Severe asthma: phenotyping to endotyping or vice versa?

Papi, Alberto; Saetta, Marina; Fabbri, Leonardo M.

doi:10.1183/13993003.00053-2017

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…Severe uncontrolled asthma treatment in daily clinical practice poses a great challenge to the pulmonologists. New strategies have been approved the recent years, implemented within a stepwise approach, taking into consideration relevant phenotypic characteristics of individuals and specific biomarkers (17,18).…”

Section: Discussionmentioning

confidence: 99%

Real‑life Cretan asthma registry focused on severe asthma: On behalf of ‘The Cretan registry of the use of Biologics in Severe Asthma’

et al. 2021

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Asthma diagnosis and management remains a challenging task for the medical community. The aim of the present study was to present the functional and inflammatory profiles of patients with difficult-to-treat asthma in a real-life clinical setting referred to the specialized asthma clinic at the University Hospital of Heraklion. The registry included a cohort of 267 patients who were referred to the severe asthma clinic. Patients were assessed with emphasis on the history of allergies, nasal polyposis or other comorbidities. Blood testing for eosinophils counts and total and specific IgE, and pulmonary function tests were performed at baseline. The median age of patients with asthma was 55 years old, 68.5% were women and 58.3% were never smokers. The vast majority presented with late onset asthma (75.7%), whereas eight (3%) patients were on oral corticosteroids. The median number of exacerbations during the last 12 months was 1 (0-3). Furthermore, 50.7% of patients had a positive serum allergy test, the median eosinophil count was 300 (188-508.5) cells/µl of blood and median total IgE level was 117.5 (29.4-360.5) IU/ml. Patients were retrospectively grouped in the following categories: Group 1, mild-moderate asthma; group 2, patients prescribed a step 4 or 5 asthma therapy according to Global Initiative for Asthma; and group 3, patients on biologic agents. Group 1 had significantly higher FEV1% than groups 2 and 3 (93.4 vs. 79.9 and 79.4%, respectively; P<0.001). Finally, the median Asthma Control Questionnaire 7 (ACQ7) score was 1.14, with patients from groups 2 and 3 presenting higher ACQ7 scores compared with group 1 patients as expected (1.1 and 2.1 vs. 0.7, respectively; P<0.001). To the best of our knowledge, this was the first real-life asthma study in Crete that demonstrated that severe asthmatics predominantly have late-onset asthma with airflow obstruction and uncontrolled symptoms.

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Section: Discussionmentioning

confidence: 99%

Real‑life Cretan asthma registry focused on severe asthma: On behalf of ‘The Cretan registry of the use of Biologics in Severe Asthma’

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…Asthma is a heterogeneous disease with different endotypes; therefore, it should be treated in an individualized and personalized way [12]. Among the most common endotypes of asthma, there are Th2-high (typically eosinophilic) and Th2-low (also known as Th1/Th17, typically neutrophilic or paucigranulocytic) [13].…”

Section: Discussionmentioning

confidence: 99%

“…Among the most common endotypes of asthma, there are Th2-high (typically eosinophilic) and Th2-low (also known as Th1/Th17, typically neutrophilic or paucigranulocytic) [13]. Th2-high asthma is usually responsive to treatment with corticosteroids, as Th2-low or Th1/Th17 asthma has predominance of neutrophil infiltration on airways and can lead to a corticosteroid-resistant severe asthma [12,14]. There is also the asthmatic endotype characterized by a high infiltration of both eosinophils and neutrophils on bronchoalveolar lavage fluid, which is denominated mixed-granulocytic asthma and is usually more severe, with high remodeling and reduced pulmonary capacity [15].…”

Section: Discussionmentioning

confidence: 99%

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Biseugenol Exhibited Anti-Inflammatory and Anti-Asthmatic Effects in an Asthma Mouse Model of Mixed-Granulocytic Asthma

et al. 2020

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In the present work, the anti-inflammatory and antiasthmatic potential of biseugenol, isolated as the main component from n-hexane extract from leaves of Nectandra leucantha and chemically prepared using oxidative coupling from eugenol, was evaluated in an experimental model of mixed-granulocytic asthma. Initially, in silico studies of biseugenol showed good predictions for drug-likeness, with adherence to Lipinski’s rules of five (RO5), good Absorption, Distribution, Metabolism and Excretion (ADME) properties and no alerts for Pan-Assay Interference Compounds (PAINS), indicating adequate adherence to perform in vivo assays. Biseugenol (20 mg·kg−1) was thus administered intraperitoneally (four days of treatment) and resulted in a significant reduction in both eosinophils and neutrophils of bronchoalveolar lavage fluid in ovalbumin-sensitized mice with no statistical difference from dexamethasone (5 mg·kg−1). As for lung function parameters, biseugenol (20 mg·kg−1) significantly reduced airway and tissue damping in comparison to ovalbumin group, with similar efficacy to positive control dexamethasone. Airway hyperresponsiveness to intravenous methacholine was reduced with biseugenol but was inferior to dexamethasone in higher doses. In conclusion, biseugenol displayed antiasthmatic effects, as observed through the reduction of inflammation and airway hyperresponsiveness, with similar effects to dexamethasone, on mixed-granulocytic ovalbumin-sensitized mice.

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“…However, a specific asthma phenotypic trait may have multiple underlying disease mechanisms linked to different mechanistic pathways (Green et al, 2002;Fahy, 2015). Therefore, it has been suggested that disease endotypes, which are defined by specific pathophysiological mechanisms, may provide a better framework for asthma research (Anderson, 2008;Perlikos et al, 2016;Papi et al, 2017;Licari et al, 2018). Biomarkers of each pathophysiological mechanism or mechanistic pathway could help to identify each endotype in the clinic, Pharmacology of GPCRs in Asthma Therapy and Drug Action allowing for drugs or therapeutic methods that specifically target the underlying causative mechanism to be used for each endotype.…”

Section: A Epidemiology Pathology and Pathophysiology Of Asthmamentioning

confidence: 99%