The effect of smoking on chronic inflammation, immune function and blood cell composition.

Smoking is the number one risk factor for cancer mortality but only 15-20% of heavy smokers develop lung cancer. It would, therefore, be of great benefit to identify those at high risk early on so that preventative measures can be initiated. To investigate this, we evaluated the effects of smoking on inflammatory markers, innate and adaptive immune responses to bacterial and viral challenges and blood cell composition. We found that plasma samples from 30 heavy smokers (16 men and 14 women) had significantly higher CRP, fibrinogen, IL-6 and CEA levels than 36 non-smoking controls. Whole blood samples from smokers, incubated for 7 h at 37 °C in the absence of any exogenous stimuli, secreted significantly higher levels of IL-8 and a number of other cytokines/chemokines than non-smokers. When challenged for 7 h with E. coli, whole blood samples from smokers secreted significantly lower levels of many inflammatory cytokines/chemokines. However, when stimulated with HSV-1, significantly higher levels of both PGE2 and many cytokines/chemokines were secreted from smokers' blood samples than from controls. In terms of blood cell composition, red blood cells, hematocrits, hemoglobin levels, MCV, MCH, MCHC, Pct and RDW levels were all elevated in smokers, in keeping with their compromised lung capacity. As well, total leukocytes were significantly higher, driven by increases in granulocytes and monocytes. In addition, smokers had lower NK cells and higher Tregs than controls, suggesting that smoking may reduce the ability to kill nascent tumor cells. Importantly, there was substantial person-to person variation amongst smokers with some showing markedly different values from controls and others showing normal levels of many parameters measured, indicating the former may be at significantly higher risk of developing lung cancer.

Three Decades of Follow-up of Adults After Recovery From Invasive Pneumococcal Pneumonia.

BACKGROUND: Streptococcus pneumoniae infection is the most common cause of community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD) carries a high case fatality rate. We investigated the lifespan of adults who recovered from IPD during a 32-year follow-up. MATERIALS AND METHODS: We determined whether adults discharged after an episode of IPD from hospitals affiliated with the Marshall University Joan C. Edwards School of Medicine in Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate analysis, life expectancy using life tables for West Virginia, years of potential life lost and serotype occurrence. RESULTS: The study group comprised 155 adults who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%) patients lived longer than their life expectancy. Of the 13 comorbid diseases analyzed, cancer and neurologic diseases and the number of comorbid diseases suffered by each patient were the significant variables associated with survival. The mean years of potential life lost was 9.936 years. Only serotype 12 of 31 serotypes recovered occurred more often in patients who survived for 11 or more years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95). CONCLUSIONS: The fact that most adult patients who recovered from IPD died before their documented life expectancy argues for the pernicious severity of IPD and the importance of immunization of adults with pneumococcal vaccines.

Clinical features of patients with recurrent invasive Streptococcus pneumoniae disease.

INTRODUCTION: Invasive Streptococcus pneumoniae (pneumococcal) disease (IPD) carries a high risk of death, approximately 15% to 20% in pneumonia, 40% in meningitis and 10% to 15% in septicemia. The occurrence of 2 or more IPD (recurrent) in the same individual is uncommon. The authors investigated the clinical features of patients with recurrent IPD to assess whether they possessed risk factors that increased their likelihood of recurrent IPD. METHODS: Between 1983 and 2010, the authors identified 27 patients with recurrent IPD during inpatient surveillance of 889 patients with IPD in Huntington, WV, by recovery of pneumococci from otherwise sterile sites. Serotype/serogroup (ST/SG) was determined by capsular swelling and the penicillin MIC by E-strip. Clinical data were abstracted from hospital charts. RESULTS: Sixteen (59%) of 27 patients were 65 years and older at first IPD, males predominated (67%), two-thirds had pneumonia and 21 (78%) had the same clinical diagnosis at both IPD. Four (80%) of 5 patients with the same ST experienced their second IPD 1 to 6 months apart, unlike most patients with discordant ST/SGs (P = 0.047). Eighty-four percent of ST/SGs were included in the 23-valent pneumococcal vaccine and occurred as often during the first and second IPD. Twenty (77%) of 26 adults suffered from comorbid diseases placing them at high risk of IPD, including multiple myeloma, HIV/AIDS, neoplasia of hematological origin and sickle cell disease. CONCLUSIONS: Recurrent IPD occurred uncommonly. Comorbid conditions including multiple myeloma and immunosuppressive/immunodeficient conditions, chronic alcoholism and splenectomy represented unique risk factors for recurrent IPD but did not predict recurrences.

