Annals of Allergy Asthma & Immunology最新文献

Background: Chronic rhinosinusitis with nasal polyps (CRSwNPs) involves persistent sinus inflammation, with emerging evidence suggesting a potential role of rhinovirus (RV) in its pathophysiology. However, whether RV exists in nasal tissues and affects the nasal mucosa after the resolution of infection symptoms remains unknown.

Objective: To investigate the prevalence and impact of silent RV infection in nasal tissues.

Methods: RV loads were detected in the nasal tissues of 47 controls and 101 patients with CRSwNP without respiratory infection. Participants were categorized into RV-positive (+), RV-negative (-), and the "gray zone" groups. Quantitative polymerase chain reaction, Western blotting, and immunofluorescence assays were used to analyze the impact of silent RV infection on the immune status of nasal tissues.

Results: Silent RV infection was prevalent in both control (34%) and CRSwNP (30.7%) tissues, with higher viral loads observed in the nasal polyps. In controls, it was associated with high expression of types 1 and 2 interferon (IFN), type 2 inflammation, interleukin (IL)-17A, and IL-10. In patients with CRSwNP, silent RV infection was associated with lower levels of type 1 IFN, IL-17A, type 2 inflammation, and IL-10 but higher levels of type 2 IFN compared with those without RV infection. Meanwhile, RV (+) nasal polyps exhibited fewer tissue eosinophils and neutrophils than RV (-) nasal polyps.

Conclusion: Silent RV infection was prevalent in the nasal tissues, with a higher viral load detected in the nasal polyps. This silent RV infection is associated with distinct immune responses in healthy controls and patients with CRSwNP, involving differential modulation of IFNs, T_H2 cytokines, IL-17A, IL-10, and eosinophil and neutrophil levels.

Background: Recent studies reveal that M1 macrophages accumulate predominantly in noneosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP). However, the precise mechanisms regulating M1 macrophages and their impact on the epithelial barrier remain unclear.

Objective: To investigate the expression and regulatory role of signaling lymphocytic activation molecule family (SLAMF)8, a molecule exclusively expressed in myeloid cells, in M1 macrophage polarization and its potential contribution to neCRSwNP development.

Methods: We evaluated SLAMF8 expression and its correlation with clinical variables using real-time quantitative polymerase chain reaction and Western blot in sinonasal mucosa samples from CRSwNP and control subjects. Immunofluorescence staining confirmed the co-expression of SLAMF8 with macrophages. After SLAMF8 knockdown, we explored the influence on macrophage M1 polarization and the effect on epithelial-mesenchymal transition (EMT) process and tight junction integrity in epithelial cells through an indirect co-culture system of M1 macrophages with human nasal epithelial cells.

Results: SLAMF8 was highly expressed on M1 macrophages in polyp tissues, notably in neCRSwNP, and correlated with disease severity indices only in neCRSwNP. SLAMF8 knockdown in THP-1 cells reduced M1 macrophage markers (CD86, iNOS, and NLRP3) and decreased secretion of inflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha). Co-culture with M1 macrophage supernatant after SLAMF8 knockdown enhanced epithelial viability, reduced EMT and apoptosis, and up-regulated tight junction markers, occludin and claudin-4, in nasal epithelial cells.

Conclusion: SLAMF8 elevation correlates with the EMT, epithelial tight junction, and disease severity in neCRSwNP. SLAMF8 up-regulation promotes M1 macrophage polarization, which facilitates EMT and impairs nasal epithelial barrier function. SLAMF8 may represent a novel therapeutic target for neCRSwNP.

Background: Donor-acquired allergy (DAA) occurs when donors transfer their allergies to recipients through solid-organ transplant (SOT). However, the risk of DAA in recipients of organs from allergic donors has not been systematically characterized.

Objective: To synthesize the available evidence on the risk of DAA in SOT recipients.

Methods: We searched Embase and MEDLINE databases for original and peer-reviewed articles related to transplant allergy since database inception to February 11, 2024. Two reviewers independently screened records, extracted data, and assessed risk of bias.

Results: The review included 24 studies with 747 SOT recipients and their 135 allergic donors in the category of food, drug, or venom. Only 40 recipients (5.4%) underwent allergy testing to donor allergens, and 23 of them had the testing done before an exposure to donor allergens. Among the 30 recipients (4.0%) who were diagnosed with having DAA based on a clinical reaction or positive allergy testing result, 19 (2.5%) had anaphylaxis to donor allergens. Only the type of SOT (lung or liver) was associated with an increased risk of DAA (odds ratio 88.0, 95% CI 22.5-481.3), with no association found for other organs.

Conclusion: Despite the uncommon occurrence, recipients of organs from allergic donors could be at risk of severe allergic reactions to donor allergens. Although infrequently performed, allergy testing to donor allergens can effectively assess the risk of developing DAA. These findings highlight the risk of DAA and underscore the importance of proactive allergy assessment to prevent unnecessary anaphylaxis in this vulnerable population.

