Leukotriene inhibitors should only be used after acute attack has settled down.
They are not licensed for acute care and don't have any immediate effect. They could be added to the treatment for chronic managemnent of the patient later.
Data are mixed but there is little downside of giving montelukast in acute asthma and there may be a benefit as evidenced by the data below.
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For example,
Thorax. 2011 Jan;66(1):7-11. doi: 10.1136/thx.2010.135038. Epub 2010 Oct 18.
Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial.
Ramsay CF, Pearson D, Mildenhall S, Wilson AM.
Source
Department of Respiratory Medicine, Norfolk & Norwich University Hospital, Norwich, UK. [email protected]
Abstract
BACKGROUND:
Although leukotriene receptor antagonists have an established role in the management of patients with chronic asthma, their efficacy in an acute asthma exacerbation is not fully known.
METHODS:
87 adults with acute asthma requiring hospitalisation were randomly assigned to receive either montelukast 10 mg or placebo on admission and every evening thereafter for 4 weeks (when they were reviewed as outpatients). All patients were admitted under the care of a consultant chest physician and received full care for acute asthma according to the British Thoracic Society guidelines. The primary end point was the difference in peak expiratory flow (PEF) between active and placebo treatment the morning following admission.
RESULTS:
Primary end point data were analysed for 73 patients. At study entry, patients who received montelukast (n=37) had a mean (±SD) PEF of 227.6 (±56.9) l/min (47.6% predicted) and those who received placebo (n=36) had a PEF of 240.3 (±99.8) l/min (49.6% predicted). The morning after admission, patients who received montelukast achieved a PEF of 389.6 (±109.7) l/min (81.4% predicted) compared with 332.3 (±124.9) l/min (69.8% predicted) for placebo (p=0.046). The mean difference between treatment groups was 57.4 l/min (95% CI of 1.15 to 113.6 l/min or 1.95-21.2% predicted).
CONCLUSION:
In acute asthma exacerbations the additional administration of oral montelukast results in a significantly higher PEF the morning after admission than that achievable with current standard treatment.
ANOTHER EXAMPLE is with iv monteluakst
J Allergy Clin Immunol. 2010 Feb;125(2):374-80. doi: 10.1016/j.jaci.2009.11.015.
A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma.
Camargo CA Jr, Gurner DM, Smithline HA, Chapela R, Fabbri LM, Green SA, Malice MP, Legrand C, Dass SB, Knorr BA, Reiss TF.
Source
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. [email protected]
Abstract
BACKGROUND:
Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies.
OBJECTIVE:
To evaluate efficacy of intravenous montelukast as adjunctive therapy for acute asthma.
METHODS:
A total of 583 adults with acute asthma were treated with standard care during a < or = 60-minute screening period. Patients with FEV(1) < or =50% predicted were randomly allocated to intravenous montelukast 7 mg (n = 291) or placebo (n = 292) in addition to standard care. This double-blind treatment period lasted until a decision for discharge, hospital admission, or discontinuation from the study. The primary efficacy endpoint was the time-weighted average change in FEV(1) during 60 minutes after drug administration. Secondary endpoints included the time-weighted average change in FEV(1) at various intervals (10-120 minutes) and percentage of patients with treatment failure (defined as hospitalization or lack of decision to discharge by 3 hours postadministration).
RESULTS:
Montelukast significantly increased FEV(1) at 60 minutes postdose; the difference between change from baseline for placebo (least-squares mean of 0.22 L; 95% CI, 0.17, 0.27) and montelukast (0.32 L; 95% CI, 0.27, 0.37) was 0.10 L (95% CI, 0.04, 0.16). Similar improvements in FEV(1)-related variables were seen at all time points (all P
Thank you for brief review!
I Think the documentation of the effect of leukotrien inhibitors must be done as dose response trials with much higher does than normally used. The documentation when the drug was introduced showed that not 10 but 1000 mg was tolerated without significant side effects. However, Merk found it suitable to them to show that 10 and 5 mg were the doses to be used. I assume since the cost was lower and significant effect could be documented. I repeatedly asked for documentation of the possibly higher effect of higher doses, but never got any data or support for trials.
We know that receptors are up regulated when asked for by the immune system. I have no data at hand on the up regulation of leukotriene receptors, but before this and the dose response of Singulair in severe asthma has been documented I think the question will not be solved.
However, as said, it has no known drawback to give it even in higher doses. At least in Europe, it is possible to prescribe a drug on an indication that is not approved by the authorities - on the risk of the doctor. I would take that risk if I handled a patient with severe asthma.
The use of LTRA's in life-threatening asthma has not been tested. The data on it's use in non life-threatening asthma exacerbation is limited and is not in it's favor.
There is not any documentation for life-threatening asthma attacks. There are a few data on the use in less severe attacks and I think that a proportion of patients should respond positively along with the other treatment of course.
Normlly, I certainly do not use non-documenteddrugs. However in htis case it would be logic tl give Singulair despite the manufacturer has no documentation. It is an inhibitor. Most guidelines recommend epinephrine and some in addition steroids and antihistamines for treatment of anaphyaxis - despite there are no double blind trials. The pharmacology and biological actrivity of montelucast tells me it must be benificial for patients with severe asthma even though not documented. Waiting for documentation by Merk would not help patients. Non-Commercially supported trials will never come, since the impact is proably limited, but not risky.
In life threatening attack of asthma, the most severe of all asthma attacks, based on evidences (see comments of Michael Wechsler) and guidelines (GINA 2012), leucotriene modifiers have no imediate efect. We should follow all recomended steps in order to save patients,s life.
