Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children.

Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC), and ß-Crosslaps (ß-CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC, and ß-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in ß-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate, and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the ß-CTx-to-OC ratio was inversely associated with 25(OH)D (-1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and ß-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker ß-CTx was observed.

[Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine]. / Leitlinie zur Spirometrie. Leitlinie der Deutschen Atemwegsliga, der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin zur Spirometrie.

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.

Early life risk factors of being overweight at 10 years of age: results of the German birth cohorts GINIplus and LISAplus.

OBJECTIVE: To develop a prediction model that quantifies the risk of being overweight at 10 years of age. SUBJECTS/METHODS: In total, 3121 participants from the GINIplus (German Infant Nutritional Intervention plus environmental and genetic influences on allergy development) and LISAplus (Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics) German birth cohorts were recruited. We predicted standardized body mass index (BMI) at 10 years of age using standardized BMIs from birth to 5 years. Parental education, family income and maternal smoking during pregnancy were considered as covariates. Linear and logistic regression models were used to evaluate the impact of risk factors on BMI and on being overweight at 10 years of age, respectively. RESULTS: Birth weight, standardized BMI at 5 years (60-64 months) (ß=0.77; 95% confidence interval (CI): 0.73-0.81) and maternal smoking during pregnancy were positively associated with standardized BMI at 10 years of age. Standardized BMI and overweight at 5 years were strongest predictors of being overweight at 10 years. Conversely, high parental education conferred a protective effect (ß=-0.15; 95% CI: -0.29 to -0.01). Being overweight at 5 years (60-64 months) increased the risk of being overweight at 10 years of age with odds ratios above 10. Among children who were predicted to be overweight at 10 years, cross-validation results showed that 76.8% of female subjects and 68.1% of male subjects would be overweight at 10 years of age. CONCLUSION: BMI and being overweight at 5 years of age are strong predictors of being overweight at 10 years of age. The effectiveness of targeted interventions in children who are overweight at 5 years of age should be explored.

Association of gas cooking with children's respiratory health: results from GINIplus and LISAplus birth cohort studies.

UNLABELLED: Previous studies have found inconsistent results on the association between asthma in children and gas cooking emissions. We aimed to assess the effects of the long-term exposure to gas cooking on the onset of asthma and respiratory symptoms, focusing on wheezing, in children from two German birth cohorts: LISAplus and GINIplus. A total of 5078 children were followed until the age of 10 years. Asthma, wheezing, gas cooking, and exposure to other indoor factors were assessed through parental reported questionnaires administered periodically. Logistic and multinomial regressions adjusting for potential confounders were performed. The prevalence of asthma and persistent wheezing was higher among children exposed to gas cooking but the results were not statistically significant. Exposure to gas cooking was positively associated (P-value < 0.05) with exposure to other indoor factors (dampness, environmental tobacco smoke, and pets). Our results did not show a statistically significant association between the exposure to gas cooking and children's respiratory health. PRACTICAL IMPLICATIONS: These analyses are consistent with the assumption of no effect of the exposure to low doses of nitrogen dioxide. The strong positive associations found between gas cooking and other indoor factors highlight the importance of considering other indoor factors when assessing health effects of gas cooking. Low-dose exposure to indoor nitrogen dioxide through gas cooking might not contribute to increase the risk of asthma and respiratory symptoms in children.

Maternal compliance with nutritional recommendations in an allergy preventive programme.

AIMS: To assess maternal compliance with nutritional recommendations in an allergy preventive programme, and identify factors influencing compliance behaviour. METHODS: Randomised double-blind intervention study on the effect of infant formulas with reduced allergenicity in healthy, term newborns at risk of atopy. Maternal compliance with dietary recommendations concerning milk and solid food feeding was categorised. RESULTS: A total of 2252 newborns were randomised to one of four study formulas. The drop out rate during the first year of life was 13.5% (n = 304). The rates of high, medium, and low compliance to milk feeding during weeks 1-16 were 83.4%, 4.0%, and 7.5%; the corresponding rates to solid food feeding during weeks 1-24 were 60.0%, 12.1%, and 22.9%. In 5.1% of subjects no nutritional information was available. Low compliance was more frequent among non-German parents, parents with a low level of education, young mothers, smoking mothers, and those who weaned their infant before the age of 2 months. CONCLUSIONS: Evaluation of allergy preventive programmes should take into account non-compliance for assessing the preventive effectiveness on study outcome.

