Improving follow-up of abnormal cancer screens using electronic health records: trust but verify test result communication.

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response. METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. We identified the source of test result communication breakdown, and developed an intervention to fix the problem. Explicit medical record reviews measured timely follow-up (defined as response within 30 days of positive FOBT) pre- and post-intervention. RESULTS: Data from 11 interviews and tracking information from 490 FOBT alerts revealed that the software intended to alert primary care practitioners (PCPs) of positive FOBT results was not configured correctly and over a third of positive FOBTs were not transmitted to PCPs. Upon correction of the technical problem, lack of timely follow-up decreased immediately from 29.9% to 5.4% (p<0.01) and was sustained at month 4 following the intervention. CONCLUSION: Electronic communication of positive FOBT results should be monitored to avoid limiting colorectal cancer screening benefits. Robust quality assurance and oversight systems are needed to achieve this. Our methods may be useful for others seeking to improve follow-up of FOBTs in their systems.

NOVEL AMINO ACID TRANSPORTER-TARGETED RADIOTRACERS FOR BREAST CANCER IMAGING

Breast cancer is the most common malignancy among women in the world. Its 5-year survival rate ranges from 23.4% in patients with stage IV to 98% in stage I disease, highlighting the importance of early detection and diagnosis. 18F-2-Fluoro-2-deoxy-glucose (18F-FDG), using positron emission tomography (PET), is the most common functional imaging tool for breast cancer diagnosis currently. Unfortunately, 18F-FDG-PET has several limitations such as poorly differentiating tumor tissues from inflammatory and normal brain tissues. Therefore, 18F-labeled amino acid-based radiotracers have been reported as an alternative, which is based on the fact that tumor cells uptake and consume more amino acids to sustain their uncontrolled growth. Among those radiotracers, 18F-labeled tyrosine and its derivatives have shown high tumor uptake and great ability to differentiate tumor tissue from inflammatory sites in brain tumors and squamous cell carcinoma. They enter the tumor cells via L-type amino acid transporters (LAT), which were reported to be highly expressed in many cancer cell lines and correlate positively with tumor growth. Nevertheless, the low radiosynthesis yield and demand of an on-site cyclotron limit the use of 18F-labeled tyrosine analogues. In this study, four Technetium-99m (99mTc) labeled tyrosine/ AMT (α-methyl tyrosine)-based radiotracers were successfully synthesized and evaluated for their potentials in breast cancer imaging. In order to radiolabel tyrosine and AMT, the chelators N,N’-ethylene-di-L-cysteine (EC) and 1,4,8,11-tetra-azacyclotetradecane (N4 cyclam) were selected to coordinate 99mTc. These chelators have been reported to provide stable chelation ability with 99mTc. By using the chelator technology, the same target ligand could be labeled with different radioisotopes for various imaging modalities for tumor diagnosis, or for internal radionuclide therapy in future. Based on the in vitro and in vivo evaluation using the rat mammary tumor models, 99mTc-EC-AMT is considered as the most suitable radiotracer for breast cancer imaging overall, however, 99mTc-EC-Tyrosine will be more preferred for differential diagnosis of tumor from inflammation.

