[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

Long-Term Respiratory Support for Children and Adolescents in Austria: A National Survey.

BACKGROUND: Population-based data on pediatric patients on long-term respiratory support (LTRS) in Austria are lacking. This study aimed to record the pediatric departments active in this field, as well as number and characteristics of patients on LTRS. METHODS: A national cross-sectional study was carried out by means of questionnaires sent to all pediatric departments in Austria. RESULTS: All departments answered to the questionnaires. On June 1st, 2013, the reference day for this study, 12 of the 41 pediatric departments in Austria were active in the field. At this time, these centers were caring for 143 patients, 111 (77.6%) of them under 18 years, which corresponds to a prevalence of 7.4 per 100 000. The patients suffered from neuromuscular disorders (44%), other neurological disorders (18.9%), disorders of respiratory drive (9.1%), obstructive sleep apnea (8.4%), thoracal and spinal diseases (8.4%), pulmonary disorders (4.9%) and other diseases (6.3%). Continuous positive airway pressure was used in 6.3%, non-invasive ventilation in 60.1% and invasive ventilation in 33.6% of the patients, respectively. LTRS was performed at home in 92.3%. CONCLUSION: LTRS represents a common management strategy in children and adolescents with a variety of disorders. Census reports such as this one provide the basis for appropriate planning of resource allocation. The age distribution of our patients shows the need for structured transition into adult care.

Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data.

BACKGROUND: Genome-wide association studies (GWAS) repeatedly identified 1q23 (FCER1A), 5q31 (RAD50-IL13 and IL4), and 12q13 (STAT6) as major susceptibility loci influencing the regulation of total serum IgE levels. As GWAS may be insufficient to capture causal variants, we performed fine-mapping and re-genotyping of the three loci using 1000 Genomes Project datasets. METHODS: Linkage disequilibrium tagging polymorphisms and polymorphisms of putative functional relevance were genotyped by chip technology (24 polymorphisms) or MALDI-TOF-MS (40 polymorphisms) in at least 1303 German children (651 asthmatics). The effect of polymorphisms on total serum IgE, IgE percentiles, and atopic diseases was assessed, and a risk score model was applied for gene-by-gene interaction analyses. Functional effects of putative causal variants from these three loci were studied in silico. RESULTS: Associations from GWAS were confirmed and extended. For 1q23 and 5q31, the majority of associations were found with mild to moderately elevated IgE levels, while in the 12q13 locus, single-nucleotide polymorphisms (SNPs) were associated with strongly elevated IgE levels. Gene-by-gene interaction analyses suggested that the presence of mutations in all three loci increases the risk for elevated IgE up to fourfold. CONCLUSION: This fine-mapping study confirmed previous associations and identified novel associations of SNPs in 1q23, 5q31, and 12q13 with different levels of serum IgE and their concomitant contribution to IgE regulation.

A role of FCER1A and FCER2 polymorphisms in IgE regulation.

BACKGROUND: Both FCER2 and FCER1A encode subunits of IgE receptors. Variants in FCER1A were previously identified as major determinants of IgE levels in genome-wide association studies. METHODS: Here we investigated in detail whether FCER2 polymorphisms affect IgE levels alone and/or by interaction with FCER1A polymorphisms. To cover the genetic information of FCER2, 21 single-nucleotide polymorphisms (SNPs) were genotyped by Illumina HumanHap300 BeadChip (5 SNPs) and the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS; 14 SNPs) in at least 1303 Caucasian children (651 asthmatics) (ISAAC II/ MAGICS population); genotypes of two SNPs were imputed. RESULTS: SNP rs3760687 showed the most consistent effect on total serum IgE levels (b [SE] = -0.38 [0.16]; P = 0.016), while FCER2 polymorphisms in general were predominantly associated with mildly-to-moderately increased IgE levels (50th and 66th percentiles). Gene-by-gene interaction analysis suggests that FCER2 polymorphism rs3760687 influences IgE levels mainly in individuals not homozygous for the risk allele of FCER1A polymorphism rs2427837, which belongs to the major IgE-determining tagging bin in the population. CONCLUSION: FCER2 polymorphism rs3760687 affects moderately elevated total serum IgE levels, especially in the absence of homozygosity for the risk allele of FCER1A SNP rs2427837.

Polymorphisms in the IRF-4 gene, asthma and recurrent bronchitis in children.

