Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

PURPOSE: World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. METHODS: This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. RESULTS: ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). CONCLUSIONS: The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

The impact of hospitalization on mortality in patients with connective tissue disease-associated interstitial lung disease: a medical records review study.

BACKGROUND: Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. METHODS: We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and non-hospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. RESULTS: We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. CONCLUSIONS: Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.

The impact of hospitalization on mortality in patients with connective tissue disease-associated interstitial lung disease: a medical records review study

Abstract Background Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. Methods We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and nonhospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. Results We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. Conclusion Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.

The impact of air pollution on asthma: clinical outcomes, current epidemiology, and health disparities.

INTRODUCTION: Air pollution has been shown to have a significant impact on morbidity and mortality of respiratory illnesses including asthma. AREAS COVERED: Outdoor air pollution consists of a mixture of individual pollutants including vehicle traffic and industrial pollution. Studies have implicated an array of individual components of air pollution, with PM2.5, NO2, SO2, and ozone being the most classically described, and newer literature implicating other pollutants such as black carbon and volatile organic compounds. Epidemiological and cohort studies have described incidence and prevalence of pollution-related asthma and investigated both acute and chronic air pollution exposure as they relate to asthma outcomes. There is an increasing body of literature tying disparities in pollution exposure to clinical outcomes. In this narrative review, we assessed the published research investigating the association of pollution with asthma outcomes, focusing on the adult population and health care disparities. EXPERT OPINION: Pollution has multiple deleterious effects on respiratory health but there is a lack of data on individualized pollution monitoring, making it difficult to establish a temporal relationship between exposure and symptoms, thereby limiting our understanding of safe exposure levels. Future research should focus on more personalized monitoring and treatment plans for mitigating exposure.

Risk Factors for COVID-19 in a Retired FDNY WTC-Exposed Cohort.

We evaluated the incidence and risk factors for COVID-19 in a prospectively followed cohort of Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed workers, thus reducing the potential for selection bias, a limitation in published studies of hospitalized individuals. Participants were retired FDNY WTC-exposed rescue/recovery workers with ≥1 medical visit between 1 March 2020 and 1 August 2021. The cumulative incidence was calculated using self-reported COVID-19 diagnoses. Cox regression was performed to evaluate the association of WTC-exposure and COVID-19, adjusting for history of comorbidities, age, race, work assignment (emergency medical service providers vs. firefighter), and sex. The cumulative incidence of COVID-19 was 130 per 1000. The adjusted models showed the risk of infection was greater in those with highest WTC exposure versus less exposure (hazard ratio (HR) = 1.14 (95% CI 1.00-1.31)). Older age was associated with a lower risk of infection HR = 0.97 (95% CI 0.96-0.98). WTC-associated diseases (obstructive airways disease and interstitial lung disease) were not COVID-19 risk factors. This study is the first to show an association between WTC exposure and the risk of COVID-19. While participants are retired from FDNY work, the youngest individuals may still be in the workforce, explaining why younger age was a significant risk for COVID-19.

Severe asthma in adult, inner-city predominantly African-American and latinx population: demographic, clinical and phenotypic characteristics.

INTRODUCTION: The burden of asthma morbidity with co-existing atopy among the racial/ethnic minorities in the socio-economically disadvantaged NYC borough of the Bronx is unusually high. The multidisciplinary Montefiore Asthma Center (MAC) provides guideline-based treatment to this high-risk population through the joint efforts of Allergists/Immunologists, Pulmonologists, and on-site health educators. METHODS: The objective of this prospective, observational study was to define the demographic and clinical characteristics of severe asthma, evaluate improvement in asthma severity and lung function through the course of treatment at the MAC, and describe the asthma phenotypes of the patients managed at the MAC. Adults with severe asthma receiving treatment at the MAC were followed from their first to their last visit at the MAC. Patient demographics, along with asthma severity and co-existing allergies, were assessed. Possible phenotypes were defined (based on presence or absence of atopy, age at asthma onset, and blood eosinophil counts). RESULTS: 227 patients were included in the final analysis, of which 55.5% were Hispanic and 33.9% identified as non-Hispanic Black. Ninety-one percent (91%) of our cohort was found to be atopic and allergic rhinoconjunctivitis (ARC) was the most commonly identified co-existing allergic condition (86.3%). Mean Asthma Control Test (ACT) scores improved from 11.1 (± 4.9) at the initial visit to 14.8 (± 6.1) at the last visit. The spirometric values did not improve despite treatment at MAC. CONCLUSION: A multidisciplinary severe asthma center is an ideal setting to phenotype patients and offer personalized guideline-based management and education to adults with severe asthma.

