Severe Chronic Rhinosinusitis Research Articles

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps.

The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation. To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence. Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP. Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01). Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.

Patient-Reported Outcomes with Benralizumab in Patients with Severe Eosinophilic Asthma and Severe Chronic Rhinosinusitis with Nasal Polyps

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) and severe eosinophilic asthma (SEA) are common comorbidities characterised by type 2 inflammation associated with increased expression of interleukin 5. Methods: Eight patients with SEA and severe CRSwNP attended the Scottish Centre for Respiratory Research as part of a clinical trial (EudraCT number 2019-003763-22). Following an initial 4-week run-in period (baseline) when patients took their usual inhaled and intranasal corticosteroid treatment for SEA and CRSwNP, they all received subcutaneous benralizumab 30 mg q4w for 12 weeks. Results: Following 12 weeks of benralizumab, no significant differences were detected in nasal global symptom visual analogue score (VAS), hyposmia VAS, total nasal symptom score, or peak nasal inspiratory flow. In contrast, Asthma Control Questionnaire significantly improved along with near-complete depletion of peripheral blood eosinophils by 99%, while eosinophil-derived neurotoxin fell by 72%. Conclusions: Greater improvements in patient-reported outcomes related to asthma were observed than with CRSwNP in response to benralizumab.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

Health-Related Quality of Life Impairment Among Patients with Severe Chronic Rhinosinusitis with Nasal Polyps in the SINUS-24 Trial.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease with a high symptom burden. Data are lacking on the comparative health status of patients with CRSwNP. This analysis compared baseline physical and mental health-related quality of life (HRQoL) and overall health status of patients with severe CRSwNP enrolled in a Phase 3 clinical trial with general population norms and with other chronic diseases. In this post hoc cross-sectional analysis of baseline data from the SINUS-24 study (NCT02912468), HRQoL was measured using the 36-item Short Form (SF-36) questionnaire and general health status was measured using the EuroQol-5 Dimension visual analog scale (EQ-VAS). Analyses included the intention-to-treat (ITT) population and subgroups defined by prior sinonasal surgery, systemic corticosteroid use, and coexisting asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Scores were compared with published values for population norms (50for SF-36 physical component summary (PCS) and mental component summary (MCS), 70.4-83.3 for EQ-VAS) and for rheumatoid arthritis, type 2 diabetes, and asthma. In the ITT population (n=276), mean SF-36 physical component summary (PCS), SF-36 mental component summary (MCS), and EQ-VAS scores were below general population norms (46.4, 48.6, and 66.0, respectively). Mean SF-36 PCS and EQ-VAS scores were below population norms across all subgroups; mean SF-36 MCS scores were below the population norm in all subgroups except no prior surgery. SF-36 PCS and MCS scores from SINUS-24 were generally similar to other chronic diseases, except SF-36 PCS which was lower in rheumatoid arthritis. EQ-VAS scores in SINUS-24 were lower than in other chronic diseases. HRQoL scores weakly correlated with objective measures of disease severity. In patients with severe CRSwNP, including those with coexisting asthma/NSAID-ERD, HRQoL was worse than population norms and as burdensome as diseases such as type 2 diabetes, asthma, and rheumatoid arthritis.

Biologicals in severe chronic rhinosinusitis with nasal polyps: translation to clinical practice while waiting for head-to-head studies.

Chronic rhinosinusitis with nasal polyps (CRSwNP) affects 1.0-2.6% of the population (1) and results in relevant direct and indirect costs. Recently, several randomized controlled trials (RCTs) with Type 2-targeting biologicals (anti-IL4Rα, anti-IL5R, anti-IL5 and anti-IgE) opened a new treatment field for patients refractory to first-line treatments (2,3).

Mepolizumab (Nucala)

&#x0D; CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.&#x0D; The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.&#x0D; This review assesses mepolizumab (Nucala), 100 mg/mL for subcutaneous injection.&#x0D; Indication: As add-on maintenance treatment with intranasal corticosteroids in adult patients with severe chronic rhinosinusitis with nasal polyps inadequately controlled by intranasal corticosteroids alone.&#x0D;

The Impact of Social Determinants and Air Pollution on Healthcare Disparities in Chronic Rhinosinusitis With Nasal Polyps.

