Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD.

Abstract

The role of glucocorticoids in the treatment of chronic obstructive pulmonary disease (COPD) is controversial. We have previously described high numbers of neutrophils and high concentrations of the inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and of the cell activation markers eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO), and human neutrophil lipocalin (HNL) in COPD patients as compared with controls, and have postulated that the cytokines TNF-alpha and IL-8 play a role in propagating the inflammatory response in COPD. We have now studied the effects of inhaled and oral glucocorticoids on these inflammatory indices in induced sputum. Initially, we studied the effect of a 2-wk course of inhaled budesonide (800 mg twice daily for 2 wk) in 13 patients with severe COPD (mean FDV1: 35% predicted). There was no clinical benefit in either lung function or symptom scores, and no significant change in the inflammatory indices as measured by total and differential cell counts and concentrations of TNF-alpha eosinophil activation markers ECP and EPO, and neutrophil activation markers MPO and HNL. Because the lack of anti-inflammatory effect might have been due to poor drug delivery as a result of severe airflow limitation, we undertook a study examining the antiinflammatory effect of oral prednisolone (30 mg daily for 2 wk) in patients with COPD and undertook the same measurements in 10 patients with atopic asthma. Sputum eosinophil numbers, ECP, and EPO were significantly reduced in the asthmatic patients but were not modified in COPD. This confirms the clinical impression that inhaled steroids have little antiinflammatory effect, at least in the short term in this group of patients, and suggests that the inflammatory process in COPD is resistant to the antiinflammatory effect of glucocorticoids.

How Do Corticosteroids Work in Asthma?

“…In COPD, inflammation is not suppressed by corticosteroids and there is no reduction in inflammatory cells, cytokines, or proteases in induced sputum, even with oral corticosteroids (63,64). Corticosteroids do not suppress neutrophilic inflammation in the airways, and corticosteroids may prolong the survival of neutrophils (65).…”

“…There is a striking reduction in the activity and expression of HDACs in the peripheral lung of patients with COPD (68). Even in patients with COPD who have stopped smoking, the steroid resistance persists (63,64), and these patients are known to have continuing oxidative stress (69).…”

Monitoring the allergic inflammation

“…(50,51). This in particular has been shown for patients with asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (8,9,19,50,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69). The greatest problem with sputum measurement is to obtain sputum, as sputum production has to be induced in those subjects who are not spontaneous producers.…”

“…The numbers of eosinophil granulocytes in sputum have been estimated in this way by the measurement of ECP in the extract and there is a large number of publications showing that the numbers of eosinophils measured in this way are well correlated to disease activity in asthma and how the numbers are reduced as a consequence of corticosteroid treatment. In patients with COPD it has been shown that treatment success with corticosteroids is related to the eosinophilic inflammation in the bronchi as measured by sputum ECP (60,70). An interesting alternative to sputum could be the measurement in saliva, as we showed recently that asthmatics had significantly raised levels of ECP in saliva and that the levels were reduced by corticosteroid treatment (71).…”

Obstructive Lung Disease.

“…Therefore, it is highly beneficial to avoid exposure to the allergen. Use of inhaled corticosteroids is very effective medication (4,6). The agents act via various pharmacological effects to suppress production of inflammatory cytokines as well as the function of eosinophils and lymphocytes, and to enhance formation of anti-inflammatory substances and expression of p-adrenergic receptors.…”