scholarly journals Pharmacometabolomics of Bronchodilator Response in Asthma and the Role of Age-Metabolite Interactions

Metabolites ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 179 ◽  
Author(s):  
Rachel S. Kelly ◽  
Joanne E. Sordillo ◽  
Sharon M. Lutz ◽  
Lydiana Avila ◽  
Manuel Soto-Quiros ◽  
...  

The role of metabolism in modifying age-related differential responses to asthma medications is insufficiently understood. The objective of this study was to determine the role of the metabolome in modifying the effect of age on bronchodilator response (BDR) in individuals with asthma. We used longitudinal measures of BDR and plasma metabolomic profiling in 565 children with asthma from the Childhood Asthma Management Program (CAMP) to identify age by metabolite interactions on BDR. The mean ages at the three studied time-points across 16 years of follow-up in CAMP were 8.8, 12.8, and 16.8 years; the mean BDRs were 11%, 9% and 8%, respectively. Of 501 identified metabolites, 39 (7.8%) demonstrated a significant interaction with age on BDR (p-value < 0.05). We were able to validate two significant interactions in 320 children with asthma from the Genetics of Asthma in Costa Rica Study; 2-hydroxyglutarate, a compound involved in butanoate metabolism (interaction; CAMP: β = −0.004, p = 1.8 × 10−4; GACRS: β = −0.015, p = 0.018), and a cholesterol ester; CE C18:1 (CAMP: β = 0.005, p = 0.006; GACRS: β = 0.023, p = 0.041) Five additional metabolites had a p-value < 0.1 in GACRS, including Gammaminobutyric acid (GABA), C16:0 CE, C20:4 CE, C18.0 CE and ribothymidine. These findings suggest Cholesterol esters and GABA may modify the estimated effect of age on bronchodilator response.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot Kaur Grewal ◽  
Shruti Chandra ◽  
Alan Bird ◽  
Glen Jeffery ◽  
Sobha Sivaprasad

AbstractTo evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nadia abdelaty Abdelkader ◽  
Moustafa Hamed Abdelaleem ◽  
Mohammed El-Gharib Abo El- maaty ◽  
Heba Ismail Aly ◽  
Sayed Ahmed Sayed

Abstract Background Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and it is also a common cause of death in patients with chronic liver disease. The curative treatment options for HCC that are currently available are surgical resection, liver transplantation and radiofrequency ablation .Despite progressive improvements in the efficacy of RFA, the survival of patients with HCC who undergo RFA remains disappointing, mainly due to frequent intrahepatic recurrence of HCC after RFA. Aim of the work To evaluate the role of transient elastography (as an indirect indicator to degree of liver fibrosis) in prediction of denovo recurrence of hepatocellular carcinoma after radiofrequency ablation in hepatitis C related hepatocellular carcinoma .And to compare between transient elastography and other non invasive fibrosis indices in prediction of denovo recurrence of hepatocellular carcinoma after radiofrequency ablation hepatitis C related hepatocellular carcinoma Patients and methods This prospective cohrt study was conducted on hepatocellular carcinoma patient, who underwent radiofrequency ablation in Tropical Medicine Department in Eldemerdash and Ain Shams Specialized Hospital, HCC clinic Ain Shams University Hospitals, Cairo, Egypt between march, 2017 and May, 2019. Data of the patient, who underwent radiofrequency ablation during the study period, were reviewed and the patients who fulfilled the inclusion criteria were enrolled into this study. The patients who fulfilled the inclusion criteria and underwent radiofrequency ablation were followed up for 12 months. Results TE revealed 28 patients with F4 and only 2 patients with F3, the mean measurement of liver stiffness was (22.45 ± 10.36) KPa. There was a significant negative correlation between LS and denovo recurrence of HCC (mean of LS in patients with complete response was 17.19 ± 3.32 and the mean of LS in patient with denovo recurrence was 36,94 ± 5.93,with the The best cut off value ≥24.65 (p value &lt; 0.001)). There was no significant correlation between CDC, FIB4, API scores and denovo recurrence of HCC. Also it was found that the LS was significantly associated with prediction of manifestation of hepatic decompensation after RFA (means of LS in patient without manifestation decompensation after RFA (p value &lt;0.001) .Regarding prediction of mortality, LS at cut off value &gt; 42 .75 (p value = 0,031) was significantly associated with prediction of mortality after one year of RFA. As regard serum non invasive fibrosis indices our results showed correlation between FIB4 score and hepatic decompensation after one year of intervention (the mean of FIB4 score in patients ascites and jaundice was 6.05 ± 4.71 (p value = 0.05) ).Therewas no statistically significant correlation between CDS and API with hepatic decompensation after RFA .As regard role of serum non invasive fibrosis indices in prediction of mortality after RFA, FIB4 score, CDS and API were statistically non significant. Conclusion Our data suggest that LS measurement is a useful predictor of HCC de novorecurrence overall survival and possibility of hepatic decompensation after RFA


