Peggy S. Lai

Exposures to Molds in School Classrooms of Children with Asthma

Students spend a large portion of their day in classrooms which may be a source of mold exposure. We examined the diversity and concentrations of molds in inner‐city schools and described differences between classrooms within the same school.

Association Between Allergen Exposure in Inner-City Schools and Asthma Morbidity Among Students

Importance Home aeroallergen exposure is associated with increased asthma morbidity in children, yet little is known about the contribution of school aeroallergen exposures to such morbidity. Objective To evaluate the effect of school-specific aeroallergen exposures on asthma morbidity among students, adjusting for home exposures. Design, Setting, and Participants The School Inner-City Asthma Study was a prospective cohort study evaluating 284 students aged 4 to 13 years with asthma who were enrolled from 37 inner-city elementary schools in the northeastern United States between March 1, 2008, and August 31, 2013. Enrolled students underwent baseline clinical evaluations before the school year started and were then observed clinically for 1 year. During that same school year, classroom and home dust samples linked to the students were collected and analyzed for common indoor aeroallergens. Associations between school aeroallergen exposure and asthma outcomes during the school year were assessed, adjusting for home exposures. Exposures Indoor aeroallergens, including rat, mouse, cockroach, cat, dog, and dust mites, measured in dust samples collected from inner-city schools. Main Outcomes and Measures The primary outcome was maximum days in the past 2 weeks with asthma symptoms. Secondary outcomes included well-established markers of asthma morbidity, including asthma-associated health care use and lung function, measured by forced expiratory volume in 1 second. Results Among 284 students (median age, 8 years [interquartile range, 6-9 years]; 148 boys and 136 girls), exposure to mouse allergen was detected in 441 (99.5%) of 443 school dust samples, cat allergen in 420 samples (94.8%), and dog allergen in 366 samples (82.6%). Levels of mouse allergen in schools were significantly higher than in students’ homes (median settled dust level, 0.90 vs 0.14 µg/g; P < .001). Exposure to higher levels of mouse allergen in school (comparing 75th with 25th percentile) was associated with increased odds of having an asthma symptom day (odds ratio, 1.27; 95% CI, 1.05-1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory volume in 1 second (95% CI, –6.6 to –1.5; P = .002). This effect was independent of allergic sensitization. None of the other indoor aeroallergens were associated with worsening asthma outcomes. Conclusions and Relevance In this study of inner-city students with asthma, exposure to mouse allergen in schools was associated with increased asthma symptoms and decreased lung function. These findings demonstrate that the school environment is an important contributor to childhood asthma morbidity. Future school-based environmental interventions may be beneficial for this important public health problem.

Long-term respiratory health effects in textile workers.

Purpose of review Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed byssinosis. The purpose of this review is to evaluate the effect of long-term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications, such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Recent findings Cessation of exposure to cotton dust leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population ratio as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton dust-related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Summary Textile dust-related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers.

Dynamic Data During Hypotensive Episode Improves Mortality Predictions Among Patients With Sepsis and Hypotension

Objectives:To determine if a prediction rule for hospital mortality using dynamic variables in response to treatment of hypotension in patients with sepsis performs better than current models. Design:Retrospective cohort study. Setting:All ICUs at a tertiary care hospital. Patients:Adult patients admitted to ICUs between 2001 and 2007 of whom 2,113 met inclusion criteria and had sufficient data. Interventions:None. Measurements and Main Results:We developed a prediction algorithm for hospital mortality in patients with sepsis and hypotension requiring medical intervention using data from the Multiparameter Intelligent Monitoring in Intensive Care II. We extracted 189 candidate variables, including treatments, physiologic variables and laboratory values collected before, during, and after a hypotensive episode. Thirty predictors were identified using a genetic algorithm on a training set (n = 1500) and validated with a logistic regression model on an independent validation set (n = 613). The final prediction algorithm used included dynamic information and had good discrimination (area under the receiver operating curve = 82.0%) and calibration (Hosmer–Lemeshow C statistic = 10.43, p = 0.06). This model was compared with Acute Physiology and Chronic Health Evaluation IV using reclassification indices and was found to be superior with an Net Reclassification Improvement of 0.19 (p < 0.001) and an Integrated Discrimination Improvement of 0.09 (p < 0.001). Conclusions:Hospital mortality predictions based on dynamic variables surrounding a hypotensive event is a new approach to predicting prognosis. A model using these variables has good discrimination and calibration and offers additional predictive prognostic information beyond established ones.

