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Wenting Luo,&ast; Shuwen Yang,&ast; Huimin Huang, Liting Wu, Zhangkai J Cheng, Peiyan Zheng, Jinping Zheng, Baoqing Sun Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Jinping Zheng Email sunbaoqing@vip.163.com; 18928868238@163.comObjective: Peanut is one of the most frequently reported allergens causing severe allergies in western countries. In China, however, there have been few reports of severe allergies caused by peanuts. We investigated the peanut allergen components sensitization and cross-reaction with pollen allergen in Chinese Southerners with allergic rhinitis and/or asthma.Methods: Total IgE (tIgE) and specific IgE (sIgE) antibodies against Ara h 1, Ara h 8, Juglans pollen, Platanus pollen, birch pollen, Bet v 1, Bet v 4, and cross-reactive carbohydrate determinant (CCD) of 58 allergic patients, of whom 33 were peanut-sIgE positive and 25 were negative, were detected by the ImmunoCAP system. The relationships between peanut allergen and pollen allergens were analyzed.Results: A 9.1% (3/33) of the patients with peanut sensitization were sensitized to Ara h 8, while 21.2% (7/33) were sensitized to Ara h 1. The peanut-sensitized group had significantly higher positive rates for sIgE antibodies against CCD (69.7% vs 4.0%), Juglans pollen (87.9% vs 12.0%), Platanus pollen (90.9% vs 16.0%), and birch pollen (60.6% vs 4.0%) than the peanut tolerance group (all P < 0.05). Spearman correlation showed that peanut-sIgE were significantly correlated with sIgE to CCD (rs=0.859), Juglans pollen (rs=0.772), Platanus pollen (rs=0.838) and birch pollen (rs=0.816).Conclusion: The majority of patients sensitized to peanut allergen in Southern China tested positive for multiple pollen allergens. Peanut sensitization was highly correlated with Platanus, Juglans, and birch pollen sensitization, which suggested there may be cross-reactions between peanut and pollen allergens. Clinicians should pay attention to distinguish diagnosis in clinical peanut allergy diagnosis and treatment.Keywords: peanut sensitization, pollen allergen, specific IgE, cross-reactivity, CCD

Background and Objectives The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to predict patient prognosis. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) are known prognostic biomarkers. However, the clinical or pathophysiological differences in patients with these biomarkers have not been well evaluated. We investigated the clinical and pathophysiological differences through the comparison of SP-A and KL-6 levels before and after treatment. Methods This study included retrospective data from 91 patients who were treated for ILD between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed up for 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were found to be significantly correlated (rs = 0.523, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (% predicted values of diffusing capacity for carbon monoxide [DLCO], forced vital capacity [FVC], and forced expiratory volume in 1 s [FEV1]). Patients were divided into four groups based on their Delta SP-A and Delta KL-6 levels in a cluster analysis (G1, G2, G3, and G4). Both SP-A and KL-6 were elevated in the G1 group, with all the patients enrolled classified as progressive or unchanged, and 86.4% of patients showed improved disease activity in the G4 group, where both SP-A and KL-6 levels were reduced. In the G2 group, only SP-A levels decreased post-treatment, indicating an improvement in respiratory function; the patients were not at the end stage of the disease. Only the SP-A levels increased in the G3 group with immunosuppressive treatment. Conclusions Reduced serum SP-A and/or KL-6 levels are associated with improved lung function in patients with ILD. Some patients only showed a decrease in SP-A levels could prognosis an improvement in respiratory function. When only SP-A is increased, it may imply that the patients are at an early stage of disease progression. As a result, for proper disease monitoring, measuring both markers is important.

Haisheng Hu,1,&ast; Xiangqing Hou,2,&ast; Wenting Luo,1 Yusi Li,2 Huimin Huang,1 Xiaoying Huang,1 Baoqing Sun,1 Xiaohua Douglas Zhang2 1Department of Allergy and Clinical Immunology, First Affiliated Hospital of Guangzhou Medical University (State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health), Guangzhou, People’s Republic of China; 2Faculty of Health Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing SunDepartment of Allergy and Clinical Immunology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20 8306 2865Email sunbaoqing@vip.163.comXiaohua Douglas ZhangFaculty of Health Sciences, University of Macau, Taipa, Macau, People’s Republic of ChinaTel +86 853 88224813Email douglaszhang@um.edu.moAbstract: This study investigated the molecule sensitized pattern of atopic dermatitis patients who co-sensitized to shrimp, cockroaches, crab and house dust mites allergens and promoted the development of clinical accurate diagnosis and treatment.Keywords: specific immunoglobulin E, sIgE, atopic dermatitis, cross-reaction

The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2’s predictive value for patients’ restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission ( P < 0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability ( P

Background Intrauterine hyperglycemia can harm a fetus's growth and development, and this can be seen in the umbilical cord blood metabolism disorder. However, the metabolites and metabolic mechanisms involved in the condition remain unknown. Methods Targeted metabolomics using liquid chromatography and MetaboAnalyst were conducted in this study to explore differences in metabolites and metabolic pathways between individuals with hyperglycemia or well-controlled gestational diabetes mellitus (GDM) and healthy controls. Results Univariate analysis found that the hyperglycemic and healthy control groups differed in 30 metabolites, while the well-controlled GDM and the healthy control groups differed only in three metabolites-ursodeoxycholic acid, docosahexaenoic acid, and 8,11,14-eicosatrienoic acid. Most of these metabolic variations were negatively associated with neonatal weights. Further research showed that the variations in the metabolites were primarily associated with the metabolic pathways of linoleic acid (LA) and alpha-linolenic acid (ALA). Conclusion Gestational hyperglycemia and well-controlled GDM, which may play a major role by inhibiting the LA and ALA metabolic pathways, have detrimental effects on cord blood metabolism. Impact The main point of this paper is that intrauterine hyperglycemia has a negative effect on cord blood metabolism mainly through the linoleic acid and alpha-linolenic acid metabolic pathways. This is a study to report a new association between well-controlled GDM and cord blood metabolism. This study provides a possible explanation for the association between intrauterine hyperglycemia and neonatal adverse birth outcomes.

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease–GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating disease.

Dysregulated immune response and abnormal repairment could cause secondary pulmonary fibrosis of varying severity in COVID-19, especially for the elders. The Krebs Von den Lungen-6 (KL-6) as a sensitive marker reflects the degree of fibrosis and this study will focus on analyzing the evaluative efficacy and predictive role of KL-6 in COVID-19 secondary pulmonary fibrosis. The study lasted more than three months and included total 289 COVID-19 patients who were divided into moderate (n=226) and severe groups (n=63) according to the severity of illness. Clinical information such as inflammation indicators, radiological results and lung function tests were collected. The time points of nucleic acid test were also recorded. Furthermore, based on Chest radiology detection, it was identified that 80 (27.7%) patients developed reversible pulmonary fibrosis and 34 (11.8%) patients developed irreversible pulmonary fibrosis. Receiver operating characteristic (ROC) curve analysis shows that KL-6 could diagnose the severity of COVID-19 (AUC=0.862) and predict the occurrence of pulmonary fibrosis (AUC = 0.741) and irreversible pulmonary fibrosis (AUC=0.872). Importantly, the cross-correlation analysis demonstrates that KL-6 rises earlier than the development of lung radiology fibrosis, thus also illuminating the predictive function of KL-6. We set specific values (505U/mL and 674U/mL) for KL-6 in order to assess the risk of pulmonary fibrosis after SARS-CoV-2 infection. The survival curves for days in hospital show that the higher the KL-6 levels, the longer the hospital stay (P

