Apparatus and method for assisting breathing

Abstract

To provide apparatuses and methods of use for treating a subject in need of assistance with breathing, where, in some embodiments, the subject suffers from airflow obstruction or the subject suffers from chronic obstructive pulmonary disease.SOLUTION: A method of treating a subject comprising: (a) sensing when a subject is exhaling; and (b) delivering a stimulus to the subject's thorax or abdomen during at least part of the expiratory phase of breathing in response to said sensing, so as to assist the subject with exhalation. The method includes decreasing the subject's end expiratory lung volume (EELV) as compared with the subject's EELV when unassisted.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 61 / 436,010, filed January 25, 2011, which is incorporated herein by reference in its entirety. [Background technology]

[0002]

[0002] Diseases affecting the respiratory system are significant causes of morbidity and mortality. Chronic obstructive pulmonary disease (COPD) is a common disease whose prevalence is expected to increase significantly over the next 20 years. COPD can have a debilitating effect on patients' daily functioning and quality of life. Pharmacological therapies, such as bronchodilators and corticosteroids, are widely used in the treatment of COPD. Various non-pharmacological treatments are also available. However, a significant proportion of patients experience persistent symptoms despite such interventions. There is a need for innovative approaches to help manage COPD. Summary of the Invention [Problem to be solved by the invention]

[0003]

[0003] In some aspects, the present invention provides methods of treating a subject, the methods comprising: (a) sensing when the subject is exhaling; and (b) delivering a stimulus to the subject's chest or abdomen during at least a portion of the expiratory phase of breathing in response to the sensing to assist the subject's exhalation. In some embodiments, the subject is suffering from chronic obstructive pulmonary disease (COPD). In some embodiments, the subject is suffering from pulmonary hyperinflation. In some embodiments, performing the method reduces the subject's end-expiratory lung volume (EELV) compared to the subject's EELV when unassisted. In some embodiments, the subject has an abnormally high EELV in the absence of the stimulus. In some embodiments, the subject is suffering from dynamic hyperinflation in the absence of the stimulus. In some embodiments, step (a) comprises detecting respiratory movement of the subject's chest or abdomen. In some embodiments, step (a) comprises detecting respiratory movement of the subject's chest or abdomen using inductive plethysmography. In some embodiments, step (a) comprises detecting respiratory movement of the subject's chest or abdomen using strain gauges. In some embodiments, sensing is performed at least in part using a sensor incorporated into an adhesive patch suitable for placement on the subject's skin. In some embodiments, sensing occurs external to the subject. In some embodiments, the stimulus is delivered external to the subject. In some embodiments, sensing occurs external to the subject and the stimulus is delivered external to the subject. In some embodiments, the sensor, the device, or both are incorporated into clothing or a belt. In some embodiments, the sensor and the device are incorporated into the same clothing or belt. In some embodiments, step (b) comprises delivering electrical stimulation to one or more expiratory muscles and / or to efferent nerve(s) supplying one or more expiratory muscles, the stimulation being sufficient to cause contraction of the muscle(s) or increase the expiratory force generated by the muscle(s). In some embodiments, step (b) comprises delivering electrical stimulation to one or more abdominal muscles. In some embodiments, step (b) comprises delivering electrical stimulation to the rectus abdominis muscle.In some embodiments, step (b) comprises delivering electrical stimulation to one or more lower internal intercostal muscles of the anterior chest. In some embodiments, step (b) comprises mechanically compressing the subject's abdomen or lower anterior chest. In some embodiments, step (b) comprises applying pressure to the subject's abdomen or lower anterior chest using an inflatable compartment. The method includes mechanically compressing the subject's abdomen or lower anterior chest using a device that can be adjusted to accommodate the stimulation. In some embodiments, the stimulation is not delivered while the subject is inhaling. In some embodiments, the method further includes determining that the subject has at least one sign or symptom indicative of an abnormally high EELV. In some embodiments, the method further includes determining that the subject has COPD. In some embodiments, the stimulation is delivered near the beginning of exhalation, e.g., within 0.01 seconds and 0.25 seconds of the beginning of exhalation. In some embodiments, the stimulation is delivered during some but not all respiratory cycles within a session. In some embodiments, the method includes analyzing the subject's breathing pattern or activity level and adjusting one or more stimulation parameters based at least in part on the analysis. In some embodiments, the subject is intubated or recently extubated.

[0004]

[0004] In another aspect, the present invention provides an apparatus comprising: (a) a sensor suitable for sensing when a subject is exhaling; and (b) a device adapted to deliver stimulation to the subject's chest or abdomen during at least a portion of the subject's expiratory phase in response to a signal generated by the sensor. According to certain embodiments of the present invention, the stimulation is effective to assist the subject's exhalation. In some embodiments, the stimulation is electrical stimulation that stimulates one or more expiratory muscle(s). In some embodiments, the device stimulates at least some abdominal muscles, e.g., the rectus abdominis. In some embodiments, transcutaneous electrical stimulation is used. In some embodiments, the stimulation is effective to assist the subject's exhalation. In some embodiments, the stimulation is effective to cause a decrease in the subject's EELV compared to the subject's EELV in the absence of the stimulation. In some embodiments, the sensor comprises a strain gauge. In some embodiments, the sensor comprises a respiratory induction plethysmography sensor or a piezoelectric sensor. In some embodiments, the sensor is incorporated into an adhesive patch suitable for placement on the subject's skin. In some embodiments, the sensor is physically connected to the device. In some embodiments, the sensor is in wireless communication with the device. In some embodiments, the device comprises means for delivering electrical stimulation to one or more of the subject's expiratory muscle(s). In some embodiments, the device comprises an abdominal muscle stimulator. In some embodiments, the device comprises a respiratory inductive plethysmography sensor or a piezoelectric sensor and an abdominal muscle stimulator. In some embodiments, the device comprises means for mechanically compressing the lower anterior chest or abdomen. In some embodiments, the sensor, the device, or both are incorporated into a garment or belt. In some embodiments, the sensor and device are incorporated into the same garment or belt. In some embodiments, the device comprises an inflatable compartment that, when inflated, mechanically compresses the subject's lower anterior chest or abdomen. In some embodiments, the device comprises a power supply. In some embodiments, the power supply is attached to the device.In some embodiments, the device comprises a control unit that allows the subject to turn the device on or off. In some embodiments, the control unit allows the device to be set into one of two or more modes. In some embodiments, the control unit allows selection of a stimulation protocol, one or more stimulation parameters, posture, and / or physical activity. In some embodiments, the device comprises a sensor, a signal conditioning unit, a controller, and a stimulation device. In some embodiments, the device comprises a controller that analyzes the subject's breathing pattern or activity level and adjusts one or more stimulation parameters based at least in part on the analysis. In some embodiments, a method of treating a subject includes providing a device of the present disclosure to the subject. In some aspects, a method of making the device includes: (a) providing a sensor suitable for sensing when the subject is exhaling; (b) providing a device adapted to deliver stimulation to the subject's chest or abdomen, where the stimulation is effective to assist the subject's exhalation; and (c) causing the sensor to communicate with the device and deliver stimulation thereto during at least a portion of the exhalation phase of the subject's breathing. and coupling the sensor and the device such that the sensor and the device can communicate with each other. In some embodiments, the apparatus comprises any of the components or features described herein.

[0005]

[0005] In some aspects, the method includes delivering electrical stimulation to one or more of the subject's expiratory muscle(s) or to efferent nerve(s) supplying the muscle(s) to cause increased contraction of at least some of the muscle(s), selectively during the expiratory phase of the subject's breathing. In some embodiments, the method includes (a) sensing when the subject is exhaling, and (b) delivering the stimulation to cause increased contraction of at least some of the muscle(s) during at least a portion of the subject's expiratory phase of breathing. In some embodiments, the stimulation is not delivered while the subject is inhaling.

[0006]

[0006] In some aspects, the apparatus comprises: (a) a sensor suitable for sensing when the subject is exhaling; and (b) a device adapted to deliver electrical stimulation to at least some of the subject's expiratory muscles during at least a portion of the subject's expiratory phase in response to a signal generated by the sensor, the stimulation being effective to cause or increase contraction of the muscle(s) during at least a portion of the subject's expiratory phase. In some embodiments, the sensor comprises a respiratory inductive plethysmography sensor, and the device is adapted to deliver stimulation to at least some of the subject's abdominal muscles. In some embodiments, the sensor, the device, or both are incorporated into clothing or a belt. In some embodiments, the sensor comprises a piezoelectric sensor, and the device is adapted to deliver stimulation to at least some of the subject's abdominal muscles. In some embodiments, the sensor stimulates at least the rectus abdominis. In some embodiments, the apparatus is capable of operating in two or more modes, and at least one mode includes delivering, in response to a signal generated by the sensor, a tactile stimulation sufficient to be felt by the subject but not effective to affect expiratory muscle contraction. In some embodiments, the timing of the tactile stimulation is selected to prompt the subject to expel at least a particular amount, or for at least a particular period of time.

[0007]

[0007] In some aspects, the apparatus comprises: (a) a sensor suitable for sensing when the subject is exhaling; and (b) a device adapted to deliver electrical stimuli to at least some of the subject's expiratory muscles during at least a portion of the expiratory phase of the subject's breathing in response to a signal generated by the sensor, wherein at least some of the stimuli are tactile stimuli, the timing of which is selected to prompt the subject to exhale sufficiently to meet a target. In some embodiments, the target includes exhaling at least a specific amount or for at least a specific period of time. In some embodiments, the apparatus comprises a controller that determines the appropriate stimuli based, at least in part, on analyzing the subject's breathing over one or more previous respiratory cycles.

[0008]

[0008] In some aspects, the present invention provides an abdominal muscle stimulation belt comprising a respiratory effort sensor. In some embodiments, the abdominal muscle stimulation belt comprises a respiratory effort sensor comprising a piezoelectric sensing element. In some embodiments, the respiratory effort sensor is an integral part of the abdominal muscle stimulation belt.

[0009]

[0009] In some aspects, the invention provides methods of promoting increased abdominal muscle strength in a subject, the methods comprising: (a) sensing when the subject is breathing in; and (b) stimulating contraction of at least one of the subject's expiratory muscles during at least a portion of the inspiratory phase of breathing in response to the sensing. In some embodiments, the subject is suffering from an obstructive respiratory disease.

[0010]

[0010] In some aspects, the present invention provides a method of assisting breathing in a subject in need thereof, comprising: (a) sensing when the subject is exhaling; and (b) in response to the sensing, delivering a tactile stimulus to the subject during at least a portion of the exhalation phase of breathing, wherein the tactile stimulus serves as a cue to assist the subject in timing the contraction of the subject's expiratory muscles. In some embodiments, the subject is instructed to continue exhaling or continuing to contract their expiratory muscles while continuing to sense the stimulus. In some embodiments, the method comprises determining, at least in part, an appropriate stimulus to deliver during exhalation based on analyzing the subject's breathing over one or more previous respiratory cycles. In some embodiments, the method comprises determining, at least in part, whether to deliver the tactile stimulus or a stimulus to stimulate contraction of one or more expiratory muscles during exhalation based, at least in part, on analyzing the subject's breathing over one or more previous respiratory cycles. In some embodiments, the subject is suffering from COPD.

[0011]

[0011] All articles, books, patent applications, patents, other publications, websites, and databases mentioned herein are incorporated herein by reference. In the event of a conflict between this specification and any of the incorporated references, the present specification (including any amendments thereof) shall control. Unless otherwise indicated, art-accepted meanings of terms and abbreviations are used herein. The term "exhalation" is used interchangeably with "expiration," "expiratory phase of breathing," or "breathing out." The term "inhalation" is used interchangeably with "inspiration," "inspiratory phase of breathing," or "breathing in." The section headings herein are for convenience only and should not be construed as limiting the invention.

[0012]

[0012] Non-limiting information regarding the risk factors, epidemiology, etiology, diagnosis, and management of COPD can be found in, for example, the "Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease" (updated 2009), available on the Global Initiative on Chronic Obstructive Pulmonary Disease, Inc. (GOLD) website (www.goldcopd.org), also referred to herein as the "GOLD report," the American Thoracic Society / European Respiratory Society Guidelines, available on the ATC website at www.thoracic.org / clinical / copd-guidelines / resources / copddoc.pdf, and the "ATC / ERS Guidelines," also referred to herein as the "ATC / ERS Guidelines." Society Guidelines (2004), and may be found in standard textbooks on internal medicine such as Cecil Textbook of Medicine (20th ed.), Harrison's Principles of Internal Medicine (17th ed.), and / or standard textbooks focusing on pulmonary medicine. [Brief explanation of the drawings]

[0013]

[0013] [Figure 1] 1 is a diagram illustrating the various lung volumes and capacities associated with breathing. Definitions and information regarding methods useful for measuring these volumes and capacities can be found, for example, in ATS / ERS Task Force Standardization of Lung Function Testing: Standardization of the measurement of lung volumes (2005). [Figure 2]1 is a graph showing static respiratory volumes and vital volumes illustrating a healthy adult (left) and an adult with COPD (right). It will be appreciated that there is variability between both healthy individuals and individuals with COPD. [Figure 3] FIG. 1 is a block diagram of a device for providing electrical stimulation to a subject's expiratory muscles, e.g., synchronized with exhalation. DETAILED DESCRIPTION OF THE INVENTION

