Faculty Bibliography

BACKGROUND: The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members. METHODS: Comparative data from these events were collected to derive indications for future preparedness. Information from the primary sources and a literature review addressed: i) exposure assessment; ii) exposed populations; iii) health surveillance; iv) follow-up and research outputs; v) observed physical and mental health effects; vi) treatment and benefits; and vii) outreach activities. RESULTS: Exposure assessment was conducted in Seveso, Chernobyl and Fukushima, although none benefited from a timely or systematic strategy, yielding immediate and sequential measurements after the disaster. Identification of exposed subjects was overall underestimated. Health surveillance, treatment and follow-up research were implemented in Seveso, Chernobyl, Fukushima, and at the WTC, mostly focusing on the workers and responders, and to a lesser extent on residents. Exposure-related physical and mental health consequences were identified, indicating the need for a long-term health care of the affected populations. Fukushima has generated the largest scientific output so far, followed by the WTCHP and Chernobyl. Benefits programs and active outreach figured prominently in only the WTC Health Program. The analysis of these programs yielded the following lessons: 1) Know who was there; 2) Have public health input to the disaster response; 3) Collect health and needs data rapidly; 4) Take care of the affected; 5) Emergency preparedness; 6) Data driven, needs assessment, advocacy. CONCLUSIONS: Given the long-lasting health consequences of natural and man-made disasters, health surveillance and treatment programs are critical for management of health conditions, and emergency preparedness plans are needed to prevent or minimize the impact of future threats.

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.

INTRODUCTION: Small airway dysfunction occurs following WTC dust exposure, but its role in producing symptoms is unclear. METHODS: Methacholine challenge (MCT) was used to assess the relationship between onset of respiratory symptoms and small airway abnormalities in 166 symptomatic WTC dust-exposed patients. Forced oscillation testing (FOT) and respiratory symptoms were assessed during MCT. FOT parameters included resistance at 5 and 20 Hz (R5 and R20 ) and the R5 minus R20 (R5-20 ). RESULTS: Baseline spirometry was normal in all (mean FEV1 100 + 13% predicted, mean FEV1 /FVC 80 + 4%). MCT revealed bronchial hyperreactivity by spirometry in 67 patients. An additional 24 patients became symptomatic despite minimal FEV1 change (<5%); symptom onset coincided with increased R5 and R5-20 (P > 0.001 vs. baseline). The dose-response of FOT (reactivity) was greater compared with subjects that remained asymptomatic (P < 0.05). CONCLUSIONS: FOT during MCT uncovered reactivity in small airways as a mechanism for respiratory symptoms in subjects with inhalational lung injury. Am. J. Ind. Med. 59:767-776, 2016. (c) 2016 Wiley Periodicals, Inc.

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.

PURPOSE OF REVIEW: Scleroderma and other autoimmune-induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc)-associated pulmonary hypertension, which remains a leading cause of death with only a 50-60% of 2-year survival rate. RECENT FINDINGS: Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During coevolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. SUMMARY: Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases.

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.