Faculty Bibliography

BACKGROUND:National and international asthma guidelines and reports do not include control tools that combine impairment assessment with exacerbation history in one instrument. OBJECTIVE:To analyze performance of the composite Asthma Impairment and Risk Questionnaire (AIRQ®) in assessing both domains of control and predicting exacerbation risk compared to Global Initiative for Asthma's 4-question symptom control tool (GINA SCT), Asthma Control Test (ACTTM), and physician expert opinion (EO) informed by GINA SCT responses and appraisal of GINA-identified risk factors for poor asthma outcomes. METHODS:Multivariable logistic regressions evaluated AIRQ and GINA SCT as predictors of ACT. McNemar's test compared the proportion of patients categorized at baseline as completely or well-controlled by each assessment but with current impairment or prior- and subsequent-year exacerbations. RESULTS:The analysis included 1064 patients aged ≥12 years; mean(SD) age 43.8(19.3) years; 70% female; 79% White; 6% Hispanic or Latino. AIRQ and GINA SCT were highly predictive of ACT well-controlled versus not well- and very poorly controlled (ROC AUC AIRQ=0.90, GINA SCT=0.86, P=0.03 AIRQ vs GINA SCT) and ACT very poorly controlled versus well- and not well-controlled asthma (ROC AUC AIRQ=0.91, GINA SCT=0.87, P=0.01 AIRQ vs GINA SCT). AIRQ rated fewer patients as completely or well-controlled who had current impairment (P<0.01) or with prior- and subsequent-year exacerbations (P<0.001) compared with GINA SCT, ACT, and EO. CONCLUSION/CONCLUSIONS:Relative to other control tools and EO informed by GINA SCT and risk factors for poor asthma outcomes, AIRQ performs better in assessing both domains of current control and predicting exacerbation risk.

BACKGROUND:The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, yes/no, equally weighted control tool. Lower scores indicate better control. Seven impairment items reflect prior 2-week symptoms, and three risk items assess prior 12-month exacerbations. The Follow-up AIRQ for use between annual assessments has a 3-month recall period for exacerbation items. OBJECTIVE:To evaluate the responsiveness of the AIRQ over time and identify a minimal important difference (MID). METHODS:AIRQ longitudinal study data were analyzed from patients with asthma aged ≥12 years. Anchor-based methods assessed differences in AIRQ scores relative to Patient Global Impression of Change (PGIC), the accepted MIDs for St. George's Respiratory Questionnaire (SGRQ) and Asthma Control Test (ACT), and exacerbation occurrence over 12 months. Baseline and 12-month data reflected 12-month recall AIRQ scores; Follow-up AIRQ scores were utilized for 3-, 6-, and 9-month analyses. RESULTS:1070 patients were included. PGIC "much improved" was associated with AIRQ mean score changes from baseline to months 3, 6, 9, and 12 of -2.0, -1.9, -1.9, and -1.8, respectively. Mean AIRQ score change among patients who met the SGRQ MID (≥4-point decrease) was -1.8 at 6 and 12 months. AIRQ mean scores decreased from baseline by -2.2 to -2.5 points at months 3, 6, 9, and 12 for patients who met the ACT MID (≥3 point increase). A 2-point higher baseline AIRQ score was associated with a 1.7 odds ratio of 12-month exacerbation occurrence (95% CI 1.53-1.89). CONCLUSION/CONCLUSIONS:A change score of 2 is recommended as the AIRQ MID.

Introduction: Known carcinogens in the dust and fumes from the destruction of the World Trade Center (WTC) towers on 9 November 2001 included metals, asbestos, and organic pollutants, which have been shown to modify epigenetic status. Epigenome-wide association analyses (EWAS) using uniform (Illumina) methodology have identified novel epigenetic profiles of WTC exposure. Methods: We reviewed all published data, comparing differentially methylated gene profiles identified in the prior EWAS studies of WTC exposure. This included DNA methylation changes in blood-derived DNA from cases of cancer-free "Survivors" and those with breast cancer, as well as tissue-derived DNA from "Responders" with prostate cancer. Emerging molecular pathways related to the observed DNA methylation changes in WTC-exposed groups were explored and summarized. Results: WTC dust exposure appears to be associated with DNA methylation changes across the genome. Notably, WTC dust exposure appears to be associated with increased global DNA methylation; direct dysregulation of cancer genes and pathways, including inflammation and immune system dysregulation; and endocrine system disruption, as well as disruption of cholesterol homeostasis and lipid metabolism. Conclusion: WTC dust exposure appears to be associated with biologically meaningful DNA methylation changes, with implications for carcinogenesis and development of other chronic diseases.

