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Montelukast in the management of allergic rhinitis

Jaime A Lagos and Gailen D Marshall

Division of Clinical Immunology and Allergy, University of Mississippi Medical Center, Jackson, MS, USA

ABSTRACT

Allergic rhinitis is the most common atopic disorder seen in the outpatient clinic setting diagnosed by history, physical exam and objective testing. According to the Allergic Rhinitis and its Impact on Asthma (ARIA) document, it is classified by chronicity (intermittent or persistent), and severity which is based on symptoms and quality of life (mild, or moderate/severe). It has enormous socioeconomic costs and significant reduction in quality of life. Allergen avoidance should be implemented, particularly in children, to reduce level of exposure; unfortunately efforts are often inadequate. Montelukast, a novel medication, is an antagonist to the leukotriene receptor. It is nonsedating, dosed once daily, and has a safety profile similar in adults and children with approval down to 6 months of age. A review of the literature undoubtedly establishes montelukast as a viable alternative for the treatment of seasonal allergic rhinitis. Its benefits are equivalent to antihistamines, when used as monotherapy, but less than intranasal corticosteroids. The addition of an antihistamine to montelukast does appear to have added benefits and at times is reported to be equivalent to intranasal corticosteroids.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936314/

 

 

 

HNO. 2012 Apr 26. [Epub ahead of print]

[Mechanism of action of nasal glucocorticosteroids in the treatment of allergic rhinitis : Part 2: Practical aspects of application.]

[Article in German]

von Bernus LHögger PPfaar OKlimek L.

Source

Zentrum für Rhinologie und Allergologie, An den Quellen 10, 65183, Wiesbaden, Deutschland.

Abstract

Allergic rhinitis (AR) is the single most common allergic disease and one of the most common chronic diseases. It affects approximately 25-30% of the population, and can substantially worsen patients' medical conditions, reduce quality of life, and contribute to absenteeism from work or school. It is also responsible for substantial direct and indirect economic burdens on the health care system.The medical management of allergic rhinitis includes several available pharmacotherapies, such as α-sympathomimetics, anticholinergic drugs, natural saline or other nasal rinses, mast cell-stabilizing agents, topical and systemic antihistamines, topical and systemic glucocorticosteroids, leukotriene-receptor antagonists and the new monoclonal antibodies following a stepwise approach. Allergen-specific immunotherapy is the only treatment option that interferes with the natural course of the disease and, besides allergen elimination, is thought to be the only causative treatment option.Nasal glucocorticosteroids (nGCS) are thought to be the most effective treatment choice for controlling the symptoms of AR. Double-blind, randomized clinical trials have demonstrated greater efficacy of nGCSs versus placebo, antihistamines or montelukast for relief of all nasal symptoms, especially congestion. Therefore, especially in the management of AR-related nasal inflammation and congestion, nGCSs are considered the most appropriate treatment. Patients should be informed that symptom improvement can be expected after 2-4 days for intermittent rhinitis and after up to 2-3 weeks for persistent rhinitis. The medication has to be taken regularly and not as "on-demand" treatment. Adherence to treatment also affects outcomes, and this may be influenced by patient preferences for the sensory attributes of an individual drug and the awareness of possible side effects.More recently, safety studies have shown that the newer nGCS agents have improved safety profiles compared with older nGCS agents. The newer nGCS drugs have been found to have minimal adverse effects on growth and hypothalamic-pituitary-adrenal-axis function in children. This review will discuss the pathophysiology of allergic inflammation in the nasal mucosa and the mechanism of action of nGCSs; also the efficacy and safety of nGCSs will be discussed by focusing on clinical evidence.

http://www.ncbi.nlm.nih.gov/pubmed/22532282

  

  

A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist.

Leonard C. Altman, Zev Munk, James Seltzer. Nancy Noonan  Ji Zhang, Theodore F. Reiss,

Seattle, Wash., Houston, Tex., San Diego, Calif., and Rahway, N.J

Abstract 

Background: The cysteinyl leukotrienes are important mediators of bronchial asthma. The clinical effect of montelukast, a potent cysteinyl leukotriene-receptor antagonist, was investigated in a randomized, placebo-controlled, multicenter, parallel-group, dose-ranging study.

