Assessing pulmonary function in 3-year-old children using respiratory oscillometry: a validation study in rural Guatemala. Investigator's R functions for quality control.

Open MIND · 2026-02-23

R Code developed by investigators to perform quality control of oscillometry measurements collected with the Tremoflo C-100 Airwave Oscillometry System (THORASYS Thoracic Medical Systems, Montreal, Quebec, Canada) at 7 to 41 Hertz multifrequency range.

Early-life liquefied petroleum gas cooking intervention and lung function in Guatemalan children: A randomized clinical trial

Annals of the American Thoracic Society · 2026-04-17

RATIONALE: Household air pollution is a risk factor for obstructive lung diseases. OBJECTIVES: We estimated the effect of an early-life liquefied petroleum gas cooking intervention on childhood lung function. METHODS: The multi-country Household Air Pollution Intervention Network trial randomized 800 pregnant women (9-19 weeks gestation, 18-34 years) in Guatemala to receive a gas cookstove and free fuel intervention or continue cooking with biomass until the child is aged 1 year. The present analysis includes only Guatemalan children. At age 3 years, we measured lung function using oscillometry at 7-41 Hertz (Tremoflo C-100, Thorasys). Outcomes were resistance and reactance at 7 Hertz, area of reactance, resistance at 19 Hertz, resistance difference between 7 and 19 Hertz, and, as exploration, resistance across frequencies. Upper airway artifacts were removed using Tremoflo software. The effect of the intervention was estimated using linear regression models, unadjusted and adjusted (height, weight, age, sex). Children with respiratory infections during a 7-day recall period were excluded. RESULTS: Valid oscillometry was obtained from 525/750 (70%) 3-year-olds. Among the 225 missed oscillometry tests, 129/750 (17%) were due to the children not being willing to perform the measurements. We did not find evidence of an effect on prespecified oscillometry outcomes. Exploratory analysis suggested that resistance across the frequency spectrum was lower in intervention than control participants (adjusted difference: -0.31 cmH2O*S/L, 95% CI: -0.59, -0.03). CONCLUSIONS: Gas cooking compared to biomass cooking from mid-gestation through infancy was not associated with improved prespecified oscillometry outcomes in 3-year-old children. However, lowered resistance across all frequencies in the intervention arm suggests the intervention may have positively impacted airway caliber. Further studies are warranted, including exposure-response analysis and lung function trajectories.

Assessing pulmonary function in 3-year-old children using respiratory oscillometry: a validation study in rural Guatemala

ERJ Open Research · 2026-04-16

Background Respiratory oscillometry may be important for understanding early-Iife lung function, but evidence supporting its use in Guatemala is limited. We assessed the validity and reliability of respiratory oscillometry in three-year-old Guatemalan children and whether these improve with quality control (QC). Methods We measured respiratory oscillometry resistance and reactance at 7 Hertz (R7 and X7), the frequency dependence of resistance (R7-R19), and the area of reactance (AX) in 666 Household Air Pollution Intervention Network trial children during home visits. Standard measurement QC removed artifacts using commercial software and selected the first three measurements with an R7 coefficient of variation ≤15%. Alternative investigators’ methods varied in QC procedures. We evaluated validity as the proportion of variability in tests predicted by the child's height (R 2 ) and, in a subset of 50 children, as agreement with test results after manual QC by a pediatric pulmonologist. Reliability was assessed by the intraclass correlation (ICC) of repeated tests. Results We collected oscillometry in 542 children. Height explained 5–15% of the variability in R7, X7, and AX, but none in R7-R19. The correlation between standard and manually cleaned tests ranged from 0.66 to 0.97, depending on the parameter. Among first-tests, between-day ICCs using the standard method for R7, R7-R19, X7, and AX were 0.68, 0.45, 0.60, and 0.71, respectively, and the best between-day ICCs using an alternative method were 0.75, 0.57, 0.69, and 0.74, respectively. Discussion We demonstrated good validity and reliability of respiratory oscillometry measurements collected at home from pre-school-aged Guatemalan children. Investigators’ automated QC methodology performed equally or better than standard methodology.

Assessing pulmonary function in 3-year-old children using respiratory oscillometry: a validation study in rural Guatemala. Investigator's R functions for quality control.

Zenodo (CERN European Organization for Nuclear Research) · 2026-02-23

R Code developed by investigators to perform quality control of oscillometry measurements collected with the Tremoflo C-100 Airwave Oscillometry System (THORASYS Thoracic Medical Systems, Montreal, Quebec, Canada) at 7 to 41 Hertz multifrequency range.

