Current asthma guidelines and use of montelukast
- Gastroepato
- Pneumology
- Asthma guidelines
They provide and emphasize the importance of taking early treatment and
anti-inflammatory therapy using inhaled corticosteroids (spray) as the optimal
initial therapy. Since, however, asthma is not controlled only in this way, it
is important to associate to this therapy a drug that is montelukast, a therapy
that blocks the leukotrienes, responsible for the mediation of inflammatory
responses and the chronicity of the picture, for action on eosinophils.
Furthermore, the use of montelukast reduces the dosage of corticosteroids.
Moreover, during the asthmatic attack and the resulting bronchostasis it is
imperative to use a stimulating beta2, which initially may also be simple
salbutamol (ventolin).
Patient treatment
The treatment of the asthmatic patient, according to the indications of the most
recent and accredited lines (Boulet 2006, NHI 2007, NAEPP 2007, BTS 2008, GINA
2008), includes various international and national expectations. Drug therapy is
the cornerstone of the treatment of asthma. In fact, if the diagnosis of asthma
has been correctly carried out, a pharmacological therapy appropriate to the
type and severity of asthma is able to control most of the patients.
Remove trigger factors
Drug therapy is not the only therapeutic intervention to be done in asthma
because it is very important to identify and remove the factors triggering the
disease, both those etiologically important (ubiquitous or professional
allergens, respiratory infections, etc.) and those that act exclusively as
factors triggering bronchospasm (such as exercise, irritants such as
environmental pollutants, climatic factors, food components such as preserved
foods, certain foods, eg peanuts, strawberries, shellfish etc.
Definition of the severity level of the asthmatic pathology
At the time of the first observation of the patient and therefore the diagnosis,
the definition of the level of severity of asthma is useful for deciding the
type and extent of drug treatment based on the levels of asthma.
Level 1, intermittent: symptoms appear less than once per week, normal PEF and
exacerbations are short-lived and infrequent; nocturnal symptoms appear less
than twice a month. FEV1> 80% of the theoretical and the variability of PEF
20-30%
Level 2, persistent:> 1 times a week and <1 time a day the occasional flare-ups
that disturb sleep; > 2 times a month nocturnal symptoms;
Level 3, moderate persistent: the riacuti are frequent and disturb sleep and
daily life; nocturnal symptoms occur> once a week; FEV1 60-80% of the
theoretical, the variability of PEF> 30%
Level 4, severe persistent: the symptoms are small and important, very frequent
exacerbations, reduce limited physical activity; frequent; FEV1 <60% of
theoretical, PEF variation> 30%
Therapy
It is advisable to start with the recommended therapy for level 2 or level 3,
depending on the severity of initial illness. The choice of pharmacological
treatment must be based on the most recent literature, widely accepted in the
most recent guidelines. The drugs currently available for the treatment of
asthma. Regular treatment must include one or more background medications and
always include inhaled corticosteroids at different doses, to be chosen in
relation to the initial severity level of the disease, to the patient's
characteristics (age, triggers, etc.) and to the previous experience therapeutic.
It is advisable to start with the recommended therapy for the level
2 or level 3, depending on the severity of initial illness.
First therapeutic choice: anti-inflammatory corticosteroids inhalers: -
beclometasone HFA action - budesonide - fluticasone - flunisolide +
bronchodilators beta2-agonists long-term inhalers
Second therapeutic choice: anti-inflammatory antileukotrienes anti-action IgE
chromos- oral corticosteroids, + Slow-releasing oral theophylline
bronchodilators, long-lasting anticholinergic inhalers.
Exacerbations are more frequent in those with asthma difficult to treat, but may
appear in all asthmatic patients, even those with apparently milder forms of the
disease. Therefore, the warning to use the fast-acting drug (salbutamol) at the
appearance of occasional symptoms and to keep it at all times should be
available to all patients. The frequency of the additional use of salbutamol
should be memorized by the patient and reported to the patient, as it represents
one of the elements for assessing the achievement of control. Although some
studies have shown that the need for formoterol (instead of salbutamol) allows
to improve the control of asthma, this option should not be recommended outside
the so-called maintenance and need strategy that uses the budesonide combination
/ formoterol
Recommended therapy
For the control of isolated symptoms, triggered by known factors or not, or to
prevent the appearance of symptoms for known triggers (such as exercise)
• fast acting inhaled beta2-agonists (salbutamol, terbutaline)
To treat possible asthma exacerbations
• increase (2-4 times) of the dose of long-acting corticosteroids and / or
beta2-agonists for regular use, for 1-2 weeks
• use of the budesonide / formoterol combination in patients who already do it
regularly
• short cycle of oral corticosteroids (prednisone 25-50 mg per day for 5-10 days)
Regarding the use of montelukast antileukotrienes and cortisone, following is a
milestone study.
Studio Ramsay: bronchial inflammation in asthma.