Methods: After a 3-week, single-blind, placebo run-in period, 343 asthmatic patients (FEV1 40% to 80% of the predicted value with an improvement in FEV1 of at least 15% [absolute value] after receiving inhaled β-agonists on at least two occasions) were randomly assigned to one of six treatment groups: placebo; 10, 100, or 200 mg once daily montelukast in the evening; or 10 or 50 mg twice daily montelukast for a 6-week, double-blind treatment period followed by a 1-week placebo washout period. All patients used inhaled, short-acting β-agonists as needed.

Results: All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints. The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 (10.30%; 95% CI: 5.56 to 15.04), as-needed β-agonist use (-0.98 puffs; 95% CI: -1.53 to -0.44), morning peak expiratory flow rate (18.80 L/min; 95% CI: 8.62 to 28.98), physicians' and patients' global evaluations, and asthma-specific quality-of-life scores were all significant (p ≤ 0.050). The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment.

Conclusion: Montelukast caused a significant improvement in chronic asthma at an oral, once daily evening dose as low as 10 mg. (J Allergy Clin Immunol 1998;102:50-6.)

http://www.jacionline.org/article/S0091-6749(98)70054

 

 

 

 

Allergy Asthma Proc. 2012 Mar;33(2):17-22.

Efficacy of prophylactic treatment with montelukast and montelukast plus add-on loratadine for seasonal allergic rhinitis.

Yamamoto HYamada TSakashita MKubo SSusuki DTokunaga TOgi KTerasawa YYamashita SKayano YMasada MKimura YFujieda S.

Source

Division of Otorhinolaryngology-Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Science, University of Fukui, Fukui, Japan.

Abstract

Cysteinyl leukotriene and leukotriene receptor occupancy have been linked to several processes in seasonal allergic rhinitis (SAR), including nasal congestion, rhinorrhea, and recruitment of inflammatory cells. We investigated whether add-on loratadine, an antihistamine, might be effective for SAR patients showing unsatisfactory control of symptoms with the leukotriene receptor antagonist (LTRA) montelukast alone. Patients with SAR caused by Japanese cedar pollen (SAR-JCP; mean age, 29.4 years) were given prophylactic montelukast for 1 month before peak JCP dispersal. Patients recorded the severity of the symptoms (sneezing, rhinorrhea, nasal congestion, and ocular symptoms) daily on visual analog scale (VAS). We selected patients with VAS scores of >50 for any of the symptoms just before the peak pollen season (March 2 to March 8) and designated them as "poorly controlled" patients. Then, in the peak JCP season (from March 9), we conducted a randomized, double-blind, placebo-controlled study to determine whether add-on loratadine might be effective for these "poorly controlled" patients. Montelukast alone was effective, as evaluated by improvement of the VAS scores, in 95 of the 137 patients (69.3%). Add-on loratadine significantly decreased the total scores for nasal symptoms (p < 0.05), sneezing (p < 0.05), and rhinorrhea (p < 0.05) when compared with placebo. The symptoms of SAR in two of three SAR-JP patients could be controlled (VAS score[s] under 50) by prophylactic treatment with montelukast alone under the condition of mild JCP dispersal. Furthermore, the effect of add-on antihistamine on sneezing and rhinorrhea was found in selected SAR-JCP patients.

http://www.ncbi.nlm.nih.gov/pubmed/22525385

 

 

 

Management of persistent allergic rhinitis: evidence-based treatment with levocetirizine


Joaquim Mullol,1 Claus Bachert,2 and Jean Bousquet3

1Unitat de Rinologia, Servei d'Otorinolaringologia, ICEMEQ, Hospital Clinic, IDIBAPS, Barcelona, Spain

2Department of Oto-Rhino-Laryngology, University Hospital, Ghent, Belgium

3Clinique des Maladies Respiratoires, University Hospital and INSERM U454, Hospital Arnaud de Villeneuve, CHU Montpellier, France