Background:House-dust mites (HDM) allergen is one of the most important allergens in southern China; however, studies on the Dermatophagoides pteronyssinus components are relatively lacking.Objective:This study analyzed the molecular components of D. pteronyssinus in patients with allergic asthma (AS) and/or allergic rhinitis (AR) sensitized to D. pteronyssinus, and aimed to improve HDM immunotherapy in southern China.Methods:Allergen component-resolved diagnosis detection technology was used to detect the serum levels of specific immunoglobulin E (sIgE) to D. pteronyssinus allergen components (Der p 1, 2, 3, 5, 7, 10, and 23) in patients who were sensitized to D. pteronyssinus and with AR (n = 106), AS (n = 144), or AR combined with AS (n = 134).Results:The highest positive rates ofD. pteronyssinuscomponents were Der p 1 (94.8%), followed by Der p 2 (77.6%), Der p 23 (62.5%), Der p 7 (34.6%), Der p 5 (17.7%), Der p 10 (12.2%), and Der p 3 (2.6%). Patients with AR+AS had the highest positive rates to Der p 2 (85.8%), Der p 23 (62.7%), Der p 7 (40.3%), Der p 5 (25.0%), and Der p 10 (16.4%). Der p 1 had the highest positive rate in patients with AR (95.3%). The Der p 3 positive rate in patients with AS (6.0%) was higher than that in patients with AR (0.0%, χ2= 6.872, p < 0.05) and patients with AR+AS (0.7%, χ2= 6.063, p < 0.05) Among the patients with AR+AS, 19.1% were co-sensitized to Der p 1, Der p 2, Der p 23, and Der p 7. Interestingly, only one patient with AR was exclusively sensitized to Der p 23. An optimal scale analysis showed that Der p 5, Der p 23, and Der p 7 had strong connection (Cronbach α = 93.7%).Conclusion:Der p 1 and Der p 2 were the main sensitization components of D. pteronyssinus, and patients with AS+AR had the highest positive rate for five of seven D. pteronyssinus allergen components. This research can provide suggestions for personalized HDM-specific immunotherapy in southern China.

BackgroundCritically ill coronavirus disease 2019 (COVID-19) patients may suffer persistent systemic inflammation and multiple organ failure, leading to a poor prognosis.Research questionTo examine the relevance of the novel inflammatory factor heparin-binding protein (HBP) in critically ill COVID-19 patients, and evaluate the correlation of the biomarker with disease progression.Study design and methods18 critically ill COVID-19 patients who suffered from respiratory failure and sepsis, including 12 cases who experienced a rapidly deteriorating clinical condition and six cases without deterioration, were investigated. They were compared with 15 age- and sex- matched COVID-19-negative patients with respiratory failure. Clinical data were collected and HBP levels were investigated.ResultsHBP was significantly increased in critically ill COVID-19 patients following disease aggravation and tracked with disease progression. HBP elevation preceded the clinical manifestations for up to 5 days and was closely correlated with patients’ pulmonary ventilation and perfusion status.InterpretationHBP levels are associated with COVID-19 disease progression in critically ill patients. As a potential mediator of disease aggravation and multiple organ injuries that are triggered by continuing inflammation and oxygen deficits, HBP warrants further study as a disease biomarker and potential therapeutic target.

Objective Bermuda grass pollen is a common inhaled allergen. The aim of this study was to investigate the molecular sensitization patterns to major pollen allergens (Bermuda grass, Mugwort and Timothy grass) and cross-reactive carbohydrate determinants (CCD) in Bermuda grass sensitized patients in southern China. Methods Serum specific IgE (sIgE) levels of Bermuda grass allergen components (Cyn d 1 and Cyn d 12), Timothy grass allergen components (Phl p 1, Phl p 4, Phl p 5, Phl p 7 and Phl p 12), Mugwort allergen components (Art v 1, Art v 3 and Art v 4) and CCD were detected in 78 patients sensitized to Bermuda grass via EUROBlotMaster system. Results Compared with CCD-positive patients, those with negative CCD results had significant higher positive rates of Cyn d 1 (47.8% vs 14.5%), Phl p 1 (26.1% vs 7.3%), Phl p 12 (21.7% vs 3.6%) and Art v 4 (26.1% vs 3.6%) (all p < 0.05). Patients

OBJECTIVE This was the first multicentre study assessing the sensitisation patterns in patients with severe asthma by different occupations as well as different regions of China, and aimed to provide evidence for the prevention of sensitised patients with severe asthma. METHODS A total of 676 adults were included and assigned to three cohorts. Cohort A was comprised of severe asthma patients without smoking (n = 454), cohort B comprised severe asthmatic patients who were ex-smokers (n = 149), and cohort C comprised non-asthma individuals (n = 73). All study subjects underwent testing of serum sIgE level of house dusts mix (hx2), foods mix (fx5), moulds mix (mx2), tree pollen mix (tx4) and weed pollen mix (wx5) simultaneously. RESULTS Overall, the positive rates of hx2, fx5, mx2, tx4 and wx5 were 37.6%, 11.9%, 16.6%, 9.0% and 9.5% in severe asthmatic patients, respectively. Comparing cohort A with cohort B, the hx2 positive rates in cohort A were higher in fulltime homemaker (30.0% vs. 0.0%) and medical staff (40.0% vs. 0.0%, P

Summary The diagnosis of coronavirus 19 (COVID-19) relies mainly upon viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody detection is convenient, safe and highly sensitive. Immunoglobulin (Ig)M and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. COVID-19 patients, divided into a severe and critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results and other data were recorded for all patients. Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are more effective for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe and critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.

Background The importance of lipid mediators in allergic diseases has been long recognized, whereas little is known about their role in allergic bronchopulmonary aspergillosis (ABPA). We investigated whether lipid mediators are associated with ABPA. Methods We recruited 12 ABPA patients, 23 asthma patients and 12 healthy control in our study. Serum of 11 ABPA patients were collected before and following treatment. 36 polyunsaturated fatty acid metabolites were measured in serum samples by using liquid chromatography–mass spectrometry. This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, with ethics number GYFYY-2016-73. Results Levels of arachidonic acid (AA), 15(S)-hydroxyeicosatetraenoic acid (HETE), 12(S)-HETE, 8(S)-HETE, 5(S)-HETE, LTB4, PGB2, 12(S)-hydroxyeicosapentaenoic acid (HEPE), 12-hydro-xyheptadecatrienoic acid (HHTrE) were significantly higher in ABPA patients than that in HC groups. Compared with asthma group, ABPA group expressed lower levels of 15(S)-hy-droperoxyeicosatetraenoic acid (HPETE), 5(S)-HPETE, 13(S)-hydroperoxyoctadecadienoic acid (HPODE) and 9(S)-HPODE. In APBA patients, AA level was positively correlated with serumtotal IgE (tIgE). The levels of 12(S)-HPETE, 15(S)-HEPE and 12(S)-HEPE correlated with Asp-ergillus fumigatus specific IgE(A. fumigatus sIgE) positively. Peripheral blood eosinophilia correlated with high levels of 12(S)-HETE and 15(S)-HETE. In addition, the serum levels of15(S)-HETE and 12(S)-HETE in ABPA subjects both declined with the decrease of tIgE, A. fumigatus sIgE and sIgG concentrations after treatment. Conclusions We present data regarding the role of polyunsaturated fatty acid metabolites in APBA for the first time. Most of the tested metabolites increased in ABPA when co-mpared with healthy controls and 15(S)-HETE and 12(S)-HETE may play a role in the pat-hogenesis of ABPA. These findings can provide new ideas for diagnosis, therapy and mon-itor of ABPA.

