Faculty Bibliography

BACKGROUND:The characteristics of community members exposed to World Trade Center (WTC) dust and fumes with Chronic Obstructive Pulmonary Disease (COPD) can provide insight into mechanisms of airflow obstruction in response to an environmental insult, with potential implications for interventions. METHODS:We performed a baseline assessment of respiratory symptoms, spirometry, small airway lung function measures using respiratory impulse oscillometry (IOS), and blood biomarkers. COPD was defined by the 2019 GOLD criteria for COPD. Patients in the WTC Environmental Health Center with <5 or ≥5 pack year smoking history were classified as nonsmoker-COPD (ns-COPD) or smoker-COPD (sm-COPD), respectively. MAIN RESULTS/RESULTS:= 0.007). CONCLUSIONS:Spirometry findings and small airway measures, as well as inflammatory markers, differed between patients with ns-COPD and sm-COPD. These findings suggest potential for differing mechanisms of airway injury in patients with WTC environmental exposures and have potential therapeutic implications.

The World Trade Center Environmental Health Center (WTC EHC), is a federally designated clinical center of excellence for surveillance and treatment of WTC disaster exposed community members (WTC Survivors). Cognitive impairment (CI) has been extensively described in WTC responders and a concern for progressive impairment in all WTC disaster exposed groups has been raised. Cognitive status, however, has not been systematically characterized in the WTC Survivor population. We describe cognitive status in a subgroup of the Survivor population referred for mental health evaluation (N = 480) in the WTC EHC as measured by scores on the Montreal Cognitive Assessment (MoCA) instrument, and examine their association with WTC exposures and individual-level covariates including PTSD and depression screening inventory scores. In regression analyses, probable cognitive impairment (MoCA score < 26) was found in 59% of the study subjects and was significantly associated with age, race/ethnicity, education, income, depression and PTSD scores. Being caught in the dust cloud on 11 September 2011 was significantly associated with cognitive impairment even after controlling for the above. These data suggest an association with cognitive dysfunction in WTC Survivors with exposure to the toxic dust/fumes and psychological stress from the 9/11 terrorist attack and warrant further systematic study.

On 11 September 2001 the World Trade Center (WTC) in New York was attacked by terrorists, causing the collapse of multiple buildings including the iconic 110-story 'Twin Towers'. Thousands of people died that day from the collapse of the buildings, fires, falling from the buildings, falling debris, or other related accidents. Survivors of the attacks, those who worked in search and rescue during and after the buildings collapsed, and those working in recovery and clean-up operations were exposed to severe psychological stressors. Concurrently, these 'WTC-affected' individuals breathed and ingested a mixture of organic and particulate neurotoxins and pro-inflammogens generated as a result of the attack and building collapse. Twenty years later, researchers have documented neurocognitive and motor dysfunctions that resemble the typical features of neurodegenerative disease in some WTC responders at midlife. Cortical atrophy, which usually manifests later in life, has also been observed in this population. Evidence indicates that neurocognitive symptoms and corresponding brain atrophy are associated with both physical exposures at the WTC and chronic post-traumatic stress disorder, including regularly re-experiencing traumatic memories of the events while awake or during sleep. Despite these findings, little is understood about the long-term effects of these physical and mental exposures on the brain health of WTC-affected individuals, and the potential for neurocognitive disorders. Here, we review the existing evidence concerning neurological outcomes in WTC-affected individuals, with the aim of contextualizing this research for policymakers, researchers and clinicians and educating WTC-affected individuals and their friends and families. We conclude by providing a rationale and recommendations for monitoring the neurological health of WTC-affected individuals.