Allergic rhinitis (AR) is a major health problem that can significantly impair quality of life (QoL). The former classification of AR comprises seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR), which do not adequately reflect the clinical course and presentation of AR. The Allergic Rhinitis and its Impact on Asthma (ARIA) classification is based on the duration of symptoms and their severity. Persistent AR (PER) is experienced for periods longer than 4 days/week and for more than 4 consecutive weeks, and may feature mild or moderate-to-severe disease based on the impairment of QoL and symptom severity. Oral antihistamines are a standard treatment option in AR. New second generation antihistamines have a rapid onset of action, are highly effective on AR symptoms, and some were even shown to relieve nasal congestion. Levocetirizine is a potent histamine H1-receptor antagonist with proven efficacy in both SAR and PAR, and it is the best studied therapeutic option in persistent AR. The Xyzal in Persistent Rhinitis Trial (XPERTTM) studied 551 patients with PER, showing that levocetirizine (5 mg/day compared with placebo) significantly improved nasal symptoms as early as the first week and for the 6 months of study, with significant improvement in nasal congestion after 6 weeks of treatment. Levocetirizine also improved QoL, was well tolerated, and produced substantial societal and employer cost savings. Thus, levocetirizine is the first tested standard treatment for PER using ARIA classification, and shows prompt short-term and long-term relief of symptoms, improves patients' QoL, and provides economic benefits to employers and the society.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1661632/

 

  

  

Efficacy and safety of montelukast in adults with asthma and allergic rhinitis

J.Chr. Virchow,  C. Bachert

Summary 

Several clinical studies have confirmed the effectiveness of montelukast 10 mg orally in adults with both asthma and allergic rhinitis. The objective of this phase IV study was to investigate the efficacy and safety of montelukast 10 mg in adults with both asthma and allergic rhinitis in a real-life setting. Data from 5855 patients (mean age: 42.8±15.4 years) were collected and analyzed following treatment for 4-6 weeks. Efficacy was analyzed by comparing baseline values of: general, day- and night-time improvement in asthma symptoms, need for rescue medication or inhaled corticosteroids (ICSs), general and specific improvement in allergic rhinitis symptoms, reduction in rhinitis medication use, and general and specific quality of life (QoL) improvement with values collected at the end of the observation period of 4-6 weeks. Following treatment with 10 mg montelukast 86.5%   of patients reported a strong or marked improvement in day-time asthma symptoms and 88.5%   reported improvement in night-time symptoms. A similarly high proportion of patients had a strong or marked improvement in all symptoms of allergic rhinitis (i.e. sneezing/itching (84%), rhinorrhea (81.7%), nasal congestion (79.3%), watery eyes (78.4%) and red or burning eyes (77.7%). The use of asthma and rhinitis medication was also reduced. 92.3%   of all patients intended to continue montelukast therapy. Overall QoL was "very good" or "good" in 85.2% of patients   and a "strong" or "marked" improvement in each of the four domains of sleep, work, everyday life and physical activity. Montelukast was well tolerated. Adverse drug reactions occurred in 14 out of 6158 patients. None of the adverse events was serious. Accordingly, montelukast 10 mg is a safe and effective treatment for patients with both asthma and allergic rhinitis.

http://www.resmedjournal.com/article/S0954-6111(06)00113-2/abstract

 

 

 

 

 

 

Inflamm Allergy Drug Targets. 2012 Mar 28. [Epub ahead of print]

Efficacy of montelukast as added therapy in patients with chronic idiopathic urticaria.

Khan SLynch N.

Source

Department of Immunology, Frimley Park Hospital NHS Foundation Trust, Frimley, Surrey, GU16 7UJ, United Kingdom. sujoykhan@gmail.com.

