Patients with hypertension diagnoses were older, and more likely to be female,and have lower education levels than those without hypertension diagnoses, for most survey years. Overall adherence levels were poor (mean score 2 of 6), and levels of adherence to non-pharmacological habits did not significantly differ between patients with and without hypertension diagnoses. However, overall adherence levels improved significantly among patients with hypertension diagnoses: from 2.09 in 1998 to 2.27 in 2012 (p = 0.007), particularly regarding sufficient vegetable/seaweed consumption (p = 0.03), maintaining a normal weight (p = 0.03), and avoidance of smoking (p < 0.001). Awareness of hypertension is increasing, but hypertensive Korean patients demonstrate poor overall adherence to non-pharmacological hypertension management guidelines. These findings suggest that well-planned education programs should be continued after hypertension is diagnosed.This study aimed to compare levels of adherence to non-pharmacological guidelines between patients with and without hypertension diagnoses, and examined temporal changes in adherence during recent decades. We used data from the Korean National Health and Nutrition Examination Survey (1998–2012), including 13,768 Korean hypertensive patients aged ≥ 30 years who were categorized according to the presence or absence of a hypertension diagnosis, based on blood pressure and self-reported information. Adherence to the guidelines was calculated for 6 components, including dietary and lifestyle habits. A multivariable generalized linear regression model was used. The proportion of hypertensive patients aware of their condition increased from 33.4% in 1998 to 74.8% in 2012 ( Although hypertension has a high prevalence in Asian populations, its management and patient adherence to lifestyle recommendations have not been a priority . AccordiHypertension is both preventable and manageable by modifying diet and lifestyle , as indiAlthough better adherence to guidelines is associated with enhanced health benefits through improved blood pressure control, limited information is available regarding the population-level adherence to these guidelines among hypertensive Korean patients. In Korea, the guidelines for management of hypertension were primarily developed by the Ministry of Health and Welfare (MHW)  and the In 2001, the MHW established the National Hypertension Center, a national organization that links researchers and health care providers to develop effective strategies for preventing hypertension in South Korea. The aim of the National Hypertension Center was to decrease the prevalence of hypertension and related complications, and increase opportunities for education on hypertension as a means of facilitating self-management, through a variety of national interventions, particularly via establishment of a community-based program at public health centers. After 2007, case management programs for hypertensive patients were implemented, and consisted of visiting and interviewing by trained health professionals. Several prior reports have examined the effects of this case management program. So et al.  reportedWe analyzed data from the KNHANES 1998–2012, a nationally representative cross-sectional survey that used a complex, stratified, multistage, probability-cluster sampling approach. The protocols and measurements of the KNHANES have been described in detail elsewhere . BrieflyAll participants signed an informed consent form, and the study was approved by the Institutional Review Board (IRB) of the Korea Centers for Disease Control and Prevention, who also provided formal ethics approval for the KNHANES data sets .Adults at or above 30 years of age tend to exhibit changes in metabolic processes with age –21; suchDemographic and lifestyle characteristics including age, sex, education, household income, smoking, alcohol consumption, and physical activity were collected through a health interview questionnaire. Smoking status was categorized as never, former, or current. Alcohol intake was calculated by multiplying the servings of alcohol consumed in 1 sitting by the frequency of consumption. Physical activity information could not be obtained for the 1998 and 2001 surveys, and some details were omitted from the 2005 and 2007 surveys. Thus, physical activity variables were used to calculate metabolic equivalents (METs [h/week])  from theDietary information was obtained through a single 24-hour recall method, and the participants were asked to recall every consumed food item, as well as meal times, eating places, and the quantity of food consumed (volume [ml] or weight [g]). All consumed foods were coded and transformed to nutrients, including carbohydrate and sodium, on the basis of the Food Composition Table by the Rural Development Administration . Consump2]), and “normal weight” was defined based on the report from the World Health Organization for Asian populations. BMI values falling into the range 18.5 kg/m2 ≤ BMI < 23 kg/m2 were considered normal weight, and those where the BMI was ≥ 23 kg/m2 were considered overweight/obese Limited sodium intake (< 2000 mg/day)Sufficient intakes of fresh vegetables and seaweeds Moderate carbohydrate consumption  [Lifestyle components]Moderate alcohol consumption (≤ 2 cups per day for men and ≤ 1 cup per day for women)2 ≤ BMI < 23 kg/m2)Maintaining a normal weight  to 6 (the highest adherence).P-values were based on 2-sided tests, and significance was determined at α = 0.05. Statistical analyses were performed using SAS V9.2 .All statistical analyses were conducted with consideration of the complex survey design that used a multistage, stratified, clustered sampling approach to obtain a study sample representative of the entire non-institutionalized South Korean population. Descriptive statistics of participants were obtained by determining weighted frequency distributions of categorical variables and weighted means ± standard error of continuous variables. Characteristics of patients with and without hypertension diagnoses were compared using the chi-square test for categorical variables or the t-test for continuous variables. Multivariable generalized linear regression analysis was performed using the SAS PROC SURVEYREG command, which provides means and 95% confidence intervals (CI), to give estimates of adherence levels for diagnosed and undiagnosed hypertension. p for trend < 0.001). One-third of hypertensive patients graduated high school or higher, and two-thirds of them were obese (BMI ≥ 23 kg/m2). Smoking rates significantly decreased from 34.8% in 1998 to 14.6% in 2012 (p for trend < 0.001), while a significant decrease was also observed for physical activity levels (p for trend < 0.001) during the recent survey years of 2008 to 2012.Demographic and lifestyle information for Korean hypertensive patients is summarized in p for trend < 0.001, Among hypertensive patients, the proportion of diagnosed cases was 33.4% in 1998. This substantially increased until 2010, then plateaued in the 2011–2012 survey years (p < 0.001) and were more likely to be female (p < 0.001), than those without; these differences were observed for all survey years. In addition, the group with hypertension diagnoses was more likely to have greater waist circumference, lower levels of education, and lower prevalence of current smoking than the group without hypertension diagnoses, for most survey years.2) than patients with hypertension diagnoses; however, such an observation was only made in 1998 (undiagnosed: 0.33 points vs diagnosed: 0.23 points). The guidelines with the greatest adherence ratings were avoidance of smoking (0.61–0.84 points) and moderate alcohol consumption (0.49–0.65 points). However, nutrient-related guidelines, such as limiting sodium intake (0.07–0.20 points), moderate carbohydrate consumption (0.10–0.21 points), and sufficient intakes of fresh vegetables and seaweeds (0.15–0.24 points) exhibited poor adherence.Levels of adherence to the 6 non-pharmacological guidelines among patients with and without hypertension diagnoses during the 1998–2012 survey years were examined in a multivariable linear regression after adjusting for age, sex, education, household income, alcohol consumption, and smoking status . Adherenp < 0.001), and from 0.62 in 1998 to 0.77 in 2012 among undiagnosed patients (p < 0.001). However, adherence to moderate alcohol consumption decreased from 0.71 in 1998 to 0.57 in 2012 among diagnosed patients (p < 0.001), and from 0.62 in 1998 to 0.43 in 2012 among undiagnosed patients (p < 0.001). Adherence to sufficient vegetable/seaweed consumption (p = 0.03) and maintaining a normal weight (p = 0.03) improved over time for diagnosed subjects only. Overall adherence to the 6 non-pharmacological guidelines ranged between 2.09–2.27 and 2.07–2.03 among patients with and without hypertension diagnoses, respectively; however, improvement was significant in diagnosed patients only (p = 0.007).p for trend < 0.001), and from 153.59 mmHg in 1998 to 142.64 mmHg in 2012 among undiagnosed patients (p for trend < 0.001). The average levels of DBP decreased by 11.33 mmHg during 14 years for diagnosed patients (p for trend < 0.001), but no significant change in DBP was observed for undiagnosed patients . Overall, both SBP and DBP tended to be higher in undiagnosed patients than diagnosed patients for most survey years.During recent decades, the proportion of patients diagnosed with hypertension has rapidly increased. However, overall levels of adherence to non-pharmacological guidelines for blood pressure management have been poor, and a hypertension diagnosis was not associated with better adherence to the guidelines when compared to persons with undiagnosed hypertension, for most survey years. Overall adherence levels improved slightly among patients with hypertension diagnoses. However, this was not observed among patients with undiagnosed hypertension between the 1998–2012 survey years. Smoking rates were relatively low and decreased substantially over time for both patients with and without hypertension diagnoses. Improvements in adherence may be responsible for positive reductions in blood pressure, particularly for patients with hypertension diagnoses whose blood pressure has significantly decreased over the 14 survey years.Our results demonstrate that awareness of hypertension has improved over the past decade in Korea, and remained stable in 2010–2012, with a high proportion of the hypertensive population reporting a diagnosis (74.5–78.5%). According to cumulative scientific reports, similar awareness levels have been reported in the US, however, relatively low levels of awareness have been observed in China. A National Health and Nutrition Examination Survey (NCHS) data brief  reportedIn addition, hypertension awareness was associated with other factors. For example, patients who were diagnosed were older , 32, morPatient awareness of hypertension is important for achieving blood pressure control, because it provides opportunities to change diet and lifestyle habits, and initiate pharmacological therapy where warranted. In the European Investigation into Cancer and Nutrition-NL cohort, subjects aware of their hypertension were more likely to adhere to the guidelines, particularly for fat and fiber intake, alcohol restriction, and achievement and maintenance of a healthy weight . HoweverOne of the least followed guidelines was limiting sodium intake, which is particularly important for hypertensive patients. High sodium intake is known to increase sympathetic nervous system activity and cardiac output, and eventually increases the risk of hypertension and its complications such as cardiovascular disease . ObservaAlthough the overall levels of adherence to non-pharmacological guidelines were poor, and did not differ between patients with and without hypertension diagnoses for all survey years, there were significant positive changes in adherence levels among patients with hypertension diagnoses in recent decades. These improvements were apparent in adherence to avoiding smoking, sufficient vegetable/seaweed consumption, and maintenance of a normal weight. This may be a positive sign of government effort  to improve patient self-management skills for hypertension. In fact, in this population, we observed a trend towards decreasing blood pressure levels, particularly for patients with hypertension diagnoses. Focused interest and investment in education programs for hypertensive patients will be necessary at the population level, and improvements in levels of adherence to non-pharmacological guidelines for hypertension will be key to reducing the public health burden of complications secondary to hypertension.Our study has several strengths. By obtaining a large population and representative data from the KNHANES, our results are more generalizable to the South Korean hypertensive population. In addition, to our knowledge, this may be the first study to examine levels of adherence to non-pharmacological guidelines, considering diagnosis status as well as changes over time.Limitations of this study should also be considered. Although blood pressure was measured by trained medical staff and the average used to identify diagnosed and undiagnosed hypertension, misclassification may exist, as identification of hypertension was based on self-reported information, whereby confounders, such as the “white coat” phenomenon, may change the observed results. In addition, this was a cross-sectional study and therefore could not examine changes over time within individual. Dietary and nutrient intake levels were evaluated using a 1-day 24-h recall method, which could have resulted in misclassification. Finally, our participants were recruited from 1998 to 2012, and our definition of non-pharmacological guidelines was primarily based on 2 guidelines, the “Dietary Guidelines for Disease Management” (2010) and the “2013 Korean Hypertension Treatment Guidelines” (2013). The first edition of the Korean Hypertension Treatment Guidelines (2004) was not considered in our definition, but was almost identical to the 2013 Korean Hypertension Treatment Guidelines with respect to non-pharmacological components.In conclusion, awareness of hypertension may be important for patients to control blood pressure. However, awareness itself may be insufficient to motivate patients to change their dietary and lifestyle behaviors. Thus, it is critical to improve patient education efforts to better manage hypertension and improve compliance with dietary and lifestyle recommendations, such that blood pressure can be controlled aggressively to prevent long-term complications.


Intraabdominal hypertension (IAH) produces detrimental effects on tissue perfusion. A putative underlying mechanism is the decrease in abdominal perfusion pressure . Nevertheless, the benefits of increasing blood pressure on tissue perfusion are controversial.To describe the effects of IAH on regional and microcirculatory intestinal blood flow, renal blood flow, and urine output, as well as their responses to increases in blood pressure induced by norepinephrine.2 (ΔPCO2), and urine output. IAH (20 mm Hg) was generated by intraperitoneal instillation of warmed saline. After 1 h of IAH, sheep were randomized to control (n = 8) or norepinephrine (n = 8) groups for 1 h. In this last group, mean arterial pressure was increased about 20 mm Hg by means of norepinephrine. A sham group (n = 8) was also studied.In 24 anesthetized, mechanically ventilated, and fluid-resuscitated sheep, we measured systemic hemodynamics, left renal and superior mesenteric artery blood flows, villi microcirculation, ileal intramucosal-arterial PCOIn this experimental model of IAH, the gut and the kidney displayed contrasting responses. While intestinal blood flow and villi microcirculation remained unchanged, renal perfusion and urine output were severely compromised. The increase in blood pressure with norepinephrine failed to improve these variables.


Systolic blood pressure (SBP) increases steadily with age and bears an independent continuous relationship with the incidence of cardiovascular events. Low-grade inflammation is a suspected pathomechanism causing vascular aging and promote coronary artery disease (CAD). Recent animal studies give evidence that Toll-like receptor 4 (TLR4) modulate inflammation and contribute to age-dependent SBP increase. However, there are no data about TLR4 and age-dependent blood pressure increase in human.We therefor investigate a human cohort of 2679 patients with CAD aged between 50–80 years. Genotypes were determined for the TLR4 single nucleotide polymorphism rs4986790 (TLR4 896A/G). Patients were stratified according to tertiles of age and the upper tertile was compared to lower tertiles.P < 0.05) and lower pulse pressure  as compared to TLR4 896A/A allele carrier.In this cohort we show that older patients with the TLR4 896 G allele had significantly lower SBP  contains supplementary material, which is available to authorized users. Systolic blood pressure (SBP) increases steadily with age and bears an independent continuous relationship with the incidence of cardiovascular events . More thChronic low-grade inflammation plays a crucial role in hypertension during aging –9. This The role of TLR4 polymorphism in CAD and myocardial infarktion was inconsistant in the literature , 17. RecP < 0.05). This is also correlated to a reduced number of hypertensive patients in this group (Table p < 0.05). Univariate analysis confirmed age (p < 0.001) and sex (p < 0.001) as commonly known blood pressure modulating risk factors in all tertiles of the cohort. Interestingly TLR4 G polymorphism shows a significant association for SBP (p = 0.017) (Table p < 0.001) and pulse pressure (p = 0.026) only in the upper age tertile (age ≥70 and <80 years) . Multivariate analysis of the upper age tertile confirm TLR4 896 G polymorphism as independent predictor of SBP and hypertension  . Dividinup Table . Pulse p p < 0.00 and sex on Table Table 1CoThis analysis demonstrates in humans that 896G allele carriers older than 70 years reveal lower SBP suggesting an effect of TLR4 signaling on SBP increase with aging.The increasing incidence of hypertension with age is thought to be a physiological process which develops with vascular aging mediated by low-grade inflammation and oxidative stress. Animal studies demonstrated that oxidative stress is acutely induced in the aortic tissue by Toll like receptor 4 (TLR4) ligands. TLR4 are present in different vascular beds and TLR4 ligands have been shown to induce chronic low-grade inflammation and oxidative stress in vascular smooth muscle cells , 23. EveWe investigated the human TLR4 SNP rs4986790  in 2679 patients with history of myocardial infarction . This poVascular aging is accompanied by vascular damage. Pulse pressure is an accepted parameter of vascular damage. Our data confirm that patients without the functional TLR4 SNP have a pulse pressure increase with age corresponding to the general human population , 30. By a-error of 0.05.The probability of a false negative association result because of population stratification is relatively low, because the study participants were consecutively recruited from a defined geographic area of southern Germany with limited recent immigration. The sample size allowed an analysis with 80 % power to detect a six mmHg decrease of SBP among the carriers of the 896G allele at a two-sided In summary, our data indicate for this large cohort of patients with myocardial infarction that carriers of the TLR4 SNP rs4986790 starting from the age of 70 years have a lower SBP and pulse pressure. We propose that TLR4 signaling influences age-dependent SBP increase in CAD patients.We demonstrate an association between the TLR4 SNP rs4986790 genotype and age-dependant blood pressure increase in large cohort of patients with coronary artery disease.Participants were examined at 1. Medizinische Klinik rechts der Isar, Technischen Universität München or Deutsches Herzzentrum München. Between 1993 and 2002, patients with myocardial infarction between the ages of 50 to 80 years were enrolled in a dedicated registry. Written informed consent for genetic analysis was obtained from all individuals. In no case, consent was withdrawn. Out of this cohort, patients with cardiogenic shock and advanced heart insufficiency defined as a SBP < 100 mmHg were excluded, finally reaching a cohort size of 2679 individuals. SBP and DBP were determined under standardized conditions in the laying position . Pulse pressure was calculated from systolic and diastolic blood pressure. Clinical and laboratory data were prospectively collected in an online database. Source data check was done with 20 % of the data. The Institutional Ethics Committee approved the study protocol and the reported investigations were in accordance with the principles of the current version of the Declaration of Helsinki.The diagnosis of myocardial infarction was defined according to the European Society of Cardiology. Briefly, patients presenting with chest pain lasting >20 min combined with ST-segment elevation or pathological Q waves on a surface electrocardiogram. Patients with myocardial infarction had to show either an angiographically occluded infarct-related artery or regional wall motion abnormalities corresponding to the electrocardiographic infarct localization or both. Systemic arterial hypertension was defined as a systolic blood pressure of ≥140 mmHg and/or a diastolic blood pressure of ≥90 mmHg, on at least two separate occasions, or anti-hypertensive treatment. Hypercholesterolemia was defined as a documented total cholesterol value ≥240 mg/dL (≥6.2 mmol/L) or current treatment with cholesterol-lowering medication. Persons reporting regular smoking in the previous 6 months were considered as current smokers. Diabetes mellitus was defined as the presence of a fasting glycaemia ≥126 mg/dL or patients on antidiabetic treatment.TLR4 gene, TLR4A allele) deposited under accession number AF177765 in GenBank (http://www.ncbi.nlm.nih/entrez/). The primers used for amplification of the 896A/G SNP  were 5′ TTGAAGAATTCCGATTAGCATACTTAGAC 3′ and 5′ TCACCAGGGAAAATGAAGAAACAT 3′. Allele-specific signalling was accomplished with the use of the fluorogenic dyes 6-carboxy-fluorescein (FAM) and VIC (proprietary dye of Applied Biosystems) which were attached to the 5′ end of the probe oligonucleotides. Minor groove binder (MGB) groups were conjugated with the 3′ end of the oligonucleotides to facilitate formation of stable duplexes between the probes and their single-stranded DNA targets. The structures of the probes were as follows : FAM-5′ CCTCGATGATATTATTGACT 3′-MGB (for 896A), VIC-5′ CTCGATGGTATTATTG 3′-MGB (for 896G) [BccI  (896A/G SNP). The results obtained with the different methods were fully corresponding, which demonstrated the reliability of the TaqMan systems that were used for genotyping of the 896A/G SNPs in the entire study population. Genotype determination was done by workers who had no knowledge of clinical, laboratory, or angiographic data of the individuals enrolled in the study.A blood sample was drawn from each participant during the regular routing examination for coronary artery angiogram. Genomic DNA was extracted from peripheral blood leukocytes with the QIAamp DNA Blood Kit  or the High Pure PCR Template Preparation Kit . Genotype analysis was performed with allele-specific fluorogenic oligonucleotide probes in an assay combining the polymerase chain reaction (PCR) and the 5′ nuclease reaction . Primers and probes were established with the Primer Express software  after import of a DNA sequence (Homo sapiens or 896G) . Oligonuχ2 test or Fisher's exact test, as appropriate. Continuous variables are expressed as mean ± SD and compared by means of the unpaired, two-sided t test. Genotype frequencies in the case group were compared with values predicted by Hardy–Weinberg equilibrium with the use of the χ2 test. Univariate analysis was performed for the whole cohort, upper age tertile and both lower age tertiles. Multivariate analysis used age, gender and hypercholesterolemia. Level of significance was set at p < 0.05.Patients in the cohort were divided by age into tertiles. In order to investigate the age-related effect, the lower two tertiles were summarized (age ≥50 and <70) and compared with the upper tertile (age ≥70 and <80). The association was examined by the univariate analysis using Spearman’s correlation test. The analysis consisted of comparing separate genotype distributions, between the age tertiles of patients with MI. Association analyses for SBP and DBP were conducted using linear regression, and analyses for dichotomous hypertension using logistic regression Discrete variables are expressed as counts (percentage) and compared with the use of the


