A new research paper by Bill Brashier and Sundeep Salvi of the Chest Research Foundation, Marigold Complex at Kalyaninagar, Pune, India, notes that measuring lung function is an important component in the decision making process for patients with obstructive airways disease (OAD). Not only does lung function measurement help clinicians in arriving at a specific diagnosis, but also in evaluation of disease severity so that appropriate pharmacotherapy can be prescribed, helping to determine prognosis evaluating response to therapy.

The article, entitled “Measuring Lung Function Using Sound Waves: role of the forced oscillation technique and impulse oscillometry system” (Breathe (Sheff). 2015 Mar;11(1):57-65. doi: 10.1183/20734735.020514 ) is published in the Open Access journal Breathe.

Drs. Brashier and Salvi observe that airway obstructive diseases are becoming more prevalent due to rapid urbanization, the pressures of modern living and sheer ignorance, and contend that doctors need to constantly update their knowledge and the public must be made more aware of the risk factors, signs and symptoms of these disorders. They cite Government of India Ministry of Health estimates of 28 million people with asthma and 17 million with COPD, with projected metrics for 2016 putting the asthma figure at 35 million and COPD at 22 million.

In their Breathe paper, Drs. Brashier and Salvi note that spirometry is currently the most commonly performed lung function test in clinical practice and considered to be the gold standard diagnostic test for asthma and COPD. However, they note that spirometry is not an easy test to perform because the forceful expiratory and inspiratory maneuvers require good patient co-operation. Children aged five years or younger, elderly people and individuals with physical and cognitive limitations are unable to perform spirometry easily.

An alternative lung function measuring method known as FOT/IOS is preferable in such cases. Drs. Brashier and Salvi note that in 1956, DuBois et al. described the forced oscillation technique (FOT) as a tool to measure lung function, using sinusoidal sound waves of single frequencies generated by a loudspeaker and passed into the lungs during tidal breathing. They explain that the output was a measure of respiratory impedance (Zrs), which included the respiratory resistance (Rrs) and respiratory reactance (Xrs) measured over a range of frequencies (usually from 3 to 35Hz). These parameters provided valuable information about the mechanical properties of the airways and lung parenchyma.

The investigators observe that the FOT device’s main advantages are that the procedure is easy to perform and provides information about the lung different from that yielded by spirometer testing, and that it provides very good time resolution with measures of respiratory resistance. Early FOT instruments allowed only one sound frequency to be passed at a time, so measuring Zrs over a range of sound frequencies took a long time. However, some more recent FOT devices can process sound waves of two or three different frequencies simultaneously thus increasing efficiency and saving precious time.

A further refinement came in 1975 when Michaelson et al. developed a computer-driven loudspeaker output to apply bursts of square wave oscillatory pressures of multiple sound frequencies and analyzed the pressure-flow relationship using spectral analysis. This improvized technique of FOT that could use multiple sound frequencies at one time was called the impulse oscillometry system (IOS). Drs. Brashier and Salvi note that temporal resolution of IOS is slightly inferior to FOT and it sends pulses of pressure waves inside the lungs that can be a bit uncomfortable for the patient. However, they say IOS provides extensive description of oscillatory pressure-flow relationships over a range of frequencies between 4 and 32Hz and gives better mathematical analyses of resistance and reactance using the fast fourier transform (FFT) technique. Moreover, the mixed multi-frequency waveform provides improved signal-to-noise characteristics, and this new technique was subsequently refined over the years by Jaeger and became commercially available in 1998.

The researchers observe that both FOT and IOS are widely used in pediatric clinics across the world as well as in several lung physiology laboratories as a valuable clinical research tool whose main advantage is that the patient needs to perform simple tidal breathing maneuvers that require less effort and co-operation than spirometry, meaning children and the elderly can therefore perform this test easily. Moreover, it can be performed in patients on ventilators and also during sleep.

They also point to one of the most remarkable features of FOT/IOS in relation to spirometry as being that it has much greater sensitivity to detect peripheral airways obstruction, noting that in most cases, spirometry does not provide a clear indication of peripheral airway obstruction regardless of whatever information is contained in the flow-volume curve and the forced expiratory flow at 2575% of forced vital capacity (FEF2575%). FOT/IOS are therefore more sensitive instruments to detect small airways obstruction in patients with asthma and chronic obstructive pulmonary disease (COPD), and more recently, the within-breath analysis of Rrs and Xrs has been shown to help differentiate between asthma and COPD and also offer more useful information about the pathophysiology of asthma and COPD, which the spirometer does not.

However, the investigators say that despite the advantages of FOT/IOS in terms of its noninvasiveness and lack of dependency on patient cooperation, the FOT has not yet become standard methodology for routine assessment of lung function in clinical practice, noting that while obtaining respiratory impedance values is easy, interpretation of resistance and reactance curves and the derived parameters requires training and experience, and is a difficult task for an untrained pulmonologist, which they deduce may be one of the main reasons why FOT/IOS has not progressed as much as it should have.

They conclude that more recently, attempts have been made to develop machine learning algorithms that help make diagnosis easy and automated, with Amaral et al. recently reporting that using k-nearest neighbor and random forest classifiers, which are different types of machine learning algorithms, it was possible to diagnose and categorize COPD airway obstruction and also assist clinicians in tracking disease progression, evaluating risk of future disease exacerbations and guiding therapy.

“These are still early days,” they observe, “but in the future we are likely to see diagnostic algorithms being developed for asthma, COPD and other lung diseases for FOT and IOS which will help clinicians tremendously.”

Dr. Bill Brashier is the Director – Scientific Operations at Genesis Institute of Cellular Medicine, and a qualified Chest specialist with training in Cell biology from the National heart and Lung Institute, Imperial College, London, UK.

Prior to his current assignment, Dr. Brashier was Head of Academic Clinical and Cell biology Research at the Chest Research Foundation in Pune, India, and also Principal Coordinating Investigator for stem cell clinical trials conducted under Regenetek Therapies, India.

He singlehandedly founded the Cell biology Unit at the Chest Research Foundation, and has been involved with stem cell research with Regenetek Therapies India, involved in autologous stem cell separation and implantation in patients with neuro-degenerative diseases, and been implemental in training doctors on disease mechanisms in India, Sri Lanka, Kenya and the Middle East.

Dr. Brashier’s current research is on development of local defense cells from circulating stem cells in humans. He is also researching the role of mesenchymal stem cells in immune-modulation in management of chronic inflammatory diseases of the respiratory and nervous system.

Dr. Sundeep Salvi is Director of the Chest Research Foundation, a state-of-the art research institute dedicated to research and education in the field of respiratory diseases, with a major focus on Obstructive Airways Diseases. Dr. Salvi is an Honorary Senior Lecturer at Imperial College, London, a Visiting Faculty at Johns Hopkins University in Baltimore, Maryland, and a PhD guide at the University of Pune, India.

After completing his specialization in Respiratory Medicine at the University of Pune, Dr. Salvi spent eight years in the UK researching effects of air pollution on the human lung, and earning a PhD from the University of Southampton. He returned to India in 2002, and helped in establishing the Chest Research Foundation, where he has been actively involved in driving research in the field of Obstructive Airways Disease and contributed significantly to that field.

Dr. Salvi’s main area of research and clinical interest is asthma and COPD, with a particular focus on in non-smoking COPD on which he was invited to write a review article for the Lancet and has been conducting pioneering research in this field in India.

Sources:
Breathe
National Center for Biotechnology Information (NCBI)
The Chest Research Foundation
Genesis Institute of Cellular Medicine

Image Credits:
The Chest Research Foundation
Genesis Institute of Cellular Medicine