Indoor heat exposure in Baltimore: does outdoor temperature matter?

Heat exposure of a population is often estimated by applying temperatures from outdoor monitoring stations. However, this can lead to exposure misclassification if residents do not live close to the monitoring station and temperature varies over small spatial scales due to land use/built environment variability, or if residents generally spend more time indoors than outdoors. Here, we compare summertime temperatures measured inside 145 homes in low-income households in Baltimore city with temperatures from the National Weather Service weather station in Baltimore. There is a large variation in indoor temperatures, with daily-mean indoor temperatures varying from 10 °C lower to 10 °C higher than outdoor temperatures. Furthermore, there is only a weak association between the indoor and outdoor temperatures across all houses, indicating that the outdoor temperature is not a good predictor of the indoor temperature for the residences sampled. It is shown that much of the variation is due to differences in the availability of air conditioning (AC). Houses with central AC are generally cooler than outdoors (median difference of - 3.4 °C) while those with no AC are generally warmer (median difference of 1.4 °C). For the collection of houses with central or room AC, there is essentially no relationship between indoor and outdoor temperatures, but for the subset of houses with no AC, there is a weak relationship (correlation coefficient of 0.36). The results presented here suggest future epidemiological studies of indoor exposure to heat would benefit from information on the availability of AC within the population.

Home interventions are effective at decreasing indoor nitrogen dioxide concentrations.

UNLABELLED: Nitrogen dioxide (NO2 ), a by-product of combustion produced by indoor gas appliances such as cooking stoves, is associated with respiratory symptoms in those with obstructive airways disease. We conducted a three-armed randomized trial to evaluate the efficacy of interventions aimed at reducing indoor NO2 concentrations in homes with unvented gas stoves: (i) replacement of existing gas stove with electric stove; (ii) installation of ventilation hood over existing gas stove; and (iii) placement of air purifiers with high-efficiency particulate air (HEPA) and carbon filters. Home inspection and NO2 monitoring were conducted at 1 week pre-intervention and at 1 week and 3 months post-intervention. Stove replacement resulted in a 51% and 42% decrease in median NO2 concentration at 3 months of follow-up in the kitchen and bedroom, respectively (P = 0.01, P = 0.01); air purifier placement resulted in an immediate decrease in median NO2 concentration in the kitchen (27%, P < 0.01) and bedroom (22%, P = 0.02), but at 3 months, a significant reduction was seen only in the kitchen (20%, P = 0.05). NO2 concentrations in the kitchen and bedroom did not significantly change following ventilation hood installation. Replacing unvented gas stoves with electric stoves or placement of air purifiers with HEPA and carbon filters can decrease indoor NO2 concentrations in urban homes. PRACTICAL IMPLICATIONS: Several combustion sources unique to the residential indoor environment, including gas stoves, produce nitrogen dioxide (NO2), and higher NO2 concentrations, are associated with worse respiratory morbidity in people with obstructive lung disease. A handful of studies have modified the indoor environment by replacing unvented gas heaters; this study, to our knowledge, is the first randomized study to target unvented gas stoves. The results of this study show that simple home interventions, including replacement of an unvented gas stove with an electric stove or placement of HEPA air purifiers with carbon filters, can significantly decrease indoor NO2 concentrations.

Dose-response relationships between mouse allergen exposure and asthma morbidity among urban children and adolescents.

Home mouse allergen exposure is associated with asthma morbidity, but little is known about the shape of the dose-response relationship or the relevance of location of exposure within the home. Asthma outcome and allergen exposure data were collected every 3 months for 1 year in 150 urban children with asthma. Participants were stratified by mouse sensitization, and relationships between continuous measures of mouse allergen exposure and outcomes of interest were analyzed. Every tenfold increase in the bed mouse allergen level was associated with an 87% increase in the odds of any asthma-related health care use among mouse-sensitized [Odds Ratio (95% CI): 1.87 (1.21-2.88)], but not non-mouse-sensitized participants. Similar relationships were observed for emergency department visit and unscheduled doctor visit among mouse-sensitized participants. Kitchen floor and bedroom air mouse allergen concentrations were also associated with greater odds of asthma-related healthcare utilization; however, the magnitude of the association was less than that observed for bed mouse allergen concentrations. In this population of urban children with asthma, there is a linear dose-response relationship between mouse allergen concentrations and asthma morbidity among mouse-sensitized asthmatics. Bed and bedroom air mouse allergen exposure compartments may have a greater impact on asthma morbidity than other compartments.

