Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription using cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper specification.

For adult and pediatric CF sinusitis, ESS yielded clinical improvement as measured primarily by sinonasal symptoms and endoscopic findings. It is unclear if surgical intervention modifies lower airway disease. Future prospective studies with predetermined, objective, and validated outcome measures are needed to determine the effectiveness of surgical intervention for CF-related CRS. Overall evidence Grade B/C.

Biologic therapies may prove beneficial in the treatment of recalcitrant nasal polyposis in select populations. In meta-analysis, anti-IL5 therapy demonstrates a reduction in nasal polyp score. Anti-IgE therapy reduces nasal polyp score in patients with severe comorbid asthma. Additional high-level evidence is needed to assess clinical efficacy.