L-theanine, an amino acid contained in green tea leaves, is known to block the binding of L-glutamic acid to glutamate receptors in the brain, and has been considered to cause anti-stress effects by inhibiting cortical neuron excitation. Both L-theanine and caffeine, which green tea contains, have been highlighted for their beneficial effects on cognition and mood.In this study, we investigated the effects of orally administered L-theanine or caffeine on mental task performance and physiological activities under conditions of physical or psychological stress in humans. Fourteen participants each underwent three separate trials, in which they orally took either L-theanine + placebo, caffeine + placebo, or placebo only.The results after the mental tasks showed that L-theanine significantly inhibited the blood-pressure increases in a high-response group, which consisted of participants whose blood pressure increased more than average by a performance of a mental task after placebo intake. Caffeine tended to have a similar but smaller inhibition of the blood-pressure increases caused by the mental tasks. The result of the Profile of Mood States after the mental tasks also showed that L-theanine reduced the Tension-Anxiety scores as compared with placebo intake.The findings above denote that L-theanine not only reduces anxiety but also attenuates the blood-pressure increase in high-stress-response adults. To live a healthier life in so-called high-stress modern society, a growing interest in natural, minimally processed, nutritional, and healthy foods is spreading around the world, and many kinds of functional food ingredients have recently become widely used due to their health benefits. L-theanine became one of those popular items since its multiple roles in the central and autonomic nervous systems received attention. Animal studies have revealed that L-theanine affected dopamine and serotonin concentrations in the brain, underlying its anxiolytic effect,2. SeverCaffeine, another major component of green tea, also has behavioral effects on autonomic nervous activities, and these effects are thought to be the opposite those of L-theanine. Caffeine is a CNS-stimulating drug that acts as an adenosine receptor antagonist in the brain,11. AdenIn this study, we investigated the effects of L-theanine or caffeine on mental task performance and the change in blood pressure caused by mental tasks as psychological stress and by the cold pressor test as physical stress.The experiment conducted in this study was approved by the research ethics committee of the University of Shizuoka, and was carried out in accordance with the Declaration of Helsinki.Sixteen healthy volunteers  participated in the experiment individually at similar times of the day at an interval of 7 days. The data from two women were excluded from the analyses because they were absent on at least 2 experiment days owing to temporary illness. All participants were requested to avoid eating or drinking, except for water, from 3 h before the start of each trial.A cross-over, randomized, placebo-controlled design was used in this study. In total, three separate trials were performed, in which the participants orally took either L-theanine  + placebo, caffeine  + placebo, or placebo only on each day. Dextrin  was used as the placebo. All sample capsules were taken with 250 mL warm water at about 25°C. Treatments were allocated using a Latin square design such that the order of treatments was counterbalanced across participants.Yokogoshi et al. reportedAfter each sample was taken, an auditory oddball target detection task (DT) lasting for 5 min each and an arithmetic mental task (AT) lasting for 10 min each were both imposed twice as the psychological stress load. In the DT, participants were required to click the left button of a computer mouse as quickly as possible to target stimuli  that occur infrequently and irregularly within a series of standard stimuli . The AT required participants to add two numbers (each from 1 to 9) that were being displayed on a PC monitor and to enter the answer through the keyboard quickly and accurately. The number and accuracy of the answers to the second AT, which was taken from 26 min to 36 min after each sample intake, were used for data analysis.A cold pressor test (CPT) was taken to establish physical acute stress. ParticiThe Profile of Mood States (POMS) and the visual analogue scales (VAS) for subjective ratings on mood state were also completed before the intake as a basic control and after all of the mental tasks were finished.The short version of POMS was used to assess distinct affective mood states. POMS is a popular tool that is widely used among psychologists and scientists in many fields. Six identifiable mood or affective states can be measured and were used for analysis in this study: Tension-Anxiety (T-A), Depression-Dejection (D), Anger-Hostility (A-H), Vigor-Activity (V), Fatigue-Inertia (F), and Confusion-Bewilderment (C).VAS comprised five scales including feelings of fatigue, relaxation, arousal, pressure, and tension. At the end of each trial, the subjects used the scales to rate their painful feelings about accomplishing the CPT and their feelings of annoyance about DT and AT.Arterial pressure in each participant’s left thumb was recorded continuously by Finometer Pro . Simultaneously, skin temperature of the back of the left hand was recorded using a BioAmplifier . The sampling rate was 200 Hz. As baseline data, both the blood pressure and skin temperature were measured for 1 min before the intake. Measurement after mental tasks (AMT) was also made for 1 min at 44 min after the intake of each sample, followed by measurement for 4 min after CPT was started.Baseline data were calculated by averaging the 1 min data before each intake. Differences in blood pressure and skin temperature from the baseline were calculated using the mean value of every 10-s epoch for the above measurements after intake. The first 10-s epoch of the AMT was described as AMT1, and the second, third, fourth, fifth, and sixth 10-s epochs were described as AMT2, AMT3, AMT4, AMT5, and AMT6, respectively. Similarly, CPT1 to CPT6 for the CPT epochs, and RP1 to RP18 for epochs during the 3-min recovering period after the 1 min CPT were named respectively and used for the analysis.Figure Data were analyzed using IBM SPSS Statistics version 19. Prior to the primary statistical analysis, separate, one-way, repeated measures ANOVAs of the baseline data were conducted to ascertain any chance baseline differences across study days prior to the treatments.L-theanine reduced blood pressure in spontaneously hypertensive rats but not in rats with normal blood pressure,7. Thus post hoc test was applied to data groups with significant main effect (P <0.05). Differences in POMS and VAS scores were analyzed using the nonparametric Friedman test to detect differences in treatments. The Wilcoxon signed rank test was further carried out to evaluate the changes among treatments.Differences in blood pressure and skin temperature from the basic control were calculated and used for a repeated-measures ANOVA with group (high-response group and low- response group), treatment , and epoch . Repeated-measures ANOVA with group and treatment was also applied to the task performance data. A Tukey’s honestly significant difference (HSD) P=0.049). The high-response group revealed main effects of treatment significantly at AMT4, AMT5, and AMT6 and showed a trend at AMT3 =6.958, 5.500, 7.195, and 2.994, P=0.010, 0.020, 0.009, 0.088). As shown in Figure P=0.082), and showed a significant effect of lower value in the AMT4, AMT5, and AMT6 periods compared with that of the placebo intake condition . Caffeine intake showed a trend of lower systolic blood pressure than the placebo condition only at AMT4, AMT5, and AMT6 .Changes in systolic blood pressure and diastolic blood pressure are summarized in Table t AMT3  and of group =3.361, P=0.092). In the high-response group, treatment affected diastolic blood pressure at AMT4 and AMT6 =7.932, 4.300, P=0.006, 0.039), and lower values were obtained by L-theanine  or caffeine intake  than in the placebo condition. Diastolic blood pressure did not differ significantly among the treatments in the other periodsDiastolic blood pressure in the AMT period revealed trends for the main effect of treatment =2.577, No treatment effect was found in the low-response group in any of the periods of the blood pressure measurements.Skin temperature was not affected by the different sample intakes in each group or two groups together in this study (data not shown).2=6.000, 6.048, P=0.050, 0.049), and L-theanine intake decreased T-A score below that in the placebo condition (P=0.004).Figure No difference was obtained among treatments in each group or two groups together for VAS assessments.P=0.054), and participants answered more questions after caffeine intake than after placebo intake (P=0.052). There was no effect on the accuracy of the answers.There was no interaction effect between group and treatment. Over two groups together, treatment tended to affect the number of answers in AT =3.261, Oral administration of L-theanine significantly changed both systolic and diastolic blood pressures in the high-response group during the latter part of AMT compared with the placebo condition. These results demonstrated the possibility that L-theanine can attenuate blood pressure elevation induced by mental tasks. This finding agreed with the blood pressure-reducing effect of L-theanine intake reported in another study, in which theanine inhibited the blood-pressure increase resulting from caffeine intake. The AMTStress may not directly cause hypertension, but it can lead to repeated blood pressure elevations, which can eventually lead to hypertension. With thContrary to our hypothesis, caffeine also tended to inhibit blood-pressure elevation in this study, and it did not show opposite effects to L-theanine on blood pressure raised by psychological stress. Suleman and Siddiqui (1997 to 2004) suggested that caffeine raised blood pressure during stress by elevating the resting baseline from which the response was measured and not by potentiating the acute blood pressure stress response. The psyOn the other hand, neither L-theanine nor caffeine decreased the rise in blood pressure caused by CPT compared with the placebo. This might be attributable to the difference in the mechanism between blood pressure elevation by psychological stress and that by the physical stress of pain. Further studies are needed to confirm this and to investigate how L-theanine or caffeine influences the autonomic nervous system responses under other kinds of physical stress.At last, due to the limitation on the amount of female participants in this study, the possible effects of their menstrual period are difficult to be discussed this time. Thus, there is a possibility that the results might be different if the number of participants is large enough to sort them into four groups: two male groups (the high- and the low-response groups) and two female groups . We would like to confirm this with larger numbers of both male and female participants in future.Our results suggested that L-theanine not only reduces anxiety but also attenuates the rise in blood pressure in high-stress-response adults. In addition, neither L-theanine nor caffeine showed any effect on decreasing the rise in blood pressure caused by strong physical stress, such as the CPT used in this study.A-H: Anger-hostility; AMT: Measurement after mental tasks; ANOVA: Analysis of variance; AT: Arithmetic mental task; C: Confusion-bewilderment; CPT: Cold pressor test; D: Depression-dejection; DT: Auditory oddball target detection task; F: Fatigue-inertia; HSD: Tukey’s honestly significant difference; POMS: Profile of Mood States; T-A: Tension-anxiety; V: Vigor-activity; VAS: Visual analogue scales.The authors declare that they have no competing interests.AY conceived and designed the study, performed the experiments and the statistical analysis, and drafted the manuscript. MM and SM helped to carry out the experiments and to perform data analysis. HY conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors have read and approved the final manuscript.