[Myasthenia gravis following lupus erythematosus disseminatus]. / Ein Fall von Myasthenia gravis nach Lupus erythematodes disseminatus.

Report on a 15 1/4 year old girl who developed Lupus erythematodes disseminatus when she was 9 years old. Four years later Myasthenia gravis occurred leading to myasthenic crisis in her 16th year of life. The special course of the disease and the diagnostic of Myasthenia gravis are discussed.

[Significance of measurement of the oscillatory resistance to respiration in children. (author's transl)]. / Die Bedeutung der oszillatorischen Atemwiderstandsmessung im Kindesalter.

The oscillatory resistance to respiration (Ros) was measured in 218 children and 260 adults using the Siregnost FD5 (Siemens, Erlangen), and compared with whole body plethysmography (Raw) and with spirometry. There was a markedly better correlation between Ros and Raw (r=0.82;n=88) in children than in adults (r=0.53;n=260). Whereas additional recording of the phase angle in children does not yield any substantial additional information, it is of diagnostic importance in adults. Comparison of Ros with the spirometric values yielded the following sequence of decreasing correlation coefficients (linear regression): FEV1.0, PEF, V 75, MMEF, V 50, V 25, whereas in adults these relationships cannot be described by means of a linear correlation. The results enable us to conclude that in paediatric pneumology an alternative use of whole-body plethysmography and of oscillatory method appears justified.

[Pluriglandular insufficiency due to transfusion haemosiderosis in Blackfan-Diamond anaemia (author's transl)]. / Pluriglanduläre Insuffizienz infolge Transfusionshämosiderose bei Blackfan-Diamond-Anämie.

The article reports on a boy aged 16 1/2 years suffering from transfusion haemosiderosis associated with corticoid-resistant blackfan diamond anaemia. Besides hepatosplenomegalia and cardiomegalia, the course of the disease was mainly determined by the deficient functioning of several endocrine glands. The diagnosis revealed primary hypothyroidism, hypoparathyroidism and partial insufficiency of the pituitary gland.

[The value of measurements of oscillatory resistance in the evaluation of lung function. A comparative study in adults and children (author's transl)]. / Die Bedeutung der oszillatorischen Atemwiderstandsmessung in der Lungenfunktionsdiagnostik: Eine vergleichende Untersuchung bei Erwachsenen und Kindern.

Measurements of total oscillatory impedance (ROS) together with spirometric and body plethysmographic determinations were made in adults and children and the results were compared. In adults (n = 260) correlation was less close (r = 0.53) than it was in 88 children (r = 0.82). Even if ROS was of similar magnitude the phase shift between pressure and flow tended to be more negative than it was in children. These differences are presumably due to anatomical differences between the adult and the growing lung. In interpretation of the results it is suggested that the differences in the ratio: airways compliance/airways resistance reflect changes arising from age and disease processes.

[Comparison of the oscillatory measurement of airway resistance with plethysmography and spirometry in juvenile patients]. / Vergleich der oszillatorischen Atemwiderstandsmessung mit der Plethysmographie und der Spirometrie im Kindesalter.

In 78 children (age 4 to 17 years, height 102 to 179 cm) with and without clinical signs of airway obstruction, spirometric and plethysmographic measurements were compared with the forced oscillation method for determination of resistance to breathing (Ros). Ros was measured with a recently developed apparatus (Siregnost FD5. Siemens) and showed a close correlation with resistance (r = 0.84; n = 78). The spirometric values did not, however, exhibit a definite relationship to Ros. This study demonstrates that airway obstruction in children can be equally well estimated by oscillatory and plethysmographic techniques. Compared with plethysmography, determination of Ros has the particular advantage of being better tolerated by young subjects.