Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. METHODS: The GA2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. CONCLUSION: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.

Pharmacodynamic considerations in the treatment of pulmonary hypertension in infants: challenges and future perspectives.

INTRODUCTION: Pulmonary hypertension (PH) in infants is a life-threatening disease with a high mortality. It is treated with different drugs that act upon the three different pathways involved in its development. Studies on the drug pharmacodynamics are sparse, however. AREAS COVERED: This review reports a search on the currently available literature in English on drug pharmacodynamics in infants with PH. The search yielded 2499 citations in the EMBASE, MEDLINE, COCHRANE, Web of Science, PubMed Publisher and Google Scholar databases since 1961. Of these, 1691 did not meet the research question. Eventually, 655 articles were of interest, including 44 randomized controlled trials on PH in infants. These articles cover all PH medications used in infancy. EXPERT OPINION: Mortality of PH in infancy has dropped considerably over the past years. iNO is widely used, followed by sildenafil - both orally and intravenously in contrast to the exclusively oral use in adults. In adults, the pharmacodynamic effects of the different medications are tested using the 6-minute walking test, changes in the NYHA classification, or by invasive measurement of pulmonary pressure. Reliable data of pharmacodynamics tested in adequate series or in randomized controlled trials in children are lacking, however, for most of these medications.

Management of pulmonary hypertension in neonates with congenital diaphragmatic hernia.

Pulmonary hypertension associated with congenital diaphragmatic hernia is still one of the major challenges in neonatal intensive care units. Several relevant pathways in its pathogenesis have been described and studied, but the absence of well-designed randomized controlled trials and the scattered data on the pharmacokinetics and pharmacodynamics of most of the drugs used in these patients hamper progress significantly. This review aims to give an overview of current management strategies in the antenatal and neonatal phase, and provides founded clinical recommendations.

Challenges in non-neonatal extracorporeal membrane oxygenation.

This review will address the different challenges for the use of non-neonatal extracorporeal membrane oxygenation (ECMO). It will discuss the available evidence for the use of pediatric ECMO in respiratory and circulatory failure, focusing on indications and contra-indications and choice of ECMO mode. Furthermore we will try to define optimal treatment goals, identify primary outcome parameters and calculate the expected need for non-neonatal ECMO per 1.000.000 inhabitants.

Infant eczema, infant sleeping problems, and mental health at 10 years of age: the prospective birth cohort study LISAplus.

BACKGROUND: Cross-sectional studies suggest an association between eczema and mental health problems, possibly modified by sleeping problems, but prospective evidence is missing. We aimed to prospectively investigate the relationship between infant eczema (within first 2 years of age), infant sleeping problems (within first 2 years of age), and the risk of mental health problems at 10 years of age. METHODS: Between 1997 and 1999, a population-based birth cohort was recruited in Munich, Leipzig, Wesel, and Bad Honnef, Germany, and followed until 10 years of age. Physician-diagnosed eczema, parent-reported sleeping problems, and known environmental risk factors for atopy were regularly assessed until 10 years of age. Mental health was measured using the Strengths and Difficulties Questionnaire (parent version) at 10 years of age. We applied logistic regression modeling adjusting for environmental and lifestyle factors, allergic comorbidity, and family history of eczema. RESULTS: From the original cohort of 3097 neonates, 1658 (54%) were followed until age 10, while 1578 (51%) were eligible for analysis. In the fully adjusted model, children with infant eczema were at increased risk of hyperactivity/inattention at 10 years of age [odds ratio (OR) 1.78; 95% confidence interval (95% CI) 1.02-3.09]. Infant eczema with concurrent sleeping problems predicted emotional problems [OR 2.63; 95% confidence interval (95% CI) 1.20-5.76] and conduct problems (OR 3.03; 95% CI 1.01-9.12) at 10 years of age. CONCLUSIONS: Infant eczema with concurrent sleeping problems appears to be a risk factor for the development of mental health problems.

Evaluation of possible tissue damage in patients undergoing extracorporeal shock wave lithotripsy employing C-reactive protein.

Extracorporeal shock wave lithotripsy (ESWL) has become the most common treatment for stones in the upper urinary tract. Tissue injury related to ESWL has been documented. C-reactive protein (CRP) is the classical acute-phase protein most recognized as an early marker in diseases characterized by inflammation and tissue injury. Possible tissue trauma by ESWL was evaluated by serial CRP determinations in 150 patients with kidney stones, whose follow-up was uneventful. The mean CRP-concentration prior to ESWL was 6.34 mg/l. The majority of patients did not show any further elevation of CRP-levels. Mean CRP-levels were 7.62 mg/l on the first, 6.12 mg/l on the third and 5.09 mg/l on the fifth day after ESWL. No correlation was observed between the number of shock waves and CRP levels. Judged by CRP-determinations tissue damage induced by ESWL can be considered to be minimal as no marked CRP-elevations could be observed in patients with an uneventful follow-up after ESWL.

Comparing the effects of perinatal and later childhood lead exposure on neuropsychological outcome.

Blood lead values (PbB) from cord blood and maternal samples as well as present PbB from venous blood samples were available for 114 six- to seven-year-old children living in or near the city of Nordenham (FRG). These children represented 30% of all children born between July 1975 and August 1976 in the district hospital (N = 383). The range of cord blood PbB was 4-31 micrograms/100 ml (mean = 8.2 micrograms/100 ml) and of maternal PbB was 4-30 micrograms/100 ml (mean = 9.3 micrograms/100 ml), whereas the range for present PbB was 3.9-22.8 micrograms/100 ml (mean = 8.2 micrograms/100 ml). The degree of correlation between maternal and cord blood PbB was 0.79, despite the poor technical quality of many cord blood samples as compared to maternal blood samples (less coagulation). These children were given a battery of neurophysiological and neuropsychological tests. The present report is restricted to psychological performance measures. The test battery covered intelligence (reduced Wechsler Intelligence Scale for Children), visual-motor performance (Bender Test, GFT), serial reaction performance (Wiener Reaction Device), and cued as well as choice reaction times. After correction for confounding by means of stepwise multiple-regression analysis, few significant associations between blood lead levels and performance deficit occurred. In general the degree of association was somewhat stronger for present PbB than for perinatal PbB: With increasing present PbB there was a borderline drop of performance IQ (P less than 0.1), as well as a significant disruption of serial reactions, which was more pronounced for the difficult (P less than 0.01) than for the easier version of the Wiener Device (P less than 0.05). A similar but less pronounced pattern of associations was observed for maternal PbB but not for cord blood PbB. Some influence of perinatal lead exposure on later performance can, thus, still be detected if, in addition to cord blood PbB, maternal PbB is taken into account as well.

Neuropsychological effects of lead in children: interactions with social background variables.

Following a short and selective summary of findings from psychological studies on lead-induced cognitive dysfunction in man, our own studies in lead-exposed children are briefly described in more detail. These studies, run in the cities of Duisburg and Stolberg, were based on tooth lead levels as the principal indicator of long-term cumulative lead exposure. From a comprehensive sample of neuropsychological outcome measures, only few significant findings emerged, namely lead-related deficits of visual-motor integration and of reaction performance, but not of general intelligence. Without exception, the observed lead effects were small compared to those of social background. An interesting interaction was found between lead exposure and social background for visual-motor integration and for reaction performance: for both these measures, but not for intelligence, the degree of association between performance deficit and lead exposure was more pronounced in socially disadvantaged children than in those from a more middle-class background. This finding was tentatively discussed within a transactional model of development. The common practice of simply controlling the effects of confounding social factors by analysis of covariance or related techniques appears doubtful in this context.