Search

Ageing is accompanied by reduced functioning of the immune system, termed immunesenescence which is associated with increased risk of infection and mortality. However the immune system does not operate in isolation and can be modified by many environmental factors, including stress. In this study we determined whether physical stress (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system, specifically on monocyte numbers and function. We assessed immune function in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age matched controls (28 females). Thirty-eight of the hip fracture group were found to be depressed at the 6 week sampling. No differences in peripheral monocyte count, distribution of monocyte subsets or TNFα secretion were observed between hip fracture patients and healthy controls. However we observed significantly reduced superoxide production in response to Escherichia coli in the monocytes of hip fracture patients who developed depressive symptoms compared with non-depressed hip fracture patients (p = 0.002) or healthy controls (p = 0.008) 6 weeks after the fracture which remained decreased 6 months following injury. In previous studies we have shown an effect of depression on neutrophil superoxide generation in hip fracture patients, suggesting a particular susceptibility of this aspect of immune cell function to psychological stress.

Highlight • Depressive symptoms are a major driver of reduced immunity after hip fracture., Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p = .001) or controls (p = .004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.

Although the ultimate goal of asthma treatment is to improve asthma-specific Health-Related Quality-Of-Life (HRQOL), in the UK population this is insufficiently studied. National asthma-specific HRQOL data is needed to inform strategies to address this condition.To benchmark asthma-specific HRQOL in a national survey of adults with asthma, and explore differences in this measure within subsections of the population.We analysed answers to the Marks Asthma Quality-of-Life Questionnaire (AQLQ-M) from a representative sample of 658 adults with asthma. Respondents answered asthma-specific questions to assess control, previous hospital admissions, asthma attacks and an indicator of severity. Higher scores indicate poorer HRQOL (maximum = 60). The highest quintile formed a subgroup 'Poor HRQOL'. Data were weighted to correct for any biases caused by differential non-response. Chi-square analyses were used to determine differences between good and poor quality of life and regression analyses performed to determine what factors are associated with poor HRQOL.The response rate was 49%. AQLQ-M median (IQR) scores were 5 (2-13) for the total sample (poor HRQOL = 21, good HRQOL = 3). Significant differences between good and poor HRQOL were observed in smoking status, SES, employment status and co-morbidities, but no differences were found between age groups. Those with poorly controlled asthma were significantly more likely to have poor HRQOL, ≥1 breathing related hospital admission or ≥1 asthma attack.This article provides benchmarking data on asthma-specific HRQOL. Improved strategies are needed to target interventions towards people experiencing poor HRQOL.

Background: Non-adherence to corticosteroid treatment has been shown to reduce treatment efficacy, thus compromising asthma control. Aims: To examine the experiences of treatment side effects, treatment concerns and adherence to inhaled (ICS) and oral corticosteroids (OCS) among people with asthma and to identify the degree of concordance between clinician estimates of side effects and the prevalence reported by patients. Methods: Asthma UK members were sent validated questionnaires assessing treatment concerns, experiences of side effects and adherence. Questionnaires measuring clinicians’ estimates of the prevalence of corticosteroid side effects were completed online. Results: Completed questionnaires were returned by 1,524 people taking ICS, 233 taking OCS and 244 clinicians (67% of clinicians were primary care nurses). Among people with asthma, 64% of those taking ICS and 88% of those taking OCS reported ⩾1 side effect. People reporting high adherence to ICS (t=−3.09, Pt=1.86, Pr=0.46, Pr=0.50, Pt=6.90, Pt=1.71; P Conclusions: An unexpectedly large proportion of people with asthma experienced side effects and had strong concerns about their treatment, which compromised adherence. These findings have implications for the design of interventions to optimise asthma control through improved adherence.

