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Leicester, United Kingdom

Pavord I.D.,Institute for Lung Health
Annals of the American Thoracic Society | Year: 2013

Our understanding of the clinical implications of eosinophilic airway in flammation has increased signi ficantly over the last 20 years, aided by the development of noninvasive means to assess it. This pattern of airway in flammation can occur in a diverse range of airway diseases. It is associated with a positive response to corticosteroids and a high risk of preventable exacerbations. Our new understanding of the role of eosinophilic airway inflammation has paved the way for the clinical development of a number of more speci fic inhibitors that may become new treatment options. Different defi nitions, ideas of disease, and adoption of biomarkers that are not well known are necessary to fully realize the potential of these treatments. Copyright © 2013 by the American Thoracic Society.


Scarpa M.C.,University of Padua | Kulkarni N.,Institute for Lung Health | Maestrelli P.,University of Padua
Clinical and Experimental Allergy | Year: 2014

Summary: The role of non-invasive methods in the investigation of acute effects of traffic-related air pollution is not clearly established. We evaluated the usefulness of non-invasive biomarkers in detecting acute air pollution effects according to the age of participants, the disease status, their sensitivity compared with lung function tests and their specificity for a type of pollutant. Search terms lead to 535 titles, among them 128 had potentially relevant abstracts. Sixtynine full papers were reviewed, while 59 articles were excluded as they did not meet the selection criteria. Methods used to assess short-term effects of air pollution included analysis of nasal lavage (NAL) for the upper airways, and induced sputum (IS), exhaled breath condensate (EBC) and exhaled nitric oxide (FeNO) for central and lower airways. There is strong evidence that FeNO evaluation is useful independently from subject age, while IS analysis is suitable almost for adults. Biomarker changes are generally observed upon pollutant exposure irrespective of the disease status of the participants. None of the biomarkers identified are specific for a type of pollutant exposure. Based on experimental exposure studies, there is moderate evidence that IS analysis is more sensitive than lung function tests, whereas this is not the case for biomarkers obtained by NAL or EBC. Cells and some cytokines (IL-6, IL-8 and myeloperoxidase) have been measured both in the upper respiratory tract (NAL) and in the lower airways (IS). Overall, the response to traffic exposure seems different in the two compartments. In conclusion, this survey of current literature displays the complexity of this research field, highlights the significance of short-term studies on traffic pollution and gives important tips when planning studies to detect acute respiratory effects of air pollution in a non-invasive way. © 2014 John Wiley & Sons Ltd.


Lee K.K.,Kings College London | Matos S.,University of Aveiro | Evans D.H.,Royal Infirmary | White P.,Kings College London | And 2 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Rationale: Cough can be assessed with visual analog scales (VAS), health status measures, and 24-hour cough frequency monitors (CF24). Evidence for their measurement properties in acute cough caused by upper respiratory tract infection (URTI) and longitudinal data is limited. Objectives: To assess cough long itudinally in URTI with subjective and objective outcome measures and determine sample size for future studies. Methods: Thirty-three previously healthy subjects with URTI completed cough VAS, Leicester Cough Questionnaire (LCQ-acute), and CF24 monitoring (Leicester Cough Monitor) on three occasions, 4 days apart. Changes in subjects' condition were assessed with a global rating of change questionnaire. The potential for baseline first-hour cough frequency (CF1), VAS, and LCQ to identify low CF24 was assessed. Measurements and Main Results: Mean ±D duration of cough at visit 1 was 4.1 ± 2.5 days. Geometric mean ± log SD baseline CF24 and median (interquartile range) cough bouts were high (14.9 ± 0.4 coughs/h and 85 [39-195] bouts/24 h). Health status was severely impaired. There was a significant reduction in CF24 and VAS, and improvement in LCQ, from visits 1-3. At visit 3, CF24 remained above normal limits in 52% of subjects. The smallest changes in CF 24, LCQ, and VAS that subjects perceived important were 54%,2-and 17-mm change from baseline, respectively. The sample sizes required for parallel group studies to detect these changes are 27, 51, and 25 subjects per group, respectively. CF1 (<20.5 coughs/h) was predictive of low CF 24. Conclusions: CF24, VAS, and LCQ are responsive outcome tools for the assessment of acute cough. The smallest change in cough frequency perceived important by subjects is 54%. The sample sizes required for future studies are modest and achievable. Copyright © 2013 by the American Thoracic Society.


The two poorly soluble iron containing solid aerosols of siderite (FeCO 3) and magnetite (Fe 3O 4) were compared in a 4-week inhalation study on rats at similar particle mass concentrations of approximately 30 or 100mg/m 3. The particle size distributions were essentially identical (MMAD ≈1.4 μm). The iron-based concentrations were 12 or 38 and 22 or 66mg Fe/m 3 for FeCO 3 and Fe 3O 4, respectively. Modeled and empirically determined iron lung burdens were compared with endpoints suggestive of pulmonary inflammation by determinations in bronchoalveolar lavage (BAL) and oxidative stress in lung tissue during a postexposure period of 3 months. The objective of study was to identify the most germane exposure metrics, that are the concentration of elemental iron (mg Fe/m 3), total particle mass (mg PM/m 3) or particle volume (μl PM/m 3) and their associations with the effects observed. From this analysis it was apparent that the intensity of pulmonary inflammation was clearly dependent on the concentration of particle-mass or -volume and not of iron. Despite its lower iron content, the exposure to FeCO 3 caused a more pronounced and sustained inflammation as compared to Fe 3O 4. Similarly, borderline evidence of increased oxidative stress and inflammation occurred especially following exposure to FeCO 3 at moderate lung overload levels. The in situ analysis of 8-oxoguanine in epithelial cells of alveolar and bronchiolar regions supports the conclusion that both FeCO 3 and Fe 3O 4 particles are effectively endocytosed by macrophages as opposed to epithelial cells. Evidence of intracellular or nuclear sources of redox-active iron did not exist. In summary, this mechanistic study supports previous conclusions, namely that the repeated inhalation exposure of rats to highly respirable pigment-type iron oxides cause nonspecific pulmonary inflammation which shows a clear dependence on the particle volume-dependent lung overload rather than any increased dissolution and/or bioavailability of redox-active iron. © 2011 Informa Healthcare USA, Inc.


Lotvall J.,Gothenburg University | Akdis C.A.,University of Zurich | Bacharier L.B.,Washington University in St. Louis | Bjermer L.,Lund University | And 6 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called "asthma endotypes." An "endotype" is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism. Criteria for defining asthma endotypes on the basis of their phenotypes and putative pathophysiology are suggested. Using these criteria, we identify several proposed asthma endotypes and propose how these new definitions can be used in clinical study design and drug development to target existing and novel therapies to patients most likely to benefit. This PRACTALL (PRACtical ALLergy) consensus report was produced by experts from the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. © 2010 American Academy of Allergy, Asthma & Immunology.

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