Autosomal dominant polycystic kidney disease (PKD) is the most common genetic renal disease and the fourth leading cause of end-stage renal disease in the United States. Although there is no cure for PKD, several treatments are considered to be beneficial, including blood pressure control, exercise, low-salt diet, and high volume water intake. However, levels of understanding of the importance of these treatments and adherence to these recommendations vary among patients. This study explores illness perception models of patients with PKD to reveal barriers in adherence to prescribed therapies; satisfaction with medical care; and sources of medical information.N = 190) and responded voluntarily to an introductory survey (N = 50). Seventeen PKD patients in the Bay Area were scheduled for one-on-one in-depth interviews with one trained interviewer (W-CT). Open-ended questions administered with an interview guide were used to evaluate patients’ beliefs.We designed a phenomenological interview study to evaluate illness perception models of individuals with PKD. Patients were identified from the national PKD Foundation e-mail distribution list (Mean age was 56.6 +/− 12 years (range 29–78); 65% were female. Many of the PKD patients in this study were highly motivated and willing to incorporate blood pressure, exercise, low-salt diet, and high volume water intake into their daily routines. Barriers to adherence to these therapies include personal beliefs and confusion due to unclear recommendations.These findings suggest there is variability between what patients understand about their disease and treatments and what they believe their doctors have told them. Not all physicians focus on lifestyle-based treatments, but the majority of PKD patients in our study are motivated and willing to incorporate blood pressure control, exercise, low-salt diet, and high volume water intake into their daily routines and would like specific recommendations on how to implement these. These findings support a role for further exploring patient beliefs about the disease and its necessary treatments in order to design strategies to improve communication and meet the needs of these patients.The online version of this article (doi:10.1186/s12882-017-0641-3) contains supplementary material, which is available to authorized users. Autosomal dominant polycystic kidney disease (PKD) is the most common genetic renal disease and the fourth leading cause of end-stage kidney disease in the United States . IndividDespite the absence of a cure, several recommended treatments may attenuate progression of kidney disease and / or reduce risk of cardiovascular events. These include 1) blood pressure control ; 2) exerLevels of understanding of the importance of these treatments and adherence to these recommendations may vary among patients. Illness models have been used in the study of hypertension and other chronic diseases to study barriers to adherence . The stuN = 190) and voluntarily responded to an introductory survey (N = 50). Seventeen PKD patients in the Bay Area came to UCSF for one-on-one in-depth interviews with a trained interviewer (W-CT). The characteristics of patients who responded to the survey and the interview participants are summarized in Table We designed a phenomenological interview study to evaluate illness perception models of individuals with PKD . PatientInterviews were conducted in a private classroom. Open-ended questions administered with an interview guide were used to evaluate patient beliefs on 1) the treatments available for PKD; 2) whether they had been prescribed blood pressure control, exercise, low-salt diet, and high volume water intake and their adherence to these treatments; and 3) sources of medical information. The interview guide was developed based on previous studies conducted by the authors in different patient populations , 17, as rev.com. Transcriptions were reviewed for quality, and the responses were initially organized by question on an Excel spreadsheet. The responses were then coded independently by two trained individuals (W-CT and DH). Discrepancies were discussed until consensus was established. The coded data was grouped into themes  is fine…When I started educating myself…is when I went…“You should at least take the lisinopril because you know your blood pressure is high.” Similarly, another participant initially believed that she could lower her blood pressure with exercise. She became more willing to take her blood pressure medication when a doctor “had mentioned...that I don’t have (the type of) kidney disease where your blood pressure can be lowered because of diet or exercise.”Eleven participants had been told to avoid certain types of exercise or physical activity, including contact sports and weight lifting. Two participants reported deliberately going against these recommendations because the activity helped them psychologically and they had not experienced any adverse effects Table . One parAlthough fifteen participants had been told to follow certain diets, only 5 out of 15 received these recommendations from their physician. The remainder learned of dietary restrictions from nutritionists, dieticians, family members, and articles Table . One indMany participants also reported receiving confusing or conflicting dietary recommendations. One participant recalled that her nutritionist would recommend “a portion,” which she found unhelpful because “what is a portion?” Consequently, she had done reading and used the internet for dietary recommendations. To add to the confusion, one participant recalled being referred to a program for kidney disease patients that included classes on how to eat. However, she later learned at PKD meetings that “diet care just for kidney failure is different than kidney failure from PKD” and there are “a lot of different things that (PKD patients) are not supposed to have.”Another participant summarized the challenge of having uncertain recommendations: “The hardest part is because you don’t know that any of it is actually beneficial. So part of you could just be like, screw it, I’ll just drink coffee everyday and have steak and hamburgers for dinner…Or I could be like, well it might be making my kidneys worse, so I’m going to limit everything and suffer a little bit now in hopes that maybe I’ll prolong the demise from this disease.”Several participants received conflicting information about water intake. One participant recalled, “I’ve been told to drink a lot of water or you can drink too much water and it’s going to be a bad thing for you.” She explained that her doctor always told her to stay hydrated but “doesn’t tell me what to drink.” On the other hand, she had heard at research meetings and support groups that “there’s been studies that show if you drink this much water that it will help keep you function at a steady pace.” Because “they just contradict themselves,” she “just drinks the recommended dose for any given person.”Similarly, another participant had read a study about drinking six to eight liters of water per day instead of two to three liters per day. When she mentioned this to her first nephrologist, she was told, “It does sound like a good idea.” When she switched nephrologists, the new one told her, “That study was inconclusive…drink your two liters of water a day and don’t worry about drinking any more.” As a result, the participant reported feeling “kind of left just blank like I don’t know.” Another individual reported that he “read there’s no evidence that .” However, his nephrologist “believes that it’s the right way to go.”We found that PKD patients are motivated and willing to incorporate blood pressure control, exercise, low-salt diet, and high volume water intake into their daily routines. Seventy-five percent of the participants who were prescribed blood pressure medication reported adherence, which is higher than the reported 50% medication adherence rates for chronic diseases , 16. SimThe higher adherence rates in this study may be due to the patients’ beliefs that medication and lifestyle changes are necessary for slowing the progression of their disease, as suggested by a patient who believed diet lowered her creatinine levels and another patient who became more willing to take her blood pressure medications after lifestyle changes failed to lower her blood pressure. This is consistent with the Ross et al. study describing patients’ beliefs and compliance, which found a strong correlation between compliance and belief in the necessity of the intervention .However, personal beliefs can also be a barrier to adherence. Ross et al. also found that individuals who believed they could control their blood pressure with lifestyle changes were less likely to be adherent with their medications . SimilarAnother barrier to adherence that we identified was confusion due to unclear recommendations, especially about water intake. Many participants reported receiving conflicting or confusing instructions from physicians or only receiving recommendations from non-physician sources. This is consistent with the Bell and Kravitz study showing that physicians mention the importance of physical activity/exercise, healthy eating, and sodium restriction in only 54.2%, 38.3%, and 14.2% of office visits for hypertension, respectively . This maThese findings suggest there is variability between what patients understand about their disease and prescribed treatments and what they believe their doctors have told them. First, not all physicians focus on lifestyle-based treatments, but the majority of PKD patients in our study reported desiring specific recommendations on how to implement these and sought information from non-physician sources. Many patients expressed a desire for greater engagement from their nephrologists in addressing modifiable lifestyle choices as well as greater communication. This echoes the desire for greater physician contact during the “latent period” between diagnosis and symptom manifestations observed by Baker et al. in a previous study in England . This alSecond, participants experienced confusion about recommendations, which further supports a need for improving communication between physicians and patients. While patients may be receiving varying advice due to limited evidence or different stages of kidney disease, these should be made clear to patients. Furthermore, it may be helpful to provide more specific instructions given that participants expressed confusion over vague recommendations. Studies support that providing specific instructions including the amount and frequency of water intake  achieved more consistent changes .This study has strengths and limitations. Our interview strategy allowed participants to freely express their personal beliefs, whether or not these agreed with physician recommendations. We used an interview guide but provided opportunities for participants to discuss their responses in an open-ended fashion. All interviews were conducted by a single interviewer who was not known to the patients prior to the interviews, allowing for impartiality. The strength of the qualitative method in this instance is to learn, from the patient’s perspective, how beliefs and practices regarding PKD care develop, given that there are not widely recognized or disseminated guidelines for how patients should take care of their disease. Qualitative inquiry is particularly suited to situations of ambiguity. Because guidelines for self-care in PKD are ambiguous, and can change over the course of the disease, patients need to interpret and adapt what they have heard regarding self-care. The qualitative approach employed is sensitive to variations in patient beliefs and efforts at self-care. Limitations of the study included the small number of patients represented, and the fact that all were from the Northern California region. However, the participants were drawn from many different nephrology practices and qualitative research conducted with a rigorous approach generally allows for a smaller sample size than quantitative research studies. In addition, the participants voluntarily responded to a survey sent to the national PKD foundation email list, which may be selecting for individuals who are more proactive and motivated to pursue interventions. Those who are members of the email list may also be more technologically savvy and/or of higher socioeconomic status with access to a computer and the Internet, allowing for greater exposure to information and resources. Although this may limit generalizability, the themes that emerged from these interviews represent important areas that warrant further evaluation in the broader PKD community. We recognize that a deeper exploration in a larger sample may reveal other themes and sub-themes. The current study also did not allow for obtaining physician perspectives.Overall, most PKD patients in our study were highly motivated to pursue therapies they believed to be helpful whether prescribed by a doctor or another source of information. These findings support a role for further exploring patient beliefs about the disease and its necessary treatments in order to design strategies to improve communication and meet the needs of these patients. Participants also experienced some confusion about topics including lifestyle change, which suggests the need for clarity and detail especially when prescribing lifestyle modifications.


