Pharmacotherapy of childhood asthma. An inflammatory disease.

The recognition that asthma constitutes 2 kinds of physiopathological reactions, namely bronchospasms (immediate reactions) and inflammatory responses (late reactions), suggests that the treatment should be focused against these events. Furthermore, the allergen provocation model, showing the existence of immediate and late asthmatic reactions, can be used to study the effects of different antiasthmatic drugs. Recently, the importance of inflammation in the pathogenesis of asthma in adults has led to the development of therapeutic regimens in which anti-inflammatory treatments are used frequently as a first-line step in the management of asthma. Although at the moment the hard data showing inflammation in childhood asthma are scarce, it is assumed that childhood asthma constitutes the same kind of chronic inflammatory processes as in adult asthma and that its treatment should also include anti-inflammatory drugs.     

Are hypodense eosinophils in children activated or immature?

In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils.     

Waardenburg syndrome: clinical differentiation between types I and II

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS.     

Subtelomeric deletions detected in patients with idiopathic mental retardation using multiplex ligation-dependent probe amplification (MLPA)

Subtelomeric rearrangements are responsible for 5% to 10% of cases of unexplained mental retardation. Despite their clinical relevance, methods to screen for these cytogenetically invisible abnormalities on a routine base are scarce. We screened patients with idiopathic mental retardation for subtelomeric aberrations using multiplex ligation-dependent probe amplification (MLPA). This recently developed technique is based on PCR amplification of ligated probes hybridized to chromosome ends. Currently, 41 telomeres can be screened in just two multiplex reactions. Four subtelomeric rearrangements (5.3%) were detected in a group of 75 patients with mild to severe mental retardation in combination with dysmorphic features and/or a familial history of mental retardation: two terminal 1p deletions, a terminal 1q deletion, and a terminal 3p deletion. Deletions could be verified by FISH and marker analysis. In one case the MLPA indicated a terminal 21q deletion due to a 3-bp deletion at the site of the probe, giving a false-positive rate of 1.3%. This study demonstrates that MLPA is a fast and reliable screening method, potentially suitable for use in routine diagnostics.     

Detection of hypodense eosinophils by Percoll multilayer density gradient centrifugation in subjects with normal or slightly elevated eosinophilia. Poor reproducibility and eosinophils of density < 1.077 g/ml.

In patients with marked hypereosinophilia 'hypodense' and 'normodense' eosinophils have been found after density gradient centrifugation. Subsequently this terminology has also been used in studies of patients with milder eosinophilia. However, in these cases the differentiation between normo- and hypodense eosinophils was less clear. This might be due to the high imprecision of the test of density gradient centrifugation, as demonstrated in the first part of this study: the mean within-assay variance of the number of eosinophils in the different density layers was 35%. It was calculated that the test must be performed eight times to obtain an estimate of the true mean for the individual patient. In the second part of the study, the absolute number of 'hypodense eosinophils' in groups of patients with asthma (adults and children) and rheumatoid arthritis (adults) were compared to normal controls. Although a difference in the absolute number of hypodense eosinophils between groups of patients and controls could be demonstrated, the high imprecision of the test of density gradient centrifugation suggested that the technique used was not useful in an individual with normal or slightly elevated eosinophils in the peripheral blood.     

Troponin I sensitivity and specificity for the diagnosis of acute myocardial infarction

This article describes the sensitivity and specificity of troponin I when compared to creatine kinase-MB (CK-MB) and electrocardiography (ECG) for diagnosing acute myocardial infarction (AMI). Two different lower levels for defining positive results with troponin I were evaluated. A retrospective study of 153 patients who presented to the emergency department of a community hospital supplied the pool of patients for this study. Patients included in this study were those for whom a CK-MB was ordered. The majority of these patients were evaluated for chest pain or symptoms suggesting an acute cardiac event. Of the 153 patients studied, CK-MB results were positive in 91 (59%) patients; ECG revealed AMI in 72 (47%) patients. There were 103 (67%) patients who had either positive CK-MB or ECG results. Ninety (59%) patients had a troponin I level greater than 2.0 ng/mL, and 18 (12%) patients had a troponin I level between 0.6 and 2.0 ng/mL. Seven patients whose troponin I level was between 0.6 and 2.0 ng/mL had negative CK-MB and ECG results. Therefore, 11 patients with troponin I between 0.6 and 2.0 ng/mL had AMI. Five patients with positive troponin I results (> 2.0 ng/mL) had negative CK-MB and ECG results. When a troponin I level greater than 0.6 ng/mL was used as a positive value, compared to CK-MB and ECG using either time zero or time 6 hours, the sensitivity was 94% and specificity was 81%. When troponin I greater than 2.0 ng/mL was used to define a positive test, the sensitivity was 85% and specificity was 91% when compared to CK-MB and ECG.     

Early introduction of allergenic foods for the prevention of food allergy from an Asian perspective—An Asia Pacific Association of Pediatric Allergy,Respirology & Immunology (APAPARI) consensus statement

Emerging evidence for the early introduction of allergenic foods for the prevention of food allergies, such as peanut allergy in Western populations, has led to the recent publication of guidelines in the USA and Europe recommending early peanut introduction for high‐risk infants with severe eczema or egg allergy. Peanut allergy is, however, much less prevalent in Asia compared to the West. Varying patterns of food allergy are seen even within Asian countries—such as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in Singapore and the Philippines. Customs and traditions, such as diet and infant feeding practices, also differ between Asian populations. Hence, there are unique challenges in adapting guidelines on early allergenic food introduction to the Asian setting. In this paper, we review the evidence and discuss the possible approaches to guide the timely introduction of allergenic food in high‐risk infants in Asia.     

Erratum: Rhinitis in children less than 6 years of age: current knowledge and challenges

[This corrects the article on p. 115 in vol. 1, PMID: 22053307.].