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Purpose: To evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic cough patients based on their airway inflammatory phenotype.Methods: We have studied consecutive patients attending a specialist cough clinic. 30 patients with high FeNO (> 30 ppb) and 20 patients with low FeNO (< 20 ppb) were recruited.Results: There was a significant correlation between FeNO, B-Eos and sputum eosinophil count (p < 0.001). The number of recorded coughs in 24 h and HARQ scores were significantly (p < 0.05) higher in patients with a low FeNO. In contrast to the high FeNO group (48%), the greater proportion of these patients were women (90%). LCQ scores were worse in the low FeNO group but it was not significant.Conclusion: A strong relationship between FeNO, blood eosinophils and sputum eosinophils confirming phenotypic identity was observed. Whether the observed gender disparity accounts for the different cough frequency characteristics is unknown. [ABSTRACT FROM AUTHOR]

Aim: The effect of hormone levels on the stimulation of Toll-like receptor 5 (TLR5) in the bladder is unknown. We aimed to study the effect of estradiol and progesterone on TLR5 expression and function in human bladder epithelial cells. Methods: After growing to near confluence, T24 human urinary bladder (HUB) cells were incubated in hormone-free (HF) media for 72 hours. Human urinary bladder cells were then incubated in (1) HF media, (2) estradiol media, (3) progesterone media, or (4) media containing estradiol and progesterone at physiologic concentrations. Following flagellin exposure, cells and media were collected. Toll-like receptor 5 expression and stimulated cytokine release were analyzed using enzyme-linked immunosorbent assays. Results were normalized with cellular protein assays. A TLR5 antagonist was used to confirm that stimulation from flagellin was mediated by TLR5 signaling. Results: Cultured HUB cells express TLR5 protein. Estradiol and progesterone environments suppress TLR5 expression compared to HF environment. The function of TLR5 was measured by interleukin 6 (IL-6) and monocyte chemoattractant protein 1 production after flagellin exposure. Interleukin 6 production was 75% higher in the estradiol than progesterone environment. The progesterone environment produced IL-6 levels twice that observed in HF and combined estrogen–progesterone environments. Interestingly, higher TLR5 expression was associated with lower IL-6 production. Conclusion: Our study demonstrated that TLR5 expression and functional activity as measured by IL-6 are modulated by hormones. The increase in TLR5-associated IL-6 may play a role in increasing the rate of symptomatic urinary tract infection. Likewise, low TLR5 functional activity may dampen the response of the innate immune system, thereby lessening the likelihood of a symptomatic bladder infection. [ABSTRACT FROM AUTHOR]

Protocols measuring cough sensitivity can vary in terms of nebuliser, tussive agent, single and dose response. A definitive method for measuring cough sensitivity needs to be established. The ERS guidelines recommend the KoKo DigiDoser (KD) delivery system. Study aim, was to compare the reproducibility of this citric acid (CA) cough challenge and previously established Mefar dosimeter (MD) protocol. 39 (female 26) volunteers mean age (40.4 yrs) were randomised to either KD or MD. Intra-day and inter-day reproducibility was compared. We calculated the concentration of citric acid evoking 2 coughs (C2). The geometric mean C2 (95%CI) was similar for both KD and MD, of 263 (200,339) mM and 209 (151,288) mM respectively. The mean KD C2 was not significantly different. (F = 0.807, p = 0.93) from baseline over 1, 2, and 4 hrs however, the MD demonstrated significant variability (F = 7.85, P < 0.001) Measuring mean log C2 at baseline and at 2 weeks, the KD demonstrated a stronger intraclass correlation of log C2 at baseline with 2 week log C2, ICC = 0.70 than was shown with the Mefar, ICC = 0.41 Administering CA from KD offers a reproducible cough challenge in healthy volunteers. The results correlate well with the MD challenge but offer greater intra-day and inter-day reproducibility. [ABSTRACT FROM AUTHOR]

