Relationship Between Peripheral Blood Eosinophil Count, Tissue Eosinophil Dominance and Serum Specific Immunoglobulin E Levels with Primary Chronic Rhinosinusitis Phenotype

Significance of the eosinophil cationic protein/eosinophil count ratio in asthmatic patients: its relationship to disease severity.

PurposeEosinopenia has been described in COVID-19. With this study, we aim to study the peripheral blood eosinophil counts in COVID-19 patients and to investigate whether there is an association between the peripheral blood eosinophil counts and disease severity of COVID-19.MethodsWe revised the electronical medical records of confirmed COVID-19 patients with polymerase chain reaction (PCR) assays in the Groene Hart Ziekenhuis, Gouda, The Netherlands. We divided patients in mild, moderate and severe groups based on clinical severity of COVID-19. Clinical severity was based on the therapy needed and the outcome of patients. We compared clinical characteristics, laboratory results and outcome between the three groups.ResultsOf the 230 patients included in this study, the mild, moderate and severe groups consisted of 16.5%, 45.7% and 37.8% of the included patients, respectively. The mean age was 68 years (IQR 57–78). 63% of patients were male. A significant decrease in the peripheral eosinophil counts was found corresponding to the increase of COVID-19 severity. In the mild, moderate and severe groups, the percentage of patients with eosinopenia was 73.7%, 86.7% and 94.3%, respectively (p value 0.002).ConclusionEosinopenia is significantly more frequent present in patients with a severe COVID-19.

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was <500/mm(3) in four patients, >500/mm(3) but <1,000/mm(3) in three patients, and > or =1,000/mm(3) in one patient. In three of the four patients with an initial eosinophil count of <500/mm(3), an increase to > or =500/mm(3) occurred 7-12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.

Lung cancer is the leading cause of cancer-related death globally and is often diagnosed at an advanced stage. Nivolumab represents a significant advancement for treating advanced non-small cell lung cancer (NSCLC). However, the absence of reliable biomarkers predicting treatment response hinders personalized therapy. Eosinophils play a notable role in cancer biology, particularly when treated with immune checkpoint inhibitors. Eosinophils can infiltrate tumor tissues, directly interacting with tumor cells or modifying the tumor microenvironment. This study aims to assess the potential of PD-L1 expression and peripheral blood eosinophil count in predicting treatment response and patient survival. This retrospective cohort study was conducted in three major cancer centers in Turkey, including 174 advanced NSCLC patients who had progressed after chemotherapy between July 2019 and November 2023. Demographic and clinical data, PD-L1 levels, and eosinophil counts were analyzed using SPSS 27.0. Survival analyses were performed with Kaplan-Meier and Cox regression models. Increased peripheral blood eosinophil count was positively associated with response to Nivolumab treatment and overall survival. Among treatment responders, 54.1% had eosinophil levels between 100-499 cells/mm3 before treatment, increasing to 70.8% post-treatment. In patients with high PD-L1 positivity (>50%), eosinophil levels averaged 266.0 cells/mm3, with improved survival outcomes (mean survival: 24.06 months, median: 20.0 months). Non-responders had a mean survival of 19.05 months and a median survival of 15.2 months. Peripheral eosinophil count appears to be a potential biomarker for predicting response to Nivolumab treatment and survival in NSCLC patients. Combined evaluation of eosinophil count and PD-L1 expression may enhance personalized treatment strategies. Further validation in prospective, randomized studies is necessary.

Eosinophils and Pulmonary Function: an Epidemiologic Study of Adolescents and Young Adults

Increased levels of serum pro-fibrotic cytokines have been reported in patients with systemic sclerosis (SSc). Some of these cytokines also play an important role in the differentiation and migration of eosinophils. The aim of this study was to determine whether eosinophilic inflammation is caused in SSc. We retrospectively reviewed the peripheral blood eosinophil counts in 70 untreated patients with SSc and compared them with those in patients with other major collagen diseases. We additionally evaluated a possible association with disease severity. Eosinophil counts were significantly higher levels in patients with SSc than in those with other collagen diseases, whereas total leukocyte counts were not. Eosinophil counts correlated positively with both severe interstitial lung disease (ILD; r = 0.255, p = 0.033) and modified Rodnan total skin thickness score (m-Rodnan TSS) in SSc (r = 0.347, p = 0.003), but did not correlate with ILD severity in other collagen diseases. In conclusion, peripheral eosinophil counts were higher in patients with SSc than in those with other collagen diseases and were correlated with increased disease severity. Our data suggest that eosinophilic inflammation is involved in the pathogenesis and progression of SSc.

