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Abstract Background Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Methods Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Results Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Conclusions Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.

Examining case studies from patients with interstitial lung diseases (ILDs) is important in order to evaluate current diagnosis and treatment options. Two cases will be discussed; the first case examines a patient with usual interstitial pneumonia, and the second case examines a patient with subacute ILD and elements to suggest a forme fruste presentation of an unclassifiable connective tissue disease. Each case highlights components of the differential diagnosis, as well as reviews the treatments and prognoses of these patients. The cases provide clinical pearls that are designed to enhance the reader's understanding of ILDs. [ABSTRACT FROM AUTHOR]

Introduction: Health-related quality of life (HR-QoL) is often impaired in lung cancer survivors. To inform personalized survivorship care, we identified associations between HR-QoL scores and patient-, tumor-, and treatment-factors over time., Materials and Methods: We evaluated HR-QoL scores provided at diagnosis, 6 months, 1 year, and 2 years from the Yale Lung Cancer Biorepository. HR-QoL was measured via the Functional Assessment of Cancer Therapy - Lung (FACT-L) instrument and available for a subset of patients (n = 513). Analyses were stratified by early-stage (I-II; n = 355) non-small cell lung cancer (NSCLC), advanced stage NSCLC (III-IV; n = 158), and small cell lung cancer (SCLC, n = 21). We used mixed effects modeling and multivariable analysis with covariate adjustment to examine changes in FACT-L from diagnosis to follow-up. Sensitivity analysis was performed including patients with early-stage disease and complete FACT-L scores at both baseline and year 2 (n = 91)., Results: The average FACT-L scores at diagnosis in early-stage NSCLC, advanced stage NSCLC, and SCLC were 121.0 (standard deviation (SD) 11.4), 109.2 (18.7), and 98.7 (20.2) respectively. At all timepoints, HR-QoL was higher in patients with early-stage NSCLC (vs advanced-stage disease). In patients with early- and advanced-stage NSCLC, HR-QoL was higher at years 1 and 2 than at diagnosis, though the changes did not meet clinical significance. At NSCLC diagnosis, higher HR-QoL was associated with older age, better performance status, participating in physical activity, adenocarcinoma histology, and (in advanced stage NSCLC) anticipated treatment with chemotherapy. At NSCLC follow-up, HR-QoL was higher in patients with higher BMI and better performance status., Discussion: In patients with newly diagnosed NSCLC, HR-QoL scores are impacted by patient factors, tumor factors, and treatment factors. HR-QoL is higher in patients with early-stage disease. In patients surviving 2 years, HR-QoL was higher at follow-up, though the change did not meet clinical significance. To optimize HR-QoL, lung cancer survivorship teams should prioritize comorbidity management, physical activity, healthy weight maintenance, and treatment-related side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: The coronavirus disease 2019 (COVID-19) pandemic disrupted health care systems, including implementation of lung cancer screening programs. The impact and recovery from this disruption on screening processes is not well appreciated. Herein, the radiology database of a Northeast tertiary health care network was reviewed before and during the pandemic (2013-2022). In the 3 months before the pandemic, an average of 77.3 lung cancer screening with computed tomography scans (LCS-CT) were performed per month. The average dropped to 23.3 between April and June of 2020, whereas COVID-19 hospitalizations peaked at 1604. By July, average hospitalizations dropped to 50, and LCS-CTs rose to >110 per month for the remaining year. LCS-CTs did not decline during COVID-19 surges in December of 2021 and 2022. The LCS-CT performance grew by 4.5% in 2020, 69.6% in 2021, and 27.0% in 2022, exceeding projected growth by 722 examinations. This resiliency indicates a potentially smaller impact of COVID-19 on lung cancer diagnoses than initially feared., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Native Hawaiians are proud and resilient people who have endured significant impacts from colonization. Despite being in a time of vibrant cultural revitalization, Native Hawaiians have a shorter life expectancy than other racial and ethnic groups in Hawai'i. The primary aim of this paper was to share data from the first year of a 5-year study with Native Hawaiian kūpuna (elders) on their experiences with healthcare, along with barriers to accessing healthcare. Ten kūpuna living in rural areas of Hawai'i participated in three interviews each, which were held in an informal, talk-story style. The first interview focused on establishing rapport. The second interview focused on the kūpuna's strengths, resiliencies, and what they would like to pass to the next generation. The third interview focused on the elders' experiences with healthcare, which is the focus of this paper. All ten kūpuna reported growing up with limited access to Western healthcare; rather, their families successfully treated many illnesses and injuries with lā'au lapa'au (Hawaiian herbal medicine) and other traditional healing practices, as they had done for generations. As Western medicine became more prevalent and accessible, they used both, but many preferred holistic treatments such as prayer, a return to the traditional diet, and lā'au lapa'au. As a group, the kūpuna rated their health as fair to good; two had diabetes, two had cardiovascular disease, four had neuropathies, and five were cancer survivors. The kūpuna reported high turnover among providers in rural communities. Limited access to specialists often required them to travel to Honolulu for care, which was costly and especially difficult during coronavirus disease 2019 (COVID-19). Regardless of provider ethnicity, the kūpuna appreciated those who took the time to get to know them as people and respected Hawaiian cultural practices. They advised that Western providers speak honestly and directly, have compassion, and build connections to patients and their communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kawakami, Muneoka, Burrage, Tanoue, Haitsuka and Braun.)

