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PubMed2026

Upper airway microbiome interacts with GSDMB and ORMDL3 asthma risk SNPs to influence early-life wheeze risk.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the chromosome 17q12-q21 region and, independently, early-life nasal microbiota dominated by Moraxella, Streptococcus, or Haemophilus (MSH) increase risk of chronic wheeze and asthma development. OBJECTIVE: We sought to determine whether 17q12-q21 risk SNPs and nasal microbiota interact to modulate childhood wheeze risk. METHODS: Nasal wash samples from 12-month-old infants in 2 birth cohorts, COAST (Childhood Origins of Asthma; n = 180) and URECA (Urban Environment and Childhood Asthma; n = 139), underwent 16S ribosomal RNA variable region 4 sequencing. Nasal microbiota dominated by MSH or Corynebacterium, Dolosigranulum, Staphylococcus, or Bacillus (CDSB) were assessed. Paired blood was genotyped for 9 17q12-q21 risk SNPs. Logistic regression tested interactions between 17q12-q21 SNPs and MSH or CDSB on wheeze risk in the first 3 years of life. A549 lung epithelial cells, CRISPR-edited to encode the rs7216389 risk genotype (rs7216389TT) were compared to the heterozygous (rs7216389CT) line using bulk RNA sequencing. RESULTS: SNPs, particularly those in the ORMDL3 (rs8076131; odds ratio [OR]: 1.72; 95% CI: 1.09-2.71; Pint = .031) and GSDMB (rs2305480; OR: 1.72; 95% CI: 1.09-2.71; Pint = 0.042; and rs7216389; OR: 1.73; 95% CI: 1.09-2.70; Pint = .047) genes, interact with MSH microbiota to increase early-life wheeze risk (false discovery rate Pint = .016 for all), while interactions with CDSB reduce risk. A549 airway epithelial cells homozygous for rs7216389TT exhibited decreased expression of genes involved in antimicrobial responses and neutrophil recruitment and evidence increased microbial adherence compared with the heterozygous cell line. CONCLUSION: Airway microbiota interact with SNPs at the 17q12-q21 locus in genes involved in sphingolipid metabolism and intracellular antimicrobial responses, to modulate wheeze risk.

Humans↗

PubMed2026

Infancy IgE methylation score and childhood wheezing and asthma: Multicohort study.

BACKGROUND: Early-life epigenetic programming may mediate gene-environment interactions underlying recurrent wheezing and asthma. Multi-CpG methylation scores can summarize the epigenetic potential for high IgE beyond what is captured by observed IgE levels. OBJECTIVE: We sought to establish and examine the residual effect of an epigenetic total IgE (DNAm-IgE) score on respiratory morbidity in a pediatric population. METHODS: We used data from the 35th Multicenter Airway Research Collaboration (MARC-35; n = 560), the 43rd Multicenter Airway Research Collaboration (MARC-43; n = 177), and the Boston Birth Cohort (BBC; n = 80). DNA methylation (Illumina EPIC array) was measured in blood during infancy (MARC-35, MARC-43) and in cord blood at birth (BBC). Total IgE was assessed in blood at infancy, recurrent wheezing at age 3 years, and asthma at age 6 years for all cohorts. RESULTS: MARC-35 data were used to train and evaluate a DNAm-IgE score (R = 0.502 vs total IgE). MARC-43 and BBC data were used to validate the score (R = 0.309 and R = 0.132). In meta-analyses of the 3 cohorts, 1 standard deviation of DNAm-IgE score residuals (DNAm-IgE score regressed on total IgE) was associated with recurrent wheezing (OR = 1.33 [95% confidence interval, 1.11, 1.60], Pheterogeneity = .92), while 1 standard deviation of total IgE was associated with asthma (OR = 1.45 [95% confidence interval, 1.19, 1.76], Pheterogeneity = .29). All models were adjusted for sex, race/ethnicity, and birth weight. CONCLUSION: Early-life epigenetic patterns related to total IgE may contribute to subsequent respiratory morbidity beyond measured IgE levels. The DNAm-IgE score and its residual component should be viewed as exploratory tools that require further validation and mechanistic study.

Humans↗

PubMed2024

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic susceptibility to childhood-onset asthma.

Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these "missing regulatory effects". Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Preprint↗

PubMed2024

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 μg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 μg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Humans↗

PubMed2026

Natural language processing-based model to predict radiation pneumonitis in patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy: a retrospective cohort study.

