Eosinophilic Type Research Articles

Inflammation-induced loss of CFTR-expressing airway ionocytes in non-eosinophilic asthma.

Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non-eosinophilic asthma. Non-eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non-eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non-eosinophilic asthma. Patient-derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air-liquid interface. Single cell RNA-sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma. We identified that hBECs from patients with non-eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR-expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic-dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma-like inflammatory cytokine mixture led to a reduction in ionocytes. Inflammation-induced loss of CFTR-expressing ionocytes in airway cells from non-eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target.

Concomitant Efficacy of Dupilumab in Treating Eosinophilic Esophagitis and Type 2 Asthma.

Concomitant Efficacy of Dupilumab in Treating Eosinophilic Esophagitis and Type 2 Asthma.

Difficult-To-Treat and Severe Asthma: Can Real-World Studies On Effectiveness of Biological Treatments Change the Lives of Patients?

Many different phenotypes that characterize severe asthma are supported by intricate pathomechanisms called endotypes. The latter are driven by molecular interactions, mediated by intercellular networks. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, real-world studies have confirmed the positive effects of currently available antibodies directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, as well as the receptors of interleukins-4 (IL-4) and 13 (IL-13). The best way to treat severe asthma should be chosen based on the peculiar phenotypic and endotypic traits of each patient. This will lead to relevant improvements in both clinical and functional outcomes. In particular, biological therapies can change the lives of asthma patients with a strong impact on quality of life. Unfortunately, patients with severe non-type-2 asthma, who continue to have pertinent unmet needs, are not receiving satisfactory advances within the context of biological treatments. It is also hopeful that in the next future new therapeutic strategies will be specifically implemented for these people, perhaps offering them the opportunity to improve their current, mostly inadequate asthma management.

Dual inhibition of airway inflammation and fibrosis by common β cytokine receptor blockade

BackgroundSevere asthmatics can present with eosinophilic type 2 (T2), neutrophilic or mixed inflammation that drives airway remodeling and exacerbations and represents a major treatment challenge. The common beta (βc) receptor signals for three cytokines GM-CSF, IL-5 and IL-3, that collectively mediate T2 and neutrophilic inflammation. ObjectivesTo determine the pathogenesis of βc receptor mediated inflammation and remodeling in severe asthma, and to investigate βc antagonism as a therapeutic strategy for mixed granulocytic airway disease. Methodsβc gene expression was analysed in bronchial biopsies from mild/moderate and severe asthmatics. House dust mite extract (HDM) and Aspergillus fumigatus extract (ASP) models were used to establish asthma-like pathology and airway remodeling in human βc transgenic mice. Lung tissue gene expression was analysed by RNA-sequencing. The monoclonal antibody CSL311 targeting the shared cytokine binding site of βc was used to block βc signaling. Resultsβc gene expression was increased in severe asthmatics. CSL311 potently reduced lung neutrophils, eosinophils and interstitial macrophages, and improved airway pathology and lung function in the acute steroid resistant HDM model. Chronic intranasal ASP exposure induced airway inflammation and fibrosis and impaired lung function that was inhibited by CSL311. CSL311 normalised the ASP-induced fibrosis-associated extracellular matrix gene expression network and strongly reduced signatures of cellular inflammation in the lung. Conclusionsβc cytokines drive steroid-resistant mixed myeloid cell airway inflammation and fibrosis. The anti-βc antibody CSL311 effectively inhibits mixed T2/neutrophilic inflammation and severe asthma-like pathology and reverses fibrosis gene signatures induced by exposure to commonly encountered environmental allergens.