School Endotoxin Exposure and Asthma Morbidity in Inner-city Children

BACKGROUND Endotoxin exposure is associated with airway inflammation. Children spend 6 to 8 h/d in school, yet the effect of school-specific endotoxin exposure on asthma morbidity is not well understood. METHODS In this longitudinal cohort study, 248 students with asthma, from 38 inner-city schools, underwent baseline phenotyping and follow-up. Clinical outcomes were evaluated throughout the academic school year and linked to classroom-specific dust and air endotoxin levels as well as home dust endotoxin levels. The primary outcome was maximum asthma symptom-days per 2-week period. RESULTS Classrooms had higher settled dust endotoxin levels compared with homes (14.3 endotoxin unit/mg vs 11.3 endotoxin unit/mg; P = .02). Airborne endotoxin levels exceeding recommended occupational exposure limits for adults were recorded in 22.0% of classrooms. Classroom air endotoxin levels were independently associated with increased maximum symptom-days in children with nonatopic asthma, but not in those with atopic asthma (interaction P = .03). Adjusting for home exposures, classroom endotoxin exposure was independently associated with a dose-dependent increase in asthma symptom-days for children with nonatopic asthma (adjusted incidence rate ratio, 1.16 [95% CI, 1.03-1.31]; P = .02). In these subjects, maximum symptom-days increased by 1.3 days for each 14-day period when comparing students in classrooms with the lowest endotoxin levels compared with average measured levels. CONCLUSIONS Inner-city children with asthma are exposed to high levels of airborne endotoxin at school, resulting in increased asthma symptoms in children with nonatopic asthma. Mitigation of school-related exposures may represent a strategy to decrease asthma morbidity in this population. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01756391; URL: www.clinicaltrials.gov.

School Environmental Intervention to Reduce Particulate Pollutant Exposures for Children with Asthma

BACKGROUND Home-based interventions to improve indoor air quality have demonstrated benefits for asthma morbidity, yet little is known about the effect of environmental interventions in the school setting. OBJECTIVE We piloted the feasibility and effectiveness of a classroom-based air cleaner intervention to reduce particulate pollutants in classrooms of children with asthma. METHODS In this pilot randomized controlled trial, we assessed the effect of air cleaners on indoor air particulate pollutant concentrations in 18 classrooms (9 control, 9 intervention) in 3 urban elementary schools. We enrolled 25 children with asthma (13 control, 12 intervention) aged 6 to 10 years. Classroom air pollutant measurements and spirometry were completed once before and twice after randomization. Asthma symptoms were surveyed every 3 months. RESULTS Baseline classroom levels of fine particulate matter (particulate matter with diameter of <2.5 μm [PM2.5]) and black carbon (BC) were 6.3 and 0.41 μg/m3, respectively. When comparing the intervention to the control group, classroom PM2.5 levels were reduced by 49% and 42% and BC levels were reduced by 58% and 55% in the first and second follow-up periods, respectively (P < .05 for all comparisons). When comparing the children randomized to intervention and control classrooms, there was a modest improvement in peak flow, but no significant changes in forced expiratory volume in 1 second (FEV1) and asthma symptoms. CONCLUSIONS In this pilot study, a classroom-based air cleaner intervention led to significant reductions in PM2.5 and BC. Future large-scale studies should comprehensively evaluate the effect of school-based environmental interventions on pediatric asthma morbidity.

Time-Limited Trials of Intensive Care for Critically Ill Patients With Cancer: How Long Is Long Enough?

IMPORTANCE Time-limited trials of intensive care are commonly used in patients perceived to have a poor prognosis. The optimal duration of such trials is unknown. Factors such as a cancer diagnosis are associated with clinician pessimism and may affect the decision to limit care independent of a patients severity of illness. OBJECTIVE To identify the optimal duration of intensive care for short-term mortality in critically ill patients with cancer. DESIGN, SETTING, AND PARTICIPANTS Decision analysis using a state-transition microsimulation model was performed to simulate the hospital course of patients with poor-prognosis primary tumors, metastatic disease, or hematologic malignant neoplasms admitted to medical and surgical intensive care units. Transition probabilities were derived from 920 participants stratified by sequential organ failure assessment (SOFA) scores to identify severity of illness. The model was validated in 3 independent cohorts with 349, 158, and 117 participants from quaternary care academic hospitals. Monte Carlo microsimulation was performed, followed by probabilistic sensitivity analysis. Outcomes were assessed in the overall cohort and in solid tumors alone. INTERVENTIONS Time-unlimited vs time-limited trials of intensive care. MAIN OUTCOMES AND MEASURES 30-day all-cause mortality and mean survival duration. RESULTS The SOFA scores at ICU admission were significantly associated with mortality. A 3-, 8-, or 15-day trial of intensive care resulted in decreased mean 30-day survival vs aggressive care in all but the sickest patients (SOFA score, 5-9: 48.4% [95% CI, 48.0%-48.8%], 60.6% [95% CI, 60.2%-61.1%], and 66.8% [95% CI, 66.4%-67.2%], respectively, vs 74.6% [95% CI, 74.3%-75.0%] with time-unlimited aggressive care; SOFA score, 10-14: 36.2% [95% CI, 35.8%-36.6%], 44.1% [95% CI, 43.6%-44.5%], and 46.1% [95% CI, 45.6%-46.5%], respectively, vs 48.4% [95% CI, 48.0%-48.8%] with aggressive care; SOFA score, ≥ 15: 5.8% [95% CI, 5.6%-6.0%], 8.1% [95% CI, 7.9%-8.3%], and 8.3% [95% CI, 8.1%-8.6%], respectively, vs 8.8% [95% CI, 8.5%-9.0%] with aggressive care). However, the clinical magnitude of these differences was variable. Trial durations of 8 days in the sickest patients offered mean survival duration that was no more than 1 day different from time-unlimited care, whereas trial durations of 10 to 12 days were required in healthier patients. For the subset of patients with solid tumors, trial durations of 1 to 4 days offered mean survival that was not statistically significantly different from time-unlimited care. CONCLUSIONS AND RELEVANCE Trials of ICU care lasting 1 to 4 days may be sufficient in patients with poor-prognosis solid tumors, whereas patients with hematologic malignant neoplasms or less severe illness seem to benefit from longer trials of intensive care.

