Allergic fungal rhinosinusitis

Allergic fungal rhinosinusitis is a phenotype of chronic rhinosinusitis with nasal polyposis, characterized by type 1 hypersensitivity to fungi, eosinophilic mucin with fungal hyphae in sinus secretions, and propensity for mucocele formation and bone erosion. Although its differentiation from other forms of chronic polypoid rhinosinusitis with eosinophilic mucin is sometimes problematic, type 1 hypersensitivity is a component of the disease process. Medical and surgical management can be augmented by immunotherapy directed toward the patient's specific allergen sensitivities. The primary rationale for immunotherapy is to control the allergic diathesis that may be contributing to the patient's chronic sinus inflammation.     

Biotherapy and treatment of adult primary chronic rhinosinusitis with nasal polyps: Cellular and molecular bases

The present article reviews the molecular and cellular mechanisms involved in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwCRSwNP) and underlying the action mechanisms of biotherapies. Biotherapy uses substances naturally produced by the organism or their specific antagonists targeting a proinflammatory mechanism. CRSwCRSwNP is a form of chronic rhinosinusitis (CRS), which is classically subdivided in to 2 types according to the presence of polyps. In recent years, the concept of endotypes emerged, with a more exhaustive definition of the types of CRS according to inflammatory mechanism, with a view to developing personalized treatments. CRSwNP pathophysiology is poorly understood. Polyps arise from a primary epithelial lesion in a context of chronic local inflammation, mainly type 2 in Europe, implicating eosinophils, IgE, Th2 cytokines (IL-4/IL-13, IL-5) and T and B cells. Biotherapy seems promising in CRSwNP. The present review details the various pathophysiological pathways underlying the action mechanisms of biotherapies, and the various published studies, assessing efficacy and mode of action in the treatment of CRSwNP.     

Current understanding of allergic fungal rhinosinusitis

Studying the pathophysiology of allergic fungal rhinosinusitis (AFRS) has proved challenging. While this clinical entity is easily distinguishable based on the clinical criteria set forth by Bent and Kuhn twenty-five years ago, studies examining type 2 inflammatory profiles in AFRS can make it seem more alike other CRS subtypes than it is different. Still, evolving research seems to clearly delineate this subtype from others in CRS. This review will critically evaluate the evolution of research examining the pathophysiology of AFRS and will conclude with a summary of the special considerations in the management of this fascinating disease.     

Systematic review of outcomes for endoscopic sinus surgery and subsequent aspirin desensitization in aspirin-exacerbated respiratory disease

ObjectiveTo review and evaluate outcomes of patients with aspirin-exacerbated respiratory disease (AERD) following endoscopic sinus surgery and subsequent aspirin desensitization.MethodsElectronic searches of OVID MEDLINE (1948 to September 10, 2019), EMBASE (1980 to September 10, 2019), and PubMed were performed on September 10, 2019. A systematic review of the literature was performed using the 2009 PRISMA guidelines. Studies with both preoperative and postoperative data for patients with AERD who underwent sinus surgery and aspirin desensitization were considered appropriate for inclusion. Publications were written in English and included patients aged 18 years or older.ResultsSix studies met inclusion criteria for this systematic review. The primary outcome measure was change in symptom profile measured by patient-reported quality of life scores. The results demonstrate statistically significant improvement in symptoms following endoscopic sinus surgery, with sustained improvement following aspirin desensitization. Revision surgery rates were significantly lower in patients maintained on aspirin therapy.ConclusionThis review suggests that surgery followed by aspirin desensitization results in improvement in both subjective and objective outcome measures. The adjunctive use of aspirin desensitization allows for long-term stability in symptom scores. Recurrence of polyps and worsening symptoms requiring revision surgery occurs when aspirin maintenance therapy is interrupted.     

JESREC score and mucosal eosinophilia can predict endotypes of chronic rhinosinusitis with nasal polyps

Objective

Recently, JESREC score and mucosal eosinophil count have been used to diagnose eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, it remains unknown whether the subtypes of CRS diagnosed by these criteria have different endotypes. In the present study, we investigated whether JESREC score and mucosal eosinophil count were appropriate for classification of CRS subgroups into endotypes.

