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INTRODUCTION: Uncontrolled or severe asthma results in symptomatic usage of short-acting ß2-agonist (SABA) usage. MicroRNAs (miRNAs) are posttranslational regulators that can influence asthma biology. This study aims to identify miRNAs that are associated with increased SABA usage. METHODS: Small RNA sequenced from blood serum of 1,132 children with asthma aged 6 to 14 years in the Genetics of Asthma in Costa Rica Study was used for this analysis. Logistic regression identified miRNAs in patients who required increased SABA usage. These miRNA were validated for association with SABA-induced bronchodilator responsiveness (BDR). Gene target pathway analysis was performed on validated miRNAs. RESULTS: Twenty-one miRNAs were significantly associated with increased SABA usage with OR ranging from 0.87 to 1.23. Two miRNAs, miR-378a-3p and miR-144-3p, had odds ratio 1.14 (1-1.29, p = .05) and 1.11 (1.01-1.22, p = .035), respectively, for increased SABA usage and were also significantly associated with bronchodilator response. Furthermore, a linear regression analysis involving these miRNA and bronchodilator response revealed that increased miR-378a-3p correlated with decreased BDR and increased expression of miR-144-3p correlated with improving pulmonary function with bronchodilators. In gene target Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the erythroblastosis viral oncogene signaling pathway had among one of the highest fold enrichment and p-value. CONCLUSION: Increased expression of miR-378a-3p and miR-144-3p was seen in this patient population who required increased SABA usage. There were different bronchodilatory effects seen in these two miRNAs, suggesting different potential mechanisms underlying increased SABA usage.
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INTRODUCTION: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phase III/IV clinical studies. RESULTS: Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3 months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24 h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). CONCLUSIONS: We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.
In this study we looked at how different factors affect the response to asthma treatment in people with moderate to severe asthma who are taking regular medication. Specifically, we wanted to quantify how much asthma duration, differences in the degree of symptom control and lung function, as well as smoking habit, body weight, and sex influence how well someone responds to regular maintenance therapy. Using computer simulations based on models obtained from data in a large patient population with moderatesevere asthma, we explored scenarios that reflect real-life management of patients undergoing treatment with inhaled corticosteroids alone or in combination with long-acting beta agonists over a 12-month period. We looked at how much reliever inhaler they use, how well they rate their asthma control, and how often they have asthma attacks. By considering these results together, we evaluated how well the treatments work on ongoing symptoms and/or reduce the risk of future asthma attacks. Our simulations showed that smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. This was linked to a higher risk of having asthma attacks and worse symptom control. Switching those patients who do not respond well to their initial treatment with corticosteroid to combination therapy reduced how much reliever inhaler they need. Also, the effects of fluticasone propionate/salmeterol combination therapy were greater than budesonide/formoterol. In conclusion, our study found that certain patient characteristics can predict how well someone responds to asthma treatment.
Asunto(s)
Antiasmáticos , Asma , Humanos , Asma/tratamiento farmacológico , Masculino , Femenino , Antiasmáticos/uso terapéutico , Adulto , Índice de Severidad de la Enfermedad , Persona de Mediana Edad , Simulación por Computador , Combinación Fluticasona-Salmeterol/uso terapéutico , Broncodilatadores/uso terapéutico , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (ß2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.
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In Latin-America, with 603 million inhabitants, the average prevalence of asthma is estimated at 17%, but with wide fluctuations, ranging from 5% in some cities (Mexico) to 30% in Costa Rica. The risk of severe exacerbations seems to be higher in Latin America compared with other regions. A majority of patients uses daily quick-relief medication, with the belief that it is the most important treatment because of its rapid onset of action; without treating the underlying inflammation. Overuse of short-acting beta2 agonists (SABAs) is associated with increased risk of asthma deaths in a dose-response manner. Beta2 agonists increase the severity of asthma through enhanced bronchial hyperresponsiveness and reduced lung function. Also, it has been shown that overreliance on SABA delays recognition of a potentially life-threatening asthma attack. We believe that overreliance on SABA in asthma is also an important public health issue. The fact that SABA use in GINA is not supported by a randomized trial but by an anonymous paper; makes us guess that we use SABA just because we are used to do so. In 2019 GINA strategy introduces one of the most important changes in the management of Asthma in the past 30 years, highlighting anti-inflammatory reliever therapy. A combination of low dose ICS/fast action bronchodilator will not only treat symptoms, but more importantly the underlying inflammation, protecting patients from preventable asthma attacks. After 50 years of a SABA centric approach in asthma management, it is time to leave behind a treatment based just on the bronchodilation and tackle the inflammation.
Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Asma/tratamiento farmacológico , Asma/epidemiología , Broncodilatadores/uso terapéutico , Humanos , América Latina/epidemiologíaRESUMEN
Ractopamine hydrochloride (RAC) is a ß-adrenergic agonist approved for feeding during the last 28 to 42 d prior to cattle slaughter to improve feedlot performance and carcass characteristics. Three thousand crossbred yearling steers (527 ± 2.4 kg; AVG ± SD) were used in two periods to evaluate the effects of various RAC withdrawal times on feedlot performance, health, and carcass characteristics. In Period 1, 6 blocks of 30 pens totaling 1,500 steers were utilized, which was repeated for Period 2. In a randomized complete block design, cattle were assigned to 1 of 5 treatments consisting of 1) No RAC fed (CON), 2) 12-h RAC withdrawal (12-hRAC), 3) 2-d RAC withdrawal (2-dRAC), 4) 4-d RAC withdrawal (4-dRAC), and 5) 7-d RAC withdrawal (7-dRAC). Cattle were fed for a total of 62 d, and applicable treatments were supplemented with 30.0 ppm (dry matter basis) of RAC (average dose = 322 mg per steer per day) for 33 d at the end of the feeding period, corresponding to their respective withdrawal times. Initial body weight (BW) displayed a quadratic curve, with 2-dRAC and 4-dRAC withdrawal periods having the greatest BW. Accordingly, dry matter intake (DMI) responded quadratically (P = 0.034), with 2-dRAC and 4-dRAC treatments demonstrating the greatest DMI. No significant treatment differences (P ≥ 0.641) were observed in final live BW, average daily gain (ADG), or feed efficiency. Alternatively, when using a common dressing percentage to calculate live BW, cattle on RAC treatments exhibited 7.6 kg additional live BW (P < 0.001) compared to CON cattle. Furthermore, carcass-adjusted ADG and feed efficiency did not differ (P > 0.10) between RAC treatments but were improved compared to the CON treatment (P ≤ 0.002). Hot carcass weight (HCW) was on average 4.9 kg greater (P < 0.001) for RAC treatments vs. CON, and no differences were detected (P > 0.10) among RAC treatments. Within RAC treatments, carcass cutability responded quadratically (P ≤ 0.005) to withdrawal period, with the 2-dRAC and 4-dRAC treatments containing more Yield Grade 4 and 5 and fewer Yield Grade 1 and 2 carcasses than the other RAC treatments. On the basis of the results of this experiment, feeding RAC improves dressing percentage, HCW, and carcass-adjusted BW, ADG, and feed efficiency. Furthermore, extending the RAC withdrawal period to 7 d does not have a significant impact on cattle performance or health and has minimal effects on carcass characteristics.
