Multiallergen-specific immunotherapy in polysensitized patients: where are we?

Immunotherapy. 2013 Feb;5(2):183-90

Authors: Bahceciler NN, Galip N, Cobanoglu N

Abstract
Allergen-specific immunotherapy administered by the subcutaneous route was introduced a century ago and has been shown to be effective in the management of allergic rhinitis and asthma. More recently, the sublingual administration of allergen extracts has become popular, especially in European countries, and has also demonstrated efficacy in respiratory allergic diseases. Both modes of allergen administration during immunotherapy have been shown not only to reduce symptoms and the need for medication, but also to prevent the development of additional sensitivities in monosensitized patients, as well as asthma development in patients with allergic rhinitis, with a long-lasting effect after the completion of several years of treatment. Almost all of the well-designed and double-blinded, placebo-controlled studies evaluated treatment with single-allergen extracts. Therefore, most meta-analyses published to date evaluated immunotherapy with single allergen or extracts containing several cross-reactive allergens. As a result, in general, multiallergen immunotherapy in polysensitized patients (mixture of noncross-reactive allergens) is not recommended owing to lack of evidence. Although some guidelines have recommended against the use of multiallergen mixtures, allergists commonly use mixtures to which the patient is sensitive with the rationale that effective immunotherapy should include all major sensitivities. Literature on this subject is scarce in spite of the widespread use worldwide. Here, this issue will be extensively discussed based on currently available literature and future perspectives will also be explored.

PMID: 23413909 [PubMed - in process]

Immunological aspects of phosphodiesterase inhibition in the respiratory system.

Respir Physiol Neurobiol. 2013 Feb 12;

Authors: Mokry J, Mokra D

Abstract
Phosphodiesterases (PDEs) are known as a super-family of 11 isoenzymes, which can exert various functions based on their organ distribution. Aside from non-selective PDE inhibitors (methylxanthines, e.g. theophylline) used many years in clinical settings, increasing attention is focused on the involvement of selective PDE inhibitors in therapy of obstructive airway diseases associated with chronic inflammation. There are mostly PDE3, PDE4, and PDE7 isoforms present in the respiratory system. This paper describes the mechanisms of action, adverse effects, and potential clinical use of both non-selective and selective PDE inhibitors. The focus of the review is on the influence of PDE inhibitors on the immune system.

PMID: 23415692 [PubMed - as supplied by publisher]

Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives.

Cancer Discov. 2013 Feb 15;

Authors: Dieci MV, Arnedos M, Andre F, Soria JC

Abstract
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifications, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, class-specific toxicity profiles and correctly designing clinical trials to address these different issues.

PMID: 23418312 [PubMed - as supplied by publisher]

Viral Pneumonitis Is Increased in Obese Patients during the First Wave of Pandemic A(H1N1) 2009 Virus.

PLoS One. 2013;8(2):e55631

Authors: Kok J, Blyth CC, Foo H, Bailey MJ, Pilcher DV, Webb SA, Seppelt IM, Dwyer DE, Iredell JR

Abstract
INTRODUCTION: There is conflicting data as to whether obesity is an independent risk factor for mortality in severe pandemic (H1N1) 2009 influenza (A(H1N1)pdm09). It is postulated that excess inflammation and cytokine production in obese patients following severe influenza infection leads to viral pneumonitis and/or acute respiratory distress syndrome.
METHODS: Demographic, laboratory and clinical data prospectively collected from obese and non-obese patients admitted to nine adult Australian intensive care units (ICU) during the first A(H1N1)pdm09 wave, supplemented with retrospectively collected data, were compared.
RESULTS: Of 173 patients, 100 (57.8%), 73 (42.2%) and 23 (13.3%) had body mass index (BMI) <30 kg/m(2), ≥30 kg/m(2) (obese) and ≥40 kg/m(2) (morbidly obese) respectively. Compared to non-obese patients, obese patients were younger (mean age 43.4 vs. 48.4 years, p = 0.035) and more likely to develop pneumonitis (61% vs. 44%, p = 0.029). Extracorporeal membrane oxygenation use was greater in morbidly obese compared to non-obese patients (17.4% vs. 4.7%, p = 0.04). Higher mortality rates were observed in non-obese compared to obese patients, but not after adjusting for severity of disease. C-reactive protein (CRP) levels and hospital length of stay (LOS) were similar. Amongst ICU survivors, obese patients had longer ICU LOS (median 11.9 vs. 6.8 days, p = 0.017). Similar trends were observed when only patients infected with A(H1N1)pdm09 were examined.
CONCLUSIONS: Among patients admitted to ICU during the first wave of A(H1N1)pdm09, obese and morbidly obese patients with severe infection were more likely to develop pneumonitis compared to non-obese patients, but mortality rates were not increased. CRP is not an accurate marker of pneumonitis.

PMID: 23418448 [PubMed - in process]