Comparison of subjective and objective assessment of glucocorticoid response in nasal polyps: a preliminary study

Background: Glucocorticoids (GC) therapeutic response in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) varies markedly.

Aims/Objectives: To compare the utility between subjective and objective assessment of GC sensitivity in reflecting the impact of GC on systemic and local eosinophilia in CRSwNP patients.

Material and methods: Twenty-six patients with CRSwNP were enrolled. All patients were given 30?mg of prednisone once daily for 7 days and subsequently classified into subjectively GC-sensitive and -insensitive subgroup or objectively GC-sensitive and -insensitive subgroup. The numbers of eosinophils and neutrophils in blood and polyp tissues were compared between GC-sensitive and GC-insensitive subgroup.

Results: 17/26 (65.4%) patients were subjectively and 8/26 (30.8%) patients objectively sensitive to GC treatment. The absolute number and percentage of eosinophils in blood were decreased both in GC-sensitive and -insensitive subjects after GC treatment. In addition, a significant reduction in tissue eosinophil percentage was only observed in objectively GC-sensitive subjects after GC treatment. Furthermore, the change of tissue eosinophil percentage in objectively GC-sensitive subjects was significantly higher than that in objectively GC-insensitive subjects.

Conclusions and significance: Objective assessment may better reflect oral GC response in tissue eosinophilic inflammation than subjective assessment in patients with CRSwNP.     

Objective and subjective sinonasal and pulmonary outcomes in aspirin desensitization therapy: A prospective cohort study

ObjectiveAspirin exacerbated respiratory disease (AERD) patients are challenging to manage with sinonasal and pulmonary symptoms refractory to maximal medical and surgical therapies. Our objective was to comprehensively examine objective and validated, disease-specific subjective sinonasal and pulmonary outcomes of aspirin (ASA) desensitization therapy in this patient population.MethodsProspective cohort study at an academic tertiary center. AERD patients with a history of chronic rhinosinusitis with nasal polyposis (CRSwNP), prior diagnosis of asthma, and a history of ASA sensitivity were eligible for inclusion. Patients underwent ASA desensitization using an established institutional protocol and continued on a 650 mg twice daily maintenance dose. Baseline Sinonasal Outcome Test (SNOT-22) and Asthma Control Questionnaire (ACQ) responses, acoustic rhinometry, peak flow readings, and endoscopic scoring of nasal polyps were recorded prior to desensitization and after 6 months of maintenance therapy.ResultsTwelve patients were recruited for participation and underwent desensitization. Eight patients continued maintenance therapy and follow up at 6 months. Prior to desensitization, patients reported bothersome sinonasal symptoms with a median SNOT-22 score of 30.0 ± 34.5 (interquartile range (IQR)). There was significant improvement after 6 months of maintenance therapy to a median SNOT-22 score of 18.5 ± 17.3 (p = 0.025, Wilcoxon signed rank test). Acoustic rhinometry, endoscopic scores, ACQ and forced expiratory volume values remained stable at 6 months.ConclusionsAERD patients may benefit from ASA desensitization with subjective sinonasal symptom improvement at 6 months and stable asthma and objective sinonasal measures. Further discussion is needed in the otolaryngology community regarding ASA desensitization in AERD management.     

The importance of timely diagnosis of aspirin-exacerbated respiratory disease for patient health and safety

BackgroudAspirin-exacerbated respiratory disease (AERD) is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.ObjectiveTo characterize the most common timeline for development of the clinical triad [asthma, nasal polyposis, and reactions to nonsteroidal anti-inflammatory drugs (NSAIDs)], identify barriers to prompt diagnosis of AERD, and describe indications for an aspirin challenge to facilitate accurate diagnosis.MethodsSix hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women's Hospital AERD registry. Patient reported age at disease onset of asthma, nasal polyposis, and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.ResultsOf the 697 patients identified, diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction, although there was considerable variability between patients.ConclusionsPrompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients. Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history, specifically in patients who take daily low-dose aspirin, leukotriene modifiers, avoid NSAIDs, or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.