[0014]

[0014] The present invention provides devices and methods for supporting breathing in individuals suffering from obstructive respiratory diseases. Obstructive respiratory diseases are diseases in which airflow limitation is a prominent and defining feature. Chronic obstructive pulmonary disease (COPD) encompasses a range of conditions characterized by airflow limitation that is not fully reversible even with treatment and is usually progressive. Symptoms of COPD include dyspnea (shortness of breath), decreased exercise tolerance, cough, phlegm production, wheezing, and chest tightness. Individuals with COPD may experience episodes of acute (e.g., occurring within less than a week and often within 24 hours or less) worsening of symptoms (termed COPD exacerbations), which can vary in frequency and duration and are associated with significant morbidity. They may be triggered by events such as respiratory infections or exposure to harmful particles, or may have unknown etiologies. Smoking is the most commonly encountered risk factor for COPD, and other inhalation exposures may also contribute to the onset and progression of the disease. The role of genetic factors in COPD is an area of ​​active research. A small percentage of COPD patients have a genetic deficiency of alpha-1 antitrypsin, the major circulating inhibitor of serine proteases, and this deficiency can lead to a rapidly progressive form of the disease.

[0015]

[0015] The characteristic pathophysiological features of COPD include narrowing and structural changes in the small airways and destruction of the lung parenchyma (particularly around the alveoli), most commonly due to chronic inflammation. The chronic airflow limitation observed in COPD typically involves a mixture of these factors, the relative importance of which in contributing to airflow limitation and symptoms varies from person to person. The term "emphysema" refers to the enlargement of air spaces (alveoli) distal to the terminal bronchioles, accompanied by destruction of their walls. Note that the term "emphysema" is often used clinically to refer to the condition associated with such pathological changes. Some individuals with COPD have chronic bronchitis, clinically defined as a cough accompanied by sputum production nearly every day for three months of the year for two consecutive years. Asthma is another obstructive respiratory disease, but the obstruction is usually (at least initially) reversible, i.e., with treatment and / or between asthma "attacks," the airflow through the airways of individuals with asthma is typically normal, and therefore these individuals do not have COPD. However, asthma patients may have abnormal airflow even between attacks, especially if asthma is left untreated, because the chronic inflammation associated with the disease can lead to airway remodeling, making airway obstruction at least partially irreversible. Thus, asthma patients with a fixed component of airway obstruction are considered to have COPD.

[0016]

[0016] The pathophysiological changes that occur in COPD have various adverse effects on ventilation (movement of air in and out of the lungs) and respiratory mechanics. Loss of alveolar wall and peripheral airway attachment reduces lung elastic recoil. Decreased elastic recoil, along with airway narrowing, reduces the ability of airways to remain open during expiration. Thus, airways tend to collapse prematurely during expiration. Collapse of peripheral airways during expiration obstructs airflow (sometimes referred to as "expiratory flow limitation" (EFL)), resulting in air being trapped in the lungs and leading to lung hyperinflation. Hyperinflation is considered present when the volume of gas in the lung(s) is increased compared to the predicted value for age-matched healthy individuals. Notably, COPD patients have significantly increased end-expiratory lung volume compared to healthy controls, which can result in increased total lung capacity (TLC) (see Figure 2). As known in the art, "end-expiratory lung volume" (EELV) (this term is used interchangeably herein with "functional residual capacity" (FRC)) refers to the amount of gas remaining in the lungs after passive expiration. EELV can be measured, for example, using helium dilution techniques, single- or multiple-breath nitrogen washout tests, body plethysmography, radiographic planimetry, CT scans, or other suitable methods, as known in the art. Negative expiratory pressure (NEP) techniques can be used to diagnose or assess EFL. Using this method, the degree of EFL present is assessed by examining the proportion of the expiratory phase during which airflow velocity remains unchanged when a slight negative pressure is applied to the mouth. This technique has several measurement scales, including a three-point scale, a five-point scale, and a continuous scale.

[0017]

[0017] Although tidal volume (TV) frequently remains relatively normal in individuals with COPD, periodic breathing occurs at larger-than-normal lung volumes as a result of increased EELV (see Figure 2). Residual volume (RV), the amount of air left in the lungs after a complete exhalation, is often increased in COPD, as is total lung capacity, while vital capacity remains relatively normal. Hyperinflation can be reflected by various signs on physical examination, such as relatively flat ribs, a "barrel-shaped" chest, and a prominent abdomen. Static hyperinflation refers to hyperinflation that occurs at rest and often becomes more pronounced as COPD progresses. Dynamic hyperinflation refers to an acute and variable increase in hyperinflation (e.g., as reflected by EELV) above its basal value and can occur, for example, during exercise and COPD exacerbations. It may also be assessed by measuring inspiratory volume (IC).

[0018]

[0018] COPD can lead to various changes in respiratory mechanics. Under normal physiological conditions in healthy individuals, inspiration is an active process, while expiration is passive at rest. The diaphragm is the most important inspiratory muscle. It moves downward during contraction, pushing abdominal contents downward and forward, increasing the vertical dimension of the thoracic cavity. In addition, the ribs are lifted upward and outward, expanding the thoracic cavity. The external intercostal muscles, which are adjacent to and connect with the ribs, also function in inspiration by pulling the ribs upward and forward, thus contributing to the increase in thoracic dimension. The increase in thoracic dimension generates negative pressure within the lungs, resulting in the inflow of air. Due to their elasticity, in healthy individuals under normal physiological conditions, the lungs and chest wall return to their equilibrium position after the expansion that occurs during inspiration. Therefore, expiration occurs passively. During exercise or other situations requiring increased breathing, exhalation is an active process involving the contraction of at least some of the expiratory muscles, e.g., the internal intercostal muscles, abdominal muscles (rectus abdominis, external oblique, internal oblique, and thoracic abdominal muscles). In individuals with COPD, exhalation becomes increasingly dependent on the expiratory muscles, especially during the end-expiratory phase. In addition, the increased EELV that occurs in COPD requires the inspiratory muscles (diaphragm and external intercostal muscles) to work at a higher volume than they would otherwise. "Intrinsic" positive end-expiratory pressure (PEEPi), also known as auto-PEEP, is often increased in individuals with COPD, maintaining an inspiratory threshold load on the respiratory muscles and increasing the work of breathing. Thus, for various reasons, COPD patients often breathe significantly more than healthy individuals. It takes a lot of effort and energy.