Abstract

Chronic idiopathic urticaria is a common skin disorder characterized by recurrent appearance of wheals and/or angioedema for more than 6 weeks without an identifiable cause. Consensus guidelines suggest use of leukotriene receptor antagonists (montelukast or zafirlukast) in patients whose urticaria is resistant to antihistamines. Our objectives were (1) document the efficacy of montelukast in our patients, and (2) evaluate whether any clinical features or available laboratory investigations were associated with a response to montelukast. Patients who received montelukast between the years 2008-2011 (4-year period) were retrospectively identified from clinic letters. Clinical features and laboratory investigations were collected and analyzed. The primary end point was adequate control of disease without the need for systemic steroid therapy. 25 patients (10 males and 15 females; median age, 33 years; age range, 13-66 years) with an average duration of urticaria at 3.8 years received montelukast 10mg daily. 12 patients (48%) were better on montelukast with combined anti-H1 and anti-H2 therapy, with no statistical significance between median age and duration of urticaria between males and females. In 11 patients, montelukast had no effect and in 2 patients the urticaria worsened after montelukastwas started. 15 patients had peripheral blood basopenia of which 5 patients responded to montelukast. Two patients had positive antinuclear antibody, 3 thyroid peroxidase antibodies and 4 with positive basophil histamine release. All 20 patients who had complement C3 and C4 levels done were within normal limits. Four of 6 patients (67%) with positive specific IgE responded to montelukast and combined anti-H1/H2 therapy. Almost half of our patients with chronic urticaria responded to montelukast and combined anti-H1 and anti-H2 therapy. We were unable to identify any clinical features or laboratory markers that were associated with a response to montelukast. Further studies are required to understand the failure of response of leukotriene inhibition in urticaria.

http://www.ncbi.nlm.nih.gov/pubmed/22452602

 

 

 

Management of asthma in children 0 to 4 years.

Bibliographic Source(s)

Michigan Quality Improvement Consortium. Management of asthma in children 0 to 4 years. Southfield (MI): Michigan Quality Improvement Consortium; 2010 Oct. 1 p.

isease/Condition(s)

Asthma

Guideline Category

Counseling
Evaluation
Management
Risk Assessment
Treatment

Clinical Specialty

Allergy and Immunology
Family Practice
Pediatrics
Pulmonary Medicine

Intended Users

Advanced Practice Nurses
Health Plans
Physician Assistants
Physicians

Guideline Objective(s)

  • To achieve significant, measurable improvements in the management of asthma through the development and implementation of common evidence-based clinical practice guidelines
  • To design concise guidelines that are focused on key management components of asthma to improve outcomes

Target Population

Children 0 to 4 years of age with asthma

Interventions and Practices Considered

Evaluation/Risk Assessment

  • 1. Assessment of asthma severity including symptoms, interference with normal activity, night awakenings, short-acting beta2-agonist (SABA) use, and exacerbations requiring oral steroids
  • 2. Assessment of asthma control

Management/Treatment

Step approach for asthma management:

  • 1. Patient education and environmental control
  • 2. Step 1: SABA as required
  • 3. Step 2: low-dose inhaled corticosteroid; alternative: cromolyn ormontelukast
  • 4. Step 3: medium-dose inhaled corticosteroid
  • 5. Step 4: medium-dose inhaled corticosteroid plus either a long-acting beta2-agonist (LABA)* ormontelukast
  • 6. Step 5: high-dose inhaled corticosteroid plus either a LABA* ormontelukast
  • 7. Step 6: high-dose inhaled corticosteroid plus oral corticosteroid plus either a LABA* ormontelukast
  • 8. Consult with asthma specialist at step 4 or higher; consider consult at step 3

*Currently there are no LABAs identified for use in children 0-4 years of age.

http://guideline.gov/content.aspx?id=24367&search=montelukast

 

 

 

 

Long-term management of asthma.

Bibliographic Source(s)

Finnish Medical Society Duodecim. Long-term management of asthma. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki, Finland: Wiley Interscience. John Wiley & Sons; 2007 Apr 11 [Various].

Disease/Condition(s)

Asthma

Guideline Category

Evaluation
Management
Prevention
Treatment

Clinical Specialty

Allergy and Immunology
Family Practice
Internal Medicine
Pediatrics
Pulmonary Medicine

Intended Users

Health Care Providers
Physicians
Respiratory Care Practitioners

Guideline Objective(s)

Evidence-Based Medicine Guidelines collect, summarize, and update the core clinical knowledge essential in general practice. The guidelines also describe the scientific evidence underlying the given treatment recommendations.

