Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, non-steroidal anti-inflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin-hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner. Objectives: To evaluate omalizumab efficacy against aspirin-hypersensitivity, leukotriene E₄ overproduction, and symptoms during oral aspirin challenge in aspirin-exacerbated respiratory disease using a randomized design. Methods: We performed a double-blind, randomized, cross-over, placebo-controlled, single-centre study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients aged 20–79 years with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to 3-month treatment with omalizumab or placebo, followed by >18-week washout period (cross-over design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E₄ concentration vs time curve in the intention-to-treat population during oral aspirin challenge. Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E₄ concentration vs time curve during oral aspirin challenge in the omalizumab phase (median [interquartile range], 51.1 [44.5–59.8]) was significantly lower compared with the placebo phase (80.8 [interquartile range, 65.4–87.8]) (p<0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (p<0.001). Conclusions: Omalizumab treatment inhibited urinary leukotriene E₄ overproduction and upper/lower respiratory tract symptoms during oral aspirin challenge, resulting in aspirin tolerance in 62.5% of aspirin-exacerbated respiratory disease patients. Clinical trial registration available at https://www.umin.ac.jp/ctr/index.htm, ID: UMIN000018777.

The presence of IgG antibodies (Abs) to Aspergillus fumigatus (Af) is a crucial diagnostic criterion for allergic bronchopulmonary aspergillosis (ABPA). Although precipitation is traditionally used to document IgG Abs, anti-Af serum IgG levels can also be measured by enzyme immunoassay (EIA). However, there are insufficient data on the optimal cut-offs to assess diagnostic performance of the EIA method. This study aimed to determine cut-off levels of IgG binding crude Af extracts or recombinant Asp f 1 (by ImmunoCAP®) and to compare their efficacy for ABPA diagnosis with Af-precipitating Abs. The age distribution of levels of IgG to crude extracts of Af (Af-IgG) and recombinant Asp f 1 (Asp f 1-IgG) was established using sera from 694 healthy controls (HC). Receiver operating characteristic analysis for Af-IgG and Asp f 1-IgG levels for the purpose of ABPA diagnosis was performed in 306 Af-sensitized asthma patients (including 49 ABPA), and cut-offs were determined. An age-dependent decline in the levels of Af-IgG was observed in HC. Thus, cut-offs for Af-IgG levels were determined separately by age as 60 mg/L for patients aged <55 years, and 45 mg/L for those aged ≥55 years. For Asp f 1-IgG, 6.6 mg/L was set as the cut-off regardless of age. Although such IgG testing by EIA allowed a sufficiently good diagnostic performance, Af-precipitating Abs had better diagnostic applicability for ABPA. We determined cut-offs for Af-IgG and Asp f 1-IgG measured by EIA, which can be useful in clinical settings where precipitating Abs are unavailable.

Ryu K, et al. Asia Pac Allergy. 2022 Oct;12(4):e43. https://doi.org/10.5415/apallergy.2022.12.e43

Environmental sensitivity illnesses—including fibromyalgia syndrome (FMS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and multiple chemical sensitivity (MCS)—are chronic, disabling disorders characterized by hypersensitivity to environmental stimuli, persistent fatigue, widespread pain, and neurocognitive and autonomic dysfunction. Although their diagnostic criteria differ, increasing evidence suggests overlapping clinical features and shared biological mechanisms. A unifying hypothesis highlights the gut–brain–immune axis, where alterations in the intestinal microbiome, epithelial barrier dysfunction, and aberrant immune signaling interact with central sensitization and systemic metabolic dysregulation. Recent studies demonstrate reduced microbial diversity, depletion of anti-inflammatory taxa (e.g., Faecalibacterium prausnitzii, Bifidobacterium), and enrichment of pro-inflammatory Clostridium species across these conditions. These shifts likely alter production of short-chain fatty acids, amino acid metabolites, and complex lipids, with downstream effects on mitochondrial function, neuroinflammation, and host energy metabolism. Moreover, emerging clinical interventions—including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation—suggest a potential role for microbiome-targeted therapies, though controlled evidence remains limited. This review synthesizes current knowledge on microbiome alterations in FMS, ME/CFS, and MCS, emphasizing their convergence on metabolic and immune pathways. By integrating microbial, immunological, and neurophysiological perspectives, we propose a microbiome-centered framework for understanding environmental sensitivity illnesses and highlight avenues for translational research and therapeutic innovation.

Vitamin D deficiency has been associated with a range of neurological and allergic conditions. Whether such an association exists in multiple chemical sensitivity (MCS) has not been clarified. This study aimed to compare serum 25-hydroxyvitamin D (25[OH]D) concentrations between patients with MCS and healthy controls. We conducted a case–control study including 80 patients with physician-diagnosed MCS and 5,518 controls. Serum 25(OH)D concentrations were compared using a general linear model with bias-corrected and accelerated bootstrap resampling (1,000 iterations), adjusting for age, sex, season of blood collection, smoking status, body mass index, alcohol intake, and physical activity. Vitamin D deficiency (< 20 ng/mL) was highly prevalent in both groups (78.8% in MCS vs. 75.3% in controls). Median serum 25(OH)D concentrations did not differ significantly between groups (14.6 vs. 15.6 ng/mL, p = 0.622). Adjusted analyses confirmed no statistically significant difference (adjusted difference = 1.07 ng/mL, 95% CI: −0.18 to 2.46, p = 0.119). Despite the high prevalence of vitamin D deficiency, patients with MCS did not differ significantly from controls in serum 25(OH)D concentrations. Although serum 25(OH)D concentrations did not differ significantly between groups, the findings do not exclude a mechanistic role of vitamin D. Local dysregulation of vitamin D receptor signaling or tissue-specific activation may contribute to neuroimmune sensitization in MCS, highlighting the need for system-level investigations.