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Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are neuroendocrine tumors that express somatostatin receptors (SSTRs), a phenomenon that constitutes a basis for tumor imaging and treatment with somatostatin analogues and peptide receptor radionuclide therapy. We studied the immunohistochemical expression of SSTR1-5 in 151 primary tumors, including 14 metastasized and 16 SDHB-deficient tumors. SSTR2 and SSTR3 were most abundantly present in these tumors, whereas the tumors were mostly negative for SSTR1, SSTR4, and SSTR5. All metastasized PGLs (9/9), but only one metastasized PHEO (1/5), were strongly SSTR2 positive. SSTR3 expression was lower in metastatic tumors and tumors with a high proliferation rate (MIB1 ≥ 5%), but tumors had variable individual SSTR profiles. No correlation was found between SDHB status and SSTR expression. Our results suggest that new SSTR analogues with affinity for several SSTRs could be relevant for a subgroup of patients with these tumors. Better knowledge of tumor SSTR profiles could open the door for personalized imaging and treatment in the future. Because SSTR profiles vary in PHEOs and PGLs, individual analysis is required for each tumor., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: A number of studies have clarified the tolerance mechanisms and risk factors for food allergies. Our aim was to explore food allergy symptoms by target organs, together with the risk factors and how to prevent food allergies and induce tolerance., Methods: We carried out a thorough review of studies on paediatric food allergies published in the last decade., Results: Food allergy symptoms may affect the skin, nasal and oral mucosa, conjunctivae, gastrointestinal tract or, in severe cases, the respiratory tract and cardiovascular organs. Immunoglobulin E (IgE)-mediated symptoms appear rapidly after exposure to the offending allergen, whereas non-IgE-mediated symptoms are typically delayed. The immunological processes involved in non-IgE-mediated allergic reactions are poorly understood, but T-cell activation is probably involved. There are several factors that influence the food sensitisation process: genetic predisposition, disruption of oral tolerance development, impaired skin barriers in atopic eczema and the influence of microbiomes., Conclusion: The symptoms and intensity of reactions vary considerably with regard to food allergies, and these depend on the individual's concomitant immunological and regulatory mechanisms. There is strong evidence that dietary diversity is important for children, even when they come from families with high allergy risks., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: In children, exercise-induced dyspnea is a common symptom that can be due to dysfunctional breathing. EVH test has bee used especially in elite athletes as bronchoprovocation test. Currently, there are only few studies on the EVH test. New research methods are required alongside the traditionally used tests especially due to dysfunctional breathing disorder., Purpose: The purpose of the "pilot study" was to study the usability of the EVH test with real time biofeedback in children of 10-16 years of age in the diagnostics of exercise-induced dyspnea., Methods: Six 10-16-year-old teenagers with history of exercise-induced dyspnea and three healthy control subjects were selected for the study. A 6-minute EVH test with realtime biofeedback was performed on the patients and the diagnosis was confirmed on the basis of clinical findings and spirometry follow-up either as normal, asthma or dysfunctional breathing., Results: The study was successful in the patients. In the spirometry follow-up, three patients had bronchoconstriction (FEV1 decline over 10%), dysfunctional breathing condition was observed in three patients and three control patients experienced no symptoms. Only two DFB-patients didn't reach the target level of minute ventilation due to a clinical symptom (inspiratory stridor)., Conclusion: The EVH test was successful in the 10-16-year-old children having participated in the study and the test was well tolerated. Through the study, it was possible to provoke both dysfunctional breathing disorder and bronchoconstriction in the symptomatic patients. Based on the pilot study, EVH test seems to be usable in the diagnostics of pediatric exercise-induced dyspnea but larger studies are warranted to confirm our preliminary findings., (© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Objectives: Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer., Materials and Methods: This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics., Results: AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival., Conclusion: AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.