Target Population

Patients with asthma

Interventions and Practices Considered

Non-Pharmacologic Interventions

  • 1. Patient education in self-management (inhalation techniques, drug dosing, use of peak expiratory flow meter) and regular practitioner review
  • 2. Avoidance of allergens and sensitizing chemicals
  • 3. Smoking cessation
  • 4. Caution in use of aspirin and other nonsteroidal anti-inflammatory drugs and beta-blockers
  • 5. Allergen immunotherapy
  • 6. Specialist consultation, as indicated
  • 7. Monitoring and follow-up, as indicated

Drug Therapy

  • 1. In haled short-acting beta-sympathomimetics, such as salbutamol, terbutaline, fenoterol
  • 2. Inhaled corticosteroids, such as beclomethasone, budesonide, fluticasone
  • 3. Leukotriene antagonists, such as zafirlukast ormontelukast
  • 4. Long-acting beta-sympathomimetics, such as salmeterol or formoterol
  • 5. Therapeutic trial with leukotriene antagonist or theophylline at night
  • 6. Inhaled corticosteroid, long acting beta-sympathomimetic drug and short-acting sympathomimetic in combination with one or more of the following drugs: daily dose of inhaled steroid, leukotriene antagonist; long-acting theophylline; beta-sympathomimetic in tablet form or in liquid form administered with a nebuliser, inhaled anticholinergic drug (ipratropium or oxytropium), cromoglycate or nedocromil, omalizumab
  • 7. Addition of oral corticosteroids (prednisolone, methylprednisolone) to combination therapy listed above.
  • 8. Other drug treatments for asthma (antihistamines, antibiotics, antitussives)
  • 9. Tapering of medication to maintenance levels

Note: Guideline developers considered several other non-pharmacologic and pharmacologic treatment options. For a list of these, see the "Major Recommendations" field below.

http://guideline.gov/content.aspx?id=11037&search=montelukast

 

 

 

 

Management of asthma.

Bibliographic Source(s)

Singapore Ministry of Health. Management of asthma. Singapore: Singapore Ministry of Health; 2008 Jan. 80 p. [99 references]

Disease/Condition(s)

Asthma

Interventions and Practices Considered

  • 1. Patient education
  • 2. Avoidance of smoking
  • 3. Environmental allergen avoidance
  • 4. Pharmacological management (stepped care approach based on severity of asthma)
  • Inhaled corticosteroids
  • Long-acting inhaled beta-2-agonists
  • Rapid-acting inhaled beta-2-agonists
  • Short-term "burst" oral steroids, such as prednisolone
  • Methylxanthines, such as sustained-release theophylline
  • Leukotriene modifiers
  • Ipratropium bromide as adjuvant to beta-agonist
  • Use of aerosol holding chambers (spacer devices) with metered dose inhalers (MDIs), especially in children
  • 5. Assessment of asthma control using the Asthma Control Test
  • 6. Management of acute exacerbations
  • 7. Management of asthma in pregnancy
  • 8. Management of asthma in children
  • 9. Written asthma action plan
  • 10. Referral to specialists
  • 11. Hospital admission

Major Outcomes Considered

  • Morbidity and mortality due to asthma
  • Quality of life
  • Asthma symptoms (e.g., wheezing, dyspnea, cough)
  • Peak expiratory flow (PEF)
  • Hospital admission
  • Emergency room visits or physician visits
  • Days off from work

Back to top

Recommendations

Major Recommendations

Each recommendation is rated based on the level of the evidence and the grades of recommendation. Definitions of the level of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) and the grades of recommendations (A, B, C, D and Good Practice Point [GPP]) are defined at the end of the "Major Recommendations" field.

The following is a list of major revisions or additions to the revised guidelines:

  • 1. The key change is that asthma management is now focused on achieving control of asthma, rather than on an accurate classification of disease severity into mild, moderate or severe persistent asthma, which was in the previous clinical practice guideline (CPG).
  • 2. A new classification based on control of asthma is now provided: Controlled, Partly Controlled, or Uncontrolled. This is a working scheme of management based on current opinion.
  • 3. The use of a validated, simple and robust tool, the Asthma Control Test (ACT), is recommended for the assessment of control at each clinic visit.
  • 4. Treatment is stepped up or down depending on the level of control achieved. A new treatment algorithm, based on the ACT score, is provided.
  • 5. Clinical quality indices for asthma have been revised.

