Corticosteroids, Inhaled (Respiratory)

• Inhaled respiratory corticosteroids are an integral part of asthma management and act as anti-inflammatory agents in the airways of the lung.
• Inhaled respiratory corticosteroids have similar efficacy with regard to lung function in adults with persistent asthma.
• At low to moderate doses, inhaled respiratory corticosteroids are well tolerated; however, at high doses and with longer duration of use, systemic absorption increases and leads to an increase in the risk of adverse effects.

Corticosteroids readily cross cell membranes and bind with high affinity to the glucocorticoid cytoplasmic receptor. The activated receptor binds to glucocorticoid-responsive genes and leads to induction or repression of transcription of potent anti-inflammatory or proinflammatory mediators, respectively. This mechanism takes place over a period of hours to days. For instance, corticosteroids increase the synthesis of secretory leukocyte protease inhibitor in human airway epithelial cells, important in reducing airway inflammation. Moreover, glucocorticoids indirectly inhibit the transcription of several inflammatory cytokines (eg, interleukin-1, tumor necrosis factor-alpha) and chemokines (eg, interleukin-8, monocyte chemotactic protein-1). The latter are chemotactic for leukocytes at the site of inflammation. Down regulation of cytokines leads to a reduction of expression of adhesion molecules on endothelial cells, preventing the adhesion and transmigration of leukocytes to the site of inflammation. The net effect of these processes is a reduction in edema.[50600][68680][68688][68689][68692]

Asthma is a chronic bronchial inflammatory disorder associated with increased mucus secretions and peribronchial edema composed of cell infiltrates. Acute symptoms of asthma usually arise from bronchoconstriction; chronic asthma can lead to permanent airway remodeling. The anti-inflammatory actions of inhaled respiratory corticosteroids reduce the bronchial inflammation, thereby treating respiratory symptoms associated with asthma. Asthma is associated with immunoglobulin E (IgE) hypersensitivity; therefore, it is exacerbated in the presence of aeroallergens. The allergens bridge the IgE antibodies on the surface of mast cells and other leukocytes and trigger release of chemotactic substances, which initiate an inflammatory response. This leads to mucus deposition in the lung. Corticosteroids decrease IgE synthesis, thereby reducing the bronchial hyperresponsiveness to allergens.[50599]

• Inhaled respiratory corticosteroids are the most effective prophylactic agents for mild to moderate asthma and persistent symptoms in both adults and children.[66299][69016]
• Regular treatment with inhaled respiratory corticosteroids reduces exacerbations, improves control of symptoms and lung function (eg, peak expiratory flow [PEF]), reduces airway hyperresponsiveness, and reduces hospital admissions and deaths from asthma.[66299][69016]
• Regular treatment with inhaled respiratory corticosteroids in patients with chronic obstructive pulmonary disease improves symptoms, lung function, and quality of life.[69470]
• For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) should be used with amenable inhaler types. In general, children less than 4 years old require administration with a tight-fitting face mask and spacer/VHC device to achieve optimal delivery.

Dose Ranges and Potency of Inhaled Respiratory Corticosteroids

Abbreviation: NA, not approved

^aUsual dose recommended by manufacturer. ^bAfter 1 week of inhaled corticosteroid treatment, begin slow rate of oral steroid withdrawal, not exceeding decrements of 2.5 mg/day of prednisone or equivalent; close patient monitoring is warranted. ^cMetabolized to an active metabolite that has high potentcy

Inhaled respiratory corticosteroids are similar chemically and structurally but have different pharmacodynamic properties that may result in different clinical effects.[50601] For instance, the active metabolite of ciclesonide, des-CIC, undergoes rapid hepatic metabolism into inactive metabolites upon leaving the lung [32882], therefore favoring maximum therapeutic effect in the lung while minimizing the risk of systemic adverse events.[50602]

With regard to dosing, in patients with mild or moderate persistent asthma, low doses of inhaled respiratory corticosteroids are equally efficacious for improving symptoms compared with high doses, and the dose-response relationship appears to flatten for most clinical parameters and lung function.[50599] Dose adjustments can take place depending on the progression of the asthma severity, with high doses used in patients with severe asthma. Corticosteroid responsiveness is decreased in smokers and in patients with predominantly neutrophilic inflammatory asthma.[50599]

Key Findings

• Ciclesonide, fluticasone, budesonide, and beclomethasone have similar effectiveness and efficacy with regard to lung function in adults with persistent asthma.[50605][50606]
• Fluticasone leads to increased hoarseness when given at the same dose as budesonide and beclomethasone.[50605]
• Mometasone is more effective than other inhaled steroids for oral corticosteroid-sparing effect.[50607]

Inhaled Respiratory Corticosteroid Comparative Efficacy Trials

Abbreviations: AE, adverse events; BDP, beclomethasone; BUD, budesonide; FEV₁, forced expired volume in 1 second; FVC, forced vital capacity; MD, mean difference; OCS, oral corticosteroid; OR, odds ratio; PEF, peak expiratory flow.