Allergy and asthma proceedings最新文献

Background: Allergen immunotherapy (AIT) is the most effective treatment for atopic allergic diseases, aiming to induce regulatory T cells (Treg) that modify the immune response to specific allergens, which leads to long-term tolerance and reduced symptoms. Enhancing Treg activity is crucial for improving immunotherapy outcomes. In a previous murine model study, we examined the effects of a synthetic methylated DNA oligodeoxynucleotide (ODN) from the Bl-T2 m5C motif of Bifidobacterium longum subsp. infantis. The ODN that contains the methylated BI-T2 m5C motif (methylated ODNA) sequence conjugated with ovalbumin induced Treg production, whereas ODN that contains the unmethylated BI-T2 m5C motif (unmethylated ODNB) induced proinflammatory responses, which demonstrated the potential of methylated ODNs for AIT. Objective: In building on these results, this study explored the effects of methylated and nonmethylated DNA motifs from B. longum subsp. infantis on inflammation and Treg induction, while investigating the dose-response relationships of methylated Cytosine-phosphate-Guanine (CpG) ODNs for optimal Treg stimulation in clinical applications. Methods: Serum levels of IL-17A, IL-4, IL-10, and transforming growth factor beta (TGF-β) were measured by enzyme linked immunosorbent assay (ELISA), and flow cytometry assessed splenic Treg populations in BALB/c mice receiving graded doses of methylated or unmethylated ODNs. Mice were immunized intraperitoneally with a single 100-μg dose (plan A) or multiple 25 μg (plan B) or 100 μg (plan C) doses. Calf thymic DNA served as a positive control, with phosphate-buffered saline solution and alum as negative controls. Results: Methylated ODNs significantly increased CD25⁺FOXP3⁺ Tregs compared with unmethylated ODNs and controls. Plan A (100 μg) elevated serum IL-10, which indicated effective Treg induction, whereas plan B (four 25 μg doses) did not activate Tregs. Plan C (multiple 100 μg doses) reduced Treg responses, which highlighted a critical dosing threshold for optimal Treg induction. Conclusion: This study demonstrated the potential of methylated DNA motifs as therapeutic agents in AIT. The dose-response relationships of methylated CpG ODNs from B. longum pave the way for clinical applications that target Treg activity in allergic diseases.

Backround: Rapid drug desensitization (RDD) is commonly used for immediate drug hypersensitivity reactions (DHR) across various drugs. In delayed DHRs, the conventional approach is slow desensitization; however, limitations may arise due to drug-specific or disease-related factors. With the increasing role of targeted molecular drugs in delayed DHRs, data on the efficacy of RDD in these contexts remain scarce. Objective: This case series aims to explore the rationale and outcomes of RDD in managing delayed DHRs associated with targeted therapies. Methods: We analyzed data from patients referred to a tertiary university hospital's drug allergy outpatient clinic between January 2021 and April 2024. The subjects experienced delayed DHRs during treatment with targeted drugs and, subsequently, underwent RDD. Results: The drugs administered via RDD included bevacizumab, rituximab, daratumumab, lenalidomide, bortezomib, and carfilzomib. The index reactions included maculopapular eruptions (MPE), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Delayed breakthrough reactions were observed in four of seven patients. RDD with bortezomib was unsuccessful in all three patients, and delayed reactions were observed in all patients with severe cutaneous adverse reactions (AGEP and DRESS). Conclusion: Suggesting significant success of RDD for delayed DHRs induced by targeted therapies may be overly optimistic. Nevertheless, four of seven patients, including one with AGEP, were able to continue their treatment. Managing patients with advanced diseases and delayed DHR poses notable challenges. The risk to patient survival from withholding life-saving medication must be weighed against the risks of desensitization. The low sensitivity of skin tests and the critical waiting period complicate decision-making. Given the unique contribution of targeted agents in the treatment of severe, life-threatening diseases, further research on desensitization is warranted.

