Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence.

OBJECTIVES: Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown. The breathing pattern assessment tool (BPAT) can identify BPD. Our objective was to thus investigate the prevalence of BPD, nasal airflow obstruction and measures of airway disease severity in CRS with (CRSwNP) and without nasal polyps (CRSsNP) in severe asthma. METHODS: We determined whether CRS status, peak nasal inspiratory flow (PNIF) or polyp disease increased BPD prevalence. Demographic factors, measures of airway function and breathlessness in relation to BPD status and CRS subtypes were also evaluated. RESULTS: 130 Patients were evaluated (n = 69 had BPD). The prevalence of BPD in CRS with severe asthma was 53.1%. There was no difference between BPD occurrence between CRSwNP and CRSsNP. The mean polyp grade and PNIF were not statistically different between the BPD and non-BPD group. The presence of nasal polyps did not increase breathlessness. CONCLUSIONS: BPD and CRS are commonly co-associated. CRS status and nasal obstruction per se does not increase BPD prevalence.

Doxycycline may be more clinically effective in type 2 chronic rhinosinusitis nasal polyp comorbid with asthma.

OBJECTIVE: Chronic rhinosinusitis with nasal polyp (CRSwNP) is one of the major phenotypes of chronic rhinosinusitis (CRS) with a high symptom burden. Doxycycline can be used as add-on therapy in CRSwNP. We aimed to evaluate short-term efficacy of oral doxycycline on visual analog scale (VAS) and SNOT-22 (Sino-nasal outcome test) score for CRSwNP. METHODS: Visual analog score (VAS) for nasal symptoms and total SNOT-22 scores of 28 patients who applied with the diagnosis of CRSwNP and received 100 mg doxycycline for 21 days were analyzed in this retrospective cohort study. Doxycycline efficacy was also evaluated in subgroups determined according to asthma, presence of atopy, total IgE and eosinophil levels. RESULTS: After 21-day doxycycline treatment, there was a significant improvement in VAS score for post-nasal drip, nasal discharge, nasal congestion, and sneeze, and total SNOT-22 score (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). No significant improvement was observed in VAS score for the loss of smell (p = 0.18). In the asthmatic subgroup, there were significant improvements in all VAS scores and total SNOT-22 score after doxycycline. In the non-asthmatic subgroup, there was no significant change in any of the VAS scores, but total SNOT-22 score was significantly improved (42 [21-78] vs. 18 [9-33]; p = 0.043). Improvement in VAS score for loss of smell is significant in only some subgroups like asthmatic patients, non-atopic patients, and patients with eosinophil >300 cell/µL. CONCLUSIONS: Doxycycline can be considered as an add-on treatment for symptom control in patients especially with CRSwNP comorbid with asthma.

Association of autoimmune disorders with chronic rhinosinusitis in adults.

INTRODUCTION: Increasing evidence suggests that autoimmune disorders and their immunomodulating medications may increase the risk of rhinosinusitis compared to rhinitis. GOAL: To investigate the association between autoimmune disorders and rhinosinusitis. METHODS: We performed a case-control study of patients referred to West Virginia University from August 2020 to October 2022 for rhinologic complaints. Rhinosinusitis patients were diagnosed with either chronic rhinosinusitis (CRS) or recurrent acute rhinosinusitis (RARS). These patients were compared to non-rhinosinusitis patients. Patients' characteristics, comorbidities, and type of treatment of autoimmune disorders were reviewed. RESULTS: The sample consisted of 527 rhinosinusitis [184 CRS without nasal polyps (CRSsNP), 263 CRS with nasal polyps (CRSwNP) and 80 RARS patients] patients and 564 non-rhinosinusitis patients. Patients with rhinosinusitis were more likely to be older, males, have asthma, and have current and past smoking history (all with p-value < 0.05). Autoimmune disorders, primary antibody deficiency, and immunomodulator agents were more common in rhinosinusitis patients (16.5 % vs 9.4 %, OR = 1.9, p < 0.001; 5.1 % vs 0.5 %, OR = 10.1, p < 0.001; and 3.8 % vs 1.1 %, OR = 3.7, p = 0.003 respectively). Multivariate logistic regression adjusting for confounders showed that autoimmune disorders were strongly associated with rhinosinusitis [OR = 1.6, 95 % CI = 1.10-2.48], whereas the immunomodulators did not reach statistical significance [OR = 2.4, 95 % CI = 0.87-6.47]. Subgroup analysis showed the autoimmune disorders did not significantly differ between CRS and RARS groups [OR = 1.0, 95 % CI = 0.5-2.1], or between the CRSsNP and CRSwNP groups [OR = 0.9, 95 % CI = 0.5-1.7]. CONCLUSION: Autoimmune disorders are associated with rhinosinusitis, both CRS and RARS, independently of other risk factors.

