Faculty Bibliography

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. (c) 2016 Wiley Periodicals, Inc.

The assault and subsequent collapse of the World Trade Center towers in New York City on September 11, 2001 (9/11), released more than a million tons of debris and dust into the surrounding area, engulfing rescue workers as they rushed to aid those who worked in the towers, and the thousands of nearby civilians and children who were forced to flee. In December 2015, almost 15 years after the attack, and 5 years after first enactment, Congress reauthorized the James Zadroga 9/11 Health and Compensation Act, a law designed to respond to the adverse health effects of the disaster. This reauthorization affords an opportunity to review human inhalation exposure science in relation to the World Trade Center collapse. In this Special Article, we compile observations regarding the collective medical response to the environmental health disaster with a focus on efforts to address the adverse health effects experienced by nearby community members including local residents and workers. We also analyze approaches to understanding the potential for health risk, characterization of hazardous materials, identification of populations at risk, and shortfalls in the medical response on behalf of the local community. Our overarching goal is to communicate lessons learned from the World Trade Center experience that may be applicable to communities affected by future environmental health disasters. The World Trade Center story demonstrates that communities lacking advocacy and preexisting health infrastructures are uniquely vulnerable to health disasters. Medical and public health personnel need to compensate for these vulnerabilities to mitigate long-term illness and suffering.

Case-control designs are commonly employed in genetic association studies. In addition to the case-control status, data on secondary traits are often collected. Directly regressing secondary traits on genetic variants from a case-control sample often leads to biased estimation. Several statistical methods have been proposed to address this issue. The inverse probability weighting (IPW) approach and the semiparametric maximum-likelihood (SPML) approach are the most commonly used. A new weighted estimating equation (WEE) approach is proposed to provide unbiased estimation of genetic associations with secondary traits, by combining observed and counterfactual outcomes. Compared to the existing approaches, WEE is more robust against biased sampling and disease model misspecification. We conducted simulations to evaluate the performance of the WEE under various models and sampling schemes. The WEE demonstrated robustness in all scenarios investigated, had appropriate type I error, and was as powerful or more powerful than the IPW and SPML approaches. We applied the WEE to an asthma case-control study to estimate the associations between the thymic stromal lymphopoietin gene and two secondary traits: overweight status and serum IgE level. The WEE identified two SNPs associated with overweight in logistic regression, three SNPs associated with serum IgE levels in linear regression, and an additional four SNPs that were missed in linear regression to be associated with the 75th quantile of IgE in quantile regression. The WEE approach provides a general and robust secondary analysis framework, which complements the existing approaches and should serve as a valuable tool for identifying new associations with secondary traits.

Case-control design is widely used in epidemiology and other fields to identify factors associated with a disease. Data collected from existing case-control studies can also provide a cost-effective way to investigate the association of risk factors with secondary outcomes. When the secondary outcome is a continuous random variable, most of the existing methods focus on the statistical inference on the mean of the secondary outcome. In this paper, we propose a quantile-based approach to facilitating a comprehensive investigation of covariates' effects on multiple quantiles of the secondary outcome. We construct a new family of estimating equations combining observed and pseudo outcomes, which lead to consistent estimation of conditional quantiles using case-control data. Simulations are conducted to evaluate the performance of our proposed approach, and a case-control study on genetic association with asthma is used to demonstrate the method.

The Bellevue Hospital Chest Service is unique in the annals of medical history since it is the oldest chest medicine program in the United States (1903), and was the source of clinical pulmonary fellowship training (primarily tuberculosis) and research fellowship training in its Cardiopulmonary Laboratory. Drs. Cournand and Richards shared the Nobel Prize in Physiology or Medicine in 1956 for cardiac catheterization with collection of a mixed venous sample to accurately calculate cardiac output using the Fick Principle. The Bellevue Chest Service has emerged as a leader in controlling the TB/HIV and MDR-TB epidemics, developed programs for the early detection of lung cancer, founded the World Trade Center Bellevue Environmental Center for studies of asthma and small airways function, and has constructed the William N. Rom Environmental Lung Disease Laboratory for future research.

The World Trade Center (WTC) destruction released dust and fumes into the environment. Although many community members developed respiratory symptoms, screening spirometry was usually normal. We hypothesised that forced oscillation testing would identify functional abnormalities undetected by spirometry and that symptom severity would relate to magnitude of abnormalities measured by oscillometry. A symptomatic cohort (n=848) from the Bellevue Hospital WTC Environmental Health Center was evaluated and compared to an asymptomatic cohort (n=475) from the New York City Department of Health WTC Health Registry. Spirometry and oscillometry were performed. Oscillometry measurements included resistance (R5) and frequency dependence of resistance (R5-20). Spirometry was normal for the majority of subjects (73.2% symptomatic versus 87.6% asymptomatic, p<0.0001). In subjects with normal spirometry, R5 and R5-20 were higher in symptomatic versus asymptomatic subjects (median (interquartile range) R5 0.436 (0.206) versus 0.314 (0.129) kPa.L-1.s-1, p<0.001; R5-20 0.075 (0.085) versus 0.004 (0.042) kPa.L-1.s-1, p<0.0001). In symptomatic subjects, R5 and R5-20 increased with increasing severity and frequency of wheeze (p<0.05). Measurement of R5-20 correlated with the presence and severity of symptoms even when spirometry was within normal limits. These findings are in accord with small airway abnormalities as a potential explanation of the respiratory symptoms.

BACKGROUND: Noninvasive sputum sampling has enabled the identification of biomarkers in asthmatic patients. Studies of discrete cell populations in sputum can enhance measurements compared with whole sputum in which changes in rare cells and cell-cell interactions can be masked. OBJECTIVE: We sought to enrich for sputum-derived human bronchial epithelial cells (sHBECs) and sputum-derived myeloid type 1 dendritic cells (sDCs) to describe transcriptional coexpression of targets associated with a type 2 immune response. METHODS: A case-control study was conducted with patients with mild asthma (asthmatic cases) and healthy control subjects. Induced sputum was obtained for simultaneous enrichment of sHBECs and sDCs by using flow cytometry. Quantitative PCR was used to measure mRNA for sHBEC thymic stromal lymphopoietin (TSLP), IL33, POSTN, and IL25 and downstream targets in sDCs (OX40 ligand [OX40L], CCL17, PPP1R14A, CD1E, CD1b, CD80, and CD86). RESULTS: Final analyses for the study sample were based on 11 control subjects and 13 asthmatic cases. Expression of TSLP, IL33, and POSTN mRNA was increased in sHBECs in asthmatic cases (P = .001, P = .05, and P = .04, respectively). Expression of sDC OX40L and CCL17 mRNA was increased in asthmatic cases (P = .003 and P = .0001, respectively). sHBEC TSLP mRNA expression was strongly associated with sDC OX40L mRNA expression (R = 0.65, P = .001) and less strongly with sDC CCL17 mRNA expression. sHBEC IL33 mRNA expression was associated with sDC OX40L mRNA expression (R = 0.42, P = .04) but not sDC CCL17 mRNA expression. CONCLUSIONS: Noninvasive sampling and enrichment of select cell populations from sputum can further our understanding of cell-cell interactions in asthmatic patients with the potential to enhance endotyping of asthmatic patients.