Aim: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies., Methods: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units., Results: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions., Conclusion: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Infants hospitalised for bronchiolitis undergo examinations and treatments not supported by current research evidence and we investigated practice variations with regard to Finnish children under the age of two., Methods: This prospective, multicentre cohort study was conducted in paediatric units in three university hospitals in Finland from 2008 to 2010. Hospital medical records were reviewed to collect data on clinical course, testing and treatment. Data were analysed separately for children meeting our strict definition of bronchiolitis, aged under 12 months without a history of wheezing, and a loose definition, aged 12-23 months or with a history of wheezing., Results: The median age of the 408 children was 8.1 months. Clinical management varied between the three hospitals when stratified by strict and loose bronchiolitis subgroup definitions: complete blood counts ranged from 15-95% vs 16-94%, respectively, and the other measures were chest x-ray (16-91% vs 14-72%), intravenous fluids (2-47% vs 2-41%), use of nebulised epinephrine (10-84% vs 7-50%), use of salbutamol (18-21% vs 13-84%) and use of corticosteroids (6-23% vs 60-76%)., Conclusion: The clinical management of bronchiolitis varied considerably with regard to the three hospitals and the two definitions of bronchiolitis. A stronger commitment to evidence-based bronchiolitis guidelines is needed in Finland., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Importance: Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking., Objective: To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases., Design, Setting, and Participants: The Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included., Exposures: Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years., Main Outcomes and Measures: The latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases., Results: We included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95% CI, 1.31-6.31). The late phenotype was only positively associated with allergic rhinitis., Conclusions and Relevance: Using latent class analysis, 4 phenotypes of atopic dermatitis were identified depending on the onset and course of the disease. The prevalence of asthma and food allergy by 6 years of age was strongly increased among children with early phenotypes (within age 2 years), especially with persistent symptoms. These findings are important for the development of strategies in allergy prevention.

Background: Respiratory tract infections and their symptoms are frequent during early childhood, but their risk factors, including the effect of early immune regulation, are less known. The aim of the study was to analyze whether stimulated cord blood cytokine production is associated with the frequency of respiratory tract infection symptoms or infections during the first year of life., Methods: The study population consisted of children of mothers from farm or non-farm rural environment from Austria, Finland, Germany, and Switzerland who participated in a prospective birth cohort study (PASTURE: Protection against Allergy-Study in Rural Environments) (N = 550). Cord blood samples were stimulated with the combination of phorbol ester and ionomycin (P/I) for 24 h, and the production of IL-5, IL-10, TNF-α, and IFN-γ was determined using ELISA. Information about infectious morbidity was collected using weekly diaries., Results: P/I-stimulated production of IL-5 (adjusted risk ratio (aRR) for ≤median production, 0.37; 95% confidence interval (CI), 0.25-0.55, aRR for >median production, 0.41; 95% CI, 0.27-0.61 vs. production median production, 0.39; 95% CI, 0.25-0.62 vs. production

Background: Our aim was to evaluate the association between viral findings during bronchiolitis and the use of asthma controller medication (primary outcome) and systemic corticosteroids (secondary outcome) during the first post-bronchiolitis year., Methods: We enrolled 408 children hospitalized for bronchiolitis at <24 months of age in a prospective, 3-center, 1-year follow-up study in Finland. Viruses were detected with polymerase chain reaction in nasopharyngeal aspirates. The parents underwent a structured interview during hospitalization. Twelve months later, the use of asthma medication was asked in a structured questionnaire. Multivariable logistic regression was used for statistical analysis., Results: In total, 365 (89%) children completed the 1-year follow-up. The use of long-term asthma controller medication was highest in the rhinovirus-positive group (61% vs. 15% in respiratory syncytial virus-positive group; adjusted odd ratios, 7.5; 95% confidence interval: 3.7-15.3), followed by children negative for both respiratory syncytial virus and rhinovirus (36%; adjusted odd ratios, 2.6; 95% confidence interval: 1.3-5.3). Likewise, rhinovirus etiology was associated with more courses of systemic corticosteroids during the follow-up. The main findings were similar in a subset of infants aged <12 months with first wheezing., Conclusions: Children hospitalized for rhinovirus-positive bronchiolitis used long-term asthma controller medication more often than those hospitalized for rhinovirus-negative bronchiolitis during first year after hospitalization.

In 169 Finnish infants hospitalized for bronchiolitis at age <6 months in 2008-2010, nasopharyngeal aspirates were tested by polymerase chain reaction for Bordetella pertussis and 16 viruses. Respiratory viruses were detected in 89% (71% with respiratory syncytial virus), but no infant had B. pertussis. The latter finding may reflect a positive effect from the broadening of the Finnish pertussis vaccination program in 2005.

Background: Excess moisture and visible mold are associated with increased risk of asthma. Only a few studies have performed detailed home visits to characterize the extent and location of moisture damage and mold growth., Methods: Structured home inspections were performed in a birth cohort study when the children were 5 months old (on average). Children (N = 398) were followed up to the age of 6 years. Specific immunoglobulin E concentrations were determined at 6 years., Results: Moisture damage and mold at an early age in the child's main living areas (but not in bathrooms or other interior spaces) were associated with the risk of developing physician-diagnosed asthma ever, persistent asthma, and respiratory symptoms during the first 6 years. Associations with asthma ever were strongest for moisture damage with visible mold in the child's bedroom (adjusted odds ratio: 4.82 [95% confidence interval: 1.29-18.02]) and in the living room (adjusted odds ratio: 7.51 [95% confidence interval: 1.49-37.83]). Associations with asthma ever were stronger in the earlier part of the follow-up and among atopic children. No consistent associations were found between moisture damage with or without visible mold and atopic sensitization., Conclusions: Moisture damage and mold in early infancy in the child's main living areas were associated with asthma development. Atopic children may be more susceptible to the effects of moisture damage and mold., (Copyright © 2015 by the American Academy of Pediatrics.)

