Restriction of lung volumes but normal function of pulmonary tissue in mulibrey nanism.

BACKGROUND: Mulibrey nanism (MUL) is a rare growth restriction disorder with multiple organ manifestations caused by genetic defects affecting the TRIM37 protein. A perimyocardial heart disease is the most serious manifestation. Many MUL children appear to suffer from airway obstruction related to infection or exercise, prompting use of inhaled therapies. Asthma medication is continued up to adolescence or even to adulthood due to persisting of symptoms. The pulmonary pathophysiology has previously not been evaluated in any MUL cohort. METHODS: Thirty three finnish MUL patients (median age 20 years) were investigated with several lung function tests: spirometry with bronchodilatation test, single-breath diffusing capacity for carbon monoxide, single-breath lung volume measurements with helium dilution, and thoracic gas volume, airway resistance and specific conductance measurements with a body plethysmograph. As MUL typically affects body proportions, all variables were compared with reference values and with predicted values calculated from sitting height. RESULTS: Total lung capacity and forced vital capacity were markedly reduced (total lung capacity [TLC] and forced vital capacity [FVC], P < .001, 51%-63% of predicted) and also forced expiratory volume in the first second was reduced (FEV1; P < .001, 47%-57%). No signs of airway obstruction was seen (normal FEV1/FVC and specific airway conductance SGaw). Diffusing capacity (DLCO) was decreased (P < .001, 60%-67%) but when related to alveolar volume it was increased (DLCO/VA, P < .001, 130%-148%). Bronchodilatation suggesting active asthma (FEV1 change ≥12% and ≥​​200 mL) was found only in one patient. CONCLUSION: MUL patients typically have volume restriction of the lungs, but function of the pulmonary tissue remains intact. Evidence of asthma in lung function testing at adult age is rare.

Immunohistology and remodeling in fatal pediatric and adolescent asthma.

BACKGROUND: Thickening of reticular basement membrane, increased airway smooth muscle mass and eosinophilic inflammation are found in adult fatal asthma. At the present study the histopathology of fatal paediatric and adolescent asthma is evaluated. METHODS: Post-mortem lung autopsies from 12 fatal asthma cases and 8 non-asthmatic control subjects were examined. Thickness of reticular basement membrane (RBM) and percentage of airway smooth muscle (ASM%) mass area were measured and inflammatory cells were counted. Patient records were reviewed for clinical history. RESULTS: The age range of the cases was from 0.9 to 19.5 years, eight were males and five had received inhaled corticosteroids. Thickened RBM was detected in majority of the cases without any correlation to treatment delay, age at onset of symptoms or diagnosis. In the large airways ASM was clearly increased in one third of the cases whereas the median ASM% did not differ from that in healthy controls (14.0% vs. 14.0%). In small airways no increase of ASM was found, instead mucous plugs were seen in fatal asthma. The number of eosinophils, plasmacytoid dendritic cells, macrophages, and B-cells were significantly increased in fatal asthma cases compared with controls and the two latter correlated with the length of the fatal exacerbation. CONCLUSIONS: The findings highlight the strong presence of eosinophils and mucous plugs even in small airways in children and adolescents with fatal asthma. Thickened RBM was obvious in majority of the patients. Contrary to our hypothesis, increased ASM% was detected in only one third of the patients.

Measurement of tidal breathing flows in infants using impedance pneumography.

Tidal breathing flow volume (TBFV) profiles have been used to characterise altered lung function. Impedance pneumography (IP) is a novel option for assessing TBFV curves noninvasively. The aim of this study was to extend the application of IP for infants and to estimate the agreement between IP and direct pneumotachograph (PNT) measurements in assessing tidal airflow and flow-derived indices.Tidal flow profiles were recorded for 1 min simultaneously with PNT and uncalibrated IP at baseline in 44 symptomatic infants, and after methacholine-induced bronchoconstriction in a subgroup (n=20).The agreement expressed as the mean deviation from linearity ranged between 3.9 and 4.3% of tidal peak inspiratory flow, but was associated with specific airway conductance (p=0.002) and maximal flow at functional residual capacity (V'maxFRC) (p=0.004) at baseline. Acute bronchoconstriction induced by methacholine did not significantly affect the agreement of IP with PNT. TBFV indices derived from IP were slightly underestimated compared to PNT, but were equally well repeatable and associated with baseline V'maxFRC (p=0.012 and p=0.013, respectively).TBFV profiles were consistent between IP and PNT in most infants, but the agreement was affected by reduced lung function. TBFV parameters were not interchangeable between IP and PNT, but had a similar association with lung function in infants.

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years.

BACKGROUND: Associations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear. OBJECTIVE: To report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes. METHODS: Fifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children. RESULTS: Forty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age. CONCLUSION: The lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

Bone health and risk factors of cardiovascular disease--a cross-sectional study in healthy young adults.

