Allergic sensitization to lipocalins reflects asthma morbidity in dog dander sensitized children

BackgroundSensitization to dog is an important risk factor for asthma in children, but the clinical relevance of IgE to available dog‐ and furry animal allergen molecules is uncertain.MethodsSpirometry, methacholine challenge, fraction of exhaled nitric oxide, nasal challenge with dog extract and questionnaires were performed in 59 dog‐sensitized children (age 10–18 years). Serum IgE to dog‐, cat‐, horse extracts and the allergen molecules Can f 1–6, Fel d 1, Fel d 2, Fel d 4 and Equ c 1 were evaluated.ResultsMedian numbers of positive IgE results to furry animal allergen molecules among children without asthma was 3, with asthma 5.5 and with troublesome asthma 9 (asthma vs. no asthma; p = 0.039; troublesome asthma vs. no asthma; p = 0.009). The odds ratio for asthma if sensitized to any lipocalin was 7.2 (95% confidence Interval: 1.44–35.9). Children with troublesome asthma had higher IgE levels to the lipocalins Can f 2, Can f 4 and Can f 6 compared to the rest of the study population (44 vs. 4.1 kU_A/L, p = 0.015; 5.8 vs. 0.9 kU_A/L, p = 0.018 and 1.3 vs. 0.7 kU_A/L, p = 0.03 respectively). Furthermore, a positive nasal challenge was more common among children with troublesome asthma (83% vs. 36%, p = 0.036).ConclusionsPolysensitization to furry animal allergens and lipocalins is associated with asthma in dog‐sensitized children. Children with troublesome asthma have higher IgE levels to several dog lipocalins than other dog sensitized children.Key messagePolysensitization to furry animal allergens and high IgE levels to the dog lipocalins Can f 2, Can f 4 and Can f 6 is associated with asthma severity in dog dander sensitized children. Molecular allergy diagnostics may thus help the clinicians to evaluate the impact of allergic sensitization on asthma morbidity.     

Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population

BackgroundAlthough studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals.MethodsTo identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next‐generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls).ResultsFirst, we identified 18 potentially functional rare loss‐of‐function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single‐nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10⁻⁴) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle‐ and high‐risk subjects had a 2.0‐fold (95% CI: 1.621–2.423, p = 2.624 × 10⁻¹¹) and 6.0‐fold (95% CI: 3.623–10.156, p = 7.086 × 10⁻¹²) increased risk of asthma, respectively, compared with low‐risk subjects.ConclusionThis study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.     

MALT1 in asthma children: A potential biomarker for monitoring exacerbation risk and Th1/Th2 imbalance‐mediated inflammation

BackgroundMucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) participates in the immune‐related allergic response and inflammation flare, while its clinical role in asthma children is still unknown. Herein, this study aimed to investigate MALT1 expression, and its correlation with exacerbation risk, T helper (Th)1, Th2 cells (and their secreted cytokines), as well as inflammatory cytokines in asthma children.MethodsSixty children with asthma exacerbation and 60 children with remission asthma were enrolled in this study; then their blood MALT1, Th1, Th2 cells, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), interferon‐gamma (IFN‐γ), and interleukin‐4 (IL‐4) were detected. Besides, blood MALT1 in another 20 health controls was also determined.ResultsMucosa‐associated lymphoid tissue lymphoma translocation protein 1 was highest in children with asthma exacerbation, followed by children with remission asthma, and lowest in health controls (p < 0.001). MALT1 could distinguish children with asthma exacerbation from children with remission asthma (area under the curve (AUC): 0.757, 95% CI: 0.670–0.843). In children with asthma exacerbation, MALT1 was negatively linked with IFN‐γ (p = 0.002) and Th1 cells (p = 0.050), but positively related to Th2 cells (p = 0.027) and exhibited a positive correlation trend (without statistical significance) with IL‐4 (p = 0.066); meanwhile, MALT1 was positively correlated with exacerbation severity (p = 0.010) and TNF‐α (p = 0.003), but not linked with IL‐6 (p = 0.096). In children with remission asthma, MALT1 only was negatively associated with Th1 cells (p = 0.023), but positively linked with TNF‐α (p = 0.023).ConclusionMucosa‐associated lymphoid tissue lymphoma translocation protein 1 serves as a potential biomarker for monitoring exacerbation risk and Th1/Th2 imbalance‐mediated inflammation of asthma children.     

