Leptin: does it have any role in childhood asthma?

BACKGROUND: Although there is evidence of a positive association between asthma and obesity in adults and children, very little is known about the role of leptin in asthmatic children. OBJECTIVES: The aims of this study were to evaluate the relation between leptin and parameters of atopy and asthma in children. METHODS: Body mass index (BMI) and serum leptin levels were measured in 102 (37 female, 65 male; mean age, 5.9 +/- 3.4 years) asthmatic and 33 (14 female, 19 male; mean age, 6.1 +/- 3.4 years) healthy children. Skin prick tests, total serum IgE, and pulmonary function tests were performed and were completed. RESULTS: A significant difference was observed in serum leptin levels between asthmatic and healthy children. Median (interquartile range) levels were 3.53 (2.06-7.24) ng/mL and 2.26 (1.26-4.71) ng/mL, respectively (P=.008). Subgroup analysis revealed that this difference in leptin levels was confined entirely to boys: 3.09 (1.99-7.51) ng/mL in boys with asthma versus 1.52 (1.06-3.17) ng/mL in boys without asthma (P=.003). By logistic regression analysis, we found that leptin was a predictive factor for having asthma (odds ratio, 1.98; CI, 1.10-3.55; P=.021), whereas sex, age, or BMI were not. In a stepwise multiple regression analysis including sex (P=.001), age (P=.016), BMI (P <.001), and asthma (P=.022), all of these variables were found to affect log leptin levels (R2=0.404). There was no significant sex difference in serum leptin levels among asthmatic children, whereas healthy boys had significantly lower leptin levels than healthy girls (P=.019). Atopic asthmatic subjects had significantly higher leptin levels than nonatopic asthmatic subjects (P=.038) with similar BMI. A significant, but weak, correlation was observed between leptin levels and IgE in the overall group of asthmatic children (r=0.231; P=.019). Again, this correlation was confined entirely to boys (r=0.319; P=.010). There was no relation between leptin levels and skin prick tests, pulmonary function tests, passive smoking, birth weight, and duration of breast-feeding. CONCLUSION: Our findings suggest that leptin may play a role in atopic asthma. High serum leptin levels in asthmatic boys may partly explain the higher prevalence of childhood asthma in male sex.     

Autoantibodies in the grocery shop: does quantity matter?

Testing for autoantibodies is an integrated part in the diagnostic process of many autoimmune diseases. As a consequence, the detection of autoantibodies is increasingly recognized in classification criteria and diagnostic guidelines. In this review, the question is addressed whether quantification of autoantibodies is clinically useful, not only in the diagnostic stage, but also during follow-up of patients with autoimmune diseases. It can be concluded that for a multitude of autoantibodies, there is sufficient evidence that the higher the amount of autoantibodies, the more likely that the patient has the respective autoimmune disease. Quantification is also of added value for monitoring therapeutic efficacy, although this depends on the type of therapy that is installed. The relation between rises in autoantibody levels and the occurrence of subsequent disease relapses, however, is far from absolute. Obviously, if quantification of autoantibodies is performed in the laboratory, results should also be reported quantitatively together with an appropriate interpretation for the clinician.     

Phenotypes of childhood asthma: are they real?

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long‐term outcome. Classical attempts to define phenotypes have been one‐dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi‐dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term ‘phenotype’ causing much circular debate. If phenotypes are meant to represent ‘real’ underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi‐dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children. Cite this as: B. D. Spycher, M. Silverman and C. E. Kuehni, Clinical & Experimental Allergy, 2010 (40) 1130–1141.     

Patient-practitioner agreement: does it matter?

BACKGROUND: Good communication is a crucial clinical skill. Previous research demonstrated better clinical outcomes when practitioners and patients agree about the nature of patients' core presenting complaints. We investigated the nature of this agreement and its impact on outcome among depressed primary care patients. METHOD: We compared presenting problem formulations completed by patients, GPs and therapists in a primary care randomized controlled trial of cognitive-behavioural therapy and non-directive counselling for depression. Participants compiled formulations from a list of 13 potential problems of self-completed questionnaires. Subjects scored at least 14 on the Beck Depression Inventory (BDI) at baseline. Outcome measure for this study included BDI at 4 and 12 months, failure to attend for therapy when referred, dropout from therapy and patient satisfaction. RESULTS: Among 464 trial patients, 395 received therapy. Patient baseline problem formulations included significantly more items than GPs, who identified significantly more items than therapists. Agreement levels varied according to a range of patient and professional variables. While patients in complete agreement with their therapists about their main problem after assessment had lower average BDI scores at 12 months (9.7 v. 12.8, P=0.03); we found no other significant associations between the extent of agreement and clinical outcome. There were significant (but relatively weak) associations between agreement and aspects of patient satisfaction. CONCLUSION: Our results suggest that detailed mutual understanding of the presenting complaints may be less important than agreement that the core problem is psychological, and that referral for psychological therapy is appropriate.     

Semantic errors in deep dyslexia: does orthographic depth matter?