APPLICATIONS OF EPHB4 RECEPTOR SPECIFIC PEPTIDES IN TARGETED CANCER IMAGING AND THERAPY

EphB4 receptors, a member of the largest family of receptor tyrosine kinases, are found over-expressed in a variety of tumors cells including glioma cells as well as angiogenic blood vessels. Noninvasive imaging of EphB4 could potentially increase early detection rates, monitor response to therapy directed against EphB4, and improve patient outcomes. Targeted delivery of EphB4 receptor specific peptide conjugated hollow gold nanoshells (HAuNS) into tumors has great potential in cancer imaging and photothermal therapy. In this study, we developed an EphB4 specific peptide named TNYL-RAW and labeled with radioisotope 64Cu and Cy5.5 dye. We also conjugate this specific peptide with hollow gold nanoshells (HAuNS) to evaluate targeted photothermal therapy of cancers. In vitro, 64Cu-DOTA-TNYL- RAW specifically bind to CT26 and PC-3M cells but not to A549 cells. In vivo, Small-animal PET/CT clearly showed the significant uptake of 64Cu-DOTA-TNYL-RAW in CT26 and PC-3M tumors but not in A549 tumors. Furthermore, µPET/CT and near-infrared optical imaging clearly showed the uptake of the dual labeled TNYL-RAW peptide in both U251 and U87 tumors in the brains of nude mice. In U251 tumors, Cy5.5-labeled peptide can bind to EphB4-expressing tumor blood vessels and tumors cells. But in U87 models, dual labeled peptide only could bind to tumor associated blood vessels. Also, Irradiation of PC-3M and CT-26 cell treated with TNYL-PEG-HAuNS nanopatilces with near-infrared (NIR) laser resulted in selective destruction of these cells in vitro. EphB4 targeted TNYL-PEG-HAuNS showed more photothermal killing effect on CT26 tumor model than PEG-HAuNS did. In summary, tumors with overexpression of EphB4 receptors can be noninvasively visualized by micro PET/CT with 64Cu labeled or dual labeled TNYL-RAW peptide. Targeted delivery of TNYL-RAW conjugated HAuNS into tumors can greatly improve the treatment effect of photothermal therapy. The information acquired with this study should be advantageous in improving diagnostics and future applications in photothermal ablation therapy in clinical.

Predictors of participation in genetic testing for hereditary breast and ovarian cancer

Up to 10% of all breast and ovarian cancers are attributable to mutations in cancer susceptibility genes. Clinical genetic testing for deleterious gene mutations that predispose to hereditary breast and ovarian cancer (HBOC) syndrome is available. Mutation carriers may benefit from following high-risk guidelines for cancer prevention and early detection; however, few studies have reported the uptake of clinical genetic testing for HBOC. This study identified predictors of HBOC genetic testing uptake among a case series of 268 women who underwent genetic counseling at The University of Texas M. D. Anderson Cancer Center from October, 1996, through July, 2000. Women completed a baseline questionnaire that measured psychosocial and demographic variables. Additional medical characteristics were obtained from the medical charts. Logistic regression modeling identified predictors of participation in HBOC genetic testing. Psychological variables were hypothesized to be the strongest predictors of testing uptake—in particular, one's readiness (intention) to have testing. Testing uptake among all women in this study was 37% (n = 99). Contrary to the hypotheses, one's actual risk of carrying a BRCA1 or BRCA2 gene mutation was the strongest predictor of testing participation (OR = 15.37, CI = 5.15, 45.86). Other predictors included religious background, greater readiness to have testing, knowledge about HBOC and genetic testing, not having female children, and adherence to breast self-exam. Among the subgroup of women who were at ≥10% risk of carrying a mutation, 51% (n = 90) had genetic testing. Consistent with the hypotheses, predictors of testing participation in the high-risk subgroup included greater readiness to have testing, knowledge, and greater self-efficacy regarding one's ability to cope with test results. Women with CES-D scores ≥16, indicating the presence of depressive symptoms, were less likely to have genetic testing. Results indicate that among women with a wide range of risk for HBOC, actual risk of carrying an HBOC-predisposing mutation may be the strongest predictor of their decision to have genetic testing. Psychological variables (e.g., distress and self-efficacy) may influence testing participation only among women at highest risk of carrying a mutation, for whom genetic testing is most likely to be informative. ^

The identification of child abuse in Harris County in 1998

Characteristics of child abuse cases are not well known. In this study I collected data on 70 child abuse cases that were reported to Children's Protective Services in Harris County in 1998. The purpose of this study was to determine the factors in Harris County that lead to the identification of physical and sexual abuse. In order to answer the questions of who, what, where and when relative to the discovery of abuse I applied the same questionnaire (see Appendix) to each of 35 Sexual Abuse case reports and to each of 35 Physical Abuse/Neglect case reports. Answers to the first four questions were arranged by frequency distribution to show the predominant reporter, the 10 most common indicators, the most common locale, and the most frequent timing. Tables of the age, sex, and ethnicity of the children indicate the identity of those whose victimization was most reported. In addition the relationship between the form questions and the characteristics of the children was explored. A comparison of Sexual Abuse cases with Physical Abuse/Neglect cases was conducted and the results were analyzed and recorded in the Tables. ^ Child maltreatment often has negative short and long term effects on children's mental health and development. Suicide, violence, delinquency, drug and alcohol abuse and other forms of criminality are frequently child abuse related. Early detection and treatment helps to alleviate the myriad mental and physical ailments that untreated victims present as adults. This translates into medical dollar savings. ^ The long term objectives of my research were to reduce the number of undetected and unreported child abuse cases in Harris County by formulating better educational programs and literature for medical professionals and other personnel who are in contact with children. ^

