Allergology International最新文献

Background

Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma.

Methods

The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored.

Results

Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20–35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence.

Conclusions

Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.

Background

Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders.

Methods

Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines.

Results

AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P < 0.001), restored filaggrin (Flg) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed Il17a and l17f expression, whereas baricitinib did not. Baricitinib suppressed Il4, Il19, Il33 and Ifnb expression, whereas T-5224 did not. Il1a, Il1b, Il23a, Ifna, S100a8, and S100a9 expression was cooperatively downregulated following the combined use of T-5224 and baricitinib. In vitro, T-5224 restored the expression of FLG and loricrin (LOR) (P < 0.05) and suppressed IL33 expression (P < 0.05) without affecting cell viability and cytotoxicity.

Conclusions

Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.

Background

Although it has been reported that cellular senescence is important in the pathogenesis of asthma, the differential effects of diesel exhaust particle (DEP)-induced cellular senescence on the development of asthma according to age have not been thoroughly studied.

Methods

We first confirmed that DEP induced cellular senescence in mouse lungs, and then that DEP-induced cellular senescence followed by intranasal instillation of a low-dose house dust mite (HDM) allergen resulted in murine asthma. Second, we examined age-dependent differential effects using 6-week-old (young) and 18-month-old mice (old), and tested whether the mammalian target of the rapamycin (mTOR) pathway plays an important role in this process. Finally, we performed in vitro experiments using human bronchial epithelial cells (HBEC) originating from young and elderly adults to identify the underlying mechanisms.

Results

DEP induced cellular senescence in the airway epithelial cells of young and old mice characterized by increased senescence-associated beta-galactosidase, S100A8/9, and high mobility group box 1 (HMGB1) expressions. DEP-induced cellular senescence with subsequent exposure to a low-dose HDM allergen resulted in asthma in young and old mice. Rapamycin (mTOR pathway inhibitor) administration before DEP instillation significantly attenuated these asthmatic features. In addition, after treatment with a low-dose HDM allergen, S100A9 and HMGB1 over-expressed HBEC originating from young and elderly adults greatly activated co-cultured monocyte-derived dendritic cells (DCs).

Conclusions

This study showed that DEP-induced senescence made both young and old mice susceptible to allergic sensitization and resultant asthma development by enhancing DC activation. Public health efforts to reduce DEP exposure are warranted.

Background

This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies.

Methods

Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible.

Results

Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years.

Conclusions

Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.

Background

Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders, which often coexist and interact with each other. Obesity is an important risk factor shared by them. The rate of obesity is lower in Japan versus Western countries. Hence, the co-existence of asthma and OSA has not been investigated in Japan.

Methods

Ninety-seven outpatients with asthma were recruited. Patients wore a portable monitor for sleep study. Background data, pulmonary function, blood tests, and patient-reported outcomes including gastroesophageal reflux disease, sleepiness, sleep quality, asthma control, cough and respiratory symptoms, and health status, were assessed.

Results

Of the patients, 19 (19.6 %), 40 (41.2 %), 24 (24.7 %), and 14 (14.4 %) were classified into non-, mild, moderate, and severe OSA groups. Non-OSA patients were younger than those in other groups (p < 0.05). The BMI of patients with moderate and severe OSA, was higher than that of non-OSA patients (p < 0.05). Pulmonary function, FeNO, serum IgE, and the number of peripheral eosinophils were not significantly different between groups. Nonetheless, compared with the other groups, treatment step was the highest, and the Asthma Control Test, Leicester Cough Questionnaire, COPD Assessment Test, and Asthma Health Questionnaire-33 yielded worst scores in the severe OSA group, and predicted the severe OSA after adjustment by BMI.

Conclusions

Moderate and severe OSA are highly prevalent among patients with asthma in Japan. Pulmonary function did not differ between groups. However, patients with asthma and severe OSA were linked to more asthma treatment, worse asthma control, more symptoms and cough, and worse health status.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES. The guidelines have served as a resource in the recognition and management of FPIES, contributing to an increased awareness of FPIES. Since then, new evidence has emerged, shedding light on adult-onset FPIES, the different phenotypes of FPIES, the recognition of new food triggers, center-specific food challenge protocols and management of acute FPIES. Emerging evidence indicates that FPIES impacts both pediatric and adult population. As a result, there is growing need to tailor the consensus guidelines to capture diagnoses in both patient groups. Furthermore, it is crucial to provide food challenge protocols that meet the needs of both pediatric and adult FPIES patients, as well as the subset of patients with atypical FPIES. This review highlights the evolving clinical evidence relating to FPIES diagnosis and management published since the 2017 International FPIES Guidelines. We will focus on areas where recent published evidence may support evolution or revision of the guidelines.

Background

Washing with water is not inferior to washing with soaps and detergents in children with atopic dermatitis (AD) in remission during the fall-winter seasons. We investigated whether this finding varies during summer based on the type of cleanser (soaps and detergents).

Methods

This evaluator-blinded, pragmatic, randomized, and non-inferiority study enrolled patients with AD whose eczema was controlled following regular steroid ointment application 2 days/week. For 8 ± 4 weeks, participants washed their upper and lower limbs with a cleanser on one side and with water alone on the other. Each participant chose either a weakly alkaline soap or an acidic detergent. The primary outcome was the Eczema Area and Severity Index (EASI) score at week 8 ± 4.

Results

The data of 43 of the 47 registered participants were analyzed. The median patient age was 44 (23–99) months; 28 and 15 participants chose weakly alkaline and acidic cleansers, respectively. At week 8 ± 4, EASI scores of the water and cleanser sides were 0.00 (0.00–0.40) and 0.15 (0.00–0.40), respectively (p = 0.74). The difference between both sides was 0.00 (−0.07 to 0.14); the limits of the 95 % confidence interval did not reach the pre-specified non-inferiority margin. No difference was observed in the median Patient-Oriented Eczema Measure score, number of additional steroid ointment applications, and occurrences of skin infections. There were no differences between the cleanser types in any of the results.

Conclusions

We demonstrated that washing with water was not inferior to that with a cleanser in patients with AD in the maintenance phase during summer, regardless of the type of cleanser.

Background

Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV).

Methods

This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR.

Results

Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers.

A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025).

Conclusions

Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis.