Β-agonist Administration Research Articles

Chronic acetylcholinesterase inhibition reduces the effects of physical training on ventricular contractility and coronary bed reactivity in hypertensive rats

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and β-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.

Clinical reasoning amongst paramedics using nebulised β₂ agonists to treat acute asthma exacerbations: a qualitative study

The heterogeneous nature of asthma results in a wide range of presentations during exacerbation. Despite UK pre-hospital management guidelines focusing on β₂ agonists, variables such as cause, severity, underlying health, comorbidities, and drug side effects can often make emergency treatment optimisation difficult. This article examines paramedics’ methods of observing, perceiving, interpreting, and treating asthma with β₂ agonists, often acting on limited information in rapidly evolving situations. We recruited paramedics from a single UK National Health Service ambulance Trust for qualitative semi-structured interviews. Responses underwent framework analysis to identify data similarities and differences. Fifteen qualitative interviews with paramedics revealed three main themes affecting patient management: clinician experience of presentation, adaptation of patient management approaches, and severity of side effects. Paramedics felt their ability to manage various asthma presentations was enhanced through guideline adaptation based on their own clinical experience and understanding of β₂ agonist side effects, allowing tailored responses based on a set of reinforcing factors. Inductive analysis revealed additional complexities within these themes, such as anxiety and diabetes, which may influence β₂ agonist administration and result in multiple care pathways being initiated during exacerbation. Paramedic care mirrors asthma’s complexity, accounting for a range of characteristics. A dynamic, critically thought approach enables patient management to be based on the presenting conditions rather than strict adherence to a single algorithm. Comprehending the complexities and variables in treatment can be crucial to how paramedics rationalise their treatment and optimise the care provided.

Preoperative Dexamethasone and β2 Agonist Administration to Children with Airway Foreign Bodies: Effects on Intraoperative Respiratory Complications

Background: One of the most challenging operations in children for anesthesiologists and surgeons is foreign body aspiration. Bronchospasm and desaturation may lead to bradycardia and even death. Objectives: The study aimed to evaluate the effect of preoperative dexamethasone and β2 agonist (salbutamol) administration on children who had foreign body aspiration during the rigid bronchoscopy on these undesired complications. Methods: Children were divided into two groups via random numbers table, independent of their clinical conditions. β2 agonist (salbutamol) (2.5 mg < 20 kg, 5 mg > 20 kg) and dexamethasone (0.5 mg/kg) were administrated to group 1, 30 minutes before the operation. The same agents were administrated to group 2 during anesthesia induction. The occurrence of bronchospasm, desaturation, and bradycardia was evaluated. Results: There were 27 children in each group. There was no statistically significant difference between the two groups’ time periods between the onset of the symptoms and procedure (P > 0.05). The two groups were similar in clinical aspects. Clinically, periods of spasm and desaturation were shorter, and patients recovered faster in group 1, but the bronchospasm numbers, desaturation, and bradycardia periods were similar in both groups. Conclusions: The results seem statistically similar. Since the periods of spasm and desaturation were shorter, and patients recovered faster in patients with preoperative administration of β2 agonists (salbutamol) and dexamethasone, we may suggest that a larger data set in future studies may lead to more significant results and a better conclusion.

Preoperative Dexamethasone and β2 Agonist Administration to Children with Airway Foreign Bodies: Effects on Intraoperative Respiratory Complications