Diabetes is a complex disease requiring the involvement of many health professionals. As a result, people with diabetes are faced with multiple appointments and multiple health messages to understand and make sense of. For example, blood sugar levels , foot health (and warning signs), kidney checks and eye examinations.As eye care practitioners, we are faced with the challenge of trying to talk to patients – who are often without symptoms – about their vision in relation to their diabetes. We must encourage and support them to return for eye examinations and treatment (see page 68).Whenever diabetes patients come into our eye clinics, we can also support their overall health and diabetes treatment by offering suitable information, education and support. This is important as good diabetes control helps to slow down the progression of diabetic eye disease. Here are a few practical things we can do.Send regular reminders to other health professionals in the hospital or community to advise patients with diabetes about the importance of annual eye examinations and where to go.Discuss the variety of diabetes checks and clinics the patient attends and how often. Encourage patients to keep their appointments and stay in contact with colleagues in other departments, so you can give patients all the information they need. This will help them to obtain and keep appointments.Educate patients about how to stay healthy and manage their diabetes (see panel below). This slows down the progression of diabetic eye disease. Even if patients have heard this elsewhere, change takes time, and the education (and encouragement) needs to be ongoing. Educate patients about their individual situation. Use their own retinal images to show them any changes (without blaming them!) or use the poster on pages 70–71. The far right-hand column in the poster contains suggestions for how to talk to patients about what is going on, and what is likely to happen next.‘Making lifestyle changes is difficult. We must empower patients with information and support’Making lifestyle changes is difficult. We must empower patients with information and support so they can take an active role in their own health-including coming for follow-up appointments and treatment. We can also lead by example by ensuring that we follow the advice below ourselves.With thanks to Tunde Peto and Peter Blows In order to protect you reyes from being damaged by diabetes, there are three things you must aim for:Stable blood glucose (blood sugar).Healthy blood pressure, achieved by exercising and taking any prescribed blood pressure medication.A healthy weight and low cholesterol: Achieved by a combination of eating well and exercising.All these can be achieved by taking your medication as prescribed, by following a healthy diet and by taking regular exercise. Follow the tips below to make changes to your habits. Maybe start with one change a week! This will help to protect you reyes until your next visit.Take your medication regularly. Set an alarm (e.g. using a phone) asa reminder, or ask a family member to help remind you.Eat something just before taking your medication as this will reduce the likelihood of having an upset stomach.In order to keep blood glucose levels as stable as possible, pay attention to foods that affect your blood glucose – e.g. fruit, fruit juice, potatoes, rice, and so on.Eat three regular meals a day. Missinga meal, or doing more exercise than usual, can result in hypoglycaemic episodes (low blood glucose levels). This is characterised by shaking, pounding heart, nervousness, sweating, tingling, and hunger. If left untreated, it can lead to unconsciousness.Plan meals that look like the plate in Some starchy foods/carbohydrates break down more slowly than others, and are therefore better for keeping your blood sugar stable. Where available, choose wholegrain or brown bread rather than white, whole potatoes rather than mashed, yams/sweet potatoes rather than ordinary potatoes.Eat a maximum of three portions of fruit a day – each portion at a different time of the day.Don't drink more than one glass of fruit juice per day as they are full of sugars.Avoid sugary drinks, e.g. cola – drink plenty of water instead.Avoid alcohol as it makes hypoglycaemia more likely to occur. Alcohol can raise blood pressure and lead to weight gain.Sweets, biscuits and cakes can be eaten once in a while as a treat, i.e. once a week.Avoid eating visible fat (cut it off the meat before you eat it)Avoid fried foods – steamed or baked is better.Exercise helps to lower blood pressure, glucose and cholesterol levels, improves energy levels and general well being, and promotes weight loss. Exercising for 30–50 minutes at least 4–5 times a week is best, but you can start with as little as 20 minutes 3 times a week and build it up from there. Ask for advice from a doctor.


Traditional cardiovascular risk factors in the general population are usually correlated to a better prognosis in patients with chronic heart failure (HF). Most of the studies show that blood pressure variability (BPV) has noxious effect on general population but data are missing for patients with systolic HF. The aim of this study was to assess the prognostic impact of short-term blood pressure variability (BPV) in systolic HF.p = 0.033) and severe NYHA class  were found as independent predictors of cardiac event. Patients with a systolic daytime BPV under a cut-off value of 19 mmHg had the poorest prognosis with an OR for cumulative events of 1.65 .We retrospectively studied 288 patients  referred to our tertiary center of HF for the management of their systolic HF (left ventricular ejection fraction was 28 ± 9 %). All patients underwent ambulatory blood pressure monitoring  and the prognostic impact of BPV was collected with a mean follow-up of 4.4 ± 3.1 years. Twenty-five (9 %) patients were missing for follow-up. Among the others patients, 70 (27 %) cardiovascular events  were recorded. By multivariate analysis BPV daytime (OR = 0.963, BPV is simple tool and a predictor of cardiac events in patients with systolic HF. If high blood pressure (BP), body mass index and cholesterolemia represent traditional cardiovascular risk factors in the general population, they are correlated to a better prognosis in patients with chronic heart failure (HF) –3. In a Patients were retrospectively extracted from our local database of HF and including patients referred the exploration and the management of systolic HF in of the HF unit of the University Hospital of Toulouse from 1999 to 2006. Inclusion criterions were: age over 18 years old, one systolic HF event in life, systolic dysfunction defined by left ventricular ejection fraction <45 %, ambulatory monitoring of BP in at admission. Exclusion criterions were: patients with low flow or treated with intravenous drugs such as inotropic support, infection, dialysis and incomplete ambulatory monitoring of BP.The study was approved by our local ethics committee.Twenty-four-hour ambulatory BP monitoring (ABPM) was performed as previous described in chronic HF , using tFollow up was conducted using physician, patient or family phone contacts. Patients without news within the last month after the AMBP were considered as missing for follow-up. The composite endpoint was defined by the occurrence of cardiovascular events: cardiac death or heart transplantation.t-test was used when appropriate. Nominal variables were compared using either the χ2 or Fischer tests when appropriate. Univariate analysis of the predictive factors of cardiovascular event was performed using respectively log rank and cox methods for qualitative and quantitative variables. Kaplan Meier curve and log mantel cox method were used to illustrate prognosis of high and low level of systolic BP and VBP. Variables from the univariate analysis with P < 0.1 were included in the multivariable stepwise analysis to identify independent predictors of events. Two-tailed P-values <0.05 were considered statistically significant.Continuous variables with a normal distribution are expressed as mean ± standard deviation (SD). To compare numerical data between two groups, paired and unpaired Student Two hundred and eighty eight patients  with systolic HF were included in the study. The baseline characteristics are summarized in Table p < 0.0001, respectively). Details of ABPM are shown in Table The usable of BP records during the 24-h monitoring was 87 ± 11 %. Regarding BP profile, mean systolic BP was 110 ± 15 mmHg, mean diastolic BP was 68 ± 10 mmHg and PP was 42 ± 11 mmHg during the 24-h monitoring. Mean BPV was higher on daytime versus nighttime  patients were missing for follow-up.p < 0.0001 for NYHA III/IV) with more often decompensate HF at admission  than the non-event group. This increase of congestive signs in the event group led to an increased of diuretics administration in comparison with to the non-event group . However, there was no significant difference for left ventricular ejection fraction between the two groups (p = 0.19).Among the 263 others patients, 70 (27 %) cardiovascular events were recorded including 64 (24 %) cardiac deaths and 6 (2 %) heart transplantations with a mean follow up of 4.4 ± 3.1 years. The event group display a worse functional state , daytime diastolic BP  and daytime BPV . Results according to the occurrence of events are shown in Table There was no difference for BP profile between patients with event and patients without event, except for daytime systolic BP , LVEF < 25 %, congestive CHF , decrease of natremia , increase of the clearance of creatininemia .Results of univariate analysis are summarized in Table p < 0.02), daytime systolic BP , nighttime systolic BP  daytime diastolic BP  and systolic BPV  were correlated with a decrease of cardiac events. PP and systolic Dip had not significant impact in prognosis  and severe NYHA class  as two independent predictors of cardiac events. As shown in Fig. p < 0.04). The association of NYHA and BPV gave a better prognosis  is found as an independent factor of cardiac death and/or cardiac transplantation. The daytime level of BPV, as systolic BP level, is correlated with the prognosis of patients with systolic HF. Previous study of Gibelin et al.  showed a2 in patients with CHF and healthy control subjects respectively [Decrease of BPV in patients with CHF is well described. Radaelli et al.  demonstrectively , autonomectively , pre-loaectively  are poteFor the last three decades, several studies demonstrated that usual cardiovascular risk factors become good prognosis markers in patients with CHF. Thus, high body mass index , hyperchBPV is simple tool, easily available, predictor of cardiac death and/or cardiac transplantation in patients with systolic HF. Measure of BPV could help physicians to improve the management of patients with HF by helping to better assess the prognosis and adjust the therapeutics.ABPM, ambulatory blood pressure monitoring; BP, blood pressure; BPV, blood pressure variability; HF, heart failure; PP, pulse pressure