Impact of a modified dietary plan on the health related quality of life of minority participants in the Women's Healthy Eating and Living (WHEL) Study

Advances in medical technology, in genetics, and in clinical research have led to early detection of cancer, precise diagnosis, and effective treatment modalities. Decline in cancer incidence and mortality due to cancer has led to increased number of long-term survivors. However, the ethnic minority population has not experienced this decline and still continues to carry a disparate proportion of the cancer burden. Majority of the clinical research including survivorship studies have recruited and continue to recruit a convenient sample of middle- to upper-class Caucasian survivors. Thus, minorities are underrepresented in cancer research in terms of both clinical studies and in health related quality of life (HRQOL) studies. ^ Life style and diet have been associated with increased risk of breast cancer. High vegetable low fat diet has been shown to reduce recurrence of breast cancer and early death. The Women's Healthy Eating and Living Study is an ongoing multi-site randomized controlled trial that is evaluating the high-vegetable low fat diet in reducing the recurrence of breast cancer and early death. The purpose of this dissertation was to (1) compare the impact of the modified diet on the HRQOL during the first 12-month period on specific Minorities and matched Caucasians; (2) identify predictors that significantly impact the HRQOL of the study participants; and (3) using the structural equation modeling assess the impact of nutrition on the HRQOL of the intervention group participants. Findings suggest that there are no significant differences in change in HRQOL between Minorities and Caucasians; between Minorities in the intervention group and those in the comparison group; and between women in the intervention group and those in the comparison group. Minority indicator variable and Intervention/Comparison group indicator variable were not found to be good predictors of HRQOL. Although the structural equation models suggested viable representation of the relationship between the antecedent variables, the mediating variables and the two outcome variables, the impact of nutrition was not statistically significant to be included in the model. This dissertation, by analyzing the HRQOL of minorities in the WHEL Study, attempted to add to the knowledge base specific to minority cancer survivors. ^

DNA nucleotide excision repair gene single nucleotide polymorphisms and hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by germline mutations in DNA mismatch repair(MMR) genes. The nucleotide excision repair(NER) pathway plays a very important role in cancer development. We systematically studied interactions between NER and MMR genes to identify NER gene single nucleotide polymorphism (SNP) risk factors that modify the effect of MMR mutations on risk for cancer in HNPCC. We analyzed data from polymorphisms in 10 NER genes that had been genotyped in HNPCC patients that carry MSH2 and MLH1 gene mutations. The influence of the NER gene SNPs on time to onset of colorectal cancer (CRC) was assessed using survival analysis and a semiparametric proportional hazard model. We found the median age of onset for CRC among MMR mutation carriers with the ERCC1 mutation was 3.9 years earlier than patients with wildtype ERCC1(median 47.7 vs 51.6, log-rank test p=0.035). The influence of Rad23B A249V SNP on age of onset of HNPCC is age dependent (likelihood ratio test p=0.0056). Interestingly, using the likelihood ratio test, we also found evidence of genetic interactions between the MMR gene mutations and SNPs in ERCC1 gene(C8092A) and XPG/ERCC5 gene(D1104H) with p-values of 0.004 and 0.042, respectively. An assessment using tree structured survival analysis (TSSA) showed distinct gene interactions in MLH1 mutation carriers and MSH2 mutation carriers. ERCC1 SNP genotypes greatly modified the age onset of HNPCC in MSH2 mutation carriers, while no effect was detected in MLH1 mutation carriers. Given the NER genes in this study play different roles in NER pathway, they may have distinct influences on the development of HNPCC. The findings of this study are very important for elucidation of the molecular mechanism of colon cancer development and for understanding why some mutation carriers of the MSH2 and MLH1 gene develop CRC early and others never develop CRC. Overall, the findings also have important implications for the development of early detection strategies and prevention as well as understanding the mechanism of colorectal carcinogenesis in HNPCC. ^