Systemic inflammation response index predicts the postoperative recurrence of chronic rhinosinusitis with nasal polyps: a retrospective study in the Chinese population.

PURPOSE: Endoscopic sinus surgery (ESS) is now frequently used to treat chronic sinusitis with nasal polyps (CRSwNP), but postoperative recurrence plagues many patients. We aimed to assess the value of the systemic inflammation response index (SIRI) and the systemic immune-inflammatory index (SII) for the prediction of postoperative recurrence in patients with CRSwNP. METHODS: A total of 143 patients with CRSwNP and 76 age- and sex-matched healthy subjects were enrolled. Patients were divided into the recurrence group and the non-recurrence group according to the recurrence of CRSwNP. Univariate and multivariate analyses showed independent risk factors for the recurrence. A receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of the variables and determine the optimal cut-off values. Finally, a survival analysis was conducted. RESULTS: Univariate analysis revealed that age, sex, CRP, EOS, SIRI, SII, NLR, ELR, and Lund-Mackay CT scores were significant predictors of the recurrence of CRSwNP. Multivariate analysis confirmed that SIRI (OR = 1.310, p < 0.001) and Lund-Mackay CT scores (OR = 1.396, p < 0.001) were independent predictors. SIRI (AUC = 0.761, 95% CI: 0.685-0.836) had a certain value in predicting the recurrence of CRSwNP. CONCLUSION: SIRI is a potential predictive marker of the postoperative recurrence of CRSwNP.

Is generative pre-trained transformer artificial intelligence (Chat-GPT) a reliable tool for guidelines synthesis? A preliminary evaluation for biologic CRSwNP therapy.

INTRODUCTION: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols. METHODS: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart. RESULTS: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP. CONCLUSIONS: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP.

Hypereosinophilia during dupilumab treatment in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Increased blood eosinophil count (BEC) is common in patients under dupilumab treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). This study investigated the prevalence and consequences of hypereosinophilia and to help define patients at risk. METHODS: Real-life, prospective observational cohort study of patients treated with dupilumab for severe CRSwNP. Eligible patients were adult and biological-naive (N=334). All BEC values at baseline and during treatment were reported. Patients with a follow-up of >= 1 year were included to define patients at risk for hypereosinophilia by comparing baseline BEC values (N=218). Furthermore, clinical characteristics and therapeutic consequences for patients with BEC >= 3.0 were noted. RESULTS: Hypereosinophilia developed in a minority of patients, with a peak at week 12 (16.2% with BEC >= 1.5, and 1.7% >= 3.0) in cross-sectional analysis. BEC >= 1.5 developed in 28.9% and BEC >=3.0 in 4.6% of cases with a minimal 1-year follow-up. Baseline BEC was significantly higher for patients developing BEC >= 1.5 and BEC >=3.0, with an optimal cut-off point of 0.96 to predict developing BEC >= 3.0. CONCLUSIONS: Blood eosinophil count (BEC) >= 1.5 is transient and usually abates with no therapeutic interventions and BEC >= 3.0 is rare. Hypereosinophilic syndrome did not occur and switching to a different biological was rarely employed. A baseline BEC of >=1.0 can be a reason for extra caution.

