Association of cytokine profile with prior treatment failure and revision surgery in chronic rhinosinusitis.

BACKGROUND: Inflammatory patterns in chronic rhinosinusitis (CRS) may predict disease severity, need for multiple sinus surgeries, and treatment response. This study analyzes nasal mucus inflammatory cytokine patterns in patients with (CRSwNP) and without (CRSsNP) nasal polyposis and their association with revision sinus surgery. METHODS: A total of 319 CRS patients who underwent sinus surgery were included. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Cytokine expression patterns in patients with 0, 1, and ≥2 previous surgeries were analyzed using Kruskal-Wallis and principal component (PC) regression analyses. RESULTS: There were 122 (38%) patients with CRSsNP and 197 (62%) with CRSwNP. On univariate analysis, interleukin (IL)-1ß, IL-6, IL-8, and IL-21 were associated with increasing number of sinus surgeries in CRSsNP, as were IL-2, IL-4, IL-5, IL-6, IL-9, IL-17A, and tumor necrosis factor (TNF)-α in CRSwNP. PC analysis with continuous Poisson regression in CRSwNP demonstrated that high IL-5 and IL-13 and low IL-1ß, IL-12, and IL-21 were associated with more prior surgeries. In CRSsNP low IL-13 and high IL-5 and regulated-on-activation, normal T-cell-expressed and secreted (RANTES) were associated with more prior surgeries. Age remained a significant covariate in the full regression model for CRSsNP, but was nonsignificant in CRSwNP. CONCLUSION: In CRSwNP, elevated IL-5 and IL-13 levels were higher at time of surgery in patients with more prior surgeries. Type 2 cytokines in CRSsNP demonstrated mixed associations with revision surgery. For both phenotypes, IL-10, IL-12, and IL-21 were consistently lower as number of prior surgeries increased, suggesting that treatment-resistant disease may be modulated by impairment in these signaling pathways.

[Effect of Biyanning Granules on local symptoms and immune function of chronic rhinosinusitis].

This study discusses the effect of Biyanning Granules on local symptoms and systemic immune function of patients with chronic rhinosinusitis with nasal polyps(CRSwNP) within the 6 months of treatment by glucocorticoid nasal spray after surgical treatment. To be specific, a total of 237 CRSwNP patients, treated in Otorhinolaryngology Head and Neck Surgery in Shanxi Bethune Hospital, were enrolled. All patients were treated by nasal endoscopy and classified into hormone group(Budesonide Nasal Spray after surgery), Chinese medicine group(Biyanning Granules after surgery), and combination group(Budesonide Nasal Spray+Biyanning Granules after surgery) with random number table method, 79 cases in each group, and the treatment lasted 3 months. The follow-up was performed from the day of discharge to 12 months after the surgery. The clinical effect was observed. The visual analogue scale(VAS) scores and sino-nasal outcome test-20(SNOT-20) scale scores were used to assess patient's subjective symptoms and quality of life. Lund-Kennedy endoscopic score(LKES), Japanese T&T olfactometry, and standard olfactory test were used to evaluate the objective curative effect on patients. The levels of interleukin(IL)-21, CD4~+CD25~+Foxp3~+Treg, and CD4~+Th17 in peripheral blood were analyzed. The incidence of complications, recurrence rate, and adverse reactions during treatment were also recorded. The total effective rate after treatment in the combination group was higher than that in the hormone group and Chinese medicine group(P<0.05). VAS scores and SNOT-20 scale scores were lower in the three groups after treatment than before treatment and lower in the combination group than in the other two groups(P<0.05). The improvement in LKES and T&T standard olfactometry test was better in the combination group than in the other two groups(P<0.05). Serum levels of IL-21 and CD4~+Th17 in the three groups were lower than before treatment. The levels in the combination group were lower than those in the other two groups and lower in the hormone group than in the Chinese medicine group(P<0.05). Serum CD4~+CD25~+Foxp3~+Treg level was higher in the three groups after treatment than before, higher in the combination group than in the other two groups, and higher in the Chinese medicine group than in the hormone group(P<0.05). During the treatment, no serious adverse reactions were observed. After treatment, the combination group showed no significant difference in the incidence and recurrence rate of complications from the hormone group and Chinese medicine group. In the treatment of CRSwNP with glucocorticoid, Biyanning Granules reduced the side effects of glucocorticoid and assisted glucocorticoid in alleviating the symptoms of patients. It significantly improved the curative effect, regulated immune imbalance, accele-rated the recovery of immune function, reduced the recurrence rate of inflammatory reaction, and improved the quality of life. The combination of Chinese and western treatment is more effective than glucocorticoid alone and warrants further clinical study in large sample size.