A meta-analysis: Obesity and colorectal cancer screening

Of cancer death, colorectal cancer death ranks second in the United States. Obesity is an important risk factor for colorectal cancer (1). Early detection of colorectal cancer when it is localized can effectively reduce mortality of colorectal cancer and increase survival time of patients if they are treated. Also, previous studies showed that obese women were more likely to delay breast cancer screening and cervical cancer screening than normal weight women (2-5). However, results from prior studies demonstrating the relationship between obesity and colorectal cancer screening are not consistent. This research was done to conduct a meta-analysis of previous cross-sectional studies selected from the Medline database and to evaluate the association between obesity and colorectal cancer screening. While the odds ratio was not statistically different from one, the results from this meta-analysis under the random effects model showed that obese people are slightly less likely to have colorectal cancer screening compared to normal weight individuals (OR,0.93;95% CI 0.75-1.15). This meta-analysis was particularly sensitive to one individual study (6) and the effect of obesity on colorectal cancer screening was statistically significant (OR, 0.87; 95% CI, 0.81-0.92) after removing Heo's study. Further systematic studies focused on whether the effect of obesity on colorectal cancer screening is limited to women only are suggested. ^

Modeling survival and the development of second primary tumors among Hodgkin's disease patients

Hodgkin's disease (HD) is a cancer of the lymphatic system. Survivors of HD face varieties of consequent adverse effects, in which secondary primary tumors (SPT) is one of the most serious consequences. This dissertation is aimed to model time-to-SPT in the presence of death and HD relapses during follow-up.^ The model is designed to handle a mixture phenomenon of SPT and the influence of death. Relapses of HD are adjusted as a covariate. Proportional hazards framework is used to define SPT intensity function, which includes an exponential term to estimate explanatory variables. Death as a competing risk is considered according to different scenarios, depending on which terminal event comes first. Newton-Raphson method is used to estimate the parameter estimates in the end.^ The proposed method is applied to a real data set containing a group of HD patients. Several risk factors for the development of SPT are identified and the findings are noteworthy in the development of healthcare guidelines that may lead to the early detection or prevention of SPT.^

A review of the published literature on interventions to increase compliance with follow-up outpatient medical appointments in primary care practice

Effective strategies for patient follow-up compliance in family practice are essential for the prevention and early detection of disease with the consequences of decreasing morbidity and mortality. With effective appointment reminder systems in place, physicians can better manage the overall health of their patients by providing preventive care as well. This literature review examines intervention strategies used by the authors, the compliance rate of appointment adherence using these techniques, as well as theories relating to study outcomes. The findings of this study may be used as an educational tool by practices to suggest which intervention strategies might be the most effective for their clinic.^

The effect of obesity on mammography utilization in African American women

Breast cancer continues to reign as a common cause of death for women in the United States, claiming the lives of more than an estimated 40,000 women in 2009 alone (Ries et al., 2009). A mammogram, an x-ray of the breast, can aid in early detection of breast cancer and thus more successful treatment. Screening patterns indicate African American women are less likely to utilize mammography technology when compared to their Caucasian counterparts. Additionally, the obesity epidemic in the United States remains a major public health problem. Obesity trends indicate that African American women are likely to be more obese when compared to Caucasian women. Pischon, Nöthlings, & Boeing (2008) concluded there was sufficient evidence linking breast cancer and obesity. Many researchers have identified obesity as a risk factor for breast cancer. As African American women are disproportionately burdened by both breast cancer mortality and obesity, more extensive research is needed to gain more knowledge about their association. The purpose of this study was to identify the role obesity plays in lessening an African American woman’s usage of mammography technology. Data from the 2005 National Health Interview Study were analyzed using SPSS to evaluate the relationship between body mass index (BMI) and mammography utilization in the two aforementioned populations.^ After excluding respondents from the sample who did not meet the set criteria, there were 17,666 women remaining. Of the 17,666 women, 6,156 (34.8%) had a healthy weight, 6,024 (34.1%) were overweight, and 4,285 (24.3%) were obese. About 70% of the sample population reported having had a mammogram in the last two years. Another 27.6% of women reported not receiving a mammogram within this same two year time frame. Within ethnic categories, the majority of the sample was Caucasian (64.2%) while only 15.1% of the sample was African American. The relationship between mammography usage and body mass index was not statistically significant within any body mass index categories. When analyzing the relationship between mammography usage and BMI, adjusting for ethnicity, there was also no significant difference between obese African American and obese Caucasian women. The study did find significant relationships between mammography usage and body mass index when adjusting for cancer risk OR = .79 (95% CI .72 - .85), and marital status OR = 1.18 (95% CI 1.05 - 1.34). Due to insignificant findings, there was no evidence to support the hypothesis regarding differences in mammography usage based on weight or ethnicity. Mammography screening differences based on ethnicity are widely cited. Unfortunately it is still unclear exactly where these differences lie. Obesity has been widely documented in the literature as a risk factor for many chronic diseases, including certain forms of cancer. Understanding the relationship between screening behaviors and weight can assist in the development of health promotion programs aimed at high risk groups. In order to change screening behavior and reduce mortality from breast cancer, more research is needed to identify similarities within low screening populations.^