Background: In 2013, the United States Preventive Services Taskforce instituted recommendations for annual lung cancer screening (LCS) with low-dose chest CT imaging for high-risk individuals. LCS reduces lung cancer mortality, with greater reduction observed in Black participants in clinical trials. Although racial disparities in lung cancer mortality have been well documented, less is known about disparities in LCS participation and adherence to follow-up in clinical practice., Research Question: What is the association between race and adherence to LCS follow-up?, Study Design and Methods: A systematic review was conducted through a search of published studies in MEDLINE, PubMed, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health Literature Database from database inception through October 2020. We included studies that examined rates of adherence to LCS follow-up and compared rates by race. Studies were pooled using random-effects meta-analysis., Results: We screened 18,300 titles and abstracts, and 229 studies were selected for full-text review. Nine studies met inclusion criteria; seven were included in the meta-analysis. Median adherent follow-up rate was 37% (range, 16%-82%). Notable differences among the studies included the proportion of the Black population (range, 4%-47%) and the structure of the LCS programs. The meta-analyses showed lower adherence to LCS follow-up in the Black population (OR, 0.67; 95% CI, 0.55-0.80). This disparity persisted across all malignancy risk levels determined by initial screening results., Interpretation: Lower adherence to LCS follow-up in Black compared with White patients occurs despite the higher potential lung cancer mortality benefit. Literature specifically addressing race-related barriers to LCS adherence remains limited. To ensure equity in LCS benefits, greater outreach to eligible Black patients should be implemented through increased physician education and use of screening program coordinators to focus on this patient population., Trial Registry: PROSPERO; No.: CRD42020214213; URL: http://www.crd.york.ac.uk/PROSPERO., (Published by Elsevier Inc.)

Background: Lung cancer survivors need more options to improve quality of life (QoL). It is unclear to what extent patients with advanced stage disease are willing to participate in home-based physical activity (PA) and if these interventions improve QoL. The goal of our study was to determine interest in participating in our 3-month home-based walking regimen in patients with advanced stage lung cancer. We used a randomized design to evaluate for potential benefit in PA and patient-reported outcomes., Methods: We performed an open-label, 1:1 randomized trial in 40 patients with stage III/IV non-small cell lung cancer (NSCLC) evaluating enrollment rate, PA, QoL, dyspnea, depression, and biomarkers. Compared to usual care (UC), the intervention group (IG) received an accelerometer, in-person teaching session, and gain-framed text messages for 12 weeks., Results: We enrolled 56% (40/71) of eligible patients. Participants were on average 65 years and enrolled 1.9 years from diagnosis. Most patients were women (75%), and receiving treatment (85%) for stage IV (73%) adenocarcinoma (83%). A minority of patients were employed part-time or full time (38%). Both groups reported low baseline PA (IG mean 37 (Standard deviation (SD) 46) vs UC 59 (SD 56) minutes/week; p = 0.25). The IG increased PA more than UC (mean change IG + 123 (SD 212) vs UC + 35 (SD 103) minutes/week; p = 0.051)). Step count in the IG was not statistically different between baseline (4707 step/day), week 6 (5605; p = 0.16), and week 12 (4606 steps/day; p = 0.87). The intervention improved EORTC role functioning domain (17 points; p = 0.022) with borderline improvement in dyspnea (- 13 points; p = 0.051) compared to UC. In patients with two blood samples (25%), we observed a significant increase in soluble PD-1 (219.8 (SD 54.5) pg/mL; p < 0.001)., Conclusions: Our pilot trial using a 3-month, home-based, mobile health intervention enrolled over half of eligible patients with stage III and IV NSCLC. The intervention increased PA, and may improve several aspects of QoL. We also identified potential biomarker changes relevant to lung cancer biology. Future research should use a larger sample to examine the effect of exercise on cancer biomarkers, which may mediate the association between PA and QoL., Clinical Trial Registration: Clinicaltrials.gov ( NCT03352245 ).