What patients know about irritable bowel syndrome (IBS) and what they would like to know. National Survey on Patient Educational Needs in IBS and development and validation of the Patient Educational Needs Questionnaire (PEQ).

UNLABELLED: Patient education improves clinical outcomes in patients with chronic illness, but little is known about the education needs of patients with IBS. OBJECTIVES: The objective of this study was to identify: (1) patients perceptions about IBS; (2) the content areas where patients feel insufficiently informed, i.e., "knowledge gaps" about diagnosis, treatment options, etiology, triggers, prognosis, and role of stress; and (3) whether there are differences related to items 1 and 2 among clinically significant subgroups. METHODS: The IBS-Patient Education Questionnaire (IBS-PEQ) was developed using patient focus groups and cognitive item reduction of items. The IBS-PEQ was administered to a national sample of IBS patients via mail and online. ANALYSIS: Frequencies of item endorsements were obtained. Clinically relevant groups, (a) health care seekers or nonhealth care seekers and (b) users or nonusers of the Web, were identified and grouped as MD/Web, MD/non-Web, and non-MD/Web. RESULTS: 1,242 patients completed the survey (371 via mail and 871 online), mean age was 39.3 +/- 12.5 yr, educational attainment 15 +/- 2.6 yr, 85% female, IBS duration 6.9 +/- 4.2 yr, 79% have seen an MD for IBS in the last 6 months, and 92.6% have used the Web for health information. The most prevalent IBS misconceptions included (% of subjects agreeing with the statement): IBS is caused by lack of digestive enzymes (52%), is a form of colitis (42.8%), will worsen with age (47.9%), and can develop into colitis (43%) or malnutrition (37.7%) or cancer (21.4%). IBS patients were interested in learning about (% of subjects choosing an item): (1) foods to avoid (63.3%), (2) causes of IBS (62%), (3) coping strategies (59.4%), (4) medications (55.2%), (5) will they have to live with IBS for life (51.6%), and (6) research studies (48.6%). Patients using the Web were better informed about IBS. CONCLUSION: (1) Many patients hold misconceptions about IBS being caused by dietary habits, developing into cancer, colitis, causing malnutrition, or worsening with age; (2) patients most often seek information about dietary changes; and (3) educational needs may be different for persons using the internet for medical information.

Priorities for treatment research from different professional perspectives.

The consensus conference "Advancing the Treatment of Fecal and Urinary Incontinence Through Research" had as one of its goals the development of a comprehensive list of research priorities. Experts from all disciplines that treat incontinence-gastroenterology, pediatric gastroenterology, urology, urogynecology, colorectal surgery, geriatrics, neurology, nursing, and psychology-and patient advocates were asked to identify their highest priorities for treatment-related research. Meeting participants were shown the aggregated list and invited to propose additional priorities. Treatments for fecal incontinence (biofeedback, sphincteroplasty, antidiarrheal and laxative medications, and sacral nerve stimulation) require validation by randomized, controlled trials. For urinary incontinence, the greatest need is to compare pharmacological, behavioral, and surgical treatments. Trials assessing combined treatments (e.g., biofeedback plus surgery vs. surgery alone or biofeedback alone) are also needed. New drugs are needed that target anal canal resting pressure in fecal incontinence and hypersensitivity to distention in urge urinary incontinence. It may be possible to substantially reduce the incidence of incontinence through modification of obstetric practices (e.g., avoiding episiotomies or offering elective cesarean delivery to high-risk patients), providing pelvic floor exercises before childbirth, and educating patients to avoid straining during defecation. For the elderly, practical behavioral and pharmacological treatments are needed that can postpone or avoid institutionalization. Social science research may identify ways to counteract the social stigma of fecal incontinence and assist physicians in providing patients with more comprehensive and understandable information on the risks associated with different treatment options.