Optical imaging/tracking through scattering medium is a difficult challenge. We demonstrate a method using speckles with multiple bit depths to image objects through scattering medium. The image of the object can be reconstructed even if the speckles are binary. Speckles with different bit depths are obtained by quantifying the original speckle. And we discuss the application of binarized speckles in tracking moving object. The binarized speckles can be used to recover the track with high accuracy. The range of the object's motion can be much larger than the range of memory effect, as long as the object's size and the moving step are within the range of memory effect. Imaging and tracking with low bit depth have the potential to reduce the hardware requirements of camera and storage space of images.

Background Cow’s milk (CM) is the main food allergen for toddlers and infants. Presently, studies on CM specific immunoglobulin E (sIgE) sensitization and positive distribution of CM components ALA-, CAS-, and BLG-sIgE are lacking in infants with respiratory allergic diseases, especially in southern China. This study therefore aimed to investigate the distribution of CM sensitization and the relation between its components α-lactalbumin (ALA), β-lactoglobulin (BLG) and casein (CAS) sIgE in children with respiratory allergic diseases in southern China. Methods A total of 1839 children (≤12 years) with respiratory diseases and detected CM-sIgE levels were included. Serum samples were collected from the Respiratory Diseases Bioresources Center of the National Center for Respiratory Diseases in southern China from August 2012 to July 2017. ALA-, BLG-, and CAS-sIgE were detected and questionnaires were completed in 103 children. Results A total of 36.7% children were positive for CM-sIgE. CM-sIgE levels were higher in asthmatic bronchitis (AB) group than in other allergic respiratory disease groups (all P rs = 0.833), ALA-sIgE (rs = 0.816), and CAS-sIgE (rs = 0.573) levels (all p < 0.001). Conclusions In southern China, CM-sIgE levels were higher in children with AB than in those with other respiratory allergic diseases. ALA and BLG were the main allergenic components detected in CM-sIgE-sensitized children with respiratory allergic diseases.

The emerging COVID-19 caused by SARS-CoV-2 infection poses severe challenges to global public health. Serum antibody testing is becoming one of the critical methods for the diagnosis of COVID-19 patients. We investigated IgM and IgG responses against SARS-CoV-2 nucleocapsid (N) and spike (S) protein after symptom onset in the intensive care unit (ICU) and non-ICU patients. 130 blood samples from 38 COVID-19 patients were collected. The levels of IgM and IgG specific to N and S protein were detected by ELISA. A series of blood samples were collected along the disease course from the same patient, including 11 ICU patients and 27 non-ICU patients for longitudinal analysis. N and S specific IgM and IgG (N-IgM, N-IgG, S-IgM, S-IgG) in non-ICU patients increased after symptom onset. N-IgM and S-IgM in some non-ICU patients reached a peak in the second week, while N-IgG and S-IgG continued to increase in the third week. The combined detection of N and S specific IgM and IgG could identify up to 75% of SARS-CoV-2 infected patients in the first week. S-IgG was significantly higher in non-ICU patients than in ICU patients in the third week. In contrast, N-IgG was significantly higher in ICU patients than in non-ICU patients. The increase of S-IgG positively correlated with the decrease of C-reactive protein (CRP) in non-ICU patients. N and S specific IgM and IgG increased gradually after symptom onset and can be used for detection of SARS-CoV-2 infection. Analysis of the dynamics of S-IgG may help to predict prognosis.

Aim: To compare the efficacy of single- and double-species mite allergen immunotherapy. Materials and methods: An open, pseudo-randomized, controlled study was conducted (n = 125 allergic rhinitis patients). The primary end point involved the visual analogue scale. Secondary end points included a basophil activation test and serum specific IgE and IgG4 assays. Results: Visual analogue scale analysis indicated considerable reductions in both groups. Both treatments improved quality of life and induced sIgG4 antibody production. Basophil activation and serum IgE inhibition were not evident in either treatment. Neither treatment displayed an early stage immune synergistic effect on cross-allergens. Conclusions: Both treatments were effective against allergic rhinitis, and statistical differences were not observed. Future studies may require long-term, large-scale research.

Yusi Li,1,&ast; Haisheng Hu,2,&ast; Teng Zhang,1,&ast; Guoliang Wang,1 Huimin Huang,2 Peiyan Zheng,2 Baoqing Sun,2 Xiaohua Douglas Zhang1 1Faculty of Health Sciences, University of Macau, Taipa, Macau, China; 2Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing SunDepartment of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaTel +86 2083062865Fax +86 2083062719Email sunbaoqing@vip.163.comXiaohua Douglas ZhangFaculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, ChinaTel +853 8822 4813Email douglaszhang@um.edu.moPurpose: Public health measures during COVID-19 have led to an unprecedented change in social lifestyle which might have an impact on the allergen sensitization in population. We sought to explore the prevalence patterns of serum inhalant and food allergen-specific IgE (sIgE) sensitization and serum total immunoglobulin E (tIgE) level among patients with clinical symptoms of suspected allergic diseases before and during the COVID-19 pandemic in south China.Patients and Methods: A large epidemiology study was conducted on the prevalence patterns of sIgE sensitization and serum tIgE level among 13,715 patients with allergic symptoms in south China from 2017 to 2020. Chi-square test and Fisher exact test were used to test statistical significance of allergen sensitization difference among years. Logistic regression was performed to assess the magnitudes of the differences among years by adjusted odds ratios and 95% confidence intervals.Results: The number of hospital visits for patients with suspected allergy symptoms decreased during COVID-19. The positive rates of indoor inhalant allergens (house dust mites, German cockroach, dog dander) and tIgE increased significantly in 2020, while no significant differences were found in food allergens (egg white, milk, soya bean, shrimp) before and during the COVID-19 pandemic. The odds of sIgE positives in indoor inhalant allergens and tIgE positive for 2017 and 2020 were all larger than 1.00. After grouping by age and gender, there were significant differences in the positive rates of indoor inhalant allergens and tIgE when comparing 2020 with 2017.Conclusion: The prevalence of sensitization increased significantly to indoor inhalant allergens but not to food allergens in south China during the COVID-19 pandemic.Keywords: allergy, epidemiology, specific immunoglobulin E, total immunoglobulin E

