Anti-leukotrienes versus long-acting beta2-agonists as add-on

therapy to inhaled corticosteroids for chronic asthma

(Protocol)

Ram FSF, Picot J, Ducharme FM

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane

Library 2001, Issue 3

http://www.thecochranelibrary.com

Anti-leukotrienes versus long-acting beta2-agonists as add-on therapy to inhaled corticosteroids for chronic asthma (Protocol)

Copyright © 2004 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iAnti-leukotrienes versus long-acting beta2-agonists as add-on therapy to inhaled corticosteroids for chronic asthma (Protocol)

Copyright © 2004 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

[Intervention Protocol]

Anti-leukotrienes versus long-acting beta2-agonists as add-ontherapy to inhaled corticosteroids for chronic asthma

FSF Ram1, J Picot, FM Ducharme

1National Collaborating Centre for Women’s and Children’s Health, London, UK

Contact address:

Editorial group: Cochrane Airways Group.

Publication status and date: Unchanged, published in Issue 4, 2004.

Citation: Ram FSF, Picot J, Ducharme FM. Anti-leukotrienes versus long-acting beta2-agonists as add-on therapy to in-

haled corticosteroids for chronic asthma. The Cochrane Database of Systematic Reviews , Issue . Art. No.: CD003137. DOI:

10.1002/14651858.CD003137.

Copyright © 2004 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

A B S T R A C T

This is the protocol for a review and there is no abstract. The objectives are as follows:

To determine the safety profile and magnitude of clinical benefit on asthma exacerbations, lung function, symptoms and quality of life,

resulting from the addition of long-acting beta2-agonists or anti-leukotriene agents to inhaled corticosteroids in symptomatic asthmatic

patients.

B A C K G R O U N D

Leukotrienes are inflammatory molecules, which are one of several

substances released by mast cells during the immediate response to

inhaled allergen. They are derived from arachidonic acid, the pre-

cursor of prostaglandins (Wasserman 1988, Wenzel 1997). There

are two families of leukotrienes. Leukotriene B4 acts primarily in

conditions in which inflammation is dependent on neutrophils,

such as cystic fibrosis, inflammatory bowel disease, and psoria-

sis. The second group (cysteinyl-leukotrienes) is concerned pri-

marily with eosinophil and mast cell induced bronchoconstriction

in asthma. They bind to highly selective receptors on bronchial

smooth muscle and other airway tissue (Davis 1997).

Drugs that can interfere with the production and activity

of leukotrienes have been designed. Both leukotriene synthe-

sis inhibitors and receptor antagonists have been developed.

Leukotriene synthesis inhibitors (e.g. zileuton) work by blocking

the production of many leukotrienes (e.g. B4, C4, D4, and E4)

(Georgitis 1999) in the inflammatory process by inhibiting the

enzyme 5-lipoxygenase. Leukotriene (cysteinyl) receptor antago-

nists (e.g. montelukast, zafirlukast, pranlukast) work by blocking

leukotriene D4 (LTD4) receptors (Georgitis 1999) and have been

shown beneficial in patients with asthma. Both types of leukotriene

modifiers are tablets administered orally.

Long acting beta2-agonists (LABA) has similar mode of action to

that of short acting beta2-agonists. LABAs have a slightly slower

onset of action (Lotvall 1996) than short-acting beta2-agonist but

display prolonged activation of beta2-receptors (Johnson 1995)

in bronchial smooth muscle resulting in prolonged duration of

action for up to 12 hours (Rees 1995). LABA is recommended

solely as add-on therapy to inhaled corticosteroids in patients with

moderate to severe asthma who remain symptomatic despite anti-

inflammatory therapy (BTS 1997; Boulet 1999). In many trials,

the addition of a LABA has been shown to be as or more effective

than doubling the dose of inhaled steroids (Shrewsbury 2000,

Pauwels 1997).

Asthma patients who continue to experience symptoms despite

1Anti-leukotrienes versus long-acting beta2-agonists as add-on therapy to inhaled corticosteroids for chronic asthma (Protocol)

Copyright © 2004 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

taking regular inhaled corticosteroids represent a management

challenge. Leukotriene antagonists and LABA agents may both

be considered as add-on therapy to inhaled corticosteroids. This

review will compare the relative benefits and safety profile of

adding either an anti-leukotriene agent or a LABA to patients

with asthma who are inadequately controlled by inhaled corticos-

teroids. Cochrane systematic reviews have been carried to examine

anti-leukotrienes as single agent therapy (Ducharme 2000) and as

add-on therapy to inhaled corticosteroids (Ducharme 2001).

O B J E C T I V E S

To determine the safety profile and magnitude of clinical benefit

on asthma exacerbations, lung function, symptoms and quality of

life, resulting from the addition of long-acting beta2-agonists or

anti-leukotriene agents to inhaled corticosteroids in symptomatic

asthmatic patients.

R E F E R E N C E S

Additional references

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2Anti-leukotrienes versus long-acting beta2-agonists as add-on therapy to inhaled corticosteroids for chronic asthma (Protocol)

Copyright © 2004 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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asthma. Respir Med 2000;94(2):112-118.∗ Indicates the major publication for the study

S O U R C E S O F S U P P O R T

External sources of support

• Felix Ram received funding from the Netherlands Asthma Fonds NETHERLANDS

Internal sources of support

• No sources of support supplied

3Anti-leukotrienes versus long-acting beta2-agonists as add-on therapy to inhaled corticosteroids for chronic asthma (Protocol)

Copyright © 2004 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.