BACKGROUND: Radiation pneumonitis (RP) remains a significant treatment-related toxicity in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) undergoing chemoradiotherapy (CRT). Most existing predictive models rely on static baseline demographic or dosimetry variables and lack real-time clinical applicability. We developed a novel predictive framework that integrates longitudinal symptom data extracted from clinical notes using natural language processing (NLP) with clinical and dosimetry features to improve early RP prediction. METHODS: We retrospectively identified 227 patients with locally advanced NSCLC treated with definitive CRT at a high-volume cancer center in the United States. We included all patients older than 18 years who were diagnosed between Jan 1, 2006, and Dec 31, 2022 with histologically or cytologically confirmed unresectable Stage 2 or 3 NSCLC and treated with conformal radiotherapy to a minimum dose of ≥45 Gy with or without chemotherapy. Of these, 31 RP events were identified through manual adjudication using radiologic criteria and chart review. NLP was used to extract the temporal relationship of 16 pre-specified symptoms with treatment from over 100,000 clinical notes spanning pre- and during-treatment intervals. We trained and validated machine learning models on combinations of baseline clinical data, radiation dosimetry, and NLP-derived symptom features. Model performance was evaluated using a nested cross-validation framework, with an outer cross-validation loop reserved for performance assessment and an inner cross-validation loop used for model training and integration, and summarized using area under the receiver operating characteristic curve (AUC) and partial AUC (pAUC) at high specificity thresholds. Clinical utility was evaluated using decision curve analysis (DCA). FINDINGS: The best-performing model incorporated longitudinal NLP features and achieved a median AUC of 0.759 (90% confidence interval 0.753-0.766), significantly outperforming baseline models using only dosimetry (AUC 0.613) or clinical variables (AUC 0.635). NLP-based features such as cough trajectory, shortness of breath, and wheezing were among the most important predictors. Inclusion of NLP-derived symptom data improved early identification of high-risk patients, particularly in the clinically relevant high-specificity range (pAUC 0.021 vs. 0.010 for dosimetry alone). DCA showed that the calibrated MLP model provided greater net benefit than default strategies of treating all or no patients across clinically relevant threshold possibilities. INTERPRETATION: In this early work, NLP-based extraction of longitudinal symptoms from routine clinical documentation meaningfully enhances RP prediction in patients undergoing CRT for NSCLC. This approach leverages existing electronic health record infrastructure to deliver real-time, scalable, and interpretable risk estimates, offering a pathway toward potential early intervention and personalized toxicity management. The model and DCA requires external and prospective validation before clinical deployment; as such, future work should focus on this validation and integration into clinical decision support systems. FUNDING: AstraZeneca.

Chemoradiotherapy↗

PubMed2024

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma.

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Humans↗

PubMed2026

Unveiling microbial risks in Chinese household dust: a comprehensive analysis from absolute abundance to virulence unit.

BACKGROUND: People spend the majority of their lives indoors, yet the risk and virulence potential of household microbiota remain largely unexplored, particularly in developing countries. RESULTS: Here, we conducted a nationwide survey on both dust samples and health information across 118 Chinese households. The microbiota composition and its functional units were analyzed using absolute 16S rRNA/ITS sequencing, metagenomics, and metaproteomics. Cross-domain network analysis of the core microbial communities revealed robust co-occurrence patterns in household dust. The mean absolute abundance of potentially pathogenic bacteria and fungi in households was 2.39 × 105 and 2.83 × 106 DNA copies/g dust. The potentially pathogenic community was primarily influenced by latitude, relative humidity, and average temperature. Although total absolute abundance was substantially lower in urban areas, the relative abundance of potentially pathogenic bacteria was markedly higher compared to rural environments. While urban-rural differences existed, the underlying statistical drivers were the environmental variables. The absolute abundance of potential pathogens was significantly associated with the prevalence of rhinitis, wheeze, and dermatitis in 266 participants. Children were identified as the highest-risk group from inhalation exposure of average daily dose. A total of 170 bacterial, 223 fungal virulence factors (VFs), and 370 antibiotic resistance genes (ARGs) were detected in dust and dust extracellular vesicle (EV)-associated DNA. EV-associated cargoes contributed 47.13% to the bacterial VF profiles, 11.90% to fungal VF profiles, and 44.45% to ARG profiles. Metaproteomic analysis confirmed the presence of VF profiles in dust EVs, which was further verified by curated proteomics data from 35 household pathogens. CONCLUSIONS: This study provides a comprehensive, quantitative framework linking indoor microbial exposure to health risks, highlighting EVs as a non-negligible, novel, extracellular mechanistic pathway for health impact in household environments. Video Abstract.