Objectives of Asthma Management

GPP - A successful management plan should be established for each patient in the context of a team effort that includes: the patient, relevant family member or carer, doctor, nurse/clinic assistant and pharmacist. It should involve the following elements:

  • Education-motivation
  • Self assessment and management
  • Environmental management
  • Pharmacological management

D - A new classification of asthma, guided by the level of asthma control, is recommended. (See table below). (Global Initiative for Asthma, 2006) Grade D, Level 4

Table: Levels of Asthma Control

Characteristic

Controlled
(All of the following)

Partly Controlled
(Any measure present in any week)

Uncontrolled

Daytime symptoms

None (twice or less/week)

More than twice/week

Three or more features of partly controlled asthma present

Limitations of activities

None

Any

Nocturnal symptoms/awakening

None

Any

Need for reliever/rescue treatment

None (twice or less/week)

More than twice/week

Lung function (PEFR or FEV1)*

Normal

<80% predicted or personal best (if known)

Exacerbations

None

One or more/year**

One in any week***

* Lung function is not a reliable test for children 5 years and younger.

** Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate.

*** By definition, an exacerbation in any week makes that an uncontrolled asthma week.

A - All doctors treating asthma patients should provide patient education to aid behavior change. (Refer to Tables 1 and 2 in the original guideline document for details). (Gibson et al., 2001)Grade A, Level 1+

A - House dust mite is a universal allergen. No single measure is effective to reduce exposure to mite allergens. An integrated approach including barrier methods, dust removal, environmental mite control may be partially effective and should be used. (Morgan et al., 2004) Grade B, Level 2+

GPP - During periods of haze, patients should be advised to avoid strenuous exertion outdoors. GPP

C - The possibility of occupational asthma should be considered in a working adult with newly diagnosed asthma. The range of occupational sensitizers is large, and complex. If occupational asthma is suspected, the patient should be referred to a specialist for further assessment. (Nicholson et al., 2005) Grade C, Level 2+

B - Smoking should be avoided in all patients with asthma especially pregnant women and children. (Martinez et al., 1995; Dezateux et al., 1999) Grade B, Level 2+

A - Asthma medications can be given by various routes. The best route is by inhalation, because the drugs are given directly where they are needed, into the airways. This leads to faster action, with a much reduced risk of systemic side effects. (Brown PH et al.) Grade A, Level 1+

A - Inhaled corticosteroids are best used at low to moderate doses (refer to Table 4 in the original guideline document for details). (Powel & Gibson, "Inhaled corticosteroid," 2003; Szefler et al., 2002) Grade A, Level 1+

A - Long acting beta-2-agonists, including salmeterol and formoterol, should never be used as monotherapy in asthma. (Lemanski et al., 2001; Lazarus et al., 2001) Grade A, Level 1+

A - The strategy of "add on therapy" with long acting beta-2-agonists is recommended when a low to medium-dose of inhaled corticosteroids alone fails to achieve control of asthma. (O' Byrne et al., 2005; Scicchitano et al., 2004; Rabe et al., 2006; Vogelmeier et al., 2005) Grade A, Level 1++

A - Formoterol is a long acting beta-2-agonist, which has a rapid onset of action comparable to that of a rapid acting beta-2-agonist drug. If a combination inhaler containing formoterol and budesonide is considered, it may be used for both rescue and maintenance. This has been shown to reduce exacerbations and improve asthma control in adults and adolescents at relatively low doses of treatment. (O' Byrne et al., 2005; Scicchitano et al., 2004; Rabe et al., 2006; Vogelmeier et al., 2005) Grade A, Level 1++

B - Theophylline has a bronchodilator action and also modest anti-inflammatory properties. It cannot however be used as a controller drug. It may be useful as an add-on drug in patients who do not achieve good control on inhaled glucocorticosteroids alone. (Dahl, Larsen, & Venge, 2002; Evans et al., 1997) Grade B, Level 2++

A - Leukotriene modifiers such as montelukast have a small and variable bronchodilator effect, reducing symptoms including cough, improving lung function and reducing exacerbations and airway inflammation. It can either be used as an alternative to low dose inhaled glucocorticosteroids in patients with mild persistent asthma, or as an add-on drug when low dose inhaled glucocorticosteroids or when the combination of inhaled corticosteroids with long acting beta-2-agonist have not given the desired effect. (Laviolette et al., 1999; Lofdahl et al., 1999; Price et al., 2003; Vaquerizo et al., 2003) Grade A, Level 1+

http://guideline.gov/content.aspx?id=12291&search=montelukast

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