International guidelines and local practices for colorectal cancer screening suggest an important role for several different screening tests, and for consumer choice. We aimed to determine whether choice of test improved participation in screening.A randomised comparative study offering one of six screening strategies: faecal occult blood testing (FOBT), FOBT and flexible sigmoidoscopy (FS), computed tomography colonography (CTC), colonoscopy, or one of two groups offered a choice of these strategies (one of which was sent an FOBT kit with the letter of invitation, while the other was required to request an FOBT kit by telephone if that was the test chosen).1679 people aged 50-54 or 65-69 years, randomly selected from the electoral roll in metropolitan Perth, Adelaide and Melbourne.Participation, yield of advanced colorectal neoplasia (CRN), acceptability and safety.346 (20.6%) were excluded from screening, mostly for a recent examination (165), symptoms (72) or personal or family history of colorectal neoplasia or cancer (83). 278 of the 1333 eligible (20.9%; 95% CI, 18.7%-23.1%) participated in screening. Participation was similar by age and sex, but lower in Perth than Adelaide (17.1% v 24.2%; P = 0.01). Participation by screening group was: FOBT, 27.4%; FOBT/FS, 13.7% (P0.001 compared with FOBT); CTC, 16.3% (P = 0.005); colonoscopy, 17.8% (P = 0.02); or a choice of test 18.6% ("with FOBT kit"; P = 0.03) or 22.7% ("without FOBT kit"; P = 0.3). Yield of advanced CRN was higher in participants screened by colonoscopy than FOBT (7.9% v 0.8%; P = 0.02). All tests were well accepted and no serious complications arose from screening.A choice of screening test did not improve participation. Participation by FOBT was higher than by other tests. Yield of advanced colorectal neoplasia on an intention-to-screen basis, determined by test sensitivity and participation, is likely to be a critical determinant of the effectiveness of screening strategies.

Objective To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. Design and methods Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. Results End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. Conclusions In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.

Autoimmunity increases with aging indicative of reduced immune tolerance, but the mechanisms involved are poorly defined. In recent years, subsets of B cells with immunoregulatory properties have been identified in murine models of autoimmune disorders, and these cells downregulate immune responses via secretion of IL10. In humans, immature transitional B cells with a CD19(+) CD24(hi) CD38(hi) phenotype have been reported to regulate immune responses via IL10 production. We found the frequency and numbers of CD19(+) CD24(hi) CD38(hi) cells were reduced in the PBMC pool with age. IL10 expression and secretion following activation via either CD40, or Toll-like receptors was also impaired in CD19(+) CD24(hi) CD38(hi) B cells from healthy older donors. When investigating the mechanisms involved, we found that CD19(+) CD24(hi) CD38(hi) B-cell function was compromised by age-related effects on both T cells and B cells: specifically, CD40 ligand expression was lower in CD4 T cells from older donors following CD3 stimulation, and signalling through CD40 was impaired in CD19(+) CD24(hi) CD38(hi) B cells from elders as evidenced by reduced phosphorylation (Y705) and activation of STAT3. However, there was no age-associated change in expression of costimulatory molecules CD80 and CD86 on CD19(+) CD24(hi) CD38(hi) cells, suggesting IL10-dependent immune suppression is impaired, but contact-dependent suppressive capacity is intact with age. Finally, we found a negative correlation between CD19(+) CD24(hi) CD38(hi) B-cell IL10 production and autoantibody (Rheumatoid factor) levels in older adults. We therefore propose that an age-related decline in CD19(+) CD24(hi) CD38(hi) B cell number and function may contribute towards the increased autoimmunity and reduced immune tolerance seen with aging.

Background: Hip fracture in older adults is associated with depression and frailty. This study examined the synergistic effects of depression and hip fracture on physical frailty, and the mediating role of the cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio. Methods This was an observational longitudinal study of patients with a hip fracture carried out in a hospital setting and with follow up in the community. Participants were 101 patients aged 60+ years (81 female) with a fractured neck of femur. Measurements of the ability to carry out activities of daily living (ADL), cognitive function, physical frailty and assays for serum cortisol and DHEAS were performed six weeks and six months post-hip fracture. Depressed and non-depressed groups were compared by ANOVA at each time point. Results Hip fracture patients who developed depression by week six (n = 38) had significantly poorer scores on ADL and walking indices of frailty at both week six and month six, and poorer balance at week six. The association with slower walking speed was mediated by a higher cortisol:DHEAS ratio in the depressed group. Conclusion Depression following hip fracture is associated with greater physical frailty and poorer long term recovery post-injury. Our data indicate that the underlying mechanisms may include an increased cortisol:DHEAS ratio and suggest that correcting this ratio for example with DHEA supplementation could benefit this patient population.