BACKGROUND:Asthma control is often overestimated in routine practice, and despite advances in the understanding of immunopathology and availability of new precision therapies, the burden of disease remains unacceptably high. OBJECTIVE:To compare performance of the Asthma Impairment and Risk Questionnaire (AIRQ) with patient and physician assessments and the Asthma Control Test (ACT) in identifying asthma control. METHODS:Baseline data from a longitudinal study of the AIRQ were analyzed. US patients with asthma aged ≥12 years followed in 24 specialty practices and one specialty-affiliated primary care clinic were enrolled between May and November 2019. At entry, participants completed AIRQ and ACT, and participants and physicians completed 5-point Likert scale assessments of control. RESULTS:1112 participants were enrolled (mean [standard deviation] age = 43.9 [19.3] years, 70% female, 78% White). Overall, 62% of participants rated themselves as well- or completely controlled and 54% were rated comparably by physicians. ACT classified 49% of participants as well-controlled, with 35% similarly categorized by AIRQ. Prior-year exacerbations were experienced by 32% of participants who self-rated as well- or completely controlled, 30% who were rated as well- or completely controlled by physicians, and 29% assessed as well-controlled by ACT, but only 15% of those classified as well-controlled by AIRQ. CONCLUSION/CONCLUSIONS:The burden of asthma is substantial in patients cared for by asthma specialists, and asthma control is overestimated by patients, physicians, and the symptom-based ACT. AIRQ assesses risk in addition to symptom control and may serve to improve asthma control determination by assessing prior exacerbations.

Asthma is defined as a heterogeneous disease with respiratory symptoms (wheeze, shortness of breath, chest tightness and cough) that vary over time and intensity, and variable expiratory airflow limitation. Environmental and occupational exposures contribute to its causation. WTC-related or aggravated asthma is considered a World Trace Center (WTC) Health Program certifiable disease. Criteria include defined exposures to the WTC dust and fumes, the presence of symptoms, or aggravated symptoms that are present within 5 years after the last potential for WTC dust/fume exposures (the last 9/11 exposures occurred on July 31, 2002), and a WTC-provider diagnosis of asthma. Asthma is the 3^rd most common non-cancer certification among WTC responders and survivors. In this review we provide evidence-based information on the evaluation, diagnosis, and treatment of patients with WTC-related or aggravated asthma and include peer-reviewed research findings in WTC-exposed populations.

BACKGROUND:Atopic diseases are characterized by IgE antibody responses that are dependent on cognate CD4 T cell help and T cell-produced IL-4 and IL-13. Current models of IgE cell differentiation point to the role of IgG memory B cells as precursors of pathogenic IgE plasma cells. The goal of this work was to identify intrinsic features of memory B cells that are associated with IgE production in atopic diseases. METHODS:Peripheral blood B lymphocytes were collected from individuals with physician diagnosed asthma or atopic dermatitis (AD) and from non-atopic individuals. These samples were analyzed by spectral flow cytometry, single cell RNA sequencing (scRNAseq), and in vitro activation assays. RESULTS:cells than B cells from non-atopic subjects. CONCLUSIONS:memory B cells transcribing IGHE are potential precursors of IgE plasma cells and are linked to pathogenic IgE production.

It is increasingly important to study the impact of environmental inhalation exposures on human health in natural or man-made disasters in civilian populations. The members of the World Trade Center Environmental Health Center (WTC EHC; WTC Survivors) had complex exposures to environmental disaster from the destruction of WTC towers and can serve to reveal the effects of WTC exposure on the entire spectrum of lung functions. We aimed to investigate the associations between complex WTC exposures and measures of spirometry and oscillometry in WTC Survivors and included 3605 patients enrolled between Oct 1, 2009 and Mar 31, 2018. We performed latent class analysis and identified five latent exposure groups. We applied linear and quantile regressions to estimate the exposure effects on the means and various quantiles of pre-bronchodilator (BD) % predicted forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio, as well as the resistance at an oscillating frequency of 5 Hz (R₅), frequency dependence of resistance R_5-20, and reactance area (AX). Compared with Group 5, which had low or unknown exposure and was treated as the reference group, Group 1, the local workers with both acute and chronic exposures, had a lower median of % predicted FVC (-3.6; 95% CI: -5.4, -1.7) and higher (more abnormal) measures of AX at 10th quantile (0.77 cmH₂O L^-1 s; 95% CI: 0.41, 1.13) and 25th quantile (0.80 cmH₂O L^-1 s; 95% CI: 0.41, 1.20). Results suggested heterogeneous exposures to the WTC disaster had differential effects on the distributions of lung functions in the WTC Survivors. These findings could provide insights for future investigation of environmental disaster exposures.