Background: One of the most challenging operations in children for anesthesiologists and surgeons is foreign body aspiration. Bronchospasm and desaturation may lead to bradycardia and even death. Objectives: The study aimed to evaluate the effect of preoperative dexamethasone and β2 agonist (salbutamol) administration on children who had foreign body aspiration during the rigid bronchoscopy on these undesired complications. Methods: Children were divided into two groups via random numbers table, independent of their clinical conditions. β2 agonist (salbutamol) (2.5 mg < 20 kg, 5 mg > 20 kg) and dexamethasone (0.5 mg/kg) were administrated to group 1, 30 minutes before the operation. The same agents were administrated to group 2 during anesthesia induction. The occurrence of bronchospasm, desaturation, and bradycardia was evaluated. Results: There were 27 children in each group. There was no statistically significant difference between the two groups’ time periods between the onset of the symptoms and procedure (P > 0.05). The two groups were similar in clinical aspects. Clinically, periods of spasm and desaturation were shorter, and patients recovered faster in group 1, but the bronchospasm numbers, desaturation, and bradycardia periods were similar in both groups. Conclusions: The results seem statistically similar. Since the periods of spasm and desaturation were shorter, and patients recovered faster in patients with preoperative administration of β2 agonists (salbutamol) and dexamethasone, we may suggest that a larger data set in future studies may lead to more significant results and a better conclusion.

Beta-agonist drugs modulate the proliferation and differentiation of skeletal muscle cells in vitro

Essentially employed for the treatment of airway obstructions in humans, β-agonists are also known to have an anabolic effect in animals’ skeletal muscle. In vivo and in vitro studies have attested the increase in animal body mass and the hypertrophy of muscle cells following the administration of specific β-agonists. However, the contribution of β-agonists to C2C12 myoblasts growth remains obscure. We therefore aimed to investigate the impact of β1-and β2-agonist drugs on the proliferation and differentiation of skeletal muscle cells. Direct observations and cytotoxicity assay showed that clenbuterol, salbutamol, cimaterol and ractopamine enhanced muscle cell growth and viability during the proliferation stage. Structural examinations coupled to Western blot analysis indicated that salbutamol and cimaterol triggered a decrease in myotube formation. A better comprehension of the effect of β-agonists on myogenic regulatory genes in the muscle cells is crucial to establish a specific role of β-agonists in muscle development, growth, and regeneration.

Ractopamine Hydrochloride and Estradiol + Trenbolone Acetate Implants Alter Myogenic mRNA, <i>β</i>-Adrenergic Receptors, and Blood Metabolites

Two commonly used growth promotants in the United States beef industry are β-agonists and anabolic steroid hormones. Each has been shown to increase lean muscle deposition in cattle provided treatments of each growth technology, but much is still unknown of how steroidal implants and β-agonists work in combination. It was our goal to determine the effect of implant strategy and β-agonist administration in beef feedlot heifers (n = 264). A 3 × 2 factorial randomized complete block design was used with 2 levels of OPT and 3 different durations of terminal implant (TI) windows for a total of 6 treatment groups with 9 replications. Terminal implants (20 mg estradiol/200 mg trenbolone acetate implant, Component TE-200) were provided to heifers 140 d from slaughter (TI140), 100 d from slaughter (TI100), or 60 d from slaughter (TI60). Animals receiving the later two TI being first implanted on day 0 (8 mg estradiol/80 mg trenbolone acetate implant, Component TE-IH). The second treatment of the cattle received was the orally active beta adrenergic agonist, ractopamine-hydrochloride (RH) in the form of Optaflexx®(OPT; 0 (NO) or 200 (YES) mg/hd·d-1) over the final 28 days of the trial. Thirty animals were subjected to longissimus muscle (LM) biopsies on d 0, 40, 80, 112, and at slaughter on d 140 to view mRNA levels of myogenic related genes and protein quantities of the β1-adrenergic receptor (β1 AR) and β2-adrenergic receptor (β2 AR). On the same days, blood samples were taken from 108 animals to assess changes in plasma blood urea nitrogen (BUN), non-esterified fatty acids (NEFA) and progesterone due to treatments. Relative mRNA levels of myosin heavy chain IIX (MHC IIX), AMPKα, and IGF-I were increased (P P = 0.09) due to OPT. An interaction between TI d and OPT administration caused an increase (P β2 AR was decreased (P β1 AR protein intensity tended to be lower (P P P β-adrenergic receptors, and blood metabolites in finishing beef heifers.

