Disease models of chronic inflammatory airway disease: applications and requirements for clinical trials

Curr Opin Pulm Med. 2014 Jan;20(1):37-45. doi: 10.1097/MCP.0000000000000013.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism
  • Bronchial Provocation Tests
  • Clinical Trials as Topic*
  • Humans
  • Models, Biological*
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Sputum / metabolism

Substances

  • Biomarkers