Budesonide repairs decreased barrier integrity of eosinophilic nasal polyp epithelial cells caused by PM2.5

BackgroundEosinophilic chronic rhinitis with nasal polyps (eos‐CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type‐2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type‐2 inflammation. Particular matter 2.5 (PM_2.5) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM_2.5 on the barrier function of the eos‐CRSwNP epithelium and explored the reparative function of budesonide.MethodsSamples from noninflammatory nasal mucosa and eos‐CRSwNP were collected to establish an in vitro air–liquid interface cultured model. The cells were exposed to PM_2.5 at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate‐labeled 4‐kDa dextran, quantitative real‐time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme‐linked immunosorbent assay or Luminex.ResultsPM_2.5 increased paracellular flux and downregulated TJ protein expression (zona occuldens‐1, occludin, and claudin‐1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)‐8, IL‐10, IL‐1α, and tissue inhibitor of metalloproteinase (TIMP)‐1 concentrations were significantly increased in the culture medium of cells exposed to PM_2.5, and budesonide significantly reduced the changes in IL‐8, IL‐1α, and TIMP‐1.ConclusionPM_2.5 impaired the barrier function of eos‐CRSwNP epithelial cells and increased the permeability of large molecules. PM_2.5 also increased the secretion of pro‐inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.     

室内空气污染对哮喘儿童血清miR-155水平的影响

目的:探讨室内空气污染与儿童哮喘的关系及潜在的分子机制。方法:选择176名健康受试者作为对照组,176例哮喘患儿作为哮喘组。应用实时荧光定量PCR技术检测受试者血清miR-155水平。测量甲醛(HCHO)、NO_2和颗粒(PM_(10)、PM_(2.5)和PM_1)。通过单因素和多因素logistic回归分析,评价空气污染物与哮喘风险的关系。结果:哮喘组血清miR-155水平明显高于对照组(P0.001)。两组儿童过敏史、母乳喂养史、环境烟草烟雾史、PM_(2.5)、HCHO差异与儿童哮喘发作相关(P0.05)。哮喘组血清miR-155水平与室内PM_(2.5)、HCHO水平密切相关(P0.05),对照组无此相关性。结论:哮喘患儿血清miR-155水平与室内PM_(2.5)和HCHO水平密切相关。室内空气污染加重了西安地区儿童哮喘的发生,并诱导其miR-155水平变化。     

Prenatal PM2.5 affects atopic dermatitis depending on maternal anxiety and gender: COCOA study

BackgroundThe prevalence of atopic dermatitis (AD) is increasing worldwide. Prenatal particulate matter with an aerodynamic diameter <2.5 μm (PM_2.5) and maternal anxiety during pregnancy has been suggested as a potential causes of AD. This study investigated the effects of prenatal PM_2.5 and maternal anxiety on AD and identified the critical period of PM_2.5 exposure for AD in infants.MethodsThis study included 802 children from the COCOA birth cohort study with follow‐up data at 1 year of age. PM_2.5 was estimated by land‐use regression models and prenatal anxiety was measured with a questionnaire. AD was diagnosed by doctor at 1 year of age. Logistic regression analysis and Bayesian distributed lag interaction models were applied.ResultsHigher PM_2.5 during the first trimester of pregnancy, higher prenatal maternal anxiety, and male gender were associated with AD at 1 year of age (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 1.86 [1.08–3.19], 1.58 [1.01–2.47], and 1.54 [1.01–2.36], respectively). Higher PM_2.5 during the first trimester and higher maternal anxiety during pregnancy showed an additive effect on the risk of AD (aOR: 3.13; 95% CI: 1.56–6.28). Among boys exposed to higher maternal anxiety during pregnancy, gestational weeks 5–8 were the critical period of PM_2.5 exposure for the development of AD.ConclusionsHigher PM_2.5 exposure during gestational weeks 5–8 increased the probability of AD in infancy, especially in boys with higher maternal anxiety. Avoiding PM_2.5 exposure and maternal anxiety from the first trimester may prevent infant AD.     

