A six-month study by University of Buffalo researchers has confirmed that a hand-held respiratory device called the Lung Flute made by Buffalo-based Medical Acoustics improves symptoms and health status in patients with chronic obstructive pulmonary disease (COPD). Usually caused by smoking, COPD, which includes chronic bronchitis and emphysema, and lung infections such as bronchitis and pneumonia, is a lot less discussed than heart disease and cancer, but is the third leading cause of death in the U.S.

The Lung Flute is a small, reusable, plastic device that is non-invasive, easy to use, and drug-free. It uses sound waves to break up mucus in the lungs. Unlike other devices that rely on pressure and can’t reach deep lung mucus, the Lung Flute’s technology is based on low-frequency acoustic waves that are produced by simply blowing into the device the flute-shaped device which produces a low frequency acoustic wave that clears lung mucus.

Published on Sept. 23 in the journal Clinical and Translational Medicine, the 26-week UB randomized controlled trial demonstrates that patients using the Lung Flute experience less difficulty breathing and less coughing and sputum production than a control group, which saw no change in COPD symptoms.

The Open Source article, entitled “Lung flute improves symptoms and health status in COPD with chronic bronchitis: A 26 week randomized controlled trial“ (Clinical and Translational Medicine 2014, 3:29 doi:10.1186/s40169-014-0029-y), is coauthored by State University of New York (SUNY) University of Buffalo professor and chief, division of pulmonary, critical care and sleep medicine in the Department of Medicine, UB School of Medicine and Biomedical Sciences Sanjay Sethi, MD, who is also associated with the VA WNY Health Care System; with Jingjing Yin, PhD, who earned her doctorate at UB’s Department of Biostatistics in the School of Public Health and Health Professions; and Pamela K. Anderson, who is currently manager of the Clinical Trials Office in UBs Clinical and Translational Research Center..The electronic version of this article is and can be found online at:
http://www.clintransmed.com/content/3/1/29

The coauthors note that COPD is characterized by mucus hypersecretion that contributes to disease-related morbidity, and is associated with increased mortality. The Lung Flute is a new respiratory device that produces a low frequency acoustic wave with moderately vigorous exhalation to increase mucus clearance. The UB scientists hypothesized that the Lung Flute, used on a twice-daily basis, will provide a clinical benefit to patients with COPD manifesting as chronic bronchitis.

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They observe that despite the need for efficacious, convenient, and safe treatment for mucus hypersecretion, there are few current choices and limited data to support efficacy of the ones that do exist in COPD. The Lung Flute has been classified by the Food and Drug Administration (FDA) to the family of Oscillatory Positive Expiratory Pressure (OPEP) devices, which includes the Flutter and the Acapella. Currently available mucolytics and expectorants are of unproven efficacy in COPD, and the beneficial effects of agents such as n-acetylcysteine and carbocisteine are more likely related to their antioxidant effects rather than their mucolytic effects. Mechanical means to improve mucus clearance in hypersecretory lung conditions include Oscillatory PEP devices such as the Acapella and Flutter, chest vibration and percussion and breathing techniques. However, these have not been tested systematically in stable COPD

They point out that, unlike traditional OPEP devices that use oscillatory back pressure, the Lung Flute has a unique mechanism of action based on acoustic energy. When blown into by the patient with exhalation vigorous enough to make the device’s reed oscillate, the Lung Flute generates a sound wave of 16 to 22 Hz with an output of 110 to 115 dB using 2.5 cms H2O of pressure. This sound wave has the ability to travel down the tracheobronchial tree and vibrate tracheobronchial secretions, enhancing mucociliary clearance of the lower respiratory tract, and thereby resulting in the induction of sputum. This functionality of the Lung Flute has been applied to sputum induction for diagnostic testing and for the enhancement of mucus clearance from the lower airways and is on file with Medical Acoustics) The Lung Flute is currently FDA approved and available for patient use by a health care provider prescription for both these purposes.

