Novel Functional Imaging of Changes in Small Airways of Patients Treated with Extrafine Beclomethasone/Formoterol

Abstract

Background: Inhaled formulations using extrafine particles of long-acting β₂-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. Objectives: This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Methods: Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster®; Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). Results: After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Conclusions: Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment.

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

“…FRI can be used to assess OIPs by comparing morphologic (airway volume and geometry) and ventilation changes in the segmented airways (up to the 7th generation) with clinical responses measured using conventional tests (115,116). With FRI, improvements in both airway volume and distribution of ventilation in responders to test drug have been shown (117).…”

Functional Respiratory Imaging as a Tool to Personalize Respiratory Treatment in Patients With Unilateral Diaphragmatic Paralysis

“…This results in increased sensitivity of FRI compared with PFT. 3,4 In this case report, the clinical value of FRI in personalizing and delivering the most optimal treatment is demonstrated in 2 patients with idiopathic unilateral diaphragmatic paralysis. The FRI workflow is an additional postprocessing step based on paired HRCT scans that are taken as part of routine clinical practice for these types of patients.…”

The effect of roflumilast in addition to LABA/LAMA/ICS treatment in COPD patients

“…The main concern of the large-scale studies performed was that they did not assess the effect of roflumilast in addition to a combination product such as long-acting b 2 -agonists (LABA) or long-acting muscarinic agents (LAMA) combined with inhaled corticosteroids (ICS) [2]. A novel technology called functional respiratory imaging (FRI) defines, in great detail, lung geometry and regional changes in airway volume and resistance [3][4][5]. By assessing changes close to the site of action of the intervention, the method is more sensitive (higher effect size) compared with standard pulmonary function tests (PFT) [3].…”

“…By assessing changes close to the site of action of the intervention, the method is more sensitive (higher effect size) compared with standard pulmonary function tests (PFT) [3]. This implies that the mode of action of an intervention can be assessed in a small number of patients, while maintaining sufficient power to have statistically significant results [3,4]. We performed a study aimed at investigating the mode of action of roflumilast in COPD patients on top of triple therapy (LABA/LAMA/ICS), using PFT, exercise tolerance tests, patient-reported outcomes (PRO) and FRI.…”