Effect of air filtration on house dust mite,cat and dog allergens and particulate matter in homes

BackgroundIndoor allergens (i.e. from mite, cat and dog) are carried by airborne particulate matter. Thus, removal of particles would reduce allergen exposure. This work aims to assess the performance of air filtration on particulate matter and thus allergen removal in 22 bedrooms.MethodsIndoor air was sampled (with and without air filtration) with a cascade impactor and allergens were measured using enzyme‐linked immunosorbent assay (ELISA). Particulate matter (including ultrafine particles) was also monitored.ResultsThe median of allergen reduction was 75.2% for Der f 1 (p < 0.001, n = 20), 65.5% for Der p 1 (p = 0.066, n = 4), 76.6% for Fel d 1 (p < 0.01, n = 21) and 89.3% for Can f 1 (p < 0.01, n = 10). For size fractions, reductions were statistically significant for Der f 1 (all p < 0.001), Can f 1 (PM_>10 and PM_2.5–10, p < 0.01) and Fel d 1 (PM_2.5–10, p < 0.01), but not for Der p 1 (all p > 0.05). PM was reduced in all fractions (p < 0.001). The allergens were found in all particle size fractions, higher mite allergens in the PM_>10 and for pet allergens in the PM_2.5–10.ConclusionsAir filtration was effective in removing mites, cat and dog allergens and also particulate matter from ambient indoor air, offering a fast and simple solution to mitigate allergen exposome.     

Allergy‐related diseases and early gut fungal and bacterial microbiota abundances in children

BackgroundThe early gut microbiota has been proposed as an important link between environmental exposures and development of allergy‐related diseases. Beyond the widely investigated associations between the gut bacterial microbiota, we investigated the involvement of early gut mycobiota and gut permeability in the pathogenesis of asthma, allergic rhinoconjunctivitis (AR) and eczema.MethodsIn the Probiotics in the Prevention of Allergy among Children in Trondheim trial with maternal probiotic supplementation, we collected faecal samples at four timepoints between 0 and 2 years from a cohort of 278 children. Clinical information on allergy‐related diseases was collected in a paediatric examination at 2 years and questionnaires at 6 weeks and 1, 2 and 6 years. By quantitative PCR and 16S/ITS1 MiSeq rRNA gene sequencing, we analysed the gut bacterial and fungal microbiota abundance and bacterial diversity and explored associations with allergy‐related diseases. We also measured gut permeability markers (lipopolysaccharide‐binding protein [LBP] and fatty acid‐binding protein 2 [FABP2]).ResultsChildren with higher fungal abundance at 2 years were more likely to develop asthma and AR by 6 years, odds ratios 1.70 (95% CI: 1.06–2.75) and 1.41 (1.03–1.93), respectively. We explored causal connections, and children with eczema at 1–2 years appeared to have more mature bacterial microbiota, as well as being depleted of Enterococcus genus. Although LBP and FABP2 did not correlate with eczema, increased bacterial abundance was associated with increased serum FABP2.ConclusionsWe observed positive associations between gut fungal abundance and allergy‐related disease, but increased gut permeability does not appear to be involved in the underlying mechanisms for this association. Our findings should be confirmed in future microbiota studies.     

Aberrant expression of long non‐coding RNA PVT1 in allergic rhinitis children: Correlation with disease risk,symptoms, and Th1/Th2 imbalance