Short-course administration of a traditional herbal mixture ameliorates asthma symptoms of the common cold in children.

Asthma is an increasing chronic respiratory disease affecting over 300 million people worldwide. Several studies have shown that herbal remedies may improve asthma control and reduce asthma symptoms. In this study, the effects of short-course administration of an herbal mixture (ASMATUSTM) in asthmatic children during viral respiratory tract infection, were evaluated. Forty-six children (7-12 years old) with intermittent asthma were enrolled in this double-blind randomized clinical trial. At the onset of common cold symptoms, the patients were randomly assigned to daily receive either the herbal mixture (comprised of Matricaria chamomilla, Althaea officinalis, Malva sylvestris, Hyssopus officinalis, Adiantum capillus-veneris, Glycyrrhiza glabra and Ziziphus jujube) or placebo for 5 days. Primary outcomes included day symptoms, night symptoms, and asthma attacks. Secondary outcomes included Peak Expiratory Flow Rate (PEFR), the need for β-agonist administration, oral prednisolone usage, necessity for re-visit due to uncontrolled or insupportable symptoms, as well as the number of hospital admissions and days absent from school. the herbal mixture significantly decreased the severity of coughs (p=0.049) and nighttime awakenings (p=0.029) in comparison to placebo. There was no significant reduction in wheezing, tachypnea, respiratory distress, PEF rate, absence from school, outpatient visits, asthma exacerbation, oral prednisolone or β-agonist usage and hospitalization. Short-course of herbal mixture this traditional herbal mixture, starting at the onset of signs of a viral respiratory tract infection in children with intermittent asthma, reduced cough and nights awakening. Further studies should be done to determine the most effective herbal admixture, as well as dose and duration of treatment.

When LC-HRMS metabolomics gets ISO17025 accredited and ready for official controls – application to the screening of forbidden compounds in livestock

ABSTRACTWithin the particular context of controlling chemical residues in food, an alternative to targeted approaches has emerged; it consists in the characterisation of physiological perturbations induced upon exposure of animals to a given chemical substance/class of substances to highlight suitable biomarkers addressing safety and/or regulatory issues. Metabolomics in particular has been investigated in the hope of identifying such biomarkers, and a range of studies have demonstrated the efficiency of the strategy. Until very recently, steps remained to be taken towards official or commercial implementation of corresponding tools. In particular, the lack of guidelines and criteria to validate such methods that do not target specific chemical species per se, constituted a bottleneck. In the present work, a metabolomics model dedicated to the detection of β-agonist administration in bovines has been developed and fully validated; criteria (selectivity, robustness, stability, suspicion threshold definition, false positive and false negative rates) have been proposed in agreement with EU expectations (Dec 2002/657), enabling demonstration that performances comply with screening requirements.Although some of the biomarkers involved in the prediction model remain un-elucidated, the corresponding LC-HRMS method has recently been ISO17025 accredited, allowing for the very first official implementation of a metabolomics based strategy within French National Monitoring Plans.

Improving Timeliness of β-Agonist and Corticosteroid Administration in Patients With Acute Wheezing.

Timely delivery of β-agonists and steroids to patients with acute recurrent wheezing is a key component of the National Heart, Lung, and Blood Institute recommended emergency department (ED) asthma care. We conducted an ED improvement initiative to standardize asthma care and improve time to treatments. Our multidisciplinary team identified key contributing factors to timeliness, developed key driver diagrams, implemented and refined a management pathway, designed and executed rapid cycle improvements, and implemented interventions. A time series design was used to analyze outcomes with baseline data and continuous monitoring during active intervention steps. The primary outcomes analyzed were the times to first β-agonist and steroid administration. Secondary outcomes included admission rate, ED length of stay, and ED revisits. Assignment of the Pediatric Asthma Score, our initial pathway step, occurred in most patients within the first several months. Time to first β-agonist administration decreased from the baseline mean of 76 minutes to 27 minutes. Time to steroid administration decreased from the baseline mean of 108 minutes to 49 minutes. Mean monthly admission rate remained at 22% with no special cause variation identified. The ED revisit rate was not negatively impacted and, in most months, was 0%. By standardizing asthma care in our ED and redesigning care delivery processes, care variation decreased and significant improvements in timeliness of β-agonist and steroid administration occurred.