Rationale: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, equally weighted, yes/no control tool that assesses symptom impairment and exacerbation risk. AIRQ control level (well-controlled [WC], not well-controlled [NWC], very poorly controlled [VPC]) predicts future 12-month exacerbations (odds-ratios [OR]95% Confidence Limits [CL] for >=1 exacerbation: NWC vs WC=2.1[1.6-2.9], VPC vs WC= 4.6[3.3-6.5]; AUC=0.70). We examined whether adding clinical and biomarker covariates to AIRQ improves exacerbation prediction.
Method(s): Patients completed monthly online surveys regarding exacerbation-related oral corticosteroid (OCS) use, emergency department/urgent care visits, and hospitalizations. Univariate logistic regressions to predict exacerbations were performed with relevant covariates (eg, sociodemographics, comorbidities, exacerbation history, FEV1, eosinophils, IgE, FeNO). Significant (p <=0.05) variables were included in a multivariable logistic regression with AIRQ control categories to predict exacerbations (OR[95%CL]).
Result(s): 1070 patients completed >=1 survey over 12 months (mean[SD] surveys 10.5[2.8]); 70.1% female; mean age 43.9[19.4] years; 21.5% non-White; BMI 30.6[8.7]; AIRQ WC 35%, NWC 38%, VPC 27%. 46% of patients reported >=1 exacerbation (WC 31.9%, NWC 56.6%, VPC 83.4%). In the multivariate analysis, AIRQ control category was predictive of exacerbations (NWC vs WC: OR=1.94[1.41, 2.66], VPC vs WC: OR=3.80[2.58, 5.60; AUC=0.72] as were age (10 year OR=1.12[1.02, 1.23], presence of sleep apnea (OR=1.48[1.00, 2.18]), FeNO <25 ppb (OR=1.36[1.02, 1.82]), and >=2 prior 12-month OCS courses (OR=2.46[1.50, 4.05]).
Conclusion(s): A history of multiple exacerbations and current asthma control as measured by AIRQ is strongly and independently associated with future exacerbations. Additional assessments do not significantly enhance the ability of AIRQ to predict exacerbations.
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Dyspnoea self-management is often suboptimal for patients with COPD. Many patients with COPD experience chronic dyspnoea as distressing and disabling, especially during physical activities. Breathing therapy is a behavioural intervention that targets reducing the distress and impact of dyspnoea on exertion in daily living. Using a qualitative design, we conducted interviews with 14 patients after they participated in a novel mind-body breathing therapy intervention adjunct, capnography-assisted respiratory therapy (CART), combined with outpatient pulmonary rehabilitation. Comprehensive CART consisted of patient-centred biofeedback, tailored breathing exercises, a home exercise programme and motivational interviewing counselling. We assessed participants' perceptions and reported experiences to gauge the acceptability of CART and refine CART based on feedback. Constant comparative analysis was used to identify commonalities and themes. We identified three main themes relating to the acceptability and reported benefits of CART: (1) self-regulating breathing; (2) impact on health; and (3) patient satisfaction. Our findings were used to refine and optimise CART (i.e. its intensity, timing and format) for COPD. By addressing dysfunctional breathing behaviours and dysregulated interoception, CART offers a promising new paradigm for relieving dyspnoea and related anxiety in patients with COPD.

BACKGROUND:Patients with severe asthma may remain uncontrolled despite biologic therapy in addition to standard therapy, but this disease burden has not been quantified. OBJECTIVE:To estimate the clinical and economic burden in a US national sample. METHODS:Patients who have severe asthma with indicated biologic treatment (earliest use = index date) were selected from the MarketScan database between January 1, 2013, and June 30, 2018. Inclusion criteria were continuous enrollment for 12 months postindex with a minimum of 2 biologic fills, greater than or equal to 12 years of age, evidence of medium- to high-dose inhaled corticosteroids and long-acting β-agonist combination before the index, and absence of other respiratory diagnoses and malignancies. Disease exacerbations (used to classify asthma control), health care costs, and treatment characteristics were reported during the 12-month postindex period. RESULTS:The sample included 3262 biologic patients; 88% with anti-immunoglobulin E therapy (omalizumab) and 12% non-anti-immunoglobulin E (reslizumab, mepolizumab, benralizumab). The mean age was 49 (±15) years; 64% were women. Prescriptions included inhaled corticosteroids and long-acting β-agonist (82%), systemic corticosteroids (76%), and leukotriene receptor antagonists (68%). Notably, 63% of patients presented greater than or equal to 1 asthma exacerbation (mean 1.3 per patient/year). Furthermore, 35% of patients were categorized as having controlled asthma, whereas 28% were suboptimally controlled and 29% were uncontrolled. Patients with uncontrolled disease had higher all-cause and asthma-related costs ($69,206 and $45,693, respectively) than patients with suboptimally controlled ($59,407 and $40,793, respectively) or controlled disease ($53,083 and $38,393, respectively). Furthermore, 62% of newly treated patients were persistent with their index biologic. CONCLUSION/CONCLUSIONS:Biologic therapies are effective in reducing exacerbations, but a substantial proportion of patients with severe asthma treated with current biologics continue to experience uncontrolled disease, highlighting a remaining unmet need for patients with severe uncontrolled asthma.