Predictors of airborne endotoxin concentrations in inner city homes.

Few studies have assessed in home factors which contribute to airborne endotoxin concentrations. In 85 inner city Baltimore homes, we found no significant correlation between settled dust and airborne endotoxin concentrations. Certain household activities and characteristics, including frequency of dusting, air conditioner use and type of flooring, explained 36-42% of the variability of airborne concentrations. Measurements of both airborne and settled dust endotoxin concentrations may be needed to fully characterize domestic exposure in epidemiologic investigations.

Analysis of CD4+ T-cell gene expression in allergic subjects using two different microarray platforms.

BACKGROUND: Allergic diseases are thought to involve dysregulated activation of T cells including CD4+ lymphocytes. T-cell activation results in changes in gene expression, but the optimal method to study gene expression profiles in T cells, and how this changes over time, are not known. METHODS: Circulating CD4+ T cells were obtained from subjects with atopic asthma, nonatopic asthma or nonallergic controls, and total mRNA was rapidly isolated. Atopy was defined as positive skin prick test to one of nine allergens. Gene expression was analyzed using hybridization and Affymetrix oligonucleotide arrays (Hu133A and Hu133B chips, n = 84), or by reverse transcription-polymerase chain reaction (RT-PCR) with a pathway-targeted array (Human Th1-Th2-Th3 RT(2) Profiler PCR Array, Superarray, n = 16). RESULTS: Using Affymetrix arrays, it was difficult to discern a dominant allergy-associated profile because of heterogeneity in gene expression profiles. In contrast, a Th2-like signature was evident using RT-PCR arrays with increased expression of expected genes (e.g. IL-4, 5, 9, and 13, all P < 0.05) as well as unexpected gene transcripts (e.g. osteopontin). Gene expression profiles were relatively stable over time in circulating CD4+ T cells from two subjects using both platforms. CONCLUSIONS: Unstimulated CD4+ T cells isolated from allergic subjects express a characteristic profile of genes when analyzed using RT-PCR based microarrays.

Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity.

BACKGROUND: High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. OBJECTIVE: To determine if high levels of mouse-specific IgG and IgG4 are associated with a decreased risk of mouse skin test sensitivity. METHODS: Two hundred and sixty workers of a mouse facility underwent skin prick testing and completed a questionnaire. Serum levels of mouse-specific IgG and IgG4 were quantified by solid-phase antigen binding assays. Room air samples were collected and airborne Mus m 1 was quantified by ELISA. RESULTS: Forty-nine participants had a positive skin prick test to mouse. Mouse-specific IgG was detected in 219 (84%) participants and IgG4 was detected in 72 (28%) participants. A detectable mouse-specific IgG4 level was associated with an increased risk of mouse skin test sensitivity (odds ratios (OR) 6.4, 95% confidence intervals (CI) 3.3-12.4). Mouse-specific IgG and IgG4 were both positively correlated with mouse allergen exposure (r(s)=0.31, P=0.0001, and r(s)=0.27, P=0.0006, respectively). The odds of skin test sensitivity peaked at moderate levels of IgG4, but decreased at the highest levels of mouse-specific IgG4. In contrast, the odds of skin test sensitivity increased monotonically with IgG levels. CONCLUSIONS: A detectable level of mouse-specific IgG4 is associated with an increased risk of skin test sensitivity to mouse. However, the highest IgG4 levels appear to be associated with an attenuated risk of mouse skin test sensitivity, suggesting that induction of high levels of IgG4 through natural exposure may protect against the development of allergic sensitization.

Risk factors for the development of bronchiolitis obliterans in children with bronchiolitis.

BACKGROUND: Bronchiolitis obliterans (BO) is an uncommon and severe form of chronic obstructive lung disease in children that results from an insult to the lower respiratory tract. METHODS: A case-control study of children under the age of 3 years was performed in 109 cases and 99 controls to determine risk factors for the development of BO. Participants were evaluated by immunofluorescence viral tests, pulmonary function tests, and questions to assess tobacco and other exposures. RESULTS: Bronchiolitis due to adenovirus (odds ratio (OR) 49, 95% confidence interval (CI) 12 to 199) and the need for mechanical ventilation (OR 11, 95% CI 2.6 to 45) were strongly and independently associated with an increased risk for BO. Factors not associated with post-infectious BO included age of the child, sex, and environmental tobacco exposure (either in utero or during infancy). CONCLUSIONS: Adenovirus infection and need for mechanical ventilation are significant risk factors for developing BO in children. Further research is needed to determine why these risk factors are so strong and how they may contribute to the development of the disease.

