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Asthma is a chronic inflammatory process that leads to airway narrowing, causing breath loss followed by spasms, wheezing, and shortness of breath. Within the asthmatic lungs, interaction among various immune cells and structural cells plays a significant role in orchestrating an inflammatory response in which eosinophils hold central importance. In these settings, allergens or other environmental exposures commonly drive the immune response to recruit eosinophils to the airways. The appearance of eosinophils in the airways indicates a dynamic interplay of various cell types within lung tissue and does not represent a passive effect of inflammation. The cellular cross-talk causes the persistence of eosinophilic inflammation, and if left untreated, it results in long-term damage to the airway structure and function. Further exacerbation of the condition occurs because of this. We discuss how this complex interplay of eosinophils, immune, and structural cells within the airway microenvironment leads to the distinct pathophysiological features in asthma, the variability in disease severity, and the response to biological treatments.

Anti-interleukin (IL) 5 is an effective treatment modality for inhibiting eosinophilic inflammation in patients with T2-high severe asthma. The aim of this study was to determine the clinical efficacy and serum levels of type 2 inflammatory mediators during 24 weeks of mepolizumab treatment in patients with T2-high severe asthma. Eighteen patients with T2-high severe asthma were enrolled in this study. All patients received 100 mg of mepolizumab subcutaneously every 4 weeks and were retested at 4, 12, and 24 weeks. A clinical examination, asthma control test (ACT), and spirometry were performed; fractional exhaled nitric oxide (FeNO) levels were evaluated; and blood samples were drawn at every visit. Type 2 inflammation mediator levels were measured using enzyme-linked immunosorbent assay (ELISA). The blood eosinophil level significantly decreased, the ACT score and FEV1 increased after 4 weeks of mepolizumab treatment with the same tendency after 12 and 24 weeks (p < 0.05), and the FeNO level did not change (p > 0.05). A total of 27.8% of patients reached clinical remission criteria after 24 weeks of mepolizumab treatment. IL-33 and eotaxin significantly increased (p < 0.05) while IL-5, IL-13, thymic stromal lymphopoietin (TSLP), soluble IL-5 receptor subunit alpha (sIL-5Rα), and soluble high-affinity immunoglobulin E receptor (sFcεRI) decreased, with the same tendency after 12 and 24 weeks (p < 0.05). The serum levels of immunoglobulin (Ig) E and IL-4 and IL-25 levels did not change during mepolizumab treatment compared to baseline (p > 0.05). In conclusion, treatment with mepolizumab over 24 weeks improved lung function and asthma control in T2-high severe asthma patients, with nearly one-third achieving clinical remission criteria, and affected the balance of type 2 inflammatory mediators.

In distinguishing the allergic asthma (AA) phenotype, it has been identified that specific biomarkers could assist; however, none of them are considered ideal. This study aimed to analyze three groups of biologically active substances in the serum. Twenty steroid-free AA patients, sensitized to Dermatophagoides pteronyssinus, and sixteen healthy subjects (HSs) were enrolled in this study. Blood samples were collected from all patients. Additionally, all AA patients underwent a bronchial allergen challenge (BAC) with Dermatophagoides pteronyssinus, all of which were positive, and blood samples were collected again 24 h later. The concentrations of ten biologically active substances were measured in the serum samples, using enzyme-linked immunosorbent assay (ELISA) and the Luminex® 100/200™ System technology for bead-based multiplex and singleplex immunoassays. Descriptive and analytical statistical methods were used. A p-value of 0.05 or lower was considered statistically significant. The soluble interleukin 5 receptor subunit alpha (sIL-5Rα) and thioredoxin 1 (TRX1) concentrations were significantly increased, whereas those of tyrosine-protein kinase Met (MET), pentraxin 3 (PTX3), and I C-telopeptide of type I collagen (ICTP) were decreased in the AA group compared with the HS group. A significant positive correlation was noted for sIL-5Rα with fractional exhaled nitric oxide (FeNO), blood eosinophil (EOS) count, and total immunoglobulin E (IgE) levels, and a negative correlation was noted with forced expiratory volume in 1 s (FEV1). Moreover, PTX3 showed negative correlations with blood EOS count and total IgE levels, whereas ICTP exhibited a negative correlation with the blood EOS count. In conclusion, this study demonstrated that the serum concentrations of MET, PTX3, TRX1, ICTP, and particularly sIL-5Rα could potentially serve as biomarkers of the AA phenotype.