Renin Angiotensin Aldosterone System (RAAS) plays an important role in the development of hypertension. On the other hand, hypertension is a well-known and independent risk factor for cognitive impairment. The aim of the present study was to evaluate the relationship of blood pressure control, plasma angiotensin peptides and aldosterone with cognitive functions. Forty-one patients who were under treatment with the same antihypertensive medications for at least three months were included in the study. Plasma angiotensin II, angiotensin 1-7, angiotensin IV, and aldosterone concentrations were analyzed using an enzyme-linked immunosorbent assay (ELISA). Standardized Mini Mental State Examination (SMMSE) was used to evaluate cognitive functions. When the participants were grouped according to their SMMSE scores , we determined significant differences between systolic blood pressure (SBP) levels, diastolic blood pressure levels, plasma angiotensin II and angiotensin 1-7 concentrations of the groups. When the participants were stratified according to their SBP levels , we found significant differences in SMMSE scores and plasma angiotensin IV concentrations of the groups. A negative correlation between SBP and SMMSE scores and strong linear correlations among angiotensin peptides levels were determined. The relationship found between SBP and SMMSE in the present study was compatible with the literature. Our 33 patients were using at least one angiotensin II receptor blocker (ARB). Regarding AT1 receptor blockage, the significant association between higher SMMSE scores and increased angiotensin peptides may support a finding that ARBs prevent dementia and improve cognitive function. Further larger studies are needed to confirm and prove the relation of RAAS biochemical parameters with cognitive function. The prevalence of hypertension is correlated with age, seen in nearly 50 % of individuals aged between 60-69 years and affects ¾ of people aged more than 70 years  plays an important role in the development of hypertension. RAAS, being an important mechanism in electrolyte balance and blood pressure regulation, also leads to cardiac and renal changes via neuronal, hormonal, and metabolic effects. For this reason, RAAS blockage is very important for the prevention of hypertension and its complications. RAAS is a complicated system with several parameters Figure 1. Each daThe relation between cognitive function and hypertension has become a leading area of interest in recent years. Independent from blood pressure and blood pressure control, many studies and reviews have investigated the role of RAAS in cognitive function. RAAS-blocking antihypertensive drugs affects this complex system from different points and thus leads to increased or decreased production of different metabolites. Due to their effects on RAAS system, the possible effects of antihypertensive drugs on RAAS parameters are listed in Table 1Angiotensin II is the major active mediator of RAAS system and most of its effects are provided via angiotensin type I (AT1) and type II (AT2) receptors. Effects such as vasoconstriction, aldosterone release, cardiovascular hypertrophy and hyperplasia, catecholamine release, and tubular sodium retention is provided via AT1 receptor. In addition, AT1 is responsible in the pathogenesis of atherosclerosis and cardiovascular remodeling. In general, the AT2 receptor shows antagonistic effect when compared with the AT1 receptor . The maAngiotensin 1-7 is the most pleiotropic bioactive substance of the RAAS system. Angiotensin 1-7 shows its effect via Mas receptors, which are coded by Mas proto-oncogenes and bound to G proteins. The Mas receptor was shown to be a physiologic antagonist to angiotensin II's effect over AT1 . It hasAngiotensin IV is a metabolite of angiotensin II. Other than angiotensin II receptor antagonists (ARB), RAAS-blocking agents  also block formation of angiotensin II. For this reason, RAAS blockers (excluding ARB) might also decrease angiotensin IV formation. The positive effects of angiotensin IV on cognitive processes such as learning and memory have been shown in animal studies . AlthouThe final metabolite of RAAS, aldosterone, is stimulated by angiotensin II via the AT1 receptor. Aldosterone is known to have a role in the development of cardiovascular diseases such as hypertension, left ventricular hypertrophy, heart failure, and renal failure Cognitive functions can be described as learning, memory, planning, organization, problem solving, focusing and sustaining attention, understanding the environment, and calculation, which reflect the high processing capacity of the brain. Hypertension is one of the early onset cardiovascular diseases. For this reason, hypertension is a good model to investigate the effects of systemic and cardiovascular diseases on cognitive functions  Committee on Future Directions for Cognitive Research on Aging, 2000). For evIn this study, we aimed to investigate the relation of plasma angiotensin II, angiotensin 1-7, angiotensin IV, aldosterone concentrations, and blood pressure with cognitive functions. Forty-one patients with hypertension who were under treatment with the same antihypertensive medications for at least three months and presented to Istanbul Medical Faculty Department of Clinical Pharmacology Polyclinic were included in this cross-sectional study. The study was approved by Istanbul Medical Faculty Clinical Research Ethics Committee and enrolled participants gave their written informed consent. The inclusion and exclusion criteria are listed at Table 2Blood pressure measurements were done after resting for a minimum of 5 minutes in the sitting position, measured using a clinical-trial-use approved, validated, and calibrated oscillatory blood pressure measurement device . The patients did not take caffeine-containing drinks or smoke cigarettes 30 minutes before measurement. Three measurements were taken with 5-minute intervals and blood pressure level was recorded as the average of those 3 measurements. We used a systolic blood pressure level of 140 mmHg as a cut-off point.Plasma specimens were collected to measure plasma angiotensin II, angiotensin IV, angiotensin 1-7, and aldosterone levels using an enzyme-linked immunosorbent assay (ELISA) . All specimens were collected between 08:00 and 10:00 a.m.Patients stayed for 30 minutes in the supine position before their blood was drawn. Venous blood samples were collected in 4 mL tubes with EDTA for plasma aldosterone level measurement. Samples were immediately centrifuged at 1000 rpm for 15 minutes. Venous blood samples for angiotensin peptides were collected in precooled tubes with EDTA then immediately centrifuged at 2000 rpm for 20 minutes at +4 °C and plasma was directly transported into precooled Eppendorf tubes. All samples were stored at -80 °C until required for analysis. All samples were analyzed in duplicate.th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) criteria , all paion, 2000) to evalth -75th percentiles).Statistical analyses were performed using IBM's Statistical Package for the Social Sciences (SPSS) for Windows version 21.0. The distribution of variables was tested using the Shapiro-Wilk test. For variables with normal distribution, t-test and Pearson's correlation analysis were performed. For variables without normal distribution, Mann-Whitney U test and Spearman's rho correlation analysis were conducted. The results were considered significant if p < 0.05. The results of the parametric tests are presented as mean ± standard deviation and nonparametric tests are presented as median  were consecutively enrolled in the study (see Supplementary data). The SMMSE scores of the patients resulted with a mean of 27.37 ± 2.426. Ten patients with a SMMSE score of 26 or lower were considered to have cognitive impairment. Twenty patients with SBP levels of 140 mmHg or higher were considered to have uncontrolled hypertension. The antihypertensive medications of the patients are summarized at Table 3We stratified the patients into two groups according to their SMMSE score and SBP level. The basic characteristics of the study groups were similar and there were no significant differences. The mean age and years since first diagnosis of hypertension of patients with SMMSE scores of 26 or lower were 56.1 ± 5.60 and 8.7 ± 7.66 years, respectively. The mean age and years since first diagnosis of hypertension of patients with SMMSE scores of 27 or higher were 57.84 ± 8.36 and 9.01 ± 6.75 years, respectively. The mean age and years since first diagnosis of hypertension of patients with SBP levels of 140 mm Hg or higher were 58.45 ± 7.37 and 9.53 ± 7.06 years, respectively. The mean age and years since first diagnosis of hypertension of patients with SBP levels lower than 140 mm Hg were 56.43 ± 8.15 and 8.37 ± 6.85 years, respectively. When participants were grouped as SMMSE score > 26 points (n=31) and SMMSE score ≤ 26 points (n=10), there were significant differences between systolic blood pressure (SBP) levels (p < 0.05), diastolic blood pressure (DBP) levels (p < 0.01), plasma angiotensin II (p < 0.05), and angiotensin 1-7 (p < 0.05) concentrations of the groups, whereas no significant relationship was detected with plasma angiotensin IV and aldosterone concentrations Table 4.We stratified the patients according to their SBP levels. When participants were grouped as SBP ≥ 140 mm Hg (n=20) and SBP < 140 mm Hg (n=21), the differences of SMMSE scores (p < 0.05) and plasma angiotensin IV concentrations (p < 0.05) were found significant, whereas no significant relationship was found with plasma angiotensin II, angiotensin 1-7, and aldosterone concentrations Table 5. A negative correlation between SBP and SMMSE scores , negative correlations between plasma angiotensin IV concentration and SBP , and plasma angiotensin IV concentration and DBP  were detected using correlation analysis. Besides, strong linear correlations among angiotensin peptides levels were determined. The correlations found in the present study are given in Table 6The average life span is increasing worldwide and dementia and cognitive impairment incidence is rising in parallel with the aging population. It is evident that high blood pressure levels are related with cognitive impairment, stroke, and cerebrovascular diseases. Research on the impact of RAAS, which plays a critical role in the development of hypertension, is a leading topic in current clinical trials. Although several articles have investigated the relation between RAAS and cognitive functions, it should be further investigated.In our study, patients with high systolic blood pressure resulted with low SMMSE scores. The negative correlation between systolic blood pressure and SMMSE shows that hypertension is an independent risk factor in cognitive impairment. In addition, when patients were classified as SMMSE = 26 and > 26, the difference between the diastolic blood pressure levels of the two groups was significant (p < 0.005). The importance of keeping blood pressure levels under control seemed to be important in maintaining cognitive functions in a trial of the elder population .In research published in 2011, high plasma aldosterone levels were shown to be associated with cognitive impairment. When their results were evaluated in a multiple regression analysis, age (p < 0.001), plasma aldosterone concentration (p < 0.001), and cerebral infarction history (p < 0.005) were reversely associated with SMMSE scores. Mineralo-corticoid receptor blockage was associated with cognitive impairment prevention as well as cardiovascular mortality prevention . In ourPlasma aldosterone and angiotensin concentrations might be affected by several factors such as age, drugs, Na intake, and posture of the patient. In our study, patients lied down for 30 minutes before their samples were taken and they were also informed about Na diet. Evaluating sensitive parameters such as plasma aldosterone concentrations may be required with high numbers of samples. Besides, increased aldosterone levels were shown to be related with cerebrovascular function and intensive antihypertensive treatment may benefit the most for the patients with high aldosterone levels . As a rHypertension is related with RAAS activation and endothelial dysfunction. Therefore, it can be associated with abnormal regulation of cerebral blood flow and cognitive impairment . The roThere was no correlation between angiotensin 1-7 and SMMSE scores. However, when patients were grouped with the SMMSE 26-point threshold, the difference between groups was significant (p < 0.05). Angiotensin 1-7 plays a role in peripheral vasodilatation, diuresis, and antiproliferation via NO, kinin and prostaglandin release . In patAmong all biochemical parameters, the role of angiotensin IV in RAAS was the least clarified. In the present study, plasma angiotensin IV levels of SMMSE > 26 group were higher than plasma angiotensin IV levels of SMMSE = 26 group but this difference did not reach a statistically significant level. Stimulation of the AT4 receptor had a positive effect on cognitive effects such as memory and learning in animal studies that administered angiotensin IV . Angiotensin IV is mostly localized in the brain and interacts with AT1 and AT2 receptors as well as AT4  that contained no other proteinase inhibitors and plasma samples were not extracted, which may have limited our study because it may have decreased peptide degradation. We used tubes with EDTA and performed very strict cold chain to keep the peptide degradation to a minimum.The present study has a small sample size. Nevertheless; our study can be considered as a pilot study and we found some significant findings that may be useful for further larger studies. This work was supported by Scientific Research Projects Coordination Unit of Istanbul University (Project number: 27104).th Annual Scientific Meeting of the International Society of Cardiovascular Pharmacotherapy (ISCP), 25-26 June 2015, Buenos Aires, Argentina. This study was presented as a poster presentation at the 20The authors declare that they have no conflict of interest.


