EGPA and severe asthma: mechanisms and pathophysiology

Background. An increase in blood absolute eosinophilic count is a relative commune condition associated to different disorders that includes both organ-specific and systemic diseases. The lung often represents a target organ of the eosinophilic inflammation and the differential diagnosis of the different hypereosinofilic syndromes is not simple, including reactive conditions (allergic reactions, parasitic infections, adrenal insufficiency), eosinophilia associated to solid neoplasms or hematological disorders, the idiopatic hypereosinophilic syndrome (HES) and pulmonary eosinophilic disorders : acute and chronic eosinophilic pneumonia, chronic severe asthma and the eosinophilic granulomatosis with polyangitis (EGPA or Churg-Strauss syndrome, CSS). EGPA is a rare, potentially life-threatening, systemic necrotizing vasculitis, characterized by blood eosinophilia and tissue infiltration by eosinophils, late onset asthma and rhino-sinusal disease.

Traditionally three partially overlapping phases have been described in EGPA course: a prodromic phase, with asthma, rhinosinusitis and allergic manifestations, then tissues eosinophilic infiltration and evidence of eosinophil-induced organ damage, and a third systemic phase characterized by the development of the systemic necrotizing vasculitis.

Bronchial asthma is the unifying feature of all EGPA patients being described in the 96%–100% of the patients and represents the pathognomonic feature of EGPA. It is generally an adult-onset asthma, often refractory to the traditional inhaled treatment and which might require oral corticosteroids to be properly controlled. The mean latency between the asthma onset and the vasculitic phase of the disease has been estimated around 3-9 years but it might last as long as 30 years. Differently from the hypereosinophilia in asthmatic patients, that is a common finding, the Eosinophilic Granulomatosis with Polyangiitis is a rare disease, with an annual incidence of 0.5–4.2 cases/106 inhabitants.

At time it is impossible to predict which patients with severe chronic asthma will develop a form of systemic disease, but the study and the follow-up of the biomarkers of systemic and bronchial inflammation can help us to recognize the patients with a potential risk to develop a multiorgan damage over the time and reduce the undiagnosed cases, making possible a correct therapeutic approach.

Aim. Our research project is aimed to assessing the diagnostic value of traditional and newer biomarkers in all asthmatic subjects with a suspected diagnosis of EGPA, confirming the diagnostic hypotesis and optimizing the treatment of their asthma.

Preliminary data. At time we have observed 40 patients affected by EGPA. All patients were assessed for lung function and bronchial hyperreactivity. Asthma severity was evaluated according to GINA guidelines and asthma control by ACT test. Sputum eosinophil percentages and exhaled nitric oxide (eNO) were measured. Level of systemic and inhaled therapy, serological and systemic disease features (anti-neutrophil cytoplasmic autoantibody (ANCA), blood eosinophilia, IL-2, IL-4, IL-5, eosinophil cationic protein (ECP), BVAS (Birmingham Vasculitis Activity Score) and VDI (Vasculitis Damage Index) were recorded. Nasal involvement was evaluated by nasal endoscopy, and nasal cytology was determinate. The asthma impact on the quality of life was evaluated by the short form (SF)-36 and Asthma Quality of Life Questionnaire (AQLQs). In all patients was documented a low residual disease activity but an active and severe asthma, only partially or poorly controlled, and a rhinosinusal disease with a high prevalence of nasal polyps. A persistent airflow obstruction was observed in in the majority of patients and an high level of airway inflammatory markers was detected. So we can conclude that it’s necessary to optimize inhaled and systemic therapy in patients with EGPA and severe chronic asthma and undergo the patients to a regular follow-up for their asthma.

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Dott.ssa Manuela Latorre

Graduated in Medicine and Surgery at the University of Pisa (2007) and Specialized in Respiratory Medicine at the University of Pisa (2012). Engaged in the study of patients with severe asthma and in the research in the field of hypereosinophilic syndromes, in particular: holder in 2012 of a research grant in the analysis of the functional and biological pulmonary features in Churg-Strauss syndrome, then holder of a research grant in the study of patients with severe asthma. Currently PhD on the hypereosinophilic syndromes at the University of Pisa. Author and co-author of several abstracts sent to the national and international meetings and of 3 papers published on international journals.