Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study.

Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

Long-Term Erythromycin Treatment Alters the Airway and Gut Microbiota: Data from Chronic Obstructive Pulmonary Disease Patients and Mice with Emphysema.

INTRODUCTION: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD. METHODS: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients. RESULTS: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus, and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin treatment group than in the COPD group. CONCLUSION: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.

Multiple intracellular pathogen infections with ocular pathologies associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: a case report.

BACKGROUND: Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient. CASE PRESENTATION: A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders. CONCLUSIONS: High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.

Importance of GWAS risk loci and clinical data in predicting asthma using machine-learning approaches.

INTRODUCTION: To understand the risk factors of asthma, we combined genome-wide association study (GWAS) risk loci and clinical data in predicting asthma using machine-learning approaches. METHODS: A case-control study with 123 asthmatics and 100 controls was conducted in the Zhuang population in Guangxi. GWAS risk loci were detected using polymerase chain reaction, and clinical data were collected. Machine-learning approaches were used to identify the major factors that contribute to asthma. RESULTS: A total of 14 GWAS risk loci with clinical data were analyzed on the basis of 10 times the 10-fold cross-validation for all machine-learning models. Using GWAS risk loci or clinical data, the best performances exhibited area under the curve (AUC) values of 64.3% and 71.4%, respectively. Combining GWAS risk loci and clinical data, the XGBoost established the best model with an AUC of 79.7%, indicating that the combination of genetics and clinical data can enable improved performance. We then sorted the importance of features and found the top six risk factors for predicting asthma to be rs3117098, rs7775228, family history, rs2305480, rs4833095, and body mass index. CONCLUSION: Asthma-prediction models based on GWAS risk loci and clinical data can accurately predict asthma, and thus provide insights into the disease pathogenesis.

Clinical Characteristics, Course, and Long-Term Outcomes in Patients with Talaromyces marneffei Infection: A 10-Year Retrospective Cohort Study.

INTRODUCTION: Talaromyces marneffei (T. marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T. marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. METHODS: We retrospectively analyzed 241 patients with T. marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan-Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0-68.6%) and 47.8% (95% CI 41.5-55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31-0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39-1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22-0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01-0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01-0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. CONCLUSIONS: Patients with T. marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative.

Usage, acceptability, and preliminary effectiveness of an mHealth-based integrated modality for smoking cessation interventions in Western China.

INTRODUCTION: Many smokers have not accessed professional smoking cessation assistance due to limited smoking cessation services. We developed a novel mHealth-based integrated modality for smoking cessation (WeChat + Quitline modality, WQ modality) and applied it to a large public welfare project (China Western-QUIT Program) in western China. This study evaluated the usage, acceptability, and preliminary effectiveness of the WQ modality in the population of western China. METHODS: A prospective cohort study was conducted between April and August 2021. Smokers or their relatives were recruited through online advertisements and medical staff referrals. After using the services of the WQ modality for one month, the self-reported awareness, use, and satisfaction with each service among the participants were collected by a telephone interview. We also evaluated the self-reported 7-day point prevalence of abstinence (PPA) and quit attempt rate among baseline current smokers. The usage data of each service were downloaded from quitline and WeChat platforms. RESULTS: Of the 17326 people from western China using the WQ modality, the largest number of users was WeChat official account (11173), followed by WeChat mini program (3734), WeChat group (669), and quitline (541 inbound calls, 605 outbound calls). At one month follow-up, over 70% of participants who completed the baseline survey (n=2221) were aware of WeChat-based services, and over 50% used them. However, the awareness rate (11.1%) and utilization rate (0.5%) of quitline were relatively low. The median satisfaction scores across all services were 9 out of 10 points (IQR: 8-9). Among the baseline current smokers (n=1257), self-reported 7-day PPA was 41.8% (526/1257), and another 225 smokers (17.9%) reported making a quit attempt. CONCLUSIONS: The WQ modality could be well used and accepted, and it has great potential to motivate and aid short-term smoking cessation in smokers from western China.

Association of GWAS-supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population.

BACKGROUND: Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome-wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS-supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population. METHODS: A case-control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa). RESULTS: The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048-3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001-4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls. CONCLUSION: rs3117098 may be the risk factor for asthma in Chinese Zhuang population.

Association of IL1RL1 rs3771180 and TSLP rs1837253 variants with asthma in the Guangxi Zhuang population in China.