Thoraco-abdominal asynchrony (TAA), the discordant movement of the abdomen and thorax, may impact upon health-related variables. Here, we investigated the extent to which TAA is associated with health-related variables, particularly perceived asthma control and quality of life.Ambulatory respiratory data from 43 patients diagnosed with asthma and 43 healthy age and sex-matched controls were recorded over 4 hours. Phase relation (Ph Rel Total), the percentage of time that the effects of rib cage (RC) and diaphragmatic movement result in opposite effects on intra-thoracic volume, quantified TAA. Subjects completed the Mini Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), Nijmegen questionnaire (NQ), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI), and General Health Perception (GHP) subscale of the short form 36 questionnaire'. Capnography profiling, breath-hold time (BHT), and standard spirometry were performed.The time in asynchrony was significantly greater in the asthma than in the healthy control group (Ph Rel Total = 14% (interquartile range (IQR) 8.5-20.7%) versus 10.4% (IQR 7.1-14.5%), p = .012). In patients with asthma, Ph Rel Total was weakly associated with poorer ACQ scores (r = 0.33, p = .03), and in the healthy control group with GHP (r = 0.319, p = .037). Post-hoc exploratory analysis revealed a moderate relationship in the female asthma subgroup between Ph Rel Total and AQLQ (r = -0.56, p = .003).TAA may be associated with decreased perceived asthma control. In healthy individuals, asynchrony may be associated with low perception of general health. Further studies are required to investigate if the reduction of TAA improves these health-related variables.

We investigated the efficacy and safety of daily candesartan 8/16mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension.The study used a double-blind randomized placebo-controlled crossover design. Treatment phases were of 6 weeks duration. For inclusion, patients were aged 55-84 years with sitting systolic blood pressure (SBP) 160-210 mmHg and diastolic blood pressure (DBP)95 mmHg. Nineteen patients (11 male, eight female, median age 68 years) completed the study.Compared with the placebo phase, clinic and ambulatory SBP was significantly reduced with both dose-adjusted candesartan and fixed-dose hydrochlorothiazide as monotherapy, the effect of candesartan being greater than that of hydrochlorothiazide. In combination, the effects of the two drugs were additive. Both drugs were well tolerated either as monotherapy or in combination.Both candesartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination. Candesartan was more effective than hydrochlorothiazide, although it is possible that dose adjustment only of candesartan could have enhanced its relative effectiveness.

To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril.Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet.19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours.In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.

Background: Approximately 210 million people are estimated to have chronic obstructive pulmonary disease\ud [COPD] worldwide. The burden of disease is known to be high, though less is known about those of a younger\ud age. The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a\ud cross country working-age cohort.\ud \ud Methods: A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised\ud to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods\ud specific to each country completed the full survey. Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to\ud questioning. The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale\ud and the EuroQoL 5 Dimension [EQ-5D] scale. Disease severity was measured using the 5-point MRC [Medical\ud Research Council] dyspnoea scale as a surrogate measure.\ud Results: 64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of\ud the cohort reported at least one comorbid condition. Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41]. The annual cost of healthcare utilisation [excluding treatment\ud costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500]. For those remaining in active\ud employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime\ud losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population\ud had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000\ud [£200,000] or a combined total of $141 m [£89.6 m]. As the mean age of retirees was 58.3 and average time since\ud retirement was 4 years, this suggests the average age of retirement is around 54. This would mean a high societal\ud and economic impact in all study countries, particularly where typical state retirement ages are higher, for example\ud in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and\ud China [60].\ud \ud Conclusions: Although generalisation across a broader COPD population is limited due to the varied participant\ud recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal\ud burden on working age people. Further efforts to improve COPD diagnosis and management are required.