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BACKGROUND: In April 2017 the Mexican Asthma Guidelines (GUIMA) were published. Before the launch, physicians' knowledge was explored related to key issues of the guideline. METHODS: A SurveyMonkey® survey was sent out to board-certified physicians of 5 medical specialties treating asthma. Replies were analyzed per specialty against the GUIMA evidence-based recommendations. We present the treatment part here. RESULTS: A total of 364 allergists (ALLERG), 161 pulmonologists (PULM), 34 ENTs, 239 pediatricians (PED) and 62 general practitioners (GPs) replied to the survey and 247-83-14-135-37 respectively finished it. Spirometry is not routinely indicated when asthma is very probable by ALLERG 54%, PULM 47%, ENT 39%, PED 65%, GP 64%. A fictitious case proposed to the physicians with intermittent asthma was erroneously treated with ICS by ALLERG 9%, PULM 11%, ENT 28%, PED 10%, GP 11%. The mild persistent case received mistakenly ICS-LABA by ALLERG 25%, PULM 26%, ENT 33%, PED 27%, GP 23%. The first-line option for moderate persistent asthma was ICS(median dose) instead of ICS(low)+LABA for ALLERG 29%, PULM 25%, ENT 17%, PED 27%, GP 23% and in severe asthma maintenance treatment PULM20%, ALLERG-ENT-PED-GP 22-34% failed to indicate LABA. Concerning the guidelines' recommendation to use one inhaler for maintenance & rescue in moderate-to-severe asthma, PULM45%, ALLERG-ENT-PED-GP 56-80% (p < 0.00001), erroneously indicated ICS-salmeterol could be used, instead of ICS-formoterol. Oral ß2 or theophylline are no longer recommended, but PULM 37% and ALLERG-ENT-PED-GP 42-62% (p < 0.01) still indicate their use. In severe asthma 61-73% of physicians consider adding LTRA to the treatment; only PULM38%, OTHERS12-25% consider adding tiotropium (p < 0.001) and 3-17% consider adding omalizumab, both guideline recommended add-ons. As for asthma in pregnancy, most surveyed are not aware budesonide is the 1st line option ICS. Finally, 81-97% of the group-members recognized allergen immunotherapy, as a viable add-on, in line with GINA/GEMA/GUIMA recommendations. CONCLUSIONS: An online survey could detect knowledge-gaps related to asthma treatment. Interestingly, surveyed physicians tended to over-treat the milder asthma cases, thus clearly leaving room for cost-savings. Caution should be taken in the promotion of the SMART (single-maintenance-and-reliever-treatment) approach, which can only be done with ICS-formoterol. Many physicians opt for other combinations not apt for this approach. Among all surveyed specialties there is ample room for improvement in mild and severe asthma management.
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O objetivo do trabalho foi avaliar o desempenho e as características quantitativas de carcaça de suínos machos castrados, mantidos em ambiente de conforto térmico e alimentados com dietas contendo diferentes níveis de ractopamina. Foram utilizados 48 animais, com peso médio inicial de 67,0±2,7kg, distribuídos em delineamento de blocos ao acaso composto por quatro níveis de ractopamina (0, 5, 10 e 20ppm) e seis repetições, com dois animais cada. O período experimental teve duração de 28 dias. A temperatura do ar obtida foi de 20,9±2,9°C, a umidade relativa foi de 86,7±7,3 por cento, e o Índice de Temperatura de Globo e Umidade foi de 69,6±4,0. O peso final dos animais e o consumo de ração não foram influenciados (P>0,05) pelos tratamentos. Os níveis de ractopamina influenciaram (P<0,05) o ganho de peso diário e a conversão alimentar dos suínos. Observou-se redução linear (P<0,05) da espessura de toucinho e aumento da profundidade de músculo e da porcentagem de carne magra na carcaça de acordo com o aumento dos níveis de ractopamina na dieta. O peso e o rendimento de carcaça quente e a área de olho de lombo não foram influenciados (P>0,05) pelos tratamentos. Concluiu-se que o nível ótimo de inclusão de ractopamina na dieta de suínos machos castrados e mantidos em ambiente termoneutro é de 20ppm.