TIM-4 in macrophages contributes to nasal polyp formation through the TGF-ß1-mediated epithelial to mesenchymal transition in nasal epithelial cells.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is caused by prolonged inflammation of the paranasal sinus mucosa. The epithelial to mesenchymal transition (EMT) is involved in the occurrence and development of CRSwNP. The T-cell immunoglobulin domain and the mucin domain 4 (TIM-4) is closely related to chronic inflammation, but its mechanism in CRSwNP is poorly understood. In our study, we found that TIM-4 was increased in the sinonasal mucosa of CRSwNP patients and, especially, in macrophages. TIM-4 was positively correlated with α-SMA but negatively correlated with E-cadherin in CRS. Moreover, we confirmed that TIM-4 was positively correlated with the clinical parameters of the Lund-Mackay and Lund-Kennedy scores. In the NP mouse model, administration of TIM-4 neutralizing antibody significantly reduced the polypoid lesions and inhibited the EMT process. TIM-4 activation by stimulating with tissue extracts of CRSwNP led to a significant increase of TGF-ß1 expression in macrophages in vitro. Furthermore, coculture of macrophages and human nasal epithelial cells (hNECs) results suggested that the overexpression of TIM-4 in macrophages made a contribution to the EMT process in hNECs. Mechanistically, TIM-4 upregulated TGF-ß1 expression in macrophages via the ROS/p38 MAPK/Egr-1 pathway. In conclusion, TIM-4 contributes to the EMT process and aggravates the development of CRSwNP by facilitating the production of TGF-ß1 in macrophages. Inhibition of TIM-4 expression suppresses nasal polyp formation, which might provide a new therapeutic approach for CRSwNP.

Effect of Airborne Particulate Matter on the Immunologic Characteristics of Chronic Rhinosinusitis with Nasal Polyps.

The inflammatory mechanisms of environmental pollutants in chronic rhinosinusitis (CRS) have recently been proposed. However, the mechanisms underlying the inflammatory effects of particulate matter (PM) on nasal polyp (NP) tissues remain unknown. Here we investigated the mechanism underlying the inflammatory effects of PM10 on human nasal polyp-derived fibroblasts (NPDFs). We isolated NPDFs from human NP tissues obtained from patients with CRS with NPs (CRSwNP). The NPDFs were exposed to PM10 in vitro. Immunologic characteristics were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, Western blot, and flow cytometry. Additionally, we investigated the effect of NPDF-conditioned media (CM) on the expression of CD4+ T cell inflammatory mediators. PM10-treated NPDFs significantly upregulated interleukin (IL)-6, IL-4, and IL-33 expression and CXCL1 protein levels than PM10-treated normal tissues. MAP kinase, AP-1, and NF-kB were the primary cell signaling proteins. Immune cells in NPDF-CM had elevated IL-13, IL-17A, and IL-10 expression, but no significant difference in IFN-γ, TNF-α, and IL-4 expression. Moreover, under a Th2 inducing condition, NPDF-CM-treated CD4+ T cells had increased expression of IL-13, IL-10, and IL-17, which was reversed on ST2 inhibitor addition. Our study suggests that PM10 exposure could significantly increase the Th2 inflammatory pathway in NP tissues, specifically the IL-33/ST2 pathway-mediated immune response.

