Eosinophils Target Therapy for Severe Asthma: Critical Points

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma

Omineca Miner, January, 02, 1915

BACKGROUND AND AIMS: Immature platelet fraction (IPF) represents the quote of younger and larger sized circulating platelets, a potential marker of platelet reactivity and major cardiovascular events. We aimed to assess the relationship between IPF levels and the prevalence and extent of coronary artery disease (CAD) in patients undergoing coronary angiography. METHODS: A cohort of consecutive patients undergoing coronary angiography in a single centre were included. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF levels were measured at admission by routine blood cells count (A Sysmex XE-2100). RESULTS: We included 1789 patients, divided according to quartiles values of IPF. IPF levels were directly related to active smoke (p = 0.02), and non-acute coronary syndrome as indication to angiography (p < 0.001), higher levels of haemoglobin and uric acid (p < 0.001, respectively) and lower platelet count (p = 0.003). Angiographic features did not significantly differ according to quartiles values of IPF, but for a lower degree of TIMI flow in patients with a higher percentage of reticulated platelets (p = 0.01) and a higher rate of lesions involving bifurcations (p = 0.05). IPF levels did not affect the prevalence of CAD (77% vs. 82.2% vs. 79.1% vs. 75.6%, p = 0.34, adjusted OR [95% CI] = 0.93 [0.82-1.05], p = 0.22), nor of severe left main/three-vessel CAD (28.5% vs. 34.4% vs. 32.2% vs. 33.1%, p = 0.27; adjusted OR [95% CI] = 0.99 [0.90-1.1], p = 0.88). CONCLUSIONS: The present study shows that among patients undergoing coronary angiography, the immature platelet fraction (IPF) is not associated with the prevalence and extent of coronary artery disease, and, therefore, should not be overlooked as a marker of coronary atherosclerosis