Patients with chronic obstructive pulmonary disease (COPD) often have organ dysfunction and resulting poor quality of life; however, in China little information is available regarding factors that affect their health. Here, the relationship between risk factors, activities and psychological disorders and health of patients with COPD in rural areas of Xuzhou, China was assessed.A cross-sectional study of 7597 COPD patients randomly selected by place of residence from 24,641 COPD patients who had been identified by screening of the 1.10 million health records of all residents of the target area was carried out to evaluate the relationships between risk factors, activities, psychological disorders and the ADO index . The participants were assessed by spirometry and by administering a newly designed face-to-face questionnaire, which included items on general factors, risk factors, activities and psychological disorders. Correlations between the ADO index and the items addressed by the questionnaire were calculated.P < 0.001). The ADO indices of cooks and non-cooks were 4.0 ± 2.2 and 3.5 ± 1.7, respectively (P < 0.001). The correlation coefficient between self-assessment of health status and ADO index was 0.976 (P < 0.001). Only 5.7% of patients reported no limitation of their daily living activities. The correlation coefficient between daily living activities and ADO index was 0.981 (P < 0.001). Only 5.5% of patients reported no limitation of social activities. The correlation coefficient between social activities and ADO index was 0.989 (P < 0.001), between the assessed anxiety score and ADO index 0.972 (P < 0.001), and between the assessed depression score and ADO index 0.989 (P < 0.001).The mean score of the ADO index was 3.7 ± 1.6. The ADO indices of current smokers, ex-smokers, and non-smokers were 3.9 ± 2.1, 3.7 ± 1.9, and 3.2 ± 1.5, respectively , physical strength, daily living activities, social activities, anxiety and depression. Comprehensive approaches are required for the prevention and treatment of COPD. Smokingividuals . One stuividuals .Recently, it has been recognized that COPD is a multisystem disease . In addiCOPD can cause a wide range of physical dysfunctions. Of the many symptoms of COPD, dyspnea, difficulties in daily living activities, physical mobility (exercise capacity), and anxiety and depression have the most direct impact on health status -14. For Because clinical and patient-reported outcome measures such as dyspnea, exercise capacity, physical activity, exacerbation of symptoms, health status and mortality are an essential part of the clinical assessment of COPD , the objOne limitation of only evaluating health status physiologically and clinically is that these measurements do not address patients’ social life, family and working relationships. These factors are important because they can influence both life quality and disease progression. Hence, health-related quality of life scores have also been used to evaluate the health status of COPD patients and the impact of their disease on them.In the present study, we investigated risk factors, activities, psychological disorders and the general health status of COPD patients to elucidate correlations between daily living activities, risk factors, psychology and health status of patients with COPD. Our study clarifies how the severity of COPD impacts the daily lives of affected individuals.A Basic Public Health Service survey mandating that all residents establish health records within 3 years was conducted in Jiangsu province, China from 2006. Tongshan county, in the Xuzhou city region of Jiangsu province, has 28 townships and 1.14 million inhabitants. From 1.10 million health records from this region screened by the end of 2007, 24,641 cases that fulfilled COPD diagnosis and treatment guidelines criteria were uncovered. Townships were assigned to investigation or not by simple randomization (a coin toss). Our study was conducted in association with the Basic Public Health Service. All selected patients were interviewed in their homes, analyzed for factors related to beliefs, treatments and economic burden that would make them vulnerable to further deterioration in health (18), and asked to undergo spirometry at health stations. This study was carried out over 3 months.1 (forced expiratory volume in one second)/forced vital capacity ratio < 0.7 and prebronchodilator FEV1 of < 80% of predicted value; (iii) registered at a local community health service center for > 6 months; (iv) no uncontrolled comorbidities; and (v) no COPD exacerbations over the preceding 6 weeks.A flow chart describing the patient selection process has previously been published . The folA questionnaire aimed at assessing vulnerability to deterioration in health status was designed based on domestic and foreign literature ,19-21. IThe first quality of life category was self-assessment of physical strength, which was scored by the patients as follows: ‘0’, can be as active as an asymptomatic person without shortness of breath; ‘1’, shortness of breath with day-to-day work; ‘2’, shortness of breath when climbing stairs; ‘3’, shortness of breath with light activity; and ‘4’, shortness of breath when walking one hundred steps.The second category, daily living activities, included 10 items, each scoring from 10 to 40 points as follows: 10 points, no limitation of daily living activities; 11–20 points, limitation of daily living activities; 21–30 points, severe limitation of daily living activities; and 31–40 points, extreme limitation of daily living activities.The third item, social activities, included four items each scoring from 4 to 16 points as follows: 4 points, no effect on social activities; 5–8 points, some effect on social activities; 9–12 points, severe effects on social activities; and 13–16 points, extreme effects on social activities.The fourth category, which dealt with the psychological symptoms of anxiety, included five items, each scoring from 5 to 20 points as follows: 5 points, no anxiety; 6–10 points, mild anxiety; 11–15 points moderate anxiety; and 16–20 points, severe anxiety. A score equal to or greater than 11 points was defined as anxiety.The fifth category, psychological symptoms of depression, included five items, each scoring from 5 to 20 points as follows: 5 points, no depression; 6–10 points, mild depression; 11–15 points, moderate depression; and 16–20 points, severe depression. Patients with scores of 11 or more points were classified as depressed and those with scores of less than 11 points as not depressed.For each of these 25 items there was a choice of four responses defining quantity or frequency of occurrence. The number of points assigned to each response corresponded to the number of the response. For example, response 1 scored one point, response 2 two points and so on. The total possible score was 100 points, higher scores indicating a worse quality of life as follows: 0–24 points, the patient felt very well; 25–49 points, the patient felt well; 50–75 points, the patient felt normal; and 76 points and above, the patient did not feel well. The questionnaire, which was designed by the present authors, has validity and reliability according to a pre-survey of COPD patients (unpublished data).Home interviews were conducted with 8217 COPD patients. General characteristics based on information provided by the patients regarding age, sex, employment status, education, marital status, physical activity, smoking status, family COPD history, and other conditions were recorded.The smoking status of each participant visited was classified as non-smoker, ex-smoker, or current smoker. Cigarette smoking was defined as having smoked at least 100 cigarettes during one's lifetime or having smoked continuously for at least 6 months ; if neitParticipants who were exposed to burning biomass through wood-fired stoves and cooked twice per day for at least 6 months were defined as cooks; otherwise, they were classified as non-cooks.Dyspnea was assessed according to the Medical Research Council (MRC) dyspnea scale, which classifies breathlessness into six grades (0 to 5) according to self-perceived breathlessness during daily activities . The MRCAll patients were encouraged to undergo spirometry at health stations after completing their questionnaires. Spirometry and bronchodilator response tests were carried out by trained professionals according to the standardized guidelines of the American Thoracic Society . Pulmonal (forced expiratory volume in 1 s). The scores range from 0 (best status) to 5 (worst status) for age , 0–3 for MRC score, and 0–2 for FEVl. The points for each component are summed so that the ADO index ranges from 0 to 10 (higher scores indicating greater severity). The ADO index was also translated and validated in our population (unpublished data).The validated ADO index, which is a simple risk index, was used to evaluate COPD severity  and reprχ2 and Fisher exact tests were used to analyze the relationships between qualitative data. Analysis of variance was used for comparison of multiple samples. Questionnaire scores were correlated with the ADO index using correlation analysis. Statistical significance was set at a value of P < 0.05.Data analysis was performed using the Statistical Package for Social Science (SPSS) Version 13.0 software. Quantitative variables are expressed as means  and qualitative variables as frequencies and percentages. The This study was approved by the Ethics Committee of the Xuzhou Center for Disease Control and Prevention and the Regional Ethical Vetting Board, Xuzhou, China. In addition, agreement was received from all of the relevant health centers. Informed consent was obtained from all participants in this study.In this study, 8938 patients who met the criteria were selected to participate. Four hundred and thirty-five patients declined to take part in the survey or left town, and 201 patients died during the course of the study. The questionnaires of all the remaining 8302 patients were administered and returned; of these, 85 patients completed only part of the survey, leaving 8217 surveys that were complete and valid. Six hundred and twenty patients who were < 40 years old were excluded. The remaining 7597 acceptable questionnaires were analyzed; the response rate was 85.0% . The ADO index ranged from 0 to 9 with a mean score of 3.7 ± 1.6.Table P < 0.001; current smoker vs. non-smoker, t = 192.0, P < 0.001; and ex-smoker vs. non-smoker, t = 8.6, P < 0.001.Of the 7597 patients with COPD, 6146 (80.9%) were smokers and of these 3692 were current smokers and the other 2454 patients ex-smokers. The ADO indices of current smokers, ex-smokers, and non-smokers were 3.9 ± 2.1, 3.7 ± 1.9, and 3.2 ± 1.5, respectively. There were significant differences among the three groups: current smoker vs. ex-smoker, t = 64.4, P < 0.001).Of the 7597 patients, 3426 (45.1%) cooked often or daily, and 1139 (33.2%) had been cooking for over 30 years. The ADO indices of cookers and non-cookers were 4.0 ± 2.2 and 3.5 ± 1.7, respectively. There was a significant difference between these two groups . The correlation coefficient between self-assessment of health status and ADO index was 0.976 .Patients’ self-assessed physical strength is shown in Table P < 0.001)  Figure .P < 0.001)  Figure .P < 0.001)   and their ADO index. Patients with COPD are at significantly higher risk of having depressive symptoms and their depression is associated with exacerbations of COPD and increased COPD-related hospitalization ,39. MoreThis study is limited in that we primarily focused on farmers, who have such a poor awareness of COPD that they have difficulty in accurately reporting the symptoms of COPD. Thus, our results in this skewed population may have limited applicability in other parts of China or in other countries.In summary, our study demonstrated that COPD severity is significantly correlated with behavior, physical strength, daily living activities, social activities, anxiety and depression.The authors declare that they have no competing interests.LZ and PL participated in writing the title and abstract, contributing to the writing of the manuscript drafts and reviewing the full text. YN conceptualized the study, participated in its design, title and abstract screening, full text screening, data extraction and analysis, and drafting of the manuscript. PC performed literature searches, participated in title and abstract screening, full text review, and contributed to the manuscript drafts. PZ and JY conceptualized the study; participated in its design, title and abstract screening, full text screening; and contributed to the manuscript drafts. NZ and NC contributed to the conception of the study, participated in the study design, and contributed to the manuscript drafts. HW and JZ were the lead authors of the original review, contributed to the conception of the study, participated in the study design, and contributed to the manuscript drafts. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/627/prepub


