Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children.

BACKGROUND: Attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (C1-INH-HAE) usually begin during childhood or adolescence. However, limited data are available regarding indications and modalities of treatment of children. This study evaluated recombinant human C1-INH (rhC1-INH) for HAE attacks in children. METHODS: This open-label, phase 2 study included children aged 2-13 years with C1-INH-HAE. Eligible HAE attacks were treated intravenously with rhC1-INH 50 IU/kg body weight (maximum, 4200 IU). The primary end-point was time to beginning of symptom relief (TOSR; ≥20 mm decrease from baseline in visual analog scale [VAS] score, persisting for two consecutive assessments); secondary end-point was time to minimal symptoms (TTMS; <20 mm VAS score for all anatomic locations). RESULTS: Twenty children (aged 5-14 years; 73 HAE attacks) were treated with rhC1-INH. Seventy (95.9%) of the attacks were treated with a single dose of rhC1-INH. Seven (35.0%) children were treated for four or more attacks. Overall, median TOSR was 60.0 minutes (95% confidence interval [CI], 60.0-65.0); data were consistent across attacks. Median TTMS was 122.5 minutes (95% CI, 120.0-126.0); data were consistent across attacks. No children withdrew from the study due to adverse events. No treatment-related serious adverse events or hypersensitivity reactions were reported; no neutralizing antibodies were detected. CONCLUSIONS: Recombinant human C1-INH was efficacious, safe, and well tolerated in children. Data support use of the same dosing regimen for HAE attacks in children (50 IU/kg; up to 4200 IU, followed by an additional dose, if needed) as is currently recommended for adolescents and adults.

Intrauterine exposure to polycyclic aromatic hydrocarbons, fine particulate matter and early wheeze. Prospective birth cohort study in 4-year olds.

The main goal of the study was to determine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured by PAH-DNA adducts in umbilical cord blood and early wheeze. The level of PAH-DNA adducts in the cord blood is assumed to reflect the cumulative dose of PAHs absorbed by the foetus over the prenatal period. The effect of prenatal PAH exposure on respiratory health measured by the incidence rate ratio (IRR) for the number of wheezing days in the subsequent 4 yr follow-up was adjusted for potential confounding factors such as personal prenatal exposure to fine particulate matter (PM(2.5)), environmental tobacco smoke (ETS), gender of child, maternal characteristics (age, education and atopy), parity and mould/dampness in the home. The study sample includes 339 newborns of non-smoking mothers 18-35 yr of age and free from chronic diseases, who were recruited from ambulatory prenatal clinics in the first or second trimester of pregnancy. The number of wheezing days during the first 2 yr of life was positively associated with prenatal level of PAH-DNA adducts (IRR = 1.69, 95%CI = 1.52-1.88), prenatal particulate matter (PM(2.5)) level dichotomized by the median (IRR = 1.38; 95%CI: 1.25-1.51), maternal atopy (IRR = 1.43; 95%CI: 1.29-1.58), mouldy/damp house (IRR = 1.43; 95%CI: 1.27-1.61). The level of maternal education and maternal age at delivery was inversely associated with the IRRs for wheeze. The significant association between frequency of wheeze and the level of prenatal environmental hazards (PAHs and PM(2.5)) was not observed at ages 3 or 4 yrs. Although the frequency of wheezing at ages 3 or 4 was no longer associated with prenatal exposure to PAHs and PM(2.5), its occurrence depended on the presence of wheezing in the first 2 yr of life, which nearly tripled the risk of wheezing in later life. In conclusion, the findings may suggest that driving force for early wheezing (<24 months of age) is different to those leading to later onset of wheeze. As we reported no synergistic effects between prenatal PAH (measured by PAH-DNA adducts) and PM(2.5) exposures on early wheeze, this suggests the two exposures may exert independent effects via different biological mechanism on wheeze.

Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non-smoking mothers.

Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of prenatal programming, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM(2.5)), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study, personal measurements of PM(2.5) were performed over 48 h in the second trimester of pregnancy. After delivery, infants were followed for 5 years; the interviewers visited participants in their homes to record children's respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months thereafter. In the fifth year of the follow-up, children were invited for standard lung function testing of levels of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)) and forced expiratory volume in 0.5 s (FEV(0.5)). There were 176 children of non-smoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression showed a significant deficit of FVC at the highest quartile of PM(2.5) exposure (beta coefficient = -91.9, P = 0.008), after adjustment for covariates (age, gender, birthweight, height and wheezing). Also FEV(1) level in children was inversely correlated with prenatal exposure to PM(2.5), and the average FEV(1) deficit amounted to 87.7 mL (P = 0.008) at the higher level of exposure. Although the effect of PM(2.5) exposure on FEV(0.5) was proportionally weaker (-72.7, P = 0.026), it was also statistically significant. The lung function level was inversely and significantly associated with the wheezing recorded over the follow-up. The findings showed that significant lung function deficits in early childhood are associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth.

Antihistamine medication may alleviate negative effects of prenatal exposure to polycyclic aromatic hydrocarbons (PAH) on lung function in children. Birth cohort prospective study.

The main purpose of the present study was to test the hypothesis that the depressed lung growth attributable to prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may be modified by the intake of antihistamine medications. Individual prenatal PAH exposure was assessed by personal air monitoring in 176 children who were followed over nine years, in the course of which outdoor residential air monitoring, allergic skin tests for indoor allergens, lung function tests (FVC, FEV(1), FEV(05), and FEF(25-75)) were performed. The analysis with the General Estimated Equation (GEE) showed no association between prenatal PAH exposure and lung function in the group of children who were reported to be antihistamine users. However, in the group of antihistamine non-users all lung function tests except for FEF(25-75) were significantly and inversely associated with prenatal airborne PAH exposure. The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting from PAH exposure may be caused by the allergic inflammation within lung.

[Prevalence of allergic diseases in primary school children in Cracow and surroundings--risk factors]. / Wystepowanie chorób alergicznych u dzieci w szkolach podstawowych Krakowa i okolic--próba okreslenia glównych czynników ryzyka.

Prevalence of allergic diseases has been increasing over recent decades, especially in developed countries. The aim of this study was to assess prevalence of bronchial asthma and allergic rhinitis in children of Krakow at school age, depending on home and school environment conditions. The study was carried out in two stages: questionnaire based on ISAAC questionnaire and skin prick tests in children with symptoms suggesting allergic disease were performed. Altogether 532 children from 4 primary schools (2 in central and 2 in peripheral parts of the city) were included. Symptoms suggestive of allergic disease were reported by 304 children (57.1%), including asthma in 145 (27.2%) and allergic rhinitis in 288 children (54.1%). Asthma and allergic rhinitis was previously diagnosed in 19 (4%) and 138 (26%) children respectively. In younger age groups more children reported symptoms suggestive of asthma. Pupils from schools in the center of Krakow exposed to high level of traffic significantly more frequently reported asthma and had diagnosed allergic rhinitis. Increased prevalence of allergic rhinitis symptoms was observed in children exposed to passive smoking. Skin prick tests were positive only in 29.7% of children qualified for them. The results of the study suggest that in pupils with allergic rhinitis in whom skin prick tests are weakly positive for inhaled allergens, environmental factors may play an important role in the development of clinical symptoms.

Intrauterine exposure to fine particulate matter as a risk factor for increased susceptibility to acute broncho-pulmonary infections in early childhood.

Over the last decades many epidemiologic studies considered the morbidity patterns for respiratory diseases and lung function of children in the context of ambient air pollution usually measured in the postnatal period. The main purpose of this study is to assess the impact of prenatal exposure to fine particulate matter (PM2.5) on the recurrent broncho-pulmonary infections in early childhood. The study included 214 children who had measurements of personal prenatal PM2.5 exposure and regularly collected data on the occurrence of acute bronchitis and pneumonia diagnosed by a physician from birth over the seven-year follow-up. The effect of prenatal exposure to PM2.5 was adjusted in the multivariable logistic models for potential confounders, such as prenatal and postnatal ETS (environmental tobacco smoke), city residence area as a proxy of postnatal urban exposure, children's sensitization to domestic aeroallergens, and asthma. In the subgroup of children with available PM2.5 indoor levels, the effect of prenatal exposure was additionally adjusted for indoor exposure as well. The adjusted odds ratio (OR) for incidence of recurrent broncho-pulmonary infections (five or more spells of bronchitis and/or pneumonia) recorded in the follow-up significantly correlated in a dose-response manner with the prenatal PM2.5 level (OR=2.44, 95%CI: 1.12-5.36). In conclusion, the study suggests that prenatal exposure to PM2.5 increases susceptibility to respiratory infections and may program respiratory morbidity in early childhood. The study also provides evidence that the target value of 20µg/m(3) for the 24-h mean level of PM2.5 protects unborn babies better than earlier established EPA guidelines.