BACKGROUND: Interferon-regulatory factors (IRFs) play a crucial role in immunity, not only influencing interferon expression but also T cell differentiation. IRF-4 was only recently recognized as a further major player in T cell differentiation. OBJECTIVE: As IRF-1 polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of IRF-4 variants on allergy, asthma and related phenotypes in German children. METHODS: Fifteen tagging single nucleotide polymorphisms (SNPs) in the IRF-4 gene were genotyped by MALDI-TOF MS in the cross-sectional ISAAC phase II study population from Munich and Dresden (age 9-11; N = 3099). Replication was performed in our previously established genome-wide association study (GWAS) data set (N = 1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood (MAGIC) study and reference children from the ISAAC II study. RESULTS: SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The IRF-4 variant rs9378805 was associated with recurrent bronchitis in the ISAAC population and replicated in the GWAS data set where further SNPs showed associations with recurrent bronchitis and asthma. CONCLUSIONS: We found genetic associations in IRF-4 to be associated with recurrent bronchitis in our two study populations. Associated polymorphisms are localized in a putative regulatory element in the 3'UTR region of IRF-4. These findings suggest a putative role of IRF-4 in the development of bronchitis.

Lung transplantation in children following bone marrow transplantation: a multi-center experience.

Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long-term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life-saving option for patients with end-stage lung disease that maybe offered for the treatment of GVHD. We report a multi-center experience of pediatric LTx following BMT in 11 patients age- and gender-matched with 11 controls who received LTx for end-stage lung disease secondary to CF. Overall death was 36.4% over a follow-up period of 19 months (range 3-36 months) for the cases and 27.3% for the control group followed for 17 months (range 8-32 months). Median FEV1 one yr post-transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow-up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end-stage lung disease post-BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non-existent in these cases.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Bilateral lung transplantation for pediatric idiopathic pulmonary arterial hypertension: a multi-center experience.

Many children with idiopathic pulmonary arterial hypertension (IPAH) experience disease progression despite advanced medical therapy. In these children, heart-lung or bilateral lung transplantation (BLTx) remain the only therapeutic options when other treatments fail. Data on functional outcome after BLTx in children with IPAH are limited. We report a multi-center experience of BLTx for pediatric IPAH. We performed a retrospective study including 25 centers within the International Pediatric Lung Transplant Collaborative. Children with IPAH who underwent BLTx were included (1996-2006). Twenty-three children underwent BLTx for IPAH, most of whom were in WHO class III or IV level of function pre-transplantation. At 6 months post-transplantation, 82% of children reported improvement in level of function to WHO class I. The median FEV(1) was 89% (12-126) of predicted at 12 months post-transplantation. Ten patients (44%) developed BOS at a median of 42 months (3-85), of whom five died at a median of 27 months (4-86) post-transplantation. Overall mortality was 4% at 3 months post-transplantation. The median survival for children in this cohort was 45 months (2-123). Our data suggest that BLTx is a valuable therapeutic option for children with end-stage IPAH with outcomes comparable to that after heart-lung transplantation in children with pulmonary arterial hypertension or those patients undergoing lung transplantation for other indications. In the majority of children, a good cardiopulmonary function is possible following BLTx, making BLTx a good therapeutic option and maximizing donor organ utilization by allowing more hearts to be available for children needing cardiac transplantation.

Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses.

INTRODUCTION: The immunosuppressive therapy in solid organ transplantation targets mainly the T- and B-cell-mediated immune response. However, there is evidence that it neither suppresses sensitization nor clinical manifestation of allergic diseases in organ-transplanted patients. OBJECTIVE: This study addresses the question whether allergen-specific responses are altered by systemic immunosuppression via negative effects on the T-regulatory cell compartment and a more pronounced suppression on Th1-type T-cell responses. MATERIAL AND METHODS: Peripheral blood mononuclear cells from 65 solid organ-transplanted (kidney, liver, lung) children, adolescents, and young adults and 18 healthy, matched controls were included, and their clinical and sensitization status assessed. Allergen-specific proliferation, intracellular cytokine production, frequency of forkhead box P3 (FOXP3)+ CD3+ CD4+ CD25(high) cells, mRNA expression of IL-10, transforming growth factor (TGF)-ß and FOXP3 (real-time RT-PCR) of peripheral blood mononuclear cells or bronchoalveolar lavage fluid (BAL)-derived cells, and the inhibitory capacity of T-reg cells were investigated. RESULTS: Immunosuppression led to a significantly altered regulatory marker profile expressed by enhanced TGF-ß mRNA production and a reduced frequency of FOXP3+ CD4+ CD3+ cells in solid organ transplanted individuals. FOXP3 expression in BAL cells of lung-transplanted patients was significantly decreased. Allergen-specific proliferation was not significantly altered despite long-term immunosuppression. However, suppression of allergen-specific responses via the T-regulatory cell fraction was deficient in immunosuppressed individuals. CONCLUSION: The results suggest an insufficient control of allergen-specific responses via the Treg-cell compartment under systemic immunosuppression.