Despite the availability of a wide selection of effective antihypertensive treatments and the existence of clear treatment guidelines, many patients with hypertension do not have controlled blood pressure. We conducted a qualitative study to explore beliefs and perceptions regarding hypertension and gain an understanding of barriers to treatment among patients with and without diabetes.Ten focus groups were held for patients with hypertension in three age ranges, with and without diabetes. The topic guides for the groups were: What will determine your future health status? What do you understand by "raised blood pressure"? How should one go about treating raised blood pressure?People with hypertension tend to see hypertension not as a disease but as a risk factor for myocardial infarction or stroke. They do not view it as a continuous, degenerative process of damage to the vascular system, but rather as a binary risk process, within which you can either be a winner (not become ill) or a loser. This makes non-adherence to treatment a gamble with a potential positive outcome. Patients with diabetes are more likely to accept hypertension as a chronic illness with minor impact on their routine, and less important than their diabetes. Most participants overestimated the effect of stress as a causative factor believing that a reduction in levels of stress is the most important treatment modality. Many believe they "know their bodies" and are able to control their blood pressure. Patients without diabetes were most likely to adopt a treatment which is a compromise between their physician's suggestions and their own understanding of hypertension.Patient denial and non-adherence to hypertension treatment is a prevalent phenomenon reflecting a conscious choice made by the patient, based on his knowledge and perceptions regarding the medical condition and its treatment. There is a need to change perception of hypertension from a gamble to a disease process. Changing the message from the existing one of "silent killer" to one that depicts hypertension as a manageable disease process may have the potential to significantly increase adherence rates. Hypertension is a leading cause of cardiovascular morbidity and mortality. In 2006 in the Unites States, hypertension was documented as the primary cause of death in over 56,000 deaths and as a contributing factor in an additional 250,000 deaths out of the 2.4 million deaths reported for that year . HyperteIn a study conducted between September 2005 and March 2006 in 26 countries, overall blood pressure (BP) control rate was 33.6% in men and 30.6% in women (P < 0.0001) and was lower in diabetic as compared with non-diabetic patients . If optiA recent study of 4783 patients who participated in studies whose dosing histories were available through electronic monitoring showed that among patients prescribed once a day antihypertensive drugs, non-persistence is the major problem: half of the patients stopped treatment within a year and 48% admitted to at least one "drug holiday" (not adhering to medications for a short period of time) a year . PatientPossible problems at the health system level include insufficient availability of medical services, cost of medications and poor patient adherence. The focus of this study is on the reasons that patients do not adhere, or adhere only partially to medication and lifestyle regimes.In spite of the fact that hypertension is easy to identify, and that there are a variety of pharmaceutical and non-pharmaceutical  evidence-based treatment options available, we are failing miserably at hypertension control. If we can gain an understanding of why people with hypertension who have been advised what they need to do and provided with prescriptions for inexpensive and readily available medications are not adhering to treatment, we will be able to modify the ways in which we communicate with patients in order to increase adherence. The aim of this study was to gain a deeper understanding of the beliefs, attitudes and coping mechanisms of patients with hypertension. We also aimed to examine the differences between males and females, and between younger and older age groups, and the differences between those who had an additional, more severe chronic disease; diabetes, and those who do not, in regards to hypertension and its treatment. Focus group methodology was chosen in order to generate hypotheses for further research. Better understanding of these perceptions can help both the physicians and the health system to develop effective communication strategies to increase patient adherence to hypertensive treatment.This qualitative study was conducted in a large publicly financed health maintenance organization with 1.9 million members. Membership is open to all sectors in the general population. A computerized medical record is used and complete clinical data have been collected in a central database since 1995. Based on these data, diabetes and hypertension registries have been developed. These are built using algorithms that identify members who have the disease, and are continually validated by physicians. There are over 250,000 people in the hypertension registry, of which approximately 60,000 are also in the diabetes registry. This study was approved by our institutional review board. Informed consent was not required.Participants in the patient focus-groups were randomly selected from the hypertension registry. Randomization was stratified by age, gender and diabetes status, as these factors were expected to influence patient's attitudes regarding hypertension and their mode of management. We produced a list of 150 potential participants, and patients were contacted by phone and asked to participate in focus groups on a health issue. Patients were contacted until the required number was recruited. We did not ask the reasons for non participation. Participants were not aware of the topic of the focus group. They were invited to the focus groups by an external expert provider, and were compensated for their time. This was designed to achieve diverse opinions organized by age and gender. The study design was based on several assumptions: That men and women would discuss health issues more freely in separate groups, that attitudes towards hypertension would differ between younger and older patients, and that those who have an additional chronic disease, which is perceived as more severe, may have different attitudes towards chronic disease in general, and hypertension in particular. We therefore conducted separate focus groups were for men and women with hypertension in three age ranges: 41-50, 51-60, 61-70 years , and for men and women with hypertension and diabetes in two age ranges: 51-60, 61-70 years . A lower cutoff age of 40 was selected as the majority of patients in the hypertension registry are aged 40 and over, and we felt that we should address the issue in a relatively homogenous group, as it may be that treating a much younger hypertensive is a totally different issue.Topic guides for the patient groups were developed by a multidisciplinary team which consisted of a health promotion expert, primary care physicians, nurses and social psychologists. The topic guide for the patient's focus group covered the following domains:1) What will determine your future health status .2) What do you understand by "raised blood pressure".3) How should one go about treating raised blood pressure? .These were facilitated by one of two psychologists. The male psychologist ran the male groups and the female psychologist the other groups. Each session included 7-10 participants and lasted 1.5-2 hours. Sessions began with brief introductions followed by a short discussion on health in general, and how participants view their own health. Hypertension was introduced as the subject of the study using open questions included in the topic guide. New topics were introduced after everyone wishing to express their opinions had finished doing so. Having obtained consent discussions were audio taped and transcribed verbatim, in addition to documentation of the discussion by the psychologists during the sessions. The venue selected for the sessions was not identified with any health organization. Participants were not informed at any point who is conducting the study, what the aim of the study is, or how participants were selected.The same or following day the written notes were typed and compared with the audiotape. An overview grid was constructed which provided a descriptive summary with topic headings on one axis and focus group identifiers on the other . The strWe conducted ten focus groups, with 86 patients: 42 men and 44 women Of these, 37 participants had both hypertension and diabetes. Most of the participants initially denied having "hypertension", and when coaxed, all agreed that they had a "blood pressure problem" or that occasionally their blood pressure was higher than normal. The first issue that was brought up was the issue of health in general, and future health in particular. The word/phrase codes that were dominant regarding the question of future health status were "stress" and "lifestyle". Participants did not, in general, bring up the issue of chronic illness in general, or diabetes in particular. The issue of hypertension was not mentioned by any participant. Regarding the question of "What do you understand by raised blood pressure?" the highest ranking code by far was "stress". Codes relating to chance/fate were also dominant in this part of the discussion as were health outcomes such as "stroke heart attack". The dominant codes that were recorded regarding the treatment question were "medications", "stress". Side effects came low in the ranking. The focus groups were divided according to gender because our assumption was that the medications' effect on sexual function would be an important theme. This turned out not to be the case."It is a disease like any other disease and it has treatment... pills and diet"Patients with diabetes regard hypertension as just another health problem: It is a silent disease called 'the silent killer'... it is very dangerous mainly since you do not feel it and it causes severe damage... it kills". "With hypertension you feel healthy... there are no ill effects... you take a pill and you can forget. In diabetes it