Histopathologic diagnosis of adrenocortical tumors is based on adverse features that indicate malignant potential. Proliferation index has served as a supplemental tool in assessing the malignant potential of adrenocortical tumors. None of the current histologic classification systems can sufficiently accurately predict tumors' metastatic potential. We studied 177 consecutive adult patients with primary adrenocortical tumors operated on at Helsinki University Central Hospital between 1990 and 2003, all patients with a minimum follow-up of 5 years. We determined for each tumor the Weiss score and the Weiss revisited score by Aubert. Proliferation index was measured by computer-assisted image analysis. Each of the 9 Weiss criteria and the proliferation index were then used to establish a scoring system to predict the metastatic potential of adrenocortical tumors. Use of stepwise regression analysis led us to propose a calculation: 3 × mitotic rate (>5/50 high-power fields) + 5 × presence of necrosis + proliferation index in the most proliferative area of the tumor. Using a cutoff value of 8.5, the new scoring system was able to diagnose metastatic adrenocortical carcinoma with 100% sensitivity (confidence interval [CI], 76.8%-100%) and 99.4% specificity (CI, 96.6%-100%). The corresponding sensitivity of the Weiss system was 100% (CI, 76.8%-100%), and specificity, 90.2% (CI, 84.6%-94.3%), with sensitivity of the Weiss revisited system at 100% (CI, 76.8%-100%) and specificity at 96.9% (CI, 93.0%-99.0%). The new Helsinki score thus was accurate in predicting the metastatic potential of adrenocortical tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This guideline, targeted to healthcare workers dealing with food-allergic children, provides a review on the clinical aspects of pediatric food allergy. The main updates include: elimination diets are not recommended for breast-feeding mothers; probiotics are not recommended for allergy prevention or treatment; food challenges are the basis of the diagnosis, but it can be improved by IgE component diagnostics. The treatment for severe symptoms is specific food avoidance, mildly symptomatic children should continue with versatile diet. Specific oral tolerance induction is a safe and effective treatment in most of the pediatric patients.

Objective: To determine whether hospital length-of-stay (LOS) for bronchiolitis is influenced by the causative virus: respiratory syncytial virus (RSV) or rhinovirus., Methods: This prospective study was carried out in 3 university hospitals in Finland during 2 consecutive winter seasons. We enrolled consecutive children <2 years of age hospitalized with an attending physician's diagnosis of bronchiolitis. All enrolled children were included in the primary analysis. A parallel analysis was also conducted using a stricter definition for bronchiolitis (age <12 months and no history of wheeze). Polymerase chain reaction was used to test the nasopharyngeal aspirate samples for multiple respiratory pathogens., Results: The median age of the 408 children was 8 months, 73% had no history of wheeze and their median hospital LOS was 2 days. 144 (35%) children had RSV only and 92 (23%) children rhinovirus only infections. Children with rhinovirus only had shorter duration of prehospital symptoms, higher disease severity score at entry and more often a history of wheezing (all P ≤ 0.001). Controlling for 7 demographic and clinical characteristics, those with rhinovirus only had shorter hospital LOS when compared with children with RSV only (adjusted odds ratio: 0.45; 95% confidence interval: 0.22-0.92; P = 0.03). The rhinovirus only finding was similar in the subset of 206 children with stricter diagnosis (adjusted odds ratio: 0.30; 0.06-1.49; P = 0.14)., Conclusions: Hospital LOS is associated with rhinovirus etiology of bronchiolitis. Our data call attention to the importance of both RSV and rhinovirus testing in clinical research.

Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements occur in a subgroup of non-small cell lung carcinomas (NSCLCs). The identification of these rearrangements is important for guiding treatment decisions. The aim of our study was to screen ALK gene fusions in NSCLCs and to compare the results detected by targeted resequencing with results detected by commonly used methods, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcription-PCR (RT-PCR). Furthermore, we aimed to ascertain the potential of targeted resequencing in detection of ALK-rearranged lung carcinomas. We assessed ALK fusion status for 95 formalin-fixed paraffin-embedded tumor tissue specimens from 87 patients with NSCLC by FISH and real-time RT-PCR, for 57 specimens from 56 patients by targeted resequencing, and for 14 specimens from 14 patients by IHC. All methods were performed successfully on formalin-fixed paraffin-embedded tumor tissue material. We detected ALK fusion in 5.7% (5 out of 87) of patients examined. The results obtained from resequencing correlated significantly with those from FISH, real-time RT-PCR, and IHC. Targeted resequencing proved to be a promising method for ALK gene fusion detection in NSCLC. Means to reduce the material and turnaround time required for analysis are, however, needed.

Objectives: To investigate the effect of dog and cat contacts on the frequency of respiratory symptoms and infections during the first year of life., Methods: In this birth cohort study, 397 children were followed up from pregnancy onward, and the frequency of respiratory symptoms and infections together with information about dog and cat contacts during the first year of life were reported by using weekly diaries and a questionnaire at the age of 1 year. All the children were born in eastern or middle Finland between September 2002 and May 2005., Results: In multivariate analysis, children having dogs at home were healthier (ie, had fewer respiratory tract symptoms or infections) than children with no dog contacts (adjusted odds ratio, [aOR]: 1.31; 95% confidence interval [CI]: 1.13-1.52). Furthermore, children having dog contacts at home had less frequent otitis (aOR: 0.56; 95% CI: 0.38-0.81) and tended to need fewer courses of antibiotics (aOR: 0.71; 95% CI: 0.52-0.96) than children without such contacts. In univariate analysis, both the weekly amount of contact with dogs and cats and the average yearly amount of contact were associated with decreased respiratory infectious disease morbidity., Conclusions: These results suggest that dog contacts may have a protective effect on respiratory tract infections during the first year of life. Our findings support the theory that during the first year of life, animal contacts are important, possibly leading to better resistance to infectious respiratory illnesses during childhood.

Background: Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent., Objective: To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis., Methods: A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR., Results: Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis., Conclusion: Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Congenital ciliary dysfunctions are recessively inherited disorders. The disorder is poorly recognized, if the patient has no situs inversus. The diagnosis is delayed, being made on the average at the age of over five years. The review deals with a recent European multinational survey of the occurrence, genetics, diagnostics and treatment of congenital ciliary dysfunctions. Data of Finnish pediatric patients under treatment have also been collected for the survey. The number of congenital ciliary dysfunctions found in Finland is approximately one fifth of that found in other Nordic countries.

Although most infants will recover from food allergy within the early years of life, at least one fifth will carry on with the disease until school age. Recent studies have managed to develop increased tolerance in children with food allergy by food hyposensitization with slowly increasing orally administered doses. In these studies either complete or partial increase of food tolerance for 80% of subjects has been achieved. The clinical results seem promising, and immunologic changes upon food hyposensitization look similar to those observed with other hyposensitization therapies.

Problem: The aim of this study was to investigate maternal pre-eclampsia (PE), placental abruption (PA) and atopy among offspring., Method of Study: Obstetric data was recorded from 378 women who were included into the Caesarean delivery birth cohort during 1990-1992. When their children were 15-17 years old skin prick tests (SPTs) and inhalant allergen-specific (IAS) immunoglobulin E (IgE) were determined among offspring., Results: Adolescents whose mothers had either PE or PA at the time of delivery had more atopy and especially more severe atopy as measured by the incidence of SPTs positive for > or = 5 allergens (RR: 4.28, 95% CI: 1.54-11.92; P < 0.005) and elevated IAS IgE levels (> or = 1.0 kU/L) (RR: 4.27, 95% CI: 1.08-16.99; P < 0.039). This increased risk was particularly observed in male adolescents., Conclusion: Maternal PE and PA were associated with an increased risk of severe atopy, especially in male adolescent offspring.

Objectives: Most previous studies on the association between moisture or mold problems in the home and respiratory symptoms in children were cross-sectional and based on self-reported exposure. The aim of this study was to evaluate the impact of objectively observed moisture damage and visible mold in the homes on early-life respiratory morbidity and atopic sensitization in a birth cohort., Methods: Building inspection was performed by building engineers in the homes of 396 children, and the children were followed up with questionnaires from birth to the age of 18 months. Specific immunoglobulin E levels were measured at the age of 1 year., Results: Doctor-diagnosed wheezing was associated with the severity of moisture damage in the kitchen and with visible mold in the main living area and especially in the bedroom of the child. The risk for parent-reported wheezing apart from cold increased with the severity of moisture damage in the kitchen. Moisture damage in the bathrooms or other interior spaces had no significant association with wheezing. No significant associations were observed for other end points, such as cough, or respiratory infections. There was a suggestion for an increased risk for sensitization to cat dander linked with moisture and mold exposure., Conclusions: This birth-cohort study supports previous observations that moisture mold problems in the kitchen and in the main living area increase the risk for wheezing in early childhood. The results underline the importance of assessing separately the health effects of moisture and mold problems in different areas of the home.