Allergen immunotherapy (AIT) is the only treatment that can change the course of allergic diseases. However, there has not been any research on metabolic reactions in relation to AIT with single or mixed allergens. In this study, patients with allergic rhinitis caused by Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) were treated with single-mite (Der p) and double-mite (Der p:Der f = 1:1) subcutaneous immunotherapy (SCIT), respectively. To compare the efficacy and the dynamic changes of inflammation-related single- and double-species mite subcutaneous immunotherapy (SM-SCIT and DM-SCIT), we performed visual analogue scale (VAS) score, rhinoconjunctivitis quality of life questionnaire (RQLQ) score and serum metabolomics in allergic rhinitis patients during SCIT. VAS and RQLQ score showed no significant difference in efficacy between the two treatments. A total of 57 metabolites were identified, among which downstream metabolites (5(S)-HETE (Hydroxyeicosatetraenoic acid), 8(S)-HETE, 11(S)-HETE, 15(S)-HETE and 11-hydro TXB2) in the ω-6-related arachidonic acid and linoleic acid pathway showed significant differences after approximately one year of treatment in SM-SCIT or DM-SCIT, and the changes of the above serum metabolic components were correlated with the magnitude of RQLQ improvement, respectively. Notably, 11(S)-HETE decreased more with SM-SCIT, and thus it could be used as a potential biomarker to distinguish the two treatment schemes. Both SM-SCIT and DM-SCIT have therapeutic effects on patients with allergic rhinitis, but there is no significant difference in efficacy between them. The reduction of inflammation-related metabolites proved the therapeutic effect, and potential biomarkers (arachidonic acid and its downstream metabolites) may distinguish the options of SCIT.

Approximately 30% of the world population suffers from immunoglobulin-E (IgE)-mediated allergy. IgE-mediated allergy affects the respiratory tract, the skin and the gastrointestinal tract and may lead to life-threatening acute systemic manifestations such as anaphylactic shock. The symptoms of allergy are mediated by IgE-recognition of causative allergen molecules from different allergen sources. Today, molecular allergy diagnosis allows determining the disease-causing allergens to develop allergen-specific concepts for prevention and treatment of allergy. Allergen-specific preventive and therapeutic strategies include allergen avoidance, vaccination, and tolerance induction. The implementation of these preventive and therapeutic strategies requires a detailed knowledge of the relevant allergen molecules affecting a given population. China is the world´s most populous country with around 1.4 billion inhabitants and an estimated number of more than 400 million allergic patients. Research in allergy in China has dramatically increased in the last decade. We summarize in this review article what is known about the dominating allergen sources and allergen molecules in China and what further investigations could be performed to draw a molecular map of IgE sensitization for China as a basis for the implementation of systematic and rational allergen-specific preventive and therapeutic strategies to combat allergic diseases in this country.

Zhifeng Huang,&ast; Huiqing Zhu,&ast; Runpei Lin, Liting Wu, Nairui An, Peiyan Zheng, Baoqing Sun National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Peiyan ZhengNational Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, 151 Yan Jiang Road, Guangzhou, 510120, People’s Republic of ChinaTel +86 18816781502Email sunbaoqing@vip.163.com; gdmcslxx@126.comBackground: The prevalence of allergies has increased significantly in the past decade. Further research on allergic diseases caused by furry animals is of great importance for the clinical prevention, diagnosis and treatment of allergies.Objective: To identify the sensitization profile and clinical association of various furry animal crude extracts and components based on component resolved diagnosis (CRD).Methods: A total of 211 patients with allergic rhinitis with sensitivities to cats and/or dogs were recruited, and the specific immunoglobulin E (sIgE) against various furry animals (such as dog/cat extracts and their components, pigeon, parrot, duck, chicken, sheep, rat, mouse, goose, cow and horse extracts) were measured to analyze the sensitization profiles, cross-reactivity and clinical relevance with regards to allergies.Results: A total of 91.67% of cat-sensitized patients were sensitive to Fel d 1, while only 16.03% of cat-sensitized patients responded to Fel d 2. Can f 1 and Can f 5 were the major components of dogs, and the positive rates were 23.53% and 16.18%, respectively. Twenty percent of patients were sensitized to 10 other furry animals, and the positive rate was between 0% and 19.12%. There was a significant correlation between components (Can f 1– 5 and Fel d 2) and 5 furry animals (mouse, sheep, Horse, rat, cow), especially between serum albumin (SA) (Can f 3, Fel d 2) and furry animals. Most of the animal crude extracts and components sensitization rates in patients who were SA-positive were significantly higher than that of patients who were SA-negative. In particular, for sensitization to mice, sheep, horses, rats and cows, more than 10-fold higher in patients who were SA-positive than in patients who were SA-negative. The VAS of symptoms and life of quality (LoQ) in the SA-sensitized patients was higher than that in unsensitized patients, and the patients with lipocalin sensitivities had a worse LoQ.Conclusion: Serum albumin Fel d 2 and Can f 3, as minor allergens in cats and dogs, but not lipocalin or prostatic kallikrein, is associated with other furry animals presumably due to serum albumin cross-reactivity. Patients sensitized with serum albumin had a significantly higher risk of sensitization to other animals and had a higher rhinitis VAS score.Keywords: serum albumin, furry animals, allergy rhinitis, component-resolve diagnosis, cross sensitization

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Till now, no studies have been reported on revealing mechanisms and identifying biomarkers by integratively analyzing transcriptome and proteomes of IPF patients. Here we examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways of immune system activities and inflammatory responses, while DE proteins are associated with extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of BTNL9 and PLLP and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.

Vaccines are a crucial part of the global anti-pandemic effort against COVID-19. The effects of vaccines, as well as their common influencing factors, are the most important issues that we should focus on at this time. To this end, we review statistics on immunogenicity after vaccination, using neutralizing antibodies as the main reference index. Age, infection history, and virus variants are compared, and vaccination program recommendations are made accordingly. Suggestions are made to address concerns raised by the vaccines’ shortened development cycle, as well as the emergence of immunity escape of viral variants. Finally, a brief description and future prospects are provided based on the principle of the ADE effect and previous experience with similar viruses.

Background: Component-Resolved diagnosis (CRD) can help to establish immunoglobulin E (IgE) sensitization profiles and potential risks and determines whether specific IgE is the result of primary sensitization or cross-reactivity, especially for those who are polysensitized. Methods: We recruited 432 patients with mite-sensitized respiratory allergic diseases to study the co-sensitization and cross-reactivity of the 17 allergen components in Guangdong Province, China, using the CRD method and to describe the potential association between allergen components. Results: Among the 432 patients, serum specific immunoglobulin E of the 17 components were tested by EUROIMMUN system. Der p 1 (81.48%), Der f 2 (77.78%), Der f 1 (74.07%), Der p 2 (66.20%) and Der p 23 (54.63%) were the main sensitized components in patients with mite-sensitized respiratory allergy, while the components of cockroach, crab, and shrimp had a lower positive rate. In the crude extract allergen-positive samples, Der f 2 (91.06%) and Der f 1 (86.72%) were the major sensitized components of Der f, while Der p 1 (94.52%), Der p 2 (78.36%), Der p 23 (63.29%) were the major sensitized components of Der p, And other components of Der p such as Der p 7 (34.25%), Der p 5 (17.81%), Der p 10 (12.05%), Der p 3 (1.92%) were all below 50.00%. Blo t 5 (54.55%) was one of the major components of Blo t. The positive rates of all Bla g components were as follows, rBla g 2 (15.56%) >rBla g 5 (8.89%) >rBla g 4 (4.44%) >rBla g 1 (1.11%). The positive rate of the only available pen a 1 component was 9.43%. Using hierarchical cluster and optimal scale analysis, 17 components can be roughly divided into 5 different sensitization clusters. Also, from the results of the Venn diagram, the allergen component in each cluster has a high proportion of co-sensitization and cross-reactivity. Regardless of age, total IgE levels, and disease type factors, similar sensitization profiles were observed for each component in the same category based on hierarchical clustering analysis. Conclusions: Epidemiological data on allergen components causing allergic symptoms can be further understood using CRD. Der p 1, Der p 2, Der p 23, Der f 1, Der f 2 as the primary sensitizing component of the study cohort. The positive rate for Blo t 5 was 28.01% for all populations and 54.45% for Blo t-positive samples. In addition, CRD allows us to identify more potential allergen associations such as common sensitivities and cross-reactions between component proteins. Based on these results, we suggest that when patients are identified as sensitized to a particular allergen, clinicians can pay more attention to other allergy components that are closely related to it.