Analytical and cheminformatic framework for studying drugs and their metabolites in human plasma using high resolution mass spectrometry

Exposome · 2026-01-01 · 1 citations

Abstract Pharmacological interventions are required to manage a wide array of chronic diseases. Drug metabolism is heavily influenced by individual-level genomic and environmental factors, and there is substantial variability in drug efficacy for many medications. Novel strategies are needed to evaluate drug performance and improve therapeutic effectiveness. Recent technological advancements in high-resolution mass spectrometry (HRMS) have enabled broad exposomic analyses that can evaluate how an individual metabolizes drugs. Here, we present a new analytical framework to annotate drug metabolites in human plasma samples. We performed non-targeted analyses using liquid-chromatography (LC)-HRMS and developed an analytical workflow that leverages tandem mass spectra for structural annotation of unknown molecular features. In addition to database matching, we implemented molecular networking to link parent pharmaceutical compounds to potential metabolite features using shared fragmentation patterns followed by in silico chemical formula and structure prediction. In doing so, we successfully annotated downstream metabolites of an array of pharmaceutical agents and created a new investigational pipeline towards measuring drug metabolites in human samples for which reference standards or spectra are rarely available. The analytical framework presented in this study can be used to develop new pharmacokinetic models where both the parent drugs and the metabolites are simultaneously measured and monitored. Similarly, this workflow can be applied for annotating xenobiotic chemicals in various matrices. Our results contribute to efforts in developing a personalized approach to measuring drug metabolites and may provide new opportunities to maximize therapeutic response and improve drug efficacy in humans.

Pipe and cigar use, lung function decline and clinical outcomes: an analysis of the NHLBI Pooled Cohorts Study

Thorax · 2026-03-03

Introduction Smoked tobacco is a leading risk factor for cardiopulmonary disease. Pipe and cigar use remains common among US adults, yet its risks remain insufficiently understood. Methods We analysed data from five pooled cohorts with adults enrolled from 1971 to 2011 with follow-up through 2018. Pipe/cigar use was defined by baseline self-report. Forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC ratio were measured by spirometry. All-cause mortality, coronary heart disease mortality and hospitalisation, respiratory-related mortality, and chronic obstructive pulmonary disease (COPD) mortality and hospitalisation were classified via adjudication or validated algorithms. Associations were estimated with linear mixed models and Fine-Gray subdistribution hazards models adjusted for sociodemographic and clinical factors. Results Among 22 823 participants (mean (SD) age 48.0 (15.7) years; 44.9% male sex; 70.5% white, 25.4% black, 2.4% Hispanic/Latino), 2621 (11.5%) reported ever pipe/cigar use, including 518 (2.3%) exclusive users without cigarette history. Compared with never tobacco users (n=9931), exclusive pipe/cigar use was associated with faster decline in FEV 1 (3.36 mL/year; 95% CI 1.99 to 4.72), FVC (3.73 mL/year; 95% CI 2.05 to 5.42) and FEV 1 /FVC (0.031 per year; 95% CI 0.008 to 0.054). Exclusive users had higher all-cause mortality (adjusted HR (aHR) 1.24; 95% CI 1.08 to 1.41), COPD hospitalisation/mortality (aHR 2.02; 95% CI 1.41 to 2.90) and preserved ratio impaired spirometry (aHR 1.83; 95% CI 1.24 to 2.71). Conclusion Pipe and cigar use was associated with accelerated lung function decline and increased mortality and cardiopulmonary events, including among never cigarette users. These findings underscore the need for prevention and cessation efforts targeting non-cigarette tobacco.

Circulating extracellular microRNAs as tissue-specific biomarkers of human health and disease

Nature Communications · 2026-04-27

Early pathological changes in many organ systems are difficult to detect, which creates challenges in disease prevention, diagnosis, and treatment. Here, we leverage circulating extracellular microRNAs (ex-miRNAs) to derive miRNA-based Tissue Signal (miR-TS) scores that simultaneously assess 17 tissues, including the brain, heart, liver, and lungs. Across three population-based cohorts and 10 clinical populations, miR-TS scores were robustly associated with relevant health outcomes with high tissue specificity. Using prospective data, miR-TS scores for the heart, brain, and lungs also functioned as predictive biomarkers that tracked the development of major health events, including acute myocardial infarction, cerebrovascular accidents, cognitive impairment, and airflow limitation. Finally, we demonstrated the utility of miR-TS scores in detecting tissue-specific toxicities from both acute and long-term exogenous exposures. Our results highlight the potential of circulating ex-miRNAs to function as robust biomarkers of tissue health and predict the onset of a wide range of diseases. A blood-based microRNA approach generates tissue-specific scores across multiple systems, enabling assessment of tissue health, prediction of major disease events, and detection of early tissue damage across diverse populations and exposures.