Abstract: Despite the best available clinical care, pain after surgery is a virtually universal patient experience that can have pervasive negative consequences. Given the large variability among patients in postoperative pain levels, research on novel modifiable risk factors is needed. One such factor suggested by recent experimental studies indicates that disruption of even a single night''s sleep can increase subsequent pain in healthy volunteers. In this preliminary clinical study, we tested the hypothesis that poor sleep the night before surgery would predict heightened postoperative pain. Patients (n =24) scheduled for routine breast-conserving surgical procedures for the diagnosis or treatment of cancer were recruited and wore an actigraphy device providing objective, validated measures of sleep duration and disruption (low sleep efficiency). Pain severity and interference with daily activities for the week after surgery was assessed with the Brief Pain Inventory. As hypothesized, multiple regression analyses revealed that lower sleep efficiency was a significant predictor of greater pain severity and interference, controlling for age, race, and perioperative analgesics as appropriate. Sleep efficiency was not significantly related to measures of depressed mood, emotional upset, or relaxation assessed on the morning of surgery. Patients with sleep efficiency in the lowest tertile had clinically higher levels of pain (>2 points) compared with patients in the highest sleep efficiency tertile. Sleep duration had no significant effects. This preliminary clinical study supports the possibility that sleep disruption on the night before surgery may increase patients'' experience of pain after surgery. Research to investigate the mechanisms underlying these effects and to explore the possible clinical benefits of interventions to improve patients'' sleep before surgery is now warranted. [Copyright &y& Elsevier]

Abstract: Sleep is important for health; however, poor sleep is a growing problem in many Western societies, particularly among women. Alterations in immune function following poor sleep (defined by duration and disruption) may be linked to ill health. Not yet investigated are the possible effects on stress-induced mobilization of lymphocytes. As natural killer (NK) cells are particularly responsive to acute stress, the present study examined whether sleep period duration and percentage of time awake after sleep onset (WASO) the night before a laboratory stressor would predict reduced NK cell mobilization. Sleep was monitored by actigraphy in 39 healthy women. NK cell peripheral blood numbers were determined at baseline (post-20min rest), 4min into a Stroop task, immediately post-task and 30min after task completion. Participants with high WASO had significantly less NK cell mobilization to the stressor and failed to return to baseline levels after 30min compared to women with low WASO. No effects were found for sleep period duration. Findings raise the possibility that inadequate NK cell mobilization to, and poor recovery from acute stress may be one pathway by which sleep could impact health. [Copyright &y& Elsevier]

Abstract: Sleep disruption is a growing problem that may have serious health effects. As stress-induced increases in cortisol are thought to be a key adaptive process it is important to examine how this response is affected by sleep. The current study investigated the association of four sleep parameters (objective/subjectively measured sleep quality and quantity) and subsequent salivary cortisol reactivity (maximal change from baseline) to an experimental stressor in 53 healthy women. Objective actigraphy monitoring and self-report diaries were used to assess sleep. Results revealed that individuals with lower objective sleep quality (wake percentage during sleep) had a blunted response to the experimental stressor. No associations were found between cortisol reactivity and actigraphy-derived sleep quantity, or either of the self-reported sleep variables. Results are discussed with regard to the possible adverse health effects that may result from poor sleep quality and a blunted cortisol response to stress. [Copyright &y& Elsevier]

Abstract: Heightened cardiovascular stress responsivity is associated with cardiovascular disease, but the origins of heightened responsivity are unclear. The present study investigated whether disturbances in cardiovascular responsivity were evident in individuals with a family history of cardiovascular disease risk. Data were collected from 60 women and 31 men with an average age of 21.4 years. Family history of cardiovascular disease risk was defined by the presence of coronary heart disease, hypertension, diabetes or high cholesterol in participants’ parents and grandparents; 75 participants had positive, and 16 had negative family histories. Systolic and diastolic blood pressure (BP), heart rate and heart rate variability were measured continuously for 5 min periods at baseline, during two mental stress tasks (Stroop and speech task) and at 10–15 min, 25–30 min and 40–45 min post-stress. Individuals with a positive family history exhibited significantly greater diastolic BP reactivity and poorer systolic and diastolic BP recovery from the stressors in comparison with family history negative individuals. In addition, female participants with a positive family history had heightened heart rate and heart rate variability reactivity to stressors. These effects were independent of baseline cardiovascular activity, body mass index, waist to hip ratio and smoking status. Family history of hypertension alone was not associated with stress responsivity. The findings indicate that a family history of cardiovascular disease risk influences stress responsivity which may in turn contribute to risk of future cardiovascular disorders. [Copyright &y& Elsevier]

