Inhalation therapy is a cornerstone of treating patients with chronic obstructive pulmonary disease (COPD). Inhaler types and through-device inhalation parameters influence airway drug delivery. We aimed to measure the repeatability of inhalation performance through four different commercially available inhalers.
Methods:
We recruited control subjects (n = 22) and patients with stable COPD (S-COPD, n = 16) and during an acute exacerbation (AE-COPD, n = 15). Standard spirometry was followed by through-device inhalation maneuvers using Ellipta®, Evohaler®, Respimat®, and Genuair®. Through-device inspiratory vital capacity (IVCd) and peak inspiratory flow (PIFd), as well as inhalation time (tin) and breath hold time (tbh), were recorded and all measurements were repeated in a random manner.
Results:
There was no difference in forced expiratory volume in 1 second (FEV1) between patients (S-COPD: 39 ± 5 vs. AE-COPD: 32% ± 5% predicted, p > 0.05). In controls, the IVCd was significantly reduced by all four devices in comparison with the slight reduction seen in COPD patients. In all subjects, PIF was lowered when inhaling through the devices in order of decreasing magnitude in PIFd: Evohaler, Respimat, Ellipta, and Genuair. The Bland-Altman analysis showed a highly variable coefficient of repeatability for IVCd and PIFd through the different inhalers for all COPD patients. Based on the intermeasurement differences in patients, Respimat and Genuair showed the highest repeatability for IVCd, while Genuair and Ellipta performed superior with regard to PIFd.
Conclusions:
Our study is the first to compare repeatability of inhalation performances through different inhalers in COPD patients, showing great individual differences for parameters influencing lung deposition of inhaled medication from a given device. Our data provide new insight into the characterization of inhaler use by patients with COPD, and might aid the selection of the most appropriate devices to ensure the adequate and consistent delivery of inhaled drugs.
Get full access to this article
View all access options for this article.
References
1.
GOLD. Global Strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: Available from: wwwgoldcopdorg, 2019.
2.
LiJ, SunS, TangR, HongQ, HuangQ, MasonTG, and TianL: Major air pollutants and risk of COPD exacerbations: A systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2016:11:3079–3091.
3.
LipsonDA, BarnhartF, BrealeyN, BrooksJ, CrinerGJ, DayNC, DransfieldMT, HalpinDMG, HanMK, JonesCE, KilbrideS, LangeP, LomasDA, MartinezFJ, SinghD, TabbererM, WiseRA, and PascoeSJ: Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018; 378:1671–1680.
4.
PapiA, VestboJ, FabbriL, CorradiM, PrunierH, CohuetG, GuasconiA, MontagnaI, VezzoliS, PetruzzelliS, ScuriM, RocheN, and SinghD: Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): A double-blind, parallel group, randomised controlled trial. Lancet. 2018; 391:1076–1084.
5.
HaidlP, HeindlS, SiemonK, BernackaM, and CloesRM: Inhalation device requirements for patients' inhalation maneuvers. Respir Med. 2016; 118:65–75.
6.
Dal NegroRW: Dry powder inhalers and the right things to remember: A concept review. Multidiscip Respir Med. 2015; 10:13.
7.
HodderR, and PriceD: Patient preferences for inhaler devices in chronic obstructive pulmonary disease: Experience with Respimat Soft Mist inhaler. Int J Chron Obstruct Pulmon Dis. 2009; 4:381–390.
8.
BerlinskiA: Assessing new technologies in aerosol medicine: Strengths and limitations. Respir Care. 2015; 60:833–847; discussion 847–839.
9.
LippmannM, and AlbertRE: The effect of particle size on the regional deposition of inhaled aerosols in the human respiratory tract. Am Ind Hyg Assoc J. 1969; 30:257–275.
10.
PaviaD, ThomsonM, ClarkeS, and ShannonH: Effect of lung function and mode of inhalation on penetration of aerosol into the human lung. Thorax. 1977; 32:194–197.
11.
PalmesED: Measurement of pulmonary air spaces using aerosols. Arch Intern Med. 1973; 131:76–79.
12.
CicilianiAM, LangguthP, and WachtelH: In vitro dose comparison of Respimat((R)) inhaler with dry powder inhalers for COPD maintenance therapy. Int J Chron Obstruct Pulmon Dis. 2017; 12:1565–1577.
13.
TakemuraM, MitsuiK, ItotaniR, IshitokoM, SuzukiS, MatsumotoM, AiharaK, OgumaT, UedaT, KagiokaH, and FukuiM: Relationships between repeated instruction on inhalation therapy, medication adherence, and health status in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2011; 6:97–104.
14.
UsmaniOS: Choosing the right inhaler for your asthma or COPD patient. Ther Clin Risk Manag. 2019; 15:461–472.
15.
ChrystynH, van der PalenJ, SharmaR, BarnesN, DelafontB, MahajanA, and ThomasM: Device errors in asthma and COPD: Systematic literature review and meta-analysis. NPJ Prim Care Respir Med. 2017; 27:22.
16.
HamiltonM, LeggettR, PangC, CharlesS, GillettB, and PrimeD: In vitro dosing performance of the ELLIPTA® dry powder inhaler using asthma and COPD patient inhalation profiles replicated with the electronic lung (eLung™). J Aerosol Med Pulm Drug Deliv. 2015; 28:498–506.