Blood eosinophils can be described as inflammatory-like (iEOS-like) and lung-resident-like (rEOS-like) eosinophils. This study is based on the hypothesis that eosinophilopoetins such as interleukin (IL)-3 and IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) alter the proliferative properties of eosinophil subtypes and may be associated with the expression of their receptors on eosinophils. We investigated 8 individuals with severe nonallergic eosinophilic asthma (SNEA), 17 nonsevere allergic asthma (AA), and 11 healthy subjects (HS). For AA patients, a bronchial allergen challenge with Dermatophagoides pteronyssinus was performed. Eosinophils were isolated from peripheral blood using high-density centrifugation and magnetic separation methods. The subtyping of eosinophils was based on magnetic bead-conjugated antibodies against L-selectin. Preactivation by eosinophilopoetins was performed by incubating eosinophil subtypes with IL-3, IL-5, and GM-CSF, and individual combined cell cultures were prepared with airway smooth muscle (ASM) cells. ASM cell proliferation was assessed using an Alamar blue assay. The gene expression of eosinophilopoetin receptors was analyzed with a qPCR. IL-5 and GM-CSF significantly enhanced the proliferative properties of iEOS-like and rEOS-like cells on ASM cells in both SNEA and AA groups compared with eosinophils not activated by cytokines (p < 0.05). Moreover, rEOS-like cells demonstrated a higher gene expression of the IL-3 and IL-5 receptors compared with iEOS-like cells in the SNEA and AA groups (p < 0.05). In conclusion: IL-5 and GM-CSF promote the proliferative properties of iEOS-like and rEOS-like eosinophils; however, the effect of only IL-5 may be related to the expression of its receptors in asthma patients.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy. Objectives: To evaluate left heart geometry, function, deformation parameters, and blood serum biomarker (galectin-3, sST2, endothelin-1) levels in patients with OSA, as well as to assess changes after short-term CPAP treatment. Materials and Methods: Thirty-four patients diagnosed with moderate or severe OSA, as well as thirteen patients as a control group, were included in the study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Transthoracic 2D ST echocardiography was performed before and after 3 months of treatment with CPAP; for the control group, at baseline only. Peripheral blood samples for the testing of biomarkers were collected at the time of study enrolment before the initiation of CPAP therapy and after 3 months of CPAP treatment (blood samples were taken just for OSA group patients). Results: The left ventricle (LV) end-diastolic diameter and volume, as well as LV ejection fraction (EF), did not differ between groups, but an increased LV end-systolic volume and a reduced LV global longitudinal strain (GLS) were found in the OSA group patients (p = 0.015 and p = 0.035, respectively). Indexed by height, higher LV MMi in OSA patients (p = 0.007) and a higher prevalence of LV diastolic dysfunction (p = 0.023) were found in this group of patients. Although left atrium (LA) volume did not differ between groups, OSA group patients had significantly lower LA reservoir strain (p < 0.001). Conventional RV longitudinal and global function parameters (S′, fractional area change (FAC)) did not differ between groups; however, RV GLS was reduced in OSA patients (p = 0.026). OSA patients had a significantly higher right atrium (RA) diameter and mean pulmonary artery pressure (PAP) (p < 0.05). Galectin-3 and sST2 concentrations significantly decreased after 3 months of CPAP treatment. Conclusions: OSA is associated with the left heart remodeling process—increased LV myocardial mass index, LV diastolic dysfunction, reduced LV and RV longitudinal strain, and reduced LA reservoir function. A short-term, 3-months CPAP treatment improves LV global longitudinal strain and LA reservoir function and positively affects blood serum biomarkers. This new indexing system for LV myocardial mass by height helps to identify myocardial structural changes in obese patients with OSA.