[0019]

[0019] The present invention encompasses the recognition that obstructive respiratory diseases can be treated by applying stimulation to a subject's lower chest and / or abdomen during the expiratory phase of breathing. The lower chest refers to the area of ​​the chest at or below the seventh intercostal space. In some aspects, the present invention features delivering stimulation to the lower chest and / or abdomen of a subject with an obstructive respiratory disease, where the stimulation is effective to assist the subject's exhalation. In some aspects, the present invention provides methods comprising sensing when a subject (e.g., a subject with an obstructive respiratory disease) is exhaling and delivering stimulation to the subject's lower chest or abdomen based at least in part on the sensing. In many embodiments, the stimulation is delivered to the lower anterior chest and / or abdomen. In certain embodiments, the stimulation is delivered to at least some abdominal muscles. In some aspects, the methods of the present invention reduce the subject's EELV. The present invention provides methods comprising sensing when a subject (e.g., a subject with an obstructive respiratory disease) is exhaling and delivering stimulation to the subject. Thus, the methods of the present invention involve delivering stimulation "in sync" or "in concert" with a subject's exhalation based on sensing one or more indicators of the subject's respiration. In some embodiments, the stimulation is effective to assist the subject's exhalation. In some embodiments, the stimulation is effective to train expiratory muscles to gain muscle strength and endurance. In some embodiments, a feedback system between a sensor (which senses when the patient is exhaling) and muscle stimulation teaches the patient to use the correct muscles to assist exhalation.

[0020]

[0020] As further described herein, the present invention also provides, in some aspects, devices suitable for use in one or more methods of the present invention. Thus, in one aspect, the present invention provides a device comprising: (a) a sensor suitable for sensing when a subject is exhaling; and (b) a device adapted to deliver stimulation to the subject's chest or abdomen during at least a portion of the subject's expiratory phase in response to a signal generated by the sensor. In some embodiments, the device comprises a sensor and a stimulation device that are incorporated or easily incorporated into a single unit, such as a belt, that can be worn around the subject's waist. Both (a) and / or (b) can be implantable or placed on the surface of the skin.

[0021]

[0021] In some embodiments, the methods of the present invention enhance the natural action of expiratory muscles by electrically or magnetically stimulating them or by delivering mechanical stimulation to the lower anterior chest and / or abdomen. In some embodiments, electrical stimulation delivered to expiratory muscle(s) and / or the motor nerve(s) supplying these muscles(s) will increase the force of contraction during exhalation compared to the force that would be generated in the absence of stimulation. The electrical stimulation may, for example, cause the recruitment of a greater number of motor units of one or more expiratory muscles that would be stimulated as a result of a typical motor nerve impulse in the subject, and / or cause the contraction of one or more muscles or a portion(s) of one or more muscles that would not otherwise substantially contract. While not wishing to be bound by theory, in some embodiments, the electrical stimulation may serve to automatically stimulate muscles under voluntary control, such that the subject would not need to exercise volitional control to contract such muscle(s). The mechanical stimulation may include mechanical compression of the lower anterior chest and / or abdomen, causing an increase in intrathoracic pressure, thereby assisting exhalation, at least in some embodiments.

[0022]

[0022] In some embodiments of the present invention, the effect of the stimulation is to shift the amount of periodic ventilation downward. One aspect of the present invention is the recognition that inhaling at lower lung volumes may reduce stress on the inspiratory muscles, and therefore, stimulation delivered to the inspiratory muscles has the potential to improve inspiration. For example, hyperinflation forces breathing over a higher range of lung volumes, where the inspiratory muscles are functionally weaker. Hyperinflation depresses the diaphragm vault. In some embodiments, use of an inventive device reduces such depressing of the diaphragm. By reducing hyperinflation, use of an inventive device may allow inspiratory muscle fibers(s), such as the diaphragm, to operate within a more optimal portion of their length-tension relationship. The method of the present invention may reduce inspiratory and / or respiratory muscle fatigue in patients with COPD. In COPD patients, as patients breathe more rapidly during exercise, air trapping in the lungs greatly increases, shortening the time available for exhalation and / or causing patients to begin inhaling before complete exhalation is achieved. The methods of the present invention may reduce this dynamic hyperinflation, for example, by causing air to exit the lungs more rapidly than would otherwise occur during at least a portion of exhalation, and / or by reducing the subject's EELV present at the onset of exercise.

[0023]

[0023] A feature of certain aspects of the present invention is that stimulation (whether electrical or mechanical) is appropriately timed with respect to the subject's natural exhalation to provide one or more benefits to the subject. Without limiting the present invention in any way, stimulation may result in (a) a decreased EELV compared to the subject's EELV in the absence of the stimulation, and / or (b) an increased expiratory flow rate during at least a portion of exhalation relative to the absence of the stimulation. However, stimulation preferably does not significantly increase inhalation difficulty for the subject. In at least some embodiments, stimulation does not increase the work associated with inhalation and / or does not make inhalation subjectively perceived as more difficult for the subject. In some embodiments, stimulation actually makes inhalation easier for the subject, e.g., by reducing stress on at least some muscles during inhalation and / or by making inhalation subjectively perceived as easier for the subject. In some embodiments, the methods of the present invention avoid stimulating the expiratory muscles or mechanically compressing the lower anterior chest or abdomen while the subject is inhaling (or any such stimulation is below the threshold level required to produce significant muscle contraction or compression during inhalation), and / or avoid significantly stimulating the inspiratory muscles while the subject is exhaling (or any such stimulation is below the threshold level required to produce significant contraction of the inspiratory muscles during exhalation). In many embodiments, the inspiratory muscles are not stimulated during either exhalation or inspiration (or any such stimulation is below the threshold level required to produce significant contraction of the inspiratory muscles). However, as explained herein, without wishing to be bound by theory, the subject may also benefit during inhalation. The methods of the present invention may or may not result in a change in the subject's average EELV compared to the subject's average EELV in the absence of the stimulation. The methods of the present invention may or may not result in a change in the subject's average TV compared to the subject's average TV in the absence of the stimulation. The methods of the present invention may or may not result in a change in the subject's mean respiration rate (RR).For example, some individuals suffering from obstructive pulmonary diseases such as COPD frequently take shallow breaths in an effort to compensate for their condition. The methods of the present invention may restore a more normal breathing pattern in such individuals (e.g., a higher TV and a lower RR). In other individuals suffering from obstructive pulmonary diseases, the average resting TV and RR may be approximately normal (for adults, a normal resting TV is often estimated at approximately 500 ml, and a normal resting RR is often estimated at 12-20 per minute), and the present invention may not significantly affect these values.

