Therapy and Management | Treatment | Inhalation | Inhalation -Long-term

Controller medications

Controller medications are applied daily on a long-term basis to achieve and maintain control of persistent asthma.

Glucocorticosteroids inhaled daily for at least one month significantly reduce the pathological signs of airway inflammation in asthma. Compared with other substances they are most effective in improving lung function, decreasing airway hyperresponsiveness, reducing clinical symptoms as well as frequency and severity of exacerbations and improving quality of life.

Efficacy doses of corticosteroids depend on their potency and bioavailability as well as on the inhalation device used. Although a clear relationship between dose and prevention of acute exacerbations exists, add-on therapy is preferred over increasing the dose of an inhaled corticosteroid. Due to their flat dose-response curve higher dosing provides only little benefit regarding asthma control but increases the risk of adverse effects.

Oropharyngeal candidiasis, dysphonia and coughing are locally observed side effects. Systemic adverse effects include skin thinning, adrenal suppression and decreased bone mineral density. For adults doses equivalent to 500 µg or less beclomethasone seem to be no problem concerning systemic side effects. In comparative studies budesonide and fluticasone were shown to have less systemic effects compared to beclomethasone and triamcinolone. In children no significant adverse effect on growth have been observed in daily doses of 100 to 200 µg. Generally children less than 10 years of age seem to be more susceptible than adolescents. However uncontrolled or severe asthma itself may adversely influence growth and final adult height.

Cromones reduce the IgE-dependant mediator release from mast cells and have a suppressive effect on other inflammatory cells. In mild persistent asthma cromones may be used to inhibit allergen-induced symptoms and acute airflow limitation after exposure to exercise, cold air and sulfur dioxide. Only minimal side effects like occasional coughing are observed following treatment with cromones.

Long-acting β2-agonists relax airway smooth muscle, increase mucociliary clearance, reduce vascular permeability and modulate mediator release. They also provide protection against bronchoconstrictor stimuli although this effect decreases when treatment is applied regularly. However even when used on a long-term basis the overall efficacy of long-acting β2-agonists remains unchanged over time.

Since long-acting β2-agonists do not influence chronic inflammatory changes they should always be combined with inhaled glucocorticosteroids. If steroids fail to control symptoms sufficiently β2-agonists are administered additionally before increasing the steroid dose. Add-on therapy with long-acting β2-agonists reduces clinical symptoms, improves lung function and decreases acute exacerbations as well as use of rapid-acting β2-agonists. With inhaled therapy fewer adverse effects, like cardiovascular stimulation, skeletal muscle tremor or hypokalemia, occur compared to oral medication.

Literature:

Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. 1998. Am J Respir Crit Care Med , 157: S1-S53

Kips JC, O'Connor BJ, Inman MD, Svensson K, Pauwels RA, O'Byrne PM. A long-term study of the anti-inflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma. 2000. Am J Crit Care Med , 161: 996-1001

Laitinen LA, Laitinen A, Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. 1992. J Allergy Clin Immunol , 90: 32-42

O'Byrne P. GINA Executive Commitee. Global strategy for asthma management and prevention. 2004. National Institutes of Health. Publication No 02-3659

Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, Craig TJ, Dolovich M, Drazen JM, Fagan JK, Fahy JV, Fish JE, Ford JG, Israel E, Kiley J, Kraft M, Lazarus SC, Lemanske RF Jr, Mauger E, Peters SP, Sorkness CA; Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute. Significant variability in response to inhaled corticosteroids for persistent asthma. 2002. J Allergy Clin Immunol , 109 (3): 410-418

Van Bever HP, Desager KN Lijssens N, Weiyler JJ, Du Caju MV. Does treatment of asthmatic children with inhaled corticosteroids affect their adult height? 1999. Pediatr Pulmonol , 27: 369-375

Mode of action of inhaled drugs in chronic asthma therapy

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