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

David Prime, Wilfried de Backer, Melanie Hamilton, Anthony Cahn, Andrew Preece, Dennis Kelleher, Amanda Baines, Alison Moore, Noushin Brealey, Jackie Moynihan, David Prime, Wilfried de Backer, Melanie Hamilton, Anthony Cahn, Andrew Preece, Dennis Kelleher, Amanda Baines, Alison Moore, Noushin Brealey, Jackie Moynihan

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.

Trial registration: ClinicalTrials.gov NCT01345266 NCT02076269.

Keywords: COPD; asthma; dry powder inhalers; inhalation profile; lung function.

Figures

FIG. 1.
FIG. 1.
(a) Mean (95% CI) peak pressure drop, (b) mean (95% CI) PIFR, and (c) mean (95% CI) inhaled volume (all patients). CI, confidence interval; COPD, chronic obstructive pulmonary disease; PIFR, peak inspiratory flow rate. aPatients from Study 1 only; bPatients from Study 2 only; cPooled data from Studies 1 and 2.
FIG. 2.
FIG. 2.
Correlation figures for COPD patients only for (a) PIFR (via the ELLIPTA DPI) versus FEV1 (spirometry), (b) PIFR (via the ELLIPTA DPI) versus PEFR (spirometry), and (c) PIFR (via the ELLIPTA DPI) versus PIFR (spirometry). COPD, chronic obstructive pulmonary disease; DLCO, diffusing capacity of the lung for carbon monoxide; DPI, dry powder inhaler; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; PEFR, peak expiratory flow rate; PIFR, peak inspiratory flow rate.

References

    1. Atkins PJ: Dry powder inhalers: An overview. Respir Care. 2005;50:1304–1310
    1. Berger W: Aerosol devices and asthma therapy. Curr Drug Deliv. 2009;6:38–49
    1. Ari A, and Fink JB: Guidelines for aerosol devices in infants, children and adults: Which to choose, why and how to achieve effective aerosol therapy. Expert Rev Respir Med. 2011;5:561–572
    1. Fink JB, Colice GL, and Hodder R: Inhaler devices for patients with COPD. COPD. 2013;10:523–535
    1. Ganderton D: General factors influencing drug delivery to the lung. Respir Med. 1997;91:13–16
    1. Bronsky EA, Grossman J, Henis MJ, Gallo PP, Yegen U, Della Cioppa G, Kottakis J, and Mehra S: Inspiratory flow rates and volumes with the Aerolizer dry powder inhaler in asthmatic children and adults. Curr Med Res Opin. 2004;20:131–137
    1. Clark AR, and Hollingworth AM: The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers-implications for in vitro testing. J Aerosol Med. 1993;6:99–110
    1. Riley JH, Tabberer MM, Richard N, Donald AC, Church A, and Harris SS: Use of a new dry powder inhaler to deliver umeclidinium/vilanterol in the treatment of COPD. Eur Respir J. 2013;42:880s
    1. Svedsater H, Dale P, Garrill K, Walker R, and Woepse MW: Qualitative assessment of attributes and ease of use of the ELLIPTA™ dry powder inhaler for delivery of maintenance therapy for asthma and COPD. BMC Pulm Med. 2013;13:72.
    1. Svedsater H, Jacques L, Goldfrad C, and Bleecker ER: Ease of use of the ELLIPTA dry powder inhaler: Data from three randomised controlled trials in patients with asthma. NPJ Prim Care Respir Med. 2014;24:14019.
    1. Laube BL, Janssens HM, de Jongh FHC, Devadason SG, Dhand R, Diot P, Everard ML, Horvath I, Navalesi P, Voshaar T, and Chrystyn H: What the pulmonary specialist should know about the new inhalation therapies. ERS/ISAM Task Force report. Eur Respir J. 2011;37:1308–1331
    1. Bisgaard H, Klug B, Sumby BS, and Burnell PK: Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma. Eur Respir J. 1998;11:1111–1115
    1. Burnell PKP, Small T, Doig S, Johal B, Jenkins R, and Gibson GJ: Ex-vivo product performance of Diskus and Turbuhaler inhalers using inhalation profiles from patients with severe chronic obstructive pulmonary disease. Respir Med. 2001;95:324–330
    1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use: ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6(R1). Available at Accessed February19, 2015
    1. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Last updated 2008. Available at Accessed February19, 2015
    1. British Thoracic Society Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma. Thorax. 2008;63:iv1–iv121
    1. Global Initiative for Chronic Obstructive Lung Disease: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated December 2007. Available at Accessed February19, 2015
    1. Global Initiative for Chronic Obstructive Lung Disease: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated January 2015. Available at Accessed February19, 2015
    1. Broeders ME, Molema J, Vermue NA, and Folgering HT: Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers. Eur Respir J. 2001;18:780–783
    1. Janssens JP, Pache JC, and Nicold LP: Physiological changes in respiratory function associated with ageing. Eur Respir J. 1999;13:197–205
    1. Janssens W, Vanden Brande P, Hardeman E, de Langhe E, Philps T, Troosters T, and Decramer M: Inspiratory flow rates at different levels of resistance in elderly COPD patients. Eur Respir J. 2008;3:78–83
    1. Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, Lettis S, Crim C, and Calverley PM: A once-daily inhaled corticosteroid, long-acting beta2-agonist combination, fluticasone furoate (FF) / vilanterol (VI), for the prevention of COPD exacerbations. Lancet Respir Med. 2013;1:210–223
    1. Martinez FJ, Boscia J, Feldman G, Scott-Wilson C, Kilbride S, Fabbri L, Crim C, and Calverley PM: Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: A randomised trial. Respir Med. 2013;107:550–559
    1. Donohue JF, Maleki-Yazdi MR, Kilbride S, Mehta R, Kalberg C, and Church A: Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med. 2013;107:1538–1546
    1. Celli B, Crater G, Kilbride S, Mehta R, Tabberer M, Kalberg CJ, and Church A: Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: A randomized, controlled study. Chest. 2014;145:981–991
    1. Decramer M, Anzueto A, Kerwin E, Kaelin T, Richard N, Crater G, Tabberer M, Harris S, and Church A: Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: Results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med. 2014;2:472–486
    1. Broeders MEAC, Molema J, Hop WCJ, and Folgering HTM: Inhalation profiles in asthmatics and COPD patients: Reproducibility and effect of instruction. J Aerosol Med. 2003;16:131–141
    1. Magnussen H, Watz H, Zimmermann I, Macht S, Greguletz R, Falques M, Jarreta D, and Garcia Gil E: Peak inspiratory flow through the Genuair inhaler in patients with moderate or severe COPD. Respir Med. 2009;103:1832–1837

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