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M S Abdaltawab ◽  
Z F Ismail ◽  
W M A Ebeid ◽  
S M Fawzy

Abstract Aim of the Work The aim of this work is to compare the response of treatment with ranibizumab in terms of visual acuity in cases of CNV secondary to pathological myopia versus CNV secondary to age-related macular degeneration. Methods This prospective, comparative study included ten eyes newly diagnosed as having CNV secondary to pathological myopia, and 10 eyes newly diagnosed as having subfoveal active CNV secondary to AMD. All patients had 3 monthly intravitreal Injections of 0.50 mg (in 0.05 ml of solution) ranibizumab with monthly evaluation of best corrected visual acuity (BCVA) by Landolt C chart, and also calculated in Logarithm of Minimum Angle of Resolution (Log MAR). Results pretreatment there was no significant difference between the two groups as the mean VA (Log Mar) was 1.31 ± 0.2 in AMD group and 1.17 ± 0.3 in MCNV group of P value = 0.431 and also post three IVI of ranibizumab showed no significant difference between the two groups as the mean VA (Log Mar) was 1.22 ± 0.2 for AMD and 1.22 ± 0.5 for MCNV of P value = 0.635. Conclusion there was no significant difference in BCVA between AMD and MCNV groups after three intravitreal injections of ranibizumab.


2020 ◽  
Vol 12 (2) ◽  
pp. 37-45
Author(s):  
Vesna Micevska ◽  
Tatjana Jakovska Mareti ◽  
Ilija Kirovski ◽  
Olivera Jordanova

Asthma is a chronical disease of the airways characterized by reversible obstruction of the bronchi and airway inflammation. In recent decades, the scientific interest of the vitamin D system and its role in development of asthma and other alergic diseases has been increased. Aims of this study are to mesure and compare the serum level of 25 OHD in asthmatic and healthy children and corelate the level of 25OHD and total IgE in asthmatic children. This prospective study includes 70 children at age 2 to 14, of which 32 are children with diagnosed asthma and 38 healthy children. In both  of the groups the serum level of 25 OHD was measured  and by the results 18 % of the healthy children (C) and 28% of the asthma children (E) had 25OHD  deficiency, 45%  of C and 50% of E were insufficient and 37 % of C / 22% of E were with normal 25 OHD serum level. The mean level of 25OHD in C was 27,83 +/- 10,24 and in E 20,9 ng/ml +/- 10,72. The mean levels in both groups had statistic significant difference with p-value < 0,05. According to age no statistic significant difference was found in both of the groups. There was a statisticaly significant decreased serum level of 25 OHD in asthmatic females.In the examined group (children with asthma) there was a negative linear correlation (association) of the level of 25OHD and total IgE serum level with r=- 0,55  Vitamin D serum level measurements in asthma patients gives the possibility for discovering the connection between its deficiency and development of asthma symptoms.


2019 ◽  
Vol 4 ◽  
pp. 168 ◽  
Author(s):  
Harriet Mpairwe ◽  
Pius Tumwesige ◽  
Milly Namutebi ◽  
Marble Nnaluwooza ◽  
Tonny Katongole ◽  
...  