Case Presentation: A 62-year-old nonsmoking woman with no medical history initially presented with a 3-month history of rash. A painful, erythematous exanthem had progressed from her forehead, cheeks, and upper chest to her eyes (heliotrope rash) and hands, primarily involving the extensor surface finger joints with prominent digital ulceration., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lung cancer mortality rate can be significantly reduced by up to 20% through routine low-dose computed tomography (LDCT) screening, which, however, has high sensitivity but low specificity, resulting in a high rate of false-positive nodules. Combining PET with CT may provide more accurate diagnosis for indeterminate screening-detected nodules. In this work, we investigated low-dose dynamic 18 F-FDG PET in discrimination between benign and malignant nodules using a virtual clinical trial based on patient study with ground truth. Six patients with initial LDCT screening-detected lung nodules received 90 min single-bed PET scans following a 10 mCi FDG injection. Low-dose static and dynamic images were generated from under-sampled list-mode data at various count levels (100%, 50%, 10%, 5%, and 1%). A virtual clinical trial was performed by adding nodule population variability, measurement noise, and static PET acquisition start time variability to the time activity curves (TACs) of the patient data. We used receiver operating characteristic (ROC) analysis to estimate the classification capability of standardized uptake value (SUV) and net uptake constant K i from their simulated benign and malignant distributions. Various scan durations and start times (t * ) were investigated in dynamic Patlak analysis to optimize simplified acquisition protocols with a population-based input function (PBIF). The area under curve (AUC) of ROC analysis was higher with increased scan duration and earlier t * . Highly similar results were obtained using PBIF to those using image-derived input function (IDIF). The AUC value for K i using optimized t * and scan duration with 10% dose was higher than that for SUV with 100% dose. Our results suggest that dynamic PET with as little as 1 mCi FDG could provide discrimination between benign and malignant lung nodules with higher than 90% sensitivity and specificity for patients similar to the pilot and simulated population in this study, with LDCT screening-detected indeterminate lung nodules.

Backgrounds: In China, the prevalence of chronic obstructive pulmonary disease (COPD) in persons 40 years of age or older is estimated at 8.2%, but this is likely a substantial underestimate., Methods: Eight secondary hospitals which didn't have spirometries were chosen randomly in Hunan province of central south China. Physician subjects at these hospitals underwent a one-hour training course on the Chinese COPD guidelines. Physicians answered questionnaires assessing their knowledge of the guidelines before and after the training session. The mean correct scores of questionnaires were compared before and after training. Four out of the eight hospitals were given access to spirometry. Eligible patient subjects underwent spirometry testing prior to the physician visit. After seeing the patient, physicians were asked to answer a questionnaire relating to the diagnosis and severity of COPD. Physicians were then given the results of the spirometry, and asked to answer the same questionnaire. Physicians' responses before and after receiving the spirometry results were compared., Results: 225 physicians participated in the training session. 207 questionnaires were completed. Mean scores (out of 100) before and after the training were 53.1 ± 21.7 and 93.3 ± 9.8, respectively. 18 physicians and 307 patient subjects participated in the spirometry intervention. Based on spirometric results, the prevalence of COPD was 38.8%. Physicians correctly identified the presence of COPD without spirometric data in 85 cases (76.6%); this increased to 117 cases (97.4%) once spirometric data were available. Without spirometric data, physicians incorrectly diagnosed COPD in 38 patients; this decreased to 6 patients once spirometric data were available. Spirometric data also improved the ability of physicians to correctly grade COPD severity., Conclusions: Simple educational training can substantially improve physicians' knowledge relating to COPD. Spirometry combined with education improves the ability of physicians to diagnose COPD and to assess its severity.