Mouse allergen-specific immunoglobulin G and immunoglobulin G4 and allergic symptoms in immunoglobulin E-sensitized laboratory animal workers.

BACKGROUND: High levels of allergen-specific IgG have been associated with clinical efficacy in immunotherapy studies, but whether this antibody isotype is associated with clinical tolerance in the setting of environmental exposure remains unclear. OBJECTIVE: To determine if mouse allergen-specific IgG (mIgG) and IgG4 (mIgG4) levels are associated with mouse-related symptoms among IgE-sensitized laboratory workers. METHODS: Fifty-eight workers with either skin test or serologic evidence of IgE-mediated mouse sensitization were studied. Symptom data were obtained by a questionnaire. Serum levels of mouse-specific IgG, IgG4, and IgE were quantified by a solid-phase antigen-binding assay (IgG) and RAST (IgG4 and IgE), and the relationships between mouse-specific serologic responses and mouse-related symptoms were analysed. RESULTS: Twenty-three (39.7%) participants reported mouse-related symptoms. Mouse-specific IgG and IgG4 levels were not associated with mouse-related symptoms among the study population as a whole. Among the 29 (50%) participants with detectable mouse-specific IgE (mIgE), higher mouse-specific IgG and IgG4 levels were associated with a decreased risk of symptoms, after adjusting for mIgE level (odds ratio (OR) 0.3, 95% confidence interval (CI): 0.1-1.4, and OR 0.3, 95% CI: 0.04-2.6, respectively). Higher levels of mIgG and mIgG4 remained associated with a decreased risk of symptoms after additional adjustment for sex and handling of mice (OR 0.1, 95% CI: 0.02-0.7, and OR 0.2, 95% CI: 0.02-2.1, respectively). Higher mIgG : IgE and mIgG4 : IgE ratios were also associated with a decreased risk of symptoms after adjusting for these confounders (OR 0.1, 95% CI: 0.02-0.7, and OR 0.2, 95% CI: 0.02-0.92, respectively). CONCLUSION: Among workers with detectable mIgE, higher mIgG and mIgG4 levels are associated with a decreased risk of mouse-related symptoms. High serum levels of mIgG or mIgG4 may be markers for clinical tolerance among laboratory mouse workers with detectable mIgE, but these findings need to be confirmed in larger, prospective studies.

Quality of care and outcomes of adults with asthma treated by specialists and generalists in managed care.

BACKGROUND: The growth of managed health care in the United States has been accompanied by controls on access to specialty physician services. We examined the relationship of physician specialty to treatment and outcomes of patients with asthma in managed care plans. METHODS: We conducted a mail survey of adult asthma patients who were enrolled in 12 managed care organizations and had at least 2 contacts for asthma (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.x) during the previous 24 months; we also surveyed their treating physicians. This report concerns 1954 patients and their 1078 corresponding physicians. Treatment indicators included use of corticosteroid inhalers, use of peak flow meters, allergy evaluation, discussion of triggers, and patient self-management knowledge. Outcome measures included canceled activities, hospitalization or emergency department visits, asthma attacks, workdays lost, asthma symptoms, physical and mental health, overall satisfaction with asthma care, and satisfaction with communication with physicians and nurses. RESULTS: Significant differences were noted for patients of specialists and experienced generalists compared with those of generalist physicians. Peak flow meter possession was reported by 41.9% of patients of generalists, 51.7% of patients of experienced generalists, and 53.8% of patients of pulmonologists or allergists. Compared with patients of generalists, outcomes were significantly better for patients of allergists with regard to canceled activities, hospitalizations and emergency department visits for asthma, quality of care ratings, and physical functioning. Patients of pulmonologists were more likely to rate improvement in symptoms as very good or excellent. CONCLUSIONS: In a managed health care setting, physicians' specialty training and self-reported expertise in treating asthma were related to better patient-reported care and outcomes.

Comparison of quality of care by specialist and generalist physicians as usual source of asthma care for children.

