoides microceras, Der m 1, as well as the allergens of D. pteronyssinus and D. farinae, Der p 1 and Der f 1, were analyzed in the homes of 111 asthmatic children in three climatic regions in Sweden. The numbers and species of mites were determined by microscopy, and circulating IgE antibodies against mites were measured. Der f 1 was the predominant house-dust-mite (HDM) allergen, Der p 1 the least often found, and Der m 1 represented 31% of the allergen load. However, in the Linköping area, Der m 1 was the major HDM allergen (58%). Mite counts and allergen levels correlated well. Current exposure to HDM allergens at home was associated with the serum IgE antibody response to HDM in the children with no threshold level. Of the children with IgE antibodies against HDM, 67% reacted to all three mites. Mite sensitization rates were marginally increased (7%) by the addition of IgE analysis of D. microceras to the routine analysis of IgE antibodies against D. pteronyssinus and D. farinae. Thus, Der m 1 may be an important HDM allergen and should be considered when HDM exposure data are assessed in areas with a climate like that of Sweden.

A temporary Th2 skewed immunity is essential for a successful outcome of pregnancy. It is also a hallmark of atopic disease. We recorded the number of siblings to 3667 children in relation to maternal atopy. In all, 65% of the allergic and 56% of the non-allergic mothers had more than one child (p < 0.001). These data support a hypothesis that the atopic genotype may be associated with an increased likelihood for a successful outcome of pregnancy and thus from an evolutionary point of view compensate for the less efficient host defence against microbial infections associated with this type of immunity.

Background: Indoor allergens play a major role both in sensitization and as triggers of asthma in children. The relationship between allergen exposure and sensitization to cats, dogs, and mites was studied prospectively in 100 newborn babies with a history of allergy in both parents., Methods: Skin prick tests were done with Dermatophagoides pteronyssinus, D.farinae, and cat and dog allergens in all the children at 6 and 18 months of age and in 86 children at 5 years of age. Dust samples were collected from the homes during infancy and at 5 years. The parents of the children responded to a questionnaire focused on environmental factors that could influence indoor allergen levels. In addition, dust samples were collected from the day-care centers of the sensitized children. The allergen levels were determined by ELISA., Results: The levels of the major cat allergen, Fel d 1, varied from 0.02 microg to 6.8 microg/gm (geometric mean [GM], 0.4 microg/gm) during infancy and less than 0.02 microg to 13 microg/gm dust (GM, 0.12 microg/gm) at age 5 years. Dog allergen, Can f 1, levels ranged from 0.18 microg to 590 microg/gm (GM, 3.1 microg/gm) in infancy and 0.09 microg to 13 microg/gm at age 5 years (GM, 0.6 microg/gm). Eleven children (13%) were sensitive to cats, and three were sensitive to dogs at 5 years of age. They had been exposed to similar levels of allergen as the nonsensitized children. The levels of mite allergen (Der p 1 + Der f 1) at age 1 year varied from less than 0.02 microg to 1 microg/gm dust (GM, 0.12 microg/gm) and at age 5 years from less than 0.02 microg to 3.5 microg/gm (GM, 0.05 microg/gm) dust. Only two homes contained mite allergen levels greater than 2 microg/gm dust. The levels were less than 0.3 microg/gm dust in all but one sample from the day-care centers. Only one child was sensitized to mites at age 5 years. The mite allergen level was less than 0.1 microg/gm at home, and he did not attend a day-care center., Conclusions: The findings indicate that exposure to low levels of indoor allergens in early childhood is associated with a low incidence of sensitization. However, levels well below currently suggested threshold levels may cause sensitization in children with a family history of allergy. We suggest that a fixed threshold risk level for allergic sensitization may not be appropriate in all climates.