Age related non-type 2 inflammation and its association with treatment outcome in patients with chronic rhinosinusitis with nasal polyp in Korea.

This study aimed to investigate the effect of age in patients with chronic rhinosinusitis with nasal polyp (CRSwNP). 269 patients were divided into eosinophilic and non-eosinophilic groups based on tissue eosinophilia, defined by eosinophils accounting for more than 20% of the total inflammatory cells. Patients were then further divided into younger and older groups based on the age of 35 years. Clinical characteristics including blood eosinophil, Lund Mackay score, and modified Lund-Kennedy (mLK) scores were compared. Levels of 14 cytokines from nasal tissues of an additional 78 patients were analyzed. Tissue eosinophilia was significantly associated with age and the proportion of non-eosinophilic CRSwNP was significantly higher in younger patients as compared to older patients (79.2% vs 56.6%). There was no difference in clinical characteristics and cytokine levels between the younger and older patients with eosinophilic CRSwNP. In contrast, in patients with non-eosinophilic CRSwNP, younger patients had significantly lower preoperative blood eosinophils and higher mLK scores at three and six months, postoperatively, compared to older patients. Alpha-1 antitrypsin and IL-5 levels were significantly lower in younger patients than in older patients in non-eosinophilic CRSwNP. This study suggests a potential association between age, non-type 2 inflammation and treatment outcome in CRSwNP.

IL-17A-producing sinonasal MAIT cells in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Diverse immune cells contribute to the pathogenesis of chronic rhinosinusitis (CRS), an inflammatory disease of the nasal cavity and paranasal sinuses. However, whether mucosal-associated invariant T (MAIT) cells are present in human sinonasal tissues remains unclear. Furthermore, the characteristics of sinonasal MAIT cells have not been studied in patients with CRS. OBJECTIVE: We investigated the phenotype, function, and clinical implications of MAIT cells in patients with CRS. METHODS: Peripheral blood and sinonasal tissue were obtained from patients with CRS with (CRSwNP) or without nasal polyps (CRSsNP) and healthy controls. MAIT cells were analyzed by flow cytometry. RESULTS: We found that MAIT cells are present in human sinonasal tissues from healthy controls and patients with CRS. The sinonasal MAIT cell population, but not peripheral blood MAIT cells, from patients with CRSsNP, noneosinophilic CRSwNP (NE-NP), or eosinophilic CRSwNP (E-NP) had a significantly higher frequency of activated cells marked by CD38 expression. In functional analysis, the sinonasal MAIT cell population from NE-NP and E-NP had a significantly higher frequency of IL-17A+ cells but lower frequency of IFN-γ+ or TNF+ cells than control sinonasal tissues. Furthermore, CD38 expression and IL-17A production by sinonasal MAIT cells significantly correlated with disease extent evaluated by the Lund-Mackay computed tomography score in patients with E-NP. CONCLUSIONS: Sinonasal MAIT cells exhibit an activated phenotype and produce higher levels of IL-17A in patients with CRSwNP. These alterations are associated with the extent of disease in patients with E-NP.

Cut-off value of D. pteronyssinus specific IgE in double negative patients Der p 1 and Der p 2 and its clinical repercussion.