OBJECTIVE: To determine whether care for children was more consistent with national asthma guidelines when a specialist rather than a generalist was the usual source of asthma care. DESIGN: Cross-sectional survey. SETTING: Two large managed care organizations in the United States. PARTICIPANTS: A total of 260 parents of children with asthma. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Parent reports of the physician primarily responsible for asthma care (specialist, generalist, or both equally) and whom they would call (specialist or generalist) for questions about asthma care were used to define usual source of care. We assessed consistency of care with 1997 National Asthma Education and Prevention Program guidelines using 11 indicators in 4 domains of asthma care: patient education, control of factors contributing to asthma symptoms, periodic physiologic assessment and monitoring, and proper use of medications. RESULTS: In all 4 domains, care was more likely to be consistent with guidelines when specialists were the usual source of care. These differences remained after adjustment for symptom severity, recent care encounters, and parent demographics. Greatest differences for specialist versus generalist management were for use of controller medications (odds ratio [OR] 6.7; 95% confidence interval [CI]: 1.5-30.4), ever having a pulmonary function test (OR 6.5; 95% CI: 2.4-18.1), and having been told about asthma triggers and how to avoid them (OR 5.9; 95% CI: 1.3-26.2). CONCLUSIONS: In these managed care organizations, asthma care in children was more likely to be consistent with national guidelines when a specialist was the primary provider. Greater use of specialists or altering generalist physicians' care may improve the degree to which the care of children with asthma is consistent with national guidelines.

Race and sex differences in consistency of care with national asthma guidelines in managed care organizations.

BACKGROUND: In the United States, morbidity from asthma disproportionately affects African Americans and women. Although inadequate care contributes to overall asthma morbidity, less is known about differences in asthma care by race and sex. SUBJECTS AND METHODS: To examine the relationships of race and sex with asthma care, we analyzed responses to questionnaires administered to adults enrolled in 16 managed care organizations participating in the Outcomes Management System Asthma Study between September and December 1993. Indicators of care consistent with National Asthma Education and Prevention Program (1991) recommendations were assessed. Of a random sample of 8640 patients asked to participate, 6612 (77%) completed the survey. This study focused on 5062 (14% African American, 72% women) patients with at least moderate asthma symptom severity. RESULTS: Fewer African Americans than whites reported care consistent with recommendations for medication use (eg, daily inhaled corticosteroid use, 34.9% vs 54.4%; P =.001), self-management education (eg, action plan, 42.0% vs 53.8%; P =.001), avoiding triggers (37.6% vs 53.6%; P =.001), and specialist care (28.3% vs 41.0%; P =.001). Differences in asthma care by sex were smaller and tended to favor women except for daily inhaled corticosteroid use (women vs men: 49.6% vs 58.3%; P =.001) and having specialist care (37.7% vs 43.1%; P =.001). Similar race and sex differences were observed after adjusting for age, education, employment, and symptom frequency. CONCLUSIONS: Even among patients with health insurance, disparities in asthma care for African Americans compared with whites exist and may contribute to race disparities in outcomes. Women generally reported better asthma care but may benefit from greater use of inhaled corticosteroids.

Hospitalization in amyotrophic lateral sclerosis: causes, costs, and outcomes.

OBJECTIVE: As ALS progresses, extensive supportive care is required, including multidisciplinary outpatient care and hospitalization. The authors studied the causes, health care utilization, and outcomes for hospitalized patients with ALS. METHODS: With use of the 1996 Nationwide Inpatient Sample, an administrative database representing 20% of U.S. hospitals, 1,600 hospitalizations in patients with ALS were identified and compared with 5,364,728 non-ALS hospitalizations. RESULTS: The most common concurrent diagnoses in patients with ALS were dehydration and malnutrition (574 patients, 36%), pneumonia (507 patients, 32%), and respiratory failure (398 patients, 25%). Only 38% of patients with ALS were discharged to home without home health care compared with 73% of patients with non-ALS. Fifteen percent of patients with ALS died in the hospital compared with 3% of non-ALS patients. The average length of hospital stay and charges were greater for patients with ALS than for non-ALS patients (8.4 days and $19,810 for ALS patients and 5.4 days and $11,924 for non-ALS patients). Mortality was significantly associated with emergency room admission (versus nonemergency admission; OR = 1.60), increasing age (per year; OR = 1.03), respiratory failure (OR = 3.37), and pneumonia (OR = 2.02) (p < 0.01 for all comparisons). CONCLUSIONS: Patients with ALS have lengthy and costly hospital admissions, a high in-hospital mortality rate, and few routine discharges. Recognition of the issues that precipitate hospitalization may allow development of preventive strategies.

Consistency of care with national guidelines for children with asthma in managed care.