A long time ago, the links between renal disease and malignancy were observed, however, quite recently, their importance was recognized and ‘new’ subspecialty in nephrology, namely ‘onconephrology’ was established. In the XXI century, patients with malignancy make up the most growing number of the subjects seen for nephrology consult and/or critical care nephrology services. A plethora of renal problems may be found in patients with malignancy. They may influence not only their short-term outcomes but also the adequate therapy of the underlying oncological problem. Thus, all these kidney-related issues pose an important challenge for both specialities: oncology and nephrology. In the review a spectrum of acute and chronic renal injury caused by the malignancy is presented as well as the associations between renal disease and cancer. Assessment of kidney function and its importance in patients with malignancy is also discussed as medical oncologists should check the appropriate dose of chemotherapeutic drugs in relation to the actual renal function before prescribing them to the patients. Moreover, effects of kidney function on outcomes in oncology is presented. In addition, nephrology services should better understand both the biology of malignancy with its treatment to become a valuable part treating team to yield the best possible outcome. It is important for nephrology services to be acknowledged and to take an active participation in care of oncology patients. In the XXI century patients with malignancy make up the most growing number of the subjects seen for nephrology consult and/or critical care nephrology services. The outstanding progress in the therapy of malignancy presents new possibilities and challenges for both nephrologists and medical oncologists. It is important for nephrology services to be acknowledged and to take an active participation in care of oncology patients. In addition, nephrology services should better understand both the biology of malignancy with its treatment to become a valuable part treating team to yield the best possible outcome.A long time ago, the links between renal disease and malignancy were observed, however, quite recently their importance was recognized and ‘new’ subspecialty in nephrology, namely ‘onconephrology’ was established . ChronicA plethora of renal problems may be found in patients with malignancy. They may influence not only their short-term outcomes but also the adequate therapy of the underlying oncological problem. Thus, all these kidney-related issues pose an important challenge for both specialities: oncology and nephrology. Indeed, the incidence rates for many malignancies are increased and amelioration in cancer mortality due to more effective chemotherapy, including targeted drugs, and treatment with stem cells, caused in a rise in population of cancer survivors . Some ofAKI and disturbances in electrolyte are the most common feature of kidney disease that are found in a patient with malignancy in a hospital setting. AKI in this population is linked with high morbidity and mortality. AKI incidence in these vulnerable patients depends upon type of malignancy , severity of underlying disease, complications of the disease and therapy. Several factors may potentiate the risk of AKI in these patients such as dehydration due to vomiting, diarrhea, obstruction of urinary tract, fluid and electrolyte disturbances, contrast agent administration, nonsteroidal antiinflammatory drugs (NSAIDs), nephrotoxic antibiotics, renal toxicity of some chemotherapeutic and targeted drugs –17. MoreKidneys clear same chemotherapeutics and AKI affect pharmacokinetics of these drugs. It may lead to their toxicity. On the other hand, RRT may lead to subtherapeutic levels of chemotherapeutics making treatment potentially ineffective. In addition, AKI may alter the levels of antibiotics, narcotics and other ancillary drugs leading to potential adverse effects. Thus, kidney function should be monitored carefully and drugs dose adjusted appropriately. In cases when not nephrotoxic drugs are available, it should be the preferred therapeutic option.AKI due to prerenal causes is a common finding in patients with malignancy . In thisIntratubular or extrarenal obstruction are frequent causes of AKI in patients with cancer , 25. ConGlomerular, tubulointerstitial, and vascular diseases may cause renal function impairment in patients with malignancy. In differential diagnosis type of malignancy and type of chemotherapeutic agents are to be considered. The most common glomerular pathology in malignancy include vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), membrano-proliferative or membranous glomerulonephritis and thrombotic microangiopathy (TMA) , 25. AcuIt has been recognized that novel treatment with targeted drugs offer superior patient survival rates compared with standard chemotherapy. The most commonly used cancer therapies are targeted to proteasome, vascular endothelial growth factor-VEGR and its receptor- -VEGFR, epidermal growth factor receptor- EGFR, human epidermal growth factor receptor-2-HER2, dimerizations of HER2, v-Raf murine sarcoma viral oncogene homolog B- BRAF, anaplastic lymphoma kinase-ALK, programmed cell death protein 1-PD-1 and its ligand PDL-1, receptor activator of nuclear factor kappa beta ligand- RANKL, and mammalian target of rapamycin-mTOR. However, the downside of the targeted therapies and immunotherapy is unique adverse renal toxicity, well different from that of the conventional chemotherapy –31. ThisBisphosphonates are used to prevent bone resorption. Pamidronate and zoledronate are approved for bone events prevention in patients with advanced malignancy. Nephrotoxicity of bisphosphonates include mainly nephrotic syndrome, glomerulopathies such as collapsing focal segmental glomerulosclerosis (FSGS), FSGS-non specified and minimal change disease acute tubular necrosis and acute kidney injury –55.2 (range: 4 - 256 mL/min/1.73m2). In 45.0% of patients eGFR was less than 60 mL/min/1.73m2, 55.2% were hypertensive; 20.2% were diabetic (DM) and 6.5% suffered from congestive heart failure (CHF). They stressed that although many risk factors are mentioned in the guidelines, only a few predicted CIN development after IV iodinated contrast agent administration for CT, namely: kidney failure, DM, age > 65 years and NSAIDs. Additionally, despite significant association between CIN development and cancer was revealed, the present guidelines did not contain such an information. The value gained and the risk incurred by imaging studies in general, and radiocontrast-enhanced imaging studies in particular, remain critically important questions in many medical and surgical subspecialties including oncology. Although data in oncology are very limited, it is suspected that, on the basis of existing assumptions regarding attributable risk, diagnostic studies and some interventions that might save or improve lives are being withheld from patients owing to an exaggerated fear of radiocontrast nephropathy. Therefore, the benefit of a contrast-enhanced study with the risk, likely low but likely not zero, of radiocontrast administration on the kidney should be carefully estimated as to date there have been no randomized studies of the risk of radiocontrast administration in oncology field.Contrast-induced nephropathy (CIN) is an important drawback following administration of intravascular iodinated contrast agent . In the 2), whereas SCr was normal in most patients [2 was 52.9% in IRMA-1 [2. The study was performed in a cohort of 662 subjects with a renal cortical tumor subjected to either partial or radical nephrectomy. In addition, eGFR <60 ml/min/1.73m2 was reported in 26% [2. In all, 78.6% of patients (n=1087) were administered at least one drug subjected to dose adjustment and 78.1% received at least one drug known to be nephrotoxic. This is of interest, that 56.5% of patients with CKD treated with chemotherapeutics requiring dose adjustment in case of CKD, had no dose reduction [2 was an independent predictor of mortality relative to eGFR ≥60 mL/min/1.73 m2, and it was dependent upon cancer site. After adjustment for confounders, eGFR<60 mL/min/1.73m2 was associated with higher mortality risk among patients with hematologic malignancy and gynecological cancer. They stressed that they enrolled incident rather than prevalent patients and eGFR was obtained at the time of diagnosis, to rule out the effect of anticancer treatment on kidney function.In the last years, a remarkable number of targeted drugs have shown their efficacy and benefits in various malignancies together with improved outcomes such as progression-free and/or overall survivals. Prevalence CKD is reported to be high in patients with malignancy , but thepatients . These rn IRMA-1  and 50.2n IRMA-1 , in a con IRMA-1 , the pren IRMA-1 , 79. Huan IRMA-1  reportedd in 26% . Prevaled in 26% , United d in 26% , and Japd in 26% . In the d in 26% –87. The d in 26%  study wad in 26% . In addid in 26% . The stueduction . From theduction  demonstr2, a risk for cancer was significantly higher [Wong et al.  studied y higher . In party higher . The mosy higher . On the y higher , 93. In y higher –93 In ady higher –93. It iPatients on RRT are dying mainly due to o cardiovascular disease and infections, while malignancy is relatively common in this population. About 6% of the incident hemodialyzed subjects in the USA have malignancy as a comorbidity . DespiteThere is uncertainty on validity of conventional prognostic factors and outcome data for specific malignancy in ESRD population on RRT due to the absence of randomized clinical trials. Several aspects of antineoplastic regimen in RRT are important to consider such as selection of chemotherapeutic agent, dose adjustment, timing of dialysis in relation to administration of chemotherapeutic agent, vascular access for RRT and chemotherapeutic regimen, type of dialysis and staff safety considerations. The kidney clearance of a cytotoxic drugs is important in dialyzed patients. RRT can affect clearance of chemotherapeutics in several ways than just a simple first-order kinetics. Cytotoxic agent could be cleared by dialysis. It may affect the dose given as well as the timing and characteristics of the subsequent dialysis. The preservation of vascular access for RRT is