Child↗

PubMed2025

Long COVID in Elderly COPD Patients: Clinical Features, Pulmonary Function Decline, and Proteomic Insights.

BACKGROUND: Elderly patients with chronic obstructive pulmonary disease (COPD) face a heightened risk of developing long coronavirus disease (COVID); however the exact clinical characteristics and underlying mechanisms remain unclear. METHODS: We enrolled 85 elderly COPD patients, of whom 43 reported newly onset persistent fatigue (the most dominant complaint of long COVID) within 1 year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and they were allocated to the Long-COVID group. The remaining 42 patients were assigned to the Control group. Patients completed questionnaires, pulmonary function tests, chest CT, routine laboratory tests, and blood proteomic analysis. RESULTS: Long-COVID patients had a longer course of COPD (> 5 years, 76.8% vs 52.4%) and duration of SARS-CoV-2 infection (10.0 days vs 7.0 days) (All P < 0.05), higher symptom burden, worse pulmonary ventilation function and a more rapid decrease in DLCO (All P < 0.05). Proteomic analysis indicated disruptions in inflammation and energy metabolism, potentially underlying long COVID in these patients. The machine learning model identified wheezing, the duration of SARS-CoV-2 infection, EIF2S3 (eukaryotic translation initiation factor 2 subunit gamma), current FEV1/FVC (%), and the course of COPD as key features distinguishing Long-COVID patients, and exhibited excellent performance. CONCLUSION: Elderly COPD patients with a longer COPD course and duration of COVID-19 are more prone to develop long COVID, with decreased pulmonary ventilation and diffusion ability. Disordered inflammation regulation and energy metabolism may be the potential mechanisms, highlighting the importance of monitoring inflammation and metabolic dysregulation in elderly COPD patients after recovery from COVID-19.

Humans↗

PubMed2026

First detection of African swine fever in a swine farm in Taiwan.

INTRODUCTION: African swine fever (ASF) is a highly contagious, high-consequence transboundary animal disease that poses a critical threat to global swine production and agricultural economics. Since its emergence in China in 2018, ASF has spread to over 20 Asia-Pacific countries, causing significant economic disruption. While Taiwan previously detected ASF virus several times in dead pigs drifting offshore, or in illegal pork-related products brought by international tourists and inspected at airport and seaport border controls, no local domestic swine farm had tested positive before this October 2025 ASF event. However, maintaining this disease-free status requires constant vigilance against evolving regional biosecurity threats. METHODS: The first ASF detection in a domestic swine herd in Taichung City, Taiwan, reported on October 22, 2025, was triggered by abnormal alerts of the monitoring system in the rendering plant; the index farm captured a cumulative herd mortality rate of 35.2% that exceeded the predefined threshold (3% mortality daily in the nursery to finish pigs). Five finisher pigs were submitted for diagnostic evaluation, which subsequently confirmed ASFV infection via real-time PCR, pathological examination, immunohistochemistry, virus isolation, and whole-genome sequencing. RESULTS: Affected pigs showed clinical signs including wheezing, sudden death, nasal bleeding, uncoagulated blood in the nostrils, and mild hemorrhage on the skin surface of the neck, abdomen, and buttocks. Histopathological examination revealed severe multisystemic hemorrhagic lesions. Based on assay results of the P72, P54, P30, and CD2v genes, and whole-genome sequence, phylogenetic analysis confirmed that the isolate (ASFV/TWN/2025) is a genotype I/II recombinant strain, most similar to prevailing strains isolated in China and Vietnam, sharing 99.95%-99.97% and 99.92%-99.97% nucleotide similarity of whole genome sequence, respectively. DISCUSSION: Upon confirmation of the ASF case, authorities immediately implemented a nationwide swine movement standstill for 15 days to mitigate transmission risk. To date, no secondary cases have been detected. This article details the early monitoring and rapid diagnosis process of the first case of ASF infection in a farm in Taiwan, and highlights the information from this case to provide lessons for disease diagnosis and prevention in ASF-free areas.

African swine fever↗