OBJECTIVE: Both osteoporosis and cardiovascular disease (CVD) are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low physical activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD) and turnover markers (BTMs) in apparently healthy cohort. DESIGN: A cross-sectional assessment of 155 healthy 32-year-old adults (74 males) was performed for skeletal status, CVD risk factors and lifestyle factors. METHODS: We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP), collagen I carboxy-terminal telopeptide (ICTP) and urine collagen I aminoterminal telopeptide (U-NTX), as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were assessed using DXA scanning. Associations were tested with partial correlations in crude and adjusted models. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria) with multivariate analysis. RESULTS: Osteocalcin and P1NP correlated inversely with insulin (R = -0.243, P = 0.003 and R = -0.187, P = 0.021) and glucose (R = -0.213, P = 0.009 and R = -0.190, P = 0.019), but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (R = -0.162, P = 0.053 and R = -0.093, P = 0.266) and with glucose (R = -0.099, P = 0.240 and R = -0.133, P = 0.110), respectively. Whole body BMD associated inversely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model. CONCLUSIONS: In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass, no association continued to be present. In addition to fat mass, lifestyle factors, especially physical activity, modified the associations between CVD and bone characteristics. Prospective studies are needed to specify the role of mediators and lifestyle factors in the prevention of CVD and osteoporosis.

Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

Assessing direct and indirect airway hyperresponsiveness in children using impulse oscillometry.

BACKGROUND: Airway hyperresponsiveness (AHR) is a hallmark of asthma but its assessment is usually restricted to older children who are capable of performing the maneuvers involved in spirometry. In younger children, a feasible option to perform the lung function measurement is impulse oscillometry (IOS), which requires less cooperation. OBJECTIVE: To evaluate whether assessment of AHR by IOS could differentiate children with various obstructive symptoms from one another. METHODS: One hundred twenty-one children (median age 6.0 years, range 3.7-8.1 years) were examined: 31 with probable asthma characterized by current troublesome lung symptoms, 61 with a history of early wheezing disorder (recurrent wheezing ≤24 months of age), 15 with a history of bronchopulmonary dysplasia, and 14 healthy controls. Indirect AHR was assessed by exercise and mannitol challenge tests, and direct AHR was assessed with methacholine using IOS. AHR to exercise was defined as an increase of at least 40% in respiratory resistance at 5 Hz. In the mannitol and methacholine challenges, the dose causing an increase of 40% in respiratory resistance at 5 Hz was calculated. RESULTS: AHR to exercise was good at differentiating children with current troublesome lung symptoms from those in the other groups (P < .001). AHR to methacholine separated children with current troublesome lung symptoms, early wheezing disorder, and bronchopulmonary dysplasia from the controls (P < .001), whereas the mannitol test did not distinguish among the study groups (P = .209). CONCLUSION: The methacholine and exercise challenge tests with IOS identify children with probable asthma characterized by troublesome lung symptoms and therefore may represent a practical aid in the evaluation of AHR in young children.

Breast-fed infants and their later cardiovascular health: a prospective study from birth to age 32 years.

The aim of the present study was to evaluate the impact of infant breast-feeding on cardiovascular risk in young adults. This unique study group involved 158 subjects (eighty-two females) originally collected prospectively at birth in 1975 and followed up to the age of 32 years. Frequent visits during the first year guaranteed the knowledge of the precise duration of breast-feeding. All infants received at least some breast milk. Participants were assessed for both individual cardiovascular risk factors (blood pressure, plasma lipids, homeostatic model assessment of insulin resistance and waist circumference) and the general clinical risk of cardiovascular events by calculating the Framingham risk score (FRS) and the metabolic syndrome criteria score (NCEP-ATPIII; National Cholesterol Education Program's Adult Treatment Panel III). Data on lifestyle factors were carefully collected. Linear regression analyses revealed that the effect of the duration of breast-feeding was not relevant (0·02 decrease in the FRS per one additional breast-feeding month; 95 % CI - 0·19, 0·09). Similarly, the effect of breast-feeding was minor on all of the individual cardiovascular risk factors. We used sex, physical activity, dietary fat and vitamin C, smoking and alcohol consumption as covariates. Again, logistic regression analyses detected no significant impact of the duration of breast-feeding on the risk of the metabolic syndrome according to the NCEP-ATPIII (OR 0·95, 95 % CI 0·8, 1·1). The strongest independent predictor for later CVD risk was male sex. In conclusion, in this prospectively followed cohort of young adults born at term and at weight appropriate for gestational age, the duration of breast-feeding did not have an impact on the accumulation of cardiovascular risk factors.

Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms.