Objective. The head-up tilt test is widely used for evaluation of orthostatic intolerance. Although orthostatic symptoms usually reflect cerebral hypoperfusion, the cerebral blood flow velocity (CBFv) profile in orthostatic syndromes is not well described. This study evaluated CBFv and cardiovascular patterns associated with the tilt test in common orthostatic syndromes. Methods. This retrospective study analyzed the tilt test of patients with history of orthostatic intolerance. The following signals were recorded: ECG, blood pressure, CBFv using transcranial Doppler, respiratory signals, and end tidal CO2. Results. Data from 744 patients were analyzed. Characteristic pattern associated with a particular orthostatic syndrome can be grouped into abnormalities predominantly affecting blood pressure , cerebral blood flow , and heart rate . Psychogenic pseudosyncope is associated with stable CBFv. Conclusions. The tilt test is useful add-on in diagnosis of several orthostatic syndromes. However diagnostic criteria for several syndromes had to be modified to allow unambiguous pattern classification. CBFv monitoring in addition to blood pressure and heart rate may increase diagnostic yield of the tilt test.  The head-up tilt testing is widely used in diagnosis of orthostatic intolerance. The tilting provokes blood pooling in the splanchnic and the lower extremity circulation which triggers the neural and humoral compensatory mechanisms aiming to maintain stable blood pressure and cerebral perfusion. The tilt test assesses the integrity of parasympathetic and sympathetic innervation . The tilCommon orthostatic symptoms are usually defined by heart rate and blood pressure responses to tilting. The orthostatic cerebral blood flow is less studied; even many orthostatic symptoms are due to orthostatic cerebral hypoperfusion . TherefoStandard Protocol Approvals, Registrations, and Patient Consents. The study was approved by the Institutional Review Board of the University of Massachusetts Medical School as a minimal risk study.This retrospective, single-center study included patients with history of autonomic function testing at the University of Massachusetts Medical School, Autonomic Laboratory, between years 2007 and 2014. Patients were referred for evaluation of two types of orthostatic complaints. The first group constitutes orthostatic intolerance symptoms which include dizziness, lightheadedness, unexplained falls, chronic fatigue, heaviness, chest pain, and shortness of breath. The second group includes patients with history of unexplained loss of consciousness that were referred for evaluation of suspected syncope.The details of our standardized testing protocol have been published previously . Autonom2  were used for monitoring respiratory parameters. CBFv was monitored using transcranial Doppler  with a 2 MHz probe. CBFv was obtained from the left middle cerebral artery with the Doppler probe attached to a three-dimensional positioner which kept the probe at a constant depth and angle of insonation.Heart rate was calculated from ECG. Arterial blood pressure was measured in the upper arm intermittently using an automated noninvasive oscillometric device Dinamap ProCare Monitor 100 , as well as continuously by infrared finger plethysmography . Nasal thermistor and end tidal COThe tilt responses were classified as described below.Normally heart rate increases at least 10 beats per minute (BPM) but less than 30 BMP during the tilt  3, 6]. . 6]. NorPOTS is defined by the presence of orthostatic symptoms associated with an increment of heart rate by ≥30 BPM held for more than 30 seconds when changing position from supine to upright in the absence of orthostatic hypotension . The timHistorically, OH is defined as a drop ≥20 mmHg in systolic blood pressure or ≥10 mmHg in diastolic blood pressure within three minutes of standing or head-up tilt. This definition does not take into account the baseline value; therefore a modified definition was that using a relative drop of 80% and 85% in systolic and mean blood pressure, respectively, where supine baseline is 100% .OHTN is a common syndrome with a prevalence of 1.1%  and occuSyncope is defined as a transient loss of consciousness due to global cerebral hypoperfusion . NeurallIn psychogenic syncope, also termed psychogenic pseudosyncope, consciousness is only apparently lost and global cerebral hypoperfusion is absent . In thisPST can be frequently encountered during the tilt test and may be due to underlying anxiety disorder. Paroxysmal PST in this study was defined as intermittent (duration < 2 minutes) tachycardia (heart rate > 100 bpm ) associaIST is associated with persistent or recurrent elevated heart rate (>100 BMP) at rest including supine and excessive or inappropriate heart rate increment in upright position , 18. In OCHOs is a recently described syndrome associated with reduced orthostatic cerebral blood flow velocity (CBFv) without OH, bradycardia, and excessive tachycardia . OCHOs m∗ age cm/s and 82.2–0.45 ∗ age cm/s for men and women, respectively, using the MultiDop T device . The software used in this study is an extension of the Quantitative Scale for Grading of Cardiovascular Autonomic Reflex Tests and Small Fibers from Skin Biopsies (QASAT) , also wrThe clinical variables associated with orthostatic syndromes were compared with normal responses using Wilcoxon rank test since most of the data had nonnormal distribution. Nine clinical syndromes were compared with the normal response to the tilt, for example, OH, OCHOs, OHTN, POTS, IST, PST, syncope, psychogenic syncope, and pCAF, and therefore the initial significance 0.05 was adjusted by Bonferroni correction to 0.005 (0.05/10 comparisons). All statistical analyses were performed using JMP 12.0  statistical software.Data from 744 patients were analyzed. All patients had unrevealing standardized evaluation including medical history, neurological examination, basic metabolic panel, 12-lead ECG, imaging studies (CT or MRI of the brain), and EEG if patients were referred for evaluation of syncope.669 patients were referred for evaluation of orthostatic symptoms including dizziness and 75 patients were referred for evaluation of unexplained loss of consciousness with a suspected diagnosis of syncope.The tilt test was normal in 102 subjects . HoweverFrom 669 patients evaluated for orthostatic intolerance (not syncope), the tilt test was normal in 77 patients. From 75 patients referred for evaluation of syncope, the tilt test showed normal response in 25 subjects, neutrally mediated syncope in 33 patients, and abnormal results but nonsyncope pattern in remaining patients . Addition = 97), pCAF (n = 67), and POTS (n = 67).Figures Syncope was associated with low blood pressure and CBFV . Pure syOH can be progressive Figures , and 7, OCHOs Figures , and 20 In OHTN  orthostaCharacteristic features of tachycardia syndromes  are shown in Figures Vasomotor oscillations , spuriouEight patients had pseudosyncope Figures -23 with Patients with pCAF had reduced CBFv in the supine position, had elevated cerebral vascular resistance in supine position and during the tilt, and had abnormal drop of CBFv score during the tilt .This study showed head-to-head comparisons of common tilt test patterns. Characteristic pattern associated with a particular orthostatic syndrome can be grouped into abnormalities predominantly affecting heart rate , blood pressure , and cerebral blood flow . Psychogenic pseudosyncope is associated with stable CBFv without any particular heart rate or blood pressure pattern. This study also showed that criteria for several orthostatic syndromes had to be modified to allow unambiguous pattern classifications.Orthostatic symptoms, except of syncope, are nonspecific and in general poorly correlating with orthostatic blood pressure or heart rate. This study showed that orthostatic drop in CBFv is more sensitive and specific marker of prediction of orthostatic symptoms than orthostatic blood pressure changes. Therefore CBFv is better proxy for cerebral hypoperfusion than orthostatic hypotension.Criteria for orthostatic syndromes are heterogeneous; some criteria are exclusively physiological  while the others require also the presence of symptoms, for example, POTS. Nevertheless, the information obtained from the tilt test should not be used in isolation but always on clinical ground.These syndromes share excessive heart rate increment. Primarily, it is the timing of tachycardia that distinguishes each syndrome. Using the nonmodified criteria, majority of patients with IST and PST satisfy also the POTS criteria. The ambiguities in determination of tachycardia syndromes were solved by modifying the diagnostic criteria as mentioned in the Neurally mediated syncope has a characteristic pattern. Loss of consciousness usually occurs if systolic blood pressure declines to 60 mmHg  that is PCAF is defined as low supine CBFv without supine hypotension or other hemodynamic abnormalities that can explain low CBFv. Patients with pCAF have increased cerebral vascular resistance that may be due to cerebral autoregulatory failure . CBFv isOriginal definition of OHTN included only an increase of blood pressure during the tilt while heart rate and CBFv responses to tilting were not considered. These limitations can cause diagnostic overlap with POTS since occasional rise in blood pressure during tilting can be observed in the hyperadrenergic form of POTS . FurtherTypically, the tilt test uses heart rate and blood pressure responses in classification of results . The useNo specific changes in hemodynamic parameters except of stable CBFv have been found in this study. This is in contrast with a recent study  which obAmbiguities in definition of orthostatic syndromes were removed by adjusting the diagnostic criteria. Nevertheless, the clinical significance of adjusted criteria needs to be validated in future studies.Tilt test can be used as an add-on in diagnosis of orthostatic syndromes. However diagnostic criteria for several syndromes had to be made more explicit to allow unambiguous pattern classification. To be able to classify all patterns, it is essential to monitor CBFv in addition to blood pressure and heart rate.


Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD.Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks.P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure . Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure .Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD. High blood pressure and nonalcoholic fatty liver disease (NAFLD) are two emerging clinical problems in children closely related to the epidemic of childhood obesity. NAFLD is now the most common cause of chronic liver disease in children in the United States with an estimated prevalence of 9.6%. NAFLD itself has been linked to cardiovascular disease in both children and adults. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NASH Clinical Research Network (NASH CRN) enrolled children with NAFLD in longitudinal cohort studies  and a randomized controlled trial . These studies have been described All studies were approved by the Institutional Review Boards at each participating center. Written informed consent was obtained from parents/guardians and written assent was obtained from children.All liver biopsy specimens were stained with hematoxylin-eosin and Masson's trichrome stains, and reviewed and scored centrally by the Pathology Committee according to the published NASH Clinical Research Network scoring system. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Physical measurements included height, weight, waist circumference, systolic blood pressure, and diastolic blood pressure. Blood pressure was measured and percentiles were computed as instructed in th percentile for age, sex, and height. Hypertension is defined as high blood pressure on at least three separate occasions. For this analysis we defined High blood pressure as systolic or diastolic blood pressure ≥95th percentile for age, sex and height, or the use of antihypertensive medication for a clinical diagnosis of hypertension. Persistent high blood pressure was defined as having high blood pressure at both baseline and at 48 weeks. Clinical hypertension was determined by parental or patient report that a child had a clinical diagnosis of hypertension assigned by their treating physician.The definitions for blood pressure in children are based upon the normative distribution of blood pressure in healthy children. P range from 0.12 to 0.81). Additionally, the set of risk factors was not related to the odds of missing the 48 week follow-up visit (P = 0.41).Descriptive statistics  were used to compare patients with and without elevated blood pressure; P values were determined either from Chi-square tests for categorical variables or from non-parametric two-sample Wilcoxon rank sum tests for continuous variables. Risk factors for high blood pressure were identified using multiple logistic regression models with the presence of high blood pressure as the binary outcome and a candidate set of risk factors: gender, age, race/ethnicity , BMI, GGT, LDL, glucose, insulin, and uric acid. Goodness of fit of the logistic model was assessed using a Hosmer-Lemeshow chi-square test with P>0.05 indicating adequate fit. Parallel analyses were done for risk factors for persistently high blood pressure. Characteristics of those children with and without 48 week follow-up were compared using a logistic regression model of the odds of missing-ness in relation to the risk factors; a Wald test was performed to determine whether set of characteristics differed in those children who were not evaluated at a 48 week follow-up assessment. All analyses assumed nominal, two-sided P values as statistically significant if P≤0.05. Analyses were performed using SAS version 9.3 (SAS Institute) and Stata version 13.1 (StataCorp). Sensitivity analysis of variation in risk factors by gender showed no evidence of effect modification (interaction 2. The distribution of disease severity was: NAFLD but not NASH 27.5% (136/494), borderline NASH 44.7% (221/494) and definite NASH 27.7% (137/494). The majority of participants (358/494) were boys. There was no significant difference between boys and girls with respect to age or race/ethnicity. Boys had a significantly higher BMI Z-score than girls  but no difference in BMI .There were 494 children enrolled in the NASH CRN that met all criteria and were included in the baseline analysis. A study flow chart is shown in 2; P<0.0001). Children with high blood pressure also had significantly higher GGT, LDL-cholesterol, serum fasting insulin, and uric acid values. In addition, children with high blood pressure had significantly more severe steatosis  than children without high blood pressure . As shown in The estimated prevalence of high blood pressure at baseline was 35.8% (95% CI 31.7–40.2). As shown in The estimated prevalence of persistent high blood pressure was 21.4% (95%CI 17.6–25.9). Girls with NAFLD were significantly more likely to have persistent high blood pressure than boys with NAFLD (28.4% [20.5%–38.0%] vs.18.9% [14.7%–24.0%]). As shown in At baseline, 18% (32/177) of children with high blood pressure had a clinical diagnosis of hypertension. There were 10 children taking antihypertensive medication representing 5% of those with high blood pressure and 31% of those with a clinical diagnosis of hypertension. Over the course of one year of follow-up, there were an additional 10 children diagnosed with hypertension. Antihypertensive medications were prescribed to 2 additional children who had a clinical diagnosis of hypertension at baseline and to 2 of the children subsequently diagnosed with hypertension. At week 48, 28% (23/82) of children with persistent high blood pressure had a clinical diagnosis of hypertension and 13% were taking antihypertensive medications.We studied the prevalence of high blood pressure in a longitudinal cohort study of children with NAFLD from pediatric centers across the United States. Children with NAFLD had a high rate of high blood pressure both at baseline and again at 48 weeks. The odds of having high blood pressure at baseline and high blood pressure that persisted at 48 weeks were associated with BMI, LDL-cholesterol and uric acid. Hepatic steatosis was associated with high blood pressure at baseline. Unexpectedly, girls with NAFLD had greater odds of persistent high blood pressure than boys with NAFLD.The rates of high blood pressure in children with NAFLD exceeded what would be expected based upon the contribution of obesity alone. Population-based cohort studies estimate the prevalence of high blood pressure in obese children to be 11%. NAFLD and high blood pressure share pathophysiologic factors such as systemic oxidative stress and vascular and adipose tissue inflammation, which can produce vascular endothelial dysfunction. High blood pressure in childhood tracks into adulthood. The accurate assessment of blood pressure in children with NAFLD was strengthened by the use of the NASH CRN, the largest prospectively enrolled cohort of children with NAFLD with representation from across the U.S. Participants had an accurate diagnosis of NAFLD characterized in a rigorous standardized fashion. Moreover, the inclusion of longitudinal data is rare and particularly important for blood pressure research. The study was limited by the lack of three discrete measures required to confirm a clinical diagnosis of hypertension. However, large longitudinal cohort studies have shown that a single measurement of high blood pressure in childhood is strongly associated with development of hypertension in adulthood. In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation and control should be an integral component of the clinical management of children with NAFLD.


Renal sympathetic denervation (RDN) has been and is still proposed as a new treatment modality in patients with apparently treatment resistant hypertension (TRH), a condition defined as persistent blood pressure elevation despite prescription of at least 3 antihypertensive drugs including a diuretic. However, the large fall in blood pressure after RDN reported in the first randomized study, Symplicity HTN-2 and multiple observational studies has not been confirmed in five subsequent prospective randomized studies and may be largely explained by non-specific effects such as improvement of drug adherence in initially poorly adherent patients (the Hawthorne effect), placebo effect and regression to the mean. The overall blood-pressure lowering effect of RDN seems rather limited and the characteristics of true responders are largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with apparently TRH, drug monitoring and improvement of drug adherence may prove more effective and cost-beneficial to achieve blood pressure control. In the meantime, research should aim at identifying characteristics of those patients with truly TRH who may respond to RDN. Renal sympathetic denervation (RDN) has been and is still proposed as a new treatment modality in patients with apparently treatment resistant hypertension (TRH), a condition defined as persistent blood pressure elevation despite prescription of at least 3 antihypertensive drugs including a diuretic  The role of the sympathetic system in the pathophysiology of hypertension is substantiated by a wealth of experimental and clinical arguments  paid $800 million to purchase Ardian® , the company that had developed the technology Demaria, , and morhttp://www.tctmd.com/show.aspx?id=123265). We  compared to the RDN group (n = 9). Because of sustained elevation of AMBP in the RDN treated patients at 6 months of follow-up, we stopped randomization for ethical reason according to a pre-specified decision  and produced guidelines, and corresponding author of this current review contributed to these. Medical journals were swamped by reviews and meta-analyses showing the powerful blood pressure lowering effects as recorded in observational studies and in the single available randomized study, Symplicity HTN-2. Comments pointing out the defects and inconsistencies in such meta-analysis encountered great delay in getting published ? Of course, publications of the Symplicity studies and multiple observational studies, and enthusiastic editorials and reviews in top-ranking journals  maybe a useful tool for detecting and reducing non-adherence, leading to substantial blood pressure (BP) improvement in this subset of hypertensive patients. . Fadl Elmula M. Fadl Elmula has received speaker honorarium from Medtronic and Hemo Sapiens and Anne C. Larstorp from Hemo Sapiens and Merck et Co. Alexandre Persu declares no conflict of interest.