The destruction of World Trade Center on 11 September 2001 exposed local community members to a complex mixture of known carcinogens and potentially carcinogenic substances. To date, breast cancer has not been characterized in detail in the WTC-exposed civilian populations. The cancer characteristics of breast cancer patients were derived from the newly developed Pan-Cancer Database at the WTC Environmental Health Center (WTC EHC). We used the Surveillance, Epidemiology, and End Results (SEER) Program breast cancer data as a reference source. Between May 2002 and 31 December 2019, 2840 persons were diagnosed with any type of cancer at the WTC EHC, including 601 patients with a primary breast cancer diagnosis (592 women and 9 men). There was a higher proportion of grade 3 (poorly differentiated) tumors (34%) among the WTC EHC female breast cancers compared to that of the SEER-18 data (25%). Compared to that of the SEER data, female breast cancers in the WTC EHC had a lower proportion of luminal A (88% and 65%, respectively), higher proportion of luminal B (13% and 15%, respectively), and HER-2-enriched (5.5% and 7%, respectively) subtypes. These findings suggest considerable differences in the breast cancer characteristics and distribution of breast cancer intrinsic subtypes in the WTC-exposed civilian population compared to that of the general population. This is important because of the known effect of molecular subtypes on breast cancer prognosis.

Introduction: Exertional respiratory symptoms are prominent in patients with environmental lung injury following inhalation of World Trade Center dust. Baseline pulmonary function testing in these patients is frequently normal, leaving symptoms unexplained. Although small airway dysfunction has been identified at rest, its role in producing exertional symptoms is unclear. In this study exercise evaluation with assessment of airway function was employed to uncover mechanisms for exertional dyspnea.
Method(s): 27 subjects were studied: 20 with unexplained dyspnea (normal spirometry) and 6 asymptomatic controls. Baseline pulmonary function testing was conducted along with respiratory oscillometry to assess small airway function. An incremental exercise protocol was performed that included a focused evaluation of airway function: (1) examination of tidal flow vs. volume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and (2) airway reactivity post-exercise using spirometry and oscillometry. Baseline: By design spirometry values were within normal limits in all subjects. Symptomatic individuals tended to have greater mean R5, R20, R5-20, and AX at baseline compared with asymptomatic controls (R5: 4.80+/-1.79 vs. 3.66+/-1.06; R20: 3.52+/-1.12 vs. 2.98+/-0.68; R5-20: 1.28+/-1.02 vs. 0.70+/-0.53; AX: 13.44+/-10.74 vs. 5.48+/-5.21). Exercise: Dyspnea was reproduced with exercise in symptomatic subjects (mean Borg dyspnea score 1.38+/-1.48 at baseline, 4.20+/-2.28 at peak exercise). Asymptomatic controls did not report significant dyspnea (mean Borg dyspnea score 0 at baseline, 1.60+/-1.14 at peak exercise). Expiratory flow limitation during exercise was noted in 13/20 symptomatic subjects compared with 0 controls. Post Exercise: Bronchial hyper-reactivity was evident in post-exercise spirometry (>10% decline in FEV1) in 3/20 symptomatic subjects vs. 1/6 controls; the fall in FEV1 was predominantly attributable to a fall in FVC, consistent with small airway dysfunction. An additional six symptomatic subjects demonstrated isolated small airway hyper-reactivity that was only revealed on oscillometry.
Conclusion(s): In patients with unexplained dyspnea and normal spirometry, symptoms were reproduced during exercise. Focused airway assessment uncovered small airway dysfunction both during and following exercise that contributed to the development of dyspnea