crucial and especially demanding in a patient receiving cytotoxic drugs, but the effects of quickly administered chemotherapeutics through an arterialized vein have not been adequately assessed. Thus insertion of the port for chemotherapy may be worth to consider, however, possible complications of having both port and central venous catheter, in particularly on the same site should be taken into account. Data on chemotherapeutic drugs in ESRD are very scarce. For some cytotoxic medications, it appears that ESRD subjects can tolerate standard treatment. It seems very important that a systematic approach to investigate anticancer treatment in the growing RRT population is of utmost importance, particularly for the frequent malignancies such as lung, breast, colorectal, and prostate cancers for which the data are in general under-represented relative to other less common cancers such as transitional cell cancer, cancer of the testis and leukemia.th and 95th percentile for age, both MDRD and Cockcroft-Gault formulas provide comparable data consistent with values obtained for age-specific historic inulin clearance [2) [Assessment of glomerular filtration rate is complex, cumbersome and time consuming to perform on everyday basis. However, SCr should be used to estimate GFR in subjects with stable kidney function . Moreovelearance . The Coclearance . The CKDance [2) . Currentance [2) . Howeverance [2) , 128. Itance [2) . This isance [2) .Possible association between renal function and death in malignancy are not widely studied –137. In 2 and for which drug dosages were available in the medical file were administered at least one medication with an unadjusted dose in relation to kidney function. It is very important for clinicians to handle antineoplastic drugs properly in this population. Approximately 50% of all chemotherapeutics are excreted predominantly by the kidneys in urine as unchanged drug or active metabolite(s), thus, any impairment in kidney function may lead to accumulation of potentially toxic metabolites and overdosage [2 relative to 67.1% in ‘not chemotherapy-naïve' subjects (P<0.0001). Three IV bisphosphonates were prescribed in BIRMA study i.e. ibandronic, pamidronic, and zoledronic acid. The majority of subjects with bone metastases received zoledronic acid (220 patients). It is of interest that 67.3% had an impaired GFR and 50.9% of them were classified as having CKD [2) was significantly increased in BIRMA relative to IRMA trial  [It has been reported that incidence of CKD is high in cancer patients. It is essential to stress that SCr is not appropriate for assessment of kidney function. GFR is estimated by equations such as MDRD, also in subjects with a normal SCr and even on regular visits in subjects coming for routine check-ups without administration of antineoplastic medications. It should be also considered that oncology patients are still exposed to renal and extrarenal toxicity of non-antineoplastic medications prescribed for other reasons. Janus et al.  found therdosage . The doserdosage . In addierdosage . It was erdosage . In addierdosage . In the erdosage . The preving CKD . In stagving CKD . Thus, iving CKD . In the ving CKD . In addiving CKD . Therefo<0.0001) . It may <0.0001)  included<0.0001)  reported<0.0001) . There c<0.0001) . CANcer <0.0001) . Iatroge<0.0001) . The aut<0.0001)  demonstr<0.0001) . They adin situ bladder cancer, all noninvasive papillary tumors of the bladder, and asymptomatic solitary renal cell cancers <5 cm can be waitlisted without delay [in situ Duke's A or B1 carcinoma, invasive cervical cancer, breast cancer with regional node involvement, bilateral disease, or inflammatory histology five years without evidence of recurrence is required [in situ may be waitlisted after two years’ interval. The low recurrence rates (below 10%) were reported for localized renal cell carcinoma (RCC); testicular, cervical, and thyroid cancers; and lymphomas  were noted for uterus, colon, prostate, and breast cancer and Wilms tumor, while the highest rates (over 25%) were recorded for bladder carcinoma, advanced renal cell carcinoma, sarcomas, myelomas, and both melanoma and nonmelanoma skin cancers [Kidney allograft transplantation is the best available option of treatment for most patients with ESRD , 146. Asut delay , 160. Inrequired , 160. Pa cancers , 160.Solid organ transplantation is associated with higher incidence of malignancy development relative to the general population  and seveIncreased incidence of CKD, in particular, in the elderly, are of utmost importance. Many antineoplastic agents are cleared primarily by the kidneys as unchanged drugs or active metabolites. Therefore, a decline in kidney function can potentially lead to alterations in pharmacokinetics, elevated blood levels of the drugs, and increased toxicity. It has been shown that a remarkable number of CKD subjects treated with chemotherapy require dose reduction in case of CKD, but they are not administered the adjusted dose . Thus, i


Asthma as a chronic health condition can be controlled when in addition to clinical care, adequate education and support is provided to enhance self-management. Like many other chronic health conditions improved self-management positively impacts the health-related quality of life (HRQoL). It can therefore be said that a well-structured pharmaceutical care delivery that addresses the issues related to patient education and support towards self-management stands a good chance of positively impacting asthma control.This study evaluated the impact of a structured pharmaceutical care delivery on asthma control.t-test analysis.A prospective pre-/post- intervention study of a single cohort of 77 adult out-patients visiting specialist asthma clinics in Ghana were assessed for HRQoL and peak expiratory flow rates (PEFR) one month after pharmaceutical care intervention. Pharmaceutical care intervention covered education on the health condition, pharmacotherapy and self-management issues as well as correction of inhaler-use technique, where necessary and when to urgently seek medical care. The mean difference of the HRQoL and PEFR values were subjected to paired samples t = 6.85 (p < 0.05). The mean paired difference for PEFR post intervention was 17.533 (95% CI: 2.876 - 32.190) at t = 2.384 (p = 0.02).Delivery of a structured pharmaceutical care led to a significant improvement in asthma specific quality of life and PEFR. The mean paired difference of the HRQoL for a cohort of patients with asthma post- pharmaceutical care intervention was 0.697(95% CI: 0.490 - 0.900) at This study identified important challenges with both the pharmacologic and the non-pharmacologic management of adult asthma patients. Inadequate inhaler-use skills, widespread occurrence of preventable adverse events and irregular use of preventer medicines were prevalent among patients. At one month after pharmaceutical care intervention, patients with asthma in a cohort follow-up study showed significant improvements with regard to asthma-specific quality of life, peak flow rates and knowledgeGHS-ERC: 08/9/11 of October 19, 2011. In the year 2012, non-communicable diseases (NCDs) were responsible for 38 million (68%) of the 56 million global deaths as reported by the World Health Organization (WHO) [Asthma is a chronic respiratory disease with a rising prevalence within the African region . The AstNotwithstanding these levels of occurrence, most health care systems are still organised around the acute care model which does not meet the management needs of patients with NCDs. The WHO-Innovative Care for Chronic Conditions report (2002) has suggested that supported self-management with regular follow-ups in addition to effective treatments improves the outcomes for chronically ill patients .The main stay for asthma management that conforms to this innovative care for NCDs is the continuous monitoring of the patient for asthma control and therapy adjustments that are intended to minimize the symptoms regardless of the severity of the condition , 8. StudThese trials, and especially those related to determination of effect of patient education by pharmacists on the outcomes of the disease have shown mixed results –16. SomeFurthermore most of these studies used case–control methods in community settings where the participants in the “case” group cannot be totally isolated from those in the “control” group of the study. In cases where education impacts outcome, then it must be ensured that there is no exchange between the “case” and “control” participants.It is for these reasons that this researchers opted for a single cohort study and fewer sites to allow only two trained pharmacists to undertake the interventions. The interventions were also only focused on patient understanding of the disease condition, the medications and the appropriate use of the prescribed medications. The study employed the use of the HRQoL instrument as the primary outcome measure of asthma control. Secondary outcomes were the measurements of PEFR and inhalation technique scores. This cohort trial was organised to study the hypothesis that provision of organised pharmaceutical care that focussed on patient education on prescribed medications, would improve asthma control in adult patients.t-test analysis.A prospective pre-/post- intervention study of a single cohort of adult out-patients visiting specialist asthma clinics in Ghana were assessed for HRQoL and peak expiratory flow rates (PEFR) at baseline and one month after pharmaceutical care intervention. Pharmaceutical care intervention covered education on the health condition, pharmacotherapy and self-management issues as well as correction of inhaler-use technique, where necessary and self-referral for early unscheduled review for worsening asthma condition. The mean differences in HRQoL and PEFR values were subjected to a paired samples Four out-patient clinical sites were used in the study. Two were teaching hospitals that managed referral cases from various health institutions and run specialist asthma clinics once a week. The two other hospitals were not teaching hospitals, but one runs specialist asthma clinics. All the clinical sites were located within the southern and middle belts of Ghana.t-test to compare means of continuous variables to determine the minimum important difference