Clinical treatment options oriented to the endotype of chronic rhinosinusitis

Chronic rhinosinusitis（CRS） is an inflammatory disease involving the mucosa of the nasal and paranasal sinuses for more than 12 weeks and can be classified as CRS with nasal polyp（CRSwNP） and CRS without nasal polyp（CRSsNP） depending on the phenotype. Clinical treatments reveal significant differences in disease prognosis and improvement in quality of life in patients with the same clinical phenotype. Inflammatory cells infiltration and inflammatory mediators are important factors driving CRS endotypes. In particular, CRS with predominantly eosinophilic infiltration and type 2 CRS present severe clinical symptoms, comorbidities, and high recurrence rates. CRS endotype-oriented treatment methods may better contribute to improving patient prognosis and quality of life. This article summarizes the current progress of CRS endotype research and reviews the endotype-oriented treatment options.

Markers of eosinophilic inflammation of airways in patients with fungal sensitilization

Immunological characteristics of airway inflammation in asthma patients with sensitization to various fungal allergens are not well understood, and the search for new markers is necessary to establish future targets for targeted therapy. The purpose of our study was to assess the levels of eosinophilic inflammation markers of the respiratory tract in patients with severe asthma and allergic bronchopulmonary aspergillosis, depending on the spectrum of fungal sensitization.
 The study included 31 patients with severe asthma with fungal sensitization and 29 patients with allergic bronchopulmonary aspergillosis (ABPA). The levels of total, specific IgE to fungal allergens and periostin in blood serum were determined by enzyme immunoassay. The study of basophil activation was performed by flow cytometry.
 The patients with severe asthma and sensitization to Aspergillus spp. and Alternaria spp. had significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp. in the basophil activation test when compared with the group of asthma patients with sensitization to Aspergillus spp. only. In patients with ABPA with combined sensitization, we have found significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp.
 The finding of pronounced eosinophilic type of inflammation in patients with asthma and combined sensitization to thermotolerant and thermolabile fungi may result from aggressive effect of fungal allergens on the barrier functions of bronchial epithelium, which should be taken into account when choosing therapeutic strategy and administration of immunobiological therapy.

MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability.

Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-β receptor III (TGFBR3) mRNA level by binding to its 3' UTR and reducing its stability in HNECs. TGF-βR3 was found to be a TGF-β2-specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-β2-induced phosphorylation of SMAD2 in HNECs, respectively. TGF-βR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-β2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-βR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.

Role of interleukin-5 in allergic fungal sinusitis: deeper insight

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is an allergic response characterized by type 2 inflammatory reactions mediated by T helper 2 cells (Th2). Th2 is characterized by elevated type 2 cytokines related to the humoral response, including Interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, IL-25 and IL-33. Allergic fungal sinusitis (AFS) is a distinguishable form of CRSwNP and is characterized by primary localized disease with non-invasive fungal hyphae, which causes immunoglobulin E (IgE)-mediated mucosal hypersensitivity resulting in the formation of eosinophilic mucin. Interleukin-5 (IL-5) is a pro-inflammatory factor that plays a very important role in eosinophil biology.ObjectiveTo explore the relation between IL-5 tissue protein expression and AFS.MethodsA prospective study performed on 70 patients divided into 2 groups (50 cases of AFS and 20 control who underwent septoplasty and partial inferior turbinectomy) to assess the role of IL5 in AFS compared to control.ResultsIL-5 was overexpressed in polyps of AFS patients compared to the control group denoting AFS as an eosinophilic mediated type 2 inflammation and highlighting a positive correlation with Lund MacKay radiological score and Sino-nasal Outcome Test (SNOT-22) score for severity of chronic rhinosinusitis (CRS) symptoms.ConclusionIL-5 plays a pivotal role in the pathogenesis and severity of AFS. Thus, our results provide encouraging evidence supporting targeting IL5 as an eligible therapy of promising benefits in AFS.

Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy.