BackgroundLong non‐coding RNA plasmacytoma variant translocation 1 (lnc‐PVT1) exacerbates inflammation and induces T helper (Th) 1/Th2 imbalance in allergic diseases, but its clinical role in allergic rhinitis (AR) remains unclear. Hence, we conducted this study to compare lnc‐PVT1 expression among AR children, disease controls (DCs), and health controls (HCs), aiming to investigate its clinical application in AR children.MethodsSixty AR children, 30 DCs, and 30 HCs were enrolled in the study, and then, their lnc‐PVT1 expression in peripheral blood mononuclear cell was detected. Serum interferon‐gamma (IFN‐γ), interleukin 10 (IL‐10), Th1, and Th2 cells in AR children were also analyzed. Besides, lnc‐PVT1 was also detected at Week (W)4 after treatment in AR patients.ResultsLnc‐PVT1 was upregulated in AR children compared with DCs and HCs (both p < 0.001). Lnc‐PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and total nasal symptom score (TNSS) in AR children (all p < 0.050), instead of sneezing score (p = 0.115). Lnc‐PVT1 negatively associated with Th1 cells in AR children (p = 0.028) also exhibited a negative correlation trend with IFN‐γ (but without statistical significance) (p = 0.065). Differently, lnc‐PVT1 was positively related to Th2 cells (p = 0.012) and IL‐10 (p = 0.021) in AR children. Besides, lnc‐PVT1 and TNSS were reduced at W4 after treatment in AR children (both p < 0.001); notably, lnc‐PVT1 expression decline was correlated with TNSS decline during treatment (p = 0.013).ConclusionLnc‐PVT1 works as a biomarker, whose aberrant expression is related to disease severity, Th1/Th2 imbalance, and its decrement can reflect treatment outcome in AR children.     

Inter‐alpha‐trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk,activity, and treatment outcomes of rheumatoid arthritis

ObjectiveInter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.MethodsAfter the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA.ResultsITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (r_s  = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (r_s  = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (r_s  = −0.337, p = 0.001), IL‐6 (r_s  = −0.221, p = 0.033), and IL‐17A (r_s  = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (r_s  = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).ConclusionCirculating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.     

Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

BackgroundStroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A⁻) variant with abnormal TCD velocities among Nigerian children with SCA.MethodsOne hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction.ResultsThe frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA⁻ variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).ConclusionOur study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.     

Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans

OBJECTIVE

Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels.

RESEARCH DESIGN AND METHODS

Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO₂, O₃, and PM_2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NO_x. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits.

RESULTS

Short-term (up to 58 days cumulative lagged averages) exposure to PM_2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM_2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P ≤ 0.043). The effects of short-term PM_2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes.

CONCLUSIONS

Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae.     

Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia

BackgroundVitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25‐hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25‐dihydroxyvitamin D [24,25(OH)₂D], and vitamin D metabolite ratio [VMR]) and sarcopenia.MethodsThe data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)₂D and 25(OH)D were made using solid‐phase extraction (SPE) and subsequent liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme‐linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)₂D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies.ResultsBioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non‐sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p < 0.001). In the group with a bioavailable 25(OH)D less than 1.70 ng/ml, the incidence of sarcopenia increased by 3.3 times (odds ratio: 3.33, p = 0.013).ConclusionWe demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.     

Chronic rhinosinusitis with and without nasal polyps and asthma: Omalizumab improves residual anxiety but not depression

BackgroundChronic rhinosinusitis (CRS) has a high prevalence of anxiety and depression. It is currently uncertain if treatment in patients with CRS with or without nasal polyps (CRSwNP and CRSsNP) has any impact on improving mental health outcomes. The aims here were to document anxiety and depression in patients with severe CRS and asthma already treated with appropriate medical therapy. We then evaluated whether further maximal treatment with omalizumab improved anxiety and/or depression alongside improvements in CRS and coassociated asthma.MethodsHospital Anxiety and Depression Scale (HADS) scores along with measures of CRS and asthma severity were recorded according to CRSwNP and CRSsNP status in n = 95 patients with severe CRS and asthma. Of this group, a further n = 23 had omalizumab for associated allergic asthma. Follow‐up measures were collected 16 weeks after omalizumab treatment.ResultsHADS anxiety and depression prevalence in CRS were 49.47 % and 38.95%, respectively. Within the CRSwNP and CRSsNP group 53.06% and 45.66% had raised HADS‐anxiety scores. Abnormal HADS‐depression scores were present in 40.82% and 36.95% of the CRSwNP and CRSsNP groups, respectively. Correlations for sinonasal outcome test‐22 (SNOT‐22) versus HADS total was r = 0.59 p < 0.0001, HADS‐anxiety r = 0.56 p < 0.0001 and HADS‐depression r = 0.49 p < 0.0001. Omalizumab improved anxiety in CRS (p < 0.0001) regardless of nasal polyp status (CRSwNP p = 0.0042 and CRSsNP p = 0.0078). Depression scores did not improve in either group. SNOT‐22 (p = 0.0006), asthma control questionnaire‐7 (p = 0.0019) and mini‐asthma quality of life questionnaire including emotional function (p = 0.0003 and p = 0.0009, respectively) all improved in both subgroups.ConclusionIn CRS and asthma, anxiety scores but not depression improved after omalizumab treatment. Anxiety may be closely related to airway disease severity, but depression may be independent of airway disease itself. If so, a separate mental health care pathway is needed for CRS patients with depression.     

Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea

BackgroundSystemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)‐35 and IL‐37 have been identified as novel immune‐modulating cytokines with anti‐inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL‐35 and IL‐37 in patients with OSA, and to investigate their associations with the severity of OSA.MethodsA total of 97 patients, including 67 cases of OSA and 30 age‐ and gender‐matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL‐35, IL‐37, and pro‐inflammatory cytokine IL‐1β levels were examined by ELISA.ResultsCompared with those in the control subjects, serum IL‐35, IL‐37, and IL‐1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity‐dependent increase in serum IL‐35 and IL‐37 levels was observed in patients with OSA. IL‐35 and IL‐37 levels were positively correlated with the apnea‐hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = −0.461 and −0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = −0.616 and −0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL‐35 or IL‐37 and IL‐1β levels (all p < 0.001).ConclusionThe serum levels of IL‐35 and IL‐37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL‐35 and IL‐37 may have a protective role in OSA by counteracting inflammatory responses.     

JNK pathway‐associated phosphatase illustrates low expression and negative correlations with inflammation,disease activity,and T‐helper 17 cells in inflammatory bowel disease children

BackgroundC‐Jun N‐terminal kinase pathway‐associated phosphatase (JKAP) modulates the T cell receptor and mitogen‐activated protein kinase pathway‐mediated autoimmunity, thus participating in the pathogenesis of autoimmune diseases. This study aimed to explore the clinical implication of JKAP in inflammatory bowel disease (IBD) children.MethodsC‐Jun N‐terminal kinase pathway‐associated phosphatase, tumor necrosis factor‐α (TNF‐α), interleukin‐23, interferon‐γ (T‐helper 1 secreted cytokine), and interleukin‐17A (T‐helper 17 secreted cytokine) in serum samples from 140 IBD children (including 60 Crohn''s disease (CD) children and 80 ulcerative colitis (UC) children) were detected by ELISA. Meanwhile, JKAP from serum samples of 10 healthy controls (HCs) was also detected by ELISA.ResultsC‐Jun N‐terminal kinase pathway‐associated phosphatase was reduced in CD children (median (interquartile range (IQR)): 51.6 (36.8–69.5) pg/ml) and UC children (median (IQR): 57.5 (43.4–78.5) pg/ml) compared with HCs (median (IQR): 101.8 (70.0–143.2) pg/ml) (both p < 0.05). In CD children, JKAP was negatively correlated with C‐reactive protein (CRP) (p = 0.016) and erythrocyte sedimentation rate (ESR) (p = 0.029); while in UC children, JKAP was also negatively correlated with CRP (p = 0.006) and ESR (p = 0.022). Regarding the correlation of JKAP with disease activity, it presented negative correlations with PCDAI (p = 0.001) and PUCAI (p = 0.002). Besides, JKAP was negatively related to TNF‐α (both p < 0.05) but not interleukin‐23 (both p>0.05) in CD and UC children. Additionally, JKAP was not correlated with interferon‐γ in CD or UC children (both p>0.05), while negatively correlated with interleukin‐17A in CD and UC children (both p < 0.05).ConclusionC‐Jun N‐terminal kinase pathway‐associated phosphatase shows low expression and negative correlations with inflammation, disease activity, and T‐helper 17 cells in IBD children.     

