Clinical and Translational Allergy最新文献

Background

Nasal allergen challenge (NAC) is used to investigate the effects of allergen exposure and assess treatment efficacy in allergic rhinitis (AR). This study aims to establish dose-responses to NAC using licensed silver birch (SB) pollen and house dust mite (HDM) sublingual tablets as sources of the allergen extracts in participants with AR.

Methods

Sixteen volunteers with HDM-induced perennial AR and 15 volunteers with SB pollen-induced seasonal rhinitis underwent a graded up-dosing NAC with extracts derived from HDM allergen (Acarizax®) and SB (Itulazax®) tablets, respectively. Total nasal symptom score (TNSS, range 0–12) and peak nasal inspiratory flow (PNIF) were recorded before, at 10 min and at the end of the NAC. The dose of each allergen that provoked a TNSS of at least 7 (“provoking dose 7”) in most allergic participants was identified. NACs using the “provoking dose 7” were performed on 5 non-allergic individuals to test for irritant effects. The “provoking dose 7” of HDM extract was used in a subgroup of two SB allergic, non-HDM allergic, volunteers, and vice versa for SB extract, to test for allergen specificity of the responses.

Results

Most patients experienced a TNSS of at least 7/12 at a median concentration of 1500 AU/mL for both SB pollen and HDM. The average decline in PNIF at this dose was 63.15% for SB and 63.99% for HDM. NACs using the 1500 AU/mL concentrations were performed on 5 non-allergic individuals with no symptomatic or PNIF response. 1500 AU/mL of HDM extract produced no symptoms in SB allergics nor 1500 AU/mL SB extract in HDM allergics.

Conclusion

For both SB and HDM extracts, the optimal allergen dose for NAC to cause a moderate-severity response (“provoking dose 7/12”) was 1500 AU/mL. Licensed sublingual allergen tablets provide a readily available and inexpensive source of SB and HDM extracts for use in future interventional studies in AR.

Background

Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets.

Methods

Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset.

Results

MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes.

Conclusion

Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.

Background

Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic.

Body

This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed.

Conclusion

The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

Background

An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open-label, proof-of-concept study was carried out to approach clinical efficacy of the cat food in cat-allergic patients.

Methods

After a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK-air app was used daily to assess symptoms, work productivity and medications.

Results

Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK-air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p < 0.0001). All symptoms (VAS nose, eye, and asthma), VAS work and the combined symptom-medication score significantly improved after 1 month. The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1 month (p < 0.0001) and 14% at 3 months. A sensitivity analysis in patients with uncontrolled disease at baseline found similar results.

Discussion

A cat diet containing anti-Fel d 1 antibodies was able to (i) show decreased allergic symptoms and related outcomes, (ii) inform the design and feasibility of future studies with a control arm and (iii) estimate the sample size of the study.

Study registration number: clinicaltrials.gov: NCT05656482.

Background

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nose and paranasal sinuses lasting ≥12 weeks. CRS may exist with (CRSwNP) or without (CRSsNP) nasal polyps. The aim was to evaluate conditions associated with CRS in a randomized hospital cohort. We hypothesized that comorbidities and surgical procedures differ between pediatric and adult patients.

Methods

This study consisted of hospital registry data of a random sample of rhinosinusitis patients (age range 0–89 years) with the diagnosis of J32 or J33, correspondingly, registered during outpatient visits from 2005 to 2019 (n = 1461). The covariates of interest were collected from electronic health records based on ICD-10 codes and keyword searches.

Results

Among pediatric patients (n = 104), the relative proportions of CRSsNP and CRSwNP were 86% and 14% respectively. The relative proportions of adult patients (n = 1357) with CRSsNP and CRSwNP were 60% and 40%, respectively. The following comorbidities significantly differed (p < 0.05) between pediatric and adult populations: allergy, chronic otitis media, and tonsillar diseases. In total, 41 % of the children and 46% of the adults underwent baseline endoscopic sinus surgery (ESS). Additional surgeries of the ear, nose and pharynx were significantly more common among children compared with adults. Risk of revision after baseline ESS was associated (p < 0.05) with allergy, asthma, eosinophilia, CRSwNP, immunodeficiency or its suspicion, non-steroidal anti-inflammatory drug exacerbated respiratory disease, and number of any diseases ≥2.

Conclusions

Our study showed that comorbidities differ between pediatric and adult rhinosinusitis patients, as allergy, asthma and allergy, chronic otitis media, mental health disorders, and tonsils disease were significantly more prevalent among pediatric patients. Children and adults were equally treated with ESS. Notably, children underwent additional surgery on adenoids and tonsils more frequently. The effectiveness of ESS in multimorbid adults should be assessed at an individual level.

Background

The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE-cow's milk allergy (IgE-CMA) is unknown.

Methods

A cohort of 58 patients with IgE-CMA was identified from a large scale population-based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery.

Results

While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1–3) were significantly more common in the allergic group than ≥4 feeds (p = 0.0003) and no feeds at all (p = 0.02) compared to controls (n = 116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105–194 days (the period with highest-risk for IgE-CMA) compared to 33/98 (34%) from the random control group (n = 259) (p = 0.04).

Conclusions

Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE-CMA.