Chronic obstructive pulmonary disease: a complex comorbidity of lung cancer

Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a significantly increased incidence of lung cancer and may influence treatment options and outcome. Impaired lung function confirming COPD is an independent risk factor for lung cancer. Oxidative stress and inflammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer development. COPD negatively influences the ability to deliver radical treatment options, so attempts must be made to look for alternative methods of treating lung cancer, while aiming to manage the underlying COPD. Detailed assessment and management plans utilizing the multidisciplinary team must be made for all lung cancer patients with COPD to provide the best care possible.Journal of Comorbidity 2011;1(1):45–5

Modulation of Drug Resistance in Small Cell Lung Cancer

The aim of these studies was to modulate drug resistance in small cell lung cancer (SCLC) both in the laboratory and in the clinic with verapamil. Nine small cell lung cancer cell lines have been established from both pretreatment and relapse biopsies and include a pair of cell lines from the same patient. Problems in establishing cell lines related to lack of viable tumour material and overgrowth by fibroblasts. All the cell lines have been characterised and demonstrate features characteristic of SCLC in vitro. All cell lines expressed the small cell marker enzymes dopa-decarboxylase and the BB isoenzyme of creatine kinase though the levels varied between cell lines. Pathological, immunocytochemical and ultrastructural studies were used to identify both epithelial and neuroendocrine features. Thus the cell lines could be classified into classic or variant phenotypes. Detailed cytogenetic analysis of the cell lines confirmed their human origin and all were shown to contain the 3p deletion characteristic of lung tumours. The modal chromosome number ranged from 39 to 53. The cell lines all grow as non-adherent aggregates except for a monlayer variant of LS112. Measurement of growth rates and chemosensitivity therefore proved difficult since the aggregates could not be dispersed into a viable single cell suspension. Initially measurements were attempted by computerised spheroid image analysis. This technique was slow but provided limited information for three of the cell lines (LS106, LS111 and LS112FL). However, the other cell lines tested did not grow well in this system. A tetrazolium dye-based microtitration assay was therefore modified for use with both adherent and non-adherent cell lines. The assay uses as an end point the ability of live, but not dead cells, to reduce a yellow water-soluble tetrazolium dye (MTT) to a purple water-insoluble formazan product (MTT-formazan). Initial work with this assay indicated a number of deficiencies and, in particular, at high cell density or low pH the relationship between MTT-formazan production and cell number was not linear. It was shown that by determining the optimal concentration of MTT for each cell line and by addition of a buffer at a high pH (10.5) to control the pH of the formazan product a linear relationship could be obtained. When intact aggregates were incubated with MTT, crystals of MTT-formazan were produced by the entire viable cell population of the aggregate. Furthermore, doxorubicin was shown to penetrate throughout the viable cell population of the aggregate. Thus the assay could be applied to the intact SCLC aggregates thereby avoiding the need to disrupt the clusters with the consequent loss of cell interaction and viability. The cell lines were slow growing with doubling times of between 4 and 6 days. There was a 60-fold range in sensitivity to doxorubicin (ID50, 17.5 - 1050nM). Intrinsic sensitivity to doxorubicin did not relate either to any specific characteristic of the cell lines or to the history of the patient from whose biopsy the cell line was established. However, for the pair of cell lines established from the same patient the line derived from the relapse biopsy (LS310) was five-fold more resistant to doxorubicin than the line derived from the original chemosensitive pretreatment biopsy (LS274). For the multidrug resistant SCLC cell line, H69LX10, resistance modification by verapamil was shown to be dose dependent and was maximal (10-fold) at about 6-7 muM. At clinically achievable levels of verapamil (1uM) the effect was only 2-fold. These results indicate that verapamil may have limited activity in the clinic. However, the D-stereoisomer of verapamil was shown to be an equally effective resistance modulator as the racemic mixture. Since D-verapamil is thought to be less cardiotoxic than L-verapamil it is possible that use of D-verapamil in the clinic will allow increased plasma levels of the modulator without undue cardiotoxicity. Quinidine and bepridil were also identified as modulators that have significant activity in H69LX10 cells in the laboratory at levels achievable in the clinic. An increase in sensitivity to doxorubicin (2-3 fold) in the presence of verapamil (6.6muM) was demonstrated in 5 of the 9 newly established SCLC cell lines. The sensitising effect of verapamil did not relate to patient history or to the intrinsic sensitivity of the cell line to doxorubicin. Thus, the most sensitive line (LS277) established from an untreated patient showed a 2.3-fold increase in sensitivity whereas the most resistant line (LS310) from a relapse biopsy showed no change in sensitivity when co-incubated with verapamil

Obtaining tissue diagnosis in lung cancer patients with poor performance status and its influence on treatment and survival

