Stratified medicine: drugs meet genetics

Eur Respir Rev March 1, 2013 vol. 22 no. 127 53-57

Stratified medicine: drugs meet genetics

1. Ian P. Hall⇓

+Author Affiliations

1. Division of Therapeutics and Molecular Medicine, Queen's Medical Centre, Nottingham, UK

1. I.P. Hall, Division of Therapeutics and Molecular Medicine D floor south block, Queen's Medical Centre, Nottingham, NG7 2UH, UK. E-mail:Ian.Hall@nottingham.ac.uk

Abstract

It is well recognised that genetic factors play a major role in the development of respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, whilst extensive data exist on diseases caused primarily by single gene defects, such as α₁-antitrypsin deficiency, the genetic factors responsible for the development of complex disease are only now being defined. Once the gene(s) responsible for the heritable element of disease risk are known, the next step is to identify the mechanisms underlying the pathophysiological effects of the causal mutations in these genes. This process can be time consuming, but allows a full understanding of the mechanisms underlying disease development to be obtained. This knowledge can then potentially be used to stratify patient groups within (or even across) disease boundaries and then to target therapy more effectively.

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The impact of personalised therapies on respiratory medicine

Eur Respir Rev March 1, 2013 vol. 22 no. 127 72-74

The impact of personalised therapies on respiratory medicine

1. J. Stuart Elborn⇓

+Author Affiliations

1. Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University, Belfast, UK

1. J.S. Elborn, Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University, Health Sciences Building 97 Lisburn Road BelfastBT9 7BL, UK. E-mail: s.elborn@qub.ac.uk

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Abstract

Stratified approaches to treating disease are very attractive, as efficacy is maximised by identifying responders using a companion diagnostic or by careful phenotyping. This approach will spare non-responders form potential side-effects. This has been pioneered in oncology where single genes or gene signatures indicate tumours that will respond to specific chemotherapies. Stratified approaches to the treatment of asthma with biological therapies are currently being extensively studied. In cystic fibrosis (CF), therapies have been developed that are targeted at specific functional classes of mutations. Ivacaftor, the first of such therapies, potentiates dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein Class III mutations and is now available in the USA and some European countries. Pivotal studies in patients with a G551D mutation, the most common Class III mutation, have demonstrated significant improvements in clinically important outcomes such as spirometry and exacerbations. Sweat chloride was significantly reduced demonstrating a functional effect on the dysfunctional CFTR protein produced by the G551D mutation. Symptom scores are also greatly improved to a level that indicates that this is a transformational treatment for many patients. This stratified approach to the development of therapies based on the functional class of the mutations in CF is likely to lead to new drugs or combinations that will correct the basic defect in many patients with CF.

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Assessment of biofilm by nasal cytology in different forms of rhinitis and its functional correlations

European Annals of Allergy and Clinical Immunology Vol 45, No 1 (2013) > Gelardi

Assessment of biofilm by nasal cytology in different forms of rhinitis and its functional correlations

M. Gelardi, G. Passalaqua, M.L. Fiorella, et al.

Abstract

Background: Recently, it has been reported that nasal cytology in light microscopy can identify biofilms, which appear as cyan-stained “Infectious Spots”. We assessed by the same method and in the same population, the presence of biofilms in different nasal disorders, and estimated if a correlation with the functional grade of obstruction existed. Methods: Subjects suffering from different nasal disorders, after a detailed clinical history and ENT examination, underwent nasal fibroendoscopy, skin prick test, rhinomanometry and nasal cytology. The presence of biofilm was linked to the type of disease and to the grade of obstruction. Results: Among 1,410 subjects previously studied, the infectious spot was found in 107 patients (7.6%), and this percentage reached 55.4% in subjects with cytologic signs of infectious rhinitis (presence of bacteria/fungi). Biofilms were largely more frequent in patients with adenoid hypertrophy (57.4%), followed by nasal polyposis (24%), chronic rhinosinusitis (9.5%) and non-allergic rhinitis (7.6%). Nasal cytology was normal in the remaining patients, where no infectious spot was detectable. Statistical analysis showed that nasal resistances were significantly higher in presence of biofilms in patients with adenoid hypertrophy (p=0.003), nasal polyposis (p<0 .001="" also="" and="" as="" assessed="" biofilm="" biofilms="" but="" by="" chronic="" conclusion:="" correlates="" degree="" demonstrate="" deviation="" diseases.="" div="" immune-mediated="" in="" infectious="" inflammatory="" is="" nasal="" not="" obstruction="" of="" only="" or="" p="0.001)." presence="" present="" results="" rhinitis="" rhinomanometry.="" rhinosinusitis="" septal="" significantly="" that="" the="" with="">

Keywords

Nasal cytology, biofilm, nasal obstruction, rhinitis, rhinomanometry

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ARIA classification showed better representation of allergic symptoms and QOL than did the SAR/PAR classification.