Background: Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life., Objective: We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring., Methods: Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990-1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests., Results: Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56-13.0]; OR, 2.53 [95% CI, 1.19-5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44-22.03]; OR, 3.37 [95% CI, 1.46-7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring., Conclusion: The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children.

Enzymes are high-molecular-weight proteins and highly sensitizing occupational allergens used widely in industrial processes. Lactase has been described to cause work-related respiratory and conjunctival immunoglobulin (Ig)-E-mediated sensitizations in workers in the pharmaceutical industry. In these previous reports, allergic rhinoconjunctivitis or asthma was confirmed with prick tests but not by challenge tests. Lactase previously has not been described as a cause of immediate or delayed contact skin reaction. Furthermore, there are no previous reports of lactase-specific IgE. We report a case of protein contact dermatitis and allergic rhinoconjunctivitis from occupational exposure to lactase in a pharmaceutical worker. The patient exhibited strong positive responses to lactase in prick tests. In an open application test, lactase elicited whealing, and in patch testing, lactase elicited an eczematous reaction. Serum lactase-specific IgE antibodies were demonstrated in immunospot and radioallergosorbent test assays, and lactase-IgE-binding fractions and their specificities were examined in immunoblot and immunoblot inhibition assays. The chamber challenge test was performed to detect the association between lactase sensitization and rhinoconjunctival symptoms. Our results have confirmed the previous observations that lactase can induce occupational IgE-mediated respiratory and conjunctival sensitizations, but they show that contact skin reactions caused by lactase may also occur.

Early sensitization to inhaled allergens predicts later asthma and allergy until school age, but studies on early exposure have given conflicting results. The purpose of this study was to evaluate the association between early wheezing, early exposure, or sensitization to pets and pollens and later asthma or allergy until adulthood. We have prospectively followed-up a cohort of 83 infants hospitalized for bronchiolitis in 1981-1982. Cat and dog ownership (early exposure) and inhalant allergen-specific IgE measurements (early sensitization) were registered at <3 years of age. Later, asthma and allergy were evaluated repeatedly between 3 and 20 years of age. Twenty-eight children were exposed to pets in early life, and 8 children were sensitized to pets and 10 children were sensitized to pollens. Birth season and early exposure or sensitization to pets were not significantly associated with later asthma and allergy. Wheezing was present at 3-6 years of age in 8 of 10 children sensitized to pollens (OR, 5.07; 95% CI, 1.48-17.31 versus nonsensitized), and asthma was present in 4 of 9 children at 8.5-10 years of age (OR, 9.53; 95% CI, 2.01-45.54). In multivariate analyses, early sensitization predicted asthma until 13.5-16 years of age. Seasonal rhinoconjunctivitis was not significantly associated with early exposure or sensitization to pets or pollens. In wheezing infants, early sensitization to seasonal pollens predicts subsequent wheezing and asthma until adolescence. No association was found between early exposure and sensitization to pets and later outcome.

Although eosinophilia in wheezing infants predicts subsequent wheezing, it is not known how long the association persists. Our aim was to evaluate the connection between blood eosinophilia in infancy and later wheezing/asthma until adulthood, with special attention paid to infection-induced changes in blood eosinophils. We have prospectively followed up 83 infants until adulthood after hospitalization for bronchiolitis in 1981-1982. Blood eosinophils were determined in a counting chamber on admission and on convalescence 4-6 weeks later. Data on recurrent wheezing and asthma were registered prospectively at five follow-ups until the age of 18-20 years. The median (25th-75th percentile) eosinophil count was 0.100 x 10E9/L (0.028-0.321) on admission and 0.231 x 10E9/L (0.119-0.368) on convalescence. Eosinophils during bronchiolitis or infection-induced changes in eosinophils were not associated with subsequent wheezing/asthma at any age during the follow-up. The result was similar in univariate and multivariate analyses. Respiratory syncytial virus (RSV) bronchiolitis patients had lower eosinophils on admission than non-RSV cases, but the changes induced by RSV or other infection did not differ significantly. In univariate analyses, elevated eosinophils on convalescence predicted later wheezing until 3-4 years of age. In multivariate analysis, adjusted for RSV etiology, age on admission, and histories of earlier wheezing and atopy, elevated eosinophils on convalescence predicted increased asthma risk at 2-3 years (OR, 2.26; 95% CI, 1.29-3.95), at 3-4 years (OR, 2.24; 95% CI, 1.27-3.95), and at 8.5-10 years (OR, 2.16; 95% CI, 1.01-4.64). Eosinophilia outside, but not during, infection predicted recurrent wheezing until preschool and early school years but not thereafter.

