Prognostic factors for polyp recurrence in chronic rhinosinusitis with nasal polyps

Clinically meaningful changes in efficacy outcomes in chronic rhinosinusitis with nasal polyposis

“…Although this is not routinely employed uniformly across academic centers, this is an exciting area for future research. Tissue or secretion-based sinus specimens can be evaluated via immunohistochemistry and assays identifying a broad range of inflammatory markers such as IL-2, IL-4, IL-5, IL-6, IL-13, IFN-γ, IFN-inducible T-cell a chemoattractant, TNF-α, granulocyte macrophage colony-stimulating factor, and others [37 ▪▪ ]. Studies following biologic responses have followed levels of eotaxin-3, total IgE, eosinophil cationic protein within nasal secretions [7], as well as serum thymus and activation-regulated chemokine and urinary leukotriene E 4 [12].…”

“…Most studies show at the best moderate correlation between patient-reported symptoms and objective measures of disease such as imaging or endoscopy: for example, one study did show a correlation between endoscopically confirmed polyp recurrence and radiographic metrics (modified Lund–Mackay score), endoscopic metrics (modified Lung–Kennedy score and NPS), and PROM scores [37 ▪▪ ], although another recent and large meta-analysis showed relatively poor correlation between PROMs and the same clinical measures across multiple studies [52 ▪ ]. Although there is not currently a single, all-encompassing outcome measure, there are likely ways to integrate these classes of metrics to detect significant changes in disease severity – for example, in creating a model to predict the recurrence of polyps, one group of authors combined both biomarker data (anti-dsDNA IGG, IL-5, eosinophilic cationic protein levels) with endoscopic data (modified Lund–Mackay score) and patient demographic and clinical data (age, sex, and comorbid asthma) to design a model with a sensitivity of 89% and specificity of 80% [37 ▪▪ ]. However, using polyp recurrence alone as an indicator of disease control may not necessarily capture patients who subjectively report symptomatic improvement despite the recurrence of the disease on an exam.…”

Chronic rhinosinusitis: Future treatments and unmet needs

“…In addition to the type 2 inflammatory pathway, there remain other aspects of inflammation in CRS that have not yet been targeted (Fig 1). These include the type 1/3 inflammatory pathways, coagulation cascade/fibrinolysis, B-cell activation/autoantibodies, 4 the arachidonic acid pathway, and microbes (particularly when they are organized into biofilms). 5 Fibrin deposition and dysregulation of the coagulation cascade may be important in CRSwNP pathogenesis, as eosinophilic and noneosinophilic nasal polyps demonstrate an abundance of extravascular fibrin deposition.…”

“…6 Additionally, nasal polyps accumulate highly activated plasma cells producing autoreactive antibodies and IgE. 4 Mediators of the arachidonic acid pathway are found at elevated levels in nasal polyp tissue, especially in patients with aspirin-exacerbated respiratory disease. Drugs that target these alternative mechanisms include anticoagulants/fibrinolytics, belimumab (anti-B cell-activating factor), 15lipoxygenase inhibitors, and brodalumab and secukinumab (IL-17Ra and IL-17a inhibitors, respectively).…”

“…Thus far, no single clinical phenotype or biomarker has been found to strongly predict successful disease control, although emerging evidence suggests that endotypic biomarkers can augment clinical predictors of outcomes after surgery. 4 Further validation of the most predictive features of disease is needed. Other promising avenues for CRS therapeutics include development of small molecule drugs (SMDs) in tandem with mechanisms to deliver them in a sustained topical manner.…”