of 0.5 was 60 patients. A convenience sample of 92 patients was used recruited for the study.Assuming a mean HRQoL difference size of 0.5   and a stTwo sets of data collection instruments were used in this study. The Model Pharmaceutical Care Instrument was used to collect data on participant demographics, medication profile, inhaler-use technique, perceived adverse medication events, peak expiratory flow rates symptoms and environmental trigger factors. This was used to guide participant education. Review of this data identified care-needs of every participant in the study. Care needs addressed included: understanding of disease condition and the role of the various medications; inhaler-use technique; issues of medication adherence; availability of medications; management of trigger-factors; management of adverse events, and peak flow meter assessment of lung function.The standard Asthma Quality of Life Questionnaire (AQLQ(S)) and the Peak Expiratory Flow Meter  were used to assess participant HRQoL and lung function pre and post pharmaceutical care intervention..It was adopted to measure the functional problems  that are most troublesome to adults (17–70 years) with asthma. The AQLQ(S) is an asthma-specific instrument that had been validated in clinical trials . The AQLA change in mean overall or domain score of 0.5 had been shown to represent the smallest change of importance to the patient , and a change in score of 1.0 represents a moderate change . HoweverHaving obtained an ethical clearance from the Ghana Health Service (GHS-ECH: 08/9/11) and participant consent, ninety two (92) adults with symptomatic asthma, without other active co-morbidities, who visited the out-patient clinic, were recruited into the study.Asthma patients attending regular clinical review in 4 selected hospitals located in the middle and southern belts of Ghana were recruited into the study. Eligibility for participation was limited to patients aged 17–70 years who have been medically diagnosed with asthma and had no active co-morbidities. Excluded in the study were patients whose medications were changed in their previous review visit prior to the recruitment. After giving their consent to participate in the study, a convenience sample of 92 patients was selected by selecting 10 patients out of a mean attendance of 30 patients per week from 4 hospitals for a period of 12 weeks. These participants were administered with the baseline questionnaires and provided educational intervention. These participants were followed up one month after the interventions. Fifteen (15) participants were lost to follow up. They did not show up for the post-intervention assessments. Therefore data for a total number of 77 patients from the baseline intervention were used for analysis.Two clinical pharmacists, who were trained for the study, undertook the patient assessment and provided educational intervention. The HRQoL instrument was self-administered by participants. All other participant data was collected with the “Model Pharmaceutical Care” forms. The best of 3 PEFR assessments were entered for each participant. The total score for inhaler-use technique was collated for each participant. Inhaler-use technique score was the sum of one (1) point per each correct step undertaken by participant and observed by the study pharmacist. The maximum total of 7-points score marks were based on the extension of the manufacturers’ inhalation steps as found in product leaflets. Based on their inhaler-use technique scores, participants were coached to perform all the steps correctly. The “Model Pharmaceutical Care” forms were used to administer questionnaire on “perceived” environmental trigger factors on individual participant’s asthma and adverse effects from their prescribed medications. The impact of asthma with regards to airway narrowing and the roles of “reliever” and “preventer” medicines on the airways were explained to each participant. Participant’s knowledge, PEFR and HRQoL were consecutively re-assessed in one month after the provision of the interventions.Baseline Characteristics of Asthma Out-patient Clinic ParticipantsComparison of Asthmatic Patients’ Characteristics Post Pharmaceutical Care InterventionData from the study were subjected to both descriptive and inferential statistical analysis. Data were analyzed to generate various tables and charts to demonstrate similar themes, frequencies, trends and number counts under the following themes:t-test; the mean differences in the baseline and post pharmaceutical care intervention HRQoL were analyzed.Data collected demonstrated normal distribution with same values for central tendency. Data were therefore analyzed to test the study hypothesis using a paired samples Study participants were predominantly female 61%) and had a mean age of 46 (±15) years. The mean peak expiratory flow rate was 284(±103) for the 77 participants. Most participants in the study had a minimum of high school education (97.5%) as in Table % and hadParticipants reported of widespread incidence of adverse drug events perceived to by associated with their asthma medications. Coughs and dry mouth were the most frequently reported incidence of events Table .Table 2IAlmost all participants (96%) used Salbutamol inhalers. In addition, Budesonide/formoterol (51%) and Fluticasone/salmeterol 31%) inhalers were used in various combinations , perfume/and strong scents (78%) and smoke (70%) were the most commonly mentioned environmental trigger-factors that worsened the asthma of participants Table . Other tThe quantum of change in HRQoL is displayed in Table p < 0.001). The paired mean difference at 95% CI was highest for the Symptoms domain 1.134 (0.910 – 1.360) and lowest for the Activity Limitation domain 0.548 (0.340 - 0.760).From Table p < 0.05).The mean (PEFR) at baseline was 266.5 L/min SD 85.9), which increased to 284.0 L/min (SD 103.3) after the intervention  as a result of poor asthma control due to inadequate use of inhalers. In conformity with third Expert Panel Review  and Global Initiative for Asthma  recommendations, usually after a 3-month period of well-controlled asthma there should have been a step down in therapy,  but onlyThe degree of poor inhaler-use technique identified among study participants indicates that not enough consideration has been given to the role of inhaler-use technique in patient management. It further suggests that there is insufficient patient education and counselling at the clinic and at the pharmacy, and that any education and counselling provided to the study participants in the past clearly did not adequately impact on their skills, or its impact might have diminished with time.The common major environmental trigger-factor affecting participants in this study were exposure to dust, smoke and perfume or strong scents, which suggests that another major need for intervention is education on the improved control of environmental triggers by patients within their environment.Previous studies by Mangiapane,and colleagues , using aThe paired mean difference values for the overall general HRQoL and its various domains were both clinically and statistically significant, showing benefit of the pharmaceutical care intervention to the patients in all aspects of their quality of life. The Symptoms domain had the highest mean change difference of 1.134 (95% CI: 0.910 - 1.360) and the Activity Limitation had the lowest of 0.548 (95% CI: 0.340 – 0.760). This is an indication that the various domains were impacted to different extents within the composite overall HRQoL. Barbanel and colleagues [However, Mancuso and colleagues  found ouThis study observed improvements in participants’ values at the end of the intervention as with their HRQoL.when PEFR measurements were used as a secondary measure of asthma control. However, analytical exploration of the values indicated only a weak positive correlation between the changes in the overall HRQoL and PEFR from baseline as a result of the intervention. Previous studies by , 19 amonPEFR are known to have an a diminished correlation with the FEV1 in patients with asthma,  however Outstanding are the economic implications of such intervention on the cost of asthma management. Further to any clinical significance of educational intervention, patients and health insurance schemes might make savings on asthma-related health care, cost of medications, hospitalization and emergency department visits as envisaged by –26. FutuThis study has some limitations. First, the duration of the study did not allow for the participants to be followed-up further to assess duration of the impact of the intervention or to ascertain whether the therapies of the participants with significant improvements in HRQoL were subsequently adjusted in the post- intervention months. The design of this study did not factor duration of impact of the intervention since asthma is a dynamic condition that would require continuous re-evaluation and further education in conformity to the recommendations of GINA and the EPR. Secondly, the AQLQ used in the study to assess HRQoL were not translated into any of the local languages for patients who may not be able to read and write English and thereby limited the scope of patient participation. Furthermore the study covered the southern and middle belts of the country and that may to some extent also limit the overall generalizability of the findings.This study identified important challenges with both the pharmacologic and the non-pharmacologic management of adult asthma patients. Inadequate inhaler-use skills, widespread occurrence of preventable adverse events and irregular use of preventer medicines were prevalent among patients. At one month after pharmaceutical care intervention, patients with asthma in a cohort follow-up study showed significant improvements with regard to asthma-specific quality of life, peak flow rates and knowledge.A well-structured pharmaceutical care delivery in the hospital would contribute to patient knowledge and management and eventually improve the health-related quality of life of asthma patients. This study has shown that hospital Pharmacists would need to be properly trained to assess patients with asthma and to provide the needed education to address their individual challenges associated with the condition and the management.