The allergy preventive effect of extensively (N) and partially (PH) hydrolysed cows' milk formulas compared with a regular formula (RM) was assessed in 155 infants with a family history of allergy. No cows' milk was given during the first nine months of life and no egg and fish up to 12 months of age. Breast feeding mothers avoided the same foods. At weaning the infants were randomised to one of the formula groups. The cumulative incidence of atopic symptoms at 18 months was 51, 64, and 84% in the N, PH, and RM groups, respectively. From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group, and significantly less than the PH group up to 6 (N = 25%; PH = 46%) and 9 months (N = 34%, PH = 58%). At 9 months significantly fewer infants in the N group (10%) than in the PH group (33%) had a positive skin prick test to eggs. The findings support an allergy preventive effect of an extensively hydrolysed formula, but not of a partially hydrolysed formula, during the first 18 months of life of high risk infants.

The relation between month of birth, sensitisation, and manifestations of atopy was assessed in 209 children who were followed from birth to 12-15 years. Children born during the tree pollen season were less likely to develop allergic rhinoconjunctivitis, IgE antibodies to pollen, or a positive screening test for IgE antibodies (odds ratio 0.28, 0.41, 0.35, respectively) than children born during the rest of the year. The prevalence of IgE antibodies to food and animal dander at 9 months and to atopic disease was higher in children born in the autumn and winter, that is, September to February, compared to the spring and summer (egg 20% v 6%; milk 10% v 2%). Thus sensitisation to pollen and allergic rhinoconjunctivitis is least common in children born in the spring, while birth in September to February is associated with an increased incidence of sensitisation to food and of atopic disease.

The development of symptoms possibly related to allergy or other forms of hypersensitivity was studied in a group of 638 children on two occasions: when the children were 3 and 18 months of age. Standardized questions were used to collect basic information about the child, technical characteristics of the home, and the mother's perception of the indoor climate. All reported exposure factors were analyzed in relation to the child's symptoms at 18 months of age, by logistic regression techniques. A family history of atopy was associated with a high incidence of most of the investigated symptoms. Attendance at a day nursery before 18 months of age increased the risk of recurrent colds and the need for several courses of treatment with antibiotics. If the mother smoked, the children more often suffered from protracted coughing episodes. If the child has a sibling, the risk of developing a wheeze, repeated colds, and the need for antibiotic treatment increased. No building factors, such as size of the home, heating and ventilation system, type of foundation, dampness, or presence of wall-to-wall carpets, showed a significant correlation to symptoms reported in the children. However, if the mothers reported symptoms that are often connected with "sick buildings", the children more often had eczema, dry skin, or reactions to food. The mothers' complaints about indoor air quality and climate and mucous membrane symptoms were significantly related to the type of building and presence of condensation on the windows in winter, a finding which may indicate that indoor climate factors also have some effect on the health of the children. This study reports the prevalences of symptoms until the age of 18 months. At this age, the allergic manifestations are usually nonspecific, and follow-up examinations to 4-5 years of age are needed before any definite conclusions can be drawn about the development of atopic diseases due to indoor climate factors.

The fatty acid composition of umbilical cord serum phospholipids was investigated by gas chromatography in 33 infants with allergic and 35 babies of non-allergic mothers. The relative levels of the linoleic acid metabolites C20:3, arachidonic acid (AA, C20:4) and C22:4n-6, and two alpha-linolenic acid metabolites, i.e. eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, C22:6) were significantly higher in infants of allergic mothers than in non-allergic mothers (all p < 0.05). Furthermore, an altered proportional relationship between the various fatty acids in n-6 series fatty acids and between n-3 and n-6 series fatty acids was present already at birth in infants who developed allergic disease during their first 6 years of life. These observations cannot be employed for the prediction of allergy, however, as the individual variations were considerable.