To compare the responses of suspected eosinophilic otitis media to treatment with or without a targeted biologic therapy against interleukin-4 (IL-4), IL-5, or IL-13 signaling. Retrospective review. Tertiary referral center. Subjects with type 2 chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and otitis media who underwent treatment between 2005 and 2021. Treatment with targeted biologic therapy. Pre- and posttreatment nasal endoscopy, ear examination, and audiologic evaluation. Four hundred seventy-seven subjects with type 2 CRSwNP were treated between 2005 and 2021. Sixty-two had otitis media with pre- and posttreatment evaluation. Retrospective chart review assessed pre- and posttreatment exam findings, nasal endoscopy, audiometry, and tympanometry. Nineteen subjects received a biologic therapy, whereas 43 did not. Exam, endoscopy, and tympanometry were graded for severity and compared pre- and posttreatment. Subjective ear exam and tympanometry were significantly improved with biologic therapy (control = 0.05, biologic = 0.84, p = 9.3 × 10 -5 ; control = -0.1, biologic = 0.62, p = 0.0002). Conductive hearing loss as assessed by air-bone gaps did not change between groups (control = 1.2 dB better, biologic = 1.2 dB worse, p = 0.32). Nasal endoscopy findings improved with biologic therapy relative to the control group, although not statistically significant (control = 1.04, biologic = 1.36, p = 0.22). Biologic therapies targeting interleukin-4 (IL-4), IL-5, and IL-13 signaling are potential new treatments for eosinophilic otitis media. This is the largest study demonstrating improvement in subjects with suspected eosinophilic otitis media in response to biologic therapy, and immune modulation represents a novel treatment strategy for this challenging condition. Current treatment strategies for otologic symptoms in eosinophilic disease are not tremendously effective or durable, resulting in a need for improved treatment options. To determine if targeted biologic therapy, often used for eosinophilic asthma and type 2 chronic rhinosinusitis with nasal polyposis, improves coexistent suspected eosinophilic otitis media. Treatment of suspected eosinophilic otitis media with targeted biologic therapy will result in improvement of otologic symptoms with a durable response compared with current treatment options. Level IV. Exempt. HUM00182703.

BMP-2 and IL-1β as Markers of Nasal Mucosa Inflammation in Rhinosinusitis with Nasal Polyps.

Rhinosinusitis with nasal polyps is characterized by chronic inflammation and hyperplasia of the nasal mucosa. The key mechanism for polyp formation is the expression of molecules that regulate proliferation and inflammation. We studied immunolocalization of bone morphogenetic protein-2 (BMP-2) and IL-1β in the nasal mucosa in patients aged 35-70 years (n=70, mean age 57.4±1.52 years). The typology of polyps was determined depending on the distribution of inflammatory cells, subepithelial edema, the presence of fibrosis and cysts. The immunolocalization of BMP-2 and IL-1β had the same pattern in edematous, fibrous, and eosinophilic (allergic) polyps. Goblet and connective tissue cells, microvessels and terminal sections of the glands were positively stained. BMP-2+ and IL-1β+ cells predominated in polyps of the eosinophilic type. BMP-2/IL-1β can be considered as a specific marker of inflammatory remodeling of the nasal mucosa in refractory rhinosinusitis with nasal polyps.

INFLUENCE OF AMINOCAPRONIC ACID ON THE REGRESSION OF NASAL POLYPS AND NASAL CONGESTION IN PATIENTS WITH POLYPOUS RHINOSINUSITIS