Multiple factors affect healthcare disparities in chronic rhinosinusitis (CRS) with and without nasal polyps. These factors include access to care, economic burdens to treatment, and differences in air pollution and air quality. In this paper, we will discuss how socioeconomic status, race, and air pollution burden influence healthcare disparities in the diagnosis and treatment outcomes of chronic rhinosinusitis with nasal polyps (CRSwNP). A literature search was performed via PubMed for articles related to CRSwNP, healthcare disparities, race, socioeconomic status, and air pollution in September 2022. Original studies from 2016 to 2022, landmark articles, and systematic reviews were included. We summarized these articles to cohesively discuss factors contributing to healthcare disparities in CRSwNP. Literary search produced 35 articles. Individual factors such as socioeconomic status, race, and air pollution influence CRSwNP severity and treatment outcomes. Correlations were noted with socioeconomic status, race, and air pollution exposure and CRS severity and post-surgical outcomes. Air pollution exposure was also associated with histopathologic changes in CRSwNP. Lack of access to care was a notable contributor to healthcare disparities in CRS. Healthcare disparities in the diagnosis and treatment of CRSwNP differentially affect racial minorities and individuals of lower socioeconomic status. Increased air pollution exposure in areas of lower socioeconomic status is a compounding factor. Clinician advocacy for greater healthcare access and reductions in environmental exposures for patients, among other societal changes, may help improve disparities.

Comparison of mycology between different types of chronic rhinosinusitis.

The aim of this study was to culture fungi from the nasal discharge of patients with chronic rhinosinusitis (CRS) using both a traditional and Ponikau et al's method, and subsequently compare the culture results between CRS with nasal polyps (CRSwNPs) and without nasal polyps (CRSsNPs), and between eosinophilic and noneosinophilic CRS. Eighty-one CRS patients with CRS who underwent functional endoscopic sinus surgery were enrolled. Before surgery, the severity of each patient's CRS was evaluated through an endoscopic examination and CT scan. Swab samples were collected from the middle meatus for traditional fungal cultures using cotton-tipped sticks. Afterward, the ipsilateral nasal cavity was irrigated, with the irrigated fluid processed using Ponikau et al's method for fungal culture. The endoscopic and CT scores were significantly higher in CRSwNPs than CRSsNPs, but were not different between eosinophilic CRS and noneosinophilic CRS. Using Ponikau et al's method, 61/81 (75.3%) of the specimens grew fungi. Among them, 20 of 32 (62.5%) CRSwNPs specimens and 41 of 49 (83.7%) CRSsNPs specimens grew fungi. For eosinophilic CRS specimens, 35 of 46 (76.1%) grew fungi, and 26 of 35 (74.3%) noneosinophilic CRS specimens grew fungi. The fungal culture rate was borderline significantly higher in CRSsNPs than CRSwNPs ( p = 0.058) but was not significantly different between eosinophilic CRS and noneosinophilic CRS ( p = 1). However, Cladosporium was significantly more common in CRSsNPs than CRSwNPs ( p = 0.048). Our results showed that the mycology of CRS was different between CRSwNPs and CRSsNPs.

Effects of benralizumab in a population of patients affected by severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: a real life study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe eosinophilic asthma (SEA), which may contribute to the loss of asthma control. CRSwNP and SEA share a T2-mediated mechanism and the use of some anti-asthma monoclonal antibodies has recently been extended to CRSwNP. Unlike dupilumab and omalizumab, benralizumab approval for CRSwNP is ongoing. We aimed to evaluate the efficacy of benralizumab efficacy on SEA and on CRSwNP in patients affected by both pathologies in a real life setting. 17 patients affected by both SEA and CRSwNP participated to our study. At baseline (T0) and at one year after benralizumab initiation (T1), all participants underwent spirometry, exhaled nitric oxide (FeNO), Asthma Control Test (ACT), nasal endoscopy with Nasal Polyp Score (NPS), nasal cytology and Sino-Nasal Outcome Test 22 (SNOT 22).The continuous oral corticosteroid therapy (OCS), the number of year exacerbations and the need for sinus surgery were also evaluated for each patient. At T1, a marked reduction of SNOT-22, NPS, nasal eosinophils and neutrophils count were shown compared to T0. Moreover, at T1 ACT was significantly increased and FeNO, exacerbations/year and mean OCS dosage were significantly reduced compared to T0. Our real-life study demonstrates the efficacy of benralizumab not only on SEA but also on nasal cytology and on nasal polyposis, confirming that patients affected by both SEA and CRSwNP may receive a considerable benefit from anti-IL5 receptor, treating both the comorbidities at once.