is a different story. It's a different feeling and demands my full attention... you can't forget it."All patient groups expressed the view that hypertension is less of a disease and more of a risk factor because of its potential for dramatic events: ""It is a limitation but not a disease because you feel healthy"Most patients in both groups avoid calling hypertension a disease, because of its asymptomatic nature. However patients with diabetes who already have a chronic disease label, are willing to accept that hypertension is a chronic condition. Patients without diabetes generally found it difficult to accept that hypertension is a chronic condition and see it as a physiological reaction to stress."I see it as a problem and not a disease... ""Blood pressure is a control light of the body.... When it is high it is a sign that something is wrong and you need to treat it"A recurrent theme in the discussions was that the patients attribute personal stress as a significant cause of their elevated blood pressure and as a result they view stress reduction as an effective way to control it."I learned not to get angry and not have my feelings hurt but when I get angry even about something small I feel how my blood pressure rises"The discussions exposed gaps in the patient understanding of the hypertension, its possible consequences and the factors affecting it. This was clearly expressed by the diabetic patients who reported that the explanation they received regarding diabetes was much more comprehensive than the explanation received regarding hypertension. Both groups felt that hypertension does not cause immediate damage, and is in fact similar to a time bomb, which can either explode or not. Diabetic patients specifically stated that while diabetes is an insidious disease that causes immediate damage, hypertension is more like a risk factor for future events.Patients presented a few modes of coping with hypertension, depending on their individualized perceptions regarding the disease and its treatments:A minority of the participants followed a combination of adherence to medications and "drastic" lifestyle modificationsThis mode reflects a compromise between the 'ideal treatment' and 'palatable' treatment which is reached by balancing the perceived importance of the treatment and the degree of disruption to their desired lifestyle that this treatment involves. These patients found it easier to comply with taking pills than to change their diet, quit smoking or exercise."... so I take pills, sometimes eat healthy, swim a little... I am not willing to invest everything in health, hypertension will not disrupt my lifestyle". It seems that even the random occurrences of forgetting to take a pill or to renew the prescription on time comes from a decision to not to put too much thought and effort into the treatment."I learned to control stress and according to that I lower the dosage of my pills or increase it". Out of the treatment modalities, they tend to prefer lifestyle modifications over medications which they often perceive as a mechanistic and impersonal approach.Self-adjustment: These patients modulate their doctor's orders. They believe they "know their bodies" and hence have a better ability to better control their blood pressure. They tend to overestimate the effect stress carries on blood pressure: No treatment: There are patients who not treat their blood pressure, either because they deny having elevated blood pressure or they deny the need to treat it. By denying the disease they avoid facing the anxiety that is associated with the diagnosis."If there is high blood pressure, I do not want to know... thinking of that makes me anxious... I am healthy because I feel healthy""The doctor found that I have blood pressure. The pill caused heartburn so I stopped taking it."There are patients who stopped taking anti-hypertensive medication because they view hypertension as a temporary state and not as a lifetime diagnosis. Some stopped their treatment because they had an adverse reaction and for them that was the only negative manifestation of their blood pressure: Hypertension is a small issue for me. I take pills because they are part of my life today but no more than that. Most of my energy is invested in diabetes." Others dealt with both conditions using a holistic "Full adherence" approach: " The diabetes forces me... it screams at me and in order to deal with it I need to be strict. So there is no separation of hypertension from diabetes... you live a more healthy life". Another patient stated: " If you want to live a long life you need to be active, live a strictly healthy lifestyle and deal with all disease. So that diabetes, cholesterol and hypertension are all in the same basket."Patients who also had diabetes described two different coping strategies for dealing with their hypertension. Some saw hypertension as a separate and less important part of their routine and represented by the "compromise group": "Table Listening to patients as "experts" is essential in addressing barriers to adherence with medical advice . In thisThe focus group discussions showed that in general most patients are aware of the recommendations to combine medical treatment with lifestyle modification. However, only a minority of them adhered to these recommendations. More commonly, patients choose to combine only some of the recommended treatment elements  and only to a certain extent. Patients' selection of a mode of management is influenced on the one hand by their perceptions regarding the dangers of hypertension and the necessity of treatment and by their personal experiences and beliefs about the various treatment modalities. The lay perception of stress as a dominant cause of hypertension can be found in many cultures and supports the tendency of these patients to abandon their pharmacotherapy and adopt less established treatment modalities such as meditation ,22, or, At the other end of the spectrum there are patients who focus on adhering to medications, and view it as a sufficiently appropriate substitute to the more demanding and time consuming recommended lifestyle changes.Finding better ways of communicating with patients regarding hypertension treatment, and particularly in relation to lifestyle changes is essential ,24.A possible strategy to improve hypertension management is public education both for the general population and people with hypertension . InsightStrengths and limitations: Focus group study design is used to generate a hypothesis. These focus groups enabled us to gain a deeper understanding of patients' perceptions of the term "hypertension" and of possible sources of miscommunication in the clinical setting, due to the open discussions that occurred in the groups. Holding separate focus groups for patients of different ages and genders can expose a wide range of views that are not usually expressed in the routine patient-doctor encounter. One of the major limitations of the study is that participants in the focus groups do not form a representative sample of the population. Our research design did not allow us to identify ethnic or socioeconomic differences between those who agreed to participate in the focus groups and those that declined. More importantly the mere participation in focus groups select a population with higher health awareness so it is expected that the group discussions gave an underestimated picture of patients' non adherence. It may be that the authors (ADH and LV) who were present during the discussions which formulated the topic guides may have unduly influenced their formulation.This study suggests that patients as a rule do not see hypertension as a chronic disease requiring adherence to treatment recommendations, but rather as a health condition mainly related to stress, that may actually have no consequences if left untreated. Although we found little difference between age and gender groups, patients with diabetes have a different view of hypertension than those who do not. Patient denial and non-adherence with hypertension treatment seems to be a prevalent phenomenon reflecting a conscious active choice made by the patient, based on his knowledge and perceptions regarding the medical condition and its treatment. Specifically referring to hypertension as an illness, highlighting the chronic damage caused by exposure to high values of blood pressure and providing patients with information about the importance of the various treatment modalities in a way that would address their individual reservations may improve control of both diabetes and hypertension.The authors declare that they have no competing interests.The study was conceived by ADH, VS and LV. ADH and LV ran the focus groups and edited the manuscript. IZ wrote the manuscript. VS and GH helped with the analysis, reviewed and edited the manuscript. All authors read and approved the final manuscript.There was no external funding for this research.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/13/24/prepub


Microalbuminuria is a marker of cardiovascular events. This study investigated the prevalence of microalbuminuria in the general population and the factors that can affect urinary excretion of albumin.Apparently healthy subjects who participated in a health checkup at our hospital were enrolled in this study  Urine samples were collected for the measurement of albumin concentrations, which were expressed as the ratio of urinary albumin to creatinine concentrations (UACR [mg/g Cr]). Individual salt intake was assessed by estimating the 24-hour urinary salt excretion of subjects.P < 0.0001).The mean blood pressure was 124 ± 15/76 ± 10 mmHg and 31.6%, 7.4%, and 44.1% of subjects had hypertension, diabetes mellitus, and dyslipidemia, respectively. Urinary albumin was detected in 7265 subjects . In subjects with detectable albuminuria, UACR was independently correlated with age, systolic blood pressure, serum creatinine, fasting plasma glucose, and salt intake after adjustment for possible factors (The prevalence of microalbuminuria was found to be 4.6% in the general population. The urinary excretion of albumin was closely associated with blood pressure and salt intake. These data indicated the importance of salt restriction for the prevention of cardiovascular disease and end-stage renal disease. Recent studies have established that microalbuminuria is an important cardiovascular risk factor ,2. CliniUrinary albumin excretion is also a predictor of mortality from all causes in the general population . The excThe study was performed in accordance with the principles of the Declaration of Helsinki, and the Ethics Committee of Enshu Hospital approved the study protocol. Written informed consent was obtained from all subjects prior to the start of the study.A total of 8155 persons who visited our hospital for a yearly physical checkup from April 2010 to March 2011 were screened for eligibility to be included in the present study. Subjects with incomplete data were excluded and the rest of the 7963 subjects were finally included in the present study. In addition to the routine examination of subjects in our health checkup program , urine was sampled for the measurement of urinary albumin in the morning after an overnight fast. Cross-sectional analyses were performed in order to investigate the prevalence of albuminuria and factors closely related to the urinary excretion of albumin.Urinary albumin concentrations were measured by a turbidimetric immunoassay  and are expressed as the ratio of concentrations of urinary albumin to urinary creatinine (UACR [mg/g Cr]). UACR was recorded as 0 mg/g Cr in those subjects with a urinary albumin concentration below the analytical limit. Microalbuminuria was defined according to the recommendation of the American Diabetes Association and the National Kidney Foundation (300 > UACR ≥ 30 mg/g Cr) ,10. IndiBlood pressure was measured by a standard sphygmomanometer, after subjects were seated in a chair for 5 min with their backs supported as well as their arms supported at heart level. Proper cuff size was determined based on arm circumference. Three consecutive blood pressure measurements were taken, with two minutes between each measurement, and the mean of the second and third measurements was recorded as the blood pressure. Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive medications. In this study, diabetes mellitus was defined as fasting plasma glucose ≥ 126 mg/dL or the use of anti-diabetic medications and dyslipidemia was defined as low-density lipoprotein-cholesterol (LDL-cholesterol) ≥140 mg/dL, high-density lipoprotein-cholesterol (HDL-cholesterol) < 40 mg/dL, triglyceride ≥ 150 mg/dL, or the use of antidyslipidemic medications [t tests. A corrected chi-square test was used for comparisons between categorical data. Subjects were divided into six groups . Data in the text and the tables were expressed as mean ± standard deviation. Because the distribution of UACR was skewed rightward, these values were expressed as median ± absolute deviation and were log-transformed before statistical analysis. Differences between two groups were compared by unpaired Student’s s Figure  accordin2. Urinary albumin was detected in most subjects . More than half of the subjects (53.2%), had minimal excretion levels of albumin (UACR < 5 mg/g Cr) and about 4.6% of subjects showed microalbuminuria (300 > UACR ≥ 30mg/g Cr) , male gender , SBP , serum creatinine , salt intake , smoking , ECG voltage , and use of inhibitors of the renin-angiotensin system  independently correlated with UACR after adjustment for waist circumference, uric acid, fasting plasma glucose, and dyslipidemia . In line with these observations, SBP, DBP, fasting plasma glucose, and salt intake were observed to increase with increasing urinary excretion of albumin in analyses that included all subjects . Using univariate regression analysis, UACR was correlated with age, male gender, waist circumference, BMI, SBP, serum creatinine, uric acid, fasting plasma glucose, dyslipidemia, salt intake, ECG voltage, and use of inhibitors of the renin-angiotensin system (Table This study demonstrates that the majority of the Japanese general population has detectable albuminuria but only 4.6% present with abnormal microalbuminuria. There is a close association between urinary excretion of albumin, even in normal range, and cardiovascular morbidity and mortality. This association suggests that an approach of reducing urinary albumin could be used to prevent cardiovascular disease, which is a leading cause of death. Lifestyle modification is one possible mechanism to improve urinary excretion of albumin because both salt intake and SBP independently correlate with urinary albumin.Several studies have reported on the prevalence of microalbuminuria in the general population including 7% of subjects in the PREVEND study, and 3.8% of subjects in the INTERMAP study. The prevalence of subjects with microalbuminuria in those studies are similar to the present study ,14. In cThe beneficial effects of inhibitors of the renin-angiotensin system on urinary albumin have already been established ,18-20. HAlthough the present study does not establish a causal relationship between the urinary excretion of albumin with other factors, several mechanisms underlying the observed relationship can be proposed. The kidney is an important target organ of hypertension and the relationship between increased blood pressure and albuminuria has been established. Excess salt intake produces an excess volume load and, thereby, causes an increase in intra-glomerular pressure and glomerular hyperfiltration, which results in urinary excretion of albumin. An increase in blood pressure is also involved in the mechanism underlying salt-induced albuminuria. An elevated fasting plasma glucose level indicates the presence of insulin resistance that promotes sodium re-absorption and may increase the volume load. Alternatively, endothelial dysfunction may be involved in the mechanism underlying the observed relationship between urinary excretion of albumin and other factors -23. ManyThe interpretation of the present study is limited by the following conditions. Firstly, the urinary excretion of albumin was measured only once. Secondly, study subjects were participants in our health checkup program, which could introduce a selection bias. Thirdly, clinical significance of albuminuria as a cardiovascular risk was not assessed in the present study. Finally, a causal relationship cannot be established because this was a cross-sectional study. Longitudinal follow-up studies are necessary to draw a definite conclusion.The majority of the general population has detectable urinary excretion of albumin and 4.6% show microalbuminuria. The urinary excretion of albumin was shown to be closely associated with salt intake as well as blood pressure. These data indicate the importance of dietary salt restriction for the prevention of cardiovascular disease as well as end-stage renal disease.UACR: The ratio of urinary albumin to creatinine concentrations; Cr: Creatinine; ECG: Electrocardiogram; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; LDL-cholesterol: Low-density lipoprotein-cholesterol; HDL-cholesterol: High-density lipoprotein-cholesterol.The authors declare that they have no competing interests.ST analyzed data and mainly drafted the manuscript. HT participated in the design of the study, substantially contributed to the acquisition of data. YD substantially designed the study, substantially contributed to the interpretation of the data, and critically revised the manuscript. GK participated in the design of the study and contributed to the interpretation of the data. All the authors have read and approved the final manuscript.


Leukotriene receptor antagonists (LTRAs) are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. We hypothesized that LTRAs may accelerate lung function recovery when given in an acute exacerbation.A randomized, double blind, placebo-controlled trial was conducted at the Aga Khan University Hospital to assess the efficacy of oral montelukast on patients of 16 years of age and above who were hospitalized with acute asthma exacerbation. The patients were given either montelukast or placebo along with standard therapy throughout the hospital stay for acute asthma. Improvements in lung function and duration of hospital stay were monitored.1 at discharge (p = 0.29) or length of hospital stay (p = 0.90) between the two groups. No serious adverse effects were noted during the course of the study.100 patients were randomized; their mean age was 52 years (SD +/− 18.50). The majority were females (79%) and non-smokers (89%). The mean hospital stay was 3.70 ± 1.93 days with 80% of patients discharged in 3 days. There was no significant difference in clinical symptoms, PEF over the course of hospital stay (p = 0.20 at day 2 and p = 0.47 at day 3) and discharge (p = 0.15), FEVOur study suggests that there is no benefit of addition of oral montelukast over conventional treatment in the management of acute asthma attack.375-Med/ERC-04Trial registration number: Acute asthma accounts for nearly 2 million emergency department visits and 500,000 admissions each year in the US, frequently ranking as a major contributor to time away from work and decreased productivity. Its incAsthma is associated with chronic airway inflammation with recruitment of a number of inflammatory cells including T-cells, mast cells and eosinophils. The macrophages, eosinophils and mast cells in particular have the capacity to synthesize cysteinyl leukotrienes. The interaction of these mediators with the Type 1 cysteinyl leukotriene (CysLT) receptors, located on inflammatory cells and the structural cells of the airways, is implicated in inflammatory cell infiltration, initiation of bronchial smooth muscle contraction, mucus secretion and increased vascular permeability that ultimately leads to airway narrowing.1) within 15 minutes of administration in chronic asthma with its effects lasting for a period of at least 24 hours[Montelukast is the most commonly used cysteinyl leukotrienes receptor 1 (CysLT-1) antagonist. It has been shown to improve symptoms and lung function , montelukast sodium would improve airway obstruction and clinical outcomes in acute asthma exacerbation and would subsequently decrease the duration of hospital stay.The patients were identified from the Aga Khan University Hospital (AKUH), located in Karachi, the largest metropolitan city of Pakistan. This is a 650-bed, internationally accredited tertiary care hospital that caters to the needs of a large multi-ethnic urban population. The hospital has a dedicated emergency room (ER) and a 5-bed respiratory special care unit staffed by a team of physicians and nurses trained in the management of respiratory disorders.1 < 70% predicted or PEF < 300 L/min after 30 minutes of receiving initial treatment in the ER, respiratory rate > 24 breaths/min and no improvement in symptoms such as shortness of breath or wheezing.All patients of age 16 and above who presented to the AKUH with acute asthma exacerbation were screened for enrollment in the study. Informed consent was obtained. The eligibility criteria included a diagnosis of acute asthma exacerbation that required hospitalization as defined by the Global Initiative for National Asthma (GINA) Guidelines. The cri1 > 70% predicted or PEF > 300 L/min, a history of tobacco use of >10 years, concomitant therapy with systemic corticosteroids or leukotriene modifiers at any time in the past 4 weeks at the time of admission, any concurrent acute medical condition like myocardial infarction, congestive cardiac failure, diabetic ketoacidosis or shock, acute respiratory failure requiring mechanical ventilation, and improvement in symptoms after being recruited into the study warranting discharge from the emergency department. Patients who were unwilling to consent were also excluded. Flow chart of the study is shown in Figure The patients with the following conditions were excluded from the study; age <15 years, pregnancy, FEVThis was a randomized, double-blind, placebo controlled parallel group drug trial conducted over a period of two years from February 2006 to February 2008. All patients presenting either to the emergency department or outpatient clinics of the AKUH requiring hospitalization with acute asthma exacerbation were screened for inclusion in the study. The study was approved by the Ethical Review Committee (ERC) of the Aga Khan University (375-Med/ERC-04). A written informed consent was obtained before enrollment and findings were shared with subjects interested in the study outcome on clinic follow-up. The patients underwent a baseline spirometry and peak expiratory flow (PEF) testing soon after enrollment. A brief questionnaire was used to obtain information about the duration, severity and treatment of asthma.1. The PiKo-1 test was repeated three times. The primary aim of utilizing the software was to facilitate both patient and investigator use. Each test was performed within three minutes of the previous one. The spirometry was done on admission and discharge. Other investigations like chest radiographs and arterial blood gases (ABG’s) were done if deemed necessary by the admitting team.The bedside spirometry was done using PiKo-1  software