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Background: Acute allergic reactions to messenger RNA (mRNA) vaccines are rare but may limit public health immunization efforts. Objectives: To characterize suspected allergic reactions to the first dose of coronavirus disease 2019 (COVID-19) mRNA vaccine and to assess the safety and utility of a two-step graded-dose protocol for the second dose of the Pfizer-BioNTech vaccine in patients with a history of low suspicion of anaphylaxis to their first dose. Methods: This was a retrospective evaluation of referrals to the allergy and immunology clinic for a presumed allergic reaction to the first dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) between December 17, 2020, and February 28, 2021. Recommendations for the second dose and outcomes were evaluated by trained board-certified allergists. Results: Seventy-seven patients presented with a Pfizer-BioNTech reaction (56 [72.7%]) or with a Moderna reaction (21 [27.3%]). Most patients (69.7%) had symptom onset within 4 hours. Most commonly reported symptoms were cutaneous (51.9%), cardiovascular (48.1%), and respiratory (33.8%) symptoms. Recommendations included to proceed with the single dose (70.1%), two-step graded dose (19.5%), or deferral (10.4%). Twelve of 15 patients completed the second dose with a graded-dose protocol. Of these patients, five reported at least one or more similar symptoms as experienced with their first dose. Conclusion: Of the patients with presumed allergic reactions to their first dose of COVID-19 mRNA vaccine, most were able to safely receive the second dose. For those with a low suspicion of anaphylaxis, the two-step graded protocol with the Pfizer-BioNTech vaccine was well tolerated. A graded-dose protocol could be an effective strategy for second-dose vaccination in those who may otherwise defer the second dose.

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high propensity for recurrence. Studies suggest that eosinophilia influences disease severity and surgical outcomes, but the selection of sinonasal site for measuring eosinophilia has not been examined. The aim of this study was to investigate how region-specific tissue eosinophilia affects radiographic severity, comorbidity prevalence, and polyp recurrence risk following sinus surgery.Eosinophil cationic protein (ECP) levels in uncinate tissue (UT) and nasal polyp (NP) homogenates from 116 CRSwNP patients were measured using enzyme-linked immunosorbent assay (ELISA). Clinical history, radiographic severity, and time to polyp recurrence were obtained from electronic health records. The correlations between baseline Lund-Mackay scores and comorbidities were compared between UT and NP ECP levels. Cox regression and Kaplan-Meier analysis were then performed to assess whether UT or NP ECP better predicted recurrence. Censoring occurred at 4 years or at last follow-up if there was no endoscopic diagnosis of recurrent polyps.Lund-Mackay scores were significantly correlated with UT and NP ECP (r = 0.46 and 0.26 respectively, p0.05). UT but not NP ECP was significantly higher in patients with asthma (p0.01) and aspirin-exacerbated respiratory disease (AERD) (p0.05). Polyp recurrence risk was only significantly higher for patients with eosinophilic UT tissue (hazard ratio [HR] = 2.84, p = 0.025). When measured in NP, eosinophilia did not predict recurrence.Although ECP in NP was higher than in UT tissue, eosinophilia in UT tissue was a more clinically coherent biomarker of baseline radiographic severity, comorbid asthma and AERD, and prospective polyp recurrence risk than NP eosinophilia.