Accessibility to more precise diagnostic techniques such as component resolved diagnostics (CRD), provides us with an important advance in diagnostic aspects as well as treatment. The subject of this study aims to better understand the profiles of sensitization to Der p 1, Der p 2 and Der p 23 and to know to what extent their use could help us in optimizing the decision-making for their treatment with Specific Immunotherapy. Cross-sectional study of subjects older than 5 years, diagnosed with allergy to HDM using skin prick test and sIgE, with symptoms of rhinitis and/or asthma. Total and specific IgE was determined to D. pteronyssinus, nDer p 1, rDer p 2 and rDer p 23 using ImmunoCAP. 240 patients were recruited (97.1% rhinitis and 46.25% rhinitis and asthma). Four different phenotypes were observed: positive or negative for sIgE nDer p 1 and/or IgE rDer p 2. 17% of these patients sIgE were double negative for Der p 1 and Der p 2 (increasing with age and with significantly lower sIgE levels than the rest of the groups). Using ROC curves, value less than 2.18 KUA/L for D. pteronyssinus sIgE gave us a sensitivity and specificity of 0.882 and 0.985, respectively, to double negative IgE nDer p 1 and IgE rDer p 2 group. Despite positive SPT and sIgE to D. pteronyssinus, 17% of the studied population is IgE nDer p 1 and IgE rDer p 2 double negative, with a cut-off value of 2.18 KU/L, which is very relevant for taking of decisions in prescription of AIT. The double positive population sIgE nDer p 1 and IgE rDer p 2 is associated with asthma compared to the other groups and this does not seem to be influenced by IgE rDer p 23.

Neutrophils Affect IL-33 Processing in Response to the Respiratory Allergen Alternaria alternata.

Future precision medicine requires further clarifying the mechanisms of inflammation in the severe endotypes of chronic airway diseases such as asthma and chronic rhinosinusitis (CRS). The presence of neutrophils in the airways is often associated with severe airway inflammation, while their precise contribution to the severe inflammation is largely unknown. We aimed to study the role of neutrophils in BALB/c and C57BL/6 mice exposed to Alternaria alternata (Alt). The mice were exposed to Alt extract for twelve hours or ten days to induce allergic airway inflammation. C57BL/6 mice exposed to Alt responded with eosinophilic infiltration and the characteristic IL-5 upregulation. In contrast, the inflammatory response to Alt extract in BALB/c mice was characterized by a neutrophilic response, high levels of G-CSF, and elastase in the lungs. The lack of neutrophils affected the processing of IL-33 in BALB/c mice, as was demonstrated by depletion of neutrophils through intraperitoneal injections of anti-Ly6G antibody. Our data identifies the key role of neutrophils in airway inflammation through IL-33 cleavage in the Alt-induced airway inflammation in mice, which could potentially underline the different endotypes in human disease.

sCD48 is elevated in non-allergic but not in allergic persistent rhinitis.

BACKGROUND: CD48 is a costimulatory receptor of the immune response. Interactions between CD48 and CD244 (2B4) on mast cells and eosinophils suggest that these cells can act synergistically in the 'allergic effector unit' to promote inflammation. This report explores the role of CD48 in persistent allergic (PAR) and non-allergic rhinitis (NAR). METHODS: In this study, serum was obtained from 70 subjects (45 female, 64%; mean age, 36; range 18-70 years) to estimate the levels of sCD48 and two eosinophils-related parameters, ECP and eotaxin-1/CCL11. Twenty patients with PAR, 15 patients with NAR, and 35 healthy controls were included. The intensity of rhinitis symptoms was estimated by the Total Nasal Symptom Score. We also assessed the fractional exhaled nitric oxide bronchial and nasal fractions (FeNO) and neutrophil to lymphocyte (NLR) and eosinophil to lymphocyte (ELR) ratios. RESULTS: Significantly higher sCD48 serum levels were observed in the NAR group than in the PAR and control groups, and significant correlations were found between the serum level of sCD48 and the number and percentage of eosinophils. ECP and eotaxin-1/CCL11 serum levels were also found to be significantly higher in the NAR group. CONCLUSIONS: CD48 may be involved in eosinophilic pathophysiological reactions in non-allergic rhinitis.