Workers and respirators: What factors influence medical clearance? Experience in the petrochemical industry 2004--2008

This retrospective cohort study analyzed data from more than 2200 OSHA-mandated respirator medical evaluations performed between 2004 and 2008, with information initially obtained using an online questionnaire, to determine what factors influence medical clearance and the ability to safely wear respiratory protection in a large petrochemical company.^ The employees were mostly white males with a high school education, ranging in age from 25 to 60 years of age, who had been employed with the company an average of eight years. Their work was typically performed outdoors in a rural or offshore setting. Respirators were typically required for emergency response – escape or rescue only – and/or limited to less than four hours per month.^ Approximately 90% of the population achieved medical clearance by utilizing the online questionnaire. Of the remaining 10%, 66% were cleared after additional "hands-on" medical examination exam; 28% of the individuals' jobs were modified by their supervisor in order to not use a respirator, and 6% of the individuals (n=13) were excluded from wearing a respirator on the basis of the medical examination. The primary causes for exclusion from respirator use were cardiovascular (37.5%) and respiratory (31.3%) issues, followed by psychological (18.8%) and musculoskeletal (12.5%) concerns. Ultimately, over 99% of workers evaluated under this system were found capable of using respiratory protection safely. This questionnaire has proven to be an excellent health screening tool capable of initiating early detection and further investigation of potentially serious medical conditions within a large and diverse population in multiple locations. ^

Secondary data analysis of lead screening compliance in high-risk children

Introduction. Despite the ban of lead-containing gasoline and paint, childhood lead poisoning remains a public health issue. Furthermore, a Medicaid-eligible child is 8 times more likely to have an elevated blood lead level (EBLL) than a non-Medicaid child, which is the primary reason for the early detection lead screening mandate for ages 12 and 24 months among the Medicaid population. Based on field observations, there was evidence that suggested a screening compliance issue. Objective. The purpose of this study was to analyze blood lead screening compliance in previously lead poisoned Medicaid children and test for an association between timely lead screening and timely childhood immunizations. The mean months between follow-up tests were also examined for a significant difference between the non-compliant and compliant lead screened children. Methods. Access to the surveillance data of all childhood lead poisoned cases in Bexar County was granted by the San Antonio Metropolitan Health District. A database was constructed and analyzed using descriptive statistics, logistic regression methods and non-parametric tests. Lead screening at 12 months of age was analyzed separately from lead screening at 24 months. The small portion of the population who were also related were included in one analysis and removed from a second analysis to check for significance. Gender, ethnicity, age of home, and having a sibling with an EBLL were ruled out as confounders for the association tests but ethnicity and age of home were adjusted in the nonparametric tests. Results. There was a strong significant association between lead screening compliance at 12 months and childhood immunization compliance, with or without including related children (p<0.00). However, there was no significant association between the two variables at the age of 24 months. Furthermore, there was no significant difference between the median of the mean months of follow-up blood tests among the non-compliant and compliant lead screened population for at the 12 month screening group but there was a significant difference at the 24 month screening group (p<0.01). Discussion. Descriptive statistics showed that 61% and 56% of the previously lead poisoned Medicaid population did not receive their 12 and 24 month mandated lead screening on time, respectively. This suggests that their elevated blood lead level may have been diagnosed earlier in their childhood. Furthermore, a child who is compliant with their lead screening at 12 months of age is 2.36 times more likely to also receive their childhood immunizations on time compared to a child who was not compliant with their 12 month screening. Even though there was no statistical significant association found for the 24 month group, the public health significance of a screening compliance issue is no less important. The Texas Medicaid program needs to enforce lead screening compliance because it is evident that there has been no monitoring system in place. Further recommendations include a need for an increased focus on parental education and the importance of taking their children for wellness exams on time.^

Quality of life, symptom experience, and use of complementary and alternative medicine among women with ovarian cancer

