Final Report Summary - PRESSUREOSCILLATIONS (Pressure Oscillations: A New Lung Therapy Approach)
SUMMARY
The main objective of this research is to investigate the possibility of using pressure oscillations (PO) as an effective lung therapy technique to improve the use of Continuous Positive Airway Pressure (CPAP). Devices for Obstructive Sleep Apnea (OSA) treatment. Theoretical modeling and clinical trials were conducted and were very successful in achieving the objectives of this research.
1. INTRODUCTION
Over the last three decades the continuous positive airway pressure (CPAP) device has been used as an effective way for the treatment of obstructive sleep apnea (OSA). It provides air at an elevated pressure through a nasal or facial mask, creating a pneumatic splint that keeps the pharyngeal airway open during inspiration and expiration. Approximately 2% of women and 4% of men in the middle-aged work force meet the minimal diagnostic criteria for sleep apnea syndrome.
While CPAP has been found to be an effective treatment of OSA, a number of drawbacks and negative impacts have been found for the current CPAP device. Over 45% of CPAP patients report negative side effects including discomfort, crusting or dry nose, nasal congestion (itching or rhinorrhea). Some possible negative physiological impacts caused by the effect of CPAP on cerebral blood flow have been reported in the literature. Long term use of CPAP has also shown significant changes in nasal mucosa morphology.
In recent years pressure oscillations (PO) superimposed on the breathing cycle has been an innovative and effective way of treating several lung ailments including Asthma and Respiratory Syndrome. Lab experiments have demonstrated that PO can reduce forces in contracted airway smooth muscles which are the main driving mechanism for asthma attack. It has been shown that PO can improve lung compliance, inflammatory stresses on patients and preserves surfactant function. However, investigation of PO as a treatment for OSA has not been conducted.
A controllable pressure oscillation CPAP (CPO-CPAP) has been recently developed by the IIF. This device produces pressure and oscillations in the range of previously accepted safe values and has been tested on several healthy subjects showing nearly zero discomfort. It is believed that the CPO-CPAP will be able to achieve the same treatment effectiveness of the currently used CPAP but with lower titration pressures and better improvements to patient’s conditions. However, the CPO-CPAP has not been formally evaluated for the treatment of OSA under relatively lower titration pressure.
The goals of this research may be summarized in two parts:
Part A: To investigate the potential of PO as a new treatment for OSA by conducting clinical trials and designing a theoretical model to support those trials. This will focus on: (1) conducting some theoretical modeling to determine some of the critical design parameters for this new technique, (2) conducting clinical trials to assess the usefulness of PO in reducing CPAP requirements.
Part B: There are several expected achievements from the Marie Curie Fellowship. These include, but are not limited to: Publishing the research, Presenting the results at conferences, Presenting seminars in several universities and medical devices organisation, and set recommendations for future research in this area.
2. Part A- RESEARCH DEVELOPMENT
This is the main part of the investigation and it covers some theoretical modeling and clinical trials.
2.1 Theoretical Estimation
Before starting the clinical trials some variables had to be theoretically determined in order to set the experimental setup on specific running variables. The IIF has developed some theoretical models which were essential for conducting the clinical trials. Those models have resulted in determining the necessary parameters for running the experiments.
A computer model was developed using ANSYS software to determine some of the critical parameters necessary to be implemented in the experimental setup. These include determining the natural frequencies for the back of the mouth, the uvula and other parts of the upper respiratory system. These calculations were conducted for the following scenarios:
(1) For tissue with a practical range of moisture content,
(2) Tissue with various values of physical properties such as the modulus of elasticity.
(3) As running the program is time consuming, first idealized tissue dimensions were used just to have an initial estimation of the necessary parameters and variables for the clinical trials.
(4) Accurate data were then obtained from previous upper airway MRI tests. These data were used to determine more accurate variables to be implemented in the clinical trials.
At the end of this stage specific range of parameters were recommended to be used in the experimental trials.
2.2 Clinical Trials
For Part A of the objectives, the research undertaken under this project was conducted in three stages as follows:
2.2.1 Stage one- September-November 2012
The experimental setup was shipped from the IIF labs in Auckland, New Zealand. The equipment arrived close to the end of September 2012. Upon reassembling the experimental setup, it was discovered that parts of the experimental setup were damaged due to shipment. The IIF has gone through a comprehensive redesigning and assembling of the equipment including purchasing necessary devices to have a more accurate setup.
After the experimental setup was completely ready, the medical collaborators at Lausanne University Central Hospital (CHUV) decided to conduct the trials in two steps. The first step is to determine the suitability of PO method by conducting trials on few patients including some healthy subjects. The success of this stage will help to identify the critical operation parameters and the next step in the research and whether to have more trials or change the procedure.
2.2.2 Stage two- Preliminary Clinical Trials- December 2012-March 2013
Appropriate ethical approvals were obtained though the Lausanne Central Hospital. After discussion and for convenience it was decided to use the hospital data collection software rather than the one with the experimental setup. The team at CHUV started identifying some subjects for the initial stage of the investigation. The following procedure was adopted:
1. Trials were conducted on the research team first in order to make sure of the safety and effectiveness of the methods. The experimental setup was tested on four subjects: 2 medical doctors, one research assistant and the IIF. The outcome of this step assured the safety and the comfort of the PO method adopted within the current experimental setup.
2. Based on step-1, the medical team recommended undertaking three more trials on unhealthy subjects. Three subjects with serious OSA symptoms were recruited and their consents were taken according to the ethical approval protocol. Each subject was tested under CPAP machine for a full night and then tested under the CPO-CPAP setup for the next night.
3. Data were recorded using the hospital recording unit and then analysed by the medical doctors.
The main results from this step were very successful and encouraging to move to the next extended stage of clinical trials.
2.2.3 Stage three-Extended Clinical Trials- April-August 2013.
After the success of the first stage, the medical team decided to conduct more clinical trials. 15 unhealthy subjects were recruited and treated with the new method. As in the previous stage, each patient was tested under two conditions:
(1) First night under CPAP alone and
(2) Second night using CPO-CPAP.
All the subjects had to fill an appropriate consent form. Also all subjects have shown positive response and acceptable tolerance for the current treatment method. Data was stored on the hospital computer for further analysis.
Data were later analysed by the research team and final comparison tables were obtained.
2.3 Results
The results of the clinical trials were successful with positive findings. The main outcome of this work has demonstrated that most of the tested subjects had good feedback about the technology. The proposed method has managed to reduce the titration pressure to 70% of its value with a significant reduction in the apnoea index (AI). Based on the success of the experiments, an IP application is under discussion to protect the finding of the present work.