In the present cohort, 85% of infants hospitalized for wheezing outgrew their symptoms until puberty, but 30-40% had asthma, depending on criteria, again in young adulthood. The aim of this study was to determine early predictors for adulthood asthma, bronchial reactivity, and lung function abnormalities in infants hospitalized for bronchiolitis. Fifty-two children hospitalized for bronchiolitis at < 2 years of age were restudied at the median age of 19 years. Wheezing histories and early risk factors for later asthma were recorded prospectively during infancy. The follow-up study consisted of a written questionnaire, physical examination, flow-volume spirometry, methacholine inhalation challenge, home peak expiratory flow monitoring, and skin-prick tests. In univariate analyses, parental asthma and repeated wheezing at age the age of 0-1 years and 0-2 years predicted adulthood asthma. Repeated wheezing at age the age of 0-1 years predicted later bronchial reactivity. Onset and recurrence of wheezing at < 1 year of age, parental atopy and asthma, and maternal smoking during infancy were related to subnormal lung function parameters. In multivariate logistic regression, adjusted for sex, age on admission, current smoking, and atopy in infancy and, currently, repeated wheezing both at < 1 year and < 2 years of age was an independent predictor for adulthood asthma. Parental asthma and repeated wheezing predict adulthood asthma in infants hospitalized for bronchiolitis, and maternal smoking predisposes them to lung function impairment in adulthood.

Objective: To determine the outcome until adulthood after wheezing in infancy, compared with pneumonia in infancy and with controls., Design: An 18- to-20-year prospective cohort study., Setting: Pediatric department at a university hospital, providing primary hospital care for a defined population. Patients Fifty-four children hospitalized for bronchiolitis and 34 for pneumonia at younger than 2 years, and 45 controls with no early-life wheezing or hospitalization, were studied at median age 19 years., Main Outcome Measures: A questionnaire on asthma symptoms and medication, physical examination, flow volume spirometry (FVS), methacholine inhalation challenge (MIC), home peak expiratory flow (PEF) monitoring, and skin prick testing (SPT) to common inhalant allergens. The 2 asthma definitions were physician-diagnosed asthma and previously diagnosed asthma with recent asthmatic symptoms (physician-diagnosed asthma included)., Results: By the 2 definitions, asthma was present in 30% (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.12-10.10) and in 41% (OR 1.38; 95% CI, 0.37-5.21) in the bronchiolitis group, in 15% (OR, 5.50; 95% CI, 1.87-16.14) and in 24% (OR, 2.07; 95% CI, 0.59-7.22) in the pneumonia group, and in 11% in the control group. After bronchiolitis, the FVS values were forced vital capacity (FVC), 108% (SD, 13%) of predicted; forced expiratory volume in 1 second, 98% (SD, 12%); forced expiratory volume in 1 second divided by FVC, 91% (SD, 7.6%); midexpiratory flow at 50% of the FVC, 74% (SD, 19%); and midexpiratory flow at 25% of the FVC, 74% (SD, 22%). Bronchial reactivity by MIC was present in 25 (48%) of 52 subjects in the bronchiolitis group, in 13 (42%) of 31 in the pneumonia group, and in 14 (32%) of 44 in the control group. The prevalence of atopy (positive SPTs) was 48% to 63% in the 3 groups. In a logistic regression adjusted for atopy and smoking, infantile bronchiolitis was an independent risk factor for asthma by both definitions., Conclusion: The increased risk for asthma persists until adulthood after bronchiolitis in infancy.

The effect of farming on the risk of upper airway symptoms is not clear. In this cross-sectional, population-based study, 198 female farmers, 50 nonfarmers living on a farm, and 218 nonfarmers not living on a farm, filled in a symptom questionnaire and underwent skin-prick testing with common and agricultural allergens. In the logistic regression analysis, the latter group served as a control. Several adjustments were made, including childhood farming environment. Current farming was found to decrease the risks of pet- and pollen-induced upper airway symptoms, dose-dependently with the intensity and duration of animal husbandry. Including skin-test positivity to pets in the regression models did not affect the negative association between farming and pet-induced symptoms. In contrast, animal husbandry increased the risk of farm work-induced upper airway symptoms. Animal husbandry often induces work-related upper airway symptoms. However, the present study among female adults suggests that it may also decrease the risk of pet- and pollen-induced upper airway symptoms.