Summary: A heightened cortisol awakening response (CAR) is associated with adiposity in middle-aged men, but the causal significance of this effect is not known. We hypothesised that if disturbance in cortisol secretion is involved in the development of overweight and obesity, then it might be present in normal weight adults at increased risk of obesity on account of parental adiposity. The CAR and cortisol profile over the day were measured in 33 men and 62 women aged 18–25 years. Parental adiposity was assessed with figure ratings derived from the Contour Drawing Rating Scale, and these were correlated with parental self-reported body mass index (BMI) in a subset of participants (r=0.66–0.79). In men, a positive association was observed between the CAR and their judgements of their fathers’ adiposity after controlling for age, smoking status, time of waking, and the participants’ own BMI; the correlation was 0.56 (P=0.008) for the cortisol increase between waking and 30min, and 0.47 (P=0.028) for the cortisol area under the curve. The correlation between the CAR and fathers’ own reported BMI and figures ratings were also significant. The relationship between parental adiposity and the CAR in women was inconsistent, and the associations between the CAR and opposite gender parental adiposity were not significant. Parental adiposity was not related to cortisol output over the rest of the day or to the slope between waking and evening in either sex. The results of this study suggest that disturbances of cortisol secretion may present before the emergence of heightened adiposity in young men at raised risk for obesity. [Copyright &y& Elsevier]

Abstract: Objective: Using an experimental paradigm this investigation explored whether exposure to psychological stress would produce a significant increase in acid-reflux episodes or modify subjective perceptions of gastro-oesophageal reflux (GOR) symptoms. Methods: Forty-two patients presenting with heartburn and acid regurgitation underwent 24-h oesophageal pH monitoring. During the last 90 min of this monitoring period, 21 patients received a psychological stressor, while the remaining participants were randomly assigned to a no-stress control condition. State anxiety and subjective GOR symptom ratings were obtained 1 min pretest, 1 min posttest, and 40 min posttest. Cortisol samples were collected at 10-min intervals. Results: The stressor induced a significant increase in cortisol and state anxiety; however, this was not associated with any increase in reflux. Instead, the experimental group reported a dissociation between objectively measured reflux episodes and subjective symptom ratings. A similar pattern was established for participants who reported greater state anxiety, produced larger cortisol responses, or exhibited certain stress-related personality characteristics. Conclusion: The perception of symptoms in the absence of increased reflux when one is stressed may account for low response rates to traditional treatments. This highlights a need to bridge the gap between psychosomatic research and clinical practice to develop more successful GOR therapies. [Copyright &y& Elsevier]

Summary: Socioeconomic inequalities in morbidity and mortality exist, but the psychobiological pathways that link social status and health are less clear. It has previously been reported that socioeconomic status is inversely associated with the magnitude of the cortisol response to awakening (CAR) in men and women of working age. In the present study, we tested whether larger cortisol responses would be present in an older retired population, and whether the CAR differed between men and women. The extent to which adherence to saliva sample timing also affects the CAR was investigated. Ninety three men and women aged 65–80 years took saliva samples on waking, and then 10, 20, 30 and 60min after waking. Subjective social status was assessed using the ‘ladder’ measure devised by Adler et al. (2000). Non-compliance was defined as a reported delay of 10min or more between waking and taking the first saliva sample. Cortisol levels on waking were significantly higher in the non-compliant individuals, and the CAR was blunted compared with that of compliant participants. With non-compliant participants eliminated from the analyses, we found that low social status was associated with a larger CAR after adjusting for gender, waist/hip ratio, body mass index, smoking, time of waking, chronic illness, prescription medication, education and financial strain. No association was found between CAR and education or financial strain. Women also had significantly larger CARs, independent of socioeconomic position. The results highlight the importance of controlling for non-compliance and are consistent with the notion that higher socioeconomic position protects against stress-related activation of psychobiological pathways which may contribute to variation in disease risk evident in old age. [Copyright &y& Elsevier]

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of respiratory-related morbidity and mortality. Inhaled steroids are frequently used in patients with moderate to severe disease and may lead to adrenal suppression. OBJECTIVES: The aim of this study was to compare the effect of inhaled budesonide/formoterol with inhaled fluticasone/salmeterol in severe COPD. METHODS: It was a prospective open-label crossover study of 22 patients. Adrenal suppression was measured by overnight urinary cortisol/creatinine ratio. The measurements were taken while patients were on either combination for at least 4 weeks. RESULTS: A total of 12 patients completed the study. The mean age was 64 years (8 males, 4 females). The mean FEV1 was 1 L (range, 0.5-1.8). There was no significant difference in adrenal suppression measured by overnight urinary cortisol/creatinine ratio (budesonide 5.2 ± 4.3, fluticasone 4.7 ± 3.1; 95% CI -2.2 to 1.2; P = 0.52) and urinary cortisol concentration (budesonide 51 ± 53, fluticasone 43 ± 31 [nmol/l]; 95% CI -35 to 20; P = 0.56). CONCLUSION: Inhaled budesonide and fluticasone have no significantly different effect on adrenal function in moderate to severe COPD. The adverse event profile of high-dose inhaled steroids should not influence the choice of medication. [ABSTRACT FROM AUTHOR]