Background: Children from low- and middle-income countries have poor asthma control, mainly because of poor management. The extent of this problem in Uganda is not well known, but such information would be useful to guide policy and practice. We therefore conducted a cross-sectional study among schoolchildren with asthma in urban Uganda, to assess the level of asthma control and management. Methods: Schoolchildren aged 5-17 years were enrolled, asthma was diagnosed by the study medical team. Asthma control was assessed using the Asthma Control Test and the childhood Asthma Control Test. Data on previous asthma management was obtained using interviewer-led questionnaires. Data were analysed using multiple linear and multiple logistic regression. Results: We enrolled 561 children with asthma, of whom only 56% had ever had an asthma diagnosis. We categorised asthma as well-controlled (55.5%), partly-controlled (29.5%) and poorly-controlled (15.0%). Poor asthma control was associated with increasing age (adjusted regression coefficient [95% confidence interval], p-value: -1.07 [-1.20, -0.94], p<0.0001), concurrent allergic rhinitis (-1.33 [-2.28, -0.38], p=0.006), and city residence in early life (-1.99 [-3.69, -0.29], p=0.06). Regular use of inhaled asthma medication in the last 12 months was very low; 18.1% for salbutamol and 6.7% for inhaled corticosteroids. The main barriers to inhaled asthma medication use were lack of prescription (47.6%) and inaccurate diagnosis (38.8%). Increased inhaler use was associated with tertiary education of the fathers (adjusted odds ratio [95% confidence interval], p-value: 5.19 [2.39-11.28], p<0.0001), city residence in early life (4.66 [1.79-12.43], 0.002) and an asthma diagnosis prior to enrolment (11.39 [6.35-20.43], p<0.0001). Conclusions: This study confirms that children with asthma in Uganda generally have inadequate asthma control, which is attributable to poor asthma management. This could be improved through re-training of medical workers and patient education, and by increasing availability and affordability of essential asthma medications.


2019 ◽  
Vol 3 (2) ◽  

Introduction: Early recognition of subclinical intra-amniotic infection before development of clinical Chorioamnionitis dramatically improve neonatal outcome before affection of fetal neurological function. Objective: this study was conducted to evaluate the role of procalcitonin and interleukin-6 in early prediction of intrauterine infection in pregnant women with premature rupture of membranes. Methods: This observational prospective cohort study was conducted on 100 pregnant women with preterm premature rupture of membrane (PPROM), Patients were divided into 2 groups: Group I: with normal CRP and WBCs level. Group2: with subclinical infection which was detected by elevated WBCs count >15,000 c/mm3 and / or positive CRP. This group was divided into two groups (Group (II) and Group (III) according to development of Chorioamnionitis. follow up of these patients was done to detect the cutoff value of procalcitonin and interleukin-6 as a predictive indicator of clinical intra-amniotic infection in patients with premature rupture of membrane. Results: This study showed that the mean value of maternal serum PCT concentration was higher in patients with clinical infection than its concentration in patients without infection or with subclinical infection with P-value 0.0001 which is highly significant between the studied cases and with cutoff value was >0.67ng/ml, sensitivity, specificity, PPV, NPV was 88.7%, 42.9%, 79.7% and 60% respectively and the mean value of maternal serum IL-6 concentration was also higher in patients with clinical infection than its concentration in patients without infection or with subclinical infection with P-value 0.001which is highly significant between the studied cases and with cutoff value was >11.1pg/ ml, sensitivity, specificity, PPV, NPV was 67.9%, 61.9%, 81.8% and 43.3% respectively. Conclusion: maternal serum procalcitonin is a good predictor of clinical intra-amniotic infection with good sensitivity, specificity, PPV, NPV which is nearly good as CRP which is better than serum interleukin-6 regarding sensitivity


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255213
Author(s):  
Shoji Notomi ◽  
Satomi Shiose ◽  
Keijiro Ishikawa ◽  
Yosuke Fukuda ◽  
Kumiko Kano ◽  
...  