Background: Many older patients with early stage non-small cell lung cancer (NSCLC) do not receive curative therapy. New surgical techniques and radiation therapy modalities, such as video-assisted thoracoscopic surgery (VATS), potentially allow more patients to receive treatment. The adoption of these techniques and their impact on access to cancer care among Medicare beneficiaries with stage I NSCLC are unknown., Methods: We used the Surveillance, Epidemiology and End Results-Medicare database to identify patients with stage I NSCLC diagnosed between 1998 and 2007. We assessed temporal trends and created hierarchical generalized linear models of the relationship between patient, clinical, and regional factors and type of treatment., Results: The sample comprised 13,458 patients with a mean age of 75.7 years. The proportion of patients not receiving any local treatment increased from 14.6% in 1998 to 18.3% in 2007. The overall use of surgical resection declined from 75.2% to 67.3% ( P , .001), although the proportion of patients undergoing VATS increased from 11.3% to 32.0%. Similarly, although the use of new radiation modalities increased from 0% to 5.2%, the overall use of radiation remained stable. The oldest patients were less likely to receive surgical vs no treatment (OR, 0.12; 95% CI, 0.09-0.16) and more likely to receive radiation vs surgery (OR, 13.61; 95% CI, 9.75-19.0)., Conclusion: From 1998 to 2007, the overall proportion of older patients with stage I NSCLC receiving curative local therapy decreased, despite the dissemination of newer, less-invasive forms of surgery and radiation.

Background: The importance of definitive histological subclassification has increased as drug trials have shown benefit associated with histology in nonsmall-cell lung cancer (NSCLC). The acuity of this problem is further exacerbated by the use of minimally invasive cytology samples. Here we describe the development and validation of a 4-protein classifier that differentiates primary lung adenocarcinomas (AC) from squamous cell carcinomas (SCC)., Methods: Quantitative immunofluorescence (AQUA) was employed to measure proteins differentially expressed between AC and SCC followed by logistic regression analysis. An objective 4-protein classifier was generated to define likelihood of AC in a training set of 343 patients followed by validation in 2 independent cohorts (n = 197 and n = 235). The assay was then tested on 11 cytology specimens., Results: Statistical modeling selected thyroid transcription factor 1 (TTF1), CK5, CK13, and epidermal growth factor receptor (EGFR) to generate a weighted classifier and to identify the optimal cutpoint for differentiating AC from SCC. Using the pathologist's final diagnosis as the criterion standard, the molecular test showed a sensitivity of 96% and specificity of 93%. Blinded analysis of the validation sets yielded sensitivity and specificity of 96% and 97%, respectively. Our assay classified the cytology specimens with a specificity of 100% and sensitivity of 87.5%., Conclusions: Molecular classification of NSCLC using an objective quantitative test can be highly accurate and could be translated into a diagnostic platform for broad clinical application., (Copyright © 2011 American Cancer Society.)

Purpose of the Study: Stanford's Chronic Disease Self-Management Program (CDSMP) has been proven to increase patients' ability to manage distress. We describe how we replicated CDSMP in Asian and Pacific Islander (API) communities., Design and Methods: We used the "track changes" tool to deconstruct CDSMP into its various components (e.g., recruitment and staffing) and the "adaptation traffic light" to identify allowable modifications to the original program. We monitored local leaders' fidelity of delivery of CDSMP and tracked participants' attendance, satisfaction, and 6-month outcomes., Results: Between July 2007 and February 2010, 584 completed a CDSMP workshop. Baseline and 6-month data were available for 422 (72%), including 53 Caucasians, 177 Asians, and 194 Pacific Islanders. All 3 groups realized significant decreases in social and role activity limitations and significant increases in communication with physicians. Asians and Pacific Islanders also realized significant increases in self-rated health and time spent engaging in stretching/strengthening exercise. Asians also reported significant reductions in health distress and self-reported physician visits and increases in time spent in aerobic exercise, ability to cope with symptoms, and self-efficacy., Implications: Our experience suggests that CDSMP can be modified for increased cultural appropriateness for API communities while maintaining the key components responsible for behavior change.