[0024]

[0024] The methods of the present invention may be applied for various periods of time. Such periods are called "sessions." For example, without limitation, a session may last between about 30 minutes and about 12 hours. In some embodiments, a session lasts between 1 hour and 6 hours. In some embodiments, a session lasts between 1 minute and 30 minutes. In some embodiments, a session includes multiple sub-sessions in which stimulation effective to enhance expiratory muscle contractions is delivered for relatively short periods, e.g., 1-5 or 5-10 minutes, alternating with periods in which stimulation effective to enhance expiratory muscle contractions is not delivered. The length and / or number of sub-sessions and / or periods between sub-sessions may vary independently. By way of example only, six sub-sessions, each lasting 5 minutes, may be applied over a session lasting 1 hour, with 5-minute periods between sub-sessions. In some embodiments, the length and / or number of sub-sessions and / or periods between sub-sessions are predetermined prior to the start of the session. In some embodiments, the length and / or number of sub-sessions and / or periods between sub-sessions are determined by the device during the session based, at least in part, on input from sensors providing information regarding the subject's respiration or physical activity. While not limiting the present invention in any way, it should be noted that at least some beneficial effects may occur gradually, for example, after stimulation has been applied for several breaths, as trapped air is slowly forced out of the lungs over a period of time. Thus, one or more benefits may only become apparent some time after a particular session begins. Furthermore, without wishing to be bound by theory, at least some beneficial effects may continue for a period of time after stimulation is no longer applied (i.e., after the end of a particular session). In other words, a subject may experience periods of continued benefit without continued application of stimulation. In some embodiments, sessions are timed sufficiently close together so that the subject's condition remains at least somewhat improved during the periods between sessions.It is to be understood that the present invention is not dependent on results achieved, which can reasonably be expected to vary among different subjects.

[0025]

[0025] The timing of delivery of stimulation within a respiratory cycle and its characteristics, e.g., duration and intensity, may be varied. For example, one or more of these parameters may be selected such that increased contraction of one or more expiratory muscles or increased compression of the lower anterior chest and / or abdomen occurs primarily during the first half of the expiratory phase or primarily during the second half. In some embodiments, stimulation is delivered during each respiratory cycle, while in other embodiments, stimulation may be delivered less frequently, e.g., every second, third, fourth, or fifth breath, or consecutive stimuli delivered according to a stimulation protocol may be separated by a different number of breaths. In some embodiments, stimulation is delivered between 12 and 20 times per minute, between 6 and 12 times per minute, or between 3 and 6 times per minute. In some embodiments, stimulation may be delivered substantially throughout exhalation or during only a portion of the expiratory phase of respiration, e.g., during the first or second half of exhalation. In some embodiments, delivery of stimulation begins a predetermined amount of time after the end of inspiration or a predetermined amount of time after the start of exhalation. Stimulation may be delivered during one or more time intervals during exhalation, which may be separated by intervals during which no stimulation is delivered. Furthermore, the magnitude of the stimulation may be varied continuously or discretely during such time interval(s). For example, parameters may be selected to optimize or enhance comfort and / or effectiveness for a particular subject or condition (e.g., exercise vs. rest, wakefulness vs. sleep). In some embodiments, no electrical or mechanical stimulation is delivered to the expiratory muscle(s) or to the efferents supplying them during inspiration (or the magnitude of any electrical or mechanical stimulation delivered during inspiration is not sufficient to cause contraction of the expiratory muscle(s)), and the lower anterior chest and abdomen are not mechanically compressed during inspiration.

[0026]

[0026] In some embodiments, the method includes providing a means by which an individual can control at least aspects of the stimulation. For example, the device of the present invention may have a control device that allows an individual (e.g., the subject, a caregiver, etc.) to turn the device on or off and / or select specific settings. The device may have multiple pre-programmed settings that allow one or more parameter(s) or combinations of parameters of the stimulation to be selected by the individual based on, for example, personal preference, comfort, treatment goals, and / or activity level. Examples of situations in which different stimulation parameters and / or signal adjustment procedures may be used include, for example, sleep, quiet breathing while awake (e.g., in any of various positions such as lying down, sitting, or standing), light exercise with a regular pattern (e.g., walking with little or no interruption), light exercise with an irregular pattern (e.g., activity in which the subject starts and stops walking or moving relatively frequently or at unpredictable times), etc. In some aspects, a device or method disclosed herein selects stimulation parameters and / or signal adjustment procedures based, at least in part, on the subject's breathing pattern, posture, and / or physical activity pattern. In some aspects, a device or method disclosed herein applies stimulation parameters and / or signal adjustment procedures that are selected, at least in part, on the subject's breathing pattern, posture, and / or physical activity pattern. As described further below, in some embodiments, a device is capable of distinguishing between different breathing patterns, postures, and / or physical activity patterns based, at least in part, on input from one or more sensors. In some embodiments, a method includes distinguishing between different breathing patterns, postures, and / or physical activity patterns based, at least in part, on analysis of input from one or more sensors, and, in some embodiments, delivering appropriate stimulation based, at least in part, on such analysis.

[0027] The device may be programmable so that parameters for delivering stimulation can be customized for a particular subject and stored so that a user can conveniently select parameter combinations in the future. In some embodiments, the device includes means for receiving and / or responding to voice input. For example, the device may include or access voice recognition software. In some embodiments, instructions (e.g., to turn on and off, select particular stimulation protocols, etc.) may be given to the device at least in part verbally.

[0027]

[0028] The devices and methods of the present invention may be implemented using a variety of different components, which may be combined in a variety of different ways. One aspect of the present invention is the coupling of various components (e.g., sensors, stimulation devices), for example, using an appropriate interface, so that the device as a whole functions as described herein. Suitable sensors for sensing when a subject is exhaling and appropriate electronics for interfacing the device to provide stimulation are aspects of the present invention. The interface may be implemented using hardware, software, or a combination of hardware and software, and may include analog and / or digital components. Appropriate signal processing and analysis functionality may be provided. The interface may include one or more electronic components, such as one or more amplifiers, filters, rectifiers, peak detector(s), switches, analog-to-digital converters, connectors (e.g., DIN, XLR, etc.), wires, cables, etc. In some embodiments, the device includes a signal conditioning unit, for example, as part of the interface. In some embodiments, the signal conditioning unit includes one or more amplifiers and one or more filters. The amplifier(s) may provide a signal amplification gain, for example, of 1000 to 5000, in some embodiments. In some embodiments, the device may include one or more high pass filters (e.g., as part of a signal conditioning unit). The signal conditioning system may comprise a high-pass filter (may be multiple filters) and / or one or more low-pass filter(s). The high-pass filter(s) may have a cutoff frequency, for example, in the range of 0 Hz to 1 Hz. The low-pass filter(s) may have a cutoff frequency, for example, in the range of 10 Hz to 70 Hz. Such filter(s) may be useful, for example, to eliminate or reduce noise or other artifacts. In some embodiments, different signal conditioning procedures may be utilized according to the setting. For example, different signal conditioning procedures may be used to detect or eliminate movement artifacts when the subject is walking, breathing quietly while awake, sleeping, etc.

