Gwen Skloot

The World Trade Center Disaster and the Health of Workers: Five-Year Assessment of a Unique Medical Screening Program

Background Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. Methods To characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. Results Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. Conclusion WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters.

Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study.

BACKGROUND More than 50,000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities. METHODS In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27,449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud). FINDINGS 9-year cumulative incidence of asthma was 27·6% (number at risk: 7027), sinusitis 42·3% (5870), and gastro-oesophageal reflux disease 39·3% (5650). In police officers, cumulative incidence of depression was 7·0% (number at risk: 3648), PTSD 9·3% (3761), and panic disorder 8·4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27·5% (number at risk: 4200), PTSD 31·9% (4342), and panic disorder 21·2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41·8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders. INTERPRETATION 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population. FUNDING Centers for Disease Control and Prevention and National Institute for Occupational Safety and Health.

A Prospective, Cross-sectional Survey Study of the Natural History of Niemann-Pick Disease Type B

OBJECTIVE. The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease type B and to identify efficacy end points for future clinical trials of enzyme-replacement therapy. METHODS. Fifty-nine patients who had Niemann-Pick disease type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. RESULTS. Fifty-three percent of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. CONCLUSIONS. This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy end points were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate end point in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring patient treatment responses.

Bronchodilation and bronchoprotection by deep inspiration and their relationship to bronchial hyperresponsiveness.

Bronchial hyperresponsiveness (BHR) is a cardinal feature of asthma. Airway inflammation and BHR are probably linked, but the mechanisms underlying this relationship remain elusive. BHR is closely associated with defects in the beneficial responses to lung inflation. These responses, which become apparent by the fact that healthy individuals can develop severe airway obstruction if they are exposed to methacholine in the absence of deep inspirations, include bronchodilation and bronchoprotection. Bronchodilation refers to the effect of lung inflation after the induction of airway smooth muscle tone, while bronchoprotection is used to indicate the effect prior to inhalation of a spasmogen. Mild asthmatics who manifest BHR lack bronchoprotection by lung inflation. In contrast, many of them are able to bronchodilate. In more severe disease, both functions are impaired. The lack of bronchoprotection is also found in individuals with rhinitis and BHR, but no asthma. These and other observations suggest that the mechanisms of bronchodilation and bronchoprotection may be distinct, although overlap is possible. We believe that the loss of bronchoprotection is pertinent to the phenomenon of hyperresponsiveness, but that both the bronchodilatory and bronchoprotective functions of deep inspiration interact to produce the asthmatic phenotype. In this review, we describe the phenomena of lung inflation-induced bronchodilation and bronchoprotection and detail potential mechanical and neurohumoral mechanisms accounting for these physiologic functions. In addition, possible mechanisms leading to the impairment of these functions in subjects with BHR are discussed.

Longitudinal Assessment of Spirometry in the World Trade Center Medical Monitoring Program

BACKGROUND Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. METHODS Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). RESULTS At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV(1) and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were lack of bronchodilator responsiveness at examination 1 and weight gain [corrected]. CONCLUSIONS Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, lack of bronchodilator response at examination 1 and weight gain were significantly associated with greater-than-normal lung function declines [corrected]. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

Impaired response to deep inspiration in obesity

Deep inspirations modulate airway caliber and airway closure and their effects are impaired in asthma. The association between asthma and obesity raises the question whether the deep inspiration (DI) effect is also impaired in the latter condition. We assessed the DI effects in obese and nonobese nonasthmatics. Thirty-six subjects (17 obese, 19 nonobese) underwent routine methacholine (Mch) challenge and 30 of them also had a modified bronchoprovocation in the absence of DIs. Lung function was monitored with spirometry and forced oscillation (FO) [resistance (R) at 5 Hz (R5), at 20 Hz (R20), R5-R20 and the integrated area of low-frequency reactance (AX)]. The response to Mch, assessed with area under the dose-response curves (AUC), was consistently greater in the routine challenge in the obese (mean ± SE, obese vs. nonobese AUC: R5: 15.7 ± 2.3 vs. 2.4 ± 2.0, P < 0.0005; R20: 5.6 ± 1.4 vs. 1.4 ± 1.2, P = 0.027; R5-R20: 10.2 ± 1.6 vs. 0.9 ± 0.1.4, P < 0.0005; AX: 115.6 ± 22.0 vs. 1.5 ± 18.9, P < 0.0005), but differences between groups in the modified challenge were smaller, indicating reduced DI effects in obesity. Given that DI has bronchodilatory and bronchoprotective effects, we further assessed these components separately. In the obese subjects, DI prior to Mch enhanced Mch-induced bronchoconstriction, but DI after Mch resulted in bronchodilation that was of similar magnitude as in the nonobese. We conclude that obesity is characterized by increased Mch responsiveness, predominantly of the small airways, due to a DI effect that renders the airways more sensitive to the stimulus.