Introduction: 25% of patients with lung cancer have performance status 3 or 4. A pragmatic approach to investigative procedures is often adopted based on the risks and benefits in these patients and whether tissue diagnosis is necessary for anticipated future treatment. This cohort study investigated factors influencing a clinician's decision to pursue a tissue diagnosis in patients with lung cancer and performance status 3 and 4 and to examine the association of tissue diagnosis with subsequent management and survival. Methods: All patients with lung cancer diagnosed in North Glasgow from 2009 to 2012 were prospectively recorded in a registry. We investigated the relationships between achieving a tissue diagnosis, treatment and survival. Results: Of 2493 patients diagnosed with lung cancer, 490 patients (20%) were PS 3 and 122 patients (5%) were PS 4. Tissue diagnosis was attempted in 60% and 35% patients with PS 3 and PS 4 respectively. Younger age, better performance status and having stage 4 disease were independently associated with a diagnostic procedure being performed. Only 5% of patients with poor performance status received treatment conventionally requiring a tissue diagnosis. Age, stage and performance status were independent predictors of mortality. Achieving a tissue diagnosis was not associated with mortality. Receiving treatment requiring tissue diagnosis is associated with survival benefit. Conclusions: The majority of patients with poor fitness undergo a diagnostic procedure which does not influence further treatment or affect survival. However, the cohort of patients who do undergo therapy determined by tissue diagnosis have improved survival

Quality of life in lung cancer patients: does socioeconomic status matter?

BACKGROUND: As part of a prospective study on quality of life in newly diagnosed lung cancer patients an investigation was carried out to examine whether there were differences among patients' quality of life scores and their socioeconomic status. METHODS: Quality of life was measured at two points in time (baseline and three months after initial treatment) using three standard instruments; the Nottingham Health Profile (NHP), the European Organization for Research and Cancer Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and its lung cancer supplement (QLQ-LC13). Socioeconomic status for each individual patient was derived using Carstairs and Morris Deprivation Category ranging from 1 (least deprived) to 7 (most deprived) on the basis of the postcode sector of their address. RESULTS: In all, 129 lung cancer patients entered into the study. Of these data for 82 patients were complete (at baseline and follow-up). 57% of patients were of lower socioeconomic status and they had more health problems, less functioning, and more symptoms as compared to affluent patients. Of these, physical mobility (P = 0.05), energy (P = 0.01), role functioning (P = 0.04), physical functioning (P = 0.03), and breathlessness (P = 0.02) were significant at baseline. However, at follow-up assessment there was no significant difference between patient groups nor did any consistent pattern emerge. CONCLUSION: At baseline assessment patients of lower socioeconomic status showed lower health related quality of life. Since there was no clear trend at follow-up assessment this suggests that patients from different socioeconomic status responded to treatment similarly. In general, the findings suggest that quality of life is not only the outcome of the disease and its treatment, but is also highly dependent on each patients' socioeconomic characteristics

Simple and objective prediction of survival in patients with lung cancer: staging the host systemic inflammatory response

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer

Developing a Web-Based Tool Using Information and Communication Technologies to Expand the Reach and Impact of Photovoice

Information and communication technologies are opening up vast new arenas for conducting the work of health promotion. Technology-based health promotions expand reach, standardize information and its delivery, provide opportunities for tailoring, create engaging interactivity within content delivery, provide for privacy and autonomy, improve portability, and lower delivery costs. This commentary describes the ongoing exploration and development of a web-based tool for enhancing the reach and impact of Photovoice as a community change intervention. Features of the tool use information and communication technologies that integrate the use of an online learning management system, tailored messaging, gaming technology, interactive features, and the application of social media's power to increase the capacity of communities to employ comprehensive strategies to improve the health of their communities. It will enable individuals and groups to use photos and captions to assess the physical environment, social norms, and behaviors of communities; raise community awareness of the factors contributing to ill health in their communities; mobilize stakeholders; and inform environmental strategies and policy changes. We believe that it will enhance the delivery of educational content about conducting Photovoice projects, provide features unavailable without the application of information and communication technologies, and be substantive advancement over existing Photovoice resources

Going the distance: Delivery of high school drug prevention via distance education.

The purpose of this project was to develop a technology that can be used in schools where there are insufficient resources to implement a quality drug prevention program. The specific technology—distance education via teleconferencing—allows a highly qualified teacher to deliver programs in such settings with increased quality. A promising high school drug prevention program, All Stars, Sr., was modified to be delivered using the latest technological advances in distance education. Student-level effects are reported across six mediating variables as well as past thirty-day and lifetime use of alcohol, tobacco, marijuana, ecstasy, and other illicit drugs