Factors influencing age at diagnosis of primary ciliary dyskinesia in European children.

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists. In total, 223 centres from 26 countries reported 1,009 patients aged < 20 yrs. Reported cases per million children (for 5-14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% had situs inversus. Median age at diagnosis was 5.3 yrs, lower in children with situs inversus (3.5 versus 5.8 yrs; p < 0.001) and in children treated in large centres (4.1 versus 4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p < 0.001). This strongly correlated with general government expenditures on health (p < 0.001). This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children.

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease.

Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report.

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative, which is endorsed by both academies.

Mass spectrometrical analysis of the processed metastasis-inducing anterior gradient protein 2 homolog reveals 100% sequence coverage.

Anterior gradient protein 2 homolog is a metastasis-inducing protein in a rat model of rat breast cancer and prognostic for outcome in hormonally treated breast cancer patients. Carrying out protein profiling in several mammalian cells and tissues, we detected this protein (synonym: secreted cement gland protein XAG-2 homolog) that was originally described in toad skin, in human bronchial epithelia. Tissues obtained from biopsies were homogenised and extracted proteins were run on two-dimensional gel electrophoresis. Following in-gel digestion with proteases trypsin, AspN, LysC and chymotrypsin, mass spectrometrical analysis was carried out by MALDI-TOF/TOF. The use of MS following multi-enzyme digestion of the protein resulted into 100% sequence coverage. MS/MS analysis enabled sequencing of 87% of the protein structure. This percentage does not include the signal peptide that was not observed in our protein due to processing. No posttranslational modifications were detectable and no sequence conflicts were observed. Complete analysis, unambiguous identification and characterisation of this biologically important protein could be shown, which is relevant for the definition of a marker protein that has been described so far by immunochemical methods only. Complete analysis is of importance as it forms the basis for all future work on this protein and, moreover, may serve as an analytical tool for further studies.

Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study -- 24 months results of the Study of Prevention of Allergy in Children in Europe.

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.

Long- and medium-term ozone effects on lung growth including a broad spectrum of exposure.

The effects of semi-annual and 3.5 yr mean ozone (O3) concentrations on children's forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were assessed over a study period of 3.5 yrs in 2,153 schoolchildren from 15 study sites in South Western Germany and Lower Austria. Spirometric parameters were assessed twice a year, and differences between consecutive measurements divided by days were considered as a measure of lung growth. Exposure was analysed in four classes, separately for winter and summer (semi-annual mean O3 concentrations 22-30, 30-38, 38-46, 46-54 parts per billion (ppb) in summer and 4-12, 12-20, 20-28, 28-36 ppb in winter). Regression methods for repeated measurements were used, and these revealed a significantly lower FVC (FEV1) increase estimated at -19.2 (-18.5) mL x 100 days(-1) for semi-annual mean O3 exposure in summer between 46 and 54 ppb compared to exposure between 22 and 30 ppb. However, in winter, the estimated difference in FVC (FEV1) was 16.4 (10.9) mL x 100 days(-1) between the semi-annual O3 class 28-36 ppb and the 4-12 ppb class. By means of linear regression the study found that there was no association between growth rates and mean summer O3 for FVC and FEV1 over a 3.5 yr period. The authors conclude that medium-term effects on schoolchildren's lung growth are possibly present, but are in the long-term not detectable for forced vital capacity and forced expiratory volume in one second over a 3.5 yr period due to partial reversibility.

Parental farming protects children against atopy: longitudinal evidence involving skin prick tests.