BACKGROUND Factors attributable to the level of fraction of exhaled nitric oxide (FeNO) in different age groups of asthmatic children are still lack of report. OBJECTIVE To evaluate factors associated with FeNO and the response of FeNO to inhaled steroid in different age groups of asthmatic children with allergic rhinitis. METHODS Asthmatic children aged 5 to 12 years were recruited. FeNO, lung function and bronchial hyperresponsiveness (BHR) to methacholine, skin prick testing to a panel of aeroallergens, total immunoglobulin E (T-IgE) in serum and eosinophils in blood were tested. Correlations between FeNO and the measured parameters were assessed. FeNO was measured again after the treatment of combined inhaled corticosteroid and long-acting beta-agonist (ICS/LABA) for 4 weeks. Changes in FeNO between different age groups were compared. RESULTS A total of 121 eligible subjects were enrolled in and completed this study. Asthmatic children aged 10 to 12 years old had significantly higher FeNO than those between 8 and 9 years and 5 to 7 years of children (both P

Background and objective The prevalence of asthma is greater than 20% in patients previously diagnosed with COPD. Patients with asthma-COPD overlap (ACO) are at risk of rapid progression of disease and severe exacerbations. However, in some patients with ACO, a clear distinction from COPD is very difficult by using physiological testing techniques. This study aimed to apply a novel metabolomic approach to identify the metabolites in sera in order to distinguish ACO from COPD. Methods In the study, blood samples were collected from patients with COPD, ACO, and healthy controls. Cholamine derivatization-ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to investigate serum metabolites of eicosanoids. Results A clear intergroup separation existed between the patients with ACO and those with COPD, while ACO tends to have higher serum metabolic levels of eicosanoids. A robust Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) model was found for discriminating between ACO and COPD (R2Y =0.81, Q2=0.79). In addition, there is a significant correlation between some metabolites and clinical indicators, such as hydroxyeicosatetraenoic acids (HETEs), hydroperoxyeicosatetraenoic acids (HPETEs) and FEV1/FVC. The higher values of area under the receiver operating characteristic curves (ROC) of HETEs, which were metabolized from HPETEs through lipoxygenase (LOX), indicated that they should be the potential biomarkers to distinguish ACO from COPD. Conclusion Eicosanoids can clearly discriminate different biochemical metabolic profiles between ACO and COPD. The results possibly provide a new perspective to identify potential biomarkers of ACO and may be helpful for personalized treatment.

Background Allergic diseases are increasing yearly. We aimed to evaluate the difference in allergen sensitization pattern between adults and children in southern China by analyzing a large sample size of real-life data, and to provide the evidence for formulating the prevention and management strategies. Methods Retrospective analysis was conducted on 39,813 serum allergen-specific IgE (sIgE) results collected in southern China from January to December in 2017. Sensitization patterns and how these allergens could lead to the allergic diseases were analyzed for adults and children respectively. The difference of allergen positive rate between groups was calculated using the Chi square test. Results The top five most sensitized allergens in southern China were house dust mite (28.1%), cockroach (24.3%), shrimp (19.2%), crab (15.5%) and egg white (9.9%). While cockroach had the highest positive rate in adults (29.2%), the most sensitized allergen in children was house dust mite (29.7%). The positive rates of egg white and cow’s milk in children were higher than in adults for the whole year (p

Objective Using multiplex microarray-based component resolved diagnosis (CRD) to investigate the allergen sensitization profile of allergic asthma patients in southern China. Method Serum samples from 57 polysensitized mite allergic asthmatic patients in a tertiary referral centre of southern China were tested with multiplex CRD (ISAC) for specific immunoglobulin E (sIgE) against 112 single allergen and components. Result was then compared with those from singleplex ImmunoCAP. Results With ISAC, the highest sensitization was seen for nDer f 1 (71.9%), rDer f 2 (73.7%), nDer p 1 (70.2%) and rDer p 2 (66.7%), whereas rDer p 10 and other storage mites’ components only showed 10% positivity. rFel d 1 and rCan f 1 were found positive in 29.8% and 14.0% samples respectively. Other epithelia components had less than 7.0% positive rate. Sensitization to pollen components was dominated by nCyn d 1 (17.5%) and nPhl p 4 (12.3%), Carbohydrate cross-reactive determinants (CCD) was positive in 4 patients who were also positive to nPhl p 4, nCyn d 1 and rPla a 2, and all of them have combined asthma and rhinitis. The sensitivity to mold (rAsp f 3), cockroach (nBla g 7) and Anisakis simplex component (rAni s 3) were all the same at 8.8%. 93.0% patients were sensitive to more than one component, with more than half of them (57.9%) positive to five or more components. Patients with combined asthma and rhinitis (AA + AR) were sensitive to more components than those with asthma only (AA). Positive rate to nPhl p 4 was significantly higher in patients with AA + AR than with AA only (χ2 = 4.31, P = 0.038). Compared with ImmunoCAP, ISAC showed a similar high detection rate for D. pteronyssinus and D. farinae, but only 10.0% of B. tropicalis sensitive patients were positive to rBlo t 5. Optimal scale analysis on correlation of allergens components showed rDer p 10 was associated to food allergy. Conclusion Being the first multiplex microarray based CRD study on southern Chinese, ISAC showed house dust mites components were the major allergen components led to sensitization in asthmatic patients. Patients with combined AA + AR were sensitive to more components than those with AA only. Other components with higher positive rate include pollen components nCyn d 1, nPhl P 4 and animal dander components rFel d 1 and rCan f 1. For B. tropicalis, the rBlo t 5 in ISAC may not represent the major Blomia component in southern Chinese patients.