May is National Blood Pressure Education Month, dedicated to increasing awareness and educating patients and the public about hypertension and its impact on health. Hypertension, also known as high blood pressure, is a leading risk factor for cardiovascular disease and a major cause of morbidity and mortality . In the Patients can achieve greater hypertension control by taking their medications as directed, measuring their own blood pressure, and eating a lower-sodium diet. Health-care providers and systems can use electronic health records, blood pressure monitoring, and a team-based care approach to help improve their patients’ hypertension control .http://millionhearts.hhs.gov. Additional information about hypertension is available from CDC at http://www.cdc.gov/bloodpressure.Million Hearts, a U.S. Department of Health and Human Services initiative led by CDC and the Centers for Medicare and Medicaid Services, is focusing efforts to prevent 1 million heart attacks and strokes by 2017. Million Hearts is working to reduce hypertension by 1) educating health-care professionals, health systems, insurers, employers, and individuals about the link between blood pressure control and health, and 2) empowering all persons to make healthy choices, such as preventing or quitting tobacco use and reducing salt (sodium) and trans fat consumption, to decrease the number of persons who need medical treatment and to prevent heart attacks and strokes. Additional information about Million Hearts is available at


In response to concerns raised by readers of this paper , the autAbstractThe Methods section in the Abstract should more explicitly state the nature of this study as not simply a randomized control trial, but a trial with a related observational study.The original text reads as:In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as no-treatment control so as to monitor the natural fluctuation of glucose tolerance in IGT patients.The revised text reads as:In this pilot randomized clinical trial with an additional observation group, we first compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. Then, an additional 30 IGT adults were recruited separately as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients.MethodsThe authors wish to clarify the statistical analyses and comparisons performed in their Methods sections.The original text reads as:Statistical analysisOur analyses were based on the intention-to-treat principle. Statistical analysis was performed using SPSS 19.0 Software . Repeated measurements were applied to compare primary and secondary outcomes. First, we compared the taVNS and sham taVNS groups; then, we separately compared real and sham taVNS with the no-treatment control population, to further assess and isolate the treatment effects of taVNS and sham taVNS.The revised text reads as:Our analyses were based on the intention-to-treat principle, and only subjects who had completed a data set were included in data analysis. Statistical analysis was performed using SPSS 19.0 Software . Repeated measurements were applied to compare primary and secondary outcomes. First, we compared the taVNS and sham taVNS groups; then, we separately compared real and sham taVNS with the no-treatment control condition  to further assess and isolate the treatment effects of taVNS and sham taVNS. For repeated measurements, Mauchly’s Test of Sphericity were applied, if assumptions of sphericity were violated, Greenhouse Geisser corrected degrees of freedom were applied. In addition, we also repeated the above analysis to include age, gender and BMI as covariates to adjust for the effects of factors.ResultsThe results section should more explicitly separate the comparisons between groups from solely the randomised controlled trial, and the observational comparisons which made use of both the randomised and observational data.The original text reads as:Comparison between the taVNS and sham taVNSComparison by Independent Samples t-test showed that the two groups did not differ in age (t(70) = 1.51, p = 0.14), weight (t(70) = −0.83, p = 0.41) systolic blood pressure (t(70) = 1.42, p = 0.16), diastolic blood pressure (t(70) = 0.22, p = 0.16), or BMI (t(70) = 64.07, p = 0.61) at baseline (Table 1). The gender distribution also did not differ significantly across groups  =3.29, p = 0.07). Measures of FPG (t(70) = 0.3, p = 0.77), 2hPG (t(70) = 1.96, p = 0.054) and HbAlc (t(70) = 1.12, p = 0.27) similarly did not differ between groups at baseline. Comparison of the taVNS and sham taVNS groups using repeated measures analysis of variance (ANOVA) indicated a significant difference in 2hPG between groups over the course of the experiment (F(2) = 5.79, p = 0.004)  = 1.95, p = 0.15), weight (F(2) = 0.85,p = 0.43), diastolic blood pressure (F(2) = 1.05, p = 0.37), gender distribution  = 3.29, p = 0.2), or BMI (F(2) = 2.96, p = 0.057) at baseline. Measures of FPG (F(2) = 2.86, p = 0.06), 2hPG (F(2) = 2.03, p = 0.14) and HbAlc (F(2) = 1, p = 0.37) also did not differ between groups at baseline. There was, however, a significant difference in systolic blood pressure (F(1) = 1.02, p = 0.01). Repeated measures ANOVA between the taVNS and no-treatment control indicated significant differences in FPG (F(2) = 10.62, p < 0.001), 2hPG (F(2) = 25.18, p < 0.001) and HbAlc (F(1) = 12.79, p = 0.001) between groups over the course of the 12 weeks. All effects remained significant after adjusting for age, gender, and BMI Comparison by Independent Samples t-test showed that the two groups did not differ in age (t(70) = 1.51, p = 0.14), weight (t(70) = −0.83, p = 0.41) systolic blood pressure (t(70) = 1.42, p = 0.16), diastolic blood pressure (t(70) = 0.22, p = 0.16), or BMI (t(70) = 64.07, p = 0.61) at baseline. The gender distribution also did not differ significantly across groups  =3.29, p = 0.07). Measures of FPG (t(70) = 0.3, p = 0.77), 2hPG (t(70) = 1.96, p = 0.054) and HbAlc (t(70) = 1.12, p = 0.27) similarly did not differ between groups at baseline.Comparison of the taVNS and sham taVNS groups using repeated measures analysis of variance (ANOVA) indicated a significant difference in 2hPG between groups over the course of the experiment (F(2) = 5.79, p = 0.004)  = 4.21, p = 0.044). In the taVNS group, systolic blood pressure dropped from 123.69 ± 14.14 (mean ± SD) to 118.64 ± 13.34, while in the sham taVNS group, systolic blood pressure remained at 119 ± 12. No significant differences were observed for changes in diastolic blood pressure (F(1) = 0.75, p = 0.39) or BMI (F(1) = 0.069, p = 0.79).Comparison between taVNS, sham taVNS and no-treatment control In this study, we added a separate no-treatment control group recruited from a free physical exam program at a community clinic. This group was included to better understand the natural fluctuation of outcomes in patients with IGT and to isolate the pure treatment effects from other naturally occurring factors.Analysis of variance indicated that the three experimental groups did not differ in age (F(2) = 1.95, p = 0.15), weight (F(2) = 0.85,p = 0.43), diastolic blood pressure (F(2) = 1.05, p = 0.37), gender distribution  = 3.29, p = 0.2), or BMI (F(2) = 2.96, p = 0.057) at baseline. Measures of FPG (F(2) = 2.86, p = 0.06), 2hPG (F(2) = 2.03, p = 0.14) and HbAlc (F(2) = 1, p = 0.37) also did not differ between groups at baseline. There was, however, a significant difference in systolic blood pressure (F(1) = 1.02, p = 0.01).Repeated measures ANOVA between the taVNS and no-treatment control indicated significant differences in FPG (F(2) = 10.62, p < 0.001), 2hPG (F(2) = 25.18, p < 0.001) and HbAlc (F(1) = 12.79, p = 0.001) between groups over the course of the 12 weeks. All effects remained significant after adjusting for age, gender, and BMI Table .Analysis of other secondary outcomes, with comparison between the taVNS and no-treatment control groups, indicated that there were no significant differences between the two groups in systolic blood pressure (F(1) = 0.99, p = 0.32), diastolic blood pressure (F(1) = 1.27, p = 0.27), or BMI (F(1) = 0.003, p = 0.96) over time.Repeated measures ANOVA between the sham taVNS and no-treatment control group showed that the two groups differed significantly in their levels of 2hPG (FGG(1.72) = 10.51, p < 0.001) and HbAlc (F(1) = 5.94, p = .018) over the course of the experiment. Measures of both 2hPG and HbAlc increased over the 12 weeks in the control group, and decreased over the course of the 12 weeks in the sham taVNS treatment group. After controlling for age, gender, and BMI, only the effect for change in 2hPG remained significant  = 1.44, p = 0.24), diastolic blood pressure (F(1) = 0.047, p = 0.83), or BMI (F(1) = 0.024, p = 0.88) over time.Tables 5A repeated measures analysis of variance (ANOVA) at three time points was applied, and the p values in Tables Corrected tables:DiscussionThe authors accept that the nature of their study as a pilot was unclear. The section of their Discussion dealing with limitations has therefore been amended.The original text reads as:Secondly, the treatment was only 12 weeks in duration, thus the results obtained only represent its short or mid-term effects. Further study is warranted to evaluate the long-term effects of this treatment option.The revised text reads as:Secondly, as a pilot study, the treatment was only 12 weeks in duration. Thus the results obtained only represent its short or mid-term effects. Further study is warranted to evaluate the long-term effects of this treatment option.


