Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management

Abstract

Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1–3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients.

Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choice

“…In fact, airway remodeling may occur in parallel with chronic inflammation or/and as a consequence of the inflammatory response [ 36 ]. On the other hand, the uncoupling of airway hyperresponsiveness and remodeling from airway inflammation has been recently described in T2-low asthma [ 37 , 38 ].…”

Recent insights in the role of biomarkers in severe asthma management

“…Paucigranulocytic asthma comprises another component of non-T2 asthma, and is by default defined as asthma without T2 biomarkers ( 91 ). Therefore, targeted treatment options, as well as clinically applicable biomarkers, are still largely under exploration ( 92 ). In this context, the clinically relevant issue of whether “true” non-T2 asthma really exists has been raised, as high-dose ICS and oral corticosteroids (OCS) may potentially minimize blood eosinophils and FeNO levels, therefore masking preexisting T2 inflammation ( 93 ).…”

Pendekatan Multiperspektif Dalam Manajemen Penyakit Asma

“…Terapi yang diarahkan untuk mengurangi inflamasi dapat menurunkan tingkat hiperesponsivitas saluran pernapasan dan meningkatkan pengendalian asma. 24,25,26…”