I ttotally agree! And certainly every patient should have full tratment.
What I meant was that dispite no effect has been fond, to inhibit leukottiirienes wil do no harm. To detect effects in the tratment of severe asthma attacks is not easy. It would be un-ethical not to give full treatment. It is difficult to follow a strict protocol in these cases. Therfore we sillnot see any non-disputable double blind trials with leukotrienes nor other drugs.
Do you really mean you should not give epinephrine to a patient with anphylaxis? Do you mean you should not add anti-histamines or steroids later? Even though there are no blinded randomised trials? You ad dit becase the patient may have some protection. Guidelines prescribe it but without full documentation. >In my opinion is a severe asthma attack similar to Anaphylaxis.
Use evidence based treatment when available. Use your knowledge about pharmacology when no evidence is available.
Our study published this year in BMC Pulmonary Medicine on Montelukast in Acute asthma exacerbation (non life-threatening cases) did not show any clinical or physiological benefit of this drug.
There is no established role in acute episodes and even in chronic stable asthmatics the studiess are in both the ways, and also indicated in chilren, in aspirin induced asthma, exercise induced asthma and as an adjunct to other medication in case of no response. I do not recommend its use in acute attacks.
There is no evidence to use leukotriene antagonist in life threatening attack of asthma.
Probably this comment is going to sound naive or totally subjective, but there it goes. As an asthmatic, and having received 2 courses of Singulair of one year each, 10 mg. I can tell you that you "feel" relief from the first dose. Again, that is my personal experience and also from my treating pulmonologist. Sorry for being subjective, but as pediatrician, that is also the feedback i receive from the mothers of my patients.
We'd better stick to evidence-based medicine. There is no strong evidence supporting use of LTRA'a in acute asthma.
I reiterate: While the exact role of leukotriene modifers in acute asthma has not been well established, there is little downside to their use in this setting, and some patients respond. I would not hesitate to use them.
See detailed abstracts above of the following:
Thorax. 2011 Jan;66(1):7-11. doi: 10.1136/thx.2010.135038. Epub 2010 Oct 18.
Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial.
Ramsay CF, Pearson D, Mildenhall S, Wilson AM.
CONCLUSION:
In acute asthma exacerbations the additional administration of oral montelukast results in a significantly higher PEF the morning after admission than that achievable with current standard treatment.
ALSO:
J Allergy Clin Immunol. 2010 Feb;125(2):374-80. doi: 10.1016/j.jaci.2009.11.015.
A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma.
I would agree to an extent with Michael Wechsler point but would reiterate that the first line treatment be considered initially especially in the situation of a more severe asthma exacerbation, i.e. corticosteroids, beta-agonists, and oxygen (when required) with continuous monitoring as recommended in the BTS-SIGN and GINA international guidelines.
It is very difficult to demostrate the efficacy of any antiasthma therapy in the treatment of asthma exacerbations. In fact, many studies have failed to demonstrate superiority of systemic corticosteroids over placebo. However, nobody will doubt to use this treatment in exacerbated asthma.
The same applies for montelukast.
The main problem with these studies is the use of sensitive tools to demonstrate significant differences. Clinical symptoms, PEF, FEV1 or arterial gas analysis lack sensitivity to detect differences in efficacy in short term studies (1 to 5 days). In contrast, there is more evidence supporting the efficacy of systemic corticosteroids to prevent readmission after an exacerbation.
In my opinion there is one possible way to assess the efficacy of montelukast in severe asthma exacerbations. In patients with a severe asthma exacerbation who need intubation and mechanical exacerbation is relatively easy to measure airway resistance. It is well known that ventilation of these patients is difficult and therefore a challenge in intensive care units. In these patients it will be relatively easy to asses the effects of an intravenous infusion of montelukast and placebo on airway resistance. This simple and objective measure could be more sensitive to detect effects of montelukast than by asking clinical questions or measuring PEF or FEV1.
I would like to add some aspects:
A. To randomize patients with severe asthma exacerbations correctly is very difficyúlt due to many factors prior to admission such as exposure (allergens, smoke, dust), variation in medication at adission and the last months(brand of steroids, longacting and shortacting beta-2-agonists ...) etc.
B. The evaluation by symptom scores and simple lung function tests are not (as mentioned) precice. In Clinical tirals over time, I prefer different types of provocation tests with documented precision. The proposal to use resistant in combination with infjusion/injection souds promising.
Will you do that study?
Provocation test also have important limitations. Since they are experimental do not necessarily represent the natural course of the disease. They can be used in a limited number of patients. For instance severe patients with FEV1 lower than 70% are usually excluded.
The proposal of using measurement of airway resistance was not accepted by the pharma.
Intensivists with experience in the treatment of severe asthma exacerbations know how difficult is to ventilate these patients and they are submitted to a high risk of barotruma. Any therapeutic measure that can contribute to reduce airway resistance will be welcome.
You are certainly right: During a severe exacerbation it is correct to use resistance. I have managed many severe asthmatics in intensive care and I more than aware of the difficulties to overcome the resistance.
To perform any provocation during a severe exacerbation is not ethical. It can only be used at baseline, i.e. between exacerbations.
Although there is no convincing evidence to support the use of LTRA's particularly in adults for acute asthma attack but majority of us have used it. I agree with Michael that I would not hesitate to use it if needed.
Our study titled 'A Randomized Double-blind, Placebo-controlled Trial of Oral Montelukast in Acute Asthma Exacerbation' published in
BMC Pulmonary Medicine 2013; 13-20; DOI:10.1186/1471-2466-13-20 did not show any benefit.