Maria Elena Fernandez-Beros

Characteristics of a Residential and Working Community With Diverse Exposure to World Trade Center Dust, Gas, and Fumes

Objective: To describe physical symptoms in those local residents, local workers, and cleanup workers who were enrolled in a treatment program and had reported symptoms and exposure to the dust, gas, and fumes released with the destruction of the World Trade Center (WTC) on September 11, 2001. Methods: Symptomatic individuals underwent standardized evaluation and subsequent treatment. Results: One thousand eight hundred ninety-eight individuals participated in the WTC Environmental Health Center between September 2005 and May 2008. Upper and lower respiratory symptoms that began after September 11, 2001 and persisted at the time of examination were common in each exposure population. Many (31%) had spirometry measurements below the lower limit of normal. Conclusions: Residents and local workers as well as those with work-associated exposure to WTC dust have new and persistent respiratory symptoms with lung function abnormalities 5 or more years after the WTC destruction.

Genetic Variants of TSLP and Asthma in an Admixed Urban Population

Background Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations. Objectives To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. Methodology and Main Results Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09–2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04–3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93–1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10–2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07–1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08–1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94–1.17, p = 0.33). Conclusions Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.

Application of the Asthma Phenotype Algorithm from the Severe Asthma Research Program to an Urban Population

Rationale Identification and characterization of asthma phenotypes are challenging due to disease complexity and heterogeneity. The Severe Asthma Research Program (SARP) used unsupervised cluster analysis to define 5 phenotypically distinct asthma clusters that they replicated using 3 variables in a simplified algorithm. We evaluated whether this simplified SARP algorithm could be used in a separate and diverse urban asthma population to recreate these 5 phenotypic clusters. Methods The SARP simplified algorithm was applied to adults with asthma recruited to the New York University/Bellevue Asthma Registry (NYUBAR) to classify patients into five groups. The clinical phenotypes were summarized and compared. Results Asthma subjects in NYUBAR (n = 471) were predominantly women (70%) and Hispanic (57%), which were demographically different from the SARP population. The clinical phenotypes of the five groups generated by the simplified SARP algorithm were distinct across groups and distributed similarly to those described for the SARP population. Groups 1 and 2 (6 and 63%, respectively) had predominantly childhood onset atopic asthma. Groups 4 and 5 (20%) were older, with the longest duration of asthma, increased symptoms and exacerbations. Group 4 subjects were the most atopic and had the highest peripheral eosinophils. Group 3 (10%) had the least atopy, but included older obese women with adult-onset asthma, and increased exacerbations. Conclusions Application of the simplified SARP algorithm to the NYUBAR yielded groups that were phenotypically distinct and useful to characterize disease heterogeneity. Differences across NYUBAR groups support phenotypic variation and support the use of the simplified SARP algorithm for classification of asthma phenotypes in future prospective studies to investigate treatment and outcome differences between these distinct groups. Trial Registration Clinicaltrials.gov NCT00212537

Systemic Inflammation Associated With World Trade Center Dust Exposures and Airway Abnormalities in the Local Community.

Background: Destruction of the World Trade Center (WTC) towers on September 11, 2001, released massive dust, gas, and fumes with environmental exposures for community members. Many community members have lower respiratory symptoms (LRSs) that began after September 11, 2001, and remain persistent. We evaluated whether systemic inflammation measured by C-reactive protein was associated with WTC dust exposures, persistent LRS, and lung function. Methods: Community members self-referred for the treatment of symptoms related to September 11, 2001. C-reactive protein and lung function measurements, including spirometry and forced oscillation tests (impulse oscillometry system), were included as routine analyses in patients (2007 to 2012). Results: Increased C-reactive protein levels were associated with the type of WTC dust exposure, LRS, reduced spirometry, and increased forced oscillation measurements (n = 724). Conclusions: Ongoing systemic inflammation measured years after the event was associated with WTC dust exposures, persistent LRS, and abnormal lung function in a community cohort. These findings have implications for treatment and surveillance.

Longitudinal Spirometry Among Patients in a Treatment Program for Community Members With World Trade Center-Related Illness

Objective: The course of lung function in community members exposed to World Trade Center (WTC) dust and fumes remains undefined. We studied longitudinal spirometry among patients in the WTC Environmental Health Center (WTCEHC) treatment program. Methods: Observational study of 946 WTCEHC patients with repeated spirometry measures analyzed on the population as a whole and stratified by smoking status, initial spirometry pattern, and WTC-related exposure category. Results: Improvement in forced vital capacity (54.4 mL/yr; 95% confidence interval, 45.0 to 63.8) and forced expiratory volume in 1 second (36.8 mL/yr; 95% confidence interval, 29.3 to 44.3) was noted for the population as a whole. Heavy smokers did not improve. Spirometry changes differed depending on initial spirometry pattern and exposure category. Conclusion: These data demonstrate spirometry improvement in select populations suggesting reversibility in airway injury and reinforcing the importance of continued treatment.

Improvement in severe lower respiratory symptoms and small airway function in World Trade Center dust exposed community members

OBJECTIVE Longitudinal assessment of lower respiratory symptoms (LRS) in community members with World Trade Center (WTC) exposures. METHODS Adult members of a treatment program with complete standardized visits were evaluated (n = 798). Association of demographic characteristics, mental health symptoms and lung function with trajectory of LRS between initial and monitoring visit was evaluated. RESULTS Severe LRS were present in 70% at initial and 63% at monitoring visit. Initial severe LRS were associated with WTC dust cloud exposure and mental health symptoms. Spirometry measures were not associated with LRS severity or trajectory; improvement in LRS was associated with improved lung function measured with forced oscillometry techniques. CONCLUSION Many community patients in a WTC treatment program had severe LRS associated with exposures and mental health symptoms. Improvement in LRS was associated with improvement in measures of small airway function. Am. J. Ind. Med. 59:777-787, 2016.