Inhalers are among the most commonly used devices to treat respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). With each inhalation through the inhaler, the device delivers a specific amount of medicine to the lungs. However, it is often misused as patients often have difficulty adopting the correct inhaler technique and therefore receive insufficient medication. This leads to poor disease control and increased healthcare costs.
The worldwide annual costs associated with the management of asthma and COPD are considerable from the perspective of both the health care payer and society. The research results show that the healthcare expenditure of an uncontrolled patient is more than double that of a controlled patient. 1 Studies have also found that most patients make at least one mistake when taking inhaled medications, resulting in only 7-40% of the medication being delivered to the lungs. The two biggest and most serious errors when using metered-dose inhalers (MDIs) are both related to patient inhalation. The first error is related to the coordination between the inhalation and the triggering of the dose release from the inhaler. Even a short delay can result in only 20% of the drug being delivered to the lungs. The second biggest mistake is not breathing deeply enough, which can cause 10% less medicine to reach the lungs.
To solve these problems, Sensirion AG (Stäfa, Switzerland) has developed a prototype that can be clipped onto the inhaler to measure the patient’s inhalation airflow and determine when during inhalation the inhaler is actuated.
Why measure the inhalation flow profile?
Since the two most important and serious errors in the use of inhalers are related to patient inhalation, it is important to measure the airflow through the inhaler and, for metered dose inhalers , also the time when the drug is dispensed. This provides information on whether the drug was released within the optimal window of the inhalation cycle (see Figure 1). This correlation between the timing of the dose initiation and the flow rate is a key parameter in understanding whether the drug-carrying flow has reached deep into the bronchi and reached the desired high lung deposition.
The second critical parameter is the inhaled airflow profile. Similar to the use of a spirometer, several parameters can be derived from the inhalation airflow profile that provide information about each patient’s inhalation:
Depth and length of inspiration
Complete exhalation before inspiration
Slow inhalation as directed
Pulmonary function and its evolution over time (change in inspiratory flow characteristics)
Accurate, calibrated real-time recordings of the inhalation flow profile provide this information, from which it can be determined whether the patient performed the inhalation correctly.
Other parameters of interest include inhaled volume (IV) and peak inspired flow (PIF), as well as the full inhalation airflow characteristic, as shown in Figure 2.
Subsets of parameters such as airway resistance (RAW) can also be determined from the inhalation airflow profile. The derivation of RAW is shown in Figure 3. When the inhaler is used as a spirometer-type device, all parameters are derived during regular inhalation, so there is nothing more than the patient has to do in relation to taking their medications the way they are used. at. At the same time, the device will also record if the patient has not taken the medicine, which can be used to remind the patient to adhere to the prescribed treatment.
In addition to monitoring each inhalation, important parameters can be tracked over time, providing information on correct inhaler use, drug effectiveness and disease progression. This information can be sent to the healthcare provider and also help motivate the user. This combination of drug delivery and diagnostic unit in one device is a powerful tool for improving patient outcomes.
Figure 4 shows the schematic behavior of PIF, IV and RAW as a function of time. It visualizes the positive effect of starting treatment, the stable treatment phase during regular dosing and the negative effect of stopping treatment.
How to measure the inhalation flow profile
In the past, accurate measurement of flow through the inhaler was difficult due to the lack of sufficiently robust yet sensitive devices capable of measuring the smallest flow rates. To avoid having to revalidate the inhaler with the FDA and maintain approval, the key regulatory requirement for inhaler clips is that the flow path of the inhaler remains unchanged to ensure that it does not interfere with the existing function of the inhaler. The Sensirion clip-on inhaler does just that.
Figure 5 shows the 3D printed inhaler clip containing the Sensirion SDP3x flow sensor along with a low energy Bluetooth communication chip and battery power source. The inhaler housing has not been modified.
The Bernoulli/Venturi effect explains that the acceleration of the airflow entering the inhaler caused by the patient’s inhalation creates a negative pressure at the level of the upper opening of the inhaler, around the cartridge and the opening of the attached clip. The magnitude of the negative pressure is directly related to the magnitude of the airflow rate through the inhaler to the patient and is measured by the flow sensor.
A more graphical way to understand the principle is to think of the flow configuration as a main passage bypass system (see Figure 6). When the patient inhales, the negative pressure around the inhaler opening draws a small amount of clean ambient air through the sensor bypass path and into the main inhaler passage. By measuring the bypass airflow and knowing the bypass/main pass ratio, which is provided by the inhaler/clip-on geometry, the total amount of airflow to the patient can be determined.
A MEMS-based flow sensor
There are many different methods of measuring gas flow: mechanical volumetric, float, differential pressure, ultrasonic, Coriolis, magnetic inductive and thermal, to name a few. Non-contact metering techniques between gas and sensor require relatively expensive technology and are therefore out of the question for many applications. In the classic differential pressure method, hysteresis effects and diaphragm fatigue can lead to drift problems and lack of zero point accuracy as well as poor flow sensitivity because the mechanical deflection of a diaphragm from sensor on an orifice is used to measure the pressure drop.
Measurement techniques based on thermal principles are therefore a good solution. In the simplest of these – the hot-wire anemometer – gas flow is determined via the cooling rate of an electrically heated wire with a temperature-dependent resistor. Advanced methods use a heating element and two temperature sensors, which measure heat transport through the gas. Sensirion refers to the term “microthermal flow sensors” because in the MEMS-based flow chip solution used in its SDP3x series of flow sensors, the sensor components are embedded in a millimeter-scale silicon microchip.
The airflow from the calibrated inhaler shows excellent agreement in a laboratory setting compared to a calibrated spirometer syringe or an external flow reference.
Prospects for flow measurement in smart inhalers
Adding a diagnostic unit to the medication delivery device that the patient is already familiar with is a powerful tool in the management of asthma and COPD. Poor inhalation technique results in decreased efficacy due to reduced drug deposition in the lungs, which in turn leads to increased disease severity. The solution of guiding the patient and providing direct feedback, as well as helping the patient to control disease and increase compliance, has already been shown to improve patient outcomes with delivery devices. connected drugs currently in use.
The high percentage of patients with asthma or COPD misusing their inhaler, when a trouble-free life would generally be possible with proper disease management, will continue to drive innovation for connected delivery of drugs. Accompanying the patient in the optimal treatment of his disease, not only as a simple medical tool but as a companion device to remind, frame and give a relevant overview of the treatment and the evolution of the disease, this is the direction in which the industry is moving. to advance.
- S. Sullivan, “The Burden of Uncontrolled Asthma on the U.S. Healthcare System,“Managed Care, vol. 14, no. 8, p. 4-7, 2005.