Molecular analysis of phenotypic interactions of asthma

Cytokine. 2021 Jul:143:155524. doi: 10.1016/j.cyto.2021.155524. Epub 2021 Apr 10.

Abstract

Introduction: Asthma is a heterogeneous disease characterized by multiples respiratory symptoms; this is a polygenic entity that involves a complex interaction of environmental factors and inherent to the individual. To understand the development of asthma, some phenotypes have been proposed.

Objective: This work's purpose was to explore different molecules related to asthma development and to define each phenotype's specific characteristics.

Material and methods: 96 adult patients diagnosed with asthma before any treatment were enrolled in the protocol. Spirometric parameters, circulating leukocytes, serum IgE, body mass index, exhaled nitric oxide (FENO), and leukotrienes (LTB4) in urine were determined in each patient. The presence of asthma phenotypes proposed by the Global Initiative for Asthma (GINA) were explored: A) Allergic asthma, B) Non-allergic asthma, C) Late-onset asthma, D) Asthma with persistent airflow limitation, and E) Asthma with overweight and obesity.

Results: In the cohort analyzed, we found four of phenotypes proposed by GINA; however, these phenotypes overlapped, due to this, 4 groups were integrated with allergic, non-allergic and obese patients, which were the main phenotypes. The main overlap was that of patients not-obese allergic, and was characterized by earlier onset, elevated levels of IgE, LTB4 and inflammasome related cytokines. Non-allergic patients had a significant association between interleukin (IL)-18 and IL-18 binding protein (BP) with narrow ratio between these cytokines. Finally, LTB4 had remarkable capacity to discriminate between allergic and not allergic patients.

Conclusions: Asthmatic phenotypes exist as interrelated characteristics and not as discrete entities. High levels of leukotrienes and IgE are hallmarks in the allergic phenotype of asthma.

Keywords: Allergy; Asthma; Obesity; Phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Asthma / blood
  • Asthma / diagnosis
  • Asthma / genetics*
  • Asthma / pathology*
  • Biomarkers / blood
  • Cytokines / blood
  • Eosinophils / metabolism
  • Female
  • Humans
  • Hypersensitivity / blood
  • Hypersensitivity / complications
  • Immunoglobulin E / blood
  • Inflammasomes / blood
  • Inflammation Mediators / metabolism
  • Intercellular Signaling Peptides and Proteins / blood
  • Interleukin-18 / blood
  • Interleukin-8 / blood
  • Leukotrienes / urine
  • Male
  • Middle Aged
  • Overweight
  • Phenotype
  • Transforming Growth Factor beta / blood

Substances

  • Biomarkers
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-18
  • Interleukin-8
  • Leukotrienes
  • Transforming Growth Factor beta
  • interleukin-18 binding protein
  • Immunoglobulin E