Semantic errors of oral reading by aphasic patients are said to be comparatively rare in languages with a shallow orthography. The present report concerns three bilingual brain-damaged patients who prior to their stroke were fluent in both English, an orthographically deep language, and Welsh, an orthographically shallow language. On a picture-naming task, each patient made a similar proportion of semantic errors in the two languages. Similarly, in oral reading of the corresponding words, no patient produced proportionally more semantic paralexias in English than in Welsh. The findings are discussed in relation to the summation hypothesis as invoked by Miceli, Capasso, and Caramazza (1994) to explain apparent differences in frequency of semantic errors of reading in languages differing in orthographic depth.     

Prevention of asthma: where are we in the 21st century?

Asthma is the most common chronic disease of childhood and, in the latter part of the 20th century, reached epidemic proportions. Asthma is generally believed to result from gene-environment interactions. There is consensus that a ‘window of opportunity’ exists during pregnancy and early in life when environmental factors may influence its development. We review multiple environmental, biologic and sociologic factors that may be important in the development of asthma. Meta-analyses of studies have demonstrated that multifaceted interventions are required in order to develop asthma prevention. Multifaceted allergen reduction studies have shown clinical benefits. Asthma represents a dysfunctional interaction with our genes and the environment to which they are exposed, especially in fetal and early infant life. The increasing prevalence of asthma also may be an indication of increased population risk for the development of other chronic non-communicable autoimmune diseases. This review will focus on the factors which may be important in the primary prevention of asthma. Better understanding of the complex gene–environment interactions involved in the development of asthma will provide insight into personalized interventions for asthma prevention.     

Is childhood asthma an inflammatory disease?

There is now extensive evidence that asthma results from inflammation in large and small airways, and that the degree of inflammation reflects the clinical severity of the disease. Most of this evidence, however, has come from studies in adult patients. Evidence in children comes largely from indirect studies such as measurements of peripheral blood cells and inflammatory markers, rather than from direct bronchoscopic examination. Studies in adults show that inflammation in asthma is characterized by eosinophilia, epithelial damage, and bronchial hyperresponsiveness, and that activation of allergen-specific T cells plays an important role in orchestrating the inflammatory process. In children, indirect evidence of inflammation comes from the observation that anti-inflammatory agents such as inhaled corticosteroids improve symptoms and bronchial hyperresponsiveness, reduce the number of asthma exacerbations, and limit the progressive decline in lung function. Further evidence comes from measurements of nitric oxide and hydrogen peroxide (potential inflammatory markers) in exhaled air, and of inflammatory mediators in plasma and urine. As in adults, there is evidence that lymphocytes play an important role in orchestrating the inflammatory process. The immunologic profile appears to shift from a Th1-type cytokine profile to an allergenrelated Th2-type profile prior to birth Such a Th2 predominance constitutes a risk factor for the subsequent development of bronchial hyperresponsiveness and asthma in response to allergen.     

Nitric oxide in the vasculature: where does it come from and where does it go? A quantitative perspective

Nitric oxide (NO) affects two key aspects of O2 supply and demand: It regulates vascular tone and blood flow by activating soluble guanylate cyclase (sGC) in the vascular smooth muscle, and it controls mitochondrial O2 consumption by inhibiting cytochrome c oxidase. However, significant gaps exist in our quantitative understanding of the regulation of NO production in the vascular region. Large apparent discrepancies exist among the published reports that have analyzed the various pathways in terms of the perivascular NO concentration, the efficacy of NO in causing vasodilation (EC50), its efficacy in tissue respiration (IC50), and the paracrine and endocrine NO release. In this study, we review the NO literature, analyzing NO levels on various scales, identifying and analyzing the discrepancies in the reported data, and proposing hypotheses that can potentially reconcile these discrepancies. Resolving these issues is highly relevant to improving our understanding of vascular biology and to developing pharmaceutical agents that target NO pathways, such as vasodilating drugs.     

Migraines and meditation: does spirituality matter?

Migraine headaches are associated with symptoms of depression and anxiety (Waldie and Poulton Journal of Neurology, Neurosurgery, and Psychiatry 72: 86–92, 2002) and feelings of low self-efficacy (French et al. Headache, 40: 647–656, 2000). Previous research suggests that spiritual meditation may ameliorate some of the negative traits associated with migraine headaches (Wachholtz and Pargament Journal of behavioral Medicine, 30: 311–318, 2005). This study examined two primary questions: (1) Is spiritual meditation more effective in enhancing pain tolerance and reducing migraine headache related symptoms than secular meditation and relaxation? and, (2) Does spiritual meditation create better mental, physical, and spiritual health outcomes than secular meditation and relaxation techniques? Eighty-three meditation naïve, frequent migraineurs were taught Spiritual Meditation, Internally Focused Secular Meditation, Externally Focused Secular Meditation, or Muscle Relaxation which participants practiced for 20 min a day for one month. Pre-post tests measured pain tolerance (with a cold pressor task), headache frequency, and mental and spiritual health variables. Compared to the other three groups, those who practiced spiritual meditation had greater decreases in the frequency of migraine headaches, anxiety, and negative affect, as well as greater increases in pain tolerance, headache-related self-efficacy, daily spiritual experiences, and existential well being.     

Restoring the joint line in revision TKA: does it matter?

The importance of joint line restoration in revision TKA is much debated today. This review paper gives an overview of the reasons why joint line elevation occurs so frequently in contemporary revision TKAs, what the theoretical and clinical consequences are of an elevated joint line and how it can be avoided.