Responsiveness, or sensitivity to clinical change, is important when selecting patient-reported outcome measures (PROMs) for research and clinical applications. This study compares responsiveness of PROMs used in chronic rhinosinusitis (CRS) to inform the future development of a highly responsive instrument that accurately portrays CRS patients' symptom experiences.Adult CRS patients initiating medical therapy (MT; n = 143) or undergoing endoscopic sinus surgery after failing MT (ESS; n = 123) completed the 22-item Sino-Nasal Outcome Test (SNOT-22), European Position Statement on Rhinosinusitis (EPOS) visual analog scale (VAS), and 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) at baseline and 3 months after treatment. Cohen's d and paired t statistics were used to evaluate the responsiveness of each measure.Fifty-two (36.4%) subjects and 42 (34.1%) subjects in the MT and ESS groups, respectively, completed baseline and 3-month questionnaires. Subjects with and without 3-month data were similar with respect to baseline demographics, VAS scores, and SNOT-22 scores (p0.05). In MT patients, CRS-specific measures, like VAS (d = -0.58, p0.01; t = -1.81, p0.05) and SNOT-22 (d = -0.70, p0.01; t = -3.29, p0.05) scores, were more responsive than PROMIS-29 general health domains (p0.05 for Cohen's d). In ESS patients, VAS (d = -1.97; t = -9.63, both p0.01) and SNOT-22 (d = -1.56; t = -9.99, both p0.01) scores were similarly more responsive, although changes in PROMIS-29 domains of Fatigue (d = -0.82, p = 0.01; t = -4.63, p0.01), Sleep Disturbance (d = -0.83; t = -3.77, both p0.01), and Pain Intensity (d = -1.0; t = -5.67, both p0.01) were significant. All 22 individual SNOT-22 items differed significantly after surgery, whereas only 8 items were consistently responsive after MT.For both MT and ESS patients, CRS-specific PROMs are more responsive to posttreatment clinical changes than general health measures. Still, the SNOT-22 contains items that likely decrease its overall responsiveness. Our findings also indicate that existing PROMs had a greater response to ESS than MT.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by tissue eosinophilia that is associated with poor prognosis. Recent findings that proton pump inhibitors (PPIs) directly modulate the expression of eotaxin-3, an eosinophil chemoattractant, in patients with eosinophilic diseases suggest therapeutic potential for PPIs in those with CRSwNP.We assessed the effect of type 2 mediators, particularly IL-13 and eotaxin-3, on tissue eosinophilia and disease severity in patients with chronic rhinosinusitis (CRS). Further investigation focused on PPI suppression of eotaxin-3 expression in vivo and in vitro, with exploration of underlying mechanisms.Type 2 mediator levels in nasal tissues and secretions were measured by using a multiplex immunoassay. Eotaxin-3 and other chemokines expressed in IL-13-stimulated human sinonasal epithelial cells (HNECs) and BEAS-2B cells with or without PPIs were assessed by using ELISA, Western blotting, real-time PCR, and intracellular pH imaging.Nasal tissues and secretions from patients with CRSwNP had increased IL-13, eotaxin-2, and eotaxin-3 levels, and these were positively correlated with tissue eosinophil cationic protein levels and radiographic scores in patients with CRS (P .05). IL-13 stimulation of HNECs and BEAS-2B cells dominantly induced eotaxin-3 expression, which was significantly inhibited by PPIs (P .05). Patients with CRS taking PPIs also showed lower in vivo eotaxin-3 levels compared with those without PPIs (P .05). Using intracellular pH imaging and altering extracellular KOur results demonstrated that PPIs reduce IL-13-induced eotaxin-3 expression by airway epithelial cells. Furthermore, mechanistic studies suggest that the nongastric H,K-ATPase is necessary for IL-13-mediated epithelial responses, and its inhibitors, including PPIs, might be of therapeutic value in patients with CRSwNP by reducing epithelial production of eotaxin-3.

Chronic rhinosinusitis (CRS) is a heterogeneous chronic disease characterized by local inflammation of the sinonasal tissues. The pathogenesis of CRS remains controversial, but it has been associated with the accumulation of various immune and inflammatory cells in sinus tissue.The objective of this study was to investigate the expression of the chemokine CCL23, which is known to bind to CCR1 and recruit monocytes, macrophages, and dendritic cells, in patients with CRS.We collected nasal tissue from patients with CRS and control subjects. We assayed mRNA for CCL23 by using real-time PCR and measured CCL23 protein by means of ELISA, immunohistochemistry, and immunofluorescence.CCL23 mRNA levels were significantly increased in nasal polyps (NPs) from patients with CRS with nasal polyps (CRSwNP; P .05) compared with inferior turbinate and uncinate tissue from patients with CRS or control subjects. CCL23 protein levels were also increased in NPs, although these levels were not statistically significant. Immunohistochemical analysis revealed CCL23 expression in mucosal epithelial cells and inflammatory cells, but accumulation of CCL23(+) inflammatory cells occurred only in NPs. Immunofluorescence data showed CCL23 colocalization with eosinophil cationic protein-positive eosinophils. The concentration of CCL23 in NPs positively correlated with the concentration of eosinophil cationic protein, suggesting that eosinophils are major CCL23-producing cells in NPs. Finally, we found that CCL23 protein levels were significantly increased in NPs from patients with CRSwNP with aspirin sensitivity.Overproduction of CCL23 in NPs might contribute to the pathogenesis of eosinophilic CRSwNP through the recruitment of CCR1(+) inflammatory cells, including monocytes and macrophages, and the amplification of local inflammation.