Improving Guideline-Based Care of Acute Asthma in a Pediatric Emergency Department.

Rapid repetitive administration of short-acting β-agonists (SABA) is the most effective means of reducing acute airflow obstruction in asthma. Little evidence exists that assesses process measures (ie, timeliness) and outcomes for asthma. We used quality improvement (QI) methods to improve emergency department care in accordance with national guidelines including timely SABA administration and use of asthma severity scores. The Model for Improvement was used and interventions were targeted at 4 key drivers: knowledge, engagement, decision support, and workflow enhancement. Time series analysis was performed and outcomes assessed on statistical process control charts. Asthma severity scoring increased from 0% to >95% in triage and to >75% for repeat scores. Time to first SABA (T1) improved by 32.8 minutes (47%). T1 for low severity patients improved by 17.6 minutes (28%). T1 for high severity patients improved by 3.1 minutes to 18.1 minutes (15%). Time to third SABA (T3) improved by 30 minutes (24%). T3 for low severity patients improved by 42.5 minutes (29%) and T3 for high severity patients improved by 21 minutes (23%). Emergency department length of stay for low severity patients discharged to home improved by 29.3 minutes (15%). The number of asthma-related visits between 48-hour return hospitalizations increased from 114 to 261. The admission rate decreased 6.0%. We implemented standardized asthma severity scoring with high rates of compliance, improved timely administration of β-agonist treatments, demonstrated early improvements in Emergency department length of stay, and reduced admission rates without increasing unplanned return admissions.

β-Adrenoreceptor agonists in the management of pain associated with renal colic: a systematic review

ObjectivesTo determine whether β-adrenoreceptor agonists are effective analgesics for patients with renal colic through a systematic review of the literature.SettingAdult emergency departments or acute assessment units.ParticipantsHuman participants with proven or...

Preclinical Development of New Therapy for Glycogen Storage Diseases.

Glycogen storage disease (GSD) consists of more than 10 discrete conditions for which the biochemical and genetic bases have been determined, and new therapies have been under development for several of these conditions. Gene therapy research has generated proof-of-concept for GSD types I (von Gierke disease) and II (Pompe disease). Key features of these gene therapy strategies include the choice of vector and regulatory cassette, and recently adeno-associated virus (AAV) vectors containing tissue-specific promoters have achieved a high degree of efficacy. Efficacy of gene therapy for Pompe disease depend upon the induction of immune tolerance to the therapeutic enzyme. Efficacy of von Gierke disease is transient, waning gradually over the months following vector administration. Small molecule therapies have been evaluated with the goal of improving standard of care therapy or ameliorating the cellular abnormalities associated with specific GSDs. The receptor-mediated uptake of the therapeutic enzyme in Pompe disease was enhanced by administration of β2 agonists. Rapamycin reduced the liver fibrosis observed in GSD III. Further development of gene therapy could provide curative therapy for patients with GSD, if efficacy from preclinical research is observed in future clinical trials and these treatments become clinically available.

Identifying parental preferences for corticosteroid and inhaled beta-agonist delivery mode in children with acute asthma exacerbations.

This study examines caregiver preferences of single-dose dexamethasone (DEX) versus 5-day oral prednisolone in treating acute asthma exacerbation in a pediatric emergency department (PED). A secondary objective was preference for mode of home inhaled β-agonist administration. Caregivers of patients 2 to 18 years with an acute asthma exacerbation treated in the PED completed a 1-page questionnaire including asthma history and preferences for steroids and β-agonist administration. One hundred caregivers completed the questionnaire. Within the preceding year, 79% had an asthma exacerbation and 73.7% (n = 99) were prescribed prednisolone. DEX was preferred by 79% of caregivers. Preferences were independent of caregiver demographics except in cases of prior intensive care admission, where DEX was less favored (odds ratio = 0.27, P < .046). No difference existed in mode of home β-agonist administration. Most caregivers prefer DEX in acute asthma exacerbation management. No difference exists for home β-agonists. These results may advise clinical practice in pediatric acute asthma exacerbation.

