A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA)

Abstract

BackgroundSome patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control.Methods30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation.ResultsThere was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance.ConclusionsThese data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function.Trial registration numberNCT01171365. Protocol available at http://www.clinicaltrials.gov.

Management of the patient with eosinophilic asthma: a new era begins

“…Treatment with inhaled steroids, even at very high doses, is often not sufficient to obtain control of the disease, probably because peripheral airways and paranasal sinuses cannot be reached adequately with inhaled or topical corticosteroids [ 84 , 85 ]. It has been demonstrated repeatedly that systemic corticosteroids can blunt the eosinophilic inflammatory process and improve asthma symptoms [ 86 , 87 ] and that the apparent resistance to corticosteroids in this asthma phenotype is only relative ( fig. 2 ).…”

“…Distal airway inflammation with air trapping and dynamic hyperinflation are also common in eosinophilic asthma, and should be addressed and treated if necessary. In a recent pilot study, fine-particle formulations were added to standard ICS treatment in patients with eosinophilic asthma to specifically target the distal airways [ 86 ]. The results showed that adding fine-formula ICS suppressed airway eosinophilia more than placebo, confirming earlier reports that eosinophilia in these patients is not entirely steroid resistant [ 87 ].…”

Cohort Analysis of Exacerbation Rates in Adolescent and Adult Patients Initiating Inhaled Corticosteroids for Asthma: Different Dose–Response Profile by Particle Size

“…Inflammation and patency of small airways was shown to improve with ciclesonide suggesting that it exerts an anti-inflammatory effect on small airways [13]. A real-world pilot study by Hodgson et al [31] found that, in patients with severe asthma, there was significantly less airway eosinophilia with ciclesonide than with placebo. In addition to improved asthma control, effective targeting of the small airways, at a lower dose, may have the potential to reduce local and systemic side effects [32].…”

Measuring lung function in airways diseases: current and emerging techniques

“…This may, in part, reflect a more peripheral distribution of disease, inaccessible to inhaled corticosteroids. 27,28 Current measures of lung pathophysiology cannot identify this phenotype.…”