17.
JokayA, FarkasA, FuriP, HorvathA, TomisaG, and BalashazyI: Computer modeling of airway deposition distribution of Foster((R)) NEXThaler((R)) and Seretide((R)) Diskus((R)) dry powder combination drugs. Eur J Pharmaceut Sci. 2016; 88:210–218.
18.
MillerMR, HankinsonJ, BrusascoV, BurgosF, CasaburiR, CoatesA, CrapoR, EnrightP, van der GrintenCP, GustafssonP, JensenR, JohnsonDC, MacIntyreN, McKayR, NavajasD, PedersenOF, PellegrinoR, ViegiG, WangerJ, and ForceAET: Standardisation of spirometry. Eur Respir J. 2005; 26:319–338.
19.
JonesPW, HardingG, BerryP, WiklundI, ChenWH, and Kline LeidyN: Development and first validation of the COPD Assessment Test. Eur Respir J. 2009; 34:648–654.
20.
BestallJC, PaulEA, GarrodR, GarnhamR, JonesPW, and WedzichaJA: Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999; 54:581–586.
21.
BrooksR: EuroQol: The current state of play. Health Policy. 1996; 37:53–72.
22.
BlandJM, and AltmanDG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986; 1:307–310.
23.
VestboJ, AndersonJA, CalverleyPM, CelliB, FergusonGT, JenkinsC, KnobilK, WillitsLR, YatesJC, and JonesPW: Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009; 64:939–943.
24.
SanchisJ, GichI, and PedersenS: Systematic review of errors in inhaler use: Has patient technique improved over time?. Chest. 2016; 150:394–406.
25.
GINA. Global Strategy for Asthma Management and Prevention: Available from: wwwginasthmaorg, 2019.
26.
van BovenJFM, LavoriniF, DekhuijzenPNR, BlasiF, PriceDB, and ViegiG: Urging Europe to put non-adherence to inhaled respiratory medication higher on the policy agenda: A report from the First European Congress on Adherence to Therapy. Eur Respir J. 2017; 49:1700076.
27.
MolimardM, RaherisonC, LignotS, BalestraA, LamarqueS, ChartierA, Droz-PerroteauC, LassalleR, MooreN, and GirodetPO: Chronic obstructive pulmonary disease exacerbation and inhaler device handling: Real-life assessment of 2935 patients. Eur Respir J. 2017; 49:1601794.
28.
DhamaneAD, SchwabP, HopsonS, MoretzC, AnnavarapuS, BurslemK, RendaA, and KailaS: Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients. Int J Chron Obstruct Pulmon Dis. 2017; 12:115–122.
29.
DingB, SmallM, ScheffelG, and HolmgrenU: Maintenance inhaler preference, attribute importance, and satisfaction in prescribing physicians and patients with asthma, COPD, or asthma–COPD overlap syndrome consulting for routine care. Int J Chron Obstruct Pulmon Dis. 2018; 13:927–936.
30.
ColthorpeP, VoshaarT, KieckbuschT, CuoghiE, and JauernigJ: Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium. J Drug Assess. 2013; 2:11–16.
31.
FarkasA, JokayA, BalashazyI, FuriP, MullerV, TomisaG, and HorvathA: Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort((R)) Turbuhaler((R)) dry powder fixed combination aerosol drug. Eur J Pharmaceut Sci. 2016; 93:371–379.
32.
FeldmanGJ, SousaAR, LipsonDA, TombsL, BarnesN, RileyJH, PatelS, NayaI, ComptonC, and Alcazar NavarreteB: Comparative efficacy of once-daily umeclidinium/vilanterol and tiotropium/olodaterol therapy in symptomatic chronic obstructive pulmonary disease: A randomized study. Adv Ther. 2017; 34:2518–2533.
33.
MitchellJ, NewmanS, and ChanHK: In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review. AAPS PharmSciTech. 2007; 8:E110.
34.
IvancsoI, BocskeiR, MullerV, and TamasiL: Extrafine inhaled corticosteroid therapy in the control of asthma. J Asthma Allergy. 2013; 6:69–80.
35.
MullerV, GalffyG, EszesN, LosonczyG, BizziA, NicoliniG, ChrystynH, and TamasiL: Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation. BMC Pulmon Med. 2011; 11:40.
36.
MullerV, GalffyG, OroszM, KovatsZ, OdlerB, SelroosO, and TamasiL: Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: An analysis of salbutamol Easyhaler data. Int J Chron Obstruct Pulmon Dis. 2016; 11:93–101.
37.
DingB, SmallM, BergstromG, and HolmgrenU: COPD symptom burden: Impact on health care resource utilization, and work and activity impairment. Int J Chron Obstruct Pulmon Dis. 2017; 12:677–689.
38.
LaubeBL, JanssensHM, de JonghFH, DevadasonSG, DhandR, DiotP, EverardML, HorvathI, NavalesiP, VoshaarT, and ChrystynH: What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011; 37:1308–1331.
39.
LeinerS, ParkinsD, and LastowO: Inhalation devices and patient interface: Human factors. AAPS J. 2015; 17:457–461.