A Rare Case of Pulmonary Hypertension With Potential Vascular Origin in a 29 Year-old Pregnant Female

American Journal of Respiratory and Critical Care Medicine · 2025-05-01

Abstract History: A 29-year-old woman who was 8 weeks pregnant (G1P0) presented to an outpatient clinic with worsening dyspnea on exertion and recent episodes of syncope. She reported a 10-year history of recurrent syncope. Data: An echocardiogram revealed right ventricular (RV) enlargement and reduced RV function. A chest computed tomography angiography (CTA) showed an enlarged pulmonary artery and upper lobe-predominant peribronchovascular ground glass opacities. Spirometry demonstrated moderately decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). The serologic test showed an elevated anti-SSA/Ro auto-antibody. Treatment with subcutaneous enoxaparin and intravenous treprostinil improved her symptoms. Repeat imaging after starting pulmonary vasodilators showed stable upper lobe-predominant peribronchovascular ground glass opacities. Given the risk to both the patient and the fetus, she was counseled on the benefits and risks of elective termination. She underwent elective termination but remained critically ill. She was then referred for lung transplant evaluation. Radiographic Figures: Representative images of the coronal (left) and axial (right) planes of the patient's non-contrast chest CT obtained on admission to the hospital demonstrate innumerable ill-defined peribronchovascular ground glass opacities throughout all five lobes (yellow arrows). Questions: 1. What could be the common differential diagnosis for opacities seen in the radiographic figures above? A. Interstitial lung disease B. Idiopathic pulmonary arterial hypertension (PAH) C. Pulmonary veno-occlusive disease (PVOD) D. Pulmonary capillary hemangiomatosis (PCH) E. All above 2. What is the primary reason for considering elective pregnancy termination in this patient? A. Risk of teratogenic effects of PAH medications on the fetus B. High maternal mortality associated with PAH in pregnancy C. Presence of elevated anti-SSA/Ro antibody D. None above 3. What is the primary gene mutation seen in PVOD? A. EIF2AK4 B. JAK2 C. ENG D. None above Discussion: This case highlights the diagnostic challenges and critical management of pulmonary hypertension in pregnancy. PVOD and PCH are extremely rare, and the risks of further investigation including biopsy were weighed against potential therapeutic benefits. The combination of anticoagulation and pulmonary vasodilators stabilized the patient, but the high maternal and fetal mortality associated with PAH in pregnancy prompted a discussion about mortality and early termination. Early recognition and aggressive management of PAH in pregnancy are essential for improving maternal outcomes. References: Eyries M et al., EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat Genet. 2014 Jan;46(1):65-9. doi: 10.1038/ng.2844.

Extracellular vesicle-encapsulated microRNA signatures of cigarette smoking and smoking-related harm

Respiratory Medicine · 2025-07-01 · 2 citations

Urinary Metal Levels and Respiratory Health in the Vapescan Study

American Journal of Respiratory and Critical Care Medicine · 2025-05-01

Abstract Rationale: Occupational metal exposures have been associated with lung diseases including asthma and emphysema. However, no prior studies have evaluated how metal levels in early adulthood affect respiratory health. We evaluated the relationship between urinary metal levels and lung function in young adults with and without history of e-cigarette use, a known source of metal exposures. Methods: The VapeScan Study recruited adults aged 18-50 years in New York City. Participants were recruited into one of four groups based on e-cigarette and cigarette use: dual e-cigarette/cigarette use, current e-cigarette/former cigarette use, exclusive e-cigarette use, or no e-cigarette/cigarette use (controls). Exclusion criteria included physician-diagnosed emphysema, chronic obstructive pulmonary disease, and bronchiectasis. Metal levels were measured in urine and corrected for urine specific gravity. Pre-bronchodilator spirometry measured the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75). Associations of baseline log-transformed metal levels with cross-sectional lung function were modeled using linear regression, while associations with longitudinal lung function were modeled using linear mixed-effect models adjusted for follow-up time. All models were adjusted for age, sex, race/ethnicity, education, height, weight, e-cigarette use, and cigarette smoking status. Results: Among 335 VapeScan participants, the mean age was 27.9±7.7 years. In total, 85 (25.3%) participants reported dual e-cigarette/cigarette use, 59 (17.6%) reported current e-cigarette/former cigarette use, 87 (25.9%) reported current e-cigarette/never cigarette use, and 105 (31.3%) reported no e-cigarette/cigarette use. Dual e-cigarette/cigarette use was associated with higher urinary copper levels (+1.24 μg/L, 95% CI 1.03, 1.49) compared to controls. In total, 538 spirometry measurements were obtained over 172.6 person-years of follow-up. In analyses of baseline lung function, each 1-interquartile range (IQR) higher urinary copper was associated with lower FEV1 (-69.71 mL, 95% CI -128.53, -10.90), FEV1/FVC (-1.41, 95% CI -2.23, -0.59), and FEF25-75 (-135.34 mL/s, 95% CI -250.33, -20.35). Similarly, in analyses of longitudinal lung function, each 1-IQR higher urinary copper was associated with lower longitudinal FEV1 (-64.59 mL, 95% CI -119.79, -9.48), FEV1/FVC (-1.03, 95% CI -1.78, -0.29), and FEF25-75 (-116.05 mL/s, 95% CI -221.71, -10.65) (Figure 1). Urinary levels of cadmium, cobalt, lead, and zinc were not associated with FEV1, FEV1/FVC, or FEF25-75. Conclusions: In a prospective cohort of young adults, higher urinary copper was associated with lower lung function. Urinary copper levels may help identify individuals with increased risk of lung function impairment and may represent a novel target for the prevention of obstructive lung diseases.