Chronic Endotoxin Exposure Produces Airflow Obstruction and Lung Dendritic Cell Expansion

Little is known about the mechanisms of persistent airflow obstruction that result from chronic occupational endotoxin exposure. We sought to analyze the inflammatory response underlying persistent airflow obstruction as a result of chronic occupational endotoxin exposure. We developed a murine model of daily inhaled endotoxin for periods of 5 days to 8 weeks. We analyzed physiologic lung dysfunction, lung histology, bronchoalveolar lavage fluid and total lung homogenate inflammatory cell and cytokine profiles, and pulmonary gene expression profiles. We observed an increase in airway hyperresponsiveness as a result of chronic endotoxin exposure. After 8 weeks, the mice exhibited an increase in bronchoalveolar lavage and lung neutrophils that correlated with an increase in proinflammatory cytokines. Detailed analyses of inflammatory cell subsets revealed an expansion of dendritic cells (DCs), and in particular, proinflammatory DCs, with a reduced percentage of macrophages. Gene expression profiling revealed the up-regulation of a panel of genes that was consistent with DC recruitment, and lung histology revealed an accumulation of DCs in inflammatory aggregates around the airways in 8-week-exposed animals. Repeated, low-dose LPS inhalation, which mirrors occupational exposure, resulted in airway hyperresponsiveness, associated with a failure to resolve the proinflammatory response, an inverted macrophage to DC ratio, and a significant rise in the inflammatory DC population. These findings point to a novel underlying mechanism of airflow obstruction as a result of occupational LPS exposure, and suggest molecular and cellular targets for therapeutic development.

Modeling indoor particulate exposures in inner-city school classrooms

Outdoor air pollution penetrates buildings and contributes to total indoor exposures. We investigated the relationship of indoor to outdoor particulate matter in inner-city school classrooms. The School Inner City Asthma Study investigates the effect of classroom-based environmental exposures on students with asthma in the northeast United States. Mixed effects linear models were used to determine the relationships between indoor PM2.5 (particulate matter) and black carbon (BC), and their corresponding outdoor concentrations, and to develop a model for predicting exposures to these pollutants. The indoor–outdoor sulfur ratio was used as an infiltration factor of outdoor fine particles. Weeklong concentrations of PM2.5 and BC in 199 samples from 136 classrooms (30 school buildings) were compared with those measured at a central monitoring site averaged over the same timeframe. Mixed effects regression models found significant random intercept and slope effects, which indicate that: (1) there are important PM2.5 sources in classrooms; (2) the penetration of outdoor PM2.5 particles varies by school and (3) the site-specific outside PM2.5 levels (inferred by the models) differ from those observed at the central monitor site. Similar results were found for BC except for lack of indoor sources. The fitted predictions from the sulfur-adjusted models were moderately predictive of observed indoor pollutant levels (out of sample correlations: PM2.5: r2=0.68, BC; r2=0.61). Our results suggest that PM2.5 has important classroom sources, which vary by school. Furthermore, using these mixed effects models, classroom exposures can be accurately predicted for dates when central site measures are available but indoor measures are not available.

Gender differences in the effect of occupational endotoxin exposure on impaired lung function and death: the Shanghai Textile Worker Study

Objective Airborne endotoxin exposure has adverse and protective health effects. Studies show men have augmented acute inflammatory responses to endotoxin. In this longitudinal cohort study we investigated the effect of long-term exposure to endotoxin in cotton dust on health, and determined whether these effects differ by gender. Methods In the Shanghai Textile Worker Study, 447 cotton and 472 control silk textile workers were followed from 1981 to 2011 with repeated measures of occupational endotoxin exposure, spirometry and health questionnaires. Impaired lung function was defined as a decline in forced expiratory volume in one second to less than the 5th centile of population predicted. Death was ascertained by death registries. We used Cox proportional hazards models to assess the effect of endotoxin exposure on the time to development of impaired lung function and death. Results 128 deaths and 164 diagnoses of impaired lung function were ascertained between 1981 and 2011. HRs for the composite end point of impaired lung function or death was 1.47 (95% CI 1.09 to 1.97) for cotton vs silk workers and 1.04 (95% CI 1.01 to 1.07) per 10 000 endotoxin units (EU)/m3-years increase in exposure. HRs for all-cause mortality was 1.36 (95% CI 0.93 to 1.99) for cotton vs silk workers and 1.04 (95% CI 0.99 to 1.08) per 10 000 EU/m3-years. The risk associated with occupational endotoxin exposure was elevated only in men. Conclusions Occupational endotoxin exposure is associated with an increase in the risk of impaired lung function and all-cause mortality in men.