Disease models of chronic inflammatory airway disease: applications and requirements for clinical trials.
OBJECTIVE
This review will discuss methodologies and applicability of key inflammatory models of respiratory disease in proof of concept or proof of efficacy clinical studies. In close relationship with these models, induced sputum and inflammatory cell counts will be addressed for phenotype-directed drug development. Additionally, important regulatory aspects regarding noninvestigational medicinal products used in bronchial challenges or clinical inflammatory models of respiratory disease will be highlighted.


RESULTS
The recognition of an ever increasing number of phenotypes and endotypes within conditions such as asthma and chronic obstructive pulmonary disease urges phenotyping of study populations already in early clinical phases of drug development. Apart from the choice of a relevant disease model, recent studies show that especially targeted therapies need to be tested in well defined disease subsets for adequate efficacy assessment. Noninvasive biomarkers, especially sputum inflammatory cell counts, aid phenotyping and are useful outcome measures for novel, targeted therapies.


CONCLUSIONS
Disease phenotyping becomes increasingly important for efficient and cost-effective drug development and subsequent disease management. Inflammatory models of respiratory disease combined with sputum biomarkers are important tools in this approach.
aDepartment of Respiratory Medicine and Allergology, Skane University, Lund, Sweden bDepartment of General Practice, University Medical Center Groningen, Groningen, The Netherlands cQuintiles Drug Research Unit, Respiratory and Inflammation Early Clinical Development dDepartment of Cardiothoracic Pharmacology, Imperial College, National Heart and Lung Institute, London, UK eDepartment of Clinical Pharmacology, Ghent University, Ghent, Belgium fQuintiles Global Allergy and Respiratory Therapeutic Delivery Unit, Madrid, Spain.
Zuzana
Z
Diamant
Graham W
GW
Clarke
Herman
H
Pieterse
Juan
J
Gispert
D015415:Biomarkers / Q000378:metabolism; D001985:Bronchial Provocation Tests; D002986:Clinical Trials as Topic; D006801:Humans; D008954:Models, Biological; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013183:Sputum / Q000378:metabolism
D015415:Biomarkers