An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a Dry Powder Inhaler.
BACKGROUND
Dry powder inhaler (DPI) users frequently exhale into their inhaler mouthpiece before the inhalation step. This error in technique compromises the integrity of the drug and results in poor bronchodilation. This study investigated the effect of four exhalation factors (exhalation flow rate, distance from mouth to inhaler, exhalation duration, and relative air humidity) on dry powder dose delivery. Given that acoustic energy can be related to the factors associated with exhalation sounds, we then aimed to develop a method of identifying and quantifying this critical inhaler technique error using acoustic based methods.


METHODS
An in vitro test rig was developed to simulate this critical error. The effect of the four factors on subsequent drug delivery were investigated using multivariate regression models. In a further study we then used an acoustic monitoring device to unobtrusively record the sounds 22 asthmatic patients made whilst using a Diskus(™) DPI. Acoustic energy was employed to automatically detect and analyze exhalation events in the audio files.


RESULTS
All exhalation factors had a statistically significant effect on drug delivery (p<0.05); distance from the inhaler mouthpiece had the largest effect size. Humid air exhalations were found to reduce the fine particle fraction (FPF) compared to dry air. In a dataset of 110 audio files from 22 asthmatic patients, the acoustic method detected exhalations with an accuracy of 89.1%. We were able to classify exhalations occurring 5 cm or less in the direction of the inhaler mouthpiece or recording device with a sensitivity of 72.2% and specificity of 85.7%.


CONCLUSIONS
Exhaling into a DPI has a significant detrimental effect. Acoustic based methods can be employed to objectively detect and analyze exhalations during inhaler use, thus providing a method of remotely monitoring inhaler technique and providing personalized inhaler technique feedback.
1 Trinity Centre for Bioengineering, Trinity College Dublin , Ireland .
Martin S
MS
Holmes
2 The Department of Medicine Respiratory Research Division, The Royal College of Surgeons in Ireland .
Jansen N
JN
Seheult
3 School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Ireland .
Peter
P
O'Connell
1 Trinity Centre for Bioengineering, Trinity College Dublin , Ireland .
Shona
S
D'Arcy
3 School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Ireland .
Carsten
C
Ehrhardt
3 School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , Ireland .
Anne Marie
AM
Healy
2 The Department of Medicine Respiratory Research Division, The Royal College of Surgeons in Ireland .
Richard W
RW
Costello
1 Trinity Centre for Bioengineering, Trinity College Dublin , Ireland .
Richard B
RB
Reilly
D000162:Acoustics; D000280:Administration, Inhalation; D000336:Aerosols; D000388:Air; D000465:Algorithms; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D016022:Case-Control Studies; D016503:Drug Delivery Systems / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D045853:Exhalation; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006813:Humidity; D001239:Inhalation; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D015999:Multivariate Analysis; D011208:Powders; D012044:Regression Analysis; D012135:Respiratory Sounds; D012815:Signal Processing, Computer-Assisted; D013018:Sound Spectrography; D013997:Time Factors
D000336:Aerosols; D001993:Bronchodilator Agents; D000068297:Fluticasone-Salmeterol Drug Combination; D011208:Powders
acoustics; diskus; dry powder inhalers; exhalation; humidity; signal processing