Human asthma phenotypes: from the clinic, to cytokines, and back again

Immunol Rev. 2011 Jul;242(1):220-32. doi: 10.1111/j.1600-065X.2011.01032.x.


A large body of experimental evidence supports the hypothesis that T-helper 2 (Th2) cytokines orchestrate allergic airway inflammation in animal models. However, human asthma is heterogeneous with respect to clinical features, cellular sources of inflammation, and response to common therapies. This disease heterogeneity has been investigated using sputum cytology as well as unbiased clustering approaches using cellular and clinical data. Important differences in cytokine-driven inflammation may underlie this heterogeneity, and studies in human subjects with asthma have begun to elucidate these molecular differences. This molecular heterogeneity may be assessed by existing biomarkers (induced sputum evaluation or exhaled nitric oxide testing) or may require novel biomarkers. Effective testing and application of emerging therapies that target Th2 cytokines will depend on accurate and easily obtained biomarkers of this molecular heterogeneity in asthma. Furthermore, whether other non-Th2 cytokine pathways underlie airway inflammation in specific subsets of patients with asthma is an unresolved question and an important goal of future research using both mouse models and human studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Airway Remodeling / immunology*
  • Allergens / immunology
  • Animals
  • Asthma / classification
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / physiopathology
  • Biomarkers / analysis
  • Child
  • Eosinophils / immunology
  • Humans
  • Immunity, Innate*
  • Inflammation / immunology*
  • Interleukin-13 / immunology*
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology
  • Nitric Oxide / analysis
  • Phenotype
  • Randomized Controlled Trials as Topic
  • Signal Transduction / immunology
  • Sputum / cytology
  • Sputum / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • Adrenal Cortex Hormones
  • Allergens
  • Biomarkers
  • Interleukin-13
  • Nitric Oxide