Corticosteroids in asthma

Barnes PJ. Efficacy of inhaled corticosteroids in asthma. J Allergy Clin Immunol 1998 102 531-8. 

Lipworth BJ. Airway and systemic effects of inhaled corticosteroids in asthma dose response relationship. Pulm Pharmacol 1996 9(l) 19-27. 

Isaksson M, Bruze M, Hornblad Y, Svenonius E, Wihl JA. Contact allergy to corticosteroids in asthma/rhinitis patients. Contact Dermatitis 1999 40(6) 327-8. 

Remington TL, Digiovine B. Long-acting beta-agonists anti-inflammatory properties and synergy with corticosteroids in asthma. Curr Opin Pulm Med. 2005 11 74-78. 

The corticosteroids used in asthma are compared in Table 26-9." Besides acute severe asthma, systemic corticosteroids are also recommended for the treatment of impending episodes of severe asthma unresponsive to bronchodilator therapy. The effects of corticosteroids in asthma are dose- and duration-dependent. This pattern is true for the adverse effects as well (Table 26-10). The clinician must balance the toxicity of chronic systemic corticosteroid therapy continually with control of asthma symptoms. Because short-term (1 to... 

Pederson S, O Byme P. A comparison of the efficacy and safety of inhaled corticosteroids in asthma. Allergy 1997 52(suppl 39) 1—34. 

Although all of the mechanisms of action of corticosteroids in asthma are not fully understood, they are potent agents for reducing mucosal edema. Corticosteroids are indicated for the asthmatic with troublesome symptoms despite full therapy. The duration of therapy required varies depending on the individual subject s clinical course. 

Note that the combined use of beta2 agonists and corticosteroids in asthma is usually beneficial. 

Rodrigo GJ, Moral VP, Marcos LG, Cas-tro-Rodriguez JA. Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review. Pulm Pharmacol Ther 2009 22(1) 9-19. 

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

Johnson M (2004) Interactions between corticosteroids and beta2-agonists in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 1 200-6... 

Airway hyperresponsiveness is defined as the exaggerated ability of the airways to narrow in response to a variety of stimuli. Although AHR exists in patients without asthma, it is a characteristic feature of asthma and appears to be directly related to airway inflammation and the severity of asthma.1,3 Treatment of airway inflammation with inhaled corticosteroids attenuates AHR in asthma but does not eliminate it.1 Clinically, AHR manifests as increased variability of airway function. Although not commonly used to diagnose asthma, AHR can be evaluated clinically using a methacholine or histamine bronchoprovocation test. 

In patients who require chronic systemic corticosteroids for asthma control, the lowest possible dose should be used. Toxicities may be decreased by alternate-day therapy or high-dose inhaled corticosteroids. 

Tantisira KG, Hwang ES, Raby BA, et al TBX21 a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc Natl Acad Sci USA 2004 28 101 18099-18104. Finotto S, Neurath MF, Glickman JN, et al Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 2002 295 336-338. 

Fluticasone is a potent corticosteroid that is available as a nasal spray indicated in allergic rhinitis (hay fever) and as an inhaler used in asthma. 

Beclometasone is a corticosteroid. Corticosteroids are used as prophylaxis in patients with asthma and therefore have no use in an acute attack. Bronchodilators acting as relievers are indicated for an acute attack. In asthma, patients are advised first to administer the bronchodilator, which acts very fast and then apply the corticosteroid, which has anti-inflammatory properties. 

Guilbert TW, Morgan WJ, Zeiger RS, Manger DT, Boehmer SJ, Szefler SJ et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006 354 1985-97. 

Another potential advantage of extra-fine corticosteroid aerosols is their apparently greater accessibility to peripheral airways (< mm in diameter) which appear to be poorly penetrated by conventional CFC-based aerosols. Recent data indicate that airway inflammation is present in both large and small airways, as well as alveolar tissue, and that airway wall remodeling occurs in small airways. The clinical significance of small airways involvement in asthma, its contribution to fatal asthma or to the accelerated rate of decline in lung function with age that occurs in asthma, and the consequences of treating the small airways component... 

Several inhaled corticosteroids are currently prescribed in asthma, although their availability varies between countries (Table 8). There are relatively few studies comparing efficacy of the different inhaled steroids. There appear to be some differences between inhaled corticosteroids in terms of their systemic effects at comparable anti-asthma doses. There is evidence, that all of the inhaled steroids are absorbed to some extent from the lung and hence will have some systemic activity. It is recommended, therefore, in all guidelines to give the lowest dose of inhaled steroid compatible with asthma control. 

Another review of nine trials including a total of 344 adult patients concludes that no differences can be identified among the different doses of corticosteroids in acute asthma requiring hospital admission. Low dose corticosteroids 80 mg/day of methyl-prednisolone or <400 mg/day of hydrocortisone) appear to be adequate in the initial management of these adult patients. Higher doses do not appear to offer a therapeutic advantage. 

If asthma control is not optimal, conventional advice was to increase the ICS dose. However, it is now apparent, that the dose-response effect of ICS is rather flat, so that there is little improvement in lung function after doubling the dose of inhaled steroid. An alternative strategy is to add some other class of controller drug. Several studies have shown that the combination of ICS and salmeterol or formoterol was more effective than increasing the dose of inhaled corticosteroid in terms of lung function improvement, rescue /32-agonist use, symptom control, and frequency of mild and severe asthma exacerbations. 

A major breakthrough in asthma therapy was the introduction in the 1970s of aerosol corticosteroids These agents (Table 39.3) maintain much of the impressive therapeutic efficacy of parenteral and oral corticosteroids, but by virtue of their local administration and markedly reduced systemic absorption, they are associated with a greatly reduced incidence and severity of side effects. The success of inhaled steroids has led to a substantial reduction in the use of systemic corticosteroids. Inhaled corticosteroids, along with 2-(tdreno-ceptor agonists, are front-line therapy of chronic asthma. 

All corticosteroids have the same general mechanism of action they traverse cell membranes and bind to a specific cytoplasmic receptor. The steroid-receptor complex translocates to the cell nucleus, where it attaches to nuclear binding sites and initiates synthesis of messenger ribonucleic acid (mRNA). The novel proteins that are formed may exert a variety of effects on cellular functions. The precise mechanisms whereby the corticosteroids exert their therapeutic benefit in asthma remain unclear, although the benefit is likely to be due to several actions rather than one specific action and is related to their ability to inhibit inflammatory processes. At the molecular level, corticosteroids regulate the transcription of a number of genes, including those for several cytokines. 

The corticosteroids have an array of actions in several systems that may be relevant to their effectiveness in asthma. These include inhibition of cytokine and mediator release, attenuation of mucus secretion, up-regulation of (3-adrenoceptor numbers, inhibition of IgE synthesis, attenuation of eicosanoid generation, decreased microvascular permeability, and suppression of inflammatory cell influx and inflammatory processes. The effects of the steroids take several hours to days to develop, so they cannot be used for quick relief of acute episodes of bronchospasm. 

WUliams DM. Clinical considerations in the use of inhaled corticosteroids for asthma. Pharmacotherapy 2001 21 38S 8S. 

Deaths due to adrenal insufficiency have occurred in asthma patients during and after transfer from use of long-term systemic corticosteroids to less systemically available inhaled corticosteroids. 

Corticosteroids and cromolyn are also useful in asthma. Corticosteroids inhibit eicosanoid synthesis and thus limit the amounts of eicosanoid mediator available for release. Cromolyn appears to inhibit the release of eicosanoids and other mediators such as histamine and platelet-activating factor from mast cells. 

---