Heterogeneity of asthma with nasal polyposis phenotypes: A cluster analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) affects a significant number of asthmatic patients and is notably associated with a more difficult-to-control asthma and marked inflammation. We need more studies on this specific asthma phenotype and its possible subphenotypes, in order to better individualize treatments. AIM: The aim of this study is to identify and characterize subphenotypes of asthma patients with CRSwNP using clinical, physiological and inflammatory variables. METHODS: K-means cluster analysis was performed on 17 clinical, physiological, and inflammatory variables from 1263 patients of all asthma severity and on a subpopulation of patients with asthma and CRSwNP. Study was registered on ClinicalTrials.gov (NCT03694847). RESULTS: On the overall population, three groups were identified. Cluster T1 (n = 708) are young, have a short asthma duration and a low prevalence of CRSwNP. Cluster T2 (n = 263) have the longest asthma duration and Cluster T3 (n = 292) are older with the shortest asthma duration. Patients in Clusters T2 and T3 have similar prevalences of CRSwNP. On the subpopulation of asthma with CRSwNP, three clusters were also identified. Cluster S1 (n = 83) have mild-to-moderate asthma with normal lung function. Clusters S2 (N = 53) and S3 (N = 42) include patients with severe asthma and decreased lung function, but those in Cluster S2 have a longer asthma duration, whereas those Cluster S3 have late-onset asthma. CONCLUSIONS: Despite coexistence of asthma and CRSwNP, not all patients have the same evolution of their asthma. Different phenotypes of asthma with CRSwNP can be identified and exploration of the characteristics of these subgroups could lead to a better individualized, targeted management.

Different aspects of severe asthma in real life: Role of Staphylococcus aureus enterotoxins and correlation to comorbidities and disease severity.

BACKGROUND: Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non-invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: The aim of this retrospective study was to evaluate the prevalence of SE-IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics. RESULTS: A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)-IgE positive. We found a meaningful association between SEB-IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB-IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB-IgE-positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB-IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB-IgE sensitization as an independent risk factor for developing asthma. CONCLUSIONS: Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine.

Risk Factors for Abnormal Small Airway Function Indicators in Nasal Polyp Patients with and without Asthma.

INTRODUCTION: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. METHODS: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. RESULTS: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient's blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25-75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25-75% %pred. CONCLUSION: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.

Real-Life Experience of Biologic Treatment for Asthma on Chronic Rhinosinusitis: A Finnish Cohort.

INTRODUCTION: Biologics are used in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this retrospective study was to evaluate the effects of biologics initiated for asthma on coexistent CRS and the influence of comorbid factors, including aspirin-exacerbated respiratory disease (AERD) and secretory otitis media (SOM). METHODS: A review of electronic health records (2009-2020) at a Finnish tertiary center was conducted to identify CRS patients treated with biologics for their asthma. We identified the type of biologic and treatment response, by comparing nasal polyp score (NPS), sinonasal outcome test (SNOT)-22, need for oral corticosteroids (OCS) and antibiotics, frequency of visits, and endoscopic sinus surgeries (ESS) pretreatment and during treatment. RESULTS: 55 patients were treated with anti-immunoglobulin E (IgE) (n = 18) or anti-interleukin-5/5-receptor (IL-5/5R) (n = 37) biologics. Treatment lasted for an average of 4.1 years. Seventy-five percent (n = 41) had CRSwNP and 25% (n = 14) had CRSsNP. Of all patients, 24% (n = 13) had comorbid AERD and 22% (n = 12) had SOM. Biologic therapy reduced the need for OCS courses (anti-IgE, n = 17, p = 0.03; anti-IL-5/5R, n = 35, p = 0.01) and for daily OCS in anti-IL-5/5R (n = 35, p = 0.001) but not in anti-IgE patients (n = 16, p = 0.07). Biologics also improved NPS by 0.5 point (n = 32, p = 0.009) and SNOT-22 by 14 points (n = 7, p = 0.02) in CRSwNP patients. The overall discontinuation rate was 37.7% (n = 20) and was independent of type of biologic. CONCLUSION: Treatment with anti-IgE and/or anti-IL-5/5R biologics reduced the overall need for OCS medication in individuals with asthma and concomitant CRS, but despite this, the discontinuation rate was high.

Prevalence and Severity Distribution of Type 2 Inflammation-Related Comorbidities Among Patients with Asthma, Chronic Rhinosinusitis with Nasal Polyps, and Atopic Dermatitis.