BACKGROUND: Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies. METHODS: Thirty-nine infants (median age 0.9 years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies. RESULTS: The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1ß, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine. CONCLUSIONS: A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aire⁻/⁻ mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD.

Very low birth weight and respiratory outcome: association between airway inflammation and hyperresponsiveness.

BACKGROUND: The respiratory outcomes after preterm birth have changed, and it is unclear whether increased airway hyperresponsiveness (AHR) later in childhood is associated with airway inflammation. OBJECTIVE: To investigate the association between AHR and fractional exhaled nitric oxide (FeNO), including the alveolar concentration of nitric oxide, in school-age children with very low birth weight (VLBW). METHODS: Twenty-nine children with VLBW, 33 children with a history of early wheeze, and 60 healthy controls underwent a FeNO measurement and bronchial challenge test with histamine. Atopy was assessed with skin prick tests. RESULTS: Children with VLBW had well-preserved baseline lung function but significantly increased AHR, expressed as the dose response slope (P < .001). Geometric mean FeNO levels were similar between VLBW children and healthy controls, and a history of bronchopulmonary dysplasia had no effect. In the VLBW and early wheeze groups, AHR was associated with FeNO (r = 0.47, P = .01, and r = 0.43, P = .013, respectively), but in a stratified analysis, this association was significant only in atopic individuals. By using the multiple flow FeNO technique, the bronchial nitric oxide flux rather than alveolar nitric oxide concentrations were associated with AHR in both children with early wheeze and VLBW. CONCLUSION: We conclude that in VLBW children AHR is related to FeNO but only in atopic individuals. Similar to children with early wheeze, this association is dependent on bronchial flux rather than alveolar nitric oxide concentration. It is likely that AHR is modified by atopic inflammation rather than by inflammatory process due to prematurity.

The effect of montelukast on respiratory symptoms and lung function in wheezy infants.

Our aim was to investigate the effectiveness of montelukast in recurrently wheezy infants. We randomised 113, 6-24-month-old children with recurrent wheezing to receive either placebo or montelukast daily for an 8-week period. The primary end-point was symptom-free days. The secondary aims were to evaluate the effect of montelukast on rescue medication, on lung function, airway responsiveness and exhaled nitric oxide fraction (FeNO). Clinical response and FeNO were determined, the functional residual capacity (FRC) and specific airway conductance (sGaw) were measured using an infant whole-body plethysmograph, the maximal flow at functional residual capacity (V'max,FRC) was recorded using the squeeze technique and airway responsiveness was evaluated by performing a dosimetric methacholine challenge test. There was no significant difference in changes in weekly symptom-free days between the montelukast and the placebo group (3.1-3.7 days versus 2.7-3.1 days, p = 0.965). No significant differences were detected in the secondary end-points, i.e. use of rescue medication, FRC, sGaw, V'max,FRC, FeNO or airway responsiveness between groups. Montelukast therapy did not influence the number of symptom-free days, use of rescue medication, lung function, airway responsiveness or airway inflammation in recurrently wheezy, very young children.

Neuroendocrine cell hyperplasia of infancy: a prospective follow-up of nine children.

Neuroendocrine cell hyperplasia of infancy (NEHI) has recently been described as an obstructive airway disease that affects infants aged 1-24 months, and presents typically with tachypnoea, crackles and hypoxia. The pathogenesis of the disease is unknown. We describe the clinical course of nine infants with radiologically and histologically confirmed NEHI. Host or environmental factors were not associated with the disease development. All infants with lung function tests demonstrated findings consistent with severe irreversible peripheral airway obstruction, assessed with whole body plethysmography (6/6) or the rapid thoracoabdominal compression technique (5/5). While the symptoms abated in all infants, six infants developed a non-atopic asthma during the follow-up. Systemic or inhaled corticosteroid treatment did not affect the duration of the symptoms. NEHI may mimic severe asthma and thus this entity should be taken into account when evaluating infants with chronic respiratory symptoms.

Salmeterol and fluticasone in young children with multiple-trigger wheeze.