OBJECTIVE: To evaluate the consistency of pediatric asthma care with the National Asthma Education and Prevention Program Guidelines. DESIGN: Cross-sectional survey at 2 managed care organizations in the United States (winter 1997-1998). The participants were parents of children (n = 318) age 5 to 17 years with asthma. There were no interventions. The outcome measures were indicators of care in 4 domains: (1) periodic physiologic assessment, (2) proper use of medications, (3) patient education, and (4) control of factors contributing to asthma severity. RESULTS: Of 533 eligible patients with asthma, 318 (60%) parents responded; 59% of children were male, 76% were white, and 60% were aged 5 to 10 years. Deficiencies in care were identified in all care domains including, for patients with moderate and severe persistent symptoms, only 55% used long-term control medication daily, 49% had written instructions for handling asthma attacks, 44% had instructions for adjustment of medication before exposures, 56% had undergone allergy testing, and 54% had undergone pulmonary function testing. CONCLUSIONS: There are significant opportunities to improve the quality of care for children with asthma enrolled in managed care. A comprehensive approach to improving care may be necessary to address multiple aspects of care where opportunities exist.

The advantages and disadvantages of process-based measures of health care quality.

As consumers, payers, and regulatory agencies require evidence regarding health care qualities the demand for process of care measures will grow. Although outcome measures of quality represent the desired end results of health care, validated process of care measures provide an important additional element to quality improvement efforts, as they illuminate exactly which provider actions could be changed to improve patient outcomes. In this essay, we discuss the advantages and disadvantages of process measures of quality, and outline some practical strategies and issues in implementing them.

From a process of care to a measure: the development and testing of a quality indicator.

This paper outlines the steps in developing and implementing process measures of quality. Developing a process measure includes defining the purpose of and audiences for the measures, choosing the clinical area to evaluate, organizing the assessment team, choosing the component of the process to measure, writing the indicator specifications, performing preliminary tests of feasibility, reliability and validity, and determining scoring and analytical specifications. Given the growing evidence in the literature regarding the impact of care, and an evolving understanding of how to develop and implement process of care measures as outlined here, the future should bring the development and implementation of quality indicators that are rigorously developed and that will provide insights into opportunities to improve the quality of care.

Nocturnal asthma in children affects school attendance, school performance, and parents' work attendance.

CONTEXT: Asthma symptoms that occur at night may signal worse asthma control, but the nighttime occurrence may have additional clinical significance. To date, however, there have been few studies of the impact of nocturnal awakening from asthma on children with the disease, including problems with daytime functioning. OBJECTIVE: To determine if school absenteeism and school performance in children and work absenteeism in their parents are associated with nocturnal awakenings from asthma. DESIGN: Cross-sectional survey during the winter of 1997 through 1998. SETTING: Three managed care organizations in the United States. PARTICIPANTS: Parents of 438 children with asthma, aged 5 to 17 years, who were enrolled in managed care organizations. INTERVENTION: None. MAIN OUTCOME MEASURES: Parent's reports of number of days their child missed school and parent missed work and how often the child's education suffered because of asthma in the past 4 weeks. RESULTS: Overall, more than 40% of children had nocturnal awakenings from asthma in the past 4 weeks. Multivariate analyses were performed that adjusted for child age, race, overall symptom severity, and use of reliever medications. Compared with children who did not awaken from asthma, there were greater odds of missed school days in children who awakened 1 to 3 nights (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.1-6.2), 4 to 7 nights (OR, 4.4; 95% CI, 2.0-10.0), and more than 7 nights (OR, 14.7; 95% CI, 5.9-37.0). Similarly, there were greater odds of education suffering in children who awakened 1 to 3 nights (OR, 2.3; 95% CI, 1.4-3.7), 4 to 7 nights (OR, 2.1; 95% CI, 0.9-4.6), and more than 7 nights (OR, 2.3; 95% CI, 1. 0-5.4), and parents missing work in children who awakened 1 to 3 nights (OR, 4.0; 95% CI, 2.2-7.1), 4 to 7 nights (OR, 6.5; 95% CI, 2.7-16), and more than 7 nights (OR, 3.2; 95% CI, 1.3-7.9). Greater overall symptom severity and high use of reliever mediation were also associated with missed school, education suffering, and parent absenteeism. CONCLUSIONS: Nighttime awakenings in children with asthma may affect school attendance and performance, as well as work attendance by parents. Nighttime symptoms have independent prognostic value, even when overall asthma symptom severity is accounted for. By addressing whether there are nighttime awakenings in children with asthma, clinicians may be able to tailor the therapeutic regimen to counter these symptoms.