Everyone with risk factors of chronic kidney disease (CKD) such as high blood pressure, diabetes mellitus, metabolic syndrome, family history of CKD and proteinuria should be educated about the benefits of early identification of the disease and subsequent kidney protection through appropriate interventions.et al. about increasing awareness of chronic kidney disease and aging , the causes of ESRD were unknown  were the leading causes of CKD in the world, too. However, possibly due to lifestyle changes and increasing prevalence of obesity, diabetes and hypertension and because of more available aggressive treatment of GN, it is well established that diabetes and hypertension are now the primary causes of CKD in developed countries -6. Howev unknown . The res in 2002 , Malekma in 2009  and Sala in 2004  were alsIn some developing countries like Iran, the significant percent of patients with CKD are presented to the nephrologist with the severe symptoms of uremia and late stage of the disease. Unfortunately at this time, determining the primary causes of CKD is not possible.Renal biopsy is also not helpful and it cannot determine the cause of CKD at the end-stage of the disease. Regardless of the causes of CKD, histologic findings of kidney biopsy at the late stage of CKD are glomerulosclerosis, tubular atrophy and interstitial fibrosis and therefore renal biopsy is not helpful. In addition, in most of the patients with CKD, the sizes of kidneys are gradually decreased and kidney biopsy is not possible at the end stage. It is associated with increment risk and therefore kidney biopsy not recommended ,14.In conclusion, although the diabetic nephropathy and hypertensive nephrosclerosis are also the most common causes of ESRD in developing countries, however, possibly because of unawareness of patients with CKD and late referral of patients with CKD to the nephrologists, the causes of ESRD in the significant percent of patients in developing countries are still unknown and therefore everyone with risk factors of CKD such as high blood pressure, diabetes mellitus, metabolic syndrome, family history of CKD and proteinuria have to be educated about the benefits of early identification of the disease and subsequent kidney protection through appropriate interventions.All authors contributed to the paper equally.Ethical issues  have been completely observed by authors.The authors declared no competing interests.None.


Pseudomonas spp. of Proteobacteria and Lactobacillus spp. of Firmicutes were highly abundant in asthma and COPD. By contrast, Streptococcus, Veillonella, Prevotella, and Neisseria of Bacteroidetes dominated in the healthy oropharynx. These findings are consistent with previous studies conducted in the lower airways and suggest that oropharyngeal airway microbiota are important for understanding the relationships between the various parts of the respiratory tract with regard to bacterial colonization and comprehensive assessment of asthma and COPD.Respiratory infections are well-known triggers of chronic respiratory diseases. Recently, culture-independent tools have indicated that lower airway microbiota may contribute to pathophysiologic processes associated with asthma and chronic obstructive pulmonary disease (COPD). However, the relationship between upper airway microbiota and chronic respiratory diseases remains unclear. This study was undertaken to define differences of microbiota in the oropharynx of asthma and COPD patients relative to those in healthy individuals. To account for the qualitative and quantitative diversity of the 16S rRNA gene in the oropharynx, the microbiomes of 18 asthma patients, 17 COPD patients, and 12 normal individuals were assessed using a high-throughput next-generation sequencing analysis. In the 259,572 total sequence reads, α and β diversity measurements and a generalized linear model revealed that the oropharynx microbiota are diverse, but no significant differences were observed between asthma and COPD patients.  Asthma and chronic obstructive pulmonary disease (COPD) are common chronic inflammatory diseases of the airways, and their prevalence and mortality rates continue to increase, establishing them as leading causes of disability worldwide Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are clinically relevant contributors to asthma exacerbations, particularly when sinusitis is present Chlamydophila pneumoniae and Mycoplasma pneumoniae may also be associated with asthma Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are known to be associated with a significantly increased risk of exacerbation of COPD. However, the prevalence of bacterial pathogens in the lower airways was found to be the same during acute exacerbations and stable disease; thus, changes in bacterial load are unlikely to be an important mechanism underlying exacerbation of COPD Clinical studies of chronic respiratory diseases have been focused on their association with common respiratory viruses. Respiratory viral infections are common and usually self-limiting illnesses in healthy adults but are a major cause of exacerbations in patients with asthma and COPD Human microbiota is diverse across individuals and different sites in the body. Oral microbiota are known to be involved in upper and lower respiratory infections, which can also develop into atopic airway diseases such as allergic rhinitis and bronchial asthma Oral microbiota can trigger and strike as a critical component in conditions like Bronchial asthma and COPD Traditionally identification of bacteria in the oral cavity has been done by culturing methods. Analysis of microbiota through culture-dependent methodologies is both expensive and time-consuming in comparison with many of the available culture-independent methods. It is evident to assess minor or non-dominant populations, culture-independent strategies are important for analysis of microbial ecology. Previous studies demonstrate culture-independent approaches have revealed more diverse microbiota compared to culture-dependent microbiota, of which nearly 40–60% bacterial taxa in the mouth were uncultured or validly described Recent high throughput methods like next-generation sequencing have revolutionized the way diversity of microbial communities in varied environments, including the human body is analyzed All of the samples were collected from individuals with newly diagnosed asthma and COPD in accordance with the ethical guidelines mandated by the commission a protocol (number #12-0015) that was approved by the University’s Human Subjects Institutional Review Board (IRB) of Chung-Ang University College of Medicine, Seoul, Korea. Human subjects remain anonymous and the informed consent was written. All participants gave written informed consent for participation in the study. The current diagnosis of asthma was based on a history of wheezing, shortness of breath, and cough, which were variable in severity and frequency The first step in the analysis was extraction of DNA from the bacterial pellet that was obtained from oropharyngeal swab samples, followed by polymerase chain reaction (PCR) analysis. Samples were extracted individually by using the cetyltrimethylammonium bromide method 5′-GTATTACCGCGGCTGCTG-3′) with the MID sequence. PCR was performed in final reaction mixtures of 25 µL containing 5–25 ng of genomic DNA, each primer at 0.4 mM, 0.2 mM dNTPs , 1.5 mM MgCl2 , 2.0 U of Hot Start Taq polymerase (Takara), and 1.0 µL of reaction buffer (Invitrogen). PCR amplification was performed on a GeneAmp PCR system 9700 thermocycler  under the following conditions: initial denaturation for 5 min at 94°C, followed by 30 cycles of 30 s at 94°C, 30 s at 55°C, and 1 min at 72°C, with a final extension for 10 min at 72°C and cooling to 4°C. The PCR products were resolved on a 1.2% Seakem LE agarose gel  and visualized after ethidium bromide staining. 454 sequencing was carried out on the pooled PCR products of equal amounts. Amplicon pyrosequencing was performed using a 454/Roche GS-FLX Titanium instrument . After sequencing, the sequence file (.fna) and quality file  were recovered by MID groups. Quality control of the post-processing sequences was performed to eliminate sequences with ambiguous base calls, homopolymers >6, quality scores <Q25, read lengths <250 bp, and low-quality sequence ends and those without a 100% match to barcodes. Random sampling was used to analyze the diversity of the low reads of the sequence and the high reads of the sequence set. Tests of the sequence analysis methods are described in PRINSEQ http://www.ncbi.nlm.nih.gov/sra) with accession number SRX316595.PCR amplification of the 16S rRNA gene was performed following established procedures http://www.arb-silva.de/, Release 115) and the BLAST webpage of the NCBI. Accurate identification of organisms through comparative analysis of 16S rRNA gene sequences is strongly dependent on the quality of the database that is used. The curated Ribosomal Database Project  provides bacterial and archaeal small subunit rRNA gene sequences in an aligned and annotated format, and has achieved major improvements in the detection of sequence anomalies http://unifrac.colorado.edu/static/welcome.html). Weighted and normalized PCoA and Jackknife Environment Clusters were used to evaluate similarity among samples, where each sample represented an environment. Hierarchical cluster analysis was performed using complete linkage and UniFrac distances as a measure of similarity The nucleotide sequence homology of the amplified 16S rRNA gene V1–V3 regions was determined using the nucleotide BLAST (BLASTn) program, which is available at the SILVA website  was constructed using the final set of chosen variables. The following The parameter beta was tested at a 5% significance level by using (a).The 47 characteristics of the subjects are summarized in The diversity of microbiota in the oropharyngeal swab sample was characterized by sequencing the V1–V3 region of the 16S rRNA gene, which was amplified from genomic DNA samples of 18 asthmatic patients, 17 COPD patients, and 12 healthy controls. In total, 259,572 bacterial sequence reads were identified for three group samples with average read lengths of 273–476 bp  . The 191The Chao1 estimator of total species richness sequences in healthy controls and asthmatic and COPD patients is described in Species richness, diversity, and rarefaction calculations were