Faculty Bibliography

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

Rationale: The Asthma Impairment and Risk Questionnaire (AIRQTM) is a 10-item, equally-weighted, yes/no, composite control tool. The AIRQTM was validated in a cross-sectional study of 442 patients with asthma aged >=12 years recruited from specialty practices. The combination of selected AIRQTM questions and score range (Well-controlled: 0-1, Not Well-controlled: 2-4, and Very Poorly Controlled: 5-10 yes responses) demonstrated high sensitivity and specificity to differentiate patients on either end of the control spectrum. The current study assessed construct validity of the AIRQTM in primary and specialty care patients recruited from web-based panels by evaluating systemic corticosteroid and rescue therapy use as measures of asthma control.
Method(s): Participants aged >=18 years self-reporting asthma and use of therapies across all Global Initiative for Asthma (GINA)-step severities were included. Sociodemographic and medical history forms, the Asthma Control Test (ACTTM), and AIRQTM were completed electronically. To determine AIRQTM construct validity, ACTTM score, prior-year self-reported systemic corticosteroids for exacerbations, and rescue inhaler/nebulizer use were analyzed within provider groups relative to AIRQTM control level (general linear models with Scheffe's post hoc adjustment for pairwise comparisons).
Result(s): 1153 patients (538 primary and 615 specialty care) were included: mean (SD) age 49 (15) years; 60% female; 68% White, 15% African American, 15% Hispanic/Latino; 33% GINA 3-5; and 43% with less than college degrees. Among the panel primary and specialty care patients, the AIRQTM identified 48.7% and 25.4% as well-controlled, 33.5% and 32.8% as not well-controlled, and 17.8% and 41.8% as very poorly controlled, respectively. Control differences were supported by more primary care patients having well-controlled ACTTM scores (60.8% vs 32.4%) and fewer having >=2 courses of oral corticosteroids (21.0% vs 50.7%) or steroid injections (7.6% vs 35.3%) for asthma exacerbations or rescue inhaler use (26.2% vs 44.2%) or nebulizer treatments (8.0% vs 26.8%) >=3 times/week (p<0.0001, for each). Within provider groups, the proportion of patients with each of these indices of morbidity increased with worsening AIRQTM control level (p<0.0001, for each) (Table).
Conclusion(s): These data demonstrate the construct validity of the AIRQTM among patients in primary and specialty care, as differences in AIRQTM control levels were associated with differential proportions of patients reporting use of systemic corticosteroids for exacerbations and rescue therapy for uncontrolled symptoms. In addition to being a robust composite control tool, AIRQTM can increase awareness for all providers as to their patients' burden of disease

The destruction of the World Trade Center (WTC) towers on 11 September 2001 resulted in acute and chronic dust and fume exposures to community members, including local workers and residents, with well-described aerodigestive adverse health effects. This study aimed to characterize lung cancer in the WTC Environmental Health Center (WTC EHC) focusing on gender and smoking history. WTC EHC patients undergo an initial evaluation that includes WTC exposure information, demographics, and tobacco use. Detailed cancer characteristics are recorded from pathology reports. As of 31 December 2019, 248 WTC EHC patients had a diagnosis of lung cancer. More patients with lung cancer were women (57%) compared to men (43%). Many cases (47% women, 51% men) reported acute dust cloud exposure. Thirty-seven percent of lung cancer cases with available smoking history were never-smokers (≤1 pack-years) and 42% had a ≤5 pack-year history. The median age of cancer diagnosis in never-smoking women was 61 years compared to 66 years in men. Adenocarcinoma was more common in never-smokers compared to ever-smokers (72% vs. 65%) and in women compared to men (70% vs. 65%). We provide an initial description of lung cancers in local community members with documented exposure to the WTC dust and fumes.

(1) Background: Recent studies have reported elevated risks of multiple cancers in the World Trade Center (WTC) affected community members (also called WTC "Survivors"). The large variety of WTC-cancers created a need to develop a comprehensive cancer database. This paper describes the development of a pan-cancer database at the WTC Environmental Health Center (EHC) Data Center. (2) Methods: A new REDCap-based pan-cancer database was created using the pathology reports and available biomarker data of confirmed cancer cases after review by a cancer epidemiologist, a pathologist, physicians and biostatisticians. (3) Results: The WTC EHC pan-cancer database contains cancer characteristics and emerging biomarker information for cancers of individuals enrolled in the WTC EHC and diagnosed after 11 September 2001 and up to 31 December 2019 obtained from WTC EHC clinical records, pathological reports and state cancer registries. As of 31 December 2019, the database included 3440 cancer cases with cancer characteristics and biomarker information. (4) Conclusions: This evolving database represents an important resource for the scientific community facilitating future research about the etiology, heterogeneity, characteristics and outcomes of cancers and comorbid mental health conditions, cancer economics and gene-environment interaction in the unique population of WTC survivors.