Standardization of spirometry in assessment of responders following man-made disasters: World Trade Center worker and volunteer medical screening program

BACKGROUND Spirometry is the most commonly used pulmonary function test to screen individuals for suspected lung disease. It is also used for screening workers with exposures to agents associated with pulmonary diseases. Although the American Thoracic Society (ATS) provides guidelines for spirometers and spirometry techniques, many factors are not standardized, so that results from individual pulmonary function laboratories vary substantially. These differences can create substantial difficulties in using data pooled from multiple sites to understand health consequences of disasters that involve exposures to pulmonary toxins. This article describes the approach used to minimize these differences for a consortium of institutions who are providing medical monitoring examinations to World Trade Center (WTC) responders. The protocol improved upon the minimal ATS guidelines. METHODS Spirometric measurements were obtained before and after use of a bronchodilator. A fourth-generation spirometer was chosen that exceeded ATS spirometer accuracy standards. The accuracy was verified at the beginning of each day of testing. Technologists who performed the spirometry tests were centrally trained and certified and received regular reports on their performance. Reference values and normal ranges were obtained from the National Health and Nutrition Examination Survey (NHANES III) data set. A standardized interpretation flowchart was followed to reduce misclassification rates for airway obstruction and restriction. Patients with spirometric abnormalities were referred for more extensive diagnostic testing. RESULTS More than 12,000 spirometry tests were performed during the first examination. The 20 spirometers used at the 6 participating institutions maintained accuracy within 3% for more than 4 years. Overall, more than 80% of the test sessions met ATS quality goals. Spirometry abnormality rates exceeded those obtained for adults who participated in the NHANES III survey. CONCLUSIONS The program allowed standardization of the performance and interpretation of spirometry results across multiple institutions. This facilitated reliable and rapid diagnosis of lung disease in the large number of WTC responders screened. We recommend this approach for postdisaster pulmonary evaluations in other settings.

Inhaled steroids reduce pain and sVCAM levels in individuals with sickle cell disease: A triple‐blind, randomized trial

Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper‐reactivity) is an intrinsic component of Sickle Cell Disease (SCD) and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single‐center, longitudinal, randomized, triple‐blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 nonasthmatic individuals with SCD. Participants received once daily mometasone furoate 220 mcg dry powder inhalation or placebo for 16 weeks. The primary outcome was feasibility (the number who complete the trial divided by the total number enrolled) with prespecified efficacy outcomes including daily pain score over time (patient reported) and change in soluble vascular cell adhesion molecule (sVCAM) levels between entry and 8‐weeks. For the primary outcome of feasibility, the result was 96% (52 of 54, 95% CI 87%‐99%) for the intent‐to‐treat analysis and 83% (45 of 54, 95% CI 71%‐91%) for the per‐protocol analysis. The adjusted treatment effect of mometasone was a reduction in daily pain score of 1.42 points (95%CI 0.61‐2.21, P = 0.001). Mometasone was associated with a reduction in sVCAM levels of 526.94 ng/mL more than placebo (95% CI 50.66‐1003.23, P = 0.03). These results support further study of ICS in SCD including multicenter trials and longer durations of treatment. www.clinicaltrials.gov (NCT02061202)

Rationale and design of a comparative effectiveness trial of home- and clinic-based self-management support coaching for older adults with asthma.

Older adults with asthma face numerous barriers to effective self-management and asthma control, and experience worse outcomes than younger asthmatics. Yet, there have been no controlled trials of interventions specifically designed to improve their care and outcomes. Through a multi-stakeholder collaboration (patients, academia, community-based organizations, a state department of health, and an advocacy organization) we developed a multi-component asthma self-management support intervention to address the myriad psychosocial, functional, health status, and cognitive barriers to effective asthma self-management in adults ages 60 and older. We are recruiting 425 New Yorkers in Manhattan and the Bronx for a pragmatic randomized controlled trial with 3 arms: the intervention delivered in primary care settings or in their home, or usual care. In the intervention, care coaches use a novel screening tool to identify the specific barriers to asthma control and self-management they experience. Once identified, the coach and patient choose from a menu of actions to address it. The intervention emphasizes efficiency, flexibility, shared decision making and goal setting, communication strategies appropriate for individuals with limited cognition and literacy skills, and ongoing reinforcement and support. Additionally, we introduced asthma-specific enhancements to the electronic health records of all participating clinical practices, including an asthma severity assessment, clinical decision support, and a patient-tailored asthma action plan. Patients will be followed for 12months and interviewed at baseline, 3, 6, and 12months and data on emergency department visits and hospitalizations will be obtained through the New York State Statewide Planning and Research Cooperative System.

Cough and wheeze events are temporally associated with increased pain in individuals with sickle cell disease without asthma

Human clinical studies and murine models suggest that pulmonary inflammation is an intrinsic component of sickle cell disease (SCD) (Field et al, 2011, Morris et al, 2003, Nandedkar et al, 2008, Pawar et al, 2008, Pritchard et al, 2012, Pritchard et al, 2004) and a growing body of retrospective and cross-sectional studies demonstrates that symptoms, such as cough or wheeze, often occur without asthma and are associated with increased SCD complications (pain, acute chest syndrome and death) (Cohen et al, 2011, Field et al, 2011, Glassberg et al, 2012). To better understand the incidence of respiratory symptoms over time, and to identify the percentage of individuals without asthma who could potentially benefit from pulmonary-anti-inflammatory therapy, we conducted a prospective, longitudinal cohort study of individuals with SCD who do not have asthma.