used to analyze whether the diversity of the oropharyngeal microbial community was sufficiently covered by the sequence data. Species coverage, richness, evenness, and diversity were estimated for the combined data set for each of the bacterial sequences from the oropharyngeal samples. In addition, OTUs (5% difference) were calculated for the healthy control group and patients with asthma and COPD. Rarefaction analyses with RDP analysis curves at the OTUs reached saturation for the subjects with lower microbial diversity when the sequences of each sample type and the total number of OTUs were estimated. The diversity ranged from 29 to 410 OTUs with 95% similarity in each of the 47 samples  . The calSeven bacterial phyla were detected, but most sequences were assigned to three phyla: Firmicutes, Proteobacteria, and Bacteroidetes. In 17 of 18 asthmatic patients, the majority of bacteria belonged to Firmicutes (59.8%), at a proportion higher than that in the healthy controls (48.4%). In addition, in 17 of 17 COPD patients, 61.6% of the bacterial phyla belonged to Firmicutes. Therefore, an increase in the prevalence of Firmicutes from 59.8% in the asthma sample to 61.6% in the COPD sample was observed. In the 12 healthy control samples, Proteobacteria and Bacteroidetes composed 29.02% and 16.20% of the bacteria community, respectively. In asthmatic and COPD patients, Proteobacteria accounted for 35.61% and 28.04% of the bacteria community, respectively. However, the percentage of Bacteroidetes was drastically decreased in the asthma (2.62%) and COPD (7.17%) groups .The relative abundance of the main phyla identified in the normal control group and in the asthmatic and COPD patients was analyzed using an R script with gplots and the RColorBrewer package . The FirStreptococcus spp. (33.05%), Neisseria spp. (21.69%), Prevotella spp. (13.42%), and Veillonella spp. (8.01%). Most sequences in the bronchial asthma library were identified as Lactobacillus spp. (29.67%), Streptococcus spp. (28.34%), Pseudomonas spp. (15.80%), Neisseria spp. (6.26%), Prevotella spp. (2.49%), and Veillonella spp. (3.46%). Intriguingly, Stenotrophomonas spp. (2.94%) was present in the asthmatic group (eight of 18 patients), but largely absent from the healthy control group (0.01%) and COPD group (0.32%). Most sequences in the COPD library were identified as Lactobacillus spp. (34.50%), Streptococcus spp. (23.52%), Pseudomonas spp. (10.13%), Neisseria spp. (5.26%), Prevotella spp. (4.21%), and Veillonella spp. (3.98%).To diversity of the microbial communities present in the oropharyngeal swab samples, was determined from BLASTn analysis, where the assembled sequences showed closest relationship with their neighbouring genera. Although the three data sets showed broad taxonomic similarity, there was notable variation in each sample at the genus level. In total, 190 different bacterial genera were identified in this study: 105, 131, and 133 different genera were present in the healthy control, asthma, and COPD groups, respectively . Most seNeisseria spp. (Proteobacteria) and Prevotella spp. (Bacteroidetes) constituted 21.69% and 13.42% of the sequences, respectively, and thus comprised more than 40% of the bacterial community in the healthy control group compared to just over 10% in the asthmatic and COPD patients. When compared to the healthy controls, Lactobacillus spp. (29.67% and 34.50%) and Pseudomonas spp. (15.80% and 10.13%) were much more prevalent in patients with asthma or COPD, respectively. Lactobacillus spp. was present in 14 of 18 asthmatic patients and 15 of 17 patients with COPD, and Pseudomonas spp. was present in 10 of 18 asthmatic patients and eight of 17 patients with COPD. This was in contrast to the low frequencies of Lactobacillus spp. (0.07%) and Pseudomonas spp. (0.06%) in the healthy control population, i.e., six and four, respectively, of a total of 12 individuals. The proportion of Pseudomonas spp. decreased from 15.80% in the asthma sample to 10.13% in the COPD sample, and that of Lactobacillus increased from 29.67% in the asthma sample to 34.50% in the COPD sample. Among the phylum Bacteroidetes, populations of Prevotella spp. that were observed in the healthy control group were replaced with Pseudomonas spp. of Proteobacteria in the asthma and COPD groups  and Lactobacillus spp. (6.0006) were found with greater frequencies in the asthmatic and COPD patients. Streptococcus spp., Neisseria spp., Veillonella spp., and Prevotella spp. were found with greater frequencies in the healthy controls (p<0.0001). Jackknife clustering and PCoA were performed using Fast UniFrac We found that the three phyla and six genera in the normal controls and patients with asthma and COPD that were identified by sequencing and BLASTn analysis were significantly different in terms of frequency among samples, as indicated by the GLM statistical analysis . In the The identification of microbiota in the healthy control, asthma, and COPD groups , proved Respiratory diseases include the common cold, influenza, pharyngitis, sinusitis, bronchitis, pneumonia, asthma, and COPD, which account for more than 10% of visits to primary care physicians So far the studies of the microbial community in asthma and COPD of human airways, have targeted the lower respiratory tracts using samples such as BAL and the sputum, showing controversial results about the role of the microbiota. There are still gaps when compared to previous studies in this aspect, for instance trying to understand the role of the microbial populations in the lower respiratory tract of oropharyngeal airway in conditions like asthma and COPD which is still unclear. So it becomes imperative to get a true representation of the microbiome in these disease states.In present decade it has become possible to capture the true microbial diversity with modern high throughput culture-independent techniques which aid in comparing the microbiome between the healthy and diseased conditions. These studies can provide new information on the oropharyngeal microbiota in asthma and COPD patients. Previously, several studies investigated the links between airway bacterial concentrations and COPD, but with targeted molecular typing methods aimed at detecting specific bacterial species in the sputum Pseudomonas spp. of the phylum Proteobacteria and Lactobacillus spp. of the phylum Firmicutes prove to be the most dominant populations in asthma and COPD patients but however were not detected in the healthy oropharynx. The final conclusion from this study is the dominance of groups like, Streptococcus, Veillonella, Prevotella, and Neisseria, belonging to the phylum Bacteroidetes, in the healthy oropharynx.In the current study, we gathered comprehensive information concentrating on the whole microbial diversity of the lower respiratory tract as opposed to previous studies with a non-targeted culture independent approach. We have three main conclusions from this study. First in terms of overall diversity, the oropharyngeal airway microbiota are quite diverse but reveal only few differences between asthma and COPD patients. Secondly, p<0.0001). As observed Pseudomonas  and Lactobacillus spp.  were found to be in abundance in asthma and COPD subjects when compared to healthy individuals. This is consistent with the findings of previous diversity studies in the bronchi of asthma and COPD patients, by 16S rRNA gene-based Sanger sequencing and by the 16S rRNA PhyloChip methods in endotracheal aspirates Briefly highlighting the methodology, sequences were generated using a high-throughput GS-FLX 454 pyrosequencer and aligned using tools like PRINSEQ, RDP, and Clustal_X. A GLM analysis of the 259,572 total sequence reads reveals a rich microbial environment in the oropharyngeal airway in asthma and COPD individuals. Distance-based statistical UniFrac tests were used for detecting the changes in abundance and rare lineages Prevotella, were more frequent in controls than in adult or pediatric asthmatic or COPD patients. Sze et al. Lactobacillus species. Using 16S rRNA-based culture-independent profiling methods, Huang et al.Hilty et al. Pseudomonas, Stenotrophomonas, and Lactobacillus were found to be dominant. Whereas the main phyla reported in the bronchoalvelolar lavage fluid of COPD patients are Actinobacteria, Firmicutes, and Proteobacteria, with dominance of Pseudomonas, Haemophilus, or Stenotrophomonas. in the respective phyla Haemophilus was not found in our study of the oropharynx. Pseudomonas and Stenotrophomonas maltophilia are the most common pathogenic bacteria associated with cystic fibrosis Pseudomonas was also reported to a risk factor for severe acute exacerbation Lactobacillus is known to be involved in severe COPD and fatal lung abscess In the oropharyngeal airway of asthma and COPD patients, Streptococcus, Veillonella, Prevotella, and Neisseria of phylum Firmicutes when compared to asthmatic and COPD patients. Normally, Streptococcus species are considered to be commensal bacteria of the oral cavity; however, S. pneumoniae, S. mitis, and S. oralis are members of the viridians streptococci and are associated with pneumonia and endocarditis and are considered as opportunistic pathogens Veillonella is a type of subgingival microflora found at periodontal disease sites and is known to be a periodontopathogenic bacteria Prevotella copri was reported to be involved in inflammation In our study the healthy controls showed higher frequencies of organisms from Neisseria in smokers Neisseria was less dominant in asthmatic and COPD patients, implying that Neisseria is an important indicator of the health of the oral and upper respiratory tract. Therefore, the potential relationship between these oropharynx microbiota and chronic respiratory diseases should be evaluated.Previously, several studies reported less abundance of Previously exquisite study of the bronchial microbiome obtained from lower respiratory samples avoiding upper airway contamination in the healthy adults revealed overlapping of certain groups of bacteria similar to upper airways in six subjects Figure S1Bacterial diversity in respiratory tract samples. The graph shows rarefaction curves indicating the number of assigned operational taxonomic units in relation to the number of 16S rRNA sequences.(TIF)Click here for additional data file.Table S1Abundance table of normal, asthma and COPD.(DOC)Click here for additional data file.