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.
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.
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
Correspondence to Professor Zuzana Diamant, MD, PhD, Skane University, Dept of Respiratory Medicine & Allergology, Klinikgatan 18, S-221 81, Lund, Sweden. E-mail: email@example.com; Dr Graham W. Clarke, PhD, Respiratory & Inflammation Early Clinical Development, Quintiles Drug Research Unit, London SE1 1YR, UK. E-mail: firstname.lastname@example.org