IL-13–associated epithelial remodeling correlates with clinical severity in nasal polyposis

Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described. We sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS. Using cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls. The airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures. These results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem – Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Real World Benefits of Mepolizumab in Patients With Severe Asthma and Comorbid Chronic Rhinosinusitis With Nasal Polyps (CRSwNP): Post Hoc Analysis of REALITI-A

In clinical trials, mepolizumab reduced clinically significant exacerbations (CSEs) and maintenance oral corticosteroid (mOCS) use in patients with severe eosinophilic asthma (SEA); greater benefits were observed in patients with comorbid CRSwNP. Equivalent long-term real-world data would enhance this evidence.

Mepolizumab improvements in health-related quality of life and disease symptoms in a patient population with very severe chronic rhinosinusitis with nasal polyps: psychometric and efficacy analyses from the SYNAPSE study

BackgroundAlthough the psychometric properties of patient-reported outcome measures (e.g. the 22-item Sino-nasal Outcomes Test [SNOT-22]) in chronic rhinosinusitis with nasal polyps (CRSwNP) have been defined, these definitions have not been extensively studied in patients with very severe CRSwNP, as defined by recurrent disease despite ≥ 1 previous surgery and a current need for further surgery. Therefore, the psychometric properties of the symptoms visual analogue scales (VAS) were evaluated, and meaningful within-patient change thresholds were calculated for VAS and SNOT-22.MethodsSYNAPSE (NCT03085797), a randomized, double-blind, placebo-controlled, 52-week trial, assessed the efficacy and safety of 4-weekly mepolizumab 100 mg subcutaneously added to standard of care in very severe CRSwNP. Enrolled patients (n = 407) completed symptom VAS (six items) daily and SNOT-22 every 4 weeks from baseline until Week 52. Blinded psychometric assessment of individual and composite VAS was performed post hoc, including anchor-based thresholds for meaningful within-patient changes for VAS and SNOT-22, supported by cumulative distribution function and probability density function plots. The effect of mepolizumab versus placebo for 52 weeks on VAS and SNOT-22 scores was then determined using these thresholds using unblinded data.ResultsInternal consistency was acceptable for VAS and SNOT-22 scores (Cronbach’s α-coefficients ≥ 0.70). Test–retest reliability was demonstrated for all symptom VAS (Intra-Class Correlation coefficients > 0.75). Construct validity was acceptable between individual and composite VAS and SNOT-22 total score (r = 0.461–0.598) and between individual symptom VAS and corresponding SNOT-22 items (r = 0.560–0.780), based upon pre-specified ranges. Known-groups validity assessment demonstrated generally acceptable validity based on factors associated with respiratory health, with all VAS responsive to change. Mepolizumab treatment was associated with significantly increased odds of meeting or exceeding meaningful within-patient change thresholds, derived for this very severe cohort using six anchor groups for individual VAS (odds ratio [OR] 2.19–2.68) at Weeks 49–52, and SNOT-22 (OR 1.61–2.96) throughout the study.ConclusionsSymptoms VAS and SNOT-22 had acceptable psychometric properties for use in very severe CRSwNP. Mepolizumab provided meaningful within-patient improvements in symptom severity and health-related quality of life versus placebo, indicating mepolizumab provides substantial clinical benefits in very severe CRSwNP.

Correlation between coronary heart disease severity and subsequent chronic rhinosinusitis severity: A retrospective cohort study.

Coronary heart disease (CHD) is associated with the development of several diseases. This retrospective population-based cohort study investigated the association between CHD severity and subsequent chronic rhinosinusitis (CRS) of varying severity. We used data from Taiwan's National Health Insurance Research Database. CHD was categorized as severe if treated using a coronary artery bypass graft (CABG) and as mild if treated with percutaneous coronary intervention (PCI). The primary outcome of this study was the development of CRS or severe CRS treated using functional endoscopic sinus surgery. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CRS and severe CRS in different patient groups. We included 31,784 patients who received PCI surgery (the CHD-PCI group) and 15,892 patients who received CABG surgery (the CHD-CABG group). A total of 813 and 482 episodes of CRS occurred in the CHD-PCI and CHD-CABG groups, respectively, and 45 and 16 severe CRS events occurred in the CHD-PCI and CHD-CABG groups, respectively. Our multivariable analysis demonstrated that the incidence of CRS in the CHD-CABG group was significantly higher than that in the CHD-PCI group (aHR: 1.196, 95% CI: 1.064-1.280, P = 0.0402), but the two groups had similar incidence rates of severe CRS (aHR: 0.795, 95% CI: 0.456-1.388, P = 0.5534). Subgroup analyses revealed that the association between CHD severity and CRS development was more significant among men (P = 0.0016). In conclusion, we determined that severe CHD treated with CABG was associated with a higher incidence of subsequent CRS, and this association was more prominent among men.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Dupilumab provides early and durable improvement ofsymptoms in patients with chronic rhinosinusitis withnasal polyps.

