Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA^® Dry Powder Inhaler

Abstract

Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8–110.6 L/min (range: 41.6–142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability. Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler.

Inhaler Devices for Delivery of LABA/LAMA Fixed-Dose Combinations in Patients with COPD

“…In an in vitro study that replicated inhaler-specific patient inhalation profiles that were previously recorded in vivo using the Electronic Lung (eLung TM ), drug dose delivery via the Ellipta Ò DPI was consistent across the range of patient representative inhalation parameters for all therapies such as formoterol/ vilanterol, umeclidinium/vilanterol, and formoterol [49]. A recent study showed that patients with mild to very severe COPD could also generate sufficient inspiratory flows for optimum drug delivery via Ellipta Ò [50]; it should be noted that this may not always be true in real life.…”

Aerosol Delivery Devices for Obstructive Lung Diseases

“…Some in vitro studies indicate that the fine-particle dose from DPIs is reduced when inspiratory flow is Ͻ 60 L/min, [141][142][143][144] whereas other studies show little effect of flow. 145,146 Diskus lung delivery may be suboptimal with a peak inspiratory flow Ͻ 60 L/min.…”

“…9 In a study conducted in an out-patient research setting, using an instrumented Ellipta inhaler, severe to very severe subjects with COPD had shorter inspiratory times and tended to have impaired inspiratory flow (Ͻ 60 L/min). 144 Decreased inspiratory flow has been observed when patients with COPD are clinically stable 36,140,143,147 and during exacerbations requiring hospitalization. 125,126,128 One study in subjects with COPD recently discharged from the hospital were instructed in the use of a Diskus inhaler with the INCA smart inhaler device.…”

The Ellipta ® in Asthma and Chronic Obstructive Pulmonary disease: Device Characteristics and Patient Acceptability

“…The inspiratory flow rate is an important inhalation profile parameter because of its direct influence on the dose delivery from most DPIs. The Ellipta device produces consistent dose delivery at flow rates over 30L/min [13,15] and this covers the inhalation rates across asthma and COPD disease severity, with even patients who suffer from very severe COPD able to generate an inspiratory effort of 41.6L/min whilst using the inhaler [15,16]. The particle size and fine particle fraction of the Ellipta inhalers vary by the medication delivered.…”