The role of serum macrophage migration inhibitory factor in preoperative prediction of chronic rhinosinusitis with nasal polyps endotypes.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease and can be categorized into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). Exploring effective biomarkers to distinguish endotypes is important for personalized therapies. The present study aims to evaluate the predictive value of serum MIF in CRSwNP endotypes. METHODS: One hundred and twenty CRSwNP patients, including 51 eCRSwNP and 69 neCRSwNP, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients and 40 healthy controls (HC) were enrolled. Serum MIF levels were determined by enzyme-linked immunosorbent assay (ELISA). The patients' clinical variables were analyzed for correlations with serum MIF. Receiver operating characteristic (ROC) curve and multivariate analysis were utilized to assess the predictive value of serum MIF in CRSwNP endotypes. RESULTS: The serum MIF levels were significantly higher in CRSwNP group than CRSsNP group and HC group (P < 0.001), and the serum MIF levels were increased in eCRSwNP compared to neCRSwNP group (P = 0.006). Elevated serum MIF levels were significantly correlated with blood eosinophil (B-EOS) count (r = 0.411, P < 0.001), B-EOS percentage (r = 0.377, P < 0.001), visual analog scale score (r = 0.204, P = 0.025), tissue eosinophil (T-EOS) count (r = 0.705, P < 0.001) and T-EOS percentage (r = 0.671, P < 0.001) in CRSwNP patients. ROC curve demonstrated that serum MIF exhibited good preoperative prediction in CRSwNP endotypes (area under the curve = 0.925, P < 0.001). Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotypes. CONCLUSIONS: This was the first study identifying serum MIF as a possible specific biomarker for preoperatively distinguishing CRSwNP endotypes. Furthermore, the serum MIF levels were found to be closely associated with the degree of mucosal eosinophil infiltration.

Aspirin Actions in Treatment of NSAID-Exacerbated Respiratory Disease.

Non-steroidal Anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyposis, chronic rhinosinusitis, adult-onset asthma and hypersensitive reactions to cyclooxygenase-1 (COX-1) inhibitors. Among the available treatments for this disease, a combination of endoscopic sinus surgery followed by aspirin desensitization and aspirin maintenance therapy has been an effective approach. Studies have shown that long-term aspirin maintenance therapy can reduce the rate of nasal polyp recurrence in patients with N-ERD. However, the exact mechanism by which aspirin can both trigger and suppress airway disease in N-ERD remains poorly understood. In this review, we summarize current knowledge of aspirin effects in N-ERD, cardiovascular disease, and cancer, and consider potential mechanistic pathways accounting for the effects of aspirin in N-ERD.

Serum IgE Predicts Difference of Population and Allergens in Allergic Diseases: Data from Weifang City, China.

BACKGROUND: Immunoglobulin E (IgE) is the most important promoter of allergic inflammation. However, there are few systematic studies on IgE in age range, genders, disease spectrum, and time regularity. AIM: To screen the common allergens, allergen spectrum, and IgE difference between type 2 inflammatory allergic diseases and other allergic diseases in Weifang, China. METHODS: A retrospective study was performed by estimating patients' clinical data suffering from allergic diseases (urticaria, pollinosis, allergic rhinitis, atopic dermatitis, and bronchial asthma) between May 2019 and April 2020 using an allergen detection kit of Macro-Union Pharmaceutical. RESULTS: 732 of the 1367 patients showed different antigen positive, and the positive rate was 53.5%. The most common allergens were dust mites, mixed fungi, Artemisia pollen, cat/dog dander, and cockroaches. There were 27.0% (369/1367) of the patients with single positive allergen-specific IgE (sIgE), 26.5% (363/1367) with multiple-positive IgE. The total immunoglobulin E (tIgE) levels varied with gender, age, and type of disease. There was a difference in the distribution of allergens between children and adults. A positive correlation between the serum-specific IgE and the corresponding local inhaled allergen density was observed. CONCLUSIONS: In this study, we found that type 2 inflammatory allergic diseases have higher serum IgE and a higher probability of inhaled sIgE positive. According to age, gender, and condition, serological IgE detection of allergens provides new insight into the early diagnosis and prevention of allergic diseases.