[0028]

[0029] FIG. 3 shows an exemplary block diagram of a device in an embodiment. As depicted in FIG. 3, the exemplary device includes a sensor 10 that provides input to a signal conditioning unit 20. The signal conditioning unit 20 processes the signal (e.g., using instruments such as an amplifier, filter(s), etc.). The processed signal serves as an input to a controller 30. The controller 30 analyzes the signal, determines whether and when to provide an output to an electrical stimulator 40, and, as appropriate, delivers the output to the electrical stimulator 40. The electrical stimulator 40 generates electrical stimuli that are delivered to the subject via electrode(s) 50. In some embodiments, the control unit 30 receives additional input, such as from a user control unit (not depicted in FIG. 3) or from one or more additional sensor(s) or signal conditioning unit(s) (not depicted in FIG. 3) that processes signals from such sensor(s). For example, in some embodiments, the controller 30 receives input from a user control unit that selects one or more stimulation parameters or selects a particular stimulation protocol or mode. In some embodiments, in addition to providing input to the electrical stimulator 40, the controller 30 provides input to one or more devices, such as a computer, a display, a data storage unit, an electronic transmission device, etc.

[0029]

[0030] Materials, components, and parts for use in the devices of the present invention may be selected to provide a comfortable, relatively lightweight, portable device that can be conveniently used by a subject. In some embodiments, materials, components, and parts may be selected so that the total weight of the device is about 0.5 kg to 2 kg or less. In some embodiments, the device is wearable and light enough so that, at least in some embodiments, a subject can perform most activities of daily living while using the device. In some embodiments, the device is simple and convenient for a subject to wear and use, so that the subject can adopt the device with minimal or no assistance.

[0030]

[0031] In some embodiments, the devices of the present invention, in addition to providing breath sensing and stimulus delivery as described herein, collect, store, analyze, display, and / or transmit physiological data from a subject. In some embodiments, the devices of the present invention may be used to sense various characteristics of a subject's breathing (in addition to the sensing required to determine when a subject is exhaling) and / or to detect or measure other physiological variable(s) or event(s), such as heart rate, blood pressure, oxygen saturation, temperature, etc. The devices may detect, collect, and optionally analyze, store, and / or transmit, for example, respiratory frequency, tidal volume, work of breathing, events such as coughing, and / or any other physiological variable(s) or event(s) of interest. Information may be stored in the device, downloaded to a computer or data storage device, and / or transmitted (e.g., wirelessly) to a remote location, either directly by the device or by the computer. In some embodiments, the technology used in LifeShirt® (VivoMetrics; Ventura, CA), for example, sensing, The remote location may be used or modified for use with the device of the present invention for data collection and / or data transmission purposes. The device may provide useful monitoring of health-related variables (e.g., cardiac parameters) in addition to assisting a subject's breathing. The remote location may be, for example, a facility where personnel access data and / or are available to respond to or initiate alerts, data storage centers, etc. Electronic transmission may occur over a communications network, e.g., the Internet. In some embodiments, the remote location is at least 1 km away.

[0031]

[0032] A "computer" in the context of the present invention may be, for example, a smartphone, a personal digital assistant, a personal computer (which may be a laptop, desktop, notebook, or tablet computer), etc. Optionally, a device of the present invention interfaces with a computer, which may include or be connected to a display, keyboard, mouse, or other peripherals. Optionally, information indicative of respiration and / or indicative of operation of a device of the present invention may be visually displayed. For example, waveforms associated with respiration may be displayed, and / or stimulation parameters may be displayed. In some embodiments, one or more lung volumes or vital capacity, work of breathing, respiratory movement or effort, and / or respiratory rate, or any physiological variable of interest reported by a sensor may be displayed. Thus, the present invention provides a system comprising any device as described herein and a computer in communication with the device, either through a physical connection or wirelessly.

[0032]

[0033] Non-limiting descriptions of exemplary materials, components, parts, and packaging approaches that may be used in the devices and / or methods of the invention are described herein, for example, in the following sections. It should be understood that the invention encompasses the use of different materials, components, parts, and / or packaging means. Components, parts, materials, etc. may be freely combined in any reasonable combination, and the resulting devices and methods of use thereof are within the scope of the invention. In some aspects, the invention encompasses the modification of various components or parts, e.g., commercially available components or parts, to facilitate their use in the devices and / or methods of the invention. Such modified components or parts are aspects of the invention.

[0033]

[0034] Method and sensor for sensing exhaled breath - Patent Application 20070122997

[0035] Various approaches and sensor types may be used to sense when a subject is exhaling. Generally, sensors useful in the present invention detect any of a variety of physical quantities that change during breathing and generate a signal, typically an electrical signal, indicative of the magnitude of the physical quantity and / or the rate of change of the magnitude of the physical quantity. Thus, a sensor may comprise a detection or sensing element and a transduction element, which, for example, converts mechanical energy into electrical energy and provides an output signal in the form of a voltage or current. Such element(s) may be at least partially located within a suitable housing, which may, for example, be at least partially composed of textile, plastic, or other suitable material. The housing may provide a means for attaching the sensor to a component of a device or to a subject. In some embodiments, the sensor may be implantable and may sense one or more properties within the body (e.g., by sensing abdominal pressure). The implantable element(s) and / or their housing may be made, at least in part, from a biocompatible material suitable for implantation. The description herein of various modalities and sensors available for sensing respiration is not intended to contradict the understanding of those skilled in the art and should not be construed as limiting the present invention. do not have.

[0034]

[0036] In some embodiments of the present invention, airflow is measured, for example, using one or more pressure and / or temperature sensors. For example, a thermal sensor (which may comprise a thermistor or a pyroelectric material (e.g., a pyroelectric crystal)) generates a signal based on temperature changes driven by the warm air of exhalation and the relatively cool air of inhalation passing over the sensor and can be used to determine when a subject is exhaling. A pressure-based airflow sensor generates a signal in response to changes in pressure generated by inhalation and exhalation and can similarly be used to determine when a subject is exhaling. The pressure and / or temperature sensor may be placed nasally or orally.

