Current Management of Asthma Patients with Corticosteroid Resistance

Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

“…CsA has minimal effects on monocytes or mononuclear phagocytes (6,190) but inhibits the recruitment of antigen-presenting cells and antigen presentation (190,220,221) and disrupts lymphokine-dependent T cell-macrophage interactions (190). CsA blocks mast cell degranulation and inhibits leukotriene synthesis (219) and suppresses LTC4 generation by lung mast cells, histamine, and LTC4 release from basophils (28). CsA has negligible effects on polymorphonuclear phagocyte recruitment or function (6,190).…”

“…Its effects should be greatest early in the course of the disease, when the role of T cells is most pronounced (6). However, T-cell independent mechanisms undoubtedly contribute to the antiinflammatory effects of CsA, both in animal models (222) and humans (6,28,29).…”

“…The use of cytotoxic agents has escalated dramatically, even though firm data supporting their use may be lacking. These agents have been used as therapy for pulmonary vasculitis (10)(11)(12)(13)(14), chronic interstitial lung disorders (e.g., idiopathic pulmonary fibrosis, interstitial pneumonitis/fibrosis associated with rheumatic disorders, sarcoidosis) (1-7, [15][16][17][18][19][20][21][22][23][24][25][26], acute paraquat intoxication (27), and, more recently, asthma (28)(29)(30).…”

“…Interpretation of clinical trials for all of these interstitial lung disorders is clouded by the lack of validated objective standards to assess disease activity and marked heterogeneity in clinical features, presentation, and prognosis. More recently, immunosuppressive agents have been used to treat corticosteroid-dependent or -refractory asthma (28)(29)(30)(40)(41)(42)(43)(44)(45)(46)(47). In all of the studies in asthma, immunosuppressive agents were combined with corticosteroids.…”

“…Although asthma is common, the disease is well controlled in the vast majority of patients with inhaled corticosteroids and bronchodilators. Fewpatients manifest corticosteroid resistance severe enough to warrant consideration of novel agents (28).…”