Internet-based tapering of oral corticosteroids in severe asthma: a pragmatic randomised controlled trial.

BACKGROUND: In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal strategy for tapering oral corticosteroids is unknown. OBJECTIVE: To investigate whether an internet-based management tool including home monitoring of symptoms, lung function and fraction of exhaled nitric oxide (FE(NO)) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life. METHODS: In a 6-month pragmatic randomised prospective multicentre study, 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies: according to conventional treatment (n=43) or guided by a novel internet-based monitoring system (internet strategy) (n=52). Primary outcomes were cumulative sparing of prednisone, asthma control and asthma-related quality of life. Secondary outcomes were forced expiratory volume in 1 s (FEV1), exacerbations, hospitalisations and patient's satisfaction with the tapering strategy. RESULTS: Median cumulative sparing of prednisone was 205 (25-75th percentile -221 to 777) mg in the internet strategy group compared with 0 (-497 to 282) mg in the conventional treatment group (p = 0.02). Changes in prednisone dose (mixed effect regression model) from baseline were -4.79 mg/day and +1.59 mg/day, respectively (p < 0.001). Asthma control, asthma-related quality of life, FEV1, exacerbations, hospitalisations and satisfaction with the strategy were not different between groups. CONCLUSIONS: An internet-based management tool including home monitoring of symptoms, lung function and FE(NO) in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life. Clinical trial registration number Clinical trial registered with http://www.trialregister.nl (Netherlands Trial Register number 1146).

Increased granzyme A expression in type II pneumocytes of patients with severe chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with increased numbers of CD8(+) cytotoxic T lymphocytes (CTLs) in the lung, but the functional activity of CTLs remains unknown. Granzyme A (GrA) and B (GrB) are serine proteases considered to be important effector molecules of CTLs and natural killer cells. OBJECTIVE: To investigate protein and mRNA expression of GrA and GrB in peripheral lung tissue from patients with COPD and control subjects with normal lung function. METHODS: Paraffin-embedded sections of surgical lung specimens from 22 patients with COPD (FEV(1), 22% predicted; GOLD stage 4) and 15 control subjects (FEV(1), 108% predicted) were immunostained for GrA and GrB, and semiquantified on a 3-point scale. Messenger RNA expression in total lung, specific cell types enriched for by laser capture microdissection, and freshly isolated primary cells were determined by reverse transcriptase-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: GrA and GrB immunoreactivity was observed in CD8(+) CTLs and CD57(+) natural killer cells, but also in type II pneumocytes and alveolar macrophages in both groups. Bronchiolar epithelium stained positive for GrA, but negative for GrB. These observations were confirmed by reverse transcriptase-polymerase chain reaction on total lung, laser capture microdissection-enriched specific cell types and freshly isolated primary type II pneumocytes. The scores of GrA-expressing type II pneumocytes were significantly higher in patients with COPD versus control subjects. CONCLUSIONS: GrA and GrB mRNA and protein are detectable in human lung tissue. GrA expression is increased in type II pneumocytes of patients with very severe COPD. These results indicate that GrA may be important in the development of COPD.