Drusen are known to be the important hallmark to predict the development of age-related macular degeneration (AMD). The prevalence of drusen is lower in Asians compared with Caucasians so that the role of signs constituting early AMD is not well established in Asian populations as in Western countries. In this study, we retrospectively investigated clinical characteristics and 5-year incidence of neovascular AMD (nAMD) in the fellow eye of unilateral nAMD patients. Of 296 consecutive unilateral nAMD patients who had been followed up more than 5 years, 170 typical AMD, 119 polypoidal choroidal vasculopathy, and 7 retinal angiomatous proliferation were included. To examine factors associated with nAMD occurrence in the fellow eye, drusen and pigmentary abnormality in the fellow eye were classified into 4 categories; Category 1: no or small drusen < 63 μm (37.2%), Category 2: 63–125 μm medium drusen or pigmentary abnormality (22.2%), Category 3: large drusen > 125 μm (25.0%), Category P: pachydrusen (15.5%). The mean sub-foveal choroidal thickness (SFCT) was Category 1: 276 μm, Category 2: 308 μm, Category 3: 246 μm, and Category P: 302 μm, respectively. Of note, SFCT in Category 2 and Category P was significantly larger than those of Category 3. Finally, the 5-year incidence of nAMD in the fellow eye was 32/296 (10.8%); Category 1: 0/110 (0%), Category 2: 12/66 (18.2%), Category 3: 20/74 (27.0%), and Category P: 0/46 (0%). Thus, signs of intermediate AMD (large drusen) as well as those of early AMD, especially the pigmentary abnormality, may contribute to development of bilateral nAMD in Japanese patients.


BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e024545 ◽  
Author(s):  
Monica Lakhanpaul ◽  
Lorraine Culley ◽  
Tausif Huq ◽  
Deborah Bird ◽  
Nicky Hudson ◽  
...  

ObjectiveThis paper draws on the data from the Management and Interventions for Asthma (MIA) study to explore the perceptions and experiences of asthma in British South Asian children using semi-structured interviews. A comparable cohort of White British children was recruited to identify whether any emerging themes were subject to variation between the two groups so that generic and ethnicity-specific themes could be identified for future tailored intervention programmes for South Asian children with asthma.SettingSouth Asian and White British children with asthma took part in semi-structured interviews in Leicester, UK.ParticipantsThirty three South Asian and 14 White British children with asthma and aged 5–12 years were interviewed.ResultsBoth similar and contrasting themes emerged from the semi-structured interviews. Interviews revealed considerable similarities in the experience of asthma between the South Asian and White British children, including the lack of understanding of asthma (often confusing trigger with cause), lack of holistic discussions with healthcare professionals (HCPs), an overall neutral or positive experience of interactions with HCPs, the role of the family in children’s self-management and the positive role of school and friends. Issues pertinent to South Asian children related to a higher likelihood of feeling embarrassed and attributing physical activity to being a trigger for asthma symptoms.ConclusionsThe two ethnicity-specific factors revealed by the interviews are significant in children’s self-management of asthma and therefore, indicate the need for a tailored intervention in South Asian children.


2002 ◽  
Vol 18 (3) ◽  
pp. 128-137 ◽  
Author(s):  
Valerie O’Toole Baker ◽  
Janet Friedman ◽  
Rita Schmitt

Death rates from asthma have increased or remained stable over the past decade despite increased knowledge about the pathophysiology and improved treatment of the disease, a fact that is both puzzling and disconcerting. Some children with asthma experience severe and life-interfering exacerbations separated by long periods of normal lung function and no symptoms. Asthma management plans are developed by primary care providers and the family. School nurses implement and monitor the child’s response to the plan. Therefore, the school nurse needs current information about asthma management. Part I of this two-part series describes the pathophysiology of asthma and the types, risk factors, and current trends in management of the disease. The role of the school nurse in asthma management is outlined, including how he or she can influence environmental factors that precipitate asthma symptoms or exacerbations. Part II will discuss the role of the school nurse in pharmacologic management of asthma. Complementary alternative medicine for asthma management will be described, as well as health teaching for the child with asthma and their family.


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