[0035]

[0037] In some embodiments, changes in one or more dimensions of the chest or abdomen are detected as an individual exhales and / or inhales. The dimension(s) may include one or more of the three major dimensions of the chest: anterior-posterior, lateral, and vertical. Thus, such dimensions can detect movement associated with inhalation / exhalation and / or changes in chest and / or abdominal volume that occur with breathing. The sensor may include piezoelectric, optical waveguide, and / or electrically conductive materials. For example, the sensor may be a piezoelectric sensor that uses the piezoelectric effect to measure strain or pressure and convert it into an electrical signal. Piezoelectric sensors can be fabricated as known in the art, for example, using piezoelectric ceramic or single crystal materials. Such sensors may be used to measure airflow and / or respiratory movement. Piezoelectric sensors that include crystals output a signal when the crystals are compressed or stretched, generating a voltage. In some embodiments, the piezoelectric sensor includes a polymer with piezoelectric properties. The polymer may be provided as a film. For example, in some embodiments, polyvinylidene fluoride (PVDF), e.g., as a PVDF membrane, is used as the sensing element in a piezoelectric sensor. In some embodiments, the piezoelectric sensor indirectly represents changes in capacitance by capturing strain in a rubber band or belt that is transferred to the piezoelectric sensor. Such a belt or band is fastened around the chest or abdomen to measure changes in tension during breathing. Other types of strain gauges can be used as sensors. Electrically conductive fibers may be incorporated into the electrically conductive strip or band and used as the sensing element. In some embodiments, changes in the chest dimension(s) cause changes in the resistance of the electrically conductive strip or band. In some embodiments, changes in the chest dimension(s) cause changes in the inductance of the band's electrically conductive strip.

[0036]

[0038] Piezoelectric sensors that can be used to sense respiration, and materials useful for such sensor(s), are described, for example, in U.S. Pat. No. 6,383,143, PCT Application Publication No. WO / 2008 / 136980, and references therein. Philips Piezoelectric respiratory effort sensors and bands available from Respironics (Murrysville, PA) or Scientific Laboratory Products, Ltd. (SLP) (St. Charles, Illinois and Tel-Aviv, Israel) or Dymedix, Inc. (Shoreview, MN) may be used. For example, in some embodiments, the SleepSense™ Piezoelectric Crystal Respiratory Effort Kit (product number 1370) available from SLP, or the PerfectFit™ Effort Belt available from Dymedix, Inc., or the P1420 or P1460 or similar piezoelectric respiratory effort sensors available from Philips Respironics are used.

[0037]

[0039] Techniques for sensing respiration (and determining when a subject is exhaling) include inductive plethysmography and impedance plethysmography. Inductive plethysmography involves measurements based on the inductance or mutual inductance of conductive elements placed around a body part of a subject, for example, around the subject's chest and / or abdomen. Respiratory inductive plethysmography (RIP) in some embodiments of the present invention utilizes the principle that a changing (e.g., oscillating) current applied through a loop of wire generates a magnetic field. Suitable wires are placed around the subject's chest and / or abdomen (often around both the chest and abdomen), and a signal is transmitted through the wires. Respiratory movement changes the area surrounding the wire, thereby changing one or more characteristics of the signal (e.g., its frequency). The change in signal represents the change in area that occurs with breathing and can be used, among other things, to determine when a subject is exhaling. A RIP sensor can generate a signal representing, for example, changes in tidal volume over time. As exhalation begins, a plateau in the TV or the onset of a decrease in TV occurs. RIP sensors are well known in the art. See, for example, U.S. Patent Nos. 5,131,399, 5,913,830, PCT Publication Nos. WO / 2001 / 003581, WO / 2006 / 03429, etc. The wire of a RIP sensor is typically contained within a belt or band, which in some embodiments encircles the rib cage and abdomen at approximately the level of the nipples and navel. The band or belt may, in certain embodiments, be between about 1 and 5 cm wide. They may be at least partially made of a stretchable material or may include sections made of a stretchable material to allow for a close fit. In some embodiments, the RIP sensor comprises two sinusoidal wire coils that are insulated and disposed within two approximately 2.5 cm (about 1 inch) wide, lightweight, elastic, and optionally adhesive bands. The transducer bands are placed around the rib cage under the axillae and around the abdomen at navel level. They are connected to an oscillator and subsequent frequency demodulation electronics to obtain a digital waveform.During inspiration, the cross-sectional area of ​​the rib cage and abdomen increases, changing the self-inductance of the coils and their frequency of oscillation, with the increase in cross-sectional area proportional to lung volume. The electronics convert this change in frequency into a digital respiratory waveform whose amplitude is proportional to the amount of air inhaled.

[0038]

[0040] RIP sensors available from Philips Respironics or Scientific Laboratory Products (SLP) may be used in the devices of the present invention, for example, the zRIP DuraBelt inductance respiratory effort sensor (Philips Respironics) or SleepSense® sensor (SLP) may be used.

[0039]

[0041] In some embodiments of the invention, position sensor feedback is used, for example, to adjust the calibration of a respiration sensor, eg, a RIP sensor, for example, after a subject changes position.

[0040]

[0042] In some embodiments, impedance plethysmography is used to sense when a subject is exhaling.

[0041]

[0043] The device can include multiple sensors (e.g., 2, 3, 4, 5 or more), which can be of the same or different types (e.g., RIP and piezoelectric). The signals generated by the multiple sensors can provide a better indication of when the subject is exhaling (compared to the accuracy obtainable with a single sensor). The timing of the exhalation may be analyzed to improve accuracy in determining when, for example, in some embodiments, multiple sensor(s) must generate a signal indicative of exhalation to trigger delivery of a stimulus.

[0042]

[0044] In some embodiments, the sensor is equipped with means to allow integration or reversible attachment to clothing or a belt.

[0043]

[0045] In certain embodiments, one or more implanted sensor(s) are used, which in some embodiments may directly detect action potentials or muscle contractions.

[0044]

[0046] It should be understood that "sensing when a subject is exhaling" is used broadly to encompass any suitable method for determining an appropriate time to deliver a stimulus (e.g., within a particular respiratory cycle consisting of inhalation and exhalation), for example, to at least assist exhalation. In some embodiments, the device senses the onset of exhalation. For example, a change from inhalation to exhalation may be detected by detecting a change from inward to outward airflow and / or by detecting that one or more increasing chest dimensions have reached a plateau or are decreasing. It will be understood that the event(s) or phenomenon detected to determine when a subject is exhaling may occur during inspiration. For example, as inspiration ends during each breath, inspiratory flow rate and chest expansion rate typically decrease. A decrease in inspiratory flow rate and / or chest expansion rate may be detected and serve as a means of determining that the expiratory phase of breathing will occur shortly thereafter. It will also be understood that different sensing modalities may not produce identical results compared to those that would be obtained using, for example, spirometry. The present invention encompasses variations in the absolute timing of stimulus delivery that would result from the use of different sensing modalities, for example, compared to the timing that would occur if spirometry were used to determine when a subject is exhaling.