The objectives of this dissertation were to determine the quality of life in women with ovarian cancer and the association of their physical and emotional well-being with the number of symptoms, duration of symptoms, and the scores of common symptoms of ovarian cancer; to study the prevalence of complementary and alternative medicine techniques for symptom relief and its association with the number of symptoms, age, education, insurance, comorbidity, and satisfaction with medical care they received, and their pre-diagnostic experience of symptoms.^ This study was based on a secondary data analysis of a study of early detection of ovarian cancer. A sample of 139 women with ovarian cancer was recruited and was administered a questionnaire comprised of questions on their quality of life, their symptoms and what they did about the symptoms, whether they used any complementary and alternative medicine techniques, and other medical conditions they had. Out of this sample, 53 patients underwent in-depth interviews relating to their symptoms before the diagnosis and their experiences with the health care system leading to the ovarian cancer diagnosis. ^ In article #1, ovarian cancer patients were observed to have significantly poorer quality of life on all subscales and summary scores except pain, compared to that of the general population of US women. Physical well-being scores were negatively associated with the number of symptoms before diagnosis and a significant negative association of comorbidity index was observed with physical well-being. Higher education and increase in time since diagnosis was found to have better physical scores. Emotional well-being scores showed marginally significant associations with number of symptoms and bloating. ^ In article #2, a thematic content analysis of the ovarian cancer patients’ interviews revealed that on recognition of their symptoms women first assumed their symptoms to be a normal transient occurrence due to a pre-existing disease condition, or due to some other disease. A series of misattributions of their symptoms on their and their doctors’ part impacted their health care seeking.In article #3, a significantly greater likelihood of CAM use with an increase in the number of symptoms was observed.^ Based on the foregoing results, it is important to educate women on possible signs of ovarian cancer and also to educate doctors about the results of current research regarding ovarian cancer diagnosis. This will help to avoid a delay in getting a diagnosis and improve women’s quality of life. It emphasizes the diagnosis of ovarian cancer in earlier stages by more sensitive screening techniques. This study emphasizes the importance of consideration of comorbidity in any quality of life research. Additionally, educating women in the safe use of CAM techniques carries immense significance because the efficacy and safety of many of the currently advertized CAM products has not been scientifically validated. Further research is needed to confirm the findings of this study. ^

BRONCHOALVEOLAR LAVAGE AND GALLIUM-67 LUNG SCANNING IN THE EVALUATION OF ASBESTOS-EXPOSED INDIVIDUALS

In this study, an attempt is made to evaluate certain parameters that might indicate the beginning of a certain fibrogenic activity in the lung parenchyma, even before such changes become visible on the chest x-ray. The hypothesis is that studies such as certain bronchoalveolar immunological characteristics and Gallium-67 lung scans may be more sensitive indicators of parenchymal lung damage in response to asbestos inhalation than conventional radiographic criteria. If so, then in those cases where the criteria for the diagnosis of asbestosis lack the presence of parenchymal changes, it would be unwise to deny the diagnosis unless further investigations, such as the bronchoalveolar lavage fluid analysis and the Gallium-67 lung scan techniques, are made available.^ Four groups of individuals have been included in this study. The volunteer group showing no history of asbestos exposure with normal chest x-rays has been used as a normal healthy comparison group. The other three groups are all asbestos-exposed but differ as to their findings in the chest radiographs. One has parenchymal changes (0/1 or more, ILO Classification), the second has no parenchymal but pleural changes, and the third has neither.^ The most significant laboratory parameter for bronchoalveolar lavage, in this study, is that of Neutrophils (PMNs). All three asbestos-exposed groups showed no differences when compared with each other, while such differences were statistically significant when such groups were separately compared with the normal comparison group. A similar finding existed also when the Helper: Suppressor T-Cell ratios were compared, and found to be higher in all the asbestos-exposed groups.^ Another sensitive test is that of Gallium-67 lung scan. This was found to be positive in some patients where parenchymal changes were absent. Even in some of those who showed neither parenchymal nor pleural changes in their chest x-ray showed positive test results. Such changes indicate a state of an underlying pathogenic process that is still undetectable by conventional radiography. This highly recommends the future application of such tests for the early detection of active pulmonary disease, especially in those who show no parenchymal changes in their chest x-rays. (Abstract shortened with permission of author.) ^