Experimental rhinovirus 16 infection in moderate asthmatics on inhaled corticosteroids
| Autor: | Phillip Monk, Rachel Pestridge, Jonathan Macintyre, James Roberts, Ajerico del Rosario, Chang Xiao, Sebastian L. Johnston, Rona Beegan, Peter Adura, Tatiana Kebadze, Eleanor Reed, Christine B. Boxall, James E. Gern, Victoria Cornelius, Ratko Djukanovic, Juliya Aniscenko |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
Rhinovirus medicine.disease_cause Polymerase Chain Reaction Adrenal Cortex Hormones medicine Humans Nose Asthma Inflammation Analysis of Variance Picornaviridae Infections Lung business.industry Interferon-beta medicine.disease 3. Good health Chemokine CXCL10 medicine.anatomical_structure Immunology Sputum Respiratory virus Nasal Lavage medicine.symptom business Biomarkers Respiratory tract |
| Zdroj: | European Respiratory Journal |
| ISSN: | 1399-3003 0903-1936 |
| Popis: | To the Editor : The majority of asthma exacerbations are associated with respiratory virus infections, mostly rhinoviruses (RVs) [1], due to enhanced inflammation in the airways [2]. These occur despite symptom control with inhaled corticosteroids (ICS) [3]. Experimental RV infection is a valuable tool for studying virus-induced exacerbations [2, 4], but has, to date, involved only corticosteroid-naive asthmatics. We have, therefore, modified a validated infection protocol [4] to inoculate 11 subjects whose asthma was well controlled with ICS. As this was the first experimental infection in patients at risk of severe exacerbations, a cautious study design was implemented. All subjects were followed-up twice daily by SMS text messages during the study. We used RV16, a strain used safely in previous studies, which replicates in vitro to a similar extent but induces less inflammation and cell death than other strains [5]. We also chose a 10-fold lower inoculation dose of the same stock used in previous studies [6]. The design allowed for dose escalation if necessary (this proved to be unnecessary as all subjects developed cold symptoms at this dose). As a final precaution, the delivery device generated particles of 30–100 μm, restricting delivery to the nose (aerosols ≥16 μm are deposited in the upper respiratory tract (URT) [7]), thus closely mimicking natural infection, i.e. limiting direct lung exposure during inoculation. Symptoms of URT infection, asthma, and measurements of lower respiratory tract (LRT) function were recorded post-inoculation. Infection was confirmed by quantitative (q)PCR for RV16 in nasal lavage and sputum and by determining serum anti-RV16 titres. At least a ≥four-fold increase in titres in convalescent serum or shedding of RV16 in the airways was evidence of successful infection. We also studied innate immune responses … |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|