Allergology International最新文献

Background

Despite clinical implications, the pathogenesis of mucus plugging in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) remains unclear. We hypothesized that distinct airway microbiomes might affect mucus plugging differently among ACO, asthma, and COPD and among different extents of airway eosinophilic inflammation.

Methods

The sputum microbiome, sputum cell differential count, and mucus plug score on computed tomography were cross-sectionally evaluated in patients with chronic airflow limitation.

Results

Patients with ACO, asthma, or COPD were enrolled (n = 56, 10, and 25). Higher mucus plug scores were associated with a greater relative abundance of the phylum Proteobacteria (rho = 0.29) only in patients with ACO and a greater relative abundance of the phylum Actinobacteria (rho = 0.46) only in patients with COPD. In multivariable models including only patients with ACO, the presence of mucus plugs was associated with a greater relative abundance of the phylum Proteobacteria and the genus Haemophilus, independent of smoking status, airflow limitation, and emphysema severity. Moreover, the mucus score was associated with a greater relative abundance of the genus Streptococcus (rho = 0.46) in patients with a high sputum eosinophil count (n = 22) and with that of the genus Haemophilus (rho = 0.46) in those with a moderate sputum eosinophil count (n = 26).

Conclusions

The associations between mucus plugging and the microbiome in ACO differed from those in COPD and asthma. Greater relative abundances of the phylum Proteobacteria and genus Haemophilus may be involved in mucus plugging in patients with ACO and moderate airway eosinophilic inflammation.

Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma is indicated in cases of HDM-sensitized allergic asthma with normal lung function. HDM-SCIT improves asthma symptoms and AHR, and decreases the medication dose. Importantly, AIT can improve other allergic diseases complicated by asthma, such as allergic rhinitis, which can also contribute to the improvement of asthma symptoms. Several studies have suggested that HDM-SLIT also attenuates the risk of asthma exacerbations, and improves lung function in asthma cases with allergic rhinitis. Furthermore, AIT can modify the natural course of allergic diseases, including asthma. For example, the effects of AIT are maintained for at least several years after treatment discontinuation. AIT can prevent the onset of asthma when introduced in allergic rhinitis, and can also inhibit or reduce new allergen sensitizations. Recent data have suggested that AIT may suppress non-targeted allergen-induced immune responses in addition to targeted allergen-induced responses, and suppress infections of the lower respiratory tract by enhancing IFN responses.

Background

To avoid complete elimination of hen eggs (HE) from diet, we introduced a very-low-dose (VLD) oral food challenge (OFC) in patients with severe HE allergy in 2019. Herein, we investigated the efficacy of VLD HE OFC for achieving the full dose OFC.

Methods

Patients with an overt allergic reaction to LD (1/32 HE [≤100 mg]) or less, egg white (EW) protein within 6 months were included. In the VLD group, patients not achieving full-dose OFC (1/2 HE: 1600 mg EW protein) within 2 years were excluded. We retrospectively compared the rate of passing a full-dose OFC between patients who underwent a LD OFC before 2019 (LD group) and those who underwent a VLD OFC (1/100 HE: 32 mg EW protein) after 2019 (VLD group). The period for passing the full-dose OFC was evaluated using Kaplan–Meier survival analysis.

Results

We enrolled 411 and 111 patients in the LD and VLD groups, respectively. The median age at OFC initiation was 2.2 [1.5–3.6] and 2.1 [1.4–3.2] years in the LD and VLD groups, respectively. EW- and ovomucoid-specific IgE levels were 38.3 (12.5–72.9) and 21.0 (8.3–46.2) kU_A/L in the LD group and 49.8 [18.8–83.9] and 32.1 [15.6–67.8] kU_A/L in the VLD group, respectively. Over 4 years, the LD and VLD groups passed the full-dose OFC at rates of 70 and 95%, respectively, with significant differences (log-rank test, P < 0.001).

Conclusions

VLD HE OFC may contribute to passing a full-dose OFC in patients with severe HE allergies.

Background

Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES.

Methods

This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course.

Results

The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p < 0.01). The median FHb, FLf, and FCp ratios were 3.25, 9.09, and 9.79 in the FPIES group and 1.08, 1.29, and 1.49 in the control group, respectively. In the remission group, several patients had fluctuating fecal markers despite negative OFC, and one patient was diagnosed with FPIES by OFC with increased load. Receiver operating characteristic curve analyses revealed high diagnostic performance for each fecal marker in FPIES.

Conclusions

Sequential fecal marker examination proved valuable in diagnosing Solid-FPIES and evaluating the degree of gastrointestinal inflammation.

Background

We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies.

Methods

In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]).

Results

At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was –39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: –33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified.

Conclusions

Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

Background

Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers.

Methods

We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance.

Results

Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores.

Conclusions

Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.