The prevalence and level of sensitivity to indoor allergens were studied in relation to current exposure at home in 124 children with perennial asthma living in three climatic zones of Sweden. The house dust mite (HDM) allergen levels were higher in the South than in the North (p < 0.001), while cat and dog allergen levels tended to be higher in the North than the South (n.s.). Thirty-four percent of the children were sensitive to the HDM Dermatophagoides pteronyssinus, as determined by IgE antibodies in vitro, 27% were sensitive to D. farinae, 57% to cat and 55% to dog. Sensitivity to HDM was significantly more prevalent in Southern, than in Central and Northern Sweden (p = 0.001) where the children were more often sensitive to pets (cat p = 0.005, dog p = 0.002). A significant association between the concentration of Der p I and Der fI in the house dust and both the prevalence of sensitivity to HDM and the IgE antibody levels against mites was found even at concentrations well below the commonly suggested risk level for sensitisation of 2 micrograms/g dust. No relationship was found between pet allergen concentration in the home dust and sensitivity to pets, possibly because of exposure outside home, e.g. in schools and meeting places for leisure activities. Similarly, there was no consistent association between the level of mite or pet allergen exposure at home and asthma severity as judged by symptom and medication score. The study indicates that there is no threshold value for sensitisation to mite allergens in asthmatic children, and therefore, dust allergen levels at home should be kept as low as possible in homes of children at risk for asthma.

Ninety-one high atopy-risk infants were prospectively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization. They were randomized into one of two feeding groups, i.e., a hydrolyzed, ultrafiltered cow's milk whey formula, Profylac (n = 32), or an ordinary cow's milk formula (n = 39), for 12 months, started after exclusive breast-feeding for 0-9 (median 6.0) months. Lactating mothers avoided milk, egg, and fish, as did the infants up to 12 months of age. Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group. All infants were followed-up by questionnaires, physical examinations, skin prick tests, and determination of serum total IgE and cow' milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups. However, all three infants who developed cow's milk allergy with skin symptoms belonged to the cow's milk formula group. The skin prick test with whey hydrolysate was negative in all, while with cow's milk it was positive in eight infants. Growth was similar in the three groups. The study comprises too few infants to allow us to make statistically based statements. However, the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden.

The capacity of laboratory tests and clinical signs to predict allergic manifestations up to 18 months of age was assessed in 129 newborn babies, most of whom had family members with atopic disease. The parameters assessed included family history; skin dryness; erythema toxicum; skin reactivity to histamine and IgE levels; eosinophil counts; and peripheral white blood cell, leukocyte differential, and platelet counts in cord blood (CB). Erythema toxicum and white blood cell and platelet counts were of no value as predictors of allergy. The sensitivity of family history, skin dryness, and sensitivity to histamine, as well as IgE levels and eosinophil counts, varied 25-79% and the specificity 40-74%. The efficiency was never higher than 58%. Logistic regression, applied in order to evaluate the joint predictive power of the five parameters, showed a P value of < 0.001. The estimated probability for atopy before 18 months of age was 0.33 for neonates with normal skin texture, a CB IgE of less than 0.5 kU/l, and a history of fewer than two family members with atopy. The probability increased to 0.89 for babies with a dry skin, a history of two or more atopic family members, and a CB IgE of > or = 0.5 kU/l. In conclusion, not one parameter nor any combination of them seems suitable for general screening. However, a combination of family history and CB IgE and skin assessment may be used to identify babies at high risk of allergy for participation in prevention studies.

Background: We tested the hypothesis that eosinophilia in peripheral blood and nasal mucosa of infants is an early sign of allergic disease., Methods: The appearance of eosinophilic leukocytes in peripheral blood and nasal mucosa was studied prospectively in 67 infants up to 18 months of age, with or without a family history of atopy., Results: Eosinophilia was associated with simultaneous presence or subsequent development of atopic disease at 3, 9, and 18 months of age, but not significantly so at 6 months. At 3 months children in whom atopic disease developed later during the observation period had significantly higher numbers of blood eosinophils than children without atopy (p < 0.01). Thus pronounced eosinophilia (> 7 x 10(8) cells/L) at that age was associated with moderate or severe allergic disease during the 18-month observation period. These children continued to have eosinophilia throughout the follow-up period. Blood eosinophilia at 3 months of age also correlated significantly to cord blood IgE levels and to skin prick test reactivity later during the follow-up period. Nasal eosinophilia was a common finding and therefore had little diagnostic or predictive value., Conclusions: Elevated eosinophil counts in peripheral blood of apparently healthy infants at 3 months of age is associated with a subsequent diagnosis of atopic disease.