Reply: β2-agonists and acute respiratory distress syndrome.

From the Editorialists*: In their letter, Snyder and Johnson propose a mechanism to explain why the clinical trials evaluating β2-agonists as a treatment or preventive therapy for acute respiratory distress syndrome (ARDS) have failed. They suggest that extrapulmonary effects of β2-agonists on renal Na+ handling and the cardiovascular system might have caused an increase in total body water content, offsetting their beneficial effects on alveolar fluid clearance. Activation of β2-adrenergic receptors (β2ARs) may lead to increased total body water content by decreasing renal Na+ excretion (1). In addition, engagement of β2ARs on the vasculature may cause a drop in systemic vascular resistance, necessitating the increased administration of fluids and an increase in total body water content. Several factors argue against this hypothesis. Although the systemic administration of β2-agonists in the BALTI 2 trial (2) may have affected renal Na+ handling and cardiovascular responses, the inhalation administration of β2-agonist is unlikely to have done so (3–5). Indeed, Perkins and colleagues found that β2-agonist therapy decreased extracellular lung water content in a subgroup of patients receiving inhaled β2-agonists in the BALTI prevention trial (4). Snyder and Johnson point out that patients receiving β2-agonist therapy received more cumulative fluids compared with those who did not in the ALTA trial (2,988 ± 6,614 ml in the albuterol group vs. 1,905 ± 6,388 ml in the control group; not significant) (5). Although this may be due to the effect of β2-agonists on renal Na+ excretion and caon the rdiovascular system, this disparity more likely reflects the inclusion of more patients with shock in the ALTA trial compared with the previous study (approximately one half vs. one third) (5, 6). In summary, we agree with Johnson and Snyder that many mechanisms likely play a role in the unexpected outcomes with the use of β2-agonists for the treatment or prevention of ARDS (7). However, we think the bulk of the evidence from these trials and others suggests that β2-agonist therapy reduces lung water content. Despite this improvement, these agents failed to improve or prevent ARDS. Perhaps this is because only a fraction of patients with ARDS die directly as a result of hypoxemia. The majority of deaths occur due to development of multiple organ dysfunction, and only patients with severe ARDS benefit from therapies improving oxygenation (8, 9). Alternatively, the activation of β2ARs in other cells in the lung may negate the beneficial effects of their activation in the alveolar epithelium. For example, we have recently shown that β2-agonist therapy worsens lung inflammation in a murine model of lung injury via engagement of β2ARs on macrophages (10). We agree with the authors that additional studies will be needed to distinguish the beneficial effects of β2ARs from their unwanted and harmful effects.

Denervation and β2-adrenoceptor-agonist administration on craniofacial bone density

Abstract Objective: β2-agonist medications are thought to have adverse effects on bone density. Surgical denervation and intramuscular β2-agonist injections appear to have opposing effects on skeletal muscles. The present study has been designed to assess the effects of denervation of the masseter, intramuscular injection of a β2-agonist and the combination of both procedures, on bone density in the craniofacial skeleton in rats. Materials and methods: Sprague-Dawley rats were prepared as four groups: 1. surgical sham + saline injection into the masseter (sham); 2. surgical denervation of the masseter (den.); 3. surgical denervation of the masseter + intramuscular formoterol injection into the affected muscle (den.+form.); 4. intramuscular formoterol injection into the masseter (form.). All specimens were submitted for CT examination and volumetric calculations of the mineralised bone tissue were performed. Results: The sham and form. groups had a greater volume of mineralised bone in the zygoma on the experimental side compared with the control side. The maxilla on the experimental side had a higher volume of mineralised bone in the den.+form. and form. groups compared with the sham and den. groups. The control side of the maxilla had a higher volume of mineralised bone in the den.+form. and form. groups compared with the den. group only. Conclusion: Intramuscular administration of formoterol appears to induce a bilateral increase in bone mineral density in the maxilla and the zygoma, likely explained as a secondary effect of the well-described increase in muscle mass and strength associated with β2-agonist administration.