Original Article  Open Access

|  | Full Text    |    Allergy Asthma Immunol Res. 2013 Mar;5(2):75-80. English. Published online 2012 November 27.  http://dx.doi.org/10.4168/aair.2013.5.2.75  Copyright © 2013 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease Seasonal Specificity of Seasonal Allergens and Validation of the ARIA Classification in Korea Young-Jun Chung, Il-Kwon Cho, Ki-Il Lee, Sung-Hyen Bae, Jae-Wook Lee, Phil-Sang Chung and Ji-Hun Mo Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea.  Correspondence to: Ji-Hun Mo, MD, PhD, Department of Otorhinolaryngology, Dankook University College of Medicine, 119 Dandae-ro, Dongnam-gu, Cheonan 330-997, Korea. Tel: +82-41-550-3933; Fax: +82-41-556-1090; Email:jihunmo@gmail.com Young-Jun Chung and Il-Kwon Cho contributed equally to this work. Received November 29, 2011; Revised August 16, 2012; Accepted September 06, 2012. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.  This article has been cited by 1 article in    This article has been cited by 1 article in  KoMCI Abstract Purpose In Korea, tree pollens are known to be prevalent in spring, grass pollens in summer and weed pollens in autumn. However, few studies have revealed their seasonal specificity for allergic rhinitis symptoms. An ARIA (Allergic Rhinitis and its Impact on Asthma) classification of allergic rhinitis was recently introduced and its clinical validation has not been well proved. The aim of this study was to evaluate the seasonal specificity of seasonal allergens and to validate the ARIA classification with the conventional seasonal and perennial allergic rhinitis (SAR/PAR) classification. Methods Two hundred twenty six patients with allergic rhinitis were included in this study. The patients were classified according to the sensitized allergens and the ARIA classifications. A questionnaire survey was performed and the data on the seasonal symptom score, the severity of symptoms and the SNOT (sinonasal outcome test)-20 score was obtained and the data was analyzed and compared between the conventional SAR/PAR classification and the ARIA classification. Results Seasonal pollens (tree, grass, weed) were not specific to the pollen peak season and the patients' symptoms were severe during spring and autumn regardless of the offending pollens. More than 60% of the patients with SAR showed persistent symptoms and 33% of the patients with perennial allergic rhinitis (PAR) had intermittent symptoms, showing the lack of association between the SAR/PAR/PAR+SAR classification and the ARIA classification. The ARIA classification showed better association not only with the symptomatic score, but also with the SNOT-20 score, which showed better validity than the conventional SAR/PAR classifications. Conclusions Seasonal pollens were not specific to their season of prevalence in terms of the severity of symptoms, and the ARIA classification showed better representation of allergic symptoms and quality of life (SNOT-20 score) than did the SAR/PAR classification.

Low-fat yoghurt intake was directly related to increased risk of both child asthma and allergic rhinitis

• NIHPA Author Manuscripts >
• PMC3582227

J Nutr Sci. Author manuscript; available in PMC 2013 February 26.

Published in final edited form as:

J Nutr Sci. 2012 July 6; 1: e5.

doi:  10.1017/jns.2012.5

PMCID: PMC3582227

NIHMSID: NIHMS400017

Low-fat yoghurt intake in pregnancy associated with increased child asthma and allergic rhinitis risk: a prospective cohort study

Ekaterina Maslova,^1,2,3,* Thorhallur I. Halldorsson,^3,4 Marin Strøm,³ and Sjurdur F. Olsen^1,3

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Abstract

Dairy products are important sources of micronutrients, fatty acids and probiotics which could modify the risk of child asthma and allergy development. To examine the association of dairy product intake during pregnancy with child asthma and allergic rhinitis at 18 months and 7 years in the Danish National Birth Cohort, data on milk and yoghurt consumption were collected in mid-pregnancy (25th week of gestation) using a validated FFQ (n 61 909). At 18 months, we evaluated asthma and wheeze using interview data. We assessed asthma and allergic rhinitis using a questionnaire at the age of 7 years and through registry linkages. Current asthma was defined as self-reported ever asthma diagnosis and wheeze in the past 12 months. All associations were evaluated using multivariate logistic regression. At 18 months whole milk was inversely associated with child asthma (≥5.5 times/week v. none: 0.85, 95 % CI 0.75, 0.97); the reverse was true for semi-skimmed milk (≥5.5 times/week v. none: 1.08, 95 % CI 1.02, 1.15). For yoghurt, children of women who ate low-fat yoghurt >1 serving/d had 1.21 (95 % CI 1.02, 1.42) greater odds of a medication-related ever asthma diagnosis compared with children of women reporting no intake. They were also more likely to have a registry-based ever diagnosis and report allergic rhinitis. Low-fat yoghurt intake was directly related to increased risk of both child asthma and allergic rhinitis, while whole milk appeared protective for early-life outcomes only. Nutrient components or additives specific to low-fat yoghurt may be mediating the increase in risk.

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Dr. Carmen Storm discusses the oral allergy syndrome and how it relates to food allergy. Held on Dec 17, 2012.

Dr. Carmen Storm discusses the oral allergy syndrome and how it relates to food allergy. Held on Dec 17, 2012.

COLA (Conferences On-Line Allergy) is a live series of online allergy conferences held at Children's Mercy Hospital in Kansas City, Missouri. World experts give presentations on topics related to allergy and immunology. Live conferences are held on Monday and Friday from 10-noon (central time). They can be joined by going to http://www.childrensmercy.org/cola

Dr. Manika Girdhar discusses a patient with suspected allergies and swelling who has something completely different instead.

Dr. Manika Girdhar discusses a patient with suspected allergies and swelling who has something completely different instead. Held on Jan 4, 2013.
COLA (Conferences On-Line Allergy) is a live series of online allergy conferences held at Children's Mercy Hospital in Kansas City, Missouri. World experts give presentations on topics related to allergy and immunology. Live conferences are held on Monday and Friday from 10-noon (central time). They can be joined by going to http://www.childrensmercy.org/cola

Dr. Michelle Altrich discusses new allergy/immunology laboratory tests.

Dr. Michelle Altrich discusses new allergy/immunology laboratory tests. Held on Jan 7, 2013.

COLA (Conferences On-Line Allergy) is a live series of online allergy conferences held at Children's Mercy Hospital in Kansas City, Missouri. World experts give presentations on topics related to allergy and immunology. Live conferences are held on Monday and Friday from 10-noon (central time). They can be joined by going to http://www.childrensmercy.org/cola