To evaluate within-patient symptom improvement in the dupilumab SINUS-24/-52 studies in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT02912468/NCT02898454). Patients received dupilumab 300 mg or placebo every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) on background intranasal corticosteroids. Patients daily reported symptoms of nasal congestion (NC), loss of smell (LoS) and rhinorrhoea on a scale of 0-3 (0 - no symptoms, 1 - mild, 2 - moderate, 3 - severe symptoms). The proportions of patients with moderate-to-severe symptoms (score ≥ 2) at baseline who improved to no-to-mild symptoms (score ≤ 1) were determined at Weeks 2, 24 (pooled studies) and 52 (SINUS-52). Subgroups with prior sinonasal surgery and coexisting asthma were analysed. At baseline in the pooled intention-to-treat population (n=724), the proportions of patients with scores ≥ 2 for NC, LoS and rhinorrhoea were 87, 94 and 64%, respectively. Significantly, more patients achieved scores ≤ 1 (no/mild symptoms) with dupilumab vs placebo for each symptom at each time point {Week 2 NC 12% vs 2% [odds ratio 8.9 (95% CI 3.0-26.3)], LoS 5% vs 1% [4.6 (1.3-16.8)], rhinorrhoea 9% vs 2% [4.8 (1.5-15.4)], all P < 0.05; Week 24 NC 54% vs 14% [8.7 (5.6-13.5)], LoS 43% vs 6% [14.4 (7.9-26.0)], rhinorrhoea 53% vs 16% [6.6 (4.1-10.9)], all P < 0.0001}. Results were similar in subgroups with prior surgery and coexisting asthma. Significantly, more patients achieved improvement from moderate-to-severe symptoms to no-to-mild symptoms with dupilumab than placebo, regardless of prior surgery or coexisting asthma. Improvement was observed as early as Week 2 and continued through to Week 52.

Biologic treatment for severe chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis.

Chronic rhinosinusitis with nasal polyps is often severe, debilitating and difficult to treat. Biologics that target key inflammatory pathways have the potential to treat this disease; this study aimed to evaluate their effectiveness. Systematic review and meta-analysis of randomised controlled trials of biologics in chronic rhinosinusitis with nasal polyps. Primary outcomes were extent of disease, objective disease severity and disease-specific quality of life, with outcomes measured at different end-of-treatment timepoints in different studies (range 16-52 weeks). Eleven trials were identified with 2035 participants. Ten studies reported change in polyp size, estimating a reduction of -1.25 in the treatment group. Six studies reported reduction in Lund-Mackay score where the pooled mean difference was -4.90. Five studies included peak nasal inspiratory flow with a pooled mean difference of 33.54, indicating improved nasal airflow. Seven studies reported change in olfactory score with an overall pooled effect of 6.56 suggesting improved olfaction. The SNOT-22 score in nine studies gave an overall pooled effect of -14.53, indicating improved quality of life. Biologics can be effective in treating nasal polyps, with reduction in polyp size and extent of disease, and improved sense of smell and quality of life. There is significant heterogeneity in the outcomes for individual biologics, highlighting the need for further studies.

A Decade of Clinical Advances in Chronic Rhinosinusitis: 2012–2022

The field of chronic rhinosinusitis (CRS) is constantly evolving. In the past 10 years, key advancements in basic and translational research as well as clinical studies have improved our understanding and management of CRS. Notably, treatment options have expanded to include novel therapeutic drugs, devices, and surgical techniques. Assessments of patient symptoms and their impact on quality of life have become more standardized. Progress has also been made in both determining the true prevalence of CRS and recognizing comorbidities that can impact CRS severity. Practice guidelines have also shifted from expert opinion to more data-driven analyses. This review highlights major clinical advancements made in the field of CRS over the past 10 years as well as identifies current gaps in knowledge that can form the basis for new areas of study over the next decade.