Twenty-Year Reflection on the Impact of World Trade Center Exposure on Pulmonary Outcomes in Fire Department of the City of New York (FDNY) Rescue and Recovery Workers.

After the terrorist attacks on September 11, 2001 (9/11), many rescue/recovery workers developed respiratory symptoms and pulmonary diseases due to their extensive World Trade Center (WTC) dust cloud exposure. Nearly all Fire Department of the City of New York (FDNY) workers were present within 48 h of 9/11 and for the next several months. Since the FDNY had a well-established occupational health service for its firefighters and Emergency Medical Services workers prior to 9/11, the FDNY was able to immediately start a rigorous monitoring and treatment program for its WTC-exposed workers. As a result, respiratory symptoms and diseases were identified soon after 9/11. This focused review summarizes the WTC-related respiratory diseases that developed in the FDNY cohort after 9/11, including WTC cough syndrome, obstructive airways disease, accelerated lung function decline, airway hyperreactivity, sarcoidosis, and obstructive sleep apnea. Additionally, an extensive array of biomarkers has been identified as associated with WTC-related respiratory disease. Future research efforts will not only focus on further phenotyping/treating WTC-related respiratory disease but also on additional diseases associated with WTC exposure, especially those that take decades to develop, such as cardiovascular disease, cancer, and interstitial lung disease.

Pre-COVID-19 lung function and other risk factors for severe COVID-19 in first responders.

Risk factors for #COVID19 infection and severe disease (hospitalisation or death) in NYC first responders: greater pre-pandemic rate of FEV1 decline is associated with severe COVID-19, as is emergency medical service work versus firefighting https://bit.ly/3nZPuZY.

Performance of Risk Factor-Based Guidelines and Model-Based Chest CT Lung Cancer Screening in World Trade Center-Exposed Fire Department Rescue/Recovery Workers.

BACKGROUND: Lung cancer is a leading cause of cancer incidence and death in the United States. Risk factor-based guidelines and risk model-based strategies are used to identify patients who could benefit from low-dose chest CT (LDCT) screening. Few studies compare guidelines or models within the same cohort. We evaluate lung cancer screening performance of two risk factor-based guidelines (US Preventive Services Task Force 2014 recommendations [USPSTF-2014] and National Comprehensive Cancer Network Group 2 [NCCN-2]) and two risk model-based strategies, Prostate Lung Colorectal and Ovarian Cancer Screening (PLCOm2012) and the Bach model) in the same occupational cohort. RESEARCH QUESTION: Which risk factor-based guideline or model-based strategy is most accurate in detecting lung cancers in a highly exposed occupational cohort? STUDY DESIGN AND METHODS: Fire Department of City of New York (FDNY) rescue/recovery workers exposed to the September 11, 2001 attacks underwent LDCT lung cancer screening based on smoking history and age. The USPSTF-2014, NCCN-2, PLCOm2012 model, and Bach model were retrospectively applied to determine how many lung cancers were diagnosed using each approach. RESULTS: Among the study population (N = 3,953), 930 underwent a baseline scan that met at least one risk factor or model-based LDCT screening strategy; 73% received annual follow-up scans. Among the 3,953, 63 lung cancers were diagnosed, of which 50 were detected by at least one LDCT screening strategy. The NCCN-2 guideline was the most sensitive (79.4%; 50/63). When compared with NCCN-2, stricter age and smoking criteria reduced sensitivity of the other guidelines/models (USPSTF-2014 [44%], PLCOm2012 [51%], and Bach[46%]). The 13 missed lung cancers were mainly attributable to smoking less and quitting longer than guideline/model eligibility criteria. False-positive rates were similar across all four guidelines/models. INTERPRETATION: In this cohort, our findings support expanding eligibility for LDCT lung cancer screening by lowering smoking history from ≥30 to ≥20 pack-years and age from 55 years to 50 years old. Additional studies are needed to determine its generalizability to other occupational/environmental exposed cohorts.

