The contribution of patients’ lung function to the inspiratory airflow rate achievable through a DPIs’ simulator reproducing different intrinsic resistance rates

Abstract

Background: The performance of DPIs depends on several physiological (patient-dependent) and technological (device-dependent) factors. The inspiratory airflow rate is the only active force generated and operating in the system for inducing the required pressure drop and eliciting the resistance-induced turbulence needed to disaggregate the powder through the device. The present study aimed to investigate in the most prevalent respiratory disorders whether and at what extent the inspiratory airflow rate achievable when inhaling through a DPIs’ simulator reproducing different intrinsic resistance regimens (low, mid, and high resistance) is affected by peculiar changes in lung function and/or can be predicted by any specific lung function parameter.
Methods: The inspiratory airflow rate was assessed in randomized order by the In-Check DIAL G16 at low, mid, and high resistance regimens in a sample of consecutive subjects at recruitment. Independent predictors of the probability to achieve the expected inhalation airflow rate were investigated by means of a multivariate logistic regression model, specific to the disease.
Results: A total of 114 subjects were recruited (asthmatics n=30; COPD n=50, restrictive patients n=16, and normal subjects n=18). The mean values of the expected inspiratory airflow rate achieved proved significantly different within the groups (p<0.0001), independently of sex and age. In asthmatics and in COPD patients, the mid-resistance regimen proved highly associated with the highest mean values of airflow rates obtained. Low- and high-resistance regimens were significantly less likely to consent to achieve the expected level of inspiratory airflow rate (OR<1 in all comparisons). Restrictive patients performed the lowest airflow rates at the low-resistance regimen (p<0.01). Unlike FEV1, RV in asthmatics (OR=1.008); RV and IRaw in COPD (OR=0.587 and OR=0.901, respectively), and FIF and TLC in restrictive patients (OR=1.041, and OR=0.962, respectively) proved the only sensitive predictors of the inspiratory airflow rate achievable at the different resistive regimens.
Conclusions: The intrinsic resistive regimen of DPIs can play a critical role.  The patients’ lung function profile also affects the extent of their inhalation airflow rate. Some specific lung function parameters (such as: FIF; RV; IRaw; TLC, but not FEV1) may be regarded as specific predictors in real-life. In order to optimize the DPI choice, further to the device’s technology, also the current patients’ lung function should be properly investigated and carefully assessed.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

References

Virchow JC. Guidelines versus clinical practice – which therapy and which device. Respir Med 2004;98S28-34. DOI: https://doi.org/10.1016/j.rmed.2004.07.012

Virchow JC, Crompton GK, Dal Negro RW, Pedersen S, Magnan A, Seidemberg J, et al. Importance of inhaler devices in the management of airway diseases. Respir Med 2008;102:10-9. DOI: https://doi.org/10.1016/j.rmed.2007.07.031

Clark AR, Weers JG, Dhand R. The confusing world of dry powder inhalers: It is all about inspiratory pressures, not inspiratory flow rates. J Aerosol Med Pulm Drug Deliv 2020;33:1-11. DOI: https://doi.org/10.1089/jamp.2019.1556

Wieshammer S, Dreyhaupt J. Dry powder inhalers: which factors determine the frequency of handling errors? Respiration 2008;75:18-25. DOI: https://doi.org/10.1159/000109374

Newman SP, Busse WW. Evolution of dry powder inhaler design, formulation, and performance. Respir Med 2002;96;293-304. DOI: https://doi.org/10.1053/rmed.2001.1276

Chapman KR, Fogarty CM, Peckitt C, Lassen C, Jadayel D, Dedericha J, et al. Delivery characteristics and patients’ handling of two single-dose dry powder inhalers used in COPD. Int J COPD 2011;6:353-6.

Sanchis J, Corrigan C, Levy M.L, Viejo JL. Inhaler devices-From theory to practice. Respir Med 2013;107:495-502. DOI: https://doi.org/10.1016/j.rmed.2012.12.007

Dal Negro RW, Turco P, Povero M. Patients’ usability of seven most used dry-powder inhalers in COPD. Multidiscip Respir Med 2019;14:30. DOI: https://doi.org/10.1186/s40248-019-0192-5

Kruger P, Ehrlein, Zier M, Greguletz R. Inspiratory flow resistance of marketed dry powder inhalers. Eur Respir J 2014;44:abstract 4635.