Relationship between longitudinal changes in type‐2 inflammation,immunoglobulin E sensitization,and clinical outcomes in young asthmatics

BackgroundAsthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated.ObjectiveTo study longitudinal changes in type‐2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics.MethodsAsthmatics (age 10–35 years, n = 253) were examined at baseline and at a follow‐up visit, 43 [23–65] (median [range]) months later. Subjects were analyzed using the multi‐allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen‐specific IgE antibody (sIgE) concentration: <0.10, 0.10–0.34, and ≥0.35 kU_A/L. The relationship between changes (Δ values) in type‐2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B‐Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined.ResultsAt follow up, FEV₁ and FEV₁/FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kU_A/L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B‐Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B‐Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV₁ (p < 0.05) and ΔFEV₁/FVC% (p < 0.01). Sex‐specific analysis showed that the independent association between ΔFeNO%, and ΔFEV₁ remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02).ConclusionIn young asthmatics, IgE levels declined over 43 months, whereas FeNO and B‐Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type‐2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV₁ in females.     

Anaphylactic risk related to omalizumab,benralizumab, reslizumab,mepolizumab, and dupilumab

BackgroundMonoclonal antibodies (mAbs) are novel, effective therapeutics for the treatment of inadequately controlled severe asthma. Knowledge of the anaphylaxis risks related to different mAbs is essential for their appropriate and safe administration. This study aimed to evaluate the associations between different mAbs and anaphylactic reactions by applying statistical approaches to pharmacovigilance data.MethodsThis was a retrospective study using data from the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2020. A total of 2006 reports of anaphylaxis related to benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab were obtained through data mining. The clinical characteristics of the cases were analyzed, and the risk signals of anaphylactic reactions and corresponding outcomes were investigated in the five mAbs.ResultsThe patients were mainly young and middle‐aged adults, with markedly more women than men. Omalizumab, benralizumab, reslizumab, and mepolizumab showed positive signals for anaphylaxis, while only dupilumab showed a negative signal. The risk of initial or prolonged hospitalization due to anaphylaxis was significantly higher in the benralizumab group than in the omalizumab group (42.86% vs. 28.92%, p = 0.024). Further, when anaphylaxis to omalizumab occurred, patients with asthma were more likely to have life‐threatening outcomes than those with chronic urticaria (18.0% vs. 12.9%, p = 0.022).ConclusionIn the current real‐world study, the positive anaphylaxis signals related to omalizumab, benralizumab, reslizumab, and mepolizumab suggested the need for the close monitoring of patients after drug use, and dupilumab showed a negative signal for anaphylaxis.     

The home air in agriculture pediatric intervention (HAPI) trial: Rationale and methods

BackgroundData addressing air quality effects on children with asthma in rural U.S. communities are rare. Our community engaged research partnership previously demonstrated associations between neighborhood NH₃ and ambient PM_2.5 and asthma in the agricultural lower Yakima Valley of Washington. As a next step, the partnership desired an intervention approach to address concerns about pediatric asthma in this largely Latino immigrant, farm worker community.ObjectiveThe Home Air in Agriculture Pediatric Intervention (HAPI) sought to examine the effectiveness of enrichment of an existing asthma education program with portable high-efficiency particulate air (HEPA) cleaners designed to reduce PM_2.5 and NH_3. We investigated the effect of this enriched approach on these exposures and asthma health measures.DesignWe randomized children with poorly controlled asthma to a control arm (current asthma education program) or an intervention arm (current asthma education program + placement of two indoor air cleaners in the family's home). Outcomes included (1) 14-day integrated samples of indoor air contaminants (PM_2.5 and NH₃) at baseline and one-year follow-up and (2) child asthma health metrics at baseline, midpoint (4–6 months) and one-year follow-up. These included the Asthma Control Test, symptoms days, clinical utilization, oral corticosteroid use, pulmonary function, fractional exhaled nitric oxide, and urinary leukotriene E₄ concentration.DiscussionTo our knowledge, this is the first randomized HEPA cleaner intervention designed to assess NH₃ as well as PM_2.5 and to evaluate health outcomes of children with asthma in an agricultural region.