The objective of this study was to evaluate the performance and the quantitative characteristics of barrow's carcass maintained under thermoneutral environment and fed with diets containing different ractopamine levels. Forty-eight barrows were used, with initial weight of 67.0±2.7kg, distributed in a randomized blocks design with four ractopamine levels (0, 5, 10 and 20ppm) and six replicates with two animals each. The experimental period lasted 28 days. The average temperature recorded was 20.9±2.9°C, relative humidity was 86.7±7.3 percent and BGHI was 69.6±4.0. The final weight of the animals and feed intake were not influenced (P>0.05) by treatments. The ractopamine levels influenced (P<0.05) the daily weight gain and feed conversion. There was a linear reduction (P<0.05) of backfat thickness, increase of muscle depth and the carcass lean meat percentage in accordance with the increasing of ractopamine levels in the diet. The weight, carcass yield and loin eye area were not influenced (P>0.05) by treatments. It was concluded that the ractopamine optimal level of inclusion in the diet of barrows kept under thermoneutral environment is 20ppm.
RESUMEN
The objective of this study was to evaluate the performance and the quantitative characteristics of barrow's carcass maintained under thermoneutral environment and fed with diets containing different ractopamine levels. Forty-eight barrows were used, with initial weight of 67.0±2.7kg, distributed in a randomized blocks design with four ractopamine levels (0, 5, 10 and 20ppm) and six replicates with two animals each. The experimental period lasted 28 days. The average temperature recorded was 20.9±2.9°C, relative humidity was 86.7±7.3% and BGHI was 69.6±4.0. The final weight of the animals and feed intake were not influenced (P>0.05) by treatments. The ractopamine levels influenced (P 0.05) the daily weight gain and feed conversion. There was a linear reduction (P 0.05) of backfat thickness, increase of muscle depth and the carcass lean meat percentage in accordance with the increasing of ractopamine levels in the diet. The weight, carcass yield and loin eye area were not influenced (P>0.05) by treatments. It was concluded that the ractopamine optimal level of inclusion in the diet of barrows kept under thermoneutral environment is 20ppm.
O objetivo do trabalho foi avaliar o desempenho e as características quantitativas de carcaça de suínos machos castrados, mantidos em ambiente de conforto térmico e alimentados com dietas contendo diferentes níveis de ractopamina. Foram utilizados 48 animais, com peso médio inicial de 67,0±2,7kg, distribuídos em delineamento de blocos ao acaso composto por quatro níveis de ractopamina (0, 5, 10 e 20ppm) e seis repetições, com dois animais cada. O período experimental teve duração de 28 dias. A temperatura do ar obtida foi de 20,9±2,9°C, a umidade relativa foi de 86,7±7,3%, e o Índice de Temperatura de Globo e Umidade foi de 69,6±4,0. O peso final dos animais e o consumo de ração não foram influenciados (P>0,05) pelos tratamentos. Os níveis de ractopamina influenciaram (P 0,05) o ganho de peso diário e a conversão alimentar dos suínos. Observou-se redução linear (P 0,05) da espessura de toucinho e aumento da profundidade de músculo e da porcentagem de carne magra na carcaça de acordo com o aumento dos níveis de ractopamina na dieta. O peso e o rendimento de carcaça quente e a área de olho de lombo não foram influenciados (P>0,05) pelos tratamentos. Concluiu-se que o nível ótimo de inclusão de ractopamina na dieta de suínos machos castrados e mantidos em ambiente termoneutro é de 20ppm.
RESUMEN
The objective of this study was to evaluate the performance and the quantitative characteristics of barrow's carcass maintained under thermoneutral environment and fed with diets containing different ractopamine levels. Forty-eight barrows were used, with initial weight of 67.0±2.7kg, distributed in a randomized blocks design with four ractopamine levels (0, 5, 10 and 20ppm) and six replicates with two animals each. The experimental period lasted 28 days. The average temperature recorded was 20.9±2.9°C, relative humidity was 86.7±7.3% and BGHI was 69.6±4.0. The final weight of the animals and feed intake were not influenced (P>0.05) by treatments. The ractopamine levels influenced (P 0.05) the daily weight gain and feed conversion. There was a linear reduction (P 0.05) of backfat thickness, increase of muscle depth and the carcass lean meat percentage in accordance with the increasing of ractopamine levels in the diet. The weight, carcass yield and loin eye area were not influenced (P>0.05) by treatments. It was concluded that the ractopamine optimal level of inclusion in the diet of barrows kept under thermoneutral environment is 20ppm.