A programme of clinical studies was carried out to determine the basic efficacy and safety of 2% nedocromil sodium eye drops (Tilavist) in treating allergic conjunctivitis, in 2,905 patients from 3-76 years of age. Results of all the double-masked placebo comparative studies completed to date-five in vernal keratoconjunctivitis (VKC), five in perennial (PAC) and 16 in seasonal allergic conjunctivitis (SAC)-have been assessed in a statistical overview analysis. Nedocromil sodium, administered four times daily to 153 patients with VKC, was significantly more effective than placebo (155 patients) and in the clinicians' opinion gave good control in 76% of cases, compared with 46% for placebo (p < 0.001). Patients with chronic symptoms of PAC also responded better to nedocromil sodium given four times daily (n = 146) rather than twice daily (n = 86), and significantly more patients (p < 0.001) were effectively controlled by four times daily treatment with nedocromil sodium (72%) than with placebo (47%; n = 156). Twice-daily dosage with nedocromil sodium (n = 677) was adequate for SAC, however, and the treatment was statistically better than placebo (p < 0.01-p < 0.001) whether dosed twice or four times daily. Speed of action was assessed in seven SAC studies in which 79% of all patients (n = 295) using nedocromil sodium had experienced relief of symptoms when questioned, half of them within 15 minutes and 74% during the first hour after dosing. Test treatments were well-accepted by both adults and children, and there were no major adverse events. Minor irritations reported more frequently with nedocromil sodium than placebo were stinging or burning of the eyes on application of the drops and a distinctive taste, noted by 5% of the active treatment group (n = 1,552).

We investigated the levels of mite (Der p I and Der f I) allergen in dust from bedrooms, living rooms, kitchens, and bathrooms from 130 homes of asthmatic children in three climatic zones of Sweden. Bedroom dust samples included the child's mattress, carpets, floors, and other plain surfaces. Living-room dust samples were taken from sofas and other furniture, carpets, floors, and other plain surfaces. The allergen levels were related to home characteristics, including absolute indoor humidity (AIH), relative humidity (RH), and air changes per hour (ach). Mite allergen was detected in 62% of the homes. Levels of Der p I varied between < 16 ng and 50 micrograms/g dust, and Der f I between < 16 ng and 73 micrograms/g dust. Because we have designed a composite type of dust collection in our study, the allergen levels found tend to average down the results. Mite allergen levels were higher in homes with dampness problems, in homes with a smoker, and in homes without a basement. Homes with high absolute humidity (> or = 7 g/kg) or relative humidity (> or = 45%) and poor ventilation (< 0.5 ach) contained higher levels of mite allergens than homes with lower humidity and better ventilation. However, the number of ach measurements in homes was not high, and few homes had > 0.5 ach. Sensitization to house-dust mites was more common in southern than in northern and central Sweden. High levels of house-dust mite allergen in a temperate climate where mites are not ubiquitous are thus associated with dampness problems in homes and with tobacco smoking. Our data confirm and extend previous findings that high AIH and RH and poor ventilation increase the risk of mite infestation in homes. It seems to be important and necessary to control indoor humidity and ventilation levels, to avoid high mite allergen exposure in a temperate climate, because 34% of mite-sensitized asthmatic children were exposed to levels of mite allergen < 2 micrograms/g dust in their homes. The study also shows that mite allergen levels below the suggested threshold level (2 micrograms/g dust) are associated with mite sensitivity in children with perennial symptoms of asthma.