This observational study assessed the prevalence of co-existing type 2 inflammatory conditions [T2Cs; asthma, atopic dermatitis (AD), allergic rhinitis, and chronic rhinosinusitis with nasal polyps (CRSwNP)] in patients with moderate-to-severe (M/S) type 2 asthma, M/S CRSwNP, or M/S AD, in the real-world setting. Data from 761 physicians in the US and EUR5 were sourced from Adelphi Disease-Specific Programmes covering patients with M/S asthma (n = 899), M/S CRSwNP (n = 683), and M/S AD (n = 1497). At least one T2C was identified in 66%, 69%, and 46% of M/S asthma, M/S CRSwNP, and M/S AD cohorts, respectively, and 24%, 36% and 16% had at least two T2Cs; trends were similar in the US and EUR5. In patients with M/S asthma or M/S CRSwNP, T2Cs commonly presented as mild or moderate. The comorbidity burden suggests that an integrated treatment approach is warranted to address underlying type 2 inflammation in patients with M/S type 2 diseases.

Comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: did dupilumab make a difference?

BACKGROUND: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT). METHODS: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score. RESULTS: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups. CONCLUSION: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.

A Google Trends analysis revealed global public interest and awareness of nasal polyps.

INTRODUCTION: Nasal polyps (NPs) is a common upper airway inflammatory disorder with a huge negative burden on both the quality of life and costs to patients. However, NPs patients remain undiagnosed and untreated in a timely, which may be due to a lack of disease-related awareness. Google Trends (GT) is an online and open tool, which can provide real-world data on health informatics worldwide. OBJECTIVES: This study aimed to explore global public interest and awareness in nasal polyps (NPs) by performing a GT analysis. METHODS: Data on relative search volume (RSV) for NPs globally were collected by the public website Google Trends from January 2007 to December 2021. Top-related topics, rising-related topics, and regions were extracted for further analysis. Seasonal variation analysis, the latitude difference analysis, and the rising-related topics between the developed countries and the developing countries were analyzed. A P value less than 0.05 was considered statistically significant. RESULTS: The average searching strength showed an overall increasing trend, although with slight fluctuation. The public interest of NPs focuses on the symptoms and treatment for NPs and changes with time. For seasonal variation countries, the peak for the RSV occurred in winter and the bottom in summer. A region in higher latitudes may yield more RSV than that in lower latitudes. The rising-related topics in the recent 5 years reflected the significant differences in treatment and public interest of NPs between the developed and developing countries. CONCLUSIONS: Google Trends analysis revealed global public interest and awareness of the evolution of trends and related topics in nasal polyps over time. Geographic distribution and seasonal variation may be potential trigger factors for NPs, and the public's interest in treatment especially biologics is rising.

Revision of endoscopic sinus surgery in adults: A population-based study in Taiwan.

OBJECTIVE: This study aimed to elucidate the revision rate, time to revision, and factors associated with revision of endoscopic sinus surgery (ESS) in Taiwan. DESIGN: Retrospective study. SETTING: Population-based analysis. PARTICIPANT: We identified all in-hospital patients, aged >20 years, who underwent ESS between 2000 and 2008 from the Taiwan National Health Insurance Research Database, and followed up with them until 2018. MAIN OUTCOME MEASURES: Factors associated with revision surgery were analyzed using multivariable Cox proportional hazard model. RESULTS: Overall, 66 592 patients were identified (mean age, 46.3 years; 62% males). The revision rate was 14.5% (9644/66 592) and time to revision surgery was 5.9 years. Multivariable Cox proportional hazard model showed that young age, male gender (hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.13-1.23), having nasal polyposis (HR = 1.17; 95% CI, 1.12-1.22), having allergic rhinitis (HR = 1.08; 95% CI, 1.04-1.13), having asthma (HR = 1.26; 95% CI, 1.14-1.39), and surgical time of >4 h (HR = 1.11; 95% CI, 1.06-1.16) were associated with increased risk of revision surgery. Concurrent septal surgery (HR = 0.81; 95% CI, 0.76-0.87), turbinate surgery (HR = 0.91; 95% CI, 0.85-0.97), or septal and turbinate surgery (HR = 0.68; 95% CI, 0.64-0.73) were associated with decreased risks of revision surgery. CONCLUSION: In Taiwan, risk factors for revision ESS are young age, male gender, having nasal polyposis, having allergic rhinitis, having asthma, and long surgical times. Concurrent septal or turbinate surgery decreases the risk of revision.

Clinical and cytokine patterns of uncontrolled asthma with and without comorbid chronic rhinosinusitis: a cross-sectional study.