Dose-dependent relationship between prenatal exposure to fine particulates and exhaled carbon monoxide in non-asthmatic children. A population-based birth cohort study.

OBJECTIVES: The main goal of the study was to assess possible association between fetal exposure to fine particulate matter (PM2.5) and exhaled carbon monoxide (eCO) measured in non-asthmatic children. MATERIAL AND METHODS: The subjects include 118 children taking part in an ongoing population-based birth cohort study in Kraków. Personal samplers of PM2.5 were used to measure fine particle mass in the fetal period and carbon monoxide (CO) in exhaled breath from a single exhalation effort at the age of 7. In the statistical analysis of the effect of prenatal PM2.5 exposure on eCO, a set of potential confounders, such as environmental tobacco smoke (ETS), city residence area, sensitization to house dust allergens and the occurrence of respiratory symptoms monitored over the seven-year follow-up was considered. RESULTS: The level of eCO did not correlate with the self-reported ETS exposure recorded over the follow-up, however, there was a positive significant relationship with the prenatal PM2.5 exposure (non-parametric trend p = 0.042). The eCO mean level was higher in atopic children (geometric mean = 2.06 ppm, 95% CI: 1.58-2.66 ppm) than in non-atopic ones (geometric mean = 1.57 ppm, 95% CI: 1.47-1.73 ppm) and the difference was statistically significant (p = 0.036). As for the respiratory symptoms, eCO values were associated positively only with the cough severity score recorded in the follow-up (nonparametric trend p = 0.057). In the nested multivariable linear regression model, only the effects of prenatal PM2.5 and cough severity recorded in the follow-up were related to eCO level. The prenatal PM2.5 exposure represented 5.1%, while children's cough represented only 2.6% of the eCO variability. CONCLUSION: Our study suggests that elevated eCO in non-asthmatic children may result from oxidative stress experienced in the fetal period and that heme oxygenase (HO) activity in body tissues may be programmed in the fetal period by the exposure to fine particulate matter.

Early wheeze as reported by mothers and lung function in 4-year-olds. Prospective cohort study in Krakow.

SUMMARY: The purpose of the study was to check the hypothesis that early wheezing as reported by mothers would be associated with reduced lung function in 4-year olds. Study participants were recruited prenatally, as part of a prospective cohort study on the respiratory health of young children exposed to various ambient air pollutants. After delivery, infants were followed over 4 years and the interviewers visited participants at their home to record respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months in the 3rd and 4th years. In the 4th year of follow-up, children were invited for standard lung function testing by spirometry quantified by forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced expiratory volume in 0.5 sec (FEV(0.5)) levels. Out of 258 children attending spirometry testing 139 performed at least two acceptable exhalation efforts. Cohort children with acceptable spirometric measurements did not differ with respect to wheezing experience and exposure characteristics from those without. The study shows that episodic wheeze was reported in 28.1% of 4-year olds, 6.5% had transient wheeze, and 4.3% had recurrent wheeze. There was an increased frequency of wheezing symptoms and their duration in transient and recurrent wheezers. Adjusted multivariable regression models for gender and height showed that children who reported more than two episodes of wheezing at any point over the follow-up had FVC values lower by 120.5 ml (P = 0.016) and FEV(1) values lower by 98.3 ml (P = 0.034) compared to those who did not report any wheezing; children experiencing more than 10 wheezing days by age 4 showed FVC deficit of 87.4 ml (P = 0.034) and FEV(1) values of 65.7 ml (P = 0.066). The ratios of FEV(1)/FVC%, and FEV(0.5)/FVC% were neither associated with wheezing episodes nor wheezing days. In recurrent wheezers, lung function decrement amounted to 207 ml of FVC, 175 ml of FEV(1), and 104 ml of FEV(0.5). In conclusion, our findings show that wheezing experience during early postnatal life may be associated with lung function deficit of restrictive character in preschool children and detailed history of wheeze in early postnatal life, even though not physician-confirmed, may help define the high risk group of children for poor lung function testing.