Background: The objective of this study was to evaluate the diagnostic value of serological markers Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), SP-D, chemokine ligand 2 (CCL2), and chemokine 13 (CXCL13) in idiopathic interstitial pneumonia (IIP). Methods: Patients with IIP aged 18–80 years from the First Affiliated Hospital of Guangzhou Medical University were enrolled in this retrospective case-control study. Data on the general patient characteristics, laboratory test results, chest high-resolution CT, and pulmonary function test results were collected. The diagnosis of idiopathic pulmonary fibrosis (IPF) was based on the international practice guidelines for the diagnosis and treatment of IPF, a collaborative effort published by the American Thoracic Society (ATS)/European Respiratory Association (ERS), Japanese Respiratory Society, and Latin American Thoracic Society. The diagnostic criteria of non-IPF (N-IPF) followed the consensus classification of the IIPs, which was jointly issued by the ATS and ERS in 2002. The diagnosis of interstitial pneumonia with autoimmune features (IPAF) was based on the official research statement on IPAF, which was jointly issued by the ATS and ERS in 2015. Serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were measured. The differences in the expression of these biomarkers and their correlation with the severity of the disease were analyzed. The sensitivity, specificity, cutoff value, and area under the curve (AUC) value for each of the indices were determined using the receiver operating characteristic (ROC) curve analysis. Findings: Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, ­SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. The detection of these markers was found to have better diagnostic efficacy in patients with IIP than in those with pneumonia. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93–0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide (DLCO; r = –0.36, –0.37, –0.36, –0.30, respectively; all p < 0.05). Although their expression levels along with that of SP-D were elevated in patients with IPF, N-IPF, and IPAF, it was difficult to distinguish between these 3 conditions by detecting the 5 serum biomarkers together. Our findings indicate that the serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enriched the study on serum markers for IIPs. Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93–0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the DLCO (r = –0.36, –0.37, –0.36, –0.30, respectively; all p < 0.05). Our findings indicate that the serum levels of KL-6, ­SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enrich the study on serum markers in IIPs. Interpretation: Although the combined detection of KL-6, CCL3, and CXCL13 significantly improves the diagnosis of IIP, detection of all the 5 markers together is unable to distinguish between IPF, N-IPF, and IPAF.

BACKGROUND Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported. OBJECTIVE Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring. METHODS Untargeted metabolomics using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR-DDT-13003728). RESULTS Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)-hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p

Wenting Luo,* Huimin Huang,* Peiyan Zheng, Jinping Zheng, Baoqing Sun Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baoqing Sun; Jinping ZhengDepartment of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong Province, People’s Republic of ChinaTel +86-20-8306-2865Email sunbaoqing@vip.163.com; 18928868238@163.comObjective: The presence of cross-reactive carbohydrate determinants (CCDs) may cause false-positive results in vitro allergen sIgE tests. In this paper, we focused on pollen sensitisation and its relationship with CCD in patients with respiratory allergic diseases in South China. A CCD inhibition test was conducted to assess whether patients were truly allergic to pollen or whether their sIgE was caused by a CCD cross-reaction, thus providing an important basis for clinical diagnosis and treatment.Methods: Patients with known serologic pollen sensitization were selected, and sIgE of mugwort, tree mix 20 (willow/poplar/elm tree), common ragweed, Humulus scandens, peanut, soybean and CCD was detected via the EUROBlotMaster system. Thirteen CCD-sIgE negative patients and 33 CCD-positive patients were selected, and their serum samples were subjected to the CCD inhibition test.Results: We found that 66.0% to 95.9% of patients sensitised to pollen and seed food allergens were co-sensitized to CCD. Additionally, 73.0% to 100% of the sIgE tests for pollen and seed food allergens turned negative after inhibition, mostly for allergens from Humulus scandens (100%, 15/15), followed by mugwort and peanut (85.2%, 23/27), ragweed (81.5%, 22/27), soybean (80.0%, 20/25), and tree pollen (73.0%, 19/26).Conclusion: CCD causes false positives in the in vitro allergen sIgE tests of patients with respiratory allergic diseases in South China. Attention should be paid to the use of CCD inhibitors in diagnosing in vitro allergies because of their importance in diagnosing and treating local allergic diseases.Keywords: pollen allergen, food allergen, false-positive, cross-reactive carbohydrate determinants, CCD, special IgE, EUROBlotMaster

This work proposes an underwater wireless optical communication (UWOC) system based on computational temporal ghost imaging (CTGI) and a low-bandwidth high-sensitivity avalanche photodiode. After measuring the attenuation coefficient of water, a series of neutral density filters is used to attenuate the optical power to estimate the distance of UWOC. Experimental results show that under the conditions of 4 GHz transmitting frequency and 144.37 m estimated distance, through CTGI, we can achieve error-free transmission, and the peak signal-to-noise ratio is much higher than on–off keying. Additionally, after adopting the segmented reconstruction method, under the condition of 4 GHz transmitting frequency and 193.10 m estimated distance, we can also achieve error-free transmission. At the same time, the relationship between UWOC performance and the number of segments is also studied. This research provides a novel UWOC technique that enables high-frequency transmission signals to be detected by a low-bandwidth photodetector for long-distance UWOC.

Background Allergic rhinitis is one of the most common nasal inflammatory diseases among children. Assessment of clinical symptoms, skin prick test and serum immunoglobulin E (IgE) are common methods used to diagnose allergic rhinitis and assess inflammation degree in clinical settings. However, via blood tests assess eosinophils inflammation is invasive, and may cause fear in children. It makes have burden of the diagnosis of allergic rhinitis. Nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) are noninvasive, inexpensive, and can provide immediate results. These methods may therefore be preferable to assess the inflammation of allergic rhinitis. Methods This study was a retrospective analysis. We recruited 61 children with allergic rhinitis from November 2019 to March 2020. The participants were assessed using the FeNO and nNO tests. We also administered questionnaires and carried out traditional allergen and blood tests. We analyzed the relationship between diagnosis results and FeNO and nNO levels before and after the treatment of allergic rhinitis, to investigate the clinical application of FeNO and nNO levels for assess eosinophilic inflammation of allergic rhinitis in children. Results We observed a significant association both FeNO, nNO level with eosinophils, total IgE. In different levels of eosinophils (EOS), the correlation of detection parameters had obvious change. FeNO and nNO levels were obvious higher compared to pre-treatment. Conclusions Using NO concentration can indicates the extent of allergic inflammation and can measure allergy treatment effects combine other influence indexes. The combined use of FeNO and nNO levels may be a useful method for assess the degree of eosinophilic inflammation of allergic rhinitis in children.

Background: Because of the limited epidemiological evidence on the association between acute air pollutants and allergy, there is a need to investigate this association, especially between the short-term exposure to air pollution and the serum Immunoglobulin E (IgE)-mediated allergy. Methods: A total of 39,569 IgE test results and demographic characteristics were obtained in the First Affiliated Hospital of Guangzhou Medical University between August 2012 and September 2019. Ninety-nine specific allergens were tested according to clinical diagnosis. The logistic regression was used to assess the effects of CO, NO2 and PM2.5 exposure on the risk of sensitization to specific inhalant/food allergens. Generalized additive models with multivariate adjustments were utilized to model the exposure-response relationship. Stratified analyses were performed to estimate the reliability of correlations in various subgroups. Findings: Single-pollutant models indicate that the 3-day moving average (lag2–4) of CO, PM2.5 or NO2 is associated with the increased risk for allergic diseases related to specific inhaled allergens. In multi-pollutant models, the adjusted Odds Ratio (OR) 95% (Confidence Interval, CI) increases by 8% (95% CI, 2%–15%) for per increment of 0.2 mg/m3 in CO levels, and rises by 8% (95% CI, 2%–13%) for each increase of 16.3 μg/m3 in PM2.5 concentration. The associations are stronger in youngsters (