The Safety and Utility of Phenobarbital Use for the Treatment of Severe Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a common reason for admission to a medical intensive care unit (MICU) and requires significant hospital resource utilization. Benzodiazepines are first-line therapy for AWS in many intensive care units. We propose the use of symptom-triggered phenobarbital for the treatment of AWS as a safe alternative to benzodiazepines. METHODS: This was a retrospective observational study of a 4-year period, 2011 to 2015, of all patients with AWS admitted to the MICU of 1 tertiary care hospital and treated with phenobarbital. A symptom-triggered protocol was used. Resolution of AWS was assessed with the Richmond Agitation Sedation Scale to goal score of 0 to -1. The Charlson Comorbidity Index was used as an index of patient illness severity. Complications associated with phenobarbital use and/or the AWS admission were analyzed. RESULTS: Data of 86 AWS patient encounters were analyzed. The mean Clinical Institute Withdrawal Assessment for Alcohol-Revised score of patients admitted to the MICU with AWS was 19 ± 9. The mean phenobarbital dose administered during the MICU stay was 1977.5 ± 1531.5 mg. There were a total of 17 (20%) intubations. The most frequent cause of mechanical ventilation in patients with AWS was loss of airway clearance, followed by hemodynamic instability secondary to upper gastrointestinal bleeding and the corresponding need for endoscopy. CONCLUSIONS: Sole use of phenobarbital use for control of AWS may be a safe alternative to benzodiazepines. Further study is needed to correlate phenobarbital serum levels with clinical control of AWS.

Long-term Cardiovascular Disease Risk Among Firefighters After the World Trade Center Disaster.

Importance: Published studies examining the association between World Trade Center (WTC) exposure on and after September 11, 2001, and longer-term cardiovascular disease (CVD) outcomes have reported mixed findings. Objective: To assess whether WTC exposure was associated with elevated CVD risk in Fire Department of the City of New York (FDNY) firefighters. Design, Settings, and Participants: In this cohort study, the association between WTC exposure and the risk of CVD was assessed between September 11, 2001, and December 31, 2017, in FDNY male firefighters. Multivariable Cox regression analyses were used to estimate CVD risk in association with 2 measures of WTC exposure: arrival time to the WTC site and duration of work at the WTC site. Data analyses were conducted from May 1, 2018, to March 8, 2019. Main Outcomes and Measures: The primary CVD outcome included myocardial infarction, stroke, unstable angina, coronary artery surgery or angioplasty, or CVD death. The secondary outcome (all CVD) included all primary outcome events or any of the following: transient ischemic attack; stable angina, defined as either use of angina medication or cardiac catheterization without intervention; cardiomyopathy; and other CVD (aortic aneurysm, peripheral arterial vascular intervention, and carotid artery surgery). Results: There were 489 primary outcome events among 9796 male firefighters (mean [SD] age on September 11, 2001, was 40.3 [7.4] years and 7210 individuals [73.6%] were never smokers). Age-adjusted incident rates of CVD were higher for firefighters with greater WTC exposure. The multivariable adjusted hazard ratio (HR) for the primary CVD outcome was 1.44 (95% CI, 1.09-1.90) for the earliest arrival group compared with those who arrived later. Similarly, those who worked at the WTC site for 6 or more months vs those who worked less time at the site were more likely to have a CVD event (HR, 1.30; 95% CI, 1.05-1.60). Well-established CVD risk factors, including hypertension (HR, 1.41; 95% CI, 1.10-1.80), hypercholesterolemia (HR, 1.56; 95% CI, 1.28-1.91), diabetes (HR, 1.99; 95% CI, 1.33-2.98), and smoking (current: HR, 2.13; 95% CI, 1.68-2.70; former: HR, 1.55; 95% CI, 1.23-1.95), were significantly associated with CVD in the multivariable models. Analyses with the all-CVD outcome were similar. Conclusions and Relevance: The findings of the study suggest a significant association between greater WTC exposure and long-term CVD risk. The findings appear to reinforce the importance of long-term monitoring of the health of survivors of disasters.

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5' untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis.

