Original Articles: High-Dose Methylprednisolone as Initial Therapy in Patients with Acute Bronchospasm

Schneider, Sandra; Pipher, A; Britton, H L; Borok, Zea; Harcup, Craig

doi:10.3109/02770908809071365

Cited by 47 publications

(11 citation statements)

References 15 publications

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“…These results are interesting because the concentrations used were within the therapeutic range if methylprednisolone is given in bolus megadoses (see e.g. Barile and Lavalle, 1992;Bracken et al, 1992;Schneider et al, 1988). The underlying mechanism remains unexplained, although we have proposed that methylprednisolone works by direct effects on membranes.…”

Section: Top-down Control Analysismentioning

confidence: 61%

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin‐A‐stimulated thymocytes

Buttgereit

Grant

Müller

et al. 1994

European Journal of Biochemistry

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The glucocorticoid methylprednisolone has clinically important anti;inflammatory effects at high concentrations through unknown mechanisms. Methylprednisolone at 0.2 mg/107 cells inhibits respiration in Concanavalin-A(ConA)-stimulated thymocytes from rats by about 20%. We have used topdown elasticity analysis to identify the blocks of reactions within oxidative phosphorylation in thymocytes whose kinetics are significantly affected by treatment with methylprednisolone. At this concentration methylprednisolone greatly inhibited the reactions of substrate oxidation and increased mitochondrial proton leak but did not significantly affect the synthesis and turnover of ATP by the phosphorylating system. Metabolic control analysis showed that oxygen consumption by ConAtreated thymocytes was controlled largely (0.51) by the phosphorylating system but also by proton leak (0.32) and substrate oxidation (0.17); this is similar to the distribution of control in hepatocytes, suggesting that this pattern may be general in cells. Methylprednisolone lowered control by the phosphorylating system to 0.26 and raised control by substrate oxidation to 0.37. From these results we conclude that the inhibition of respiration in ConA-stimulated thymocytes by methylprednisolone at this concentration results from an inhibition of substrate oxidation and a smaller stimulation of mitochondrial proton leak, with only a minor contribution of any effects within the phosphorylating system.The therapeutic effects of glucocorticoids are mostly receptor-mediated. However, clinical observations and experimental findings suggest that there are also rapid direct effects that are not mediated by induction or repression of specific genes. It is well known that the application of methylprednisolone in megadoses is an effective treatment in acute situations of autoimmune diseases (see e.g. Barile and La- Abbreviations. ConA, concanavalin A ; C, overall flux control coefficient; E , overall elasticity coefficient, J,,, or J,, total rate of oxygen consumption; J , rate of oxygen consumption required to pump protons out at a rate equal to their rate of return through the phosphorylating system ; JL, rate of oxygen consumption required to pump protons out at a rate equal to their rate of return through the proton leak; A tym, mitochondrial membrane potential; FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone; Ph,MeP+, triphenylmethylphosphonium cation ; Ph,MePBr, triphenylmethylphosphonium bromide ; P/O ratio, ATP molecules synthesized0 atom consumed; ADP/O ratio, ADP molecules consumed/O atom consumed. The superscripts and subscripts S, L and P refer to the three blocks of reactions that produce or consume dtyy,: substrate oxidation (cytosolic catabolic reactions, citric acid cycle, electron transport chain), proton leak (leak of protons and any proton-transporting cation cycles across the mitochondrial inner membrane) and the phosphorylation system (ATP synthesis and transport, all cellular ATP-consuming reactions) respectively. valle, 1992; de Gla...

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Section: Top-down Control Analysismentioning

confidence: 61%

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin‐A‐stimulated thymocytes

Buttgereit

Grant

Müller

et al. 1994

European Journal of Biochemistry

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“…Hence, data in terms of lung function are more encouraging. [4041] In terms of effect on exacerbation relapse after discharge from the ED, most studies showed less relapse with systemic corticosteroids[3542] although others did not. [43] One important issue with all these studies is the low number of recruited patients.…”

Section: Clinical Evidence Of the Effect Of Corticosteroids In Acute mentioning

confidence: 99%

Corticosteroids in the treatment of acute asthma

Alangari

2014

Ann Thorac Med

117

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Asthma is a prevalent chronic disease of the respiratory system and acute asthma exacerbations are among the most common causes of presentation to the emergency department (ED) and admission to hospital particularly in children. Bronchial airways inflammation is the most prominent pathological feature of asthma. Inhaled corticosteroids (ICS), through their anti-inflammatory effects have been the mainstay of treatment of asthma for many years. Systemic and ICS are also used in the treatment of acute asthma exacerbations. Several international asthma management guidelines recommend the use of systemic corticosteroids in the management of moderate to severe acute asthma early upon presentation to the ED. On the other hand, ICS use in the management acute asthma has been studied in different contexts with encouraging results in some and negative in others. This review sheds some light on the role of systemic and ICS in the management of acute asthma and discusses the current evidence behind their different ways of application particularly in relation to new developments in the field.

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“…2,3 Furthermore, although corticosteroids are traditionally thought to exert their effect over hours rather than minutes, there is theoretical and clinical evidence of acute treatment effects. 4 – 6 A meta-analysis 7 summarizing 12 randomized trials has shown that the use of SC within 1 hour of ED arrival significantly improves pulmonary function and reduces the odds of hospital admission by 60%. The evidence also suggests little benefit for higher doses 8 or for intravenous treatment.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with delayed use or nonuse of systemic corticosteroids in emergency department patients with acute asthma

Tsai

Rowe

Sullivan

et al. 2009

Annals of Allergy, Asthma & Immunology

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Background Little is known about factors associated with systemic corticosteroid (SC) use in emergency department (ED) patients with acute asthma. Objective To determine the patient and system factors associated with delayed use or nonuse of SCs in the ED. Methods We analyzed the asthma component of the National Emergency Department Safety Study. Patients with acute asthma in 62 urban EDs in 23 US states between 2003 and 2006 were identified. The primary outcome measure was the pattern of SC use in the ED, which was categorized as timely use (≤60 minutes), delayed use (>60 minutes), or nonuse. Multinomial logistic regression was performed to identify factors associated with delayed use or nonuse of SCs. Results A total of 2,559 of 3,798 patients with acute asthma (67.4%) received SCs. Of these, the median door-to-SC time was 62 minutes (interquartile range, 35–100 minutes), with 1,319 patients (51.5%) having delayed SC treatment. Nonuse of SCs was largely explained by markers of asthma exacerbations (never intubated for asthma, lower respiratory rate, and higher oxygen saturation). In contrast, in addition to these factors, delayed SC treatment was associated with age of 40 years or older, female sex, longer duration of symptoms, ED presentation between 8 AM and 11:59 PM, and ED with a longer average patient wait time. Conclusions Physicians in the ED seem to appropriately administer SCs to higher-acuity asthmatic patients; however, the additional nonmedical factors represent opportunities to improve the timeliness of SC treatment in the ED.

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Original Articles: High-Dose Methylprednisolone as Initial Therapy in Patients with Acute Bronchospasm

Cited by 47 publications

References 15 publications

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin‐A‐stimulated thymocytes

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin‐A‐stimulated thymocytes

Corticosteroids in the treatment of acute asthma

Factors associated with delayed use or nonuse of systemic corticosteroids in emergency department patients with acute asthma

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