Is there any role for allergen avoidance in the primary prevention of childhood asthma?

In this article we discuss 3 hypotheses to attempt to understand why preventive measures thus far studied with the aim of preventing (or delaying) the development of asthma have shown such disappointing results. The most likely explanation is that the development of a multifactorial disease, such as asthma, is extremely difficult, if not impossible, to prevent by eliminating only one risk factor. In a meta-analysis we investigated the effect of a multifaceted and monofaceted intervention in 10 prospective birth cohorts of a total of 3473 children on a diagnosis of asthma. Multifaceted intervention studies had an odds ratio (OR) of 0.73 (95% CI, 0.55-0.97), whereas the monointervention studies had an OR of 1.22 (95% CI, 0.83-1.78) in patients younger than 5 years and an OR of 0.52 (95% CI, 0.32-0.84) versus 0.93 (95% CI, 0.66-1.31) in patients older than 5 years. We therefore hypothesize that studies with a multifaceted approach will have a much greater chance of being successful than studies using a monofaceted approach, with the latter being unlikely to yield a clinically relevant reduction of asthma.     

Race disparities in childhood asthma: does where you live matter?

OBJECTIVE: This study investigates whether racial/ethnic disparities in childhood asthma prevalence can be explained by differences in family and neighborhood socioeconomic position (SEP). METHODS: Data were from the 2001 Rhode Island Health Interview Survey (RI HIS), a statewide representative sample of 2,600 Rhode Island households, and the 2000 U.S. Census. A series of weighted multivariate models were fitted using generalized estimating equations (GEE) for the logistic case to analyze the independent and joint effects of race/ethnicity and SEP on doctor-diagnosed asthma among 1,769 white, black and Hispanic children <18 years old. RESULTS: Compared with white children, black children were at increased odds for asthma and this effect persisted when measures of family and neighborhood SEP were included in multivariate models (AOR: 2.49; 95% Cl: 1.30-4.77). Black children living in poverty neighborhoods had substantially higher odds of asthma than Hispanic and white children in poverty areas and children in moderate- and high-income neighborhoods (AOR: 3.20: 95% Cl: 1.62-6.29). CONCLUSION: The high prevalence of asthma among black children in poor neighborhoods is consistent with previous research on higher-than-average prevalence of childhood asthma in poor urban minority communities. Changing neighborhood social structures that contribute to racial disparities in asthma prevalence remains a challenge.     

Do cytokines have any role in Wilson's disease?

The aim of this study was to determine the serum cytokine levels in patients with Wilson's disease (WD) and correlate with phenotype, therapeutic status and laboratory data. In this cross-sectional study, the serum levels of cytokines were estimated in 34 patients (M : F, 23 : 11; drug-naive, 11) with WD (mean age: 13.8 +/- 8.6 and 19.6 +/- 9.03 years) and compared with 30 controls. The following serum cytokines were analysed using enzyme-linked immunosorbent assay: (i) tumour necrosis factor (TNF)-alpha, (ii) interferon (IFN)-gamma, (iii) interleukin (IL)-2, (iv) IL-6 and (v) IL-4. Serum TNF-alpha (P < 0.001), IFN-gamma (P = 0.005) and IL-6 (P < 0.001) were detectable in WD compared with controls. However, serum level elevation of IL-4 (P = 0.49) and IL-2 (P = 0.11), although detectable compared with controls, was statistically insignificant. The disease severity and therapeutic status did not affect the cytokines. Presence of anaemia, leucopenia, thrombocytopenia, pancytopenia and hepatic dysfunction did not influence cytokine levels. There was a significant negative correlation between IL-6 and ceruloplasmin (P = 0.04) and anti-inflammatory cytokines (IL-4) and copper level (P = 0.01). Serum cytokines, both proinflammatory and anti-inflammatory subtypes, were elevated significantly in patients with WD. Further studies would establish their role in its pathogenesis.     

Telomerase: does it have an application in tumour pathology?

The study of ageing and cell senescence has led to the recent interest in telomeres and telomerase. Telomeres are known to play a role in chromosomal replication and each time cells divide these telomeres shorten. Telomere shortening occurs with increased age. Telomerase is the main factor involved in the preservation of telomere length and therefore its activation is mooted to play a role in the immortalisation of cells. It is in this that our interest lies as it is thought that telomerase has a role to play not only in cell immortalisation but also in the development of neoplasia. Much research has been carried out in this exciting field with the aim of elucidating the role telomerase plays in carcinogenesis. This review is an attempt to summarise the recent advances in this area, which is striving to establish if telomerase does indeed have a role to play in either the early diagnosis of carcinoma or as a marker of prognosis.     

Hypersomnia in inter-episode bipolar disorder: does it have prognostic significance?

Background

Hypersomnia in inter-episode bipolar disorder has been minimally researched. The current study sought to document the prevalence of hypersomnia in a sample of inter-episode patients with bipolar disorder and to examine the relationship between hypersomnia and future bipolar depressive symptoms.

Methods

A total of 56 individuals with bipolar disorder (51 type I + 5 type II) who were currently inter-episode, along with 55 non-psychiatric controls, completed a baseline assessment, including semi-structured interviews for psychiatric diagnoses, sleep disorders, and a battery of indices that included assessment of hypersomnia. Approximately 6 months later, participants were recontacted by telephone and mood was re-evaluated.

Results

Three of six indices suggested that approximately 25% of participants with bipolar disorder endorsed symptoms of hypersomnia in the inter-episode period. Within the bipolar group, hypersomnia in the inter-episode period was associated with future depressive symptoms. This finding was independent of baseline depressive symptoms and medication use.