Background and objectivesGenome-wide association studies identified single-nucleotide polymorphisms (SNPs) at the 17q21 locus conferring increased risk for childhood-onset asthma. Little is known about how these SNPs impact adult asthma patients. We sought to examine an adult population for associations between rs7216389 (17q21-associated SNP) and features of asthma including fractional exhaled nitric oxide (FeNO), eosinophil counts, and age of asthma onset.MethodsSubjects were genotyped at SNP rs7216389. The geometric mean of FeNO measurements and peripheral blood eosinophil counts from 2008 to 2015 were collected. Demographics and medical history were collected including self-reported allergy diagnoses and age of asthma onset. Eosinophils, monocytes, and peripheral blood mononuclear cells (PBMCs) were isolated for the examination of ORMDL3 expression.ResultsFeNO levels from 157 genotyped subjects (31CC, 72CT, and 54TT) and peripheral eosinophil counts from 252 genotyped subjects (46CC, 122CT, and 84TT) were analyzed. In a sub-group analysis of asthma subjects, the number of attributable T alleles was associated with significantly lower age of asthma onset (P=0.03) and greater FeNO levels (geometric mean 30.0 ppb TT, 20.0 ppb CT, 20.0 ppb CC, P=0.02). In the total cohort of subjects, the T allele was associated with a higher percentage of individual eosinophil counts >200/mm3 (45% TT, 26% CT, 24% CC, P=0.005). Eosinophils expressed ORMDL3 mRNA and protein.ConclusionIn adult subjects, the number of T alleles at SNP rs7216389 corresponds to significantly greater FeNO levels and peripheral eosinophil counts. The expression of ORMDL3 in eosinophils suggests that they may participate in mediating the asthma risk associated with the 17q21 locus.

Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Most symptoms of chronic rhinosinusitis manifest in adulthood, in this connection it is not always possible to assume the endotype of the disease by phenotype in a child. An early identification of the disease’s endotype is necessary for optimization of diagnosis and choice of personalized management of children with chronic rhinosinusitis. Objective. To develop an algorithm for diagnosis of endotypes of chronic rhinosinusitis in children. Patients and methods. The study included 160 children diagnosed with «chronic rhinosinusitis». Inflammatory markers, namely IL-5, IFN-γ, IL-17α, TNF-α, IL-22, IL-6, IL-33, IL-35, ECP, MPO, TGF-β1, total IgE, were determined in the blood serum and nasal secretion by enzyme immunoassay. The endotypes of chronic rhinosinusitis were determined by cluster analysis. The coupling of the endotypes with the phenotypes of the disease was done and markers with high discriminant power for each endotype were identified. Results. After comparison of the coupling between phenotypes and all endotypes, it has been found that the phenotype of chronic rhinosinusitis with polyps and concurrent diseases (allergic rhinitis and bronchial asthma) has the Th-2 endotype by nasal secretion markers, but 3 different subendotypes by blood serum markers. The phenotype of chronic rhinosinusitis without polyps and concomitant pathology has the same set of markers in nasal secretion and in blood serum — Th-1 endotype. The phenotype of chronic rhinosinusitis associated with hypertrophy of the pharyngeal lymphatic ring has its own endotype with high degree of coupling. Conclusions. ECP and IL-33 are nasal secretion markers for the Th-2 endotype, IFN-γ is the Th-1 endotype marker, IL-35, MPO and TGF-β1 are markers for the endotype associated with hypertrophy of the pharyngeal lymphatic ring. The blood serum markers can be used for the identification of subendotypes of the Th-2 endotypes: IL-17 and IL-22 — for the subendotype of chronic rhinosinusitis with polyps, ECP — for the subendotype with allergic rhinitis, a decrease in the IL-35 level — for the subendotype with high risk of bronchial asthma development.