Diabetes mellitus (DM) and essential hypertension are common conditions that are frequently present together. Both are considered risk factors for cardiovascular disease and microvascular complications and therefore treatment of both conditions is essential. Many papers were published on blood pressure (BP) targets in diabetic patients, including several works published in the last 2 years. As a result, guidelines differ in their recommendations on BP targets in diabetic patients. The method by which to control hypertension, whether pharmacological or non-pharmacological, is also a matter of debate and has been extensively studied in the literature. In recent years, new medications were introduced for the treatment of DM, some of which also affect BP and the clinician treating hypertensive and diabetic patients should be familiar with these medications and their effect on BP. In this manuscript, we discuss the evidence supporting different BP targets in diabetics and review the various guidelines on this topic. In addition, we discuss the various options available for the treatment of hypertension in diabetics and the recommendations for a specific treatment over the other. Finally we briefly discuss the new diabetic drug classes and their influence on BP. Essential hypertension and diabetes mellitus (DM) are both extremely common conditions and therefore it is not surprising that their co-existence is extremely prevalent. Since both are considered risk factors for coronary artery disease, cerebrovascular disease, renal failure and congestive heart failure, treatment of both conditions is essential. Whether blood pressure (BP) should be lowered to a different target in diabetic patients has been a debate for many years. Current guidelines are inconsistent regarding BP target in diabetic patients. Whereas several guidelines recommend a BP goal of <140/90 mmHg , some reHypertension is twice more common in diabetics than in non-diabetics , but theThe co-existence of DM and hypertension significantly increase the risk for coronary heart disease , left veThe BP targets in diabetic hypertensive individuals are controversial. For many years it was common practice to aim for BP targets lower than 130/80 mmHg in non-proteinuric diabetic patients. This was based on evidence from several large studies, including The Hypertension Optimal Treatment (HOT) study, the United Kingdom Prospective Diabetes Study (UKPDS) 38 and the Action in Diabetes and Vascular disease Controlled Evaluation (ADVANCE) trial –31. HoweIn the International Verapamil SR/Trandolapril (INVEST DM) study there was no difference in short term outcome in diabetic patients with coronary artery disease despite achievement of significantly lower BP (<130 mmHg vs. <140 mmHg) and in fact, there was an increased in the long term all-cause mortality in the more tightly controlled group . In the However, the results of the recent systolic blood pressure intervention trial (SPRINT) raised again the discussion what should be the target BP in diabetic patients. The SPRINT randomized 9361 persons with systolic BP > 130 mmHg and increased CV risk, but without type 2 DM, to a systolic BP target <120 mmHg (intensive treatment) or a target of <140 mmHg (standard treatment). At 1 year, the mean systolic BP was 121.4 mmHg in the intensive treatment group and 136.2 mmHg in the standard-treatment group. The study was stopped early after a median follow-up of 3.26 years owing to 25% lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (P < 0.001). All-cause mortality was also lower by 27% in the intensive treatment group (P = 0.003) . Rates oOne approach is to explain why the results of the SPRINT should not be applied to diabetic patients and, unlike our previous thoughts BP targets in diabetic patients should be higher than in non-diabetics. DM has a negative influence on arteriolar function and blood flow autoregulation that shifts the pressure/flow relationship. Therefore diabetic patients are more vulnerable to compromised blood flow to vital organs when BP reaches a critical low point.The opposite approach is that the results of the SPRINT should be applied to diabetic patients, since in most previous trials the benefits of BP reduction in diabetic patients were at least as good if not better than in non-diabetic individuals , 42. To In the ACCORD study, despite the failure to show a decrease in primary endpoints in the intensive treatment arm the rate of stroke was significantly lower in the intensive than in the usual treatment arm . It is pSeveral differences in the design of the studies may also explain the different results. ACCORD had lower event rates than initially predicted because of a lower CV risk profile in participants. The exclusion of participants aged >80 years led to a younger group of patients in ACCORD than in SPRINT. The mean age for ACCORD was 62 years and for SPRINT was 68 years.Participants in the BP arm of the ACCORD were also at lower risk because patients with dyslipidemia were assigned to the lipid arm and were excluded from the BP arm.Another significant difference in the design of the SPRINT and ACCORD studies was the use of diuretics. The treatment regimen for hypertension in the ACCORD study often used hydrochlorthiazide, and the SPRINT study primarily used chlorthalidone.In addition, the complexity of the factorial study design in ACCORD may have made it less likely that a statistically significant difference could be demonstrated. This may suggest that if diabetic patients were included in the SPRINT they would also benefit from intensive BP lowering.When we try to explain the reason for the difference between the SPRINT and the ACCORD it should be emphasized that the results of the SPRINT are provocative. In the recent Heart Outcomes Prevention Evaluation (HOPE)–3 trial 12,705 participants at intermediate risk who did not have CV disease were randomized to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo and were followed for 5.6 years. The first co-primary outcome was the composite of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke; the second co-primary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. Therapy with candesartan plus hydrochlorothiazide was not associated with a lower rate of major CV events than placebo despite a BP decrease of 6.0/3.0 mmHg in the active treatment group. The only subgroup who benefited from BP lowering was the subgroup of participants with initial systolic BP > 143.5 mmHg . A recenOne explanation is the technique of BP measurements. In the SPRINT, BP was measures with an automated oscillometric office BP method that eliminated the need for a human to participate in the actual measurement and therefore reduces the white coat effect. Compared with a reasonably well-done standard office-based BP, the use of an automated oscillometric office BP method will yield a systolic BP that is 7–10 mmHg lower in the same patient, measured on the same day. If this is true the systolic BP of 120 mmHg in the SPRINT is equivalent to almost 130 mmHg in clinical practice. Thus, it is reasonable to suggest in high risk patients a target systolic BP of <130 rather than <120 mmHg.To solve the discrepancy between the various studies and to find out what should be the target systolic BP several meta- analysis were recently published Table .Table 1MA meta-analysis of 49 trials including 73,738 patients (most of them diabetic) showed that at BP values greater than 140 mmHg, BP reduction was associated with a decrease in mortality and CV morbidity. On the other hand, BP reduction in patients with initial BP values <140 mmHg resulted in increased CV mortality and a tendency towards increased overall mortality . AnotherThus it seems that a target of systolic BP < 130 mmHg is reasonable in most diabetic patients. In elderly diabetic patients (>80 years) but otherwise healthy, a BP target of <140–150/90 mmHg is reasonable. Lower BP levels may be adequate if tolerated by the patients. BP levels should be monitored closely in the sitting and the standing position and the treatment should be tailored to prevent excessive fall in BP .Although previous guidelines recommended strict BP control in diabetic patients , 54, thiNon-pharmacological anti-hypertensive therapy includes weight loss, increased potassium-based diet (DASH- dietary Approach to Stop Hypertension- style diet), low sodium consumption (below 2400 mg/day), moderation of alcohol intake and regular physical activity and exercise. Although the CV benefits of lifestyle interventions were not evaluated in diabetic patients, their implementation seems reasonable in diabetics since they may positively affect glycemia and lipid profile. Therefore their adoption for all diabetic patients with BP values >120/80 mmHg was recommended by recent ADA standards of care .Angiotensin converting enzyme inhibitors (ACEI), and angiotensin receptor blockers (ARBs) have long been considered the cornerstone of anti-hypertensive treatment in diabetic patients. Previous studies have demonstrated that both renin-angiotensin-aldosterone system (RAAS) blockers, ACEI and ARB, are associated with prevention of new onset DM in hypertensive patients  and are The use of beta blockers has been discouraged in diabetic patients due to its potential adverse metabolic effects, including an increase in triglyceride levels, a decrease in HDL cholesterol levels, weight gain, masking hypoglycemia and impairing insulin sensitivity . In addiCCBs are considered a potential first-line treatment for hypertensive diabetics, particularly in the elderly with isolated systolic hypertension . CCBs haAlthough there has been concern that diuretics might increase the risk for the development of diabetes mellitus  due to tThere are no specific studies which evaluated the efficacy of alpha blockers in diabetic patients. Alpha blockers do not adversely affect glucose metabolism or lipid profile, but they have been reported to be less effective than chlorthalidone for prevention of stroke and heart failure , 81 and Low dose spironolactone was found to be effective in controlling BP in patients with hypertension and diabetes . The addMore than two-thirds of hypertensive individuals are inadequately controlled on mono therapy . Most diIn the last decade there is a surge of new anti-diabetic medications working on different pathways in insulin production and glucose disposal. Some of these agents have beneficial effects on BP and may prove as important agents for the control of hypertension in diabetic individuals. In this paragraph we will discuss these classes of agents and the evidence for their effect on elevated BP in both normotensive and hypertensive individuals.Glucagon-like-polypeptide 1 analogues (GLP1a) lead to a clinically significant weight loss in both diabetics and non-diabetics , 97 and DPP4 inhibitors elevate endogenous GLP1 through inhibition of the endogenous substance responsible for its degradation. Several studies reported that these agents produce a modest decrease in BP –103, othThree representatives of this new class of anti-diabetics are currently in the market-canagliflozin, dapagliflozin and empagliflozin. Some others are under development. Although agents differ in their affinity for the sodium-glucose transporter, their clinical efficacy is quite similar. All three have similar efficacy in terms of glucose control and all are associated with significant weight loss . All thrIn addition, these drugs were reported to have a positive effect on the circadian rhythm in rats who developed hypertension . The mecCurrent evidence does not support a more stringent BP control strategy for all diabetic patients and the evidence to support stringent control in certain diabetic patients is also inconclusive. In elderly diabetic patients (>80 years) BP levels should be less than 140–150/90 mmHg and should be monitored closely in the sitting and the standing position and the treatment should be tailored to prevent excessive fall/decrease in BP. This is reflected in recommendations in most current BP treatment guidelines. The choice of anti-hypertensive agent is supported by minimal evidence although RAAS blockers are usually used as first-line agents. When requiring more than one agent for the control of hypertension in diabetics, calcium antagonists or diuretics are probably appropriate as second line agents. New agents used for the treatment of diabetes may aid in the control of hypertension and a diagnosis of hypertension in a diabetic person may influence the clinician’s choice to use a certain anti-diabetic treatment.In addition to lowering BP it is very important to control all other risk factors in diabetic patients. This heterogeneous treatment model, relates directly to general trends in modern medicine, reflecting an aspiration for individually tailored medicine, adapted specifically for the particular demographic and biologic characteristics of each patient.