Upregulation of Basonuclin1 Is Associated with p63-Involved Epithelial Barrier Impairment and Type-2 Helper T-cell Inflammation in Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Tumor protein p63 has been shown to be important for epithelial dysfunction, including epithelial barrier defects and mucosal inflammation, in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Basonuclin1 (BNC1), an epithelial-specific transcriptional factor, is a direct downstream target of p63 and thus might be involved in the pathogenesis of CRSwNP. OBJECTIVE: We sought to investigate whether BNC1 was associated with p63-mediated epithelial barrier defects and nasal mucosal inflammation in CRSwNP. METHODS: Nasal tissue biopsies were obtained from 91 patients to CRSwNP, 49 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 28 control subjects. Immunohistochemistry and immunofluorescence staining were used to determine the distribution of BNC1 in tissues and localization in cells, respectively. Quantitative PCR was performed to detect the expression levels of BNC1, TP63, epithelial barrier proteins, and type-2 helper T-cell inflammation-related genes. RESULTS: BNC1 mRNA expression was significantly elevated in the tissues in CRSwNP patients compared with CRSsNP (1.96-fold, p = 0.0003) and control groups (2.40-fold, p < 0.0001). BNC1 staining was strongly positive in the nasal epithelium and co-localized with p63-positive epithelial cells. The expression of BNC1 mRNA was strongly correlated with TP63 mRNA level both in tissue biopsies (r = 0.78, p < 0.0001) and epithelial scrapings (r = 0.97, p < 0.0001). BNC1 expression was also positively correlated with epithelial barrier protein genes (CDH1, CLDN1, CLDN4, TJP1, and TJP2) and epithelial genes involved in TH2 inflammation (IL33, CCL26, CLC, and ALOX15). CONCLUSIONS: Overexpression of BNC1 may be associated with increased expression of TP63, and possibly contribute to the epithelial barrier defects and TH2 inflammation in CRSwNP.

Association Between Microbiota and Nasal Mucosal Diseases in terms of Immunity.

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.

The impact of COVID-19 outbreak on the incidence of acute invasive fungal rhinosinusitis.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) is aggressive morbidity affecting immunocompromised patients. Coronavirus disease 2019 (COVID-19) may allow secondary fungal disease through a propensity to cause respiratory infection by affecting the immune system leading to dysregulation and reduced numbers of T lymphocytes, CD4+T, and CD8+T cells, altering the innate immunity. The aim of this study is to evaluate the incidence of acute invasive fungal rhinosinusitis (AIFRS) in COVID-19 patients. METHODOLOGY: Data for acute invasive rhinosinusitis was obtained from the Otorhinolaryngology departments at our tertiary hospital at the period from January 2017 to December 2020. Then the risk factors of comorbid diseases and fungal types between post-COVID-19 and non-COVID-19 groups regarding the incidence of AIFRS are compared. RESULTS: Consequently, the incidence of AIFRS showed a more significant difference (P < 0.05) in post-COVID-19 patients than in non-COVID-19 especially in immunocompromised patients, diabetic, renal, and liver dysfunction patients as well as patients with risk factors of AIFRS. The most common organisms affecting patients with AIFRS are Rhizopus oryzae, Aspergillus fumigatus, and Absidia mucor. CONCLUSIONS: The incidence of AIFRS is markedly prominent in post-COVID-19 patients than in those of non-COVID-19, especially in immunocompromised, diabetic, renal, and liver dysfunction patients and patients with risk factors for rhinosinusitis.

Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

Rethinking neutrophils and eosinophils in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) often is characterized by an eosinophilic inflammatory pattern, nowadays referred to as type 2 inflammation, although the mucosal inflammation is dominated by neutrophils in about a third of the patients. Neutrophils are typically predominant in 50% of patients with CRS without nasal polyps, but also are found to play a role in patients with severe type 2 CRS with nasal polyp disease. This review aims at summarizing the current understanding of the eosinophilic and neutrophilic inflammation in CRS pathophysiology, and provides a discussion of their reciprocal interactions and the clinical impact of the mixed presentation in patients with severe type 2 CRS with nasal polyps. A solid understanding of these interactions is of utmost importance when treating uncontrolled severe CRS with nasal polyps with biologicals that are preferentially directed toward type 2 inflammation. We here focus on recent findings on both eosinophilic and neutrophilic granulocytes, their subgroups and the activation status, and their interactions in CRS.

CD48 Expression on Eosinophils in Nasal Polyps of Chronic Rhinosinusitis Patients.

INTRODUCTION: The pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNPs) is not yet completely understood. Based on current knowledge, the infiltration of mast cells and eosinophils in nasal polyps (NPs) plays an important role. This study aimed to investigate the interplay of asthma and allergy etiopathology in CRSwNPs patients by specifically studying tissue mast cells and eosinophils and the pro-inflammatory marker CD48. METHODS: Immunohistochemistry was used to assess eosinophils, mast cells, and CD48 expressing eosinophils infiltrating NPs, and flow cytometry was used to assess surface receptors expression on eosinophils from digested NPs. RESULTS: Immunohistochemical analyses showed that mast cell infiltration in NPs is higher in allergic patients in comparison to nonallergic patients; eosinophils infiltration in asthmatic NPs was significantly elevated in comparison to the nonasthmatic NPs, and membrane CD48 (mCD48) expression on eosinophils infiltrating nonallergic asthmatic NPs was highly elevated in comparison to the other subgroups. Similarly, mCD48 and its high-affinity ligand m2B4's expression on eosinophils from enzymatically digested NPs were significantly higher in nonallergic asthmatics in comparison to allergic asthmatics. CONCLUSIONS: Eosinophil infiltration in NPs for asthmatic patients, and mast cell infiltration for allergic patients, may be used as reliable biomarkers for endotyping CRSwNPs. In addition, CD48 in asthmatic patients who developed CRSwNPs could be regarded as a potential target for treatment.

Antibody deficiencies are more common in adult versus pediatric recurrent acute rhinosinusitis.

PURPOSE: To evaluate the frequency and types of humoral immunodeficiencies (HID) in pediatric and adult patients with recurrent (RARS). Patients with HID commonly present with upper respiratory tract infections. Their pathophysiology in children is different than adult counterparts. It is unknown how HID affects those two age groups. MATERIALS AND METHODS: We performed a retrospective chart review of pediatric (<18 years old) and adult (18 years and older) patients who were evaluated in our pediatric and adult rhinology clinic between July 2010 and December 2020 and had the diagnosis of recurrent (>3 times/year) rhinosinusitis. Patients with cystic fibrosis, Aspirin Exacerbated Respiratory Disease (AERD), and ciliary dyskinesia were excluded. Demographic data and associated conditions were reviewed. Immunologic evaluation included complete blood cell count (CBC) with differential, serum immunoglobulin G, A, and M levels, and baseline and post-vaccination pneumococcal antibody titers. RESULTS: There were 135 patients who met the inclusion criteria. 86 patients (63.7%) were children, 49 patients (36.3%) were adults. 46.5% of the pediatric patients and 45% of the adult patients were female. 17.4% of children had abnormal immunologic findings: 8 had hypogammaglobulinemia (p < 0.0001), 2 had specific antibody deficiency (SAD), and 5 had selective IgA deficiency. 32.7% of adults (p < 0.0001) had abnormal immunologic findings: 4 had hypogammaglobulinemia, 11 had SAD (p < 0.0001), and 1 patient had both IgA deficiency and SAD. CONCLUSION: Humoral immunodeficiency, specifically SAD, seems to be more common in adult versus pediatric RARS that is refractory to treatment.