Rachel Zeig-Owens

Background: Persistent respiratory symptoms are common in Fire Department of the City of New York (FDNY) rescue/recovery workers following the World Trade Center (WTC) collapse on 11 September 2001 and some continue to experience symptoms despite normal spirometry without bronchodilator response. Respiratory oscillometry is a sensitive method for detecting small airways dysfunction and identifies abnormalities undetected by spirometry. This study evaluated whether respiratory oscillometry is associated with respiratory symptoms among workers with normal spirometry, and qualitatively assessed this association stratified by serum eosinophilia. Methods: We analysed a cohort of FDNY WTC-exposed rescue/recovery workers who completed same-day respiratory oscillometry, spirometry and symptom questionnaires. We included only those with normal spirometry without obstruction, defined as forced expiratory volume in 1 s (FEV ₁ ), forced vital capacity (FVC) and FEV ₁ /FVC greater than the lower limit of normal and no bronchodilator response. Logistic regression estimated associations between oscillometry z-scores (as continuous variables in separate models) and symptom burden. Models were adjusted for age, race, WTC arrival time, smoking status and body mass index. Analyses were also stratified by eosinophilia status. Results: Resistance at 5 Hz (R5) was associated with persistently high symptom count (odds ratio (OR) 1.36, 95% CI 1.11–1.66) and high symptom severity (OR 1.32, 95% CI 1.05–1.67). Frequency dependence of resistance (the difference between resistance at 5 Hz and resistance at 20 Hz (R5–R20)) was also associated with persistently high symptom count (OR 1.31, 95% CI 1.11–1.56). Associations for R5 and R5–R20 were greatest in those with eosinophilia (≥300 cells·μL ⁻¹ ). Conclusion: In symptomatic individuals with normal spirometry, oscillometry is sensitive for detecting airways dysfunction, supporting our hypothesis that persistent, severe symptoms are attributable to disease in the small airways. Larger associations with eosinophilia identify a phenotype that may inform early intervention and treatment.

Posttraumatic stress disorder (PTSD) has been linked to impaired physical function, which in turn predicts falls, morbidity, and mortality. However, few studies have used objective measures such as handgrip strength to assess physical function. In this cross-sectional study, we investigated associations of average PTSD symptom severity and symptom domain severity with measures of maximum handgrip strength and handgrip asymmetry from 11/2021–12/2023, among 381 male firefighters and emergency medical responders who responded to the World Trade Center disaster, using covariate-adjusted linear regression models. PTSD was diagnosed using the Structured Clinical Interview for the DSM-5 in 17% of responders. Greater overall PTSD average symptom severity was associated with weaker maximum handgrip strength (β = −4.43 lbs; 95%; CI: −8.77, −0.09; p = 0.045). Higher re-experiencing symptom severity was associated with weaker maximum handgrip strength (β = −4.17 lbs; 95% CI: −8.13, −0.22; p = 0.039). Avoidance symptoms were associated with weaker handgrip strength in adjusted models (β = −4.14 lbs; 95% CI: −7.56, −0.73; p = 0.018), and associated with a larger negative difference assessing for hand asymmetry (β = −2.20 lbs; 95% CI: −4.18, −0.22; p = 0.029). Findings suggest that PTSD may contribute to long-term physical decline, even in populations with high baseline fitness.

Prevalence of somatic mutation (VAF ≤ 25%) in WTC-exposed responders

Mutational signatures for changes seen in WTC-exposed responders below the age of 60

Environmental exposures are linked to precancerous hematologic conditions, but studies in cohorts with well-defined exposures are limited. We sequenced blood samples from a large cohort of first responders exposed to the aerosolized dust and carcinogens from the 9/11 World Trade Center (WTC) disaster and observed a significantly higher prevalence of clonal hematopoiesis (CH) mutations when compared with two sets of control cohorts after controlling for age, race, and sex. Younger exposed first responders exhibited unconventional CH mutations, with defective DNA repair signatures. Leukemia risk was elevated (3.7% vs. 0.6%; OR = 5.73) in WTC-exposed responders with CH versus without CH. Exposure to particulate matter collected from WTC site impaired healthy stem cells while expanding Tet2-mutant CH clones in mice. The inflammation sensor IL1RAP was overexpressed in murine CH, and genetic knockdown inhibited mutant clone growth in vivo. This study links discrete environmental exposure to hematopoietic mutations and leukemia, identifying IL1RAP as a novel therapeutic target in CH.Significance:This study identifies elevated CH with distinct, nonclassical mutations in 9/11 first responders, particularly younger individuals, and links CH to increased leukemia risk. Findings suggest broader relevance to other genotoxic environmental exposures and highlight IL1RAP as a critical driver of CH expansion and a promising therapeutic target for inflammation-driven malignancies.See related commentary by Safina and van Galen, p. 2406

Mutational signatures for changes seen in WTC-exposed responders above the age of 60