Chronic rhinosinusitis with nasal polyposis (CRS with NP) is a clinical syndrome including several clinical phenotypes and endotypes with differences in pathophysiology and is divided into neutrophilic (non-type 2) and eosinophilic (type 2) according to the dominant endotype, which is the most severe variant associated with therapy resistance and frequent recurrence. Such pheno-endotype requires personalized treatment, and pharmacotherapy based on endotyping is prospective. Aminocapronic acid (ACA) competitively inhibits plasminogen and plasmin formation, inhibits C3a and C5a, which can affect the pathophysiological mechanisms of eosinophilic inflammation and polypous growth, since, in addition to hemostatic properties, it also has desensitizing, anti-enzymatic, and anti-proliferative properties.
 The aim of the research: to evaluate the influence of additional administration of aminocapronic acid on the degree of regression of nasal polyps in comparison with patients receiving standard therapy of Chronic rhinosinusitis with nasal polyposis according to clinical recommendations.
 Material and methods. The study included 120 outpatients, divided into two groups: the main (n - 60) and control (n - 60) ones. The average age of the main group was 45.8 years; the control group was 47.0 years. Patients were prescribed basic treatment (irrigation therapy with saline solutions and mometasone furoate), and in the main group – additionally aminocapronic acid (ACA). The evaluation of treatment effectiveness was based on the analysis of the dynamics of nasal congestion and the regression of nasal polyps at V2 (day 5±1), V3 (day 10±1), V4 (day 20±1) and V5 (day 30±1) compared to V0. Indications for surgical treatment were determined at V3.
 Results. The use of aminocapronic acid in Chronic rhinosinusitis with nasal polyposis contributes to a reliable reduction in the severity of the main clinical symptoms (rhinorrhea, postnasal drip, nasal congestion, reduced sense of smell), nasal congestion starting from V2, regression of polyps – from V3 compared to patients of the control group. This ensured a statistically significant 25% reduction in the number of operated patients: 56.7% in the main group versus 81.7% in the control (p<0.05). Conservative treatment was continued by 43.3% of patients of the main group and by 18.3% of patients of the control group (p<0.05). After the operated patients were removed from the groups, they did not significantly differ in the dynamics of regression of nasal congestion and nasal polyps at V4 and V5 (p>0.05). Differences in the results of treatment are attributed to the clinical effects of Aminocapronic acid (ACA), since the group characteristics of the patients were commensurable.
 Conclusions:
 
 the additional appointment of Aminocapronic acid (ACA) to patients with Chronic rhinosinusitis with nasal polyposis contributes to a faster regression of nasal congestion associated with edematous changes of the mucous membrane of the nasal cavity, compared to the regression of polyps during the fifth day of treatment;
 there is a significant difference in the severity of symptoms in the main group during the 10th day of treatment compared to patients in the control group;
 the reliable positive dynamics of clinical symptoms correlates with a reliable, at 25%, decrease in the number of operative interventions in the main group.

Hemodynamic Analysis and Diagnosis Based on Multi-Deep Learning Models

This study employs nine distinct deep learning models to categorize 12,444 blood cell images and automatically extract from them relevant information with an accuracy that is beyond that achievable with traditional techniques. The work is intended to improve current methods for the assessment of human health through measurement of the distribution of four types of blood cells, namely, eosinophils, neutrophils, monocytes, and lymphocytes, known for their relationship with human body damage, inflammatory regions, and organ illnesses, in particular, and with the health of the immune system and other hazards, such as cardiovascular disease or infections, more in general. The results of the experiments show that the deep learning models can automatically extract features from the blood cell images and properly classify them with an accuracy of 98%, 97%, and 89%, respectively, with regard to the training, verification, and testing of the corresponding datasets.

Eosinophilic oesophagitis and type 2 inflammation multimorbidity: an opportunity for biologic treatment

Eosinophilic oesophagitis is a chronic inflammatory disorder of the oesophagus, diagnosed by clinical symptoms of oesophageal dysfunction and histological evidence of eosinophilic infiltration of the oesophagus with a minimum threshold of 15 eosinophils per high-power field, in the absence of other systemic and local causes of oesophageal eosinophilia.1 Cumulative data suggest that eosinophilic oesophagitis is driven by a type 2 inflammatory response, associated with the release of key cytokines including IL-4, IL-5, and IL-13.

