| Popis: |
There has been a considerable amount of progress in the treatment of asthma providing a highly acceptable quality of life for the majority of patients. Cortisone remains the main medication in severe asthma. But despite the effective reduction in bronchial inflammation provided by cortisone, it is somewhat disappointing that nothing better has been found after a half-century of use. Actually, we have done better. Inhaled cortisone allows application of the active substance in situ, avoiding the inconvenience of systemic administration. In addition, doses can be given in micrograms instead of milligrams. Corticodependency and corticoresistance are the two main problems encountered. Corticodependency is a very heterogeneous highly individual phenomenon. In some corticodependent patients, respiratory function is nearly normal and stable while in others, respiratory function cannot be controlled readily and frequent hospitalizations in the intensive care unit are required. Weaning is a long-term process which must be planned as part of an overall management program. Corticoresistance, in our experience a rather rare condition, involves abnormal cell response to corticoids with abnormal or impaired production of cytokins, interleukin 4 and interleukin 5. A decrease in the number and binding capacity of corticosteroid receptors may also be involved. Cytoplasmic regulation rather than the receptor gene itself would be implicated. By modifying the corticosteroid receptors it would theoretically be possible to override corticorestistance and, by targeting the bronchial epithelium, disassociate the local anti-inflammatory effects of cortisone and the deleterious systemic effects. Understanding the mechanism of action of corticosteroids in patients with severe asthma is one of the challenges facing medicine in the 21st century. |