OBJECTIVE: IL-1 receptor-like 1 (IL1RL1) and thymic stromal lymphopoietin (TSLP) play important roles in asthma in various ways. IL1RL1 rs3771180 and TSLP rs1837253 single nucleotide polymorphisms (SNPs) are associated with asthma in some European nationals but not in Zhuang people. Accordingly, this study aimed to determine the associations of IL1RL1 rs3771180 and TSLP rs1837253 with asthma in Zhuang people. METHODS: We performed a case-control study to observe the association between the two polymorphisms and asthma in a Guangxi Zhuang cohort consisting of 123 asthmatic patients and 100 healthy controls. These individuals were recruited from the Department of Respiration of the First Affiliated Hospital of Guangxi Medical University. Multiplex PCR assay was used to identify the genotype of rs3771180 and rs1837253. Data were analyzed with SPSS 22.0 and SHEsis. RESULTS: rs1837253 showed significant differences between asthmatic and control groups in allele comparison (OR = 2.15; 95% CI = 1.27-3.63; P = 0.004), as well as in the homozygote (OR = 4.83; 95% CI = 1.47-16.47; P = 0.012), heterozygote (OR = 2.69; 95% CI = 1.20-6.00; P = 0.016), and dominant (OR = 3.01; 95% CI = 1.39-6.52; P = 0.005) genetic models. However, the genotype frequencies of rs3771180 did not obviously differ. CONCLUSION: rs1837253 is associated with asthma susceptibility and may increase the risk of asthma in Zhuang people in Guangxi.

Epidemiology of childhood asthma in mainland China (1988-2014): A meta-analysis.

BACKGROUND: After the promotion of the two-child policy in recent years, the population of children in mainland China was bound to have a rapid growth, which would bring great challenges to public health. A number of cross-sectional studies on the epidemic of childhood asthma in mainland China were recently conducted, and varied prevalences were reported. Thus, knowing the epidemiology of childhood asthma in mainland China is of great necessity. OBJECTIVE: Our study aimed to summarize the pooled prevalence of childhood asthma in mainland China and its time trend, gender difference, regional distribution, and age structure. METHODS: Studies that reported the prevalence of childhood asthma in mainland China were identified via a systematic data base search through July 1, 2016. Meta-analysis was used to estimate the prevalence of childhood asthma and its subgroups, including gender, age groups, years, and regions. The regional distribution of the prevalence was set by province with the help of a geographic mapping software. The autoregressive integrated moving average model was used to predict the current prevalence of asthma. RESULTS: A total of 117 studies published from 1988 to 2014 in mainland China with a total sample size of 2,678,696 were included. The overall current prevalence and lifetime prevalence of childhood asthma was 2.112% (95% confidence interval [CI], 1.977-2.247%) and 2.502% (95% CI, 2.166-2.838%), respectively. The difference of the prevalences between male and female patients was significant: odds ratio 1.54 (95% CI, 1.47-1.62) for the current prevalence and odds ratio 1.61 (95% CI, 1.47-1.77) for the lifetime prevalence. CONCLUSION: The prevalence of childhood asthma in mainland China was low but has been increasing remarkably since 1998. Boys are more likely to have asthma throughout most of their childhood. Preschoolers (3-6 years old) showed a higher prevalence than the other age groups. The current prevalence of childhood asthma probably increased slightly from 2017 to 2019.

Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies.

BACKGROUND AND OBJECTIVE: A number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case-control studies was thus performed. METHODS: A literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations. RESULTS: Arg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179-2.609, I2 = 16.9%, studies  = 2, case  = 314, control  = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417-0.769, I2 = 0.0%, studies  = 11, case  = 1693, control  =  502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434-0.856, I2 = 0.0%, studies  = 11, case  = 1693, control  = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768-0.971, I2 = 46.9%, n = 18, case  = 3160, control  = 3433). CONCLUSIONS: None of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population.

Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: an updated meta-analysis of case-control studies.

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta-analyses have reported inconclusive results. Therefore, an updated meta-analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant 'null' genotype was compared with wild-type 'present' in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case-control studies were suitable for inclusion in the meta-analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192-1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293-2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051-1.781) and adults (OR = 1.859; 95% CI: 1.183-2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204-4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018-1.667), Africa (OR = 2.175; 95%CI: 1.560-3.031) and Latin America (OR = 2.265; 95%CI: 1.375-3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101-4.025) and Russian (OR = 2.747; 95% CI: 1.071-7.046) populations. This meta-analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.

A disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms and the risk of asthma: a meta-analysis.

Polymorphisms in the ADAM33 gene have been associated with asthma, but the data are controversial. Therefore, we reviewed the related studies and quantitatively summarized the associations between ADAM33 polymorphisms and asthma risk using meta-analysis. A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to estimate the association between ADAM33 polymorphism and asthma risk. A total of 29 case-control studies referring to 14 SNPs were identified: rs2280091(T1), rs2787094(V4), rs528557(S2), rs2280090(T2), rs511898(F+1), rs44707(ST+4), rs3918396(S1), rs543749(V-1), rs574174(ST+7), rs597980(ST+5), rs2853209(S+1), rs2280089(T+1), rs612709(Q-1), and rs3746631(V5). The results indicated that S1, V-1, V5, S+1, S2, ST+4, ST+7, ST+5, and Q-1 were not associated with asthma. Significant associations were found with the T1, V4, F+1 and T+1 polymorphisms in the overall population. In the subgroup analysis by ethnicity, a positive result was only found for the T1, V4, F+1 and T2 polymorphisms in Asia but not in Europe or Latin America. This meta-analysis provides evidence that the T1, V4, F+1, T2, and T+1 polymorphisms in the ADAM33 gene are risk factors for asthma, especially in the Asian population.