Future Directions in Bronchiectasis Research

https://doi.org/10.1016/j.ccm.2021.12.005Get rights and content

Section snippets

Key points

  • One of the main research priorities in bronchiectasis is to address the complexity and heterogeneity of this disease.

  • In the era of multi-omics approaches, there is an urgent need to generate data to better stratify patients in endotypes.

  • Personalized medicine is required, and it will be achieved by the application of omics technologies and stratification tools to uncover such biomarkers.

  • Future research studies involving cluster strategies and network analyses are needed to integrate data for

Validated biomarkers

For years, sputum color has been the most affordable qualitative lung infection biomarker in clinical practice for patients with bronchiectasis.9 The green color of sputum reflects pulmonary neutrophilic inflammation, through the green neutrophil protein myeloperoxidase, which is increased during exacerbations.10 However, nowadays multiple studies have been published to find quantifiable biomarkers in blood and lung samples with a diagnostic, therapeutic, or even prognostic role of the disease,

Genetics and epigenetics

Recent advances in lung biology involving genetic studies have allowed to identify genetic variants associated with lung functions and to provide novel evidence for understanding the pathogenesis in airway diseases.

In 1989, genetics approaches allowed to know the mutations in the gene responsible for cystic fibrosis (CF), the most common and lethal autosomal recessive disorder in Caucasians.45 This gene encodes for a protein called cystic fibrosis transmembrane conductance regulator (CFTR), and

Microbiome

Understanding the contribution of airway infection to the pathophysiology of bronchiectasis is a critical step toward the prevention of disease progression. The traditional quantitative microbiological cultures can provide useful data in the assessment of treatment response. Novel analyses in bronchiectasis have revealed that the total airway bacterial load can classify patients depending on their response to antibiotic treatment, being the good responders to inhaled antibiotics for those

Other relevant omics

As airway diseases are complex and multifactorial, there is a need to integrate multiple aspects that may play a role in the prognosis of the disease. The available omics technologies also provide data about protein (proteomics), RNA expression (transcriptomics), metabolites (metabolomics), lipid mediators (lipidomic), and glycans level (glycomic).54 Although few studies have been reported in bronchiectasis using these approaches, an increase in their application is expected in the next few

Personalized medicine

The term precision or personalized medicine has been proposed to define treatments targeted to the needs of individual patients based on genetic, biomarker, phenotypic, or psychosocial characteristics, that distinguish a given patient from other patients with similar clinical presentations.56 The main objective of precision medicine is to improve clinical outcomes for individual patients while minimizing unnecessary side effects for those likely to respond to a given treatment. In patients with

Summary

Emerging evidence suggests that endotypes exist in the bronchiectasis population. For that reason, bronchiectasis treatment is challenging, and many recent randomized controlled trials have failed to prove any clinical improvement. In the era of multi-omics approaches, there is an urgent need to generate data to better stratify patients in endotypes for the development of personalized medicine. The integration of multiple aspects into systems biology studies, such as genomics, microbiome,

Clinics care points

  • Clinical and biological heterogeneity is the main cause of clinical trial failures in bronchiectasis.

  • Research focused on the identification of endotypes and treatable traits in bronchiectasis will help us to move toward the development of a personalized medicine.

  • NE is currently the most promising biomarker and therapeutic target in bronchiectasis.

  • Further studies applying omics technologies and integrating data in network analyses are needed to find new local and systemic biomarkers with

Disclosure

The authors have nothing to disclose.

First page preview

First page preview
Click to open first page preview

References (62)

  • J.K. Quint et al.

    Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study

    Eur Respir J

    (2016)
  • S. Aliberti et al.

    Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration

    Eur Respir J

    (2016)
  • R. Faner et al.

    Network medicine, multimorbidity and the lung in the elderly

    Eur Respir J

    (2014)
  • A. Agustí et al.

    Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine

    Am J Respir Crit Care Med

    (2011)
  • T. Cruz et al.

    Multi-level immune response network in mild-moderate chronic obstructive pulmonary disease (COPD)

    Respir Res

    (2019)
  • J.D. Chalmers et al.

    Sputum colour in non-CF bronchiectasis: the original neutrophil biomarker

    Respirology

    (2014)
  • R.A. Stockley et al.

    Assessment of airway neutrophils by sputum colour: correlation with airways inflammation

    Thorax

    (2001)
  • P.J. Cole

    Inflammation: a two-edged sword - the model of bronchiectasis

    Eur J Respir Dis

    (1986)
  • M.C. Mckelvey et al.

    Targeting proteases in cystic fibrosis lung disease Paradigms

    Prog Potential

    (2020)
  • F.L. Dente et al.

    Neutrophilic bronchial inflammation correlates with clinical and functional findings in patients with Noncystic fibrosis bronchiectasis

    Mediators Inflamm

    (2015)
  • S.C.H. Chan et al.

    Sputum sol neutrophil elastase activity in bronchiectasis: differential modulation by syndecan-1

    Am J Respir Crit Care Med

    (2003)
  • R. Amitani et al.

    Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium

    Am J Respir Cell Mol Biol

    (1991)
  • J.D. Chalmers et al.

    Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis

    Am J Respir Crit Care Med

    (2017)
  • H.R. Keir et al.

    Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition

    ERJ Open Res

    (2019)
  • A. Gramegna et al.

    Sputum neutrophil elastase in bronchiectasis: a Southern European cohort study

    Eur Respir J

    (2020)
  • S. Finch et al.

    Pregnancy zone protein is associated with airway infection, neutrophil extracellular trap formation, and disease severity in bronchiectasis

    Am J Respir Crit Care Med

    (2019)
  • H.R. Keir et al.

    Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study

    Lancet Respir Med

    (2021)
  • C. Bonnans et al.

    Remodelling the extracellular matrix in development and disease

    Nat Rev Mol Cell Biol

    (2014)
  • K.J. Greenlee et al.

    Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted

    Physiol Rev

    (2007)
  • S.L. Taylor et al.

    Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis

    Ann Am Thorac Soc

    (2015)
  • L. Zheng et al.

    Overexpression of matrix metalloproteinase-8 and -9 in bronchiectatic airways in vivo

    Eur Respir J

    (2002)
  • Cited by (5)

    • Bronchiectasis

      2023, Presse Medicale
    View full text