β2-Agonists and Acute Respiratory Distress Syndrome

β₂-Agonists and Acute Respiratory Distress Syndrome

Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD

The administration of β2-agonists to patients with airways obstruction often results in transient decrease in PaO2 despite concomitant bronchodilation. This effect is potentially dangerous for patients suffering from acute exacerbation of COPD (AECOPD). In this study, we investigated the effect of indacaterol 150μg and 300μg on the arterial blood gas tensions of hospitalised patients with AECOPD. We explored the acute effects on arterial blood gases and spirometry of two doses of indacaterol Breezhaler (150 and 300μg) in 12 patients hospitalised because of an AECOPD in 2 non-consecutive days under open-label, randomized, crossover conditions, with blind evaluation. Blood specimens were taken just before the inhalation and at 15, 30, 60, 120, 240 and 360min after inhalation of each treatment, and spirometry was performed at the same time points. Both doses of indacaterol did not cause significant changes in blood gases, although some patients with relatively well-preserved PaO2 presented transient episodes of oxygen desaturation that normalize spontaneously in a very short time. Moreover, they induced a significant mean increase in FEV1 and FVC, although the improvement caused by indacaterol 300μg was larger. Indacaterol up to 300μg is a potent bronchodilator that may induce small, transient decrease in PaO2 mainly in patients with relatively well-preserved PaO2. There appeared to be no clinical consequences of these PaO2 abnormalities in patients suffering from AECOPD.

Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in response to formoterol administration in rat skeletal muscle

Administration of β2-agonists triggers skeletal muscle anabolism and hypertrophy. We investigated the time course of the molecular events responsible for rat skeletal muscle hypertrophy in response to 1, 3 and 10 days of formoterol administration (i.p. 2000μg/kg/day). A marked hypertrophy of rat tibialis anterior muscle culminated at day 10. Phosphorylation of Akt, ribosomal protein S6, 4E-BP1 and ERK1/2 was increased at day 3, but returned to control level at day 10. This could lead to a transient increase in protein translation and could explain previous studies that reported increase in protein synthesis following β2-agonist administration. Formoterol administration was also associated with a significant reduction in MAFbx/atrogin-1 mRNA level (day 3), suggesting that formoterol can also affect protein degradation of MAFbx/atrogin1 targeted substrates, including MyoD and eukaryotic initiation factor-3f (eIF3-f). Surprisingly, mRNA level of autophagy-related genes, light chain 3 beta (LC3b) and gamma-aminobutyric acid receptor-associated protein-like 1 (Gabarapl1), as well as lysosomal hydrolases, cathepsin B and cathepsin L, was significantly and transiently increased after 1 and/or 3 days, suggesting that autophagosome formation would be increased in response to formoterol administration. However, this has to be relativized since the mRNA level of Unc-51-like kinase1 (Ulk1), BCL2/adenovirus E1B interacting protein3 (Bnip3), and transcription factor EB (TFEB), as well as the protein content of Ulk1, Atg13, Atg5–Atg12 complex and p62/Sqstm1 remained unchanged or was even decreased in response to formoterol administration. These results demonstrate that the effects of formoterol are mediated, in part, through the activation of Akt-mTOR pathway and that other signaling pathways become more important in the regulation of skeletal muscle mass with chronic administration of β2-agonists.

