Prednisone-dependent asthma: inflammatory indices in induced sputum

Abstract

The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated.The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose. This treatment was continued until a clinical exacerbation occurred. Prednisone 30 mg daily was then given again for one week.The mean duration of prednisone reduction was 7.4 weeks and the median dose was 7.5 mg . day -1. Increases in sputum eosinophils preceded increases in blood eosinophils by 4 weeks and worsening of symptoms and forced expiratory volume in one second by 6 weeks. The clinical exacerbation was also accompanied by sputum neutrophilia and increases in sputum eosinophil cationic protein (ECP), fibrinogen and interleukin (IL)-5. Treatment with prednisone suppressed median sputum eosinophilia (from 16.3 to 0%, p<0.001), decreased sputum ECP (from 7,480 to 700 mg . L -1 , p=0.01), but did not improve neutrophil numbers, fibrinogen or IL-5.The results show that the reduction of prednisone treatment in prednisonedependent asthmatics evokes a severe airway eosinophilic inflammatory response. Clinical and blood indices deteriorate later than those in sputum suggesting that sputum examination may be useful to identify the minimum regular dose of prednisone required in these patients. Eur Respir J 1999; 13: 15±21.

Neutrophilic airway inflammation and IL‐17

“…It remains a paradox that IL-8 production in bronchial epithelial cells, bronchial smooth muscle cells, fibroblasts, monocytes and in venous endothelial cells is inhibited by glucocorticoids in vitro, whereas the number and activity of airway neutrophils in patients with severe asthma and COPD, respectively, is not (5,39,(46)(47)(48)(49)(50)(51). Nor is IL-8 inhibited by a glucocorticoid in patients with COPD (39).…”

Induced sputum cell counts: their usefulness in clinical practice

“…Abnormalities in differential cell counts re-emphasize the occurrence of different types of inflammation and their different causes (table 2), Airway inflammation is not airway inflammation is not airway inflammation! An increase in sputum eosinophils is regarded as characteristic of asthma and can be induced by inhaled allergen [34,35] or chemical sensitizers [36,37] in sensitized subjects and by a reduction in steroid treatment in steroiddependent asthma [21,38,39]. Serial measurements during periods at work and periods away from work can be used in the investigation of occupational asthma ( fig.…”

“…Sputum eosinophils are more sensitive and specific for the presence of asthma than blood eosinophils or serum eosinophilic cationic protein (ECP) [19] or the more recently introduced analysis of nonrespiratory gases in exhaled air such as nitric oxide (NO) [20]. Sputum eosinophils are more responsive to change, increasing ahead of clinical variables [21] and exhaled NO during exacerbations [22], and respond more slowly to treatment [23]. It would therefore not be surprising if clinicians were poor at judging whether airway inflammatory was present surprising or not [24].…”

Intérêt de la mesure de l’inflammation en clinique dans l’asthme

“…Les neutrophiles semblent jouer un rôle dans le calibre des voies respiratoires alors que les éosino-philes sont plus liés à l'hyperréactivité bronchique [22,51] . L'éosinophilie se développe plusieurs semaines avant l'apparition des exacerbations [39,52] et c'est dans ce cadre qu'une stratégie d'adaptation du traitement basée sur l'analyse de l'inflammation des voies respiratoires prend tout son sens dans la prévention des exacerbations. Un taux d'éosinophiles dans l'expectoration supérieur à 9,5 % permettrait de prédire une augmentation du nombre d'exacerbations chez les patients porteurs d'une obstruction fixe [40] .…”