Differential serum protein markers and the clinical severity of asthma

Super User Thursday, 26 June 2014 19:03
 

Authors: Norbert Meyer,1,2 Sarah Janine Nuss,1 Thomas Rothe,1 Alexander Siebenhüner,1 Cezmi A Akdis,2Günter Menz1

Published Date April 2014 Volume 2014:7 Pages 67 - 75

DOI: http://dx.doi.org/10.2147/JAA.S53920
1Hochgebirgsklinik Davos, Davos-Wolfgang, Switzerland; 2Swiss Institute of Allergy and Asthma Research (SIAF), Davos Platz, Switzerland

Background: Asthma is a heterogeneous disease characterized by different clinical phenotypes and the involvement of multiple inflammatory pathways. During airway inflammation, many cytokines and chemokines are released and some are detectable in the sera.
Objective: Serum chemokines and cytokines, involved in airway inflammation in asthma patients, were investigated.
Methods: A total of 191 asthma patients were classified by hierarchical cluster analysis, including the following parameters: forced expiratory volume in 1 second (FEV1), eosinophil cationic protein (ECP) serum levels, blood eosinophils, Junipers asthma symptom score, and the change in FEV1, ECP serum levels, and blood eosinophils after 3 weeks of asthma therapy. Serum proteins were measured by multiplex analysis. Receiver operating characteristic (ROC) curves were used to evaluate the validity of serum proteins for discriminating between asthma clusters.
Results: Classification of asthma patients identified one cluster with high ECP serum levels, increased blood eosinophils, low FEV1 values, and good FEV1 improvement in response to asthma therapy (n=60) and one cluster with low ECP serum levels, low numbers of blood eosinophils, higher FEV1 values, and no FEV1 improvement in response to asthma therapy (n=131). Serum interleukin (IL)-8, eotaxin, vascular endothelial growth factor (VEGF), cutaneous T-cell-attracting chemokine (CTACK), growth-related oncogene (GRO)-α, and hepatocyte growth factor (HGF) were significantly different between the two clusters of asthma patients. ROC analysis for serum proteins calculated a sensitivity of 55.9% and specificity of 75.8% for discriminating between them.
Conclusion: Serum cytokine and chemokine levels might be predictors for the severity of asthmatic inflammation, asthma control, and response to therapy, and therefore might be useful for treatment optimization.

Keywords: asthma, cluster, phenotype, serum cytokines
 
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The role of macrolides in asthma: current evidence and future directions

Super User Wednesday, 25 June 2014 14:45
The Lancet Respiratory Medicine
 
The Lancet Respiratory Medicine, Early Online Publication, 17 June 2014
doi:10.1016/S2213-2600(14)70107-9 Cite or Link Using DOI
This article can be found in the following collections: Infectious Diseases (Anti-infective therapy); Respiratory Medicine (Asthma)
 

The role of macrolides in asthma: current evidence and future directions

Ernie H C Wong MBBS a b c dJames D Porter MSc a b cMichael R Edwards PhD a b cProf Sebastian L Johnston FRCP a b c d Corresponding AuthorThis email address is being protected from spambots. You need JavaScript enabled to view it.

Summary

Macrolides, such as clarithromycin and azithromycin, possess antimicrobial, immunomodulatory, and potential antiviral properties. They represent a potential therapeutic option for asthma, a chronic inflammatory disorder characterised by airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Results from clinical trials, however, have been contentious. The findings could be confounded by many factors, including the heterogeneity of asthma, treatment duration, dose, and differing outcome measures. Recent evidence suggests improved effectiveness of macrolides in patients with sub-optimally controlled severe neutrophilic asthma and in asthma exacerbations. We examine the evidence from clinical trials and discuss macrolide properties and their relevance to the pathophysiology of asthma. At present, the use of macrolides in chronic asthma or acute exacerbations is not justified. Further work, including proteomic, genomic, and microbiome studies, will advance our knowledge of asthma phenotypes, and help to identify a macrolide-responsive subgroup. Future clinical trials should target this subgroup and place emphasis on clinically relevant outcomes such as asthma exacerbations.
 
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Serum uric acid and the risk of respiratory disease: a population-based cohort study

Juan Carlos Ivancevich Wednesday, 11 June 2014 13:30

Thorax doi:10.1136/thoraxjnl-2014-205271

  • Respiratory epidemiology
  • Original article
Open Access
  1. Laura J Horsfall
  2. Irwin Nazareth
  3. Irene Petersen

+Author Affiliations

  1. Research Department of Primary Care and Population Health, Institute of Epidemiology and Health Care, University College London, London, UK
  1. Correspondence toDr Laura Horsfall, Research Department of Primary Care and Population Health, University College London Medical School, Royal Free Campus, London NW3 2PF, UK;This email address is being protected from spambots. You need JavaScript enabled to view it.
  • Received 11 February 2014
  • Revised 13 May 2014
  • Accepted 16 May 2014
  • Published Online First 5 June 2014

Abstract

Introduction Uric acid is the most abundant molecule with antioxidant properties found in human blood serum. We examined the relationship between serum uric acid and the incidence of respiratory disease including any effect modification by smoking status.