Background: Few studies have addressed the relationship between sensitization and the development of atopic disease over many years., Objective: To study the temporal relationship between the appearance of IgE antibodies in serum and atopic disease, we studied 324 children from three different groups, who were followed up prospectively from birth for 4, 12, and 15 years, respectively., Methods: Serum samples were obtained at various ages and analyzed for IgE antibodies against egg white, cow's milk, wheat, animal dander, house dust mite, birch and timothy with Phadebas RAST (Kabi Pharmacia Diagnostics AB, Uppsala, Sweden) or Pharmacia CAP system. In addition, a screening test for atopy, the Phadiatop Paediatric test (Kabi Pharmacia Diagnostics AB) was performed. Presence of atopic disease was assessed by means of clinical examination, interviews, and questionnaires., Results: In 135 children IgE antibodies were detected at least once to at least one allergen. Antibodies to egg white appeared in 46 children before or at 2 years of age: in 57% of them IgE antibodies to inhalants developed within the next 2 years, and in 19 of 25 (76%) IgE antibodies to inhalants developed before or at 12 to 15 years. Antibodies to inhalant allergens appeared in 55 children during the first 4 years of life and in 64 before 12 to 15 years. Among the former 48% and among the latter 32% had previously detectable egg white antibodies. Atopic disease appeared before or at age 4 years in 80% of the 40 children with IgE antibodies against egg white up to 9 months of age and in 69% of the 58 children who had a positive Phadiatop Paediatric test result in infancy., Conclusions: IgE antibodies in children are usually associated with current or later topic disease. Sensitization to foods in infants is usually associated with appearance of IgE antibodies to inhalants later in life.

The atopy-predictive value of cord blood (CB) cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) in mononuclear leukocytes (MN) was studied prospectively in 57 neonates. Reliable determination of cAMP-PDE was achieved in only 20 CB samples. The levels tended to be higher in infants developing signs of atopy up to 18 months of age. The combination of CB cAMP-PDE and family history (FH) of allergy showed a higher predictive value (P = 0.040) than each of them separately (P = 0.370 and P = 0.102, respectively). The cAMP-PDE levels in CB also correlated to FH of allergy/atopy in accordance with earlier studies (P = 0.027). In conclusion, determination of cAMP-PDE in neonates may have some predictive value, but it is not suitable for general screening.

The role of psychosocial factors in the development of wheezing was studied prospectively in 100 infants with a strong family history of allergy. The entire family participated in a standardized family test when the children were 3 and 18 months of age. The ability to adjust to demands of the situation ("adaptability") and the balance between emotional closeness and distance ("cohesion") were assessed from videotapes by independent raters. Families rated as functional in both aspects were classified as "functional" and otherwise as "dysfunctional." Based on records of symptoms kept by the parents and on results of physical examinations at 6 and 18 months of age, the children were classified as healthy or as having recurrent wheezing, recurrent infections, or eczema. An unbalanced family interplay was common (37%) at 3 months but did not predict development of illness. If the child remained healthy and the family did not experience any further stress, family interaction was functional 15 months later. If, however, the child acquired anxiety-provoking symptoms, such as wheezing, a high proportion of families continued or began to have dysfunctional interaction patterns. When the healthy children were 18 months of age, only 12% of their families were dysfunctional, compared with 26%, 46%, and 52%, respectively, of the families of children with eczema, recurrent infections, and obstructive symptoms (p < 0.01). We conclude that dysfunctional family interaction seems to be a result rather than the cause of wheezing in infancy.

Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (> = 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350 AU/l than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.