Introduction: Approximately 10 to 15% of non-small cell lung cancer patients will be assigned a stage classification according to the 7th edition of TNM that differs from that assigned by the 6th edition (the "stage shifters"). This apparent upstaging or downstaging of tumors may affect patient management, as many clinicians formulate stage-based management strategies. However, the staging system revision was not designed to evaluate treatment, and attempts to make parallel adjustments in treatment plans may not be justified., Methods: Lung cancer clinicians were surveyed at four lung cancer symposia. Treatment of the "stage shift" patients was evaluated in the International Association for the Study of Lung Cancer database and National Cancer Database., Results: Overall, 77% of surveyed clinicians indicated they would alter patient management in response to a change in stage designation.The analysis of the data in the International Association for the Study of Lung Cancer database was not directed at supporting treatment changes. Despite the similar overall prognosis within each of the "stage shift" subgroups in the National Cancer Database, the treatment was decidedly heterogeneous., Conclusions: The perception that a stage change should lead to a change in management exists. The revision of the lung cancer staging system does not provide any direct information to indicate the superiority of one treatment approach over another. Assuming that overall prognosis of a subgroup is strongly linked to a specific treatment and that a particular outcome, therefore, warrants a change in treatment is not justified. Thus, making changes in management solely in response to upstaging or downstaging in the new stage classification system is not justified.

Background: Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results., Methods: Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA(R), a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome., Results: Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005)., Conclusions: Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.

Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTOR in carcinogenesis, its prognostic potential in lung cancer has not been investigated. Here, we quantitatively assessed mTOR protein expression in two large data sets to investigate the impact of mTOR expression on patient survival., Experimental Design: Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess mTOR expression in a training cohort of 167 lung cancer patients. An independent cohort of 235 lung cancer patients (from a second institution) was used for validation., Results: Tumors expressed mTOR in the cytoplasm in 56% and 50% of the cases in training and validation cohorts, respectively; mTOR expression was not associated with standard clinical or pathologic characteristics. Patients with high mTOR expression had a longer median overall survival compared with the low expressers (52.7 versus 38.5 months; log rank P = 0.06), which was more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively)., Conclusions: mTOR expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTOR into clinical decisions.

Objectives: To evaluate individuals at high risk for tuberculosis exposure who had a history of a positive tuberculin skin test (TST) result in order to determine the prevalence of unsuspected negative TST results. To confirm these findings with the QuantiFERON-TB test (QFT), an in vitro whole-blood assay that measures tuberculin-induced secretion of interferon-gamma., Methods: This survey was conducted from November 2001 through December 2003 at 3 sites where TST screening is regularly done. Detailed histories and reviews of medical records were performed. TSTs were placed and read by 2 experienced healthcare workers, and blood was drawn for QFT. Any subject with a negative result of an initial TST during the study (induration diameter, <10 mm) underwent a second TST and a second QFT. The TST-negative group comprised individuals for whom both TSTs had an induration diameter of <10 mm. The confirmed-negative group comprised individuals for whom both TSTs yielded no detectable induration and results of both QFTs were negative., Results: A total of 67 immunocompetent subjects with positive results of a previous TST were enrolled in the study. Of 56 subjects who completed the TST protocol, 25 (44.6%; 95% confidence interval [CI], 31.6%-57.6%) were TST negative (P<.001). Of 31 subjects who completed the TST protocol and the QFT protocol, 8 (25.8%; 95% CI, 10.4%-41.2%) were confirmed negative (P<.005)., Conclusions: A significant proportion of subjects with positive results of a previous TST were TST negative in this study, and a subset of these were confirmed negative. These individuals' TST status may have reverted or may never have been positive. It will be important in future studies to determine whether such individuals lack immunity to tuberculosis and whether they should be considered for reentry into tuberculosis screening programs.

Cigarette smoking is claiming an increasing health toll among women, with rising morbidity and mortality related to lung cancer and COPD. Whether women are more susceptible to the effects of cigarettes with regard to carcinogenesis and development of COPD remains controversial. Gender differences clearly exist in certain aspects of cigarette-related disease, including histologic distribution of lung cancer and the ability of smokers to quit. It is likely that gender differences also exist in the reasons that individuals choose to smoke. Understanding those reasons will be important in developing targeted programs for smoking cessation and in addressing the challenge of the prevention of smoking initiation in women.