Clinical symptoms of chronic rhinosinusitis with nasal polyps (eosinophilic and non-eosinophilic) are related to sinus computed tomography but not to endoscopic findings

BackgroundIn the clinical assessment of chronic rhinosinusitis with nasal polyps (CRSwNP), evaluation of symptoms, nasoendoscopy findings and sinus computed tomography (CT) scan staging is employed in the management plan. Although prior studies have been done to assess the correlation of the three modalities in CRSwNP, such evaluation in patients with eosinophilic and non-eosinophilic types of CRSwNP requires further investigation. The aim of this study was to correlate the sinus CT scan staging to symptom and endoscopic scores in both types of CRSwNP. Material and methodPatients with CRSwNP were classified into 2 types, eosinophilic and non-eosinophilic. Both types were assessed by Sino-Nasal Outcome Test 22 (SNOT-22) symptom score, nasal endoscopy Lund Kennedy grading (LK) score and sinus CT Lund Mackay (LM) staging score. All three modalities were correlated. ResultsForty-four patients were recruited for this study. There was significant correlation between sinus CT and symptom scores in the eosinophilic (r=.51, p=.031) and the non-eosinophilic (r=.76, p<.001) types. There was no significant correlation between symptom and nasoendoscopic scores in the eosinophilic (r=.12, p=.641) and the non-eosinophilic (r=.22, p=.276) types. There was also no significant correlation between sinus CT and nasoendoscopic scores in the eosinophilic (r=.20, p=.418) and the non-eosinophilic (r=.14, p=.508) types. ConclusionsSinus CT staging correlates well with the symptom score for both the eosinophilic and the non-eosinophilic types of CRSwNP. The good correlation suggests both modalities are a reliable guide for their evaluation and management planning.

Reduced bronchodilator reversibility correlates with non-type 2 high asthma and future exacerbations: A prospective cohort study

BackgroundGiven that airway obstruction in asthma is not always fully reversible, reduced bronchodilator reversibility (BDR) may be a special asthma phenotype. ObjectiveTo explore the characteristics of BDRhigh/low phenotypes (defined using two BDR criteria) and their associations with asthma exacerbations (AEs). MethodsAfter baseline assessments, all patients were classified into BDRhigh or BDRlow phenotypes. This study consisted of 2 parts. Part I was a 12-month prospective observational cohort study designed to identify the clinical characteristics and associations with future AEs in BDRhigh/low phenotypes (n = 456). Part II, designed as a post hoc analysis of the data obtained in Part I, was conducted to assess the association between BDRhigh/low phenotypes and treatment responsiveness (n = 360). ResultsSubjects with BDRlow phenotypes had better baseline asthma symptom control and was negatively associated with eosinophilic asthma and type 2 (T2) high asthma. During the 12-month follow-up, those with BDRlow phenotypes had a higher risk of severe AEs (SAEs) (guideline-based criterion: RRadj = 2.24, 95% CI = [1.25, 3.68]; Ward's criterion: RRadj = 2.46, 95% CI = [1.40, 4.00]) and moderate-to-severe AEs (MSAEs) (guideline-based criterion: RRadj = 1.83, 95% CI = [1.22, 2.56]; Ward's criterion: RRadj = 1.94, 95% CI = [1.32, 2.68]) in the following year according to logistic regression models. Similar findings were obtained with negative binominal regression models. BDRlow phenotype was a risk factor for an insensitive response to anti-asthma treatment (guideline-based criterion: ORadj = 1.96, 95% CI = [1.05, 3.65]; Ward's criterion: ORadj = 2.01, 95% CI = [1.12, 3.58]). ConclusionWe identified that BDRlow phenotype was associated with non-T2 high asthma and future AEs. These findings have clinically relevant implications for asthma management.

The role of leukotriene receptor blockers in the treatment of allergic rhinitis in combination with chronic rhinosinusitis with nasal polyps