BackgroundImmunoglobulin E (IgE) plays an important role in asthma, but a few cases exhibited extremely high levels of serum total IgE. This study aimed to investigate the profiles of complications, severity, and sensitizations in asthma patients with serum total IgE level >1000 kUA/L.MethodsWe retrospectively analyzed 170 asthma patients with serum total IgE levels >1000 kUA/L from the in-patient database of First Affiliated Hospital of Guangzhou Medical University from January 2014 to June 2019. Available information including age, gender, body mass index (BMI), diagnosis, results of blood routine, pulmonary function, fractional exhaled nitric oxide (FeNO), induced sputum (if any), IgE (both total and specific) and medication records were analyzed. ResultsAbout 15% patients had at least one complication, and 78.82% patients were positive for at least one allergen. The top two complications were airway infections (44.71%) and rhinosinusitis (41.18%), followed by hypertension and/or cardiovascular diseases (20.59%) and COPD (12.94%). And in patients without sensitization, rhinosinusitis accounted for the highest proportion over all complications (45.83%). Serum total IgE levels did not differ among patients with different complications. Overall, mites had the highest positive rate (59.4%). In minors, the positive rates of mites (81.25% vs. 54.35%, P P P P P A. fumigatus specific IgE levels. ConclusionsIn asthma patients with markedly increased serum total IgE levels (>1000 kUA/L), the most common two complications were airway infections and rhinosinusitis despite of sensitization. A. fumigatus specific IgE levels were closely associated with total IgE levels and asthma severity.

Combination of nucleic acid and specific antibody testing is often required in the diagnosis of COVID-19, but whether patients with different nucleic acid and antibody results have different laboratory parameters, severities and clinical outcomes, has not yet been comprehensively investigated. Thus, according to different groups of nucleic acid and antibody results, we aimed to investigate the differences in demographic characteristics, and laboratory parameters among the different groups and predict their clinical outcomes. In our study, nasopharyngeal swab nucleic acids and antibodies were detected by reverse-transcription polymerase chain reaction and chemiluminescence, respectively. Patients with confirmed COVID-19 with different severities, were divided into the PCR+Ab+, PCR+Ab−, and PCR−Ab+ groups. Demographic characteristics, symptoms, comorbidities, laboratory parameters, and clinical outcomes were compared among the three groups. The correlation of antibodies with laboratory parameters and clinical outcomes was also explored, and antibodies were used to predict the timing of nucleic acid conversion. We found that a total of 364 COVID-19 patients were included in the final analysis. Of these, a total of 184, 37, and 143 patients were assigned to the PCR+Ab+, PCR+Ab−, and PCR−Ab+ groups, respectively. Compared to patients in the PCR+Ab− or PCR− Ab+ groups, patients in the PCR+Ab+ group presented worse symptoms, more comorbidities, more laboratory abnormalities, and worse clinical outcomes (P < 0.05). In addition, the levels of IgG, IgM, and IgA were all significantly correlated with the days of hospitalization, days of PCR turning negative, and multiple laboratory parameters (P < 0.05). Meanwhile, combined IgM, IgA, and IgG predicted the days of PCR turning negative within 1 week. The best performance was achieved when the cut-off values of IgM, IgG, and IgA were 3.2, 1.8 and 0.5, respectively, with a sensitivity of 73% and specificity of 82%. In conclusion, COVID-19 patients who were both positive for nucleic acids and antibodies presented with worse clinical features, laboratory abnormalities, and clinical outcomes. The three specific antibodies were positively correlated with clinical outcomes and most laboratory parameters. Furthermore, antibody levels can predict the time of nucleic acid conversion.

BACKGROUND Allergic bronchopulmonary aspergillosis (ABPA) is an airway disease caused by Aspergillus (mainly Aspergillus fumigatus). OBJECTIVE To evaluate the diagnostic performance of four fungal-related allergen-specific immunoglobulin E (sIgE) detection systems. METHODS A total of 99 patients with ABPA and 30 control patients admitted to the First Affiliated Hospital of Guangzhou Medical University from 2017 to 2019 were included in the study. Four allergen detection systems were used to detect Aspergillus-related sIgE. RESULTS The 99 patients were divided into two groups based on the total IgE. Fluorescence immunoassay for fungal mixtures detected positive rates of 100% and 81% in the Confirmed and Probable groups, respectively. For Aspergillus fumigatus, the positive rates were 90.2% and 87.9%, respectively. In the detection of sIgE of fungal mixtures in all ABPA patients, the sensitivity of System 1 was 90.9%, which was higher than for the other three systems (System 2, 38.4%; System 3, 44.4%; System 4, 52.5%), All four systems have excellent specificity ( > 90.0%) and had higher consistency in the Confirmed group than in the Probable group (P < 0.05). Consistency for the Aspergillus mixture and Aspergillus fumigatus detected by fluorescence immunoassay was 90.2% and 86.2% in the Confirmed and Probable groups, respectively. CONCLUSIONS Despite the many methods used to detect fungal-related sIgE, the ImmunoCAP system has the best clinical diagnostic performance. It is recommended that this method be used to detect fungal (mixtures or Aspergillus fumigatus) sIgE in order to reduce the missed diagnosis rate of ABPA.

Background: Public health measures during COVID-19 have led to an unprecedented change in social lifestyle which might have an impact on the allergen sensitization in population. We sought to explore the prevalence patterns of serum allergen-specific IgE (sIgE) sensitization and serum total immunoglobulin E (tIgE) level among patients with clinical symptoms of suspected allergic diseases before and during the COVID-19 pandemic in south China. Methods: We assessed cross-sectional datasets from the First Affiliated Hospital of the Guangzhou Medical University from 2017 to 2020. Data on clinical symptoms of the patients with suspected allergic diseases in the hospital were collected and data from February to June in each year were extracted. Chi-square test and Fisher exact test were used to test statistical significance among years. Adjusted odds ratios and 95% confidence intervals were used to assess the magnitudes of the differences among years. Findings: The number of hospital visits for patients with suspected allergy symptoms decreased compared with previous years during COVID-19. For inhalant allergens, there was a statistically significant difference (P

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant threat to human health, but its clinical manifestations vary greatly among individuals. Early detection and treatment are important for severely ill patients to improve their prognosis and reduce the risk of death. Methods: In the present study, serum markers were detected and analyzed in moderately ill and severely ill patients. Results: The results found that there were statistically significant differences in age, serum Krebs von den Lungen-6 (KL-6) and Immunoglobulin A (IgA) levels between severely ill patients and moderately ill patients (P < 0.05). The cut-off of using KL-6 alone for the diagnosis of severely ill patients was 298.91 U/mL, with an AUC of 0.737, a sensitivity of 100%, and a specificity of 43%. When the diagnosis was performed using KL-6 in combination with Interleukin-6 (IL-6), an indicator of infection, the AUC was 0.776, with a sensitivity and specificity of 82% and 69%, respectively. When the three above were used in combination for diagnosis, the AUC was 0.785, and the sensitivity and specificity were 100% and 59%, respectively. After rehabilitation, the serum levels of KL-6, C-reactive protein (CRP), as well as antibodies, IgA, IgM and IgG, were significantly lower than those in the early stage of hospitalization. Conclusion: In the present study, KL-6 and IgA were found to have some diagnostic efficacy for severely ill patients with COVID-19, but larger cohort studies are still needed for further confirmation, which in turn improves the diagnostic and therapeutic efficiency of severely ill patients.