Predictors of pain control in patients undergoing flexible bronchoscopy.

The purpose of this study was to assess the extent to which patients undergoing flexible bronchoscopy (FOB) experience pain and to identify patient factors and process of care factors that are associated with pain. We conducted a prospective cohort study on 481 patients undergoing FOB. Overall control of pain during FOB was the primary outcome. The mean age of the patients was 48 yr, 50% were male, and 32% required supplemental oxygen prior to FOB. Pain control was excellent in 36% of patients, but 10% considered it to be fair or poor. Patient factors associated with excellent pain control were excellent health (versus poor health, OR = 6.25 [95% CI, 2.28-16.67]), more education (college education versus high school education, OR = 1.72 [95% CI, 1.05-2.86]), and not having asthma (OR = 2.86 [95% CI, 1.09-7.14]). Process of care factors associated with excellent pain control were not being bothered by scope insertion (versus bothered, OR = 3.65 [95% CI, 1.99-6.98]), no memory of FOB (versus some memory, OR = 2.33 [95% CI, 1.24-4.44]), and higher ratings of information about the procedure (per 1-point increase on a 12-point scale, OR = 1.57 [95% CI, 1.41-1.78]). This is the first large-scale, prospective study to evaluate patient and process of care factors that influence pain control during FOB. It demonstrated that there are patient characteristics and process of care factors that need to be considered when evaluating pain during bronchoscopy. Improved preparation of patients with lower education, inferior health status, and asthma may lead to decreased pain during FOB. Bronchoscopists may be able to reduce pain during FOB by identifying methods to decrease pain on scope insertion, by improving the information provided to patients, and by achieving greater levels of amnesia during FOB.

Utility of on-site cytopathology assessment for bronchoscopic evaluation of lung masses and adenopathy.

STUDY OBJECTIVES: To determine the extent to which on-site cytopathology assessment improves diagnostic yield when sampling lung nodules or masses and/or hilar or mediastinal lymphadenopathy by fiberoptic bronchoscopy (FOB). DESIGN: Prospective cohort study. SETTING: Two teaching hospitals in Baltimore, MD. PATIENTS: Consecutive adult patients (>/= 18 years) undergoing FOB for evaluation of lung nodules or masses and/or hilar or mediastinal lymphadenopathy. INTERVENTION: Prospective collection of data on patient factors and details of the procedure on standardized report forms. MEASUREMENTS AND RESULTS: The primary outcome measure was a new diagnosis obtained by FOB. On-site assessment was used in 81 of 204 cases (40%), and overall diagnostic yield was 62%. Yield was greater when on-site cytopathology assessment was used, in unadjusted analysis (81% vs 50%, p < 0.001) and in a multivariate model (odds ratio, 4.5; 95% confidence interval, 2.1 to 10.0). Other significant predictors of a new diagnosis included older patient age, higher dose of narcotic used during FOB, and shorter procedure time. CONCLUSIONS: We conclude that diagnostic yield was greater when on-site cytopathology was used to assist FOB evaluation of intrathoracic adenopathy and/or lung nodules or masses. Increasing the use of on-site cytopathology assessment may improve the quality of FOB services.

c-Myc suppresses the tumorigenicity of lung cancer cells and down-regulates vascular endothelial growth factor expression.

The c-myc oncogene is frequently amplified in cells grown from lung tumors and has been linked to the malignancy of these cancers. In support of this, c-myc transfection enhances the in vitro proliferation and soft agar cloning of human small cell lung cancer (SCLC) cells. In this study, we surprisingly found that c-myc expression suppressed the formation of tumors by SCLC cells in athymic nude mice. c-myc expression down-regulated the protein and transcript for vascular endothelial growth factor (VEGF) in these SCLC cells, as well as VEGF transcript in rat fibroblasts manipulated for c-myc expression and in liver cells of c-myc-transgenic mice. Finally, bivariate and multivariate analyses demonstrated that the probability of tumor formation from lung cancer cell lines was negatively correlated with the relative expression of c-Myc, positively correlated with the relative expression of VEGF, and that the latent time to tumor formation was increased by the expression of c-Myc and decreased by the expression of VEGF. We hypothesize that, for lung cancer cells, c-Myc suppresses the formation of tumors in vivo by down-regulating VEGF, and that the amplification of c-myc seen in cells grown from lung tumors with a poor prognosis is an artifact of selection for growth in vitro.