Background. Leukotrienes play an important role in the pathogenesis of allergic rhinitis (AR) and eosinophilic type of chronic rhinosinusitis with nasal polyps (CRSwNP). There is a phenotype of CRSwNP in combination with AR, which has specifics of local inflammation.The aim of our study was to investigate the efficacy of using an antileukotriene drug in the treatment of AR in combination with CRSwNP.Materials and methods. 63 patients with AR and bilateral CRSwNP after endoscopic bilateral polypotomy were randomly divided into 2 groups. In the 1st group 32 people (age 50.28 ± 1.37 years) were prescribed a basic therapy with nasal spray of mometasone furoate at a daily dose of 400 µg in combination with montelukast 1 tab. 10 mg at night, in the 2nd group 31 people (age 50.31 ± 1, 16 years old) received only mometasone furoate monotherapy. Endoscopic examination of the nasal cavity was performed once every 3 months. The follow-up period was 1 year.Results. After 3 months in the 1st group of patients there was a recurrence of polyp growth was observed in 25% of cases, in the 2nd group in 35.5% of patients (p &lt; 0.05). After 6 months, the number of relapses of CRSwNP decreased to 15.6% of cases in group 1 and to 22.6% in group 2 (p &lt; 0.05). After 9 months in group 1 recurrence of NP was recorded in 12.5% of patients and nasal polyps were completely absent during endoscopic examination in 9.4% of cases, in the 2nd group, relapse was detected in 19.35% of patients (p &lt; 0.05). 1 year after surgery, in group 1, relapse of NP was found in 12.5% of patients with AR and in 12.5% of cases was remission of the pathological process with cancellation of basic therapy. In group 2, recurrence of NP was in 16.1% of cases, there were no reasons for withdraw treatment of intranasal glucocorticosteroids in this group.Discussion. The clinical effectiveness of the addition of Montelukast to basic therapy has been reflected in a reduction in the growth rate of polyposic vegetation, the number of repeated operations and the stabilization of the flow of chronic inflammatory process.Conclusions. In the case of the clinical phenotype of AR with CRSwNP, the addition of a leukotriene receptor blocker montelukast to the basic therapy of intranasal glucocorticosteroids made it possible to improve drug control of both diseases and reduce the frequency of CRSwNP relapses.

Novel Biological Therapies for Severe Asthma Endotypes.

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research.

Diagnostic markers of exacerbation of chronic obstructive pulmonary disease in workers exposed to industrial aerosols and tobacco

Introduction. Chronic obstructive pulmonary disease (COPD) is one of the most common occupational diseases registered in workers exposed to dust for a long time. This disease significantly worsens the quality of life, requires constant monitoring in the centers of occupational pathology and regular preventive measures. The proportion of COPD in the structure of occupational diseases has not changed significantly for decades, high rates of disability and premature mortality characterized this disease. The study aims to research the diagnostic parameters of COPD exacerbation under the influence of industrial aerosols and tobacco in the clinic of occupational diseases. Materials and methods. Researchers examined 153 patients with occupational COPD (toxic gases and inorganic dust). The comparison group consisted of 103 patients with smoking COPD. We established the diagnosis of COPD in accordance with the criteria of GOLD 2011. The duration of the study was 5 years. The authors conducted a complex of clinical and laboratory studies in all patients with an emphasis on the diagnostic parameters of COPD exacerbation and lung function. The critical significance level is p=0.05. Results. The development of occupational COPD under the influence of industrial aerosols and tobacco affects the frequency and predominant phenotype of exacerbations. Rare but severe exacerbations, mainly with eosinophilic type of inflammation, are present in COPD from the action of toxic gases. They respond well to therapy with systemic GCS. With COPD from the action of dust, hospitalization is not necessary for short-term exacerbations with neutrophilic type of inflammation, since such exacerbations respond to therapy with bronchodilators, and a significant proportion of exacerbations require the use of antibacterial therapy. Also, in COPD from the action of toxic gases, the experience of exposure to aerosols and gases of the production environment is an independent predictor of any exacerbations. But we do not have data on the significance of the length of service and the intensity of dust exposure. Conclusion. The risks of exacerbations of occupational COPD and the predicted features of their course depend on the etiological production factor, its intensity and duration of exposure. Clinical features determine different tactics of treatment and prevention of health deterioration. With the severity of COPD exacerbation from the action of toxic gases, symptoms of emphysema and hypoxemia are characteristic, with COPD from the action of dust, symptoms of bronchial obstruction, emphysema and hypoxemia are characteristic. Obtained results can use to construct risk meters of exacerbations and the scale of effectiveness of rehabilitation measures, to revise the standards of treatment and prevention of patients with COPD of professional genesis, as well as for the differential diagnosis of occupational obstructive pulmonary disease. Limitations. The study was conducted on the basis of Novosibirsk State Medical University and on the basis of the City Clinical Hospital No. 2. The limitations of the study may be the unidirectionality of the study performed and the small sample of patients participating in the research. Ethics. All patients have signed an informed consent form. The study program, the content of the informed consent, and the materials of the article were approved by the local ethics committee of Novosibirsk State Medical University and City Clinical Hospital No. 2.

Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease.

Chronic rhinosinusitis with nasal polyps is affecting up to 3% of Western populations. About 10% of patients with nasal polyps also suffer from asthma and intolerance to aspirin, a syndrome called aspirin-exacerbated respiratory disease. Although eosinophilic inflammation is predominant in polyps of both diseases, phenotypic differences in the tissue-derived microenvironment, elucidating disease-specific characteristics, have not yet been identified. We sought to obtain detailed information about phenotypic and transcriptional differences in epithelial and immune cells in polyps of aspirin-tolerant and intolerant patients. Cytokine profiles in nasal secretions and serum of patients suffering from aspirin-exacerbated respiratory disease (n = 10) or chronic rhinosinusitis with nasal polyps (n = 9) were assessed using a multiplex mesoscale discovery assay. After enrichment for immune cell subsets by flow cytometry, we performed transcriptomic profiling by employing single-cell RNA sequencing. Aspirin-intolerant patients displayed significantly elevated IL-5 and CCL17 levels in nasal secretions corresponding to a more pronounced eosinophilic type 2 inflammation. Transcriptomic profiling revealed that epithelial and mast cells not only complement one another in terms of gene expression associated with the 15-lipoxygenase pathway but also show a clear type 2-associated inflammatory phenotype as identified by the upregulation of POSTN, CCL26, and IL13 in patients with aspirin-exacerbated respiratory disease. Interestingly, we also observed cellular stress responses indicated by an increase of MTRNR2L12, MTRNR2L8, and NEAT1 across all immune cell subsets in this disease entity. In conclusion, our findings support the hypothesis that epithelial and mast cells act in concert as potential drivers of the pathogenesis of the aspirin-exacerbated respiratory disease.

Potential clinical complications of Orise™ gel use, a new submucosal lifting agent: experience from a tertiary care center and review of the literature.

BackgroundEndoscopic mucosal resection (EMR) involves forming a fluid cushion in the submucosal area with a lifting agent, followed by superficial resection. Orise™ gel is one of the commonly used lifting agents for EMR. We present a case series and literature review that analyzes the characteristic histopathological findings and clinical implications observed where Orise™ gel was used before EMR.MethodsColon resection specimens and prior EMR specimens where Orise™ gel was used were reviewed for patients undergoing EMR between January 2018 and December 2020. The literature review included relevant studies from the Medline and Cochrane databases from January 2018 to December 2020.ResultsA total of 12 colon polyp EMRs using Orise gel were performed during the study period. Seven patients (58.34%) underwent surgical resection. Histological examination revealed that, after the EMR procedure, the Orise™ gel material changed its morphological characteristics over time from a basophilic (bluish) non-inflamed pattern to an eosinophilic (pink) type pattern, eliciting a foreign body reaction. The endoscopic appearance and examination of the excised specimens weeks after injection gave the impression of a mass in some cases. The material was also present transmurally and in some cases in the peri-intestinal adipose tissue.Conclusions It was observed that Orise™ gel use elicits a foreign body-type granulomatous reaction. This potential side effect may lead to overdiagnosis of a mass/lesion and unnecessary surgical interventions. This case series and review of the literature aims to increase awareness of the changes caused by Orise™ gel in the gastrointestinal tract.