The researchers conducted a 26 week randomized, non-intervention controlled, single center, open label trial in 69 patients with COPD and Chronic Bronchitis at the Veterans Affairs Western New York Healthcare System (Buffalo VA). The primary endpoint was change in respiratory symptoms measured with the Chronic COPD Questionnaire (CCQ). Secondary endpoints included general health status, assessed by the St. George Respiratory questionnaire (SGRQ), BODE (Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity). The (BODE) score was measured repeatedly in the study. “The BODE index provides a more comprehensive assessment of COPD patients,” explains principal investigator Dr. Sethi. “As the disease worsens, the BODE index goes up as it did in the control group. But for patients using the Lung Flute, the BODE index stayed flat.”

Drs. Sethi and Yin and Ms. Anderson report that while the control patients did not demonstrate any significant changes in the primary endpoint (CCQ change at 26 weeks of +0.01, p=0.8), a trend (p=0.08) to decrease (improvement) in the CCQ (-0.23 at 26 weeks) was seen with the Lung Flute. Furthermore, a significant improvement in the symptom domain of the CCQ was seen only with the lung flute (-0.42, p=0.004). Health status (SGRQ) improvement, was also only seen with the Lung Flute (-3.23, p=0.03). The BODE score increased in the control group (3.31 at baseline, 4.14 at 26 weeks), however it remained stable in the Lung Flute arm (3.16 at baseline and 26 weeks), with the changes from baseline being significantly different between the two arms (p=0.01). There was a trend for less exacerbations in the Lung Flute group (p=0.07). Adverse effects were minor, with only one patient discontinuing treatment because of lack of efficacy. Serious adverse effects seen were all determined to be unrelated to the device use.

There were two deaths in the Lung Flute group and none in the control group. There were serious adverse events in both groups, most commonly hospitalization due to COPD or co-morbid conditions. None of the deaths and serious adverse events were determined to be related to Lung Flute use. One patient complained of increased cough with the Lung Flute. There were no study withdrawals related to the adverse effects with the use of the Lung Flute. When asked at the end of the study visit, 85 percent of the patients that were randomized to the lung flute indicated that they found the device to be efficacious and would like to continue using it as a regular part of their COPD care regimen.

In addition to the improvements in symptoms and health status, several of the secondary endpoints also demonstrated the benefit of the Lung Flute in COPD. The Lung Flute appeared to stabilize the BODE score, primarily through preventing the progressive decrement in 6 minute walk distance and increase in dyspnea seen in COPD. Furthermore, a trend to reduction of exacerbations was seen. These observations need to be confirmed in the future with studies that are of appropriate size and duration to definitively assess treatment benefit in these aspects of COPD.

The researchers caution that while the mechanism of action that results in clinical benefits of Lung Flute in COPD is presumed to be increased mucocilary clearance of tracheobronchial secretions, a limitation of this study was the absence of direct measurement of mucociliary clearance. Other limitations of the study include it being a single site study of relatively small size, and the lack of blinding, which is difficult in device studies. However, of note, all endpoints in this study were either patient reported outcomes (CCQ, SGRQ, mMRC) or were objective measures (Spirometry, 6 minute walk distance). Subjective investigator assessments of treatment effects were therefore avoided in this trial, minimizing bias. Furthermore, the control group clearly showed either no change or slight worsening in all these parameters as expected.

They conclude that Lung Flute is a safe and effective treatment in COPD with chronic bronchitis, providing a wide array of benefits, noting that the cost of chronic care of COPD continues to grow with expansion of the possible medication regimen that could be used in these patients, observing that each additional medication also places the patient at increased risk of adverse effects. Moreover, none of the standard treatments, inhaled bronchodilators, inhaled corticosteroids or phosphodiestrase inhibitors have demonstrated effects to improve mucociliary clearance in COPD. Consequently, the Lung Flute represents a welcome addition to the armamentarium for treatment of COPD because of its potential unique mechanism of action, low cost and safety.

“This study confirms that the Lung Flute improves symptoms and health status in COPD patients, decreasing the impact of the disease on patients and improving their quality of life,” says Dr. Sethi in a UB release. “[It]confirms and extends the results of a previous, 8-week study of 40 patients that was conducted in 2010 to obtain FDA approval for the Lung Flute.” The device is approved by the Food and Drug Administration (FDA) to treat COPD and other lung diseases characterized by retained secretions and congestion. It also is approved by FDA to obtain deep lung sputum samples for laboratory analysis and pathologic examination.

