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Adverse effects during specific oral tolerance induction: in home phase.

Adverse effects during specific oral tolerance induction: in home phase.

Allergol Immunopathol (Madr). 2011 Jul 28;

Authors: Barbi E, Longo G, Berti I, Matarazzo L, Rubert L, Saccari A, Lenisa I, Ronfani L, Radillo O, Ventura A

BACKGROUND: Specific oral tolerance induction (SOTI) is a promising approach for severe food allergies. There are little data in the literature regarding the home-phase of SOTI, not only with regard to type and frequency of adverse reactions but also regarding the most suitable treatment and protocol. AIMS: To define the incidence and severity of adverse reactions, possible risk factors, and the safety and effectiveness of the home-phase of an original SOTI protocol in a large group of children with severe cow's milk (CM) allergy, after the hospital "rush" phase. METHODS: The study was conducted by recording in-home phase adverse events, success and failure as reported by parents, and calling families. Adverse reactions were treated following the International Guidelines, arbitrarily modified by introducing nebulised epinephrine for respiratory reactions, oral beclomethasone for acute gastric pain and oral cromolyn for recurrent gastric pain. RESULTS: Out of 140 patients, 132 were contacted; eight were inaccessible (follow-up 2-84 months). The number of adverse reactions was 1 in every 100 doses. The reactions were treated with nebulised epinephrine (221 reactions), IM epinephrine (6 reactions), and other drugs. Patients with high specific IgE levels (greater than 100kU(A)/L) and lower CM dose (less than 5ml) at the end of in-hospital phase showed a higher risk both for number of reactions and use of nebulised epinephrine. CONCLUSIONS: The home phase of SOTI was characterised by a significant number of adverse reactions, mostly managed with an acceptable rate of side effects. Nebulised epinephrine played a pivotal role in respiratory reactions.

PMID: 21802824 [PubMed - as supplied by publisher]

Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide.

Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide.

Br J Pharmacol. 2011 Aug 9;

Authors: Kelly M, King E, Rider C, Gwozd C, Holden N, Eddleston J, Zuraw B, Leigh R, O'Byrne P, Newton R

Background and purpose:  Inhaled corticosteroids are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor, reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the glucocorticoid receptor on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking inhaled corticosteroids (ICS), we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma. Experimental approach:  Bronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-polymerase chain reaction for the corticosteroid-inducible genes (official gene symbols with aliases in brackets); TSC22D3 (GILZ), DUSP1 (MKP-1), both anti-inflammatory effectors, and FKBP5 (FKBP51), a regulator of glucocorticoid receptor function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis. Key results:  Compared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects. Conclusions and implications:  Expression of the corticosteroid-induced genes, GILZ and FKBP51, is upregulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease glucocorticoid receptor-dependent transcription may correspondingly affect corticosteroid efficacy.

PMID: 21827450 [PubMed - as supplied by publisher]

The effect of hypoxia on cognitive performance in patients with chronic obstructive pulmonary disease.

Air travel may cause significant hypoxia in passengers with chronic obstructive pulmonary disease (COPD). It is not known whether this level of hypoxia will cause impairment in cognitive function.

The aim of this study was to determine the effect of hypoxia on cognitive performance in patients with COPD when Pa(O2) was decreased <6.6 kPa.

In ten patients with moderate to severe COPD trail making tasks and complex figure tasks were used to assess cognitive performance when the patients breathed 21% O(2), and when Pa(O2) was decreased to <6.6 kPa. During administration of 21% O(2), Pa(O2) was 9.5 (8.9-10.2) kPa. When Sp(O2) was decreased to 85% via manipulation of the FI(O2) (inspired fraction of oxygen) Pa(O2), decreased to 6.1 (5.9-6.2) kPa. No short term deterioration in visual search, mental flexibility or visuospatial constructional ability was detected when Pa(O2) was decreased to <6.6 kPa.

The results show that short term exposure to hypoxia had no adverse effect on cognitive function.

C reactive protein and alpha1-antitrypsin: relationship between levels and gene variants.

The first step in laboratory diagnosis of alpha1-antitrypsin deficiency (AATD) is the determination of alpha1-antitrypsin (AAT) serum levels; these levels in turn are influenced by the inflammatory status. C reactive protein (CRP) has been proposed as a marker of systemic inflammation. Single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with differences in baseline CRP levels.

The purpose of this study was to investigate the relationship between CRP and AAT in the AATD diagnostic setting and to verify whether variations in the CRP gene could influence CRP. We determined AAT and CRP levels in 362 consecutive dried blood spot (DBS) samples submitted for AATD diagnosis and genotyped 3 CRP gene SNPs (rs1205, rs3093077, and rs3091244) associated with variations in serum CRP concentrations. To this aim, we developed a method to measure CRP in a DBS with a good correlation with CRP measurement in serum (r2=0.9927).

We showed then that systemic inflammatory status parallels increased levels of AAT (80% of subjects with intermediate AATD and a CRP>0.8 mg/dL had an AAT level above the cut-off of 113 mg/dL) and that this increase might mask the presence of AATD variants. No association was detected between CRP levels and the 3 CRP gene polymorphisms.

Simultaneous determination of CRP and AAT is useful in the correct diagnosis of heterozygotes carrying intermediate AATD genotypes; their genetic influence on the CRP level is negligible.

Nutrition management for the patient requiring prolonged mechanical ventilation.

Patients requiring prolonged mechanical ventilation are often medically complex and present with a wide range of pulmonary conditions, including neuromuscular diseases, chronic pulmonary diseases, and chronic critical illness.

These patients present the nutrition support professional with many challenges. However, accurate nutrition assessment, timely and effective nutrition interventions, and careful monitoring will help patients meet their medical and nutrition goals.

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