Background The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to determine patients’ prognoses. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) were known biomarkers as a monitor of the prognoses. However, the clinical or pathophysiological differences of those biomarkers are not well evaluated. Therefore, through the comparison of the changes of SP-A and KL-6 levels before and after treatment, we investigated the clinical or pathophysiological differences which are embodied by those markers. Methods This study included retrospective data for 71 patients treated for ILD at the First Affiliated Hospital of Guangzhou Medical University between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed for at least 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were significantly correlated (rS = 0.482, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (P < 0.05). In a cluster analysis of delta SP-A and KL-6 levels, patients were classified into three groups. In the cluster analysis, in the group in which only SP-A levels decreased after treatment, 50.0% of patients recovered respiratory function and had a significant reduction of serum LDH levels.Conclusions Reduced serum SP-A and/or KL-6 levels were associated with improved lung function in patients with ILD. However, there were patients who showed only a reduction of SP-A levels after treatment. Thus, for proper disease monitoring, measuring both markers are important.

The clinical relevance of Krebs von den Lungen-6 (KL-6) levels in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to evaluate the correlation between KL-6 levels, laboratory parameters, and clinical outcomes. We enrolled 364 patients with confirmed COVID-19 who were hospitalized within 1 week of symptom onset. Their serum KL-6 level was measured on admission. Demographic data, symptoms, comorbidities, and laboratory parameters were recorded at the time of admission. Days to nucleic acid conversion and days of hospitalization were defined as clinical outcomes for evaluating the clinical relevance of serum KL-6 levels in COVID-19. Patients with elevated KL-6 levels were significantly older; had more reported instances of fever, cough, fatigue, and wheezing; and a longer hospital stays than those with normal KL-6 levels; the difference was statistically significant (p

Background: It was estimated that about 10% of the population suffer from food allergy. Atopic dermatitis is often associated with food allergy. In this case report, we presented a child with atopic dermatitis who was sensitive to multiple food and inhaled allergens. Case report: A 3-year-old boy was admitted to the First Affiliated Hospital of Guangzhou Medical University due to skin allergy caused by drinking semi-hydrolyzed infant formula milk powder. Allergen test results showed that the boy was sensitive to multiple food and inhaled allergens. we conducted the follow-up interview by phone to completed the questionnaire. Conclusion: Atopic dermatitis children with multiple food allergies must pay attention to diet adjustment to prevent or delay the development of the disease.

Our study intended to longitudinally explore the prediction effect of IgA on pulmonary exudation progression in COVID‐19 patients. The serum IgA was tested with chemiluminescence method. Autoregressive moving average (ARMA) model was used to extrapolate the IgA levels before hospital admission. The positive rate of IgA and IgG in our cohort was 97% and 79.0%. The IgA was peaked in 10‐15 days after admission, and IgG was peaked at the time of admission time while HRCT and chest PA & LAT (posteroanterior oblique and lateral views) were peaked in 20‐25 days after admission. We found that the time difference between their peaks was about 10 days. Viral RNA detection results showed that the positive rate in sputum and feces were the highest. Blood gas analysis showed that deterioration of hypoxia with the enlargement of pulmonary exudation area. And alveolar‐arterial oxygen difference (A‐aDO2) and oxygenation index were correlated with IgA and IgG. The results of biopsy showed that the epithelium of lung was exfoliated and the mucosa was edematous. In severe COVID‐19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS‐CoV‐2. This article is protected by copyright. All rights reserved.

The capacity to accurately diagnosis COVID-19 is essential for effective public health measures to manage the ongoing global pandemic, yet no presently available diagnostic technologies or clinical protocols can achieve full positive predictive value (PPV) and negative predictive value (NPV) performance. Two factors prevent accurate diagnosis: the failure of sampling methods (e.g., 40% false negatives from PCR testing of nasopharyngeal swabs) and sampling-time-dependent failures reflecting individual humoral responses of patients (e.g., serological testing outside of the sero-positive stage). Here, we report development of a diagnostic protocol that achieves full PPV and NPV based on a cohort of 500 confirmed COVID-19 cases, and present several discoveries about the sero-conversion dynamics throughout the disease course of COVID-19. The fundamental enabling technology for our study and diagnostic protocol—termed SANE, for Symptom (dpo)-Antibody-Nucleic acid-Epidemiological history—is our development of a peptide-protein hybrid microarray (PPHM) for COVID-19. The peptides comprising PPHMcovid-19 were selected based on clinical sample data, and give our technology the unique capacity to monitor a patient’s humoral response throughout the disease course. Among other assay-development related and clinically relevant findings, our use of PPHMcovid-19 revealed that 5% of COVID-19 patients are from an “early sero-reversion” subpopulation, thus explaining many of the mis-diagnoses we found in our comparative testing using PCR, CLIA, and PPHMcovid-19. Accordingly, the full SANE protocol incorporates orthogonal technologies to account for these patient variations, and successfully overcomes both the sampling method and sampling time limitations that have previously prevented doctors from achieving unambiguous, accurate diagnosis of COVID-19.

Background Few studies have assessed the sensitization of mycotic allergens and Aspergillus fumigatus molecular allergens. This study aimed to investigate the relationships of A fumigatus components and mycotic allergens in allergic bronchopulmonary aspergillosis (ABPA) patients and A fumigatus (Af)‐sensitized asthma patients. Methods Serum sIgE levels of Penicillium chrysogenum, Cladosporium herbarum, Mucor racemosus, Candida albicans, Alternaria alternata, Helminthosporium halodes, and A fumigatus allergen components (Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6) were measured via the ImmunoCAP assay in 18 ABPA and 54 Af‐sensitized asthma patients in Guangzhou city, China. Results 94.44% of ABPA patients and 87.04% of Af‐sensitized asthma patients were co‐sensitized to at least one other fungal allergen. The positive rates of Asp f 1 (88.89% vs 59.26%, P, Patients with ABPA were characterized by higher levels of IgE antibodies to Asp f 1, Asp f 4, and Asp f 6 than those of Af‐sensitized asthma patients (allP

This study aimed to determine the clinical significance of Krebs von den Lungen-6 (KL-6) in patients with COVID-19, so as to find a marker with high sensitivity, specificity and easy detection to evaluate the lung injury and inflammation of COVID-19. Sixty-three COVID-19 patients and 43 non-COVID-19 patients with similar clinical phenotypes and/or imaging findings were enrolled to test the levels of KL-6 using chemiluminescent immunoassay. In addition, the blood gas, imaging and lymphocyte factors tests were collected from all participants. The data was finally analyzed using multivariate statistical analysis. The results showed KL-6 levels in COVID-19 patients were higher than those in non-COVID-19 patients (P < 0.001). Moreover, the KL-6 levels in severe and critically severe patients were significantly upregulated compared with patients with mild and common type (P < 0.05). Meanwhile, the imaging evaluation showed a significant correlation between KL-6 and pulmonary lesion area (P < 0.05). KL-6 was also found to be significantly correlated with oxygenation index and oxygen partial pressure difference of alveolar artery (PA-aDO2) (Both P < 0.01). In conclusion, KL-6 could be an indicator to evaluate the progression of COVID-19, which is parallel to the level of lung injury and inflammation in patients. Moreover, it can also reflect the pulmonary ventilation function.