Hypertension is the major contributor to cardiovascular diseases related morbidity and mortality. Blood pressure is not well controlled in the majority of patients with both diabetes and hypertension. The main objective of this study was to assess blood pressure control and its determinants among diabetes mellitus co- morbid hypertensive ambulatory patients.p-value <0.05. Patient’s written informed consent was obtained after explaining the purpose of the study. Patients were informed about confidentiality of the information obtained.Hospital based cross sectional study was conducted among diabetes mellitus co-morbid hypertensive ambulatory adult patients based on the inclusion criteria. Patient specific data was collected using structured data collection tool. Data was analyzed using statistical software package, SPSS version 20.0. To identify the independent predictors of blood pressure control, multiple stepwise backward logistic regression analysis was done. Statistical significance was considered at P = 0.002), female gender , duration of hypertension , non-adherence  and uncontrolled blood sugar are independent predictors for uncontrolled blood pressure.From a total of 131 study participants 51.14% were males with the mean (SD) age of the 50.69 ± 13.71. The mean duration of time since the diagnosis of hypertension was 7.44 ± 5.11 years. The mean (SD) SBP was 149.79 ± 16.32 mmHg, while the mean (SD) DBP was 89.77 ± 9.34 mmHg. More than one fourth (25.20%) of study participants had a controlled SBP, while about 27.48% had a controlled DBP. The overall control of BP was achieved in about 57 (43.51%) of the study participants. Older age (≥50 years) (AOR = 2.06; 95% CI: 2.65–7.79; Blood pressure control to target goal was suboptimal in the study area. Diabetic patients who were older, female, live longer duration with hypertension, non-adherent to their medications and poor glycemic control were more likely to have uncontrolled BP. Therefore, more effort should be dedicated to control the blood pressure in diabetics. Hypertension is the major contributor to the global burden of disease and to global mortality . It is dThere are several co-existing factors in diabetic patient which contribute for and accelerate the progression of the atherosclerotic vascular complications. Hypertension, which is the most prevalent and independent cardiovascular risk factor in the general population, is extremely common problem in diabetics . DiabeteDrug treatments and life style interventions can be used for the management of hypertension . SeveralThe success of blood pressure management in hypertensive individuals is determined by the integrated use of optimal dose and regimen of anti-hypertensive medications together with an intervention targeted on life style modification. These have to be guided by the knowledge of the specific characteristics of patients group. Since the success of treating hypertension has been limited, and despite well-established approaches to diagnosis and treatment, in many communities fewer than half of all hypertensive patients have adequately controlled BP. This result will be expected to be lower among diabetic co-morbid patients. To date there is no single study done in Ethiopia to assess blood pressure control among hypertensive diabetics. Thus, this study is designed to highlight the status of uncontrolled hypertension in patients with type 2 diabetes and determine the associated factors, which may affect the blood pressure management and find the bottle neck and pave the way for interventions.A hospital based cross-sectional study design was conducted in March, 2017 at ambulatory clinic of Jimma University Medical Center (JUMC) among diabetes co-morbid hypertensive patients who fulfill the inclusion criteria. JUMC is the only teaching and referral hospital in the southwestern part of Ethiopia with bed capacity of 600. Geographically, it is located in Jimma town 352 km Southwest of Addis Ababa, the capital. It provides services for approximately 9000 inpatient and 80,000 outpatient clients per year with a catchment population of about 15 million people. All ambulatory hypertensive diabetic patients aged 18 years and older who were on antihypertensive treatment for at least 6 months before the study period and were on follow-up were included in the study.The sample size was determined by using the single population proportion formula, assuming a 95% confidence interval (CI), a prevalence of 50% for blood pressure control, a 5% margin of error, and a 10% non-response rate. The final sample size was 131 diabetic hypertensive patients. Random sampling technique was used to select 131 study participants after obtaining patient list from Chronic Illness Clinic Registration Book, which had lists of 557 hypertensive patients, of which 173 were with diabetes comorbidity.A structured data collection questionnaire was developed by researchers from relevant literatures. Patient chart review and self-report was used to determine the various variables. Two trained data collectors interviewed the study participants and review patient charts and medical records for the respective information after all data collection tools are pre-tested. Before entry to SPSS for analysis, data was cleared, categorized, compiled and coded and also checked for completeness, accuracy. Any erroneous, ambiguous and incomplete data was excluded.Data was entered into computer using EpiData version 3.1 and exported to the Statistical package for Social Science (SPSS) version 22.0 for analysis. Differences between mean values was evaluated using Student’s t test while proportions was compared using the Pearson’s Chi-square test. Multivariable logistic regression analyses were used to assess the crude and adjusted effect of seemingly significant predictors of the target outcome.p-value of <0.05 was considered to be statistically significant.Categorical and continuous data was expressed as percentages and mean ± standard deviation respectively. Descriptive statistics was applied for the analysis of patient characteristics, including means, standard deviations (SD), medians, and percentiles and categorical variables was analyzed by using the chi-square test. A Ethical clearance & approval was obtained from institution review board (IRB) of Jimma University. The data that were collected from JUMC ambulatory clinic was preceded by a formal request letter from Jimma University. Written informed consent was taken from each study participant after clear orientation of the study objective. The raw data were not made available to any one and not used as the determinant of the participant. All steps in data collection and compilation were conducted and supervised by the researchers. Strict confidentiality was assured through anonymous recording and coding of questionnaires and placed in safe place. The patient got full right not to participate and as well as leave the study at any time during the study time.■ Co-morbidity: Diseases or disorders that exist together with an index disease or co-occurrence of two or more diseases or disorders in an individual.■ Controlled BP: BP < 140/90 mmHg in hypertensive diabetic patients of all ages [■ Uncontrolled BP: BP ≥ 140/90 mmHg in hypertensive diabetic patients of all ages [■ Adherent: a patient with a MMMAS score of ≥6  .■ Non adherent: a patient with a MMMAS scores of <6 .■ Physically active: an individual who perform physical exercise for at least 30 min per day for at least 5 day per week.■ Physically inactive: an individual who perform physical exercise for less than 30 min per day for less than 5 day per week .■ Controlled blood sugar: Fasting blood sugar less than 130 mg/dL .■ Uncontrolled blood sugar: Fasting blood sugar less than 130 mg/dL .Overall, 131 participants were included in this study. Majority of study participants were males 67 (51.14%). The mean weight of the respondents was 67.9 ± 13.01. The mean age of the respondents was 50.69 ± 13.71 and majority of them 67 (51.14%) were age of ≥50 years, 109 (83.20%) were married. Among the participants, 21(16.03%) were current smokers and 23 participants reported their current use of alcohol and 35 (26.72%) had no formal education and 44 (33.60%) were unemployed. About three forth of the study participants were found to be adherent to their medication according to a self-reported measure of adherence using the eight item MMMAS  of participants had a family history of hypertension and 18 (13.74%) had family history of diabetes. About 46.56% and 48.10% of patients were living with hypertension and diabetes for more than five [6% of par). About one thirds of the patients were on combination of enalapril and amlodipine followed by hydrochlorothiazide and enalapril (17.55%) combinations. About 8.40% of patients were taking triple antihypertensive medications. About two thirds of the patients were taking insulin  of the study participants  more likely to have uncontrolled BP than those <50 years. Patients with tertiary level education were 74%  less likely to have uncontrolled BP than those with no formal education. Gender was also found to have association with uncontrolled BP, in that female patients have 1.42 times more likely . Duration of hypertension since diagnosis was also associated with uncontrolled BP, in that patients with a diagnosis longer than 5 years were almost three times  more likely to have uncontrolled BP than those with a diagnosis of <5 years. Patients with a monthly BP measurement were 35% less likely to have uncontrolled BP than those with every three months BP measurement  and non-adherent patients were two times more likely to have uncontrolled BP than adherents . Patients with uncontrolled blood sugar (poor glycemic control) were almost two times  more likely to have uncontrolled BP than with controlled blood sugar , frequency of follow up, blood sugar(glycemic control), comorbidities and medication adherence showed association with BP control and hence, were used in multivariate analysis. The result of the multivariate analysis showed age to be significantly associated with uncontrolled BP in that patients aged ≥50 years were two times  and 36 (27.48%) of the study participants had a controlled SBP and DBP respectively, which is lower than a report from Saudi Arabia (40.4% and 51.6%)  and USA P = 0.002). It is similar to study done by in USA [As from this report age was significantly associated with uncontrolled BP in that patients aged greater 50 years were two times more likely to have uncontrolled BP than those younger than 50 years  less likely to have uncontrolled BP when compared to those with no formal education. This result is consistent with a result obtained from Chilean HC study which showed low education level to have a negative association with BP control [P = 0.04)). This may be is a result of a health seeking behavior, frequent adjustment in life style related factors and a tendency to adhere to antihypertensive medication among those who frequently measure their BP.Educational status was also found to be associated with BP control in which patients with tertiary education were 38% . This result is consistent with the result obtained from studies from South Africa [Adherence to therapies is a primary determinant of treatment success. Poor adherence attenuates optimum clinical benefits and therefore reduces the overall effectiveness of treatment outcome this study showed that non adherent patients were two times more likely to have uncontrolled BP than adherents  had higher odds of uncontrolled BP, which is consistent with study done in Saudi Arabia (8.3%) , Oman (8P = 0.04) more likely to develop uncontrolled BP. This study is consistent with study done in Brazil [This study also reveals that, not only comorbidity with diabetes, but also poor glycemic control is an independent predictor for uncontrolled BP. Patients with poor glycemic control had almost two times (AOR = 1. 65, 95% CI: 2. 14, 3. 32, n Brazil , by Green Brazil , Adler en Brazil  and Jansn Brazil . This con Brazil . Simply,n Brazil .Blood pressure control to target goal was suboptimal and achieved only in almost two fifth of pharmacologically treated hypertensive diabetic patients attending ambulatory clinic of Jimma University Medical Center. Diabetic patients who were older, female, live long duration with hypertension were more likely to have uncontrolled BP. These patients can be clearly identified and therefore preventive measures should concentrate on this group of patients. Older age, female gender, duration of hypertension, non-adherence and uncontrolled blood sugar are independent predictors for uncontrolled blood pressure among hypertensive diabetic patients. Monthly follow up and higher education are protective for blood pressure control.