which measures the PEF and FEVA group sample size of 50 patients in treatment (Montelukast) and 50 in placebo group achieved 80% power to detect a mean difference of 0.3 liters between the two groups with a mean of 2.2 and stanThe AKUH pharmacy played a pivotal role in the randomization of patients. The trial coordinator at the AKUH pharmacy was the key person to maintain randomization and blinding and was the only one to know the treatment status of the patient. Allocation numbers were generated and assigned to each patient found eligible to be enrolled in the study. Patients were distributed to each arm based on the allocated code. Neither the evaluators, nor the on-call admitting team were made aware of the actual treatment allocations.The patients were randomly allocated to one of the two study arms; patients in arm-1 received standard therapy and oral montelukast sodium (10 mg once daily) and those in arm-2 received standard therapy along with a placebo.All patients with acute asthma underwent clinical assessment for severity of attack and received standard therapy with oxygen and inhaled bronchodilators via jet nebulizer with salbutamol 2.5 mg and ipratropium bromide 500 mcg mixed with 2 cc of normal saline every 15 to 30 minutes. The duration of the high dose bronchodilator therapy was variable (1–4 hours) and subsequently tapered to every 6 hours depending on the symptomatic response to therapy. A dose of systemic corticosteroids in the form of hydrocortisone 200 mg IV was administered in the ER followed by 100 mg every 6 hours. The steroids were subsequently changed to oral prednisolone 0.5 mg/kg/day for 7 days. The trial design followed in the ER is shown in Figure Additional asthma therapies with aminophylline and magnesium sulphate were given on the discretion of the admitting team when asthma exacerbation was not responding to initial standard therapy after hospitalization. Antibiotics were given only if there was clinical or radiological suspicion of bacterial infection like fever >101 °F, purulent sputum production or clinical or radiological signs of consolidation. The use of antibiotic was not assessed in our study.Patients in the treatment arm 1 received oral montelukast 10 mg first dose in the ER followed by 10 mg oral dose once a day in evening for the duration of stay in the hospital. The medication was started in the ER as soon as standard therapy was administered, informed consent was obtained and a decision was made for hospitalization.The placebo was of the same appearance (color and size) and taste as the trial medication; it was prepared by the Hilton Pharma after being approved by Ministry of Health (MoH) Pakistan. The first dose was given in the ER followed by once daily for a period of duration of stay in the hospital. The trial coordinator in AKUH pharmacy managed the storage and distribution of placebo. The serial peak expiratory flow (PEF) monitoring was done; a baseline PEF value was obtained on enrolment, then at 30, 60 and 90 minutes from the baseline value, followed by every 12 hours daily until discharge. A minimum of 3 readings were obtained each time before administration of bronchodilator and the best of 3 was taken as the final value.1 over the course of hospital stay and discharge and b) duration of hospital stay.The primary outcomes of the study were a) improvement in lung function measured as PEF and FEVSecondary outcome included development of complications such as respiratory failure, cardiac arrest and/or death.For descriptive analysis mean ± standard deviation are reported for continuous variables, and number (%) for categorical variables. In univariate analyses, differences in proportions for type of treatment groups were assessed by using the Chi-square test or Fisher exact test where appropriate. For contrasts of continuous variables, independent sample t-test was used to assess the difference of means. All analyses were conducted by using the Statistical package for social science , p-values were two sided and considered as statistically significant if < 0.05.In total, 160 patients with acute asthma exacerbation were assessed for eligibility. Of the 100 enrolled patients, 50 were randomized to receive oral montelukast. The baseline characteristics of both groups are given in Table 1 (p = 0.29), where the mean values for the study and placebo groups were 1.07 ± 0.54 L/min and 1.21 ± 0.68 L/min respectively .Two patients, one from each arm, developed respiratory failure. No patient in either group was withdrawn due to worsening asthma or adverse drug effect from the study.1 at admission and discharge and PEF measured at specific intervals or length of hospital stay in patients hospitalized with acute asthma exacerbation that were given oral montelukast vs. placebo. The efficacy and tolerability profile of oral montelukast were comparable to placebo and no serious adverse effects were encountered.Our study did not reveal significant differences in pulmonary function tests measured as FEV1 and dyspnea in the ER only with 160 mg of zafirlukast[1 in patients receiving standard therapy with montelukast as compared to placebo at 10 minutes (p = 0.03), 20 minutes (p = 0.007) and two hours (p = 0.003)[The pathology of asthma triggers the arachnoid acid cascade leading to formation of leukotrienes via the 5-lipoxygenase pathway. The cysteinyl leukotrienes possess pro-inflammatory characteristics which can directly cause or potentiate airflow obstruction by increased mucosal secretion and bronchospasm. Leukotrirlukast. Other s= 0.003).1 by using oral and intravenous montelukast respectively while Todi et al. reported similar proportion of children having Modified Pulmonary Index Score ≤ 9 in both the study and control groups[To the best of our knowledge, our study is the first one to report no added benefits of using montelukast in acute asthma exacerbation in hospitalized adult population. Other studies which report similar findings mostly correspond to the pediatric population-24. Nels1 in comparison to the positive studies cited above. Another reason for failure of significant improvement might be the use of enteral route of administration. However, Dockhorn et al. conducted a study comparing the effectiveness of intravenous montelukast vs. oral montelukast vs. placebo in the setting of acute asthma. Though intravenous montelukast was quicker in onset of action with the mean percentage change in FEV1 higher at earlier time intervals (15 mins to 1 hour), this difference decreased over the time and was not significant (p > 0.05). Moreover, there was no difference in mean maximum percentage change in FEV1 from baseline between intravenous and oral montelukast (p = 0.071)[A possible reason we failed to find significant improvement is that we looked at PEFs early in the course of hospitalization instead of FEV= 0.071).This study has several limitations. Firstly, our study sample is relatively small. Secondly, we excluded patients with respiratory failure requiring positive pressure ventilation, either noninvasive or invasive. Both these factors may have impacted on the strength of difference observed in the two groups. Another limitation is the lack of biological surrogate markers like cysteinyl leukotrienes levels which have been shown to be higher in states of acute asthma exacerbation. It is pOur study suggests that there is no added benefit of using montelukast along with the standard therapy for the management of acute asthma exacerbation in hospitalized adult population. We recommend that larger scale multicenter trials would better help to evaluate the role of cysteinyl leukotrienes antagonists in treating acute exacerbations of asthma.LTRAs: Leukotriene receptor antagonists; PEF: Peak expiratory flow; FEV1: Forced expiratory volume in 1 second; AKUH: Aga Khan University Hospital; ER: Emergency roomThe authors declare that they have no competing interest.The proposal was prepared by ABSZ in consultation with NS, ASH, SJH, NR and JAK. NS, ASH, AK and AAS have analyzed and interpreted the patient data. SA assisted in statistical analysis and manuscript writing. ABSZ, NS, AK and AAS were major contributors in writing the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/13/20/prepub


Asthma trials suggest that patients reaching total disease control have an optimal Health Related Quality of Life (HRQoL). Moreover, rhinitis is present in almost 80% of asthmatics and impacts asthma control and patient HRQoL. We explored whether optimal HRQoL was reachable in a real-life setting, and evaluated the disease and patient related patterns associated to optimal HRQoL achievement.2 = 49.599; p<0.001) and well-controlled and totally controlled patients significantly differed in achieving optimal HRQoL .Asthma and rhinitis HRQoL, illness perception, mood profiles, rhinitis symptoms and asthma control were assessed by means of validated tools in patients classified according to GINA and ARIA guidelines. Optimal HRQoL, identified by a Rhinasthma Global Summary (GS) score ≤20 , was reached by 78/209 (37.32%). With the exception of age, no associations were found between clinical and demographic characteristics and optimal HRQoL achievement. Patients reaching an optimal HRQoL differed in disease perception and mood compared to those not reaching an optimal HRQoL. Asthma control was significantly associated with optimal HRQoL (χApproximately one third of the patients in our survey were found to have an optimal HRQoL. While unsatisfactory disease control was the primary reason why the remainder failed to attain optimal HRQoL, it is clear that illness perception and mood also played parts. Therefore, therapeutic plans should be directed not only toward achieving the best possible clinical control of asthma and comorbid rhinitis, but also to incorporating individualized elements according to patient-related characteristics. The goal of asthma treatment is to reach the good symptom control and to prevent disease worsening Clinical trials have demonstrated that total asthma control is an achievable target at all disease stages Results from the above trials refer to asthma patients studied in the framework of controlled clinic trials and the study design did not take comorbid rhinitis into account. Observational studies indicated that patients suffering from symptomatic rhinitis were less likely to attain good asthma control and emphasised that the presence of rhinitis symptoms influenced not only the quality of life related to the upper airways but also to lower airways and the global HRQoL score The aims of our cross-sectional study were: to assess the level of quality of life related to asthma and rhinitis in an adult population in order to evaluate whether optimal HRQoL was achievable in a real-life setting; to investigate the clinical and demographic pattern associated to optimal HRQoL achievement; to assess whether patients reaching optimal HRQoL differ in terms of illness perception and stress levels from those who do not; to investigate whether among the patients with controlled asthma, those reaching an optimal HRQoL differ in illness perception and stress levels.Asthma and rhinitis patients scheduled for a follow-up visit to the Allergy and Respiratory Departments of six Italian medical centers were recruited over a two-month period starting in November 2009. The descriptive observational study was approved by the Ethics Committee of the Azienda Ospedaliero-Universitaria San Martino di Genova and written informed consent was obtained from each patient prior to the beginning of the study.Inclusion criteria for the study were: adult age (18–75 years), comprehension of spoken and written Italian, availability to participate