Abstract: Acute mental stress tests have helped to clarify the pathways through which psychosocial factors are linked to disease risk. This methodology is now being used to investigate potentially protective psychosocial factors. We investigated whether global self-esteem might buffer cardiovascular and inflammatory responses to acute stress. One hundred and one students completed the Rosenberg Self-Esteem Scale. Heart rate and heart rate variability (HRV) were recorded for 5min periods at baseline, during two mental stress tasks, (a speech and a color-word task) and 10, 25 and 40min into a recovery period. Plasma levels of tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra) were assessed at baseline, immediately post-stress and after 45min recovery. Repeated measures analysis of variance demonstrated that heart rate levels were lower across all time points in those with high self-esteem, although heart rate reactivity to stress was not related to self-esteem. There were no differences in baseline HRV, TNF-α, IL-6 or IL-1Ra. Multiple linear regressions revealed that greater self-esteem was associated with a smaller reduction in heart rate variability during the speech task, but not the color-word task. Greater self-esteem was associated with smaller TNF-α and IL-1Ra responses immediately following acute stress and smaller IL-1Ra responses at 45min post-stress. In conclusion, global self-esteem is associated with lower heart rate and attenuated HRV and inflammatory responses to acute stress. These responses could be processes through which self-esteem protects against the development of disease. [Copyright &y& Elsevier]

Introduction: Acute exacerbations of COPD (AE-COPD) are a leading cause of health service utilisation and are associated with morbidity and mortality. Identifying the prodrome of AE-COPD by monitoring symptoms and physiological parameters (telemonitoring) has proven disappointing and false alerts limit clinical utility. We report objective monitoring of cough counts around AE-COPD and the performance of a novel alert system identifying meaningful change in cough frequency. Methods: This prospective longitudinal study of cough monitoring included chronic obstructive pulmonary disease (COPD) patients experienced in telemonitoring that had two or more AE-COPD in the past year. Participants underwent cough monitoring and completed a daily questionnaire for 90 days. The automated system identified deteriorating trends in cough and this was compared with alerts generated by an established telemonitoring questionnaire. Results: 28 patients [median age 66 (range 46–86), mean FEV-1% predicted 36% (SD 18%)] completed the study and had a total of 58 exacerbations (43 moderate and 15 severe). Alerts based on cough monitoring were generated mean 3.4 days before 45% of AE-COPD with one false alert every 100 days. In contrast, questionnaire-based alerts occurred in the prodrome of 88% of AE-COPD with one false alert every 10 days. Conclusion: An alert system based on cough frequency alone predicted 45% AE-COPD; the low false alert rate with cough monitoring suggests it is a practical and clinically relevant tool. In contrast, the utility of questionnaire-based symptom monitoring is limited by frequent false alerts. [ABSTRACT FROM AUTHOR]

Purpose Cough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent exacerbations and increased mortality. Cough increases during acute exacerbations (AE-COPD), representing a possible metric of clinical deterioration. Conventional cough monitors accurately report cough counts over short time periods. We describe a novel monitoring system which we used to record cough continuously for up to 45 days during AECOPD convalescence. Methods This is a longitudinal, observational study of cough monitoring in AE-COPD patients discharged from a single teaching hospital. Ambient sound was recorded from two sites in the domestic environment and analysed using novel cough classifier software. For comparison, the validated hybrid HACC/LCM cough monitoring system was used on days 1, 5, 20 and 45. Patients were asked to record symptoms daily using diaries. Results Cough monitoring data were available for 16 subjects with a total of 568 monitored days. Daily cough count fell significantly from mean ± SEM 272.7 ± 54.5 on day 1 to 110.9 ± 26.3 on day 9 (p < 0.01) before plateauing. The absolute cough count detected by the continuous monitoring system was significantly lower than detected by the hybrid HACC/LCM system but normalised counts strongly correlated (r = 0.88, p < 0.01) demonstrating an ability to detect trends. Objective cough count and subjective cough scores modestly correlated (r = 0.46). Conclusions Cough frequency declines significantly following AE-COPD and the reducing trend can be detected using continuous ambient sound recording and novel cough classifier software. Objective measurement of cough frequency has the potential to enhance our ability to monitor the clinical state in patients with COPD. [ABSTRACT FROM AUTHOR]