Thromboelastometry in veal calves to detect hemostatic variations caused by low doses of dexamethasone treatment

BackgroundThe illegal administration of hormones, steroids, β-agonists and other anabolic agents to productive livestock in the European Union continues, despite the long-term ban on their use and despite the measures provided under the directives to monitor certain substances and residues thereof in the interest of protecting consumer health and animal wellbeing. Often administered in low doses in the form of a drug cocktail, these compounds escape detection by common analytical techniques. The aim of this study was to determine whether low-dose dexamethasone administration (0.4 mg orally per day, for 20 days) in white-meat calves produced variations in blood coagulation, as measured by thromboelastometry. A second aim was to determine whether such variations could be valid in detecting illicit low-dose dexamethasone treatment.ResultsThe study population was 42 Friesian calves kept under controlled conditions until 6 months of age. The calves were subdivided into 2 groups: a control group (group A, n = 28) and a group treated with dexamethasone (group B, n = 14) for 20 days beginning at 5 months of age. When compared against the age-matched control group, the dexamethasone-treated calves showed a significant increase in alpha angle, maximum clot firmness and a significant decrease in clot formation time on all thromboelastometric profiles (P < 0.05). The clotting time was significantly decreased on the in-TEM® profile but increased on the ex-TEM® and fib-TEM® profiles (P <0.05). The Receiver Operating Characteristic curves, plotted for the Maximum Clot Elasticity (MCE), had a cut-off value ≥488.23 mm for in-TEM® MCE [Se 85.7%, (95% CI 57.2-98.2); Sp 100% 96.43% (95% CI 81.7-99.9] and a cut-off value ≥63.94 mm for fib-TEM® MCE [Se 92.8 (95% CI 66.1-99.8); Sp 89.3% (95% CI 71.8-97.7)]. In order to increase the sensitivity of the test two parameters (in-TEM® and fib-TEM® MCE) were used as two parallel tests; subsequently, the sensitivity rose to a point value of 99% (95% CI 85.4-99.9).ConclusionsThromboelastometry identified a state of hypercoagulability in the dexamethasone-treated subjects. Furthemore, the results of this preliminary study suggest that TEM may be useful in the detection of illicit low-dose dexamethasone treatment.

Symptomatic Viral Infection Is Associated With Impaired Response to Treatment in Children With Acute Asthma

To examine the influence of viral respiratory infection (VRI) on treatment response in acute asthma.A total of 218 children (mean age, 6.6 years) with acute asthma were recruited.Clinical symptoms were recorded, an asthma severity score was determined, and, whenever possible, a per-nasal aspirate was obtained for detection of viruses. Each child’s response to inhaled β2-agonists was assessed after 6, 12, and 24 hours.The 168 children with VRI symptoms received more treatment with inhaled β2-agonists after 6 hours (P = .01), 12 hours (P = .002), and 24 hours (P = .0005) compared with the 50 children without such symptoms. Asthma severity did not differ between the 2 groups. A per-nasal aspirate was obtained from 77% of the children. The most frequently identified virus was rhinovirus (61.4%). Among children with symptoms of a VRI, those with rhinovirus had an impaired response to β2-agonists at 6 hours (P = .032).Children with acute asthma and symptoms of VRI respond less effectively to β2-agonists after 6, 12, or 24 hours and thus may benefit from more intense therapy and monitoring.An association between viral upper respiratory infections and exacerbations of asthma has been recognized for many years and, specifically, rhinovirus appears to have a unique and stronger relationship with acute asthma in children compared with other viruses. The authors state that the identification of VRI symptoms at the initial assessment would be of potential clinical importance because children presenting clinically with such symptoms may benefit from more intensive therapy and monitoring. Potential limitations to this study included (1) the investigators were unable to obtain a per-nasal aspirate for virus detection in all study subjects; (2) as opposed to the administration of β2-agonists as the primary measure of clinical response, more objective measures, such as spirometry or use of oral corticosteroids, may have been better measures to assess; and (3) the timing of other treatment administered before presentation to the emergency department, duration of the preceding infection, and/or allergen exposure was not completely controlled for in this study. Despite these issues, this study presents interesting clinical findings.