BACKGROUND: Asthma is significantly related to chronic rhinosinusitis (CRS) both in prevalence and severity. However, the clinical patterns of uncontrolled asthma with and without comorbid CRS are still unclear. This study aimed to explore the clinical characteristics and cytokine patterns of patients with uncontrolled asthma, with and without comorbid CRS. METHODS: 22 parameters associated with demographic characteristics, CRS comorbidity, severity of airflow obstruction and airway inflammation, and inflammation type of asthma were collected and assessed in 143 patients with uncontrolled asthma. Different clusters were explored using two-step cluster analysis. Sputum samples were collected for assessment of Th1/Th2/Th17 and epithelium-derived cytokines. RESULTS: Comorbid CRS was identified as the most important variable for prediction of different clusters, followed by pulmonary function parameters and blood eosinophil level. Three clusters of patients were determined: Cluster 1 (n = 46) characterized by non-atopic patients with non-eosinophilic asthma without CRS, demonstrating moderate airflow limitation; Cluster 2 (n = 54) characterized by asthma patients with mild airflow limitation and CRS, demonstrating higher levels of blood eosinophils and immunoglobulin E (IgE) than cluster 1; Cluster 3 (n = 43) characterized by eosinophilic asthma patients with severe airflow limitation and CRS (46.5% with nasal polyps), demonstrating worst lung function, lowest partial pressure of oxygen (PaO2), and highest levels of eosinophils, fraction of exhaled nitric oxide (FeNO) and IgE. Sputum samples from Cluster 3 showed significantly higher levels of Interleukin (IL)-5, IL-13, IL-33, and tumor necrosis factor (TNF)-α than the other two clusters; and remarkably elevated IL-4, IL-17 and interferon (IFN)-γ compared with cluster 2. The levels of IL-10 and IL-25 were not significantly different among the three clusters. CONCLUSIONS: Uncontrolled asthma may be endotyped into three clusters characterized by CRS comorbidity and inflammatory cytokine patterns. Furthermore, a united-airways approach may be especially necessary for management of asthma patients with Type 2 features.

Epidemiology and treatment of patients with Chronic rhinosinusitis with nasal polyps in Germany-A claims data study.

BACKGROUND: There are different levels of severity among patients who suffer from chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, the epidemiology of CRSwNP and severe CRswNP was estimated. METHODS: A retrospective claim data analysis was conducted on adult CRSwNP patients (ICD-10: J33), and those classified as severe CRSwNP patients with inadequate disease control (based upon combinations of previous and current treatments) between 2015 and 2019. Prevalence and incidence figures were calculated and extrapolated to the German population. In addition, baseline characteristics and treatment outcomes were analysed. RESULTS: Overall, the 5-year prevalence of adult CRSwNP cases from 2015 to 2019 in Germany was 374,115 cases (about 5500 per million), with 12,989 (about 200 per million) patients being classified as severe CRSwNP with inadequate disease control, whereas 267,880 (about 3900 per million) patients were identified as having an incident CRSwNP diagnosis between 2016 and 2019. From the incident CRSwNP cohort, 80.55% had received at least one intranasal corticosteroid (INCS), 24.27% received at least 1 systemic corticosteroid (SCS), and 17.33% received at least one functional endoscopic sinus surgery (FESS) within 12 months after their incident diagnosis. CONCLUSION: Severe CRSwNP with inadequate disease control affects about 200 per million people in Germany. INCS is the first-choice treatment for most CRSwNP patients; however, for patients with severe CRSwNP, SCS are prescribed more frequently and long-term effects of these should be further investigated, especially if despite treatment, adequate disease control cannot be achieved.

Component-Resolved Diagnosis for Endotyping Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses that often coexists with asthma. The role of atopy in the development and severity of CRSwNP is still a controversial issue. OBJECTIVE: The aim of our study was to propose a systematic allergy workup to identify atopic patients in the context of CRSwNP and to characterize their allergen sensitization profile (sources/molecules). METHODS: Patients with a diagnosis of CRSwNP (n = 97) were studied in the otorhinolaryngologist and allergy settings. Demographic and clinical data were collected for each patient. Different allergen sensitization profiles (sources/molecules) were evaluated in atopic CRSwNP patients by using component-resolved diagnosis (CRD). RESULTS: In our cohort of patients, the CRSwNP was frequently diagnosed during adulthood with significant impact on health-related quality of life. Asthma and atopy were the most common comorbidities with a prevalence of asthma in the atopic group. In CRSwNP patients sensitized to grass pollens and/or to house dust mites, the CRD analysis revealed a prevalence of sensitization to species-specific allergens of Phleum pratense (Phl p1, Phl p2, and Phl p5) or Dermatophagoides pteronyssinus (Der p1 and Der p2) rather than to cross-reactive ones. CONCLUSION: To define the allergen sensitization profile in atopic CRSwNP patients by CRD, it may be useful to better characterize type 2 inflammation, thus providing a personalized endotype-driven treatment.

