Jerschow, Elina

Interleukin 33 (IL-33) is a cytokine of the IL-1 family that acts as an alarmin in both innate and adaptive immunity. IL-33 is constitutively nuclear in epithelial and endothelial cells, where its activity is limited by nuclear retention. Release of IL-33 in response to cellular stress or injury can mediate type 2 immune responses or tissue repair, depending on the local tissue environment. IL-33 activity is regulated at multiple levels, including nuclear retention, oxidation, proteolytic processing, and metabolic regulation. Following its release, oxidation rapidly suppresses IL-33 activity, while mast cell and neutrophil proteases can generate smaller active fragments that target cells expressing the IL-33 ST2 receptor. Simultaneously, tissue metabolic status influences cellular responsiveness through the mTORC1 and AMPK pathways, which link metabolic capacity to effector function. These conditions may explain why IL-33 can mediate an inflammatory response, but in other circumstances, it contributes to tissue repair. Such pleiotropic properties may also underline the variability in clinical responses to IL-33/ST2-targeted therapies across various diseases. The appreciation of IL-33 as a cytokine whose activity is conditioned by its structural, redox, and metabolic environment is critical to optimizing its therapeutic potential as a target.

Key points Staphylococcus aureus showed a significant increase in relative abundance in CRSwNP patients following endoscopic sinus surgery compared to pre‐surgery samples. Other Staphylococcus species were found to correlate positively with S. aureus in patients with nasal polyps; among those, S. caprae correlated strongly while being the most represented in samples. Patients with recurrent nasal polyp growth exhibited a substantially greater postoperative increase in the relative abundance of S. aureus .

ABSTRACT Nonsteroidal anti‐inflammatory drugs (NSAID)‐exacerbated respiratory disease (N‐ERD) is a mainly type 2 inflammatory condition that combines asthma, nasal polyps, and hypersensitivity to NSAIDs. Its pathogenesis involves both upper and lower airways, yet most studies to date have examined these compartments separately. It remains unclear whether the molecular mechanisms in the nose, sinuses, and lungs are distinct or overlapping—an important gap, given that clinical manifestations of N‐ERD involve both sites. In this review, we summarize available omics studies—transcriptomics, proteomics, metabolomics, and epigenomics—performed on upper and lower airways in patients with N‐ERD. While omics approaches have revealed new molecular insights, comparisons across studies are limited by heterogeneity in design, controls, and methodology. We emphasize the need for integrated multi‐omics analyses and standardized frameworks to better characterize the disease across airways. Such efforts are essential for identifying robust biomarkers and therapeutic targets and for moving toward a systems‐level understanding of N‐ERD.

Objective To evaluate long-term effects of COVID-19 on auditory and vestibular symptoms in a diverse cohort impacted by the initial 2020 COVID-19 infection in the pandemic's epicenter, before vaccine availability. Study Design Cohort study of individuals with confirmed COVID-19 infection, diagnosed in the March–May 2020 infection wave. A randomized, retrospective chart review of 1,352 individuals was performed to identify those with documented new or worsening auditory (aural fullness, tinnitus, hyperacusis, hearing loss) or vestibular (dizziness, vertigo) symptoms. Those with documented symptoms (613 of the 1,352 initial cohort) were contacted for a follow-up telephone survey in 2021–2022 to obtain self-report of aforementioned symptoms. Setting Academic tertiary hospital system in Bronx, NY. Patients Adults 18 to 99 years old with confirmed COVID-19 infection, alive at time of review. One hundred forty-eight charts were excluded for restricted access, incomplete data, no COVID-19 swab, or deceased at time of review. Intervention Confirmed COVID-19 infection, March to May 2020. Main Outcomes Measures Auditory and vestibular symptoms documented in 2020 medical records and by self-report on 2021 to 2022 survey. Results Among the 74 individuals with documented symptoms during the first 2020 COVID-19 wave who participated in the 2021 to 2022 follow-up survey, 58% had documented vestibular symptoms initially in 2020, whereas 43% reported vestibular symptoms on the 2021 to 2022 survey (p = 0.10). In contrast, 9% had documented auditory symptoms initially in 2020 and 55% reported auditory symptoms on the 2021 to 2022 survey (p < 0.01). Conclusions COVID-19 may impact vestibular symptoms early and persistently, whereas auditory effects may have more pronounced long-term impact, suggesting the importance of continually assessing COVID-19 patients.