Surgery is the treatment of choice for patients with stage I or II non-small cell carcinoma of the lung. Many such patients will have concurrent chronic obstructive pulmonary disease, the presence of which may increase the risk of lung resection. Prediction of surgical morbidity and mortality related to impaired pulmonary physiology should be based on evaluation of physiological parameters. Such measurements can be derived from a variety of studies including pulmonary function testing, assessment of split lung function, and measurements of exercise capacity. While there does not exist uniform agreement about threshold levels of risk related to individual tests, judicious use of widely available physiological measurements including FEV1, DL (CO), and V (O2)max should enable clinicians to make reasonable assessments of operative risk. Because surgery is clearly optimal treatment for stages I and II non-small cell lung cancer, thoughtful consideration should be given to the decision of operability in each individual case.

We evaluated the long-term effects of combined modality therapy (CMT) with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) or mechlorethamine, vincristine, prednisone, procarbazine (MOPP)/ABVD plus adjuvant low-dose (< 30 Gy) involved-field radiation therapy (LDRT) on cardiac and pulmonary functions in adult patients with Hodgkin's disease (HD). Adjuvant LDRT (mean dose, 2340 cGy) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD (n = 10) and ABVD (n = 14). The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2, respectively. Cardiac and pulmonary function tests were performed in all patients and, when available, were compared with pretreatment studies. After a median follow-up of 6.3 years, none of the patients had cardiac or pulmonary symptoms. A 4.7% overall decrease in left ventricular ejection fraction (LVEF) was observed (p = 0.03), but only one patient had a mildly decreased LVEF (47%). Diastolic function, LVEF, and left ventricular volume remained within the normal range in the other 23 patients. Mild pulmonary function study abnormalities occurred in 8 of 24 patients, 6 of whom were cigarette smokers. There were no significant changes in total lung capacity and forced vital capacity (FVC) values, but there was a 3% overall decrease in FEV1/FVC ratio (p = 0.05). In adult patients with HD, adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up. Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function.

Rheumatoid arthritis (RA) is the most common of the classic connective tissue diseases. Its manifestations in the chest are varied as the pleura, lung parenchyma, airways, and pulmonary vasculature can all be involved. The approach to a patient with RA and respiratory complaints, radiographic findings, or physiologic abnormalities requires a broad understanding of these manifestations. Moreover, the potential for therapy-related toxicity adds further complexity to the pulmonary evaluation of these patients.

Palliation of acute airway obstruction using the neodymium yttrium aluminum garnet (Nd-YAG) laser was studied in 54 patients who presented over a 42-month period to the Yale cardiothoracic surgery service. Thirty-seven patients had bronchogenic carcinoma; 27 had stage IIIB or IV disease. Nine patients had endobronchial metastases from a primary nonbronchogenic carcinoma. Eight patients had benign disease. A total of 109 Nd-YAG laser tumor ablations were performed. In addition, 32 patients underwent postoperative brachytherapy. Median survival for all patients was 12 months. Patients with bronchogenic carcinoma had a median survival of five months. Fifteen of 20 patients (75%) alive at the time of follow-up reported continued palliation as shown by an improved postoperative Karnofsky score. There was no survival benefit from Nd-YAG laser ablation of endobronchial bronchogenic carcinoma; however, the Nd-YAG laser provided good to excellent palliation in the majority of patients on long-term follow-up.

The pulmonary manifestations of collagen vascular diseases span an enormous range of clinical and radiographic findings. The breadth of these abnormalities is as diverse as the underlying diseases themselves. A comprehensive discussion of pulmonary involvement in four of these diseases, the Marfan syndrome, ankylosing spondylitis, Sjögren's syndrome, and relapsing polychondritis, is presented.

Advances in solid organ transplantation over the last several decades have made human lung transplantation a realistic possibility for selected patients with end-stage lung disease. A review of clinical indications, proper patient selection, and long-term management is presented. Infection and rejection continue to represent 2 major areas of posttransplantation complications and merit particular attention.

A potassium loading study was performed in acutely nephrectomized rats to determine the extrarenal effects of diuretics on potassium tolerance. Four diuretics were evaluated: hydrochlorothiazide, furosemide, bumetanide, and spironolactone. Following an intravenous potassium load (0.17 mEq/100 g over one hour), plasma potassium concentration rose by 2.69 +/- 0.26 to 3.67 +/- 0.20 mEq/L in all groups. There was no difference in the observed increment in plasma potassium concentration between animals receiving diuretics and control animals. These results demonstrate that, at the doses used, diuretics do not impair extrarenal potassium disposal in the rat.