Capstick TGD, Clifton IJ. Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma. Exp Rev Respir Med 2012;6:91-103. DOI: https://doi.org/10.1586/ers.11.89

Sanders MJ. Guiding inspiratory flow: Development of the in-check DIAL G16, a tool for improving inhaler technique. Pulm Med 2017;2017:1495867. DOI: https://doi.org/10.1155/2017/1495867

Berkenfeld K, Lamprecht A, McConville JT. Devices for dry powder drug delivery to the lung, AAPS Pharm Sci Tech 2015;16:479-90.

Dederichs J, Singh D, Pavkov R. Inspiratory flow profiles generated by patients with COPD through the Breezhaler inhaler and other marketed dry powder inhalers. Am J Respir Crit Care Med 2015;191:A5793.

Canonica GW, Arp J, Keegstra JR, Chrystyn H. Spiromax, a new dry powder inhaler: dose consistency under simulated real-world conditions. J Aerosol Med Pulm Drug Deliv 2015;28:309-19. DOI: https://doi.org/10.1089/jamp.2015.1216

Yakubu SI, Assi KH, Chrystyn H. Aerodynamic dose emission characteristics of dry powder inhalers using an Andersen Cascade Impactor with a mixing inlet: The influence of flow and volume. Int J Pharm 2013;455:213-8. DOI: https://doi.org/10.1016/j.ijpharm.2013.07.036

Frijlink HW, De Boer AH. Dry powder inhalers for pulmonary drug delivery. Exp Op Drug Del 2004;1:67-86. DOI: https://doi.org/10.1517/17425247.1.1.67

Lexmond AJ, Kruizinga TJ, Hagedoorn P, Rottier BL, Frijlink HW, De Boer AH. Effect of inhaler design variables on paediatric use of dry powder inhalers. PLoS One 2014;9:99304. DOI: https://doi.org/10.1371/journal.pone.0099304

Concato J, Peduzzi P, Holford TR, Feinstein AR. The importance of event per variable (EPV) in proportional hazard analysis: I. Background, goals and general strategy. J Clin Epidemiol 1995;48:1495–501. DOI: https://doi.org/10.1016/0895-4356(95)00510-2

Clark AR: The role of inspiratory pressures in determining the flow rate through dry powder inhalers; a review. Curr Pharm Design 2015;21:3973–83. DOI: https://doi.org/10.2174/1381612821666150820105800

Malmberg LP, Rytilä P, Happonen P, Haahtela T. Inspiratory flows through dry powder inhaler in chronic obstructive pulmonary disease: age and gender rather than severity matters. Int J Chron Obstr Pulm Dis 2010;5:257-62. DOI: https://doi.org/10.2147/COPD.S11474

Crompton GK. Problems patients have using pressurized aerosol inhalers. Eur J Resp Dis 1982;63:S101-4.

Brocklebank D, Ram F, Wright J, Barry P, Cates C, Davies L, et al. Comparison of effectiveness of inhaler devices in asthma and chronic obstructive airway disease: a systematic review of the literature. Health Technol Asses 2001;5:1-149. DOI: https://doi.org/10.3310/hta5260

Thomas M, Williams AE. Are outcomes the same with all dry powder inhalers? Int J Clin Pract Suppl 2005;149:33-5. DOI: https://doi.org/10.1111/j.1368-504X.2005.00726.x

Gustafsson P, Taylor A, Zanen P, Chrysyn H. Can patients use all dry powder inhalers equally well? Int J Clin Pract Suppl 2005;149:13-8. DOI: https://doi.org/10.1111/j.1368-504X.2005.00722.x

Suarez-Barcelo M, Micca JL, Clackum S, Ferguson GT. Chronic obstructive pulmonary disease in long-term care setting: current practices, challenges, and unmet needs. Curr Opin Pulm Med 2017;23:s1-28. DOI: https://doi.org/10.1097/MCP.0000000000000416

Ung KT, Rao N, Weers JG, Clark AR, Chan HK: In vitro assessment of dose delivery performance of dry powders for inhalation. Aerosol Sci Technol 2014;48:1099-110. DOI: https://doi.org/10.1080/02786826.2014.962685

Ung KT, Chan HK. Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance of certain dry powder inhalers. Eur J Pharm Sci 2016;84:46-54. DOI: https://doi.org/10.1016/j.ejps.2016.01.005

Mohammed H, Arp I, Chambers F, Copley M, Glaab V, Hammond M, et al. Investigation of dry powder inhaler (DPI) resistance and aerosol dispersion timing on emitted aerosol aerodynamic particle sizing by multistage cascade impactor when sampled volume is reduced from compendial value of 4 L. AAPS Pharm Sci Tech 2014;15:1126-37. DOI: https://doi.org/10.1208/s12249-014-0111-1

