Chronic respiratory diseases (CRDs) are a growing global health concern. Emerging evidence implicates circulating metabolites in their development and progression, but definitive causal insights into how metabolic patterns influence disease pathways remain limited. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate potential causal effects of 1400 serum metabolites on 5 major CRDs: chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pneumoconiosis. Each disease was analyzed separately; no composite CRD outcome was constructed. The inverse-variance weighted method was the primary approach, complemented by MR-Egger, weighted median, and MR-PRESSO for outlier detection and correction. Robustness was examined using sensitivity analyses, including Cochran Q for heterogeneity, MR-Egger intercept for directional pleiotropy, the MR-PRESSO global test, and leave-one-out analyses. MR analyses identified significant causal associations between multiple metabolites/metabolite ratios and the 5 CRDs, revealing distinct metabolic profiles for each disease. For COPD, we found 54 potentially causal metabolites (30 risk, 24 protective). Asthma showed 36 associations (13 risk, 20 protective). IPF had 39 (22 risk, 17 protective). Sarcoidosis exhibited the broadest signature with 69 associations (24 risk, 45 protective). Pneumoconiosis showed 53 (25 risk, 28 protective). Most signals were disease-specific; only a small subset overlapped across at least 2 diseases (e.g., four shared between COPD and sarcoidosis, two between pneumoconiosis and asthma), suggesting partially shared pathways. No metabolite displayed consistent associations across all 5 diseases. Circulating metabolites exhibit protective or detrimental causal effects on COPD, asthma, IPF, sarcoidosis, and pneumoconiosis. Effects are heterogeneous and largely disease-specific, with limited overlap across conditions, indicating predominantly distinct etiologic pathways and offering mechanistic insights that may inform risk stratification and target prioritization. Further validation using integrated multi-omics and experimental models is warranted to refine mechanisms and assess translational potential.

This manuscript describes a fatal case of a 45-year-old man who presented with severe chest pain, hypertension (198/115 mmHg), and electrocardiogram changes mimicking acute coronary syndrome (ACS) 30 h after ingesting adulterated alcohol. Uniquely, chest pain was the sole initial manifestation, without visual disturbances, gastrointestinal symptoms, or any other classic methanol features, creating a clinically convincing ACS mimic. Despite negative coronary CT angiography, dual antiplatelet loading therapy (aspirin 300 mg and clopidogrel 300 mg) was administered based on clinical suspicion of ACS, together with low-molecular-weight heparin. Three hours later, the patient developed sudden unconsciousness with unequal pupils. Arterial blood gas analysis revealed severe high-anion-gap metabolic acidosis (pH 7.08, anion gap 34 mEq/L). Toxicology confirmed methanol poisoning (blood concentration 206.85 mg/dL). The diagnosis was prompted only after two coworkers presented simultaneously with visual symptoms and bilateral basal ganglia lesions on CT-a constellation not previously reported as the diagnostic trigger in ACS-mimicking methanol poisoning. Head CT showed subarachnoid hemorrhage, which rapidly progressed to massive right basal ganglia hemorrhage (9.0 × 3.3 cm) with intraventricular extension and surrounding hypodensity consistent with necrosis. Despite hemodialysis, ethanol infusion, and emergency craniotomy, the patient died 2 weeks later. Coagulation studies revealed acidosis-induced coagulopathy (PT 15.2 s, activated partial thromboplastin time 38.6 s, INR 1.3). Critically, what distinguishes this case from prior reports of methanol-associated basal ganglia hemorrhage is the synergistic pro-hemorrhagic state created by the combination of dual antiplatelet therapy (irreversible platelet inhibition), low-molecular-weight heparin (antithrombin III potentiation), and acidosis-induced coagulopathy, superimposed on methanol-induced endothelial injury-a fatal pharmacotoxicological interaction not previously described in a single case. Emergency physicians should consider toxicological etiologies in undifferentiated chest pain with metabolic derangements and obtain early arterial blood gas analysis to avoid such fatal diagnostic errors.

Parabens, ubiquitous preservatives with endocrine-disrupting potential, may adversely affect mental and cardiometabolic health, but evidence in elderly populations is limited. This study aimed to explore the relationships between urinary parabens and the risk of major depressive disorder (MDD) and cardiovascular and metabolic diseases (CMDs) among 921 community-dwelling elderly participants (aged ≥ 60 years) in Shandong, China. Urinary paraben concentrations were quantified using LC-MS. Multivariable logistic and linear regression were employed to assess the associations between individual parabens and health outcomes. The combined effects of the paraben mixture on MDD and CMDs were evaluated using Weighted Quantile Sum (WQS) and Bayesian Kernel Machine Regression (BKMR). Subgroup analyses were conducted by sex, age, BMI, and MDD status, with multiplicative interactions tested. Positive associations were observed between urinary methylparaben (MeP), ethylparaben (EtP), and the risk of MDD and CMDs (P-trend < 0.05). Compared with the reference, participants in the highest quartiles of MeP and EtP had significantly increased risks of MDD (MeP: OR = 2.88, 95% CI: 1.50-5.56; EtP: OR = 2.11, 95% CI: 1.01-3.89). For CMDs, MeP levels were associated with increased diabetes risk (OR = 1.65, 95% CI: 1.03-2.65). EtP levels were positively correlated with hypertension risk in males (OR = 1.85, 95% CI: 1.09-3.16), with significant sex differences (P-interaction = 0.034). WQS and BKMR regression analyses revealed significant positive joint effects of the paraben mixture on both MDD and CMDs, with MeP as the primary contributor. MeP also showed a significant positive association with composite burden scores for both MDD and CMDs. MDD and PHQ-9 scores were associated with increased Mets risk. Notably, the positive association of MeP and diabetes was confined to participants without MDD (OR = 1.82, 95% CI: 1.07-3.10). These findings implicate parabens as potentially modifiable environmental risk factors contributing to the dual burden of mental and cardiometabolic disorders in aging populations.

Analizar la evolución temporal y la tendencia de las neumoconiosis en México entre 1983 y 2023, a partir de los registros del Instituto Mexicano del Seguro Social (IMSS), considerando su peso relativo en el conjunto de enfermedades laborales reconocidas.  Métodos: Estudio retrospectivo observacional basado en los registros oficiales de la Memoria Estadística del IMSS (1983-2023). Se obtuvieron los casos anuales nuevos de neumoconiosis y de enfermedades laborales, calculando la proporción anual de neumoconiosis respecto al total de enfermedades laborales. Las variaciones se analizaron mediante representación gráfica y regresión lineal simple para identificar tendencias en la morbilidad proporcional a lo largo del periodo.  Resultados: Se identificaron 11.107 casos acumulados de neumoconiosis en el periodo analizado. El número anual de casos alcanzó su máximo en 1987 y mostró una tendencia descendente sostenida a partir de 1990. La morbilidad proporcional disminuyó desde 1994, con un repunte entre 2014 y 2019 (superior al 10%) y una reducción posterior a menos del 5% desde 2020. Este comportamiento refleja una modificación en el patrón de notificación y en la estructura de las enfermedades laborales reconocidas por el IMSS.  Conclusiones: El análisis de los valores absolutos y proporcionales permitió caracterizar la evolución de las neumoconiosis en el periodo 1983-2023. Aunque se observó una disminución de su morbilidad proporcional, los incrementos observados en años recientes subrayan la necesidad de mantener una vigilancia continua, fortalecer las estrategias preventivas y optimizar la detección de enfermedades respiratorias de origen ocupacional mediante un enfoque integral de salud laboral.