Prevalence of Arnold nerve reflex in subjects with and without chronic cough: Relevance to Cough Hypersensitivity Syndrome.

INTRODUCTION: Cough is induced by stimulation of structures innervated by the vagus nerve, including the upper and lower airways and distal esophagus. The Arnold nerve reflex describes cough resulting from stimulation of the external auditory canal, which is innervated by the auricular branch of the vagus. We have recently reported the increased prevalence of this reflex in adults, but not children, with chronic cough, relative to healthy adult and pediatric subjects. The prevalence of the Arnold nerve reflex in patients with pulmonary disease but without chronic cough has not been investigated previously. METHODS: Three hundred adults and 100 children with chronic cough, 50 adults with stable pulmonary disease but without chronic cough, as well as 100 adult and 100 pediatric volunteers, underwent evaluation consisting of stimulation of the external auditory canal of each ear with a cotton-tipped applicator. Cough occurring within 10 s of stimulation was considered induced by the intervention. RESULTS: Arnold's nerve reflex was present in 23.3% of adults and 3% of children with chronic cough. The prevalence of the reflex was 2% among healthy adults and children. In adults with chronic cough, Arnold's nerve reflex was observed more commonly in women (29.3%) than men (10.5%), and was unilateral in the majority of patients (88.6%). In patients with respiratory disease but without chronic cough, Arnold nerve reflex was present in 2%. CONCLUSIONS: The greater than 11-fold prevalence of the Arnold nerve reflex in adults with chronic cough compared with healthy volunteers and adults with respiratory disease but without chronic cough, supports the concept of the Cough Hypersensitivity Syndrome (CHS), in which vagal hypersensitivity is proposed to underlie chronic refractory cough. The absence of increased prevalence among children with chronic cough suggests that CHS is an acquired condition, perhaps triggered by viral respiratory infection or other environmental factor.

Airway Disease in Rescue/Recovery Workers: Recent Findings from the World Trade Center Collapse.

PURPOSE OF REVIEW: Our goal is to summarize the airway disease literature since September 11, 2001 (9/11), focusing on studies published since 2011 in World Trade Center-exposed rescue/recovery workers. RECENT FINDINGS: Since 2011, studies have confirmed relationships between initial World Trade Center exposure intensity, severity of symptoms, airway disease diagnoses, and biomarkers of disease progression. Studies continue to document ongoing morbidity in rescue/recovery workers over 10 years after 9/11. Future research should further identify correlates of symptom persistence and new airway disease diagnoses. The unique characteristics of the airway diseases in this population warrant ongoing monitoring and treatment.

The effect of point-of-care ultrasonography on imaging studies in the medical ICU: a comparative study.

BACKGROUND: Point-of-care ultrasonography performed by frontline intensivists offers the possibility of reducing the use of traditional imaging in the medical ICU (MICU). We compared the use of traditional radiographic studies between two MICUs: one where point-of-care ultrasonography is used as a primary imaging modality, the other where it is used only for procedure guidance. METHODS: This study was a retrospective 3-month chart review comparing the use of chest radiographs, CT scans (chest and abdomen/pelvis), transthoracic echocardiography performed by the cardiology service, and DVT ultrasonography studies performed by the radiology service between two MICUs of similar size and acuity and staffing levels. RESULTS: Total number of admissions, patient demographics, and disease acuity were similar between MICUs. Comparing the non-point-of-care ultrasonography MICU with the point-of-care ultrasonography MICU, there were 3.75 ± 4.6 vs 0.82 ± 1.85 (P < .0001) chest radiographs per patient, 0.10 ± 0.31 vs 0.04 ± 0.20 (P = .0007) chest CT scans per patient, 0.17 ± 0.44 vs 0.05 ± 0.24 (P < .0001) abdomen/pelvis CT scans per patient, 0.20 ± 0.47 vs 0.02 ± 0.14 (P < .0001) radiology service-performed DVT studies per patient, and 0.18 ± 0.40 vs 0.07 ± 0.26 (P < .0001) cardiology service-performed transthoracic echocardiography studies per patient, respectively. CONCLUSIONS: The use of point-of-care ultrasonography in an MICU is associated with a significant reduction in the number of imaging studies performed by the radiology and cardiology services.

The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory.

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.