Methods A cohort with serum uric acid measured between 1 January 2000 and 31 December 2012 was extracted from The Health Improvement Network primary care research database. New diagnoses of COPD and lung cancer were ascertained based on diagnostic codes entered into the medical records.

Results During 1 002 496 person years (PYs) of follow-up, there were 3901 COPD diagnoses and 1015 cases of lung cancer. After multivariable adjustment, strong interactions with smoking status were detected (p<0.001) for both outcomes with significant negative relationships between serum uric acid and respiratory disease for current smokers but no strong relationships for never-smokers or ex-smokers. The relationships were strongest for lung cancer in heavy smokers (≥20 cigarettes per day) with predicted incidence rates 97 per 10 000 PYs (95% CI 68 to 126) in the lowest serum uric acid quintile (100–250 µmol/L) compared with a predicted 28 per 10 000 PYs (95% CI 14 to 41) in the highest quintile (438–700 µmol/L).

Conclusions Low levels of serum uric acid are associated with higher rates of COPD and lung cancer in current smokers after accounting for conventional risk factors.

This Article

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:http://creativecommons.org/licenses/by-nc/3.0/

 

Mechanisms of pathogenesis in allergic asthma: Role of interleukin-23

Juan Carlos Ivancevich Thursday, 19 June 2014 12:56
Respirology
Yanchun Li and Shucheng Hua
 

 Abstract

Asthma is a chronic airway inflammatory disease characterized by intense leukocyte and eosinophilic infiltration accompanied by mucus hypersecretion and tissue hyperresponsiveness. Recent evidence suggests that T-helper (Th)2 cells and their cytokine products orchestrate the pathology of asthma. In addition, Th17 cells are implicated in the pathogenesis of antigen-induced airway inflammation. The Th17 related cytokine interleukin (IL)-23 plays important roles in many immunological diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, psoriasis and inflammatory bowel disease. Several reports describe the role of IL-23 in the pathogenesis of allergic asthma in both human and mice. IL-23 leads to neutrophil infiltration in the airway of asthmatic mice, which is characteristic of severe asthma resulting from Th17 development and subsequently IL-17 secretion. IL-23 can also promote eosinophil infiltration in the airway, which is a hallmark of allergic asthma. These studies suggest that IL-23 could be a promoting factor in the development of allergic asthma and likewise would be a target for asthma therapy. In support of this view, trials of anti-IL-23 therapy have been attempted in human and mouse asthma models with encouraging outcomes. This review presents the role of IL-23 in asthma according to recent clinical trials and animal model studies. The proposed mechanisms of IL-23-induced airway inflammation and the agents currently being tested that target IL-23 related pathways are discussed.

Article first published online: 30 APR 2014

DOI: 10.1111/resp.12299

Full text Review PDF

 

 

Tiotropium Respimat(R) in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma

Juan Carlos Ivancevich Wednesday, 04 June 2014 13:18
Respiratory Research
Research
 
Open Access
 

Kai-Michael BeehPetra Moroni-ZentgrafOthmar AblingerZuzana HollaenderovaAnna UnseldMichael Engel and Stephanie Korn

Author Affiliations

For all author emails, please log on.

Respiratory Research 2014, 15:61  doi:10.1186/1465-9921-15-61

Published: 3 June 2014

Abstract (provisional)

Background

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat(R) (tiotropium Respimat(R)) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting beta2-agonists. To further explore the dose-response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat(R) as add-on to ICS in symptomatic patients with moderate persistent asthma.

Methods

In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotropium Respimat(R) 5 mug, 2.5 mug or 1.25 mug or placebo Respimat(R), once daily in the evening. Each treatment was administered for 4 weeks, without washout between treatment periods. Eligibility criteria included >=60% and <=90% of predicted normal forced expiratory volume in 1 second (FEV1) and seven-question Asthma Control Questionnaire mean score of >=1.5. Patients were required to continue maintenance treatment with stable medium-dose ICS for at least 4 weeks prior to and during the treatment period. Long-acting beta2-agonists were not permitted during the treatment phase. The primary efficacy end point was peak FEV1 measured within 3 hours after dosing (peak FEV1(0-3h)) at the end of each 4-week period, analysed as a response (change from study baseline).

Results

In total, 149 patients were randomised and 141 completed the study. Statistically significant improvements in peak FEV1(0-3h) response were observed with each tiotropium Respimat(R) dose versus placebo (all P < 0.0001). The largest difference from placebo was with tiotropium Respimat(R) 5 mug (188 mL). Trough FEV1 and FEV1 area under the curve (AUC)(0-3h) responses were greater with each tiotropium Respimat(R) dose than with placebo (all P < 0.0001), and both were greatest with 5 mug. Peak forced vital capacity (FVC)(0-3h), trough FVC and FVC AUC(0-3h) responses, versus placebo, were greatest with tiotropium Respimat(R) 5 mug (P < 0.0001, P = 0.0012 and P < 0.0001, respectively). Incidence of adverse events was comparable between placebo and all tiotropium Respimat(R) groups.

Conclusions

Once-daily tiotropium Respimat(R) add-on to medium-dose ICS improves lung function in symptomatic patients with moderate asthma. Overall, improvements were largest with tiotropium Respimat(R) 5 mug.

Trial registration: ClinicalTrials.gov identifier NCT01233284.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

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