Longitudinal Magnetic Resonance Imaging Detects Onset and Progression of Chronic Rhinosinusitis from Infancy to School Age in Cystic Fibrosis.

Rationale: Chronic rhinosinusitis (CRS) contributes to morbidity in patients with cystic fibrosis (CF). However, longitudinal data on CRS onset and progression is lacking. Objectives: To longitudinally evaluate CRS in CF from infancy to school age with paranasal sinus magnetic resonance imaging (MRI). Methods: A total of 64 children with CF (mean age at baseline, 1.1 ± 1.6 yr; range, 0-5 yr) underwent a mean of 5.8 ± 2.2 (range, 3-11 yr) subsequent annual MRI examinations. Additional 24 children (9.2 ± 4.4 yr; range, 3-17 yr) homozygous for the F508del mutation underwent MRI before and at least 2 months after starting lumacaftor/ivacaftor. MRI was assessed using the previously evaluated CRS-MRI score. Results: In infancy, 65-87% of paranasal sinuses were opacified, and mucosal swelling was the dominant abnormality (58-97%). At preschool age (1-5 yr), 79-94% of sinuses were opacified (P < 0.05 vs. infancy), and mucosal swelling was the most dominant abnormality (79-94%; P < 0.05). At school age (at least 6 yr), almost all sinuses were opacified (71-99%; P < 0.001-0.357 vs. preschool age), and mucopyoceles were the dominant abnormality in maxillary and frontal sinuses (53-56%; P < 0.05-0.808). The CRS-MRI sum score increased from 22.4 ± 9.6 in infancy to 34.2 ± 9.6 in preschool age (P < 0.001) and was 34.0 ± 5.7 in school age (P = 0.052). In children under lumacaftor/ivacaftor therapy, the CRS-MRI sum score (-0.5 ± 3.3; P < 0.05) and maxillary sinus subscore (-0.5 ± 1.5; P < 0.05) improved. Conclusions: Longitudinal paranasal sinus MRI detects an early onset and progression of the severity of CRS from infancy to school age, and response to lumacaftor/ivacaftor therapy in children with CF. Our data support its role in the comprehensive noninvasive monitoring of CRS in children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).

Association between outdoor air pollution and chronic rhinosinusitis patient reported outcomes

BackgroundThe aetiology of chronic rhinosinusitis (CRS) is multifactorial with a complex interplay between environmental, microbial endogenous and genetic factors. The impact of outdoor air pollution on prevalence or severity of CRS remains largely unknown.MethodsReal-life geolocation data (2017–2018, Belgium) from 278 CRS patients (2576 health records) using the mySinusitisCoach mobile application were analysed to calculate the patients’ individual exposure to outdoor air pollutants (ozone (O3), black carbon (BC), nitrogen dioxide (NO2) and particulate matter with diameter < 2.5 μm (PM2.5)) and to associate these pollutants with the patients’ sinus related symptoms measured at multiple occasions by visual analogue scale (VAS).ResultsThe adjusted seasonal model for the spring–summer (n = 1000 health entries, N = 83 patients) population revealed an increase of 6.07 (p < 0.0001) in overall CRS symptom scoring for an interquartile range (IQR) increase in exposure to O3 (26.9 μg/m3). An increase of 1.69 (p = 0.05) in total CRS symptom scoring was observed for an IQR increase of PM2.5 (7.1 µg/m3) exposure. Sex-stratified analysis in the spring–summer population showed significant interaction between air pollution and sex with male patients having higher total CRS symptom scores for an IQR increase in exposure to PM2.5 (3.52, p = 0.001), and O3 (8.33, p < 0.0001), while no significant association with symptom severity was seen in the female patients. In the analysis stratified by comorbid asthma, CRS patients with comorbid asthma had higher total CRS symptoms for an IQR increase in exposure to PM2.5 (2.58, p = 0.04) and O3 (7.72, p < 0.0001) while the patients without comorbid asthma had no significant symptom increases.ConclusionExposure to outdoor air pollution is associated with increased symptom severity in CRS patients. The extent to which CRS patients are sensitive to outdoor air pollution exposure varies per season and depends on their sex and comorbid asthma status. mHealth technology has the potential to reveal novel insights on the patients’ exposome and disease severity in the real-life situation.