Detection of Asthma Inhaler Use via Terahertz Spectroscopy.

Inhaled medications are commonplace for administering bronchodilators, anticholinergics, and corticosteroids. While they have a defined legitimate use, they are also used in sporting events as performance-enhancing drugs. These performance enhancers can be acquired via both legal (i.e., at a pharmacy through over-the-counter medications or through a prescription) and illicit (i.e., black market and foreign pharmacies) means, thus making monitoring procurement impossible. While urine tests can detect these pharmacological agents hours after they have been inhaled, there is a significant lag time before they are observed in urine. Direct detection of these inhaled agents is complicated and requires a multiplexed approach due to the sheer number of inhaled pharmacological agents. Therefore, detection of propellants, which carry the drug into the lungs, provides a simpler path forward toward detection of broad pharmacological agents. In this paper, we demonstrate the first use of terahertz spectroscopy (THz) to detect inhaled medications in human subjects. Notably, we were able to detect and quantitate the propellant, HFA-134a, in breath up to 30 min after using an asthma inhaler, enabling the use of a point-of-care device to monitor exhaled breath for the presence of propellants. We also demonstrate via simulations that the same approach can be leveraged to detect and identify next-generation propellants, specifically HFA-152a. As a result, we provide evidence that a single point-of-care THz sensor can detect when individuals have used pressure-mediated dose inhalers (pMDIs) without further modification of the hardware.

[1]  Claude C. Grigsby,et al.  Terahertz Spectroscopic Molecular Sensor for Rapid and Highly Specific Quantitative Analytical Gas Sensing. , 2022, ACS sensors.

[2]  A. Marchand,et al.  Improved detection methods significantly increase the detection window for EPO microdoses. , 2020, Drug testing and analysis.

[3]  E. Kerwin,et al.  Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler , 2020, Journal of aerosol medicine and pulmonary drug delivery.

[4]  A. Azapagic,et al.  Environmental impacts of healthcare and pharmaceutical products: Influence of product design and consumer behaviour , 2020 .

[5]  A. Litonjua,et al.  Asthma epidemiology and risk factors , 2020, Seminars in Immunopathology.

[6]  Hossam Haick,et al.  Measurement of temperature and relative humidity in exhaled breath , 2020 .

[7]  Mira Naftaly,et al.  Industrial Applications of Terahertz Sensing: State of Play , 2019, Sensors.

[8]  Klaus Schmalz,et al.  Analysis of Human Breath by Millimeter-Wave/Terahertz Spectroscopy , 2019, Sensors.

[9]  A. Cohen,et al.  Futility of current urine salbutamol doping control , 2018, British journal of clinical pharmacology.

[10]  Erik J. Saude,et al.  A systematic review of adverse drug events associated with administration of common asthma medications in children , 2017, PloS one.

[11]  V. Backer,et al.  The influence of exercise and dehydration on the urine concentrations of salbutamol after inhaled administration of 1600 µg salbutamol as a single dose in relation to doping analysis. , 2016, Drug testing and analysis.

[12]  Hye-Won Shin,et al.  Quantification of Aerosol Hydrofluoroalkane HFA‐134a Elimination in the Exhaled Human Breath Following Inhaled Corticosteroids Administration , 2015, Clinical and translational science.

[13]  P. Karaca-Mandic,et al.  The Impact of the US Food and Drug Administration Chlorofluorocarbon Ban on Out-of-pocket Costs and Use of Albuterol Inhalers Among Individuals With Asthma. , 2015, JAMA internal medicine.

[14]  Amit M. Momaya,et al.  Performance-Enhancing Substances in Sports: A Review of the Literature , 2015, Sports Medicine.

[15]  M. Hagger,et al.  Health and doping in elite‐level cycling , 2012, Scandinavian journal of medicine & science in sports.

[16]  Neil Robinson,et al.  The athlete biological passport: an effective tool in the fight against doping. , 2011, Clinical chemistry.

[17]  A. Garnham,et al.  Current markers of the Athlete Blood Passport do not flag microdose EPO doping , 2011, European Journal of Applied Physiology.

[18]  M. Sears,et al.  Asthma: epidemiology, etiology and risk factors , 2009, Canadian Medical Association Journal.

[19]  T. Biedermann,et al.  Epinephrine inhalers in emergency sets of patients with anaphylaxis , 2009, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[20]  E. Eichner Blood Doping , 2007, Sports medicine.

[21]  W. Finlay,et al.  A dry powder inhaler with reduced mouth-throat deposition. , 2006, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[22]  A. Christiansen The Legacy of Festina: Patterns of Drug Use in European Cycling Since 1998 , 2005 .

[23]  K. Middleton,et al.  Overseas‐based online pharmacies: a source of supply for illicit drug users? , 2004, The Medical journal of Australia.

[24]  F. Hartgens,et al.  Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes. , 2004, International journal of sports medicine.

[25]  R. Candau,et al.  Effects of short-term oral salbutamol administration on exercise endurance and metabolism. , 2000, Journal of applied physiology.

[26]  S. Dyubko,et al.  Microwave Spectroscopy of the Ground, ν18, 2ν18, and ν11Vibrational States of CF3CFH2 , 1999 .

[27]  M. Dolovich New delivery systems and propellants. , 1999, Canadian respiratory journal.

[28]  T. Heir,et al.  Salbutamol and high‐intensity treadmill running in nonasthmatic highly conditioned athletes , 1995, Scandinavian journal of medicine & science in sports.

[29]  J. López,et al.  ROTATIONAL SPECTRUM OF 1,1-DIFLUOROETHANE: INTERNAL ROTATION ANALYSIS AND STRUCTURE , 1995 .