A microbe-specific diagnosis in community-acquired pneumonia (CAP) is difficult in children, and studies on nonspecific chest radiographic and host response markers have been inconsistent. Serum procalcitonin (PCT) is a newly recognized, promising marker for differentiating between bacterial and viral infections. Serum PCT was measured by a luminometric assay in 190 children with CAP diagnosed in the primary healthcare setting during a population-based study in a geographically defined population. The pneumococcal, mycoplasma, chlamydia, and viral etiology of infections was studied by an extensive serologic test panel. The median PCT concentrations were 0.47, 0.46, and 0.35 ng/mL in children aged <5 years, 5-9 years, and >/=10 years (P = 0.004). An elevated PCT >1.0 ng/mL was seen in 12.1% and >2.0 ng/mL in only 2.1% of the children. No association was seen between severity (inpatient vs. outpatient care) and etiology of CAP (evidence for pneumococcal, mycoplasma, or chlamydia, vs. viral infection). We conclude that serum PCT measurements have no role in the diagnosis of bacterial CAP in children in primary healthcare settings., (Copyright 2003 Wiley-Liss, Inc.)

Aim: It has been suggested that living on a farm decreases the risk of childhood allergy, especially if farming involves livestock. The aim of this study was to examine the association between farming and allergy in children, and the influence of atopic heredity in this association., Methods: The cross-sectional data of the 7981 children aged 13-14 y who participated in the Finnish ISAAC study between the years 1994 and 1995 were used to evaluate the association between farming and allergy., Results: Living on a farm was associated with a decreased risk of current symptoms of allergic rhinoconjunctivitis among all children (aOR 0.79; 95% CI 0.63, 0.99), and with a decreased risk of hay fever, especially among those children with a parental history of hayfever (aOR 0.60; 95% CI 0.40-0.89, p = 0.072 for interaction). The children of farmers with a history of hay fever also had a decreased risk of current wheeze (aOR 0.38; 95% CI 0.12-1.24, p = 0.040 for interaction). No significant association was found between farming and either asthma or eczema. Children living on a farm with livestock had the lowest risk of allergic rhinoconjunctivitis (aOR 0.69), followed by those living on a farm without livestock (aOR 0.89) compared with the non-farming children (p-value for trend 0.024)., Conclusion: Our results support the recent findings on a decreased risk of allergy among the children living on farms. A possible differential effect of parental history of hay fever on the relation of farming environment and the risk of allergic symptoms warrant further investigation.

Background: Influence of household pets in the development of childhood asthma or atopy has been controversial., Objective: The purpose of this study was to investigate whether pet exposure in early life decreases the subsequent risk of frequent wheezing and/or allergic sensitization., Methods: This was a prospective observational birth cohort study. The setting was a large health maintenance organization in Tucson, Ariz; the subjects were a population sample of 1246 newborns enrolled at birth and followed prospectively to age 13 years. The main outcome measures were as follows: time to first report of frequent wheezing (>3 episodes in the past year), skin prick test reactivity at 6 years and 11 years of age, and total serum IgE at 9 months, 6 years, and 11 years of age., Results: Children living in households with > or =1 indoor dogs at birth were less likely to develop frequent wheeze than those not having indoor dogs (P =.004). This inverse association was confined to children without parental asthma (hazard ratio = 0.47; P <.001 [Cox regression]) and was not evident for children with parental asthma (hazard ratio = 0.96; P =.87). Adjustment by potential confounders did not change the results. Indoor cat exposure was not significantly associated with the risk of frequent wheezing. Neither cat exposure in early life nor dog exposure in early life was associated with skin prick test reactivity or total serum IgE at any age., Conclusion: Dog exposure in early life might prevent the development of asthma-like symptoms, at least in low-risk children with no family history of asthma. Nevertheless, early pet exposure does not seem to significantly influence the development of allergic sensitization.

The incidence of subcutaneous induration in 23 breast cancer patients with postmastectomy radiotherapy was investigated. The patients were treated with three different radiotherapy schedules 7. 9-9.8 years ago. The incidence was correlated with the biological effective dose (BED) at different depths from the skin surface and a best fit was obtained using an alpha/beta ratio of 2 Gy. The most representative depth at which to assess dose for subcutaneous induration was 2 mm which is near the subcutaneous fat/dermis interface.