Background: The relationship between fibromyalgia (FM) and allergic diseases remains poorly understood, despite emerging evidence that suggests a possible association. Objective: This study aimed to evaluate the prevalence of allergic comorbidities in patients with FM compared with a matched control group. Methods: We conducted a retrospective, population-based case-control study within Leumit Health Services, which caters to ∼750,000 members. Patients meeting the evolving criteria of the American College of Rheumatology from January 2002 to December 2023 were included. Control subjects were selected from the same population base but did not have a diagnosis of FM, were matched 5:1 on sex, age, and year of first membership. All diagnoses were identified by using International Classification of Diseases, Ninth Revision (ICD-9) codes up to March 2024. Results: The analysis included 15,869 patients diagnosed with FM and 79,345 matched controls. There was a predominant female representation (82.1%) in both groups. The prevalence of bronchial asthma was higher in patients with FM compared with the controls, with an odds ratio (OR) of 1.91. The patients with FM also exhibited higher rates of both nonseasonal and seasonal allergic rhinitis, with ORs of 1.60 and 1.30, respectively, and chronic rhinosinusitis without nasal polyps demonstrated an OR of 2.46. Acute allergic conjunctivitis had an OR of 2.05. Skin-related allergies such as contact dermatitis and atopic dermatitis showed ORs of 1.48 and 1.41, respectively. Furthermore, the patients with FM displayed elevated rates of various forms of urticaria and chronic pruritus, alongside higher incidences of food allergies and specific drug allergies. Anaphylactic reactions to food were notably more common in patients with FM, who presented an OR of 2.50. Conclusion: FM is associated with a higher prevalence of allergic diseases compared with the controls. Analysis of these findings suggests the need for allergological assessments in FM management.

Background: The hypertension risk in the co-occurrence of allergic diseases remains largely unknown. Objective: We aimed to investigate the association between allergic diseases co-occurrence pattern and hypertension morbidity and mortality, and to evaluate additive interaction effects between allergic diseases. Methods: A nationally representative population from the U.S. National Health Interview Survey 2012 was enrolled. Hypertension and five specific allergic diseases, including asthma, allergic rhinitis (AR), food allergy (FA), eczema, and other allergy (OA), were determined. Hypertension mortality was identified until December 31, 2019. We evaluated additive interaction effects between two allergic diseases on hypertension risk: relative excess risk due to interaction (RERI) and attributable proportion of joint effect due to interaction (AP) (shown as percentages) were calculated. For modifiable lifestyle factors with significant heterogeneity in the subgroups, we examined the effect modification. Results: Totally, 34,392 participants were enrolled. Four co-occurrence patterns of two allergic diseases were associated with an increased risk of hypertension, including AR + FA (odds ratio [OR] 2.25 [95% confidence interval {CI}, 1.52-3.35]), eczema + OA (OR 1.94 [95% CI, 1.14-3.30]), AR + eczema (OR 1.76 [95% CI, 1.18-2.64]), asthma + AR (OR 1.67 [95% CI, 1.33-2.08]). Five co-occurrence patterns of three allergic diseases were associated with increased risk of hypertension. Additive interactions were seen in AR + FA (RERI, 0.65; AP, 29%), eczema + OA (RERI, 0.43; AP, 22%), AR + eczema (RERI, 0.21; AP, 12%), and asthma + AR (RERI, 0.05; AP, 3%). The significant association between asthma + FA and hypertension was only seen among participants with a body mass index (BMI) ≥ 30 kg/m² (p = 0.021). With a median follow-up of 7.5 years, one co-occurrence pattern of asthma + FA showed a significant increased risk of hypertension mortality (hazard ratio 4.32, 95% CI: 1.52-12.23), with an additive interaction was observed (RERI, 2.33; AP, 52%). Conclusion: We identified several allergic diseases co-occurrence patterns with a significantly increased risk of hypertension morbidity and mortality. Potential biologic additive effect among allergic diseases and effect modification of BMI was found. Precision primary prevention of hypertension is necessary for patients with co-occurring allergic diseases.