Colleagues of Dr. Sethi’s in the UB medical school are now studying the Lung Flute for use in improving symptoms in asthma. The device is also being investigated for diagnostic use in tuberculosis and lung cancer.

Dr. Sethi, whose clinical practice is at the Buffalo VA, has led a series of clinical trials demonstrating the safety and efficacy of the Lung Flute, including those that played a key role in the FDA’s approval of the device for diagnostic and therapeutic uses. He notes that the study points to a potential decrease in exacerbations, flare-ups of respiratory symptoms, as a result of using the Lung Flute. Researchers are planning longer-term studies that will focus specifically on how the device affects exacerbations, a key part of what makes COPD patients sicker and leads to health care utilization.

Dr. Sethi notes that while similar devices have been developed for cystic fibrosis, the Lung Flute is the only one that has undergone extensive testing specifically for COPD patients. In a previous study comparing a device developed for cystic fibrosis with the Lung Flute, the Lung Flute was superior for COPD patients.

“All therapeutic studies on using the Lung Flute for COPD have been done here in Buffalo,” says Dr. Sethi. “We have the biggest database by far on using the device in COPD. The Lung Flute is the only one that has been tested and been clearly shown to benefit COPD patients.”

The research is the result of a partnership between UB and Medical Acoustics.

“Medical Acoustics has worked closely with UB’s medical school since the company’s founding in 2002,” says Frank Codella, chief executive officer at Medical Acoustics. “We are very fortunate to have had access to UBs vast resources, including medical researchers of the caliber of Sanjay Sethi and his team, to lead many of the Lung Flutes clinical trials.”

“Dr. Sethi is recognized as one of the leading COPD research professionals in the United States,” Mr. Codella continues. “His research has resulted in the Lung Flute receiving FDA clearances for both obtaining deep lung sputum samples for diagnostic use and for airway clearance therapy as well as a series of Phase IV studies such as the one being reported this week.”

Dr. Sethi comments: “The people at Medical Acoustics are open-minded and I was willing to help because I saw an unmet medical need. Our relationship satisfies my goal of getting therapies to patients, while it helps the company succeed, satisfying their goals of creating a viable business. That’s the way academia and industry partnerships should work.”

As chief of the division of pulmonary, critical care and sleep medicine, at UB, Dr. Sethi oversees clinical, teaching, research and administrative tasks related to the evaluation and treatment of adult patients with lung diseases and sleep disorders as well as critically ill patients. His practice is primarily located at the VA Medical Center (VA) in Buffalo; however, members of his division provide care at sites throughout Buffalo, including the UBMD clinic at Dent Tower, UBMD Sleep Center and other UB-affiliated hospitals.

Dr. Sethi also conducts research on COPD, and understanding why and how patients with COPD become more prone to lung infection is his main research interest. In addition to bench research in this field, he is also working to develop better ways to prevent and treat these infections by leading and participating in several clinical research studies in this field that are open to both veterans and the general public. Dr. Sethi also leads a multidisciplinary research team based at the VA that includes pulmonary and infectious disease physicians, post-doctoral scientists, nurse coordinators and research assistants. Through mentored research programs, their laboratories train undergraduate and graduate students, residents and fellows. He is additionally active in several professional organizations and has served as a consultant on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.

The research was funded by Medical Acoustics and by the UB Center for Advanced Biomedical and Bioengineering Technology, which is funded by NYSTAR, Empire State Developments Division of Science, Technology and Innovation.

Co-authors with Sethi are Jingjing Yin, PhD, who earned her doctorate at UBs Department of Biostatistics in the School of Public Health and Health Professions and Pamela K. Anderson, currently manager of the Clinical Trials Office in UBs Clinical and Translational Research Center.

For details on how to obtain a Lung Flute device, see:
http://lungflute.com/faq.php

Sources:
State University of New York (SUNY) University of Buffalo
Medical Acoustics

Image Credits:
State University of New York (SUNY) University of Buffalo
Medical Acoustics