xRead - Nasal Obstruction (September 2024) Full Articles

20426984, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22741 by Stanford University, Wiley Online Library on [01/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

655

Orlandi et al.

XIV.D.2 Chronic Invasive Fungal Rhinosinusitis (CIFS)

the document offers aggregate evidence on over 180 indi vidual topics, 16 of which are grade A. Interestingly, the number of individual studies cited appears to roughly dou ble with each decline in evidence between grade A and C. This phenomenon suggests that there remains a need to redirect energies toward higher quality research and the knowledge gaps revealed throughout the document which are summarized here (Table XV-1). Further analy sis of studies on CRS management reveal more than twice the number of grade A trials in CRSwNP than CRSsNP. While multiple explanations of this phenomenon may be posited, 1 stands out with important implications for future research opportunities. The presence of obvious pheno typic characteristics (eg, nasal polyps) facilitates patient recruitment into mechanistic, outcomes, and therapeutic studies at the expense of more ill-defined disease states. These patients are then more easily targeted by inves tigators and industry partners willing to perform large, expensive, high quality studies when quantitative thera peutic outcome metrics can be tied to this same pheno type. It is therefore evident that the identification of sensi tive and specific biosignatures of all CRS subtypes has the potential to fundamentally transform RS research by over coming the reliance on phenotype in any study. Prelimi nary work into AECRS, 1010,1751 CRS, 54,61 andCRSwNP 2445 endotypes have already demonstrated the feasibility of this approach. Further large scale multi-institutional studies to both identify and validate non-invasive biosignatures asso ciated with the entire spectrum of the disease therefore represents one of the single greatest unmet needs in CRS research. Among the CRS subtypes, the ICAR-RS document calls out a specific paucity of literature in the role of odon togenic infection in ARS, the contributions of viruses, allergy and immunodeficiency in RARS, and the rela tionship between allergic inflammation and nasal polyps. More generally, this compendium demonstrates that RS is a multifactorial spectrum of diseases resulting from com plex host inflammatory and environmental interactions with significant inter-patient and geographic variability. These attributes are shared by other complex airway dis eases leading to emergence of the concept of the “treatable trait.” 2446 This idea seeks to identify individual character istics which function both as biosignatures of disease and therapeutic targets. This approach has already entered the field of rhinology in the form of biologic therapies targeting specific cytokines implicated in the pathogenesis of type 2 disease. Studies reporting therapeutic efficacy in these XV.B Etiopathogenesis and the Treatable Trait

CIFS, which represents a distinct clinical entity within the spectrum IFS, is defined by its more indolent course. A recent multi-institutional study found the mean time from onset of symptoms to diagnosis was approximately 6months. 2439 In this condition, the host immune system is typically only mildly impaired and is able to mount a vigorous inflammatory response (eg, chronic corticos teroid use or DM without ketoacidosis). 2440 Histopathol ogy typically demonstrates evidence of invasive Aspergillus fumigatus accompanied by extensive chronic inflamma tion, although Zygomycetes infections have also been reported. 2441 While surgical intervention is critical for diag nosis and postoperative surveillance, debridement may be more conservative as long-term antifungal treatments are effective to address residual disease. 2415,2439 GIFS is similar to CIFS in chronicity of symptoms but distinct in histopathology and underlying host factors. This condition is seen in immunocompetent patients and is more prevalent in the Middle East, Northern Africa, and Asia. 1709,2441 The most common presenting symp tom is unilateral proptosis. 2442 As in CIFS, conservative surgery as well as long-term antifungal treatments have been shown to be effective for complete resolution. 2443 In distinguishing CIFS from GIFS, careful histopatholog ical evaluation and history of travel to or living in North ern Africa, Middle East and Asia may be helpful for diag nosis. Histopathology typically demonstrates evidence of invasive Aspergillus flavus 2441 , 2444 accompanied by fibro sis, mild inflammation and non-caseating granulomas. 2440 Aspergillus fumigatus , however, has been reported as the causative agent in some cases in North America. 2442,2443 XV Summary of Knowledge Gaps and Research Opportunities XV.A Rhinosinusitis: State of the Science The breadth and quality of research into virtually all aspects of RS has advanced considerably in the past decade. The sheer scope of the ICAR-RS document is, itself, evi dence of such progress. Across the disparate subjects of epi demiology, pathophysiology, management, and outcomes, XIV.D.3 Granulomatous Invasive Fungal Rhinosinusitis (GIFS)