We have investigated the levels of cat (Fel d I), dog (Can f I), and cockroach (Per a I) allergens in dust from bedrooms, living rooms, kitchens, and bathrooms from 123 homes of asthmatic children in three zones of Sweden with varying climates. Absolute indoor humidity (AIH), relative humidity (RH), rate of ventilation in air changes per hour (ach), and number of airborne particles were also measured. Fel d I, Can f I, and Per a I allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. The major cat allergen, Fel d I, was detected in all homes, and the concentrations varied between 16 ng and 28,000 ng/g fine dust. The dog allergen, Can f I, was detected in 85% of the homes, and the levels varied from 60 ng to 866,000 ng/g dust. Cockroach allergen was detected in only one home (40 ng/g). Fel d I and Can f I allergens were equally distributed geographically. Dust from living rooms contained significantly higher (P < 0.05) concentrations of both Fel d I and Can f I allergens than dust from bedrooms, kitchens, and bathrooms. The levels tended to be higher in homes with poor ventilation (< 0.5 ach) and in homes with wall-to-wall carpets. Significantly higher (P < 0.01) numbers of airborne particles were found in homes with high humidity (i.e., AIH > or = 7 g/kg or RH > or = 45%).(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty subjects (aged 6-20 years) with moderately severe bronchial asthma participated in an open controlled trial with intravenous immunoglobulin (IVIG) given as five monthly infusions with a mean dose of 0.8 g/kg body weight. A follow-up was performed 4 and 14 months after the treatment period. Nine of 14 children in the treatment group completed the trial. Two children experienced severe headache after the first infusion, another two patients were taken off the study for reasons unrelated to the IVIG therapy, and one patient dropped out from lack of motivation. In six of the IVIG-treated children, there was a reduction in the daily intake of inhaled steroids at an unchanged or reduced histamine reactivity. Of the remaining three children, two showed a reduction in bronchial hyperreactivity, but their steroid dose was not reduced. Six patients participated in a reference group to determine seasonal variations of symptoms. One of them improved during the study period, and the condition of the other five deteriorated, as indicated by increased medication without reduced histamine reactivity. After 14 months, there were no significant differences in clinical symptoms, nor in sensitivity to histamine between the treated patients and the controls, as the condition had improved also in the latter. We have thus been able to confirm, in a group larger than those in previously published reports, some clinical improvement of asthma by IVIG therapy at a lower dose than previously used and in children with only moderately severe disease. The effect was still present 4 months after the termination of IVIG therapy but not after 14 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Carpet and floor dust samples were collected in four different seasons, from 39 Swedish homes of babies with a family history of allergy. House-dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. Both mite and cat antigens were detected in 94% of the samples and in all homes, but the levels were low (Der p 1, range 15 ng-1944 ng/g fine dust; Der f 1, range 14 ng-264 ng/g of fine dust; Fel d 1, range 16 ng-3120 ng/g fine dust). Mite-allergen levels were significantly higher (P < 0.001) in floor dust than in carpets, and D. pteronyssinus predominated. In contrast, the levels of cat antigen were significantly (P < 0.05) higher in carpets than in floor dust. There was no clear relation between mite-allergen levels and type of house, except that the higher values were found in homes with dampness problems. Cat-allergen levels were higher than total mite-allergen content, and the highest levels were found in homes with a cat (P < 0.05). Rather high concentrations of cat allergen were also found in homes without a cat, which may explain why cat sensitization is so common in Sweden. As the prevalence of house-dust mite sensitivity is increasing in Swedish children, and as the individual patient threshold for eliciting symptoms varies, we suggest that sensitization may possibly occur at a lower exposure level than generally accepted as risk level for sensitization (2 micrograms/g dust).

Subpopulations of T and B lymphocytes and levels of serum immunoglobulins G, A, M, E and subclasses G1, G2 and G3 were studied in 45 healthy school children aged 8-16 years during four seasons of the year. There were significant increases in CD4+ T helper cells, total T lymphocytes and CD4+/CD8+ (helper/cytotoxic) T-cell ratio during the spring season. While the levels of CD8+ T cells and total B lymphocytes remained statistically unchanged during all four seasons, the levels of natural (HNK-1) killer cells and macrophages increased significantly during the autumn and summer seasons respectively. The levels of immunoglobulins G, A, M and E remained statistically unchanged during all four seasons. Girls had higher levels of CD4+ T cells and a higher CD4+/CD8+ T-cell ratio than boys. Girls also had slightly higher levels of immunoglobulin G and M. These observations suggest that seasonal variations of some immunological parameters occur in healthy children. This may be an adaptive response to variable climatic and other environmental factors. These natural variations due to seasonal changes should be taken into account when immunological tests are used in clinical investigations.

Ten atopic and five healthy individuals participated in eight conjunctival provocation tests (CPT) in an effort to improve the CPT procedure. Results were evaluated by thermography and the use of conventional criteria under various conditions. Due to considerable spontaneous variability and change in temperature already after instillation of diluent, thermography was not sensitive enough to identify positive CPT results. The precision of the CPT was within one 10-log step in all tests and in all patients. Itching appeared before erythema in 83% of subjects and within 5-8 min after instillation of the allergen. This was true also when only one eye was used for the CPT. We therefore conclude that the CPT procedure can be used in one eye every 5-8 min when indicated in clinical routine and that it is a safe, precise method.