O objetivo do trabalho foi avaliar o desempenho e as características quantitativas de carcaça de suínos machos castrados, mantidos em ambiente de conforto térmico e alimentados com dietas contendo diferentes níveis de ractopamina. Foram utilizados 48 animais, com peso médio inicial de 67,0±2,7kg, distribuídos em delineamento de blocos ao acaso composto por quatro níveis de ractopamina (0, 5, 10 e 20ppm) e seis repetições, com dois animais cada. O período experimental teve duração de 28 dias. A temperatura do ar obtida foi de 20,9±2,9°C, a umidade relativa foi de 86,7±7,3%, e o Índice de Temperatura de Globo e Umidade foi de 69,6±4,0. O peso final dos animais e o consumo de ração não foram influenciados (P>0,05) pelos tratamentos. Os níveis de ractopamina influenciaram (P 0,05) o ganho de peso diário e a conversão alimentar dos suínos. Observou-se redução linear (P 0,05) da espessura de toucinho e aumento da profundidade de músculo e da porcentagem de carne magra na carcaça de acordo com o aumento dos níveis de ractopamina na dieta. O peso e o rendimento de carcaça quente e a área de olho de lombo não foram influenciados (P>0,05) pelos tratamentos. Concluiu-se que o nível ótimo de inclusão de ractopamina na dieta de suínos machos castrados e mantidos em ambiente termoneutro é de 20ppm.
RESUMEN
The objective of this study was to evaluate the performance and the quantitative characteristics of barrow's carcass maintained under thermoneutral environment and fed with diets containing different ractopamine levels. Forty-eight barrows were used, with initial weight of 67.0±2.7kg, distributed in a randomized blocks design with four ractopamine levels (0, 5, 10 and 20ppm) and six replicates with two animals each. The experimental period lasted 28 days. The average temperature recorded was 20.9±2.9°C, relative humidity was 86.7±7.3% and BGHI was 69.6±4.0. The final weight of the animals and feed intake were not influenced (P>0.05) by treatments. The ractopamine levels influenced (P 0.05) the daily weight gain and feed conversion. There was a linear reduction (P 0.05) of backfat thickness, increase of muscle depth and the carcass lean meat percentage in accordance with the increasing of ractopamine levels in the diet. The weight, carcass yield and loin eye area were not influenced (P>0.05) by treatments. It was concluded that the ractopamine optimal level of inclusion in the diet of barrows kept under thermoneutral environment is 20ppm.
O objetivo do trabalho foi avaliar o desempenho e as características quantitativas de carcaça de suínos machos castrados, mantidos em ambiente de conforto térmico e alimentados com dietas contendo diferentes níveis de ractopamina. Foram utilizados 48 animais, com peso médio inicial de 67,0±2,7kg, distribuídos em delineamento de blocos ao acaso composto por quatro níveis de ractopamina (0, 5, 10 e 20ppm) e seis repetições, com dois animais cada. O período experimental teve duração de 28 dias. A temperatura do ar obtida foi de 20,9±2,9°C, a umidade relativa foi de 86,7±7,3%, e o Índice de Temperatura de Globo e Umidade foi de 69,6±4,0. O peso final dos animais e o consumo de ração não foram influenciados (P>0,05) pelos tratamentos. Os níveis de ractopamina influenciaram (P 0,05) o ganho de peso diário e a conversão alimentar dos suínos. Observou-se redução linear (P 0,05) da espessura de toucinho e aumento da profundidade de músculo e da porcentagem de carne magra na carcaça de acordo com o aumento dos níveis de ractopamina na dieta. O peso e o rendimento de carcaça quente e a área de olho de lombo não foram influenciados (P>0,05) pelos tratamentos. Concluiu-se que o nível ótimo de inclusão de ractopamina na dieta de suínos machos castrados e mantidos em ambiente termoneutro é de 20ppm.