Background/Objective: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a high morbidity of anosmia, yet there are few noninvasive biomarkers to measure treatment response. Nitric oxide (NO) is found in the paranasal sinuses at 100 times higher levels than in the lungs and is vital for antimicrobial and/or mucociliary activities and vasodilatory properties. Dupilumab has been shown to improve anosmia in 2 weeks as measured by the University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22), and Loss of Smell (LoS) scoring. We examined the use of NO in various collection methods to monitor anosmia improvement with dupilumab treatment. Methods: Adults with CRSwNP confirmed by computer tomography or endoscopy consented to receive dupilumab 300 mg every two weeks for 16 weeks. Subjects with polyposis despite treatment with steroids and/or a history of sinus surgery were recruited. Measurements of sinus NO (sNO) from the nostril while humming, nasal NO (nNO) while breath-holding, and fractional exhaled nitric oxide (FeNO) while exhaling were collected at baseline and at 1, 2, 4, 8, 12, 16 weeks. Olfactory impairment was measured by using the UPSIT, SNOT-22, and LoS scoring at every visit. Results: Sixteen adults, with a mean (range) age of 43 years (25-53 years) were predominantly women (12/16). Baseline mean (range) sNO values of 434 ppb (203-665 ppb) significantly increased at 2 weeks to a mean (range) of 1150 ppb (684-1616 ppb) (p < 0.05). Significant improvements in the UPSIT, SNOT-22, and LoS scores were found at 2 weeks; a weak correlation of the sNO level with the UPSIT and SNOT-22 scores was noted. No significant changes in the FeNO or nNO values were found. Significant improvement was found specifically with anosmia by the end of 2 weeks. Conclusion: Our small pilot study revealed increased sNO levels in the sinuses as early as 2 weeks after the initial dupilumab administration. Thus, in patients with CRSwNP without asthma, the sNO value has the potential to be used as a noninvasive, objective biomarker for early treatment improvement in anosmia.

Background: Hypereosinophilic syndromes (HES) are marked by persistent eosinophilia, absence of a primary cause, and evidence of eosinophil-mediated organ damage. HES presents a spectrum of clinical manifestations, with prognosis and treatment varying based on the subtype, including myeloid/lymphoid neoplasms and chronic eosinophilic leukemia, not otherwise specified. The primary treatment goal is to reduce eosinophil levels to prevent organ damage, typically by using glucocorticoids and immunosuppressive agents. However, these treatments often have limited efficacy and considerable adverse effects. Objective: Given the central role of interleukin (IL) 5 in eosinophil development and survival, this study aimed to assess the efficacy and safety of anti-IL-5 therapies in patients with HES. Methods: A systematic literature search was conducted on two data bases. The primary outcome was the reduction in absolute eosinophil count, and secondary outcomes included the incidence of flares and adverse events. Data Analysis was conducted, and forest plots were made for each outcome. Results: Four trials were included in the analysis. Ninety-five percent of the patients in the anti-IL-5 group showed a reduction in the absolute eosinophil count compared with 41% in the placebo group (risk ratio [RR] 2.32 [95% confidence interval {CI}, 1.67-3.22]; p = <0.00001; tau statistic (I²) = 0%). Anti-IL-5 therapy was associated with a lower incidence of disease flares, with 15% of the patients in the anti-IL-5 group who experienced flares compared with 30% in the placebo group (RR 0.50 [95% CI, 0.31-0.86]; p = 0.01; I² = 0%). The incidence of adverse events was similar between the two groups (RR 0.99 [95% CI, 0.91-1.07]; p = 0.81; I² = 0%). Conclusion: Anti-IL-5 therapies are effective in reducing eosinophil count and preventing disease flares in patients with HES.