in the study (informed consent signature), and a history of diagnosed allergic asthma with concomitant rhinitis While the patients were waiting for their follow-up visit, they were invited to complete the required questionnaires (see below). During the visit, the ARIA guidelines were used to establish the patient's rhinitis status The Asthma Control Test (ACT) Rhinitis symptoms were assessed using the Total 5 Symptoms Score (T5SS) that includes the following symptoms: nasal discharge (rhinorrhea), nasal congestion, itchy nose, sneezing, and itching eyes. All symptoms were graded using a score from 0 (absent) to 3 (very troublesome), with total scores ranging from 0–15.The RHINASTHMA is the only questionnaire that allows the evaluation of the impact of concomitant rhinitis and asthma on patient HRQoL The Illness Perception Questionnaire (IPQ-R) is a widely-used questionnaire that assesses patient beliefs and understanding of the illness The Profile of Mood States (POMS) is a well-established, factor-derived measure of psychological distress t-test was used to detect significant differences in the means of quantitative variables for independent samples. Spearman's rho was used to assess the relationships between variables or rank scores. Discriminant power of the POMS total score on optimal HRQoL was assessed through receiver operating characteristic (ROC) analysis. To estimate the association of each IPQ-R factor with RHINASTHMA GS scores, a linear regression model was applied .Patients were included in the statistical analysis on the basis of completeness of clinical data and completion of >90% in the PRO questionnaires. Data are presented in percentage for demographic characteristics and clinical data, as mean ± standard deviation for continuous variables investigated. Exploratory analysis of demographic and clinical data was performed using the following procedures. Pairwise associations between categorical variables were assessed through the chi-squared test for heterogeneity. Student's Out of 238 patients initially recruited for the study, 227 agreed to fill in the questionnaires. Eighteen patients were excluded from the analysis due to clinical data incompleteness or missing questionnaire answers (>10%), leaving 209 patients (mean age 45.14±16.75 years) in the final analysis group . ACT and2 = 1.753; p<0.229), rhinitis degree of severity  and asthma degree of severity .Optimal HRQoL, identified by Rhinasthma Global Summary (GS) score ≤20, was reached by 78/209 (37.32%) . Clinica2 = 49.599; p<0.001). Patients achieving optimal HRQoL showed median ACT and T5SS values greater than patients not reaching optimal HRQoL .Patients with an optimal GS score showed significantly lower T5SS score (p<0.001) and higher ACT score (p<0.001) compared to those with a GS score higher than 20. ACT score, categorized into uncontrolled (<20) and controlled (≥20) scores, was significantly associated with GS optimal score achievement  was performed. Controlled patients showed significant differences in illness perception and profile of mood states based on whether patients had achieved optimal HRQoL .The goals of this observational real-life study were to verify whether the clinical-trial HRQoL results were achievable in a real-life setting also considering the burden of comorbid rhinitis, and to explore which disease- and patient-related factors were associated with this achievement. Our study shows that optimal HRQoL is an achievable target but is rarely achieved in real life in patients suffering from allergic asthma with comorbid rhinitis.With the exception of age, the patient demographic characteristics were not associated with the achievement of optimal HRQoL; indeed, our results are in line with previous findings indicating a reduced HRQoL in older subjects Patients reaching an optimal HRQoL differed in disease perception and mood , 5 and 6Therefore, investigating which symptoms and disturbances patient associates with their disease, providing a correct education, helping them to recognize the symptomatological characteristics of asthma and rhinitis and to distinguish them from symptoms related to other pathologies, seems a necessary step in order to reach and maintain optimal HRQoL levels. Patients attaining optimal HRQoL reported lower levels of tension, depression, aggressiveness, tiredness, and confusion . If the Asthma treatment has been shown to greatly highly improve HRQoL and reduce the burden of asthma Although clinical trials have demonstrated that asthmatic patients may reach an optimal HRQoL, which implies minimal or absent disease impact on patient life, this possibility had not been explored yet in a real-life setting. The present study demonstrates that, although the majority of real-life patients with both asthma and rhinitis did not achieve optimal HRQoL, this is an achievable target. Failure to reach optimal HRQoL is related neither to disease severity nor to demographic characteristics (apart from age). Optimal HRQoL is related to asthma control and rhinitis symptoms and a significantly higher percentage of totally controlled patients reached an optimal HRQoL level. This evidence, confirming the results of clinical trials


In the assessment of hypovolemia the value of functional hemodynamic monitoring during spontaneous breathing is debated. The aim of our study was to investigate in spontaneously breathing subjects the changes in hemodynamic parameters during graded central hypovolemia and to test whether slow patterned breathing improved the discriminative value of stroke volume (SV), pulse pressure (PP), and their variations . In addition, we tested the alterations in labial microcirculation.20 healthy volunteers participated in our study. Central hypovolemia was induced by lower body negative pressure (LBNP). Continuous signals of ECG, non-invasive blood pressure and central venous pressure were recorded. During baseline and each stage of LBNP the labial microcirculation was investigated by orthogonal polarization spectral imaging, 3 minute periods of patterned breathing at 6 and 15/min respiratory rate were performed, and central venous blood gas analysis was done. Data from baseline and those of different LBNP levels were compared by analysis of variance and those of different breathing rates by t-test. Finally, we performed ROC analysis to assess the discriminative values of SV, PP, SVV and PPV.2) (p < 0.001). The proportion of perfused vessels (p < 0.001) and microvascular flow index decreased (p < 0.05). PPV increased (p < 0.001), however the magnitude of fluctuations was greater during slow patterned breathing (p < 0.001). SVV increased only during slow patterned breathing (p < 0.001). ROC analysis confirmed the best predictive value for SV . Slow patterned breathing improved the discriminative value of SVV (p = 0.0023).Moderate central hypovolemia induced by LBNP caused significant, clinically relevant falls in PP (p < 0.05) and SV and central venous oxygen saturation (ScvOFunctional hemodynamic monitoring with slow patterned breathing to control spontaneous respiration may be worthy for further study in different populations for the assessment of hypovolemia and the prediction of volume responsiveness. The recognition of hypovolemia is of critical importance in the management of our patients. This is especially important in severe civil or military mass trauma situations where a parameter or a combination of parameters would be very useful to help to triage patients who are still “stable” but are approaching cardiovascular collapse due to haemorrhage,2. FurthClinical signs and laboratory or blood gas data often help to establish the diagnosis of hypovolemia. Hemodynamic parameters such as cardiac filling pressures  and static volumetric preload parameters  have been used to approximate cardiac preload and to guide fluid therapy.Recently the so-called dynamic hemodynamic parameters have been found to be more accurate in the diagnosis of hypovolemia and fluid responsiveness-5. For cFrom investigations on cardiovascular autonomic regulation it is clear that respiration has a fundamental influence on heart rate and blood pressure fluctuations. To control the breathing of awake and cooperative subjects the method of patterned breathing is used. This means that the subjects synchronize inspiration and expiration and sometimes tidal volume to an audio or visual signal. The respiratory frequency can be centred either to the high frequency  or low frequency (around 0.1 Hz) bands of cardiovascular fluctuations, which means 15/min and 6/min rate. Doing so, the oscillations in these bands can be enhanced, especially at 6/min breathing rate when the respiratory oscillations and Mayer waves merge.To induce central hypovolemia in healthy volunteers lower body negative pressure (LBNP) is an accepted, safe and widely used method. This results in the redistribution of blood volume, which generates central hypovolemia without actual volume loss. According to previous data, the volume shift generated by −10-20 mmHg LBNP is similar to mild (400–550 ml), by −20-40 mmHg to moderate (550–1000 ml), and by greater than −40 mmHg to severe (more than 1000 ml) acute blood loss.Experimental and clinical research suggests that in circulatory failure or shock it is the alteration of the microcirculation that finally leads to tissue oxygenation problems and multiple organ failure-33. FurtThe aim of our study was to investigate the effects of mild and moderate LBNP-induced central hypovolemia on the behaviour of hemodynamic parameters, especially on PPV and SVV in spontaneously breathing subjects, and to test the hypothesis that slow patterned breathing improves their discriminative value. Furthermore, we studied the microvascular alteration caused by different levels of central hypovolemia.Our study population consisted of 20 healthy young male volunteers (age 24 ± 6 years), who provided informed consent to participation. Firstly, the subjects were familiarized with the laboratory and equipment, and were trained to perform patterned breathing. In order to control their respiration, patterned breathing was used, so they synchronized inspiration and expiration to an audio signal. Afterwards we inserted a peripherally inserted central line. We ascertained the correct position of the catheter tip by the appearance of the classic central venous pressure (CVP) wave form on the monitor. After this the subjects assumed supine position in the LBNP chamber.2 level through a mouth-piece connected to a capnograph  to confirm the subjects’ adherence to the breathing commands. All these signals were digitized by 500 Hz and recorded on-line by the Dataq/Windaq data acquisition system .We monitored the ECG, CVP and arterial oxygen saturation continuously using a bedside monitor  and arterial blood pressure by the Finapres non-invasive monitor . During the patterned breathing periods we monitored the end tidal COIn order to study microcirculation, we investigated the labial microvessels. For this the orthogonal polarization spectral (OPS) imaging technique was used . A 10× objective was placed onto the inner surface of the labia, and microscopic images were recorded on an S-VHS video recorder .2), central venous CO2 tension (PcvCO2), central venous oxygen saturation (ScvO2) and haemoglobin (Hb)  program was used. For SV calculation this program uses the pulse-contour method (modified Modelflow). First, all the signals were automatically peak-detected and manually checked. Then we calculated RR interval (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), pulse pressure (PP) and SV for the entire 3 minute periods in each study condition. Afterwards, we calculated the