Two-thirds of the children with asthma in our area use cromones and only one-third steroids as the maintenance therapy. This study aimed to evaluate our treatment policy based on the international consensus. Peak expiratory flow (PEF), dynamic spirometry and bronchodilation test results were therefore collected in 195 school-aged patients who visited our outpatient clinic in 1995. Sixty-four children (33%) used cromoglycate, 86 (44%) nedocromil and 45 (23%) inhaled steroids. Twenty-five (12%) needed combination therapy, mainly with salmeterol. Lung function results were good, and there were no significant differences between the therapeutic groups irrespective of whether pre- or postbronchodilator values were considered. PEF was decreased in eight (4%), forced expiratory volume in one second (FEVI) in four (2%) and maximum mid-expiratory flow (MMEF) in 33 (17%) patients. At least one result was decreased in 39 (20%) cases, in most cases (77%) MMEF alone. Significant rises after salbutamol inhalations were observed in 17 (9%) in PEF, in two (1%) in FEV1 and 20 (10%) in MMEF values. Thus, the bronchodilation test was positive in 33 (17%) cases, and in 22 (11%) cases it was the only sign of bronchial obstruction. Over 70% of the children with asthma can be treated with cromones by a stepwise treatment modality. Inhaled steroids can be restricted to those not controllable by cromones. Lung function tests, including postbronchodilator values, should be part of the follow-up of continuous maintenance medication for asthma.

The purpose of this study was to determine the value of serum measurements of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in diagnosing asthma in children, and to investigate the influence of concomitant allergic diseases and atopic sensitization, assessed by skin prick tests (SPT), on these markers. ECP and EPX were determined in 36 children with asthma, in 33 children with other symptoms from lower airways disease (OSLA), and in 166 control children. Sixteen children with asthma but no anti-inflammatory therapy had significantly higher concentrations of ECP and EPX (ECP: 27.5 microg/L, P < 0.001; EPX: 59.9 microg/L, P < 0.001) than the control children (ECP: 11.2 microg/L; EPX: 26.2 microg/L). In the 20 children on anti-inflammatory therapy, ECP values were similar to those of controls. The children with OSLA (ECP: 13.6 microg/L, P < 0.01; EPX: 47.2 microg/L, P < 0.001) differed significantly from controls. When using the value of 24.7 microg/L (97.5 percentile in the 68 non-atopic controls) as a pathologic upper limit for ECP, 10 (63%) of the 16 asthmatic children on no maintenance medication, two (10%) of the 20 asthmatics on maintenance therapy, and 11 (33%) of the 33 children with OSLA had high ECP; the same figure was only 18 (11%) in the 166 control children. Both ECP and EPX had a significant association with allergic disorders and with SPT reactivity. In multivariate logistic regression analysis, an elevated ECP was significantly associated with asthma (OR 2.3, 95%CI 1.1-4.9) and atopic dermatitis (2.9, 1.2-6.9), and an elevated EPX was significantly associated with asthma (2.61, 1.19-5.74) and allergic rhinoconjunctivitis (5.23, 1.46-18.73). We conclude that serum concentrations of both ECP and EPX are higher in asthmatic than in healthy children. However, other allergic diseases, such as allergic rhinoconjunctivitis, atopic dermatitis, and allergic skin sensitization also raise the concentrations of these markers. This limits their usefulness in the diagnosis of childhood asthma.

The aim of this study was to determine whether there are regional differences in the prevalence of childhood asthma in Finland. A secondary objective was to assess the concordance between a written and a video questionnaire on asthma symptoms. In 1994-1995, the self-reported prevalence of asthma symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 yrs, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The ISAAC written and video (AVQ 3,0) questionnaires were administered in the school setting. The prevalences of any wheezing during the previous 12 months in the ISAAC video questionnaire were 10% in East Finland (Kuopio County, n=2,821), 12% in South Finland (Helsinki area, n=2,771), 12% in Southwest Finland (Turku and Pori County, n=2,983), and 11% in North Finland (Lapland, n=3,032). The prevalences in the ISAAC written questionnaire were 13, 20, 15, and 16%, respectively. The surveys were performed during winter, except in Helsinki where the survey was carried out mainly during the spring pollen season. During autumn, the prevalence in the written questionnaire in Helsinki was 16%. In multivariate analysis, boys had a lower prevalence than girls, and smokers a threefold higher prevalence than nonsmokers. In conclusion, the prevalence of childhood asthma is lower in Finland than in other European countries, and may be even lower in the eastern part of the country. In contrast to the results from some other European countries, prevalences were lower in the video than in the written questionnaire, which suggests that translating the word "wheezing" into other languages, including Finnish, may produce results that cannot be compared. The strong association of smoking with wheeze both in the video and written questionnaires should be considered in further analysis of the ISAAC study.