Increasing exercise capacity and physical activity in the COPD patient.

Higher levels of exercise capacity and physical activity are desired outcomes in the comprehensive management of the COPD patient. In addition, improvements in exercise capacity and physical activity are instrumental to optimising other important therapeutic goals, such as improved health status, reduced healthcare utilisation and increased survival. Four general approaches towards increasing exercise capacity and physical activity in individuals with COPD will be discussed in this review: 1) pharmacological intervention, especially the administration of long-acting bronchodilators; 2) pulmonary rehabilitation, including exercise training and collaborative self-management; 3) behavioural interventions; and 4) web-based interventions. These are by no means the only approaches, nor are they mutually exclusive: indeed, combining them, as necessary, to meet the needs of the individual respiratory patient may promote optimal outcomes, although further research is necessary in this area.

COPD: Providing the right treatment for the right patient at the right time.

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work.

Lung Cancer Screening at a Military Treatment Facility: A Retrospective Review.

INTRODUCTION: Lung cancer is the leading cause of cancer death among men and women, accounting for more fatalities than colon, breast, and prostate cancers combined. Smoking causes about 85% of all lung cancers in the United States and is the single greatest risk factor. In 2013, the US Preventive Services Task Force (USPSTF) published initial guidelines for low-dose computed tomography lung cancer screening (LCS) among patients 55-80 years old, with a 30-pack-year history, who are current smokers or who quit within the previous 15 years. Smoking prevalence is higher among military personnel compared to the civilian population, demonstrating a need for vigilant screening. MATERIALS AND METHODS: A retrospective review of Naval Medical Center San Diego's (NMCSD) LCS data was conducted to examine screening numbers, lung cancer rates, and initial analysis of screening results. Patients were referred for screening if they met the USPSTF criteria. Between September 2013 and September 2018, 962 patients underwent LCS. A total of 1758 examinations were performed, including follow-up and annual surveillance examinations. The American College of Radiology's Lung CT Screening Reporting and Data System (Lung-RADS) was used to classify lung nodules' risk for malignancy. RESULTS: On this initial analysis, 42 enrolled patients received the diagnosis of lung cancer detected by screening. The initial calculated lung cancer rate is 4.4% (42/962) over the 5-year reporting period. The lung cancer rate among those patients with a Lung-RADS score of 3 or 4 was 31% (42/135). Thirty-seven patients were classified as having non-small cell lung cancer (NSCLC), while five were classified as having small cell lung cancer. Of the 37 NSCLC patients, 76% (28/37) were diagnosed at stage I and II, 11% (4/37) were diagnosed at stage III, and 13% (5/37) were diagnosed at stage IV. The total number of years a person smoked was a significant risk factor (P = 0.004), but not pack-years a person smoked (P = 0.052). CONCLUSIONS: These preliminary results demonstrate the success of a Military Treatment Facility (MTF)-based LCS Program in the detection of early stage lung cancer. Earlier stage detection may result in better health outcomes for affected patients. In the population studied, duration of smoking proved to be more significant than pack-years in predicting lung cancer risk. These results validate the newly dedicated resources and continued efforts to strengthen the LCS program at NMCSD and across MTFs.

The MoCA-Memory Index Score: An Efficient Alternative to Paragraph Recall for the Detection of Amnestic Mild Cognitive Impairment.

OBJECTIVE: To compare ability of 2 measures of delayed memory (word list, story paragraph) to discriminate Normal Control (NC) subjects from those with amnestic mild cognitive impairment (aMCI). METHODS: Demographic, neuropsychological, and diagnostic data contributed by 34 Alzheimer's Disease Centers to the National Alzheimer's Coordinating Center characterized 2717 individuals with a diagnosis of either NC (n=2205) or aMCI (n=512). The Montreal Cognitive Assessment-Memory Index Score (MoCA-MIS) assessed delayed word recall, and the Craft Story 21, delayed story recall. Logistic regression and receiver operator characteristic curves controlling for age, sex, and education assessed the ability of each test to differentiate NCs from subjects with aMCI. RESULTS: The MoCA-MIS had significantly better sensitivity and specificity (area under the receiver operator characteristic curve 0.83 vs. 0.80, P=0.004). At sensitivity 80%, the specificity of the MoCA-MIS was 69.1%, compared with 62.8% for the Craft Story. CONCLUSIONS: These data suggest that the MoCA-MIS, a recall score from items within the MoCA, is better at discriminating NCs from subjects with aMCI than the Craft Story. Word recall may be an efficient alternative to paragraph recall for diagnostic screening within clinical practice and research settings.

Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India.

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76-4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47-4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53-60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.

Rapidly progressive colonic dysplasia/neoplasia in a series of treated lung cancer patients: Is paclitaxel involved?

Incidence of second malignancies in patients with advanced lung cancer is not well-studied, in part because of a short survival in this patient population. Apart from a genetic predisposition, various environmental hazards may also be at play in their pathogenesis. Chronic smoking exposure decreases T-cell responsiveness and stimulates production of a variety of inhibitory cytokines. Paclitaxel has been associated with several immunosuppressive effects such as decreased numbers and activity of dendritic cells, NK-cells, and monocytes. We herein describe the first series of lung cancer patients who developed colonic polyps/colon cancer either during or immediately following chemotherapy with paclitaxel, suggesting a possible role of this agent in their pathogenesis.

Targeting the HER2 pathway for the therapy of lower esophageal and gastric adenocarcinoma.

INTRODUCTION: The mysteries of complex molecular pathways of tumorigenesis are only beginning to be unraveled. Overexpression of HER2 receptors has been associated with adverse outcomes in certain malignant solid tumors. AREAS COVERED: The authors give a focused review of the HER2 pathway and its importance for cancer cell survival. Similar to the situation in breast cancer, HER2 overexpression is seen in up to one-quarter of all gastric and gastroesophageal junction adenocarcinomas. The audience will also be familiarized with the existing HER2 targeted agents (both at the bench and at the bedside) for the therapy of gastric and gastroesophageal cancers. EXPERT OPINION: Despite recent advances, treatment of upper gastrointestinal malignancies remains a significant challenge. Trastuzumab in combination with chemotherapy is the current standard of therapy for patients with metastatic HER2-overexpressing esophageal and gastric cancers. The activity of lapatinib, an active agent in advanced HER2-positive breast cancer, is now being tested in HER2-overexpressing esophageal and gastric adenocarcinomas. A variety of monoclonal antibodies and tyrosine kinase inhibitors with affinity for HER2 are in development and may improve further the outcomes of these malignancies.