minimum and maximum RRI, SAP, MAP, CVP, PP and SV for each respiratory cycle during 1 minute of the patterned breathing periods and calculated their differences  as the respiratory fluctuations (this involved 6 respiratory cycles during 6/min and 15 cycles during 15/min breathing). In addition, we calculated PPV and SVV according to accepted formulas.For the analysis of data from the microcirculation we used a computer-assisted image analysis system . Quantitative assessment of the microcirculatory parameters was performed off-line by frame-to-frame analysis of the videotaped images. We determined red blood cell velocity (RBCV), the mean perfused capillary lengths (MPCL), the proportion of perfused vessels (PRPV) and the microvascular flow index (MFI) in accordance with accepted methods. All micData from baseline and those of different LBNP levels were compared by analysis of variance and those of the two different breathing rates by t-test. In the case of non-normal distribution of data, analysis of variance on ranks and the Mann–Whitney rank sum test were used. . In order to assess the discriminative value of data, ROC analysis was done. SV and PP during 6/min, and SVV and PPV during both respiratory rates were analysed by using data from baseline and −40 mmHg LBNP . Data are given as mean ± SD. P value below 0.05 was considered to be statistically significant.The typical recording of one subject is shown in Figure From the hemodynamic parameters MAP did not change; but RRI, SAP, CVP, PP and SV significantly decreased at −40 mmHg, and CVP and SV even at −20 mmHg LBNP. In the case of RRI, SAP, PP and SV there was also a significant difference between −20 and −40 mmHg LBNP Table .2, pO2 and ScvO2 significantly deceased at −40 mmHg LBNP, and this change was even significant between baseline and −20 mmHg in Hb, pO2 and ScvO2, and between −20 mmHg and −40 mmHg in Hb  decreased significantly between baseline and both LBNP levels, and RBCV between −20 and −40 mmHg LBNP, too Table .RRI, SAP, MAP, CVP, SV and PP data at different levels of LBNP and at different respiratory rates are shown in Table Delta RRIs were not influenced by the LBNP level, but their values were significantly greater during 6/min patterned breathing at all LBNP levels (p<0.001).SAP and MAP respiratory fluctuations increased at both 6/min and 15/min patterned breathing in moderate central hypovolemia, but in mild central hypovolemia these changes were only significant at 6/min breathing rate. The SAP respiratory fluctuations were greater at slow patterned breathing at each LBNP level (p<0.001). MAP delta increased between −20 and −40 mmHg LBNP only at 6/min patterned breathing.The CVP delta values changed significantly between baseline and mild and moderate central hypovolemia, but the fluctuations became smaller at both 6 and 15/min respiratory rate.The assessment of SV, PP, SVV and PPV gave the most interesting results. The minimum, and maximum values of SV and PP decreased in response to all levels of hypovolemia, though the delta values did not change either at 6/min nor at 15/min breathing rate. The fluctuations of both SV and PP were more pronounced at 6/min patterned breathing, and the differences were significant in all comparisons , except at baseline in SV. However, PPV increased from baseline to −40 mmHg LBNP, especially at slow patterned breathing. PPV increased also between −20 and −40 mmHg LBNP at 15/min patterned breathing. SVV only increased at slow patterned breathing in moderate central hypovolemia, though it was greater in all 3 conditions with slow respiratory rate  is the result of the increased RV output. During exhalation, the venous return and RV SV decrease, which reaches the LV a few beats later. At the same time the aortic transmural pressure decreases compared to the inspiratory value, which augments LV ejection. This dampens the effect of decreased preload, so delta down is not so prominent, as during positive pressure ventilation. In summary, the mechanism of delta up and delta down is different: during mechanical ventilation it is the delta down, during spontaneous breathing it is the delta up that is the volume sensitive, preload determined variable.There is another problem with dynamic hemodynamic parameters besides the above discussed issues. The respiratory perturbation should be great enough to cause significant preload alteration in order for clinicians to be able to assess its effects on blood pressure and left ventricular stroke volume. These effects are smaller during quiet spontaneous breathing and are clearly tidal volume dependent during mechanical ventilation-22,24,25In addition, the lag between the changes of RV and LV output is determined by the pulmonary transit time. The timing of the influence of RV output changes on the LV is clearly dependent on the heart rate (HR) and respiratory rate (RR) as well as their timing to each other. This relationship is highlighted in the work of De Backer et al.. They coBased on these findings it may be assumed that there is a need to standardize conditions, especially respiratory stimuli when assessing preload responsiveness by dynamic parameters. Perel et al. tried to achieve this with a ventilatory manoeuvre called respiratory systemic variation test (RSVT). In our The different behaviour of SVV and PPV may be explained by the fact that the relationship between SV and PP is not linear, arterial distensibility continues to decrease with progressive reduction of central blood volume,29.Finally, we were interested in how the respiratory fluctuations of CVP were influenced, because this is easy to measure and is readily available. In his early study Magder tested the hypothesis that the respiratory pattern of right atrial pressure (RAP) could be used to predict the response to a fluid challenge. He concluded that it was very unlikely that volume loading would increase cardiac output when the inspiratory fall in RAP was less 1 mmHg. AlthougThis study has some limitations, the first one being that we investigated healthy young individuals with intact autonomic regulation therefore the results cannot be extrapolated to different patient populations. Another limitation was that our subjects were fully awake and cooperative and after a short learning period could follow the breathing commands properly. The implementation of slow patterned breathing could be more difficult and even impossible in many clinical situations where patients have dyspnea, tachypnea or altered mental state. However we believe that not only during spontaneous but also during controlled mechanical ventilation there is a need to standardise the respiratory pattern when we want to assess functional hemodynamic parameters. For stroke volume analysis we used pulse-contour analysis with modified Modelflow method and verified manually the beat-to-beat automatic wave form analysis. Furthermore, when we investigated the effect of respiratory rate, we averaged data for 1 minute, from 6 and 15 respiratory cycles. Commercially available, built-in systems, with different softwares and time-averaged data could give different results.In conclusion, slow patterned breathing may allow the assessment of hypovolemia in spontaneously breathing subjects and it is worthy for further study in different conditions and populations. In Emergency Departments and wards patients are usually not equipped with arterial lines and invasive hemodynamic monitoring is not available. In this patient group, for those, who are able to sustain a specific breathing pattern for a few minutes, the use of non-invasive blood pressure monitoring coupled with functional hemodynamic monitoring, is promising.2 and ScvO2 and progressive impairment of both microvessel density and perfusion.Mild and moderate central hypovolemia induced by LBNP caused significant and clinically relevant falls in PP and SV. This was accompanied by significant and relevant decreases in PcvOPPV increased during both 6/min and 15/min patterned breathing in moderate central hypovolemia however the magnitude of fluctuations was greater during the slow respiratory rate. SVV increased only during slow breathing, and its accentuation with low respiratory rate was less pronounced then that of PPV.ROC analysis confirmed the best predictive value for SV absolute values in this group of healthy volunteers.Slow patterned breathing improved the discriminative value of SVV, but not that of PPV.2 tension; PEEP: Positive end exspiratory pressure; PP: Pulse pressure; PPV: Pulse pressure variation; PRPV: Proportion of perfused vessels; RAP: Right atrial pressure; RBCV: Red blood cell velocity; ROC: Receiver operating characteristic curve; RR: Respiratory rate; RRI: RR interval (the time of the cardiac cycle); RSVT: Respiratory systemic variation test; RV: Right ventricle; SaO2: Arterial oxygen saturation; SAP: Systolic arterial pressure; ScvO2: Central venous oxygen saturation; SV: Stroke volume; SVV: Stroke volume variation; VBG: Central venous blood gas analysis.AUC: Area under the curve; BP: Blood pressure; CVP: Central venous pressure; ECG: Electrocardiogram; FCD: Functional capillary density; GEDVI: Global end diastolic volume index; Hb: Hemoglobin; HR: Heart rate; ITBVI: Intrathoracic blood volume index; LBNP: Lower body negative pressure; LV: Left ventricle; MAP: Mean arterial pressure; MFI: Microvascular flow index; MPCL: Mean perfused capillary lenght; OPS: Orthogonal polarization spectral imaging; Paop: Pulmonary artery occlusion pressure; PcvO2: Central venous oxygen tension; PcvCO2: Central venous COThe authors declare that they have no competing interests.ÉZ and LR planned the study design, and contributed to hemodynamic data acquisition and analysis. The manuscript was written by ÉZ. VB, AN, PCs have been involved in coordination, hemodynamic data acquisition and analysis. The investigation and data analysis of the microcirculation was done by JK and IL. All authors were involved in the critical revision of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2253/13/40/prepub


Anorexia nervosa (AN) is associated with gut and non-gut symptoms e.g. orthostatic intolerance and fatigue syndromes. Elsewhere, joint hypermobility has been found in non-anorexic populations who have gut symptoms, orthostatic intolerance or fatigue syndromes. We therefore postulated that joint hypermobility may be a feature of AN.Patients from an inpatient Eating Disorders Unit and their first degree relatives underwent medical interview, joint mobility assessment, postural and ambulatory blood pressure (BP) measurements and completed a number of questionnaires. Comparisons were made with healthy sex matched controls.Patients (n=30), relatives (n=29) and controls (n=16) were aged 24.4±1.4 years (mean ± SEM), 44.7±2.9 years and 38.6±3.7 years respectively. Joint hypermobility was more common in patients (63%) than relatives (34%) and controls (13%). Gastrointestinal or orthostatic intolerance symptoms prior to onset of AN were reported by 8 and 14 patients respectively. Orthostatic tachycardia, orthostatic hypotension and blunted diurnal BP pattern were found in 58%, 21% and 50% of patients respectively.Patients with AN are characterised by a high prevalence of gut symptoms, orthostatic intolerance, and joint hypermobility. First degree relatives also have these complaints. No causal mechanism has been identified, but we hypothesise that the joint hypermobility is a possible indicator of a familial disorder of connective tissue elasticity which potentially plays a causal role in the development of the eating disorder.Anorexia Nervosa – Characteristics and Treatment stream of the 2013 ANZAED Conference.This abstract was presented in the