Background: Oral mucosal immunotherapy (OMIT) involves the use of a specifically formulated toothpaste to deliver allergenic proteins to immunologically active areas of the oral cavity. This represents a novel delivery mechanism with several features designed to improve food allergy desensitization. OMIT has advantages over other approaches to allergy immunotherapy due to its targeted delivery and simplified administration.

Objective: To determine the safety, tolerability, and adherence to OMIT with INT301 in adults with peanut allergy.

Methods: The Oral Mucosal Escalation Goal Assessment study enrolled 32 adults, aged 18 to 55 years, with peanut allergy in a 3:1 ratio to receive either an escalating dose of INT301 or a placebo. Entry criteria included a positive skin prick test result with a wheal diameter greater than or equal to 3 mm than control and/or peanut-specific IgE level greater than or equal to 0.35 kU/L. Subjects were required to fail an oral food challenge less than or equal to 100 mg dose of peanut protein. Safety and tolerability were monitored in the 48-week trial period.

Results: All active subjects (100%) tolerated the prespecified protocol at the highest dose. No moderate or severe systemic reactions were observed in the active participants. Nonsystemic adverse reactions were mostly local (oral and nasal cavities), mild and transient. Active subjects adhered to the treatment for 97% of the days in the study, with no withdrawals due to study medication.

Conclusion: In the Oral Mucosal Escalation Goal Assessment trial, INT301 met all primary and secondary end points of safety, tolerability, and adherence. Thus, OMIT seems to be a safe and convenient option for individuals with food allergies. These results support the need for further evaluation in the pediatric population.

Trial registration: ClinicalTrials.gov Identifier: NCT04603300.

Background: Chronic rhinosinusitis (CRS) is traditionally classified into CRS with or without nasal polyps and, more recently, into eosinophilic and noneosinophilic endotypes. Limited research exists on the relationship between CRS subtypes and mucociliary function. This study compares ciliary beat frequency (CBF) across CRS subtypes.

Objective: To investigate CBF across different CRS subtypes and validate spectrally encoded interferometric microscopy (SEIM) against phase-contrast microscopy (PCM) for measuring CBF.

Methods: Sinonasal mucosa from endoscopic endonasal surgery cases were imaged ex vivo at physiological temperatures using PCM and SEIM. CBF measurements were compared between disease states (control vs CRS with nasal polyps [CRSwNPs] vs CRS without nasal polyps [CRSsNPs] and control vs eosinophilic CRS vs noneosinophilic CRS) and between PCM and SEIM.

Results: CRSwNP mucosa (5.77 ± 0.12 Hz) had significantly lower CBF compared with control (6.23 ± 0.11 Hz) (P = .001). Both eosinophilic rhinosinusitis (5.74 ± 0.16 Hz; P = .005) and noneosinophilic CRS mucosa (6.00 ± 0.08 Hz; P = .03) had significantly lower CBF compared with control (6.28 ± 0.11 Hz). There was no significant difference between PCM (7.65 ± 0.60 Hz) and SEIM (7.64 ± 0.51 Hz) as a means of evaluating CBF (P = .36).

Conclusion: Among the CRS subtypes, eosinophilic, noneosinophilic, and CRSwNP are associated with lower CBF compared with healthy controls. SEIM may have value in measuring CBF.

Background: Hereditary angioedema (HAE) is a rare disorder in which unpredictable angioedema attacks significantly affect patient quality of life. Information on patient experiences and perspectives of HAE management within underrepresented racial and ethnic groups is limited.

Objective: To gain insight into the experiences and perspectives of medical care and treatment of HAE among underrepresented racial and ethnic groups in the United States.

Methods: Adult patients diagnosed with having HAE who self-identified as members of an underrepresented racial and/or ethnic group were recruited to participate in a noninterventional, observational, web-based patient survey. The questionnaire included questions on medical history, current and past treatments, resource utilization, and perceived disease severity. The patient-perceived impact of HAE on the quality of life was also measured.

Results: Overall, 139 patients participated in the survey; 33.1% were identified solely as "African American or Black" and 30.2% solely as "Hispanic, Latin American, Latin, or Latine, or Latinx." Before the diagnosis, 12.3% of the patients were satisfied with their HAE-related health care experiences. Many participants experienced difficulties obtaining an HAE diagnosis. Barriers to treatment include insufficient provider knowledge of HAE and misdiagnoses. More than 90% of the patients were satisfied with their care; however, patients reported 6 HAE attacks (median) in the past year and only 10.4% of the patients were attack free. Furthermore, 38.1% found it difficult or very difficult to cover the monthly out-of-pocket costs for HAE-related treatments and 24.6% felt that their provider sometimes/rarely/never considered their individual background when making medical decisions.

Conclusion: Barriers to HAE diagnosis and effective treatment persist among US patients from underrepresented racial and ethnic groups.