It is now recognized that asthmacan present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features.30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry.1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls.There were no significant differences in atopy and FEVPatients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes.Trial registrationhttp://www.chictr.org.cn (ChiCTR-OOC-15006221)The online version of this article (doi:10.1186/s12967-017-1264-y) contains supplementary material, which is available to authorized users. Asthma is a common and complex disorder defined as reversible airflow limitation or bronchial hyperresponsiveness with appropriate clinical symptoms . TypicalIt has been proposed since decades ago that asthma might be presented with atypical symptoms, without obvious wheezing . There iIn 1979, Corrao et al.  firstly sine qua non of asthma, CVA and CTVA have often been under-diagnosed or mis-diagnosed for their lack of wheezing, and because of poor understanding of its clinical characteristics, and lack of functional biomarkers. Although it has been nearly 40 years since the initial proposal of the pronounced heterogeneity of asthma, it remains unclear whether atypical asthma is representative of an early form of asthma. We hypothesized that different presentations of asthma might possess distinctive cellular and molecular features. This study is designed to identify similarity and to compare differences between different presentations of asthma at various levels.Because wheezing has long been considered the In an attempt to address these key questions, we analyzed history of atopy, serum immunoglobulin E (IgE), lung function, sputum eosinophil counts, FeNO, anxiety and depression scores in patients with CA, CVA, or CTVA, in comparison with healthy controls. We further performed a proteomic analysis of the sputum supernatants from these patients with CA, CVA, or CTVA to determine whether these profiles would be different.1 increase after inhaling 400 µg salbutamol; (2) a positive bronchial challenge test; (3) variability in diurnal peak expiratory flow (PEF) of more than 10% for 1 day during 1 week. For CVA, cough should be lasting more than 8 weeks. Exclusion criteria for enrollment included respiratory tract infection in the preceding 8 weeks, other chronic pulmonary diseases, history of drug or alcohol abuse or with a history of mental illness, obvious abnormal of chest HRCT, other pulmonary disease, cardiovascular diseases, significant comorbidity likely to influence the conduct of the study, pregnancy, and breast-feeding.Classic asthma, CVA, and CTVA subjects were recruited from the Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. Thirty sex-, age-, and ethnic-matched healthy control subjects were enrolled from the community. All participants gave written informed consent to participate in the study, which was approved by the Institutional Review Board for Human Studies of Second Affiliated Hospital of Zhejiang University School of Medicine . The definition of health controls and patients with asthma was according to Global Initiative for Asthma (GINA) guidelines and relevant references –11. A diFeNO was measured using a chemiluminescence analyzer  at a flow rate of 50 mL/s, according to the the American Thoracic Society/European Respiratory Society guidelines .Sputum induction was performed according to previous study . Brieflyhttp://www.promega.com/). Tryptic digests of proteins were analysed by reverse-phase HPLC/tandem MS (MS/MS). The samples were desalted by spin column , and then analyzed by an in-house packed reversed-phase C18 column (360 μm OD × 75 μm ID) connected to an Easy-nLC 1000 HPLC system by a 3 h-gradient at a flow rate of 300 nL/min. The eluted peptides were ionized and introduced into an Orbitrap Elite mass spectrometry (Thermo Orbitap) using a nanospray source. The identity of the compound and its molecular mass from m/z 300–1800 were acquired by the precursor ion scan using the Orbitrap analyzer with resolution r = 60,000 at m/z 400, followed by 20 MS/MS events in LTQ velos analysis. The top 20 most intense precursor ions in each MS scan were sequentially isolated and fragmented with a normalized energy of 35% of CID.Protein concentrations of sputum samples were estimated using a BCA Protein Assay Kit . Proteins (200 μg) from individual samples were extracted by acetone sedimentation. Acetone-precipitated samples were dissolved in 8 M urea, 100 mM Tris–HCl (pH 8.5). Proteins were reduced with 5 mM Tris-(2-carboxyethyl) phosphine (TCEP) at room temperature for 20 min. Alkylation was performed by the addition of 10 mM iodoacetamide, and the samples were incubated at room temperature for 15 min. The protein mixture was diluted four times and tyrptic digested with Trypsin at 1:100 (w/w) . In order to improve reliability and interpretability, data were log transformed and normalized by MetaboAnalyst 2.0 [Data were entered into SPSS for Windows, version 13.0 . The demographic and clinical data were presented as mean ± SD or number (percentage). Serum total IgE values were log-transformed before analysis and expressed as a geometric mean with a range of 1 SD. Categorical variables were assessed using Pearson’s Chi square tests. Comparisons of continuous data between two groups were performed by lyst 2.0 . MetaboAP < 0.001)    and Self-rating Depression Scale (SDS) (P < 0.001) than those of controls.Basic demographic characteristics for health controls and patients with all three asthmatic groups are summarized in Table Patients with CA, CVA, and CTVA were similar in levels of serum total IgE. Thirteen of the CA cases (43.3%), ten of the CVA cases (37.0%), and seven of the CTVA (23.3%) cases have a history of atopy; the prevalence of atopy was not significant different among three asthmatic groups.1 (% Predicted) in CA, CVA, and CTVA were 80.7 ± 14.6, 90.5 ± 17.6, and 84.2 ± 21.8%, respectively, with no significant differences. FEV1/FVC ratio (%) in CA, CVA, and CTVA were 74.1 ± 8.0, 80.0 ± 8.2, and 71.5 ± 15.3%, respectively. As compared with CA and CTVA, those with CVA had a higher FEV1/FVC ratio (%) (P = 0.017). Positive bronchial provocation test (BPT) in CA, CVA, and CTVA were 28 (93.3%), 22 (81.5%), and 28 (93.3%), respectively; and positive bronchial dilation test (BDT) in CA, CVA, and CTVA were 2 (6.7%), 5 (18.5%), and 2 (6.7%), respectively. There was no significant difference in the results of the bronchial challenge test and bronchodilator test among the three groups.Then we investigated pulmonary function and bronchial responsiveness for patients with CA, CVA, and CTVA. FEVRecently, numerous studies have demonstrated that anxiety and depression are common and relevant comorbidities in asthmatic patients –17. In tP < 0.01) than that of the control group (0.4 ± 0.85%) , sputum eosinophils, and FeNO. In these three groups of asthma types, we found a similar proteomic pattern with minor differences in induced-sputum supernatants. Therefore, although patients with CA, CVA, and CTVA are diagnosed on the basis of different presenting symptoms, our findings support the contention that the inflammatory mechanisms of eosinophilic inflammation are similar in CA, CVA and CTVA.The patients we recruited with CA, CVA, and CTVA had similar clinical and inflammatory characteristics with no differences with respect to atopy, serum IgE, FEVIn the present study, sputum eosinophil percentages were significantly higher in patients with CA, CVA, and CTVA than that of controls. Increased sputum and tissue eosinophil levels have been demonstrated in the patients with CA –22. In tOne of the aims of the present study was to compare the degree of airway inflammation among patients with CA, CVA, and CTVA. However, a comparison of the sputum eosinophil measurements in these three groups showed no significant differences. FeNO is validated, commonly used as a noninvasive marker of airway inflammation in asthma . FeNO meAsthma is the manifestation of multitude reactions of biological, cellular and immunological events, in which cytokines, chemokines, and inflammatory pathways associated with T helper type 2 (T(H)2)-driven adaptive immunity have been demonstrated to play a central role in its pathogenesis , 29. In In this study, we found eosinophilic inflammation in CA and CVA, and for the first time in the newly-described asthmatic condition of CTVA sputum eosinophilia. Thus these three types of asthma conditions are characterized by eosinophilia. We therefore analyzed the correlation of these newly-identified biomarkers with eosinophil counts. Interestingly, GPI and S100A12 were found to be highly associated with sputum eosinophil counts, suggesting a TH2 dependent response. Thus, this finding provides a rationale for CVA and CTVA therapies as those for CA, in the use of inhaled corticosteroids, and other potential targeted therapies for the Th2 pathway . As specSeveral limitations of this study are worth discussing. First, the findings from our study should be confirmed by other studies. Future studies were warranted to validate our findings. Second, the induced-sputum sample was used in our study, which is secreted from airways, not link to gene or something else. Thus, it may not available to conduct some further analyses such as pathway analysis. Third, most proteins in three asthmatic group were similar. Thus, we can only look for differentiating differences, while failed to mention as a total asthma group.In summary, this study show that, in patients with CA, CVA, and CTVA who have similar clinical and inflammatory characteristics in terms of eosinophilic airway inflammation, there were no dramatic differences in the spectrum and levels of proteins in sputum supernatants. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. A common therapeutic strategy might be suggested for these different presentations of asthma. This study, for the first time, performed a proteomic analysis of the sputum supernatants in different presentations of asthmatic patients. In our MS analysis of sputum samples, more than 1000 proteins were identified, among which 23 secreted proteins were higher in patients than that in controls. Differential proteins involved in immunity, inflammatory, and chemokines were analyzed. Importantly, we identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes.Additional file 1: Table S1. The proteins were identified in the sputum from patients with CA, CVA, and CTVA.Additional file 2: Figure S1. High expression of secreted protein in CA, CVA, or CTVA patients. AGT (A), ANXA1 (B), APOA1 (C), B2M (D), C5 (E), CHI3L1 (F), CTSB (G), FGA (H), FGB (I), FN1 (J), HPX (K), IL1RN (L), ITIH4 (M), ORM1 (N), PRG2 (O), and SERPINF (P). Mean values are represented as horizontal bars. *P < 0.05, **P < 0.01, ***P < 0.001; CA, classic asthma; CVA, cough-variant asthma; CTVA, chest tightness variant asthma.