Chronic rhinosinusitis (CRS) has been distinguished in primary CRS, a primary inflammatory disorder limited to airways and secondary CRS, in which the sinonasal pathology is caused by a systemic disease or a local pathologic condition. Primary CRS is in turn classified in Type 2 and Non-type 2 on the basis of the endotype and of the pattern of the immune response. Advance in the knowledge of CRS has led to new therapeutic options, among which Dupilumab (anti-IL4R). We report the clinical response to Dupilumab in two patients with cystic fibrosis and nasal polyposis, in which the coexistence of a primary and secondary CRS could not be excluded. Nasal endoscopy, smell and quality of life of the patients were evaluated at each follow-up. In the first case, increased blood eosinophils, allergy to inhalants and NSAIDs intolerance supported the suspect of primary CRS with type 2 inflammatory pattern, in addition to cystic fibrosis and the therapy was effective. In the second case the patient did not show atopy or peculiar blood test and even if the phenotype could suggest a primary CRS combined with a secondary one, the treatment was ineffective and it was suspended. Even though classifications can be helpful, they can be reductive in cases where different aetiologies overlap. The presence of a concomitant primary CRS must not be excluded a priori in patients affected by secondary CRS. Each patient must be investigated to identify endotype characteristics and select the most appropriate therapeutic option.

The negative association of smoking with the respiratory tract is well known; however, the association between smoking and chronic rhinosinusitis (CRS) has not been well characterized. To analyze whether active smoking was a risk factor for CRS development, smoking was associated with disease-specific quality of life, and smokers experience an increased symptom burden than nonsmokers. This subanalysis of the Chronic Rhinosinusitis Epidemiology Study (CRES), a prospective, questionnaire-based case-control study conducted between October 2007 and September 2013 was conducted across 30 UK tertiary/secondary care sites. Participants were identified at ear, nose, and throat outpatient clinics and classified into CRS phenotypes as per European Position Paper on Rhinosinusitis and Nasal Polyps 2012 criteria. The overall response rate of those identified to take part in the study was 66%. A total of 1535 questionnaires were returned, with 1470 considered eligible for inclusion. Data analysis was conducted in January 2020. The CRES was designed to distinguish differences in socioeconomic status, geography, medical comorbidities, lifestyle, and quality of life between patients with CRS and healthy controls. A total of 1450 patients completed the smoking question, comprising 219 controls (15.1%; mean [SD] age, 47.3 [14.9] years; 143 women [68%]), 546 participants with CRS (37.7%; mean [SD] age, 51.8 [15.3] years; 259 women [53%]) without nasal polyps (CRSsNPs), and 685 participants (47.2%; mean [SD] age, 56.0 [14.5] years; 204 women [33%]) with CRS and nasal polyps/allergic fungal rhinosinusitis (CRSwNPs+). The mean age was similar, with a greater female preponderance in the control group and male in the CRSwNP group. The greatest number of active smokers was found among control participants (33 [15%]), with a lower rate of smokers in the patients with CRSwNPs+ (9.9%) and CRSsNPs (13.9%), respectively. We found a clinically significant difference in the mean difference in Sino-nasal Outcome Test (SNOT-22) scores between active smokers and nonsmokers for both CRS phenotypes (4.49, 12.25). In both CRS subgroups active smokers had significantly worse SNOT-22 scores than nonsmokers by a mean (SD) magnitude of 10 (18.99, 24.14) points. Nonsmokers also demonstrated a higher percentage of surgical procedures (1 or more), although this was not clinically or statistically different (0.34, 1.10). This questionnaire-based case-control study demonstrated a clinically significant symptom burden associated with active cigarette smoking, with worse SNOT-22 scores in the smoking cohort by a mean magnitude of 10 points. We could find no demonstrable evidence that smoking increases the likelihood of need for revision sinus surgery. Clinicians should encourage smoking cessation alongside general CRS medical management.

Differences in urinary leukotriene E4 levels and distribution of eosinophils between chronic rhinosinusitis patients with aspirin-intolerant and -tolerant asthma.

Classification of chronic rhinosinusitis in Taiwan: A comprehensive analysis based on European Position Paper on rhinosinusitis and nasal polyps (EPOS) 2020.

We encountered a 78-year-old Japanese man with IgG4-related sialoadenitis complicated with marked eosinophilia. We diagnosed him with IgG4-RD (related disease) with a submandibular gland tumor, serum IgG4 elevation, IgG4-positive plasma cell infiltration, and storiform fibrosis. During follow-up after total incision of the submandibular gland, the peripheral eosinophil count was markedly elevated to 29,480 /μL. The differential diagnosis of severe eosinophilia without IgG4-RD was excluded. The patient exhibited a prompt response to corticosteroid therapy. His peripheral blood eosinophil count was the highest ever reported among similar cases. We also review previous cases of IgG4-RD with severe eosinophilia.

A case of allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia successfully treated with benralizumab