Haidl P, Heindl S, Siemon K, Bernacka M, Cloes RM. Inhalation device requirements for patients’ inhalation maneuvers. Respir Med 2016;118:65-75. DOI: https://doi.org/10.1016/j.rmed.2016.07.013

Buttini F, Brambilla G, Copelli D, Sisti V, Balducci AG, Bettini R, et al. Effect of flow rate on in vitro aerodynamic performance of Nexthaler in comparison with Diskus and Turbohaler dry powder inhalers. J Aerosol Med Pulm Drug Del 2016;29:167-78. DOI: https://doi.org/10.1089/jamp.2015.1220

Dal Negro RW. Dry powder inhalers and the right things to remember: a concept review. Multidiscip Respir Med 2015;10:13. DOI: https://doi.org/10.1186/s40248-015-0012-5

Laube BL, Janssens HM, De Jongh FHC, Devadason SG, Dhand R, Diot P, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-31.

Pedersen S, Hansen OR, Fuglsang G. Influence of inspiratory flow rate upon the effect of a Turbuhaler. Arch Dis Child 1990;65:308-10. DOI: https://doi.org/10.1136/adc.65.3.308

Berkenfeld K, Lamprecht A, McConville JT. Devices for dry powder drug delivery to the lung. AAPS Pharm Sci Tech 2015;16:479-90. DOI: https://doi.org/10.1208/s12249-015-0317-x

Weers J, Clark A. The impact of inspiratory flow rate on drug delivery to the lungs with dry powder inhalers. Pharm Res 2017;34:507-28. DOI: https://doi.org/10.1007/s11095-016-2050-x

Azouz W, Chetcuti P, Hosker H.S, Saralaya D, Stephenson J, Chrystyn H. The inhalation characteristics of patients when they use different dry powder inhalers. J Aerosol Med Pulm Drug Deliv 2015;28:35-42. DOI: https://doi.org/10.1089/jamp.2013.1119

Altman P, Wehbe L, Dederichs J, Guerin T, Ament B, Cardenas Moronta M, et al. Comparison of peak inspiratory flow rate via the Breezhaler®, Ellipta® and HandiHaler® dry powder inhalers in patients with moderate to very severe COPD: a randomized cross-over trial. BMC Pulm Med 2018;18:100. DOI: https://doi.org/10.1186/s12890-018-0662-0

Laube BL, Janssens HM, de Jongh FH, Devadason SG, Dhand R, Diot P, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-31. DOI: https://doi.org/10.1183/09031936.00166410

Cook CD, Mead J, Orzalesi MM. Static volume/pressure characteristics of the respiratory system during maximal efforts. J Appl Physio. 1964;19:1016-22. DOI: https://doi.org/10.1152/jappl.1964.19.5.1016

Clark AR, 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. DOI: https://doi.org/10.1089/jam.1993.6.99

Chapman KR, Fogarty CM, Peckitt C, Lassen C, Jadayel D, Dederichs J, et al. Delivery characteristics and patients’ handling of two single-dose dry-powder inhalers used in COPD. Int J Chron Obstruct Pulmon Dis 2011;6:353-63.

Mahler DA, Waterman LA, Gifford AH: Prevalence and COPD phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus. J Aerosol Med Pulm Drug Deliv 2013;26:174–9. DOI: https://doi.org/10.1089/jamp.2012.0987

Mahler DA, Waterman LA, Ward J, Gifford AH. Comparison of dry powder versus nebulized beta-agonist in patients with COPD who have suboptimal peak inspiratory flow rate. J Aerosol Med Pulm Drug Deliv 2014;27:103-9. DOI: https://doi.org/10.1089/jamp.2013.1038

Janssens W, VandenBrande P, Hardeman E, De Langhe E, Philips T, Troosters T, et al. Inspiratory flow rates at different levels of resistance in elderly COPD patients. Eur Respir J 2008;31:78-83. DOI: https://doi.org/10.1183/09031936.00024807

Published
2021-04-15
Info
Issue
Section
Original Research Articles
Conflict of interest statement
The authors declare the absence of any conflict of interest. RWD is Associate Editor of Multidisciplinary Respiratory Medicine.
Keywords:
DPIs, inspiratory airflow, intrinsic resistance, lung function, predictors, obstructive and restrictive patients, normal subjects
Statistics
  • Abstract views: 1025

  • PDF: 33
  • Supplementary: 3
  • HTML: 0
How to Cite
Dal Negro, R. W., Turco, P., & Povero, M. (2021). The contribution of patients’ lung function to the inspiratory airflow rate achievable through a DPIs’ simulator reproducing different intrinsic resistance rates. Multidisciplinary Respiratory Medicine, 16. https://doi.org/10.4081/mrm.2021.752