BACKGROUND: Treatment guidelines recommend using an inhaled corticosteroid (ICS) plus a long-acting ß(2)-agonist (LABA) for childhood asthma when the symptoms are not controlled by ICS alone, but the appropriate use of LABAs in children continues to be debated. OBJECTIVE: To compare the efficacy of an inhaled salmeterol and fluticasone propionate combination, 50/100 µg twice daily, with fluticasone propionate, 100 µg twice daily, or salmeterol, 50 µg twice daily, in children with multiple-trigger wheeze. METHODS: A total of 105 children 4 to 7 years of age with multiple-trigger wheezing based on respiratory symptoms and bronchodilator responsiveness and/or exercise-induced bronchoconstriction without a viral cold were randomized to salmeterol-fluticasone, fluticasone propionate alone, or salmeterol alone via a metered-dose inhaler and a spacer device for 8 weeks. The primary efficacy outcome was exhaled nitric oxide level. Secondary outcomes were lung function measurements via impulse oscillometry, respiratory symptoms, and rescue medication use. RESULTS: The exhaled nitric oxide levels decreased after all treatments, significantly more so after salmeterol-fluticasone and fluticasone than with salmeterol (adjusted geometric means at 8 weeks: salmeterol-fluticasone, 9.4 ppb; fluticasone, 9.3 ppb; salmeterol, 13.9 ppb; salmeterol-fluticasone vs salmeterol, P = .02; fluticasone vs salmeterol, P = .01). No treatment differences were found with respect to respiratory symptoms or median rescue use. Salmeterol-fluticasone resulted in a small but statistically significant improvement in baseline lung function compared with fluticasone. All treatments were equally well tolerated. CONCLUSION: The effects of salmeterol-fluticasone and fluticasone were comparable, although lung function improvement was better with salmeterol-fluticasone than with fluticasone alone. There is no obvious benefit in initiation therapy with salmeterol-fluticasone rather than fluticasone alone in the treatment of steroid-naive children with multiple-trigger wheeze. TRIAL REGISTRATION: Pathway of clinical trial registry of Helsinki University:http://www.hus.fi/?Path=1;28;2530;9899;9900;23618;23903;33578.

Breastfeeding and determinants of adult body composition: a prospective study from birth to young adulthood.

BACKGROUND: The impact of breastfeeding on adult body composition is controversial. We evaluated effects of lifestyle and childhood-related factors, including infant feeding, on adult body composition. METHODS: We determined total body and trunk fat and lean mass by densitometry in 158 adults who were born full-term and prospectively followed from birth to the age of 32 years. Data on various factors, extending from infancy to adulthood, with potential effect on body composition, were recorded. RESULTS: Scapular skinfold thickness at 12 months correlated with adult trunk (R = 0.22, p = 0.005) and body fat percentage (R = 0.18, p = 0.023). In linear regression analysis, current physical activity (R = -0.33, p < 0.001) and maternal BMI (R = 0.28, p = 0.002) were associated with adult body fat percentage. Gender (R = 0.78, p < 0.001) and weight gain during infancy (R = 0.147, p = 0.008) were associated with adult lean mass. In the analysis of covariance, prolonged breastfeeding tended to lead to lower fat percentage in adulthood, but no direct association with the duration of breastfeeding and adult body composition was confirmed. CONCLUSIONS: Current physical activity, growth in infancy, gender and maternal BMI influence adult body composition. Breastfeeding has an indirect influence on adult body fat accumulation by affecting growth and body adiposity in infancy.

[Congenital ciliary dysfunction in children]. / Värekarvojen synnynnäiset toimintahäiriöt lapsilla.

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.

Infant milk feeding influences adult bone health: a prospective study from birth to 32 years.

BACKGROUND: Peak bone mass, attained by early adulthood, is influenced by genetic and life-style factors. Early infant feeding and duration of breastfeeding in particular, associate with several health-related parameters in childhood. The aim of this study was to examine whether the effects of early infant feeding extend to peak bone mass and other bone health characteristics at adult age. METHODS AND FINDINGS: A cohort of 158 adults (76 males) born in Helsinki, Finland, 1975, prospectively followed up from birth, underwent physical examination and bone densitometry to study bone area, bone mineral content (BMC), and bone mineral density (BMD) at 32 years of age. Life-style factors relevant for bone health were recorded. For data analysis the cohort was divided into three equal-size groups according to the total duration of breastfeeding (BF): Short (≤3 months), Intermediate and Prolonged (≥7 months) BF groups. In males short BF is associated with higher bone area, BMC, and BMD compared to longer BF. Males in the Short BF group had on average 4.7% higher whole body BMD than males in the Prolonged BF group. In multivariate analysis, after controlling for multiple confounding factors, the influence of BF duration on adult bone characteristics persisted in males. Differences between the three feeding groups were observed in lumbar spine bone area and BMC, and whole body BMD (MANCOVA; p = 0.025, p = 0.013, and p = 0.048, respectively), favoring the Short BF group. In women no differences were observed. CONCLUSIONS: In men, early infant milk feeding may have a significant impact on adult bone health. A potential explanation is that the calcium and phosphate contents were strikingly higher in formula milk and commercial cow milk/cow milk dilutions as opposed to human milk. Our novel finding merits further studies to determine means to ensure optimal bone mass development in infants with prolonged breastfeeding.

Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years.

BACKGROUND: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years. METHODS: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit. RESULTS: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and ß agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively). CONCLUSIONS: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children.