Severe refractory asthma: Current treatment options and ongoing research

Patients with severe asthma have a greater risk of asthma-related symptoms, morbidities, and exacerbations. Moreover, healthcare costs of patients with severe refractory asthma are at least 80% higher than those with stable asthma, mainly because of a higher use of healthcare resources and chronic side effects of oral corticosteroids (OCS). The advent of new promising biologicals provides a unique therapeutic option that could achieve asthma control without OCS. However, the increasing number of available molecules poses a new challenge: the identification and selection of the most appropriate treatment. Thanks to a better understanding of the basic mechanisms of the disease and the use of predictive biomarkers, especially regarding the Th2-high endotype, it is now easier than before to tailor therapy and guide clinicians toward the most suitable therapeutic choice, thus reducing the number of uncontrolled patients and therapeutic failures. In this review, we will discuss the different biological options available for the treatment of severe refractory asthma, their mechanism of action, and the overlapping aspects of their usage in clinical practice. The availability of new molecules, specific for different molecular targets, is a key topic, especially when considering that the same targets are sometimes part of the same phenotype. The aim of this review is to help clarify these doubts, which may facilitate the clinical decision-making process and the achievement of the best possible outcomes

Folate intake and squamous-cell carcinoma of the oesophagus in Italian and Swiss men

Background: Dietary folate has been inversely related to the risk of several cancers. However, studies on the role of dietary folate in oesophageal cancer are scanty. Patients and methods: Using data from a multicentric case-control study conducted in Italy and Switzerland between 1992 and 1999, we investigated the association between dietary folate intake and oesophageal squamous-cell carcinoma (OSCC) among 351 men with incident, histologically confirmed OSCC and 875 hospital controls admitted for acute, non-neoplastic conditions, unrelated to alcohol and smoking consumption. Intake of folate and other nutrients was computed from a validated food frequency questionnaire. Results: The multivariate odds ratios (ORs) of OSCC were 0.68 (95% confidence intervals, CI: 0.46-1.00) for the highest versus the lowest tertile of folate intake, and 0.84 (95% CI: 0.72-0.99) for an increment of folate intake equal to a standard deviation (98 μg/day). The inverse relation was somewhat stronger in strata of high methionine, vitamin B6 and alcohol intake, and did not vary substantially according to age and smoking habits. Conclusion: Dietary folate was inversely related to OSCC risk in this population with high alcohol consumption and infrequent use of supplements and multivitamin

Towards precision medicine: The application of omics technologies in asthma management

Asthma is a chronic obstructive respiratory disease characterised by bronchial inflammation. Its biological and clinical features have been widely explored and a number of pharmacological treatments are currently available. Currently several aspects of asthma pathophysiological background remain unclear, and this is represent a limitation for the traditional asthma phenotype approach. In this scenario, the identification of new molecular and clinical biomarkers may be helpful in order to better understand the disease, define specific diagnostic tools and highlight relevant novel targets for pharmacological treatments. Omics technologies offer innovative research tools for addressing the above mentioned goals. However, there is still a lot to do both in the fields of basic research and in the clinical application. Recently, genome-wide association studies, microRNAs and proteomics are contributing to enrich the available data for the identification of new asthma biomarkers. A precise approach to the patient with asthma, particularly with severe uncontrolled asthma, requires new and specific therapeutic targets, but also proper tools able to drive the clinician in tailoring the treatment. On the other hand, there is a need of predictors to treatment's response, particularly in the field of biological drugs, whose sustainability implies a correct and precise selection of the patients. Translating acquired omics knowledge in clinical practice may address the unmet needs described above, but large-scale studies are required in order to confirm their relevance and effectiveness in daily practice. Thus in our opinion the application of omics is still lagging in the real-life setting

Precision Medicine in Targeted Therapies for Severe Asthma: Is There Any Place for "omics" Technology?

According to the current guidelines, severe asthma still represents a controversial topic in terms of definition and management. The introduction of novel biological therapies as a treatment option for severe asthmatic patients paved the way to a personalized approach, which aims at matching the appropriate therapy with the different asthma phenotypes. Traditional asthma phenotypes have been decomposing by an increasing number of asthma subclasses based on functional and physiopathological mechanisms. This is possible thanks to the development and application of different omics technologies. The new asthma classification patterns, particularly concerning severe asthma, include an increasing number of endotypes that have been identified using new omics technologies. The identification of endotypes provides new opportunities for the management of asthma symptoms, but this implies that biological therapies which target inflammatory mediators in the frame of specific patterns of inflammation should be developed. However, the pathway leading to a precision approach in asthma treatment is still at its beginning. The aim of this review is providing a synthetic overview of the current asthma management, with a particular focus on severe asthma, in the light of phenotype and endotype approach, and summarizing the current knowledge about "omics" science and their therapeutic relevance in the field of bronchial asthma

Fried foods, olive oil and colorectal cancer

Background: The epidemiologic evidence for an etiologic role of fried foods and heterocyclic amines in colorectal carcinogenesis is inconsistent. Patients and methods: We have investigated the relation between fried foods and colorectal cancer risk using data from a large, multicentric case-control study conducted in Italy and Switzerland between 1992 and 2000, with 1394 cases of colon cancer, 886 cases of rectal cancer and 4765 controls. Results: After allowing for major relevant covariates, the multivariate odds ratios (ORs) for an increment of one portion per week of fried foods were 0.97 [95% confidence interval (CI) = 0.93-1.01] for colon cancer and 1.04 (95% CI = 1.00-1.09) for rectal cancer. When we analyzed the type of fats mainly used for frying, we found that olive oil, but not other types of oils, appeared to protect from colon cancer risk (OR = 0.89, 95% CI = 0.82-0.98). Conclusions: Our results do not indicate a relevant role of fried foods on colorectal cancer risk. We found a possible favorable effect of (fried) olive oil on colon cancer risk but not on rectal cancer ris

Pet exposure and risk of atopic dermatitis at the pediatric age: A meta-analysis of birth cohort studies

Background: Findings on pet exposure and the risk of atopic dermatitis (AD) in children are inconsistent. Objective: With the aim to summarize the results of exposure to different pets on AD, we undertook a meta-analysis of epidemiologic studies on this issue. Methods: In August 2012, we conducted a systematic literature search in Medline and Embase. We included analytic studies considering exposure to dogs, cats, other pets, or pets overall during pregnancy, infancy, and/or childhood, with AD assessment performed during infancy or childhood. We calculated summary relative risks and 95% CIs using both fixed- and random-effects models. We computed summary estimates across selected subgroups. Results: Twenty-six publications from 21 birth cohort studies were used in the meta-analyses. The pooled relative risks of AD for exposure versus no exposure were 0.72 (95% CI, 0.61-0.85; I2 = 46%; results based on 15 studies) for exposure to dogs, 0.94 (95% CI, 0.76-1.16; I2 = 54%; results based on 13 studies) for exposure to cats, and 0.75 (95% CI, 0.67-0.85; I2 = 54%; results based on 11 studies) for exposure to pets overall. No heterogeneity emerged across the subgroups examined, except for geographic area. Conclusion: This meta-analysis reported a favorable effect of exposure to dogs and pets on the risk of AD in infants or children, whereas no association emerged with exposure to cats. \ua9 2013 American Academy of Allergy, Asthma & Immunology

Aptamers against the β-conglutin allergen: Insights into the behavior of the shortest multimeric (intra)molecular dna gquadruplex

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed