Chapter 1

Chapter II

1.1 HISTORY Glucocorticosteroids have been used to treat a variety of airway diseases since an initial study in 1950 of Carryer et al1 who reported the benefits of oral cortisone on ragweed polleninduced hay fever and asthma. This was followed by a report by Gelfand, demonstrating clin-ical benefit from inhaled cortisone in a small group of patients with both allergic or nonallergic asthma. Subsequently, a multicenter trial run by the Medical Research Council in the United Kingdom in 1956 demonstrated improvement in acute severe asthma in a placebo-controlled trial, and reports at that time described benefit in chronic asthma. This demonstrated the unequivocal benefit of corticosteroids in asthma. Subsequently, both oral and inhaled corticosteroids have evolved into the most important and useful drugs currently available to treat asthma (Level IA). The initial studies evaluating the efficacy of inhaled corticosteroids in asthma were performed on patients with moderate to severe disease. At the time of their introduction to clinical practice in the early 1970s, and for many years after this, their use was mainly limited to patients who had persisting symptoms despite aggressive oral or inhaled bronchodilator use. The increased appreciation, in the mid-1980s, of the central role of airway inflammation in the pathogenesis of all asthma (Level I),provided a rationale for the earlier introduction of inhaled corticosteroids, particularly as the ability of inhaled corticosteroids to reduce airway inflammation (Level I) and improve some of the airway structural abnormalities associated with asthma was being identified (Level I). This has led to a reappraisal of how best to use inhaled corticosteroids in the management of asthma.

Inhaled corticosteroids (ICS), also known as inhaled steroids, are the most potent antiinflammatory controller medications available for the treatment of your asthma today, and are the current mainstay of treatment once you need more than a rescue inhalerfor your asthma. Inhaled corticosteroids improve asthma control more effectively than any other agent used as a single treatment. Inhaled corticosteroids help prevent chronic asthma symptoms such as: Wheezing Chest tightness Shortness of breath Chronic cough 2.1 Inhaled Corticosteroids: What are they and how do they work? Inhaled corticosteroids prevent asthma symptoms by doing the following in your lungs:

Blocking the late-phase immune reaction to anallergen Reducing airway hyperresponsiveness Decreasing inflammation and inhibiting inflammatory cells such as mast cells, eosinophils, and basophils

Inhaled corticosteroids, sometimes referred to as inhaled steroids, are the best medication to manage asthma. They are used in all but the mildest cases of asthma. Inhaled corticosteroids are strong anti-swelling medications. People with asthma have swelling in the airways of their lungs, causing the airways to become more sensitive to asthma triggers such as allergens, dry air, smoke and viruses. Inhaled steroids reduce swelling, which improves symptoms, lung function and airway hyper-reactivity (twitchiness). A recent Canadian study (1) has

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shown that regular use of inhaled corticosteroids lowers the risk of death from asthma. 2.2 Do I Need An Inhaled Corticosteroids? You and your physician may want to consider inhaled corticosteroids if any of the following apply to you:

2.4 The following are examples of inhaled corticosteroids commonly use: Inhaled Corticosteroids: Alvesco (ciclesonide), Asmanex (mometasone), Flovent (fluticasone), Pulmicort (budesonide), Qvar (beclomethasone), Azmacort (Triamcinolone),Aerobid (Flunisolide). Combination Inhaled Corticosteroid/long-acting beta agonists: Advair (Flovent and Salmeterol), Symbicort (Pulmicort and Oxeze), Zenhale (Asmanex and formoterol)

You use rescue -agonist treatments, such as Albuterol, more than 2 days per week. You have asthma symptoms more than twice weekly. You meet certain criteria on spirometry. Your asthma interferes with your daily activities. You have needed oral steroids 2 or more times in the last year.

2.5 What Are the Common Corticosteroids Side Effects?

Inhaled

2.3 How Effective Are Inhaled Corticosteroids? Inhaled corticosteroids have been found to improve a number of important asthma outcomes such as: quality of life asthma attack frequency asthma symptoms asthma control hyperresponsiveness of your airways (decreased) need for oral steroids frequency of ER visits and hospitalizations deaths However, not all patients respond similarly to inhaled corticosteroids.

Inhaled corticosteroids have been the best treatment for asthma for more than 30 years. They are among the safest and most effective means to treat asthma. Although few side effects occur at standard doses (one to two puffs twice a day for most inhalers), some people may experience minor side effects such as hoarseness of the voice, and thrush (a yeast infection of the mouth and throat). Rinsing your mouth, or brushing your teeth after taking your medication, and using a spacer device with the aerosol puffer will decrease the chance of side effects. Children who have asthma can use inhaled corticosteroids safely over the long term. Two studies published in the New England Journal of Medicine (2, 3) reported inhaled corticosteroids do not stunt a childs growth and are not related to any other major side effects. Inhaled corticosteroids side effects can be broken down into two types:

Local adverse effects (in only one area of the body)

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Systemic effects (throughout the body)

a. Local Inhaled Corticosteroids Side Effects

control of your child's asthma. You must weigh the potential benefits of good asthma control with the small but real possible side effect of slowed growth.

Oral Candidiasis or Thrush: Thrush is one of the most common side effects of ICS; up to a third of patients developing this side effect. Lowering the dosage, using a spacer, and appropriately rinsing your mouth following inhalation all help lower your risk of thrush. Thrush also can be treated with topical or oral antifungals, such as nystatin. Dysphonia: Inhaled steroids can affect your voice, known as dysphonia. It may be prevented by using a spacer, and treated by decreasing the ICS dose temporarily and giving your vocal chords a rest. Reflex Cough and Bronchospasm: These side effects can be prevented by using a spacer and inhaling in more slowly. If needed, pretreatment with a rescue inhaler can prevent these symptoms. Inhaled Corticosteroids Side

Bone Density: Low doses of ICS do not appear to effect bone density, but there are more effects as doses are increased. If you have risk factors for osteoporosis or already have a low bone density, you may want to consider taking calcium and vitamin D supplements or a bone protecting treatment like a bisphophonate. Disseminated Varicella: This is when the chickenpox virus spreads throughout your body. While there is a theoretical risk, no cases of disseminated varicella have been reported with ICS. Kids who do not have the chicken pox during their first year of life should receive the varicella vaccine. Easy Bruising: Bruising and thinning of the skin occur in patients using ICS. The effect is dose dependent so decreasing the dose may be helpful. Cataracts and Glaucoma: Low and medium doses of ICS have not been associated with cataracts in kids, but a cumulative, lifetime effect associated with increased risk of cataract has been noted in adults. Only patients with a family history of glaucoma (elevated eye pressure) appear to have an increased risk of glaucoma with ICS use. As a result, patients on ICS should have periodic eye exams, especially if you are taking high doses or you have a family history of elevated eye pressure. Adrenal Gland Suppression: This potential side effect is extremely rare, but can occur in some people and usually at higher ICS doses.

b.Systemic Effects

While uncommon, a number of systemic effects can occur with inhaled corticosteroids. Generally, there is a higher risk with increasing doses of inhaled corticosteroids. Potential side effects include:

Poor Growth: While poor growth can result from ICS, poorly controlled asthma can also lead to poor growth in children. In general, low and medium doses of ICS are potentially associated with small, non-progressive but reversible declines in growth of children. As a result, you and your asthma provider should not only carefully monitor growth, but try to use the lowest possible dose that gets good

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Elevated Blood Sugar: ICS rarely cause elevation in blood sugar, and, if this side effect dose occur, it is almost always at higher doses of ICS.

REFERENCE

2.6 Wouldnt it be easier to take corticosteroid tablets? Some patients with more severe asthma may need treatment with oral corticosteroid tablets (prednisone), but most people can manage their asthma very well with inhaled corticosteroids. Inhaled corticosteroids have a great advantage over prednisone tablets because the medication is inhaled directly into the lungs, with less absorption by the rest of the body. This helps to lower the chance of side effects, making inhaled corticosteroids among the safest and most effective way to manage asthma. Conclusion Asthma is a chronic condition involving persistent inflammation of the bronchial tubes. Of the medicines available to treat this inflammation, steroids by inhalation are the most effective without causing the major side effects seen with long-term use of steroids in tablet form. Because the inflammation of the bronchial tubes persists even at times when ones asthma is quiet, it is important to continue to use your inhaled steroids even when feeling well. Your doctor may advise you as to when it is appropriate to stop your inhaled steroids; but for many persons with asthma, the asthmatic condition is lifelong and inhaled steroids should beand can safely becontinued indefinitely. Corticosteroids, when taken properly, are a very good way to treat asthma. They are safe and should be considered the first choice in asthma management for most cases of asthma

1. National Heart, Lung, and Blood Institute. Accessed: August 16, 2009. Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma 2. Apgar, Barbara. Tips Dari Jurnal lain: Efek samping dari Inhalasi kortikosteroid Terapi Amerika Dokter Keluarga (review).. (1999) 60 (5). 13 Januari 2008 <http://www.aafp.org/afp/991001ap/tips /6.html> 3. Barnes, NC "Karakteristik Inhalasi Kortikosteroid:. Persamaan dan Perbedaan" Primary Care Respiratory. 4. Suissa S, Ernst P. Benayoun S. Baltzan M. Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000:343:332-6. 5. Agertot L. Pedersen S. Effect of longterm treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000; 343:1064-9 6. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000:343;1054-63. 7. Global Initiative for Asthma (GINA). Global strategy for the diagnosis and management of asthma in children 5 years and younger. GINA, 2009. Accessed at April 2011. 8. Martinez FD, Wright AL, Taussig LM et al. Asthma and wheezing in the first six years of life. The 9. Group Health Medical Associates. N Engl J Med. 1995;332:133-8.

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10. 8. National Asthma Council Australia. Asthma Management Handbook 2006. Melbourne, 2006. 11. 9. Lowe L, Murray CS, Custovic A, Simpson BM. Specific airway resistance in 3-year old children: a 12. prospective cohort study. The Lancet 2002;359:1904-9. 13. 10. Gern JE, Lemanske RF, Busse WW. Early life origins of asthma. J Clin Invest 1999;104:837-43.

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