Background: Hypersensitivity reactions (HRs) to iron agents are increasing in parallel with increased use of iron preparations. Objective: We aimed to evaluate the clinical features and our previous desensitization protocol in patients with immediate hypersensitivity reactions (IHR) to iron agents. Methods: We screened the medical records of 96 patients with a history of IHRs to oral or intravenous (IV) iron agents. We evaluated clinical features and diagnostic test results. Furthermore, we assessed the safety and success rate of the desensitization protocol. Results: Forty-seven patients had a history of IHRs to oral iron preparations, whereas 49 patients had a history of IHRs to IV iron agents. Skin-prick tests (SPT) with suspected and alternative oral iron salts were performed in 52.1% of the patients, and five were positive. SPTs and intradermal tests with IV iron products were applied to 67.7% and 65.6% of the patients, respectively, and four yielded positivity. Anaphylaxis was more common in patients hypersensitive to IV iron agents (n = 33) (p < 0.001). In 15 patients for whom iron agents were mandatory, 52 successful desensitizations with ferric carboxymaltose were performed. Conclusion: Our study demonstrated that skin tests were not helpful in the diagnosis of IHRs to iron agents and the parenteral route of administration was related to more severe IHRs. Furthermore, in case of necessity, our IV desensitization protocol generated for ferric carboxymaltose is a safe, effective, and practical treatment of choice.

Background: In recent years, there has been a trend to forgo screening for peanut allergy (PA), even in infants at high risk. This study aimed to better understand the implications of screening for PA before peanut introduction. Objective: We sought to characterize the outcomes of infants who underwent PA skin testing in a tertiary-care allergy clinic. Methods: We performed a retrospective chart review between July 1, 2017, and December 31, 2020, on all infants seen in the allergy clinic who had a peanut skin-prick test and recorded their demographic and clinical characteristics as well as outcomes with regard to PA and tolerance. Results: Twenty percent of the infants screened were identified as having PA. Infants with a PA were more likely to be older at the time of testing, more likely to have another allergist-diagnosed immunoglobulin E (IgE) mediated food allergy, and more likely to have a prescription for a stronger (class VI or stronger) topical steroid. When conducted, oral food challenge was safe, with the majority of infants being treated with observation or antihistamines. A large percentage of infants with a PA developed tolerance during the follow-up period. Conversely, 5% of the infants who were initially tolerant developed a new PA. Conclusion: PA is associated with severe atopic dermatitis and other IgE-mediated food allergies. However, it is unclear if there is a benefit from screening infants before peanut introduction. It is important to monitor for resolution in the infant population.

Problem-based learning (PBL) is an interactive learning model well accepted in undergraduate medical education. Utilization of PBL in most postgraduate continuing medical education (CME) programs has been limited. The traditional didactic lecture (TDL) model alone in CME programs, although much more commonly used, may fail to assess self-efficacy, educational needs, and appropriate use of shared decision-making (SDM). These aspects of practice are essential, and assessment of these skills is necessary to ensure effective change in physician behavior to improve patient outcomes. PBL case discussions during CME breakout groups foster a participant-centered interactive environment that strengthens critical thinking, team collaboration, and clinical reasoning. Through engagement with clinically relevant cases, PBL allows for tailored educational interventions. Integrating or blending PBL with TDL engages the learners in a real-world case discussion first, followed by succinct post-PBL lectures, which are uniquely "in context" to the actual case discussion. The post-PBL lectures are designed to address knowledge gaps that may have been uncovered during the PBL case discussions and reinforce practice guidelines to correct identified misinformation by learners. The PBL approach not only improves knowledge retention but also leads to better adherence to clinical guidelines by producing significant changes in physician behavior, leading to higher-value patient care. Furthermore, PBL promotes effective and appropriate SDM. Still, there are challenges to PBL implementation in postgraduate CME, including logistical constraints and facilitator training requirements. Thus far, integration of PBL is variable across fields of medicine. Further research is needed to optimize PBL application in postgraduate training. This review advocates for a shift from passive learning systems by TDLs alone to interactive educational models, e.g., blended PBL, which synergizes the two adult learning theories.