[0045]

[0047] Electrical or magnetic stimulation and stimulation devices

[0048] In some embodiments, the device delivers electrical or magnetic stimulation to at least some of the expiratory muscles to induce muscle contraction. Targeted expiratory muscles include the rectus abdominis, external oblique, internal oblique, and transverse abdominis. (It will be understood that the electrical or magnetic stimulation may be delivered to a portion of one or more muscle(s). In other words, stimulation may be applied to only a portion of one or more muscle(s), rather than the entire muscle.)

[0049] In some embodiments, the device employs electrical muscle stimulation, which is well known in the art. EMS uses electrical impulses to elicit muscle contraction. The impulses are generated by the device and delivered through electrodes positioned in close proximity to the muscle(s) to be stimulated and / or in close proximity to the efferent nerve(s) supplying such muscle(s). For example, the electrodes may be positioned on the skin and directly over the muscle(s) to be stimulated. The device contracts the muscle (typically repeatedly) by applying pulsed current through the skin electrodes. EMS is used for a variety of purposes, such as in physical rehabilitation after injury, pain management, and sports training. EMS devices are available, for example, from Compex Technologies, Inc. (New Brighton, MN) (now DJO, Inc., V) (owned by Ista, CA), and such machines may be used in various embodiments of the present invention to deliver stimulation to at least one expiratory muscle.

[0046]

[0050] In some embodiments, stimulation is delivered to at least one abdominal muscle. Abdominal muscles of primary interest in various embodiments of the present invention are the rectus abdominis, external oblique, internal oblique, and transverse abdominis. The rectus abdominis is a pair of muscles that run vertically on both sides of the anterior abdominal wall in humans (and some other animals). The external oblique (also known as the external abdominal oblique) is the largest and most superficial (outermost) of the three squamous muscles of the anterior lateral abdomen. The internal oblique is a medial abdominal muscle located directly below the external oblique and directly above (superficially) the transverse abdominis. The transverse abdominis is a muscle layer of the anterior and lateral abdominal wall that lies deep to (layers below) the internal oblique. Nerves that supply one or more abdominal muscles include the lower five intercostal nerves, the subcostal nerve, and the iliohypogastric nerve.

[0047]

[0051] The number, shape, and location of the electrodes can vary and may be selected by one skilled in the art. For example, in some embodiments, between 2 and 16 electrodes may be used. In some embodiments, between 3 and 8 electrodes may be used. The electrodes may be substantially square, rectangular, circular, or have other shapes. Exemplary side(s) lengths of rectangular electrodes may range, for example, from about 4 cm to 16 cm. In some embodiments, at least some of the electrodes are elongated, strip-like (e.g., about 2-4 cm wide and about 12-20 cm long). The location of one or more of the stimulation electrodes may be selected to primarily stimulate, for example, the rectus abdominis muscle, or a portion(s) thereof. In some embodiments, the rectus abdominis and external oblique muscles are stimulated. In some embodiments, the electrodes are positioned on the abdomen below the costal margins and above the connective tissue. The electrodes may be positioned approximately symmetrically around the midline. In some embodiments, a single electrode is positioned approximately above the midline, and one or more electrodes are positioned approximately symmetrically on either side of the midline (e.g., one on each side). In some embodiments, the electrode or electrode arrangement may be approximately V-shaped and positioned symmetrically around the subject's midline with the tips pointing downward. In some embodiments, one or more pairs of elongated, strip-like electrodes may be positioned, for example, extending diagonally downward below the costal margins on either side of the midline. In some embodiments, the electrodes are positioned on the posterior chest to stimulate nerve roots supplying expiratory muscles. It will be understood that current may be delivered through one or more of the electrodes and returned through a different electrode(s). Furthermore, not all electrodes may be "active" during a given respiratory cycle. For example, it may be desirable to alternate between stimulating two or more different muscles or muscle groups in alternating respiratory cycles, or in consecutive respiratory cycles in which stimulation is delivered.

[0048]

[0052] The characteristics of the electrical stimulation (also referred to herein as "stimulation parameters") can be selected by one skilled in the art to cause contraction of at least some expiratory muscle(s) without adverse effects such as unacceptable discomfort or heat. Stimulation characteristics that may be selected include, for example, frequency, amplitude, duty cycle, pulse shape, pulse width, pulse duration, etc. In some embodiments, the stimulation delivered synchronously with expiration comprises a pulse train delivered between 1 Hz and 200 Hz, with a stimulation amplitude between 30 mA and 500 mA, and a pulse width between 10 μs and 100 μs, for a duration between 0.1 and 2 seconds. In some embodiments, the voltage is between 0.1 V and 5 V. It will be understood that various suitable combinations of parameters can be selected within or outside the foregoing ranges. In some embodiments, pulses between 100 μs and 1,000 μs are used. A wide range of stimulation voltages may be used. In some embodiments, a voltage between 5 V and 300 V may be used. In some embodiments, a voltage between 50 and 200 V, e.g., about 100-150 V, may be used. In some embodiments, a voltage of up to about 300 V and / or a current of up to about 100 mA may be used, e.g., with a stimulation duration of about 0.1 to 0.5 ms. In some embodiments, a high-voltage stimulation voltage of up to 1000 V and / or a current of up to 1000 mA or more may be used, e.g., with a very short stimulation duration. When stimulation is delivered externally, stimulation parameters may be selected, at least in part, based on the different depths within the body to which the stimulation is delivered.

[0049]

[0053] In some embodiments, the stimulation delivered synchronously with expiration consists of a single pulse. In some embodiments, the amplitude of one or more pulses varies within expiration. For example, the pulse(s) may be triangular, square, rectangular, sinusoidal, partial sinusoidal, sawtooth, etc. In some embodiments in which multiple pulses are delivered within an expiration period, the pulse width may vary. The variation in pulse magnitude and / or width may be linear. For example, a pulse train may begin with a 25 μs pulse width and increase linearly over a 1-second stimulation period, e.g., at 50 Hz, to a pulse width of approximately 300-400 μs. Non-limiting examples of stimulation parameters are: (1) a 1-second pulse at 45 Hz, a stimulation amplitude of 60-100 mA, and a pulse width of 25 μs; or (2) a single pulse with a stimulation amplitude between 50 mA and 450 mA and a pulse width of 200 μs. In some embodiments, stimulation parameters are selected to cause gradual rather than sudden contraction of the muscle