2000 European Respiratory Journal  
In a recent editorial in the European Respiratory Journal, VAN SCHAYCK [1] advocated the use of end-points other than forced expiratory volume in one second (FEV1) decline in the studies of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD). Since this view-point is heard increasingly often, especially from those in favour of the use of ICS in COPD, it seems worthwhile to review the basis for choosing FEV1 decline in the four recently completed largescale trials of
more » ... in COPD and to comment on the effect of ICS on other end-points in these trials. Five to 10 yrs ago there was a genuine optimism regarding the use of ICS in COPD, not as symptomatic treatment but as a medication which could modify the natural history through decreasing the excess decline in FEV1 which has been the established hallmark of COPD since the classic study of FLETCHER et al [2]. The optimism came from both the asthma experience and the growing realization that inflammatory processes are involved in COPD, as expressed in the "Dutch hypothesis" [3, 4]. It was further fuelled by a number of studies indicating a possible beneficial effect of ICS in COPD [5±7]; however, some of these studies did not differentiate COPD from asthma and others were insufficiently powered or of too short duration to actually study a potential disease modifier in COPD. For these reasons it was considered appropriate to conduct large-scale long-term studies focusing on the effect of ICS on FEV1 decline in wellcharacterized patients with COPD. The effects of ICS on FEV1 in the recent trials are wellknown and it seems sufficient to say that an initial effect is seen within 6 months and thereafter no significant effect on FEV1 decline is seen. Thus, most pulmonologists do not see ICS as a true modifier in COPD. This does not mean that ICS may have a role in COPD and we agree with VAN SCHAYCK [1] that other measures should be looked at. In our own study [8] no effect of ICS was seen on respiratory symptoms or exacerbations. It is worth noting that prevalence of respiratory symptoms actually declined over the study period in both groups, again underlining the necessity of the randomized controlled trial. In the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) publication [9] no data are given on the effect of ICS on secondary effect parameters but from several presentations we have been given the impression that no effect on symptoms and exacerbations was seen. From the Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) presentations we know that a modest but significant effect of ICS on exacerbations was found and that subsequent substratification indicates that this effect is almost entirely seen in subjects with an FEV1 <1.25 L. The effect on exacerbations translates into a clear and significant effect on health status measured with the St. George©s Respiratory Health Questionnaire; we are not aware of an effect on respiratory symptoms. From second-hand knowledge of the results of the as yet unpublished Lung Health Study II, we believe that an effect on respiratory symptoms was seen as well as an effect on "nonscheduled physician visits". From the above it is apparent that ICS do not modify the natural history of COPD by slowing the decline in FEV1 and that no consistent effects on other parameters have been seen although it seems likely that patients with severe COPD may benefit from treatment through reduction in exacerbations and thus an improvement in health status. It is desirable that the obtained data are used optimally and for this purpose a meta-analysis may be appropriate as it could better look at the effect of ICS over almost the entire spectrum of severity of COPD. In conclusion, we believe that we should acknowledge the value of results gained from the recent long-term studies of inhaled corticosteroids on forced expiratory volume in one second decline in chronic obstructive pulmonary disease and appreciate the directions pointed out and the new hypotheses raised from these data. All studies had specific aims and it is our belief that the respiratory society was actually obliged to these kind of studies for the sake of providing proper evidence for decision making. So far, only the Inhaled Steroids in Obstructive Lung Disease in Europe study has documented a long-term beneficial effect of inhaled corticosteroids on health status and before jumping to preliminary strong conclusions we should await further studies already ongoing as part of the trials of combinations of inhaled corticosteroids and long-acting bronchodilators in chronic obstructive pulmonary disease.
doi:10.1183/09031936.00.16237200 fatcat:ymrajopl6bdsvcdthjshp3djzy