Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.

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This study was designed to answer three main questions: 1) Does asthma self-management education reduce asthma morbidity? 2) Are the two programmes "Living With Asthma" and "Open Airways" equally effective in doing so? 3) Is a shortened version of these programmes (4 weeks) as effective as the longer original programme (8 weeks)?Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma, who were stratified by disease severity, gender and age, and then randomly assigned to an Experimental group which received an educational programme or to a Comparison group, which did not. Of the 312 children selected, 209 (114 Experimental and 95 Comparison) completed the educational protocol and a 1 year follow-up.Data recorded during the last 2 months of follow-up, 10 months after the educational intervention, showed that the Experimental group required significantly fewer emergency treatments: this reduction was more evident in the more severe asthma cases. In the Experimental, but not in the Comparison group, patients with more severe asthma consumed more medications than patients with milder asthma. "Open Airways" yielded, in some cases, better results than "Living with Asthma": but a type 2 error is possible. The standard and the shortened programmes proved equally effective.In conclusion, following education, regardless of receiving a short or long educational programme, asthma patients use emergency care services less and use medications more appropriately in comparison with standard care without education. This suggests that short educational programmes can be highly cost-effective in children with asthma.

The aim of this multi-centre prospective study was to evaluate the prevalence of systemic reactions to specific immunotherapy in children with allergic asthma and or rhinitis. One thousand and fifty-six children (653 boys and 403 girls), median age 8.5 years, were enrolled in this three-year prospective study. All the children were treated with injections of the following allergenic extracts: 689 of house dust mite, 291 of grass, 109 of Parietaria, 13 of Alternaria, 6 of Artemisia and 11 of Olea. Among 1056 treated children, 41 (3.7%) had systemic reactions: 40 children (3.7%) experienced mild symptoms such as asthma and/or urticaria, and only one shock (0.08%). A total of 47,247 injections were administered, and the rate of systemic reactions, according to the number of total injections was only 0.08%. According to the allergenic extract, systemic reactions occurred in 29/689 children (4.2%) treated with house dust mites extract (0.09% of the injections), in 9/291 children (3.1%) treated with grass extract (0.07% of the injections) and in 3/109 children (2.8%) treated with Parietaria extract (0.06% of the injections). The prevalence of systemic reactions was significantly higher (p < 0.0001) in the children treated with house dust mite extract in comparison with those treated with pollen extracts. All the systemic reactions appeared within 30 minutes following the administration of the extract and occurred in 37/41 cases (90.2%) with the same dose, previously tolerated. Most reactions were mild, and were readily controlled by immediate emergency treatment. There was no need for hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

We report on two Italian brothers with facial clefting, hypertelorism, urogenital anomalies including micropenis, shawl scrotum, hearing loss, caudal appendage, and umbilical hernia. We have evaluated the two cases as Malpuech syndrome. This is an extremely rare autosomal recessive syndrome.