The chronic inflammation typical of asthma is associated with an increased
number of eosinophils, mast cells and T lymphocytes in the airways, partially
reducible by treatment with inhaled corticosteroids (CSI). This process occurs
in inflammation when it chronicles, where interleukins and in particular IL-5
intervene to determine the production, activation and multiplication of
eosinophils. However, CSIs do not act effectively on cysteinyl leukotrienes (cysJs),
which play a key role in the inflammation and general pathophysiology of asthma
(recruitment of eosinophils, mucosal hypersecretion, hyperresponsiveness,
bronchoconstriction). The aim of this study was to evaluate the efficacy of
montelukast, a potent leukotriene receptor antagonist, in reducing the number of
eosinophils and mast cells in patients with mild asthma. Overall, 88 adult
patients were then treated with montelukast 10 mg / day (n = 43) or placebo (n =
45) for 6 weeks. The study showed that montelukast reduced the activated
eosinophil count by 80% from baseline and also reduced mast cells, with
reduction of inflammatory severity and asthma; in fact, already after 6 weeks,
eosinophils are reduced by about 12% on each unit of bronchial biopsy taken.
The presence of a significant infiltrate of activated eosinophils is one of the
main characteristics of the late phase of allergic inflammation in asthma.
Inflammatory mediators and different cytokines (including chemotactic substances
such as ECF-A) promote terminal differentiation and eosinophil migration.
Circulating eosinophils enter the area of allergic inflammation and migrate
through the vascular endothelium by rolling, a selectin-mediated process.
Finally, they adhere to the endothelium by means of the integrins that bind to
the adhesion molecules VCAM-1 and ICAM-1.
When invading tissues (induced by RANTES chemokines), the survival of
eosinophils is prolonged by several cytokines. Eosinophils contribute to tissue
damage in the airways by releasing products such as leukotrienes and basic
granular proteins. Montelukast as adjunctive therapy to inhaled corticosteroids
or inhaled corticosteroids and long-acting beta-2 agonists in the management of
patients with asthma and allergic rhinitis (RADAR study). Approximately 80% of
patients with asthma also suffer from allergic rhinitis and for this reason have
a greater number of asthma flare-ups and visits to the emergency room than those
without rhinitis. Asthma, however, remains poorly controlled even in patients
treated with only inhaled corticosteroids (CSIs), the drugs that the current
guidelines recommend as optimal initial therapy. The aim of the RADAR study was
to evaluate the efficacy of adjunctive therapy with montelukast 10 mg to that
with CSI or CSI plus beta-2 long-acting agonists (LABA) in 319 patients with
asthma and allergic rhinitis poorly controlled by corticosteroid treatment. The
study also assessed the efficacy of montelukast on quality of life and overall
satisfaction of patients and physicians. Well, the study showed that at 8 weeks
of treatment, asthma is better controlled in patients treated with montelukast
dosed at 10 mg / day, however, associated with small amounts of inhaled
corticosteroids with a significant reduction in symptoms of allergic rhinitis,
as evidenced by the variation in the Minimal Rhinitis Quality of Liability
questionnaire versus baseline (from 2.57 ± 1.20 to 1.12 ± 1.00; difference: 1.45
± 1.35; p <0.001).
Objectives to be achieved in the treatment of asthma
• minimize (possibly eliminate) the symptoms
• minimize (possibly eliminate) the use of drugs as needed
• maintain normal or maximal lung function
• minimize (possibly eliminate) the abnormal variability of the PEF
• prevent exacerbations
• allow a normal life, including physical activity and sport
• minimize the possible side effects of drugs, using the minimum effective doses
Objectives of the care according to GINA
If asthma is judged completely uncontrolled, it is necessary to immediately
provide an increase in the therapy (step-up), going from the level of therapy in
progress to one or more higher levels. Generally, you choose the main option of
the next level, with which to achieve control. In some cases (especially on the
basis of the clinical physiological characteristics of asthma in the individual
case) the choice of secondary options of the same level of current therapy or of
the highest levels of therapy can be considered; in these cases the eventual
achievement of the control could be slower and more difficult, but the
therapeutic load could be lightened.
If, on the other hand, asthma control has been achieved, it is opportune to
consider whether to maintain the same level of treatment or to think of its
progressive reduction; however, it would be good to wait for a period of at
least 3-6 months to maintain control before assessing the reduction in
treatment, which should be implemented by choosing the main option of the lower
level or, in special cases, the secondary options of the same level or those
lower. When the patient is in combination therapy with inhaled corticosteroids
and long-acting beta2-agonists, the reduction should be on the corticosteroid
dose (50% reduction) while maintaining that of long-acting beta2-agonist, up to
level 3 doses. Subsequently, further reduction may be envisaged, passing to the
combination with the lowest dose of inhaled corticosteroid once a day.
Step by step therapy levels
level 1 Beta 2-short-acting agonists as needed
level 2 low dose CSI or anti leukotrienes, chromones
level 3 low dose CSI + LABA or other treatment: low dose CSI + anti leukotrienes
or low dose CSI + theophylline-LR- or medium-high dose CSI
level 4 medium dose CSI + LABA or in addition of 1 or + between anti
leukotrienes and theophylline-LR
level 5 high dose CSI + LABA in addition of 1 or + between anti leukotrienes,
anti IgE (omalizumab) **, theophylline-LR, oral CS
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