Nasal polyp eosinophilia and FeNO may predict asthma symptoms development after endoscopic sinus surgery in CRS patients without asthma.

BACKGROUND: Asthma is a significant comorbidity of eosinophilic chronic rhinosinusitis (CRS). Type2-driven biomarkers such as sinus tissue eosinophilia and fractional nitric oxide (FeNO) may be utilized to detect high risk patients who develop asthma symptoms after endoscopic sinus surgery (ESS) in CRS patients. METHODS: Thirty-six CRS patients without asthma who agreed to undergo ESS between October 2015 and December 2017 were prospectively observed for 12 months following ESS. They were monitored for the development of typical asthma symptoms including dyspnea, wheezes, and cough which responded to anti-asthma medication. Biomarkers were compared between patients who developed asthma symptoms after ESS (asthma symptoms group) and those who did not (non-asthma group). Biomarker changes following ESS intervention were also evaluated. RESULTS: Six patients were lost to follow after ESS. Thus, 30 CRS patients [16 with nasal polyps (NPs) proved by surgery] were followed. Seven (23%) newly complained of asthma symptoms during follow-up. Levels of FeNO and the prevalence of eosinophilic NPs (eosinophils ≥ 70/high power fields) were significantly higher in the asthma symptom group than in non-asthma group [50.7 ppb vs 22.4 ppb for FeNO levels, and 100% (n = 3) vs 23% (n = 3) for eosinophilic NP prevalence, both p < 0.05]. Levels of sputum periostin decreased significantly by ESS in the non-asthma group. However, changes of biomarkers after ESS were comparable between the two groups. CONCLUSIONS: Eosinophils in NPs (≥70/high power fields) and preoperative FeNO may be significant biomarkers for predicting the development of asthma symptoms after ESS.

Risk factors associated with comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: a cross-sectional study.

BACKGROUND: Although 20-60% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have asthma, the risk factors associated with comorbid asthma are not clear. The aim of the study was to investigate the factors associated with asthma, and develop a practical scoring system to screen asthma comorbidity in CRSwNP patients. METHODS: This report describes a cross-sectional study with consecutive CRSwNP patients. Two cohorts of CRSwNP patients named "modelling" group and "validation" group were investigated respectively. Logistic regression analysis was performed based on demographic and clinical data collected from patients in the modelling group to determine the risk factors associated with asthma, and establish a scoring system for screening comorbid asthma. Receiver operating characteristic curve was constructed to evaluate the screening system; the optimal cut-off point was established by means of the Yoden Index. The consistency between the diagnosis of asthma by the Global Initiative for Asthma (GINA) criteria and by the screening system was assessed by Kappa value in the validation group. RESULTS: Totally 150 patients in modelling group and 78 patients in validation group were enrolled. Female gender (odds ratio [OR] = 6.4; P < 0.001), allergic rhinitis (OR = 2.9; P = 0.021), serum total (T)-immunoglobulin (Ig) E ≥ 69.0kU/L (OR = 12.0; P < 0.001), and blood eosinophil count ≥ 0.35 × 109/L (OR = 4.0; P = 0.001) were shown to be independent risk factors for asthma in patients with CRSwNP. Based on these variables, a scoring system (FAIE) ranging from 0(no risk) to 6(high risk); was developed. The area under the receiver operating characteristic curve of the system was 0.823, and the optimal cut-off value was 3 points, with sensitivity 83.8% and specificity 68.6% for screening asthma. The asthma comorbidity determined with FAIE score ≥ 3 points in the validation group, was moderately consistent with that defined by GINA (Kappa = 0.513, P < 0.001), with sensitivity 76.9% and specificity 74.4%. CONCLUSIONS: Female gender, allergic rhinitis, serum T-IgE level, and blood eosinophil count are independent risk factors for asthma comorbidity in patients with CRSwNP, and the FAIE system may be practical for screening comorbid asthma in these patients.