Limitations

Small sample size and concurrent psychopharmacology in the bipolar sample.

Discussion

Though no gold standard measure for hypersomnia currently exists, this research takes a step towards identifying a clinically and empirically useful hypersomnia assessment. This study demonstrates that hypersomnia in the inter-episode period of bipolar disorder relates to future depressive symptoms, and adds to the growing body of evidence on the importance of inter-episode symptoms predicting bipolar relapse.     

Non‐HLA genomics: does it have a role in predicting haematopoietic stem cell transplantation outcome?

Haematopoietic stem cell transplantation (HSCT) remains the only cure for many haematological neoplasms; however, the mortality rate remains high, at around 30–80%. Complications after HSCT include relapse, graft‐versus‐host disease, graft rejection and infection. High‐resolution HLA matching has improved survival in HSCT over recent years; however, GVHD still remains a serious complication. Single nucleotide polymorphisms (SNPS) within genes that are involved with an individual's capability to mount an immune response to infectious pathogens, residual leukaemia, alloantigens or genes involved in drug metabolism have been studied for their association with HSCT outcome. Indeed, over the last 15 years, several groups, including ourselves, have demonstrated that non‐HLA gene polymorphisms can be predictive of HSCT outcome. Can genetic characteristics of the patient and donor be used in the future to tailor HSCT protocols and determine GVHD prophylaxis? This review summarizes some of the recent SNP association studies in HSCT and highlights some of the disparities therein, discussing the integral problems of performing genetic association studies on diseases with complex outcomes using heterogeneous cohorts. The review will comment on recent genomewide association studies (GWAS) and discuss their relevance in this field, and it will also comment on recent meta‐analysis combining GWAS studies with other studies such as gene expression micro array data in the field of autoimmune disease and solid organ transplantation. It will mention possible novel candidate gene polymorphisms, for example SNPS in microRNAs. In addition, it will discuss some of the inherent problems associated with gene association studies including the GRIPs (genetic risk prediction studies) recommendations. In summary, this review will assess the usefulness of non‐HLA genomic studies in HSCT with regard to predicting outcome and modifying therapy.     

Gender bias in lupus: does immune response initiated in the gut mucosa have a role?

The risk of developing systemic lupus erythematosus (SLE) is approximately nine times higher among women compared to men. However, very little is understood concerning the underlying mechanisms that contribute to this gender bias. Further, whether there is a link between immune response initiated in the gut mucosa, the progression of SLE and the associated gender bias has never been investigated. In this report, we show a potential link between the immune response of the gut mucosa and SLE and the gender bias of lupus for the first time, to our knowledge. Both plasma cell‐ and gut‐imprinted‐ α4β7 T cell frequencies were significantly higher in the spleen and gut mucosa of female (SWR × NZB)F₁ (SNF₁) mice compared to that of their male counterparts. Importantly, female SNF₁ mice not only showed profoundly higher CD45⁺ immune cell densities, but also carried large numbers of interleukin (IL)‐17‐, IL‐22‐ and IL‐9‐producing cells in the lamina propria (LP) compared to their male counterparts. Intestinal mucosa of female SNF₁ mice expressed higher levels of a large array of proinflammatory molecules, including type 1 interferons and Toll‐like receptors 7 and 8 (TLR‐7 and TLR‐8), even before puberty. Our work, therefore, indicates that the gut immune system may play a role in the initiation and progression of disease in SLE and the associated gender bias.     

Lymphangiogenesis in malignant tumours: does it occur?

The development of a vascular bed is essential for solid tumour growth and metastasis. In many tumours, mean vascular density can be related to the rate of metastasis and, therefore, to prognosis. In other tumour types, such as cutaneous melanoma and head-and-neck squamous cell carcinoma, this relation is absent. Until now, the reason for this has been unclear, but since these particular tumour types are also known for their propensity to spread via the lymphatic system, it may be speculated that the presence of a pre-existing lymphatic bed and the formation of new lymphatics (lymphangiogenesis) are important factors. Growth factors involved in lymphangiogenesis during embryogenesis have been recently identified and these are also expressed in many tumour types, but the existence of tumour-induced lymphangiogenesis has not so far been reported. Partly, this could be due to the lack of reliable endothelial markers, thereby hampering a consistent evaluation of lymphatic vasculature. This editorial discusses the role of the lymphatic bed in mediating the metastasis of solid tumours, summarizes known methods to detect lymphatics, and proposes a hypothetical mechanism of tumour-induced lymphangiogenesis.     

CD10 expression in the female genital tract: does it have useful diagnostic applications?

In the female genital tract, CD10 was initially found to be expressed in endometrial stromal tumors of the uterus as well as in mesonephric remnants and related lesions and was thought to be helpful in distinguishing these tumors from their mimics. However, new studies have shown CD10 to be expressed in a wide range of tumors of the female genital tract, making this antibody of limited diagnostic value. This review discusses diagnostic applications of CD10 in the female genital tract, with emphasis on CD10 use in mesenchymal tumors of the uterus and in the differential diagnosis of mesonephric versus non-mesonephric carcinomas, where CD10 positivity alone may be misleading in the final classification of a tumor. CD10 may be useful in establishing the diagnosis of endometriosis (with the exception of the cervix), distinguishing metastatic renal clear cell carcinoma from a primary ovarian clear cell carcinoma, and distinguishing mesonephric hyperplasia from other benign glandular proliferations of the cervix.     

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.