BACKGROUND: There is growing evidence that the development of allergic sensitization can be influenced by environmental co-factors. Studies showed that growing up on a farm can protect children against allergic sensitization. However, little is known whether this 'farming effect' can only be observed in early lifetime or whether it also plays a role in later childhood. OBJECTIVE: The aim of our study was to test whether a farming environment is negatively associated with a new occurrence of skin prick test (SPT) positivity in school children. As a secondary outcome we investigated whether children living on a farm lose their allergic sensitization more frequently than other children. METHODS: In a longitudinal design, 1150 elementary school children (mean age 7.8 years, SD 0.7) were recruited from nine different areas of Austria in 1994. A questionnaire and an SPT involving seven common aero-allergens were performed at study entry and at follow-up 3 years later. RESULTS: A total of 844 children, who underwent two SPTs, were included in the analyses; 15.1% of their families reported working on a farm. Adjusting for potential confounders (parental education, number of siblings, sex, family history of allergy), parental farming was inversely related to the prevalence and new occurrence of SPT positivity [no farming 12.2%, part-time farming 6%, full-time farming 2.2% incidence; odds ratio (OR) farming vs. non-farming 0.34, 95% confidence interval (CI) 0.12-0.98]. Furthermore, children living in a farming environment were more likely to lose their SPT positivity during follow-up (no farming 14.6%, part-time farming 50%, full-time farming 60% loss of sensitization; OR farming vs. non-farming 8.06; 95% CI 2.05-31.75). No difference in the pattern of sensitization to specific allergens could be observed between farming and non-farming children. CONCLUSION: A farming environment has a strong negative effect on the development of allergic sensitization. Furthermore, the study provides evidence that atopic children living on a farm lose their SPT positivity more frequently than children from non-farming environments.

Prevention of sensitization to house dust mite by allergen avoidance in school age children: a randomized controlled study.

BACKGROUND: Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders. OBJECTIVE: To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children. METHODS: As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5-7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust-mite allergen. Control group children were given non-specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed. RESULTS: Ten children in the prophylactic group and 19 in the control group were lost to follow-up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child. CONCLUSION: Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.

Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren.

The effects of particulate matter <10 microm in diameter (PM10) and other air pollutants on lung function were assessed in 975 schoolchildren, from eight communities in Lower Austria between 1994-1997. In each community, air pollution data were collected. Spirometry was performed twice a year. PM10 concentration (mean concentration between two subsequent lung-function measures in spring and autumn (summer interval) or between autumn and spring (winter interval)) showed a mean value of 17.36 microg x m(-3) in the summer interval and 21.03 microg m(-3) in the winter interval. A slower increase in the forced expiratory volume in one second (FEV1) and midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25-75) with age in children exposed to higher summer PM10 was observed in the 3-yr study period. After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM10 by 10 microg x m(-3) was associated with a decrease in FEV1 growth of 84 mL x yr(-1) and 329 mL x s(-1) x yr(-1) for MEF25-75. Nitrogen dioxide and ozone also showed a negative effect on lung-function growth, confirming previous work. The authors concluded that long-term exposure to particulate matter <10 microm in diameter had a significant negative effect on lung-function proxy for the development of large (forced expiratory volume in one second) and small (midexpiratory flow between 25 and 75% of the forced vital capacity) airways, respectively, with strong evidence for a further effect of ozone and nitrogen dioxide on the development of forced vital capacity and forced expiratory volume in one second.

Predictors of lung function in infants at high risk of atopy: effect of allergen avoidance.

Children of atopic parents are recognised as being at higher risk of developing bronchial asthma, drawing the attention of prevention strategies towards this population. Due to recent advances, lung function abnormalities in asthmatic children may now be measured early in life. The aim ofthis investigation was to examine possible predictors of lung function development in a sub sample of high-risk infants who took part in an allergy avoidance study In 60 babies of atopic parents, measurements of upper airways inflammation were performed at 4 weeks of age, respiratory symptoms were assessed at 6 and 12 months of age, and lung function (Vmax, FRC) was measured at 18 months by the rapid thoracoabdominal compression technique. Twenty-eight babies were enrolled in an allergen avoidance program, and 32 recruited as controls. No significant differences were detected for V'max,FRC between the intervention group (mean 331 ml s(-1)) and the control group (359 ml s(-1)), P = 0.382. A multiple linear regression model could explain levels of V'max FRC by weight gain since birth (beta = -35.35 ml s(-1) kg(-1), P = 0.022) and by eosinophilic cationic protein (ECP) (beta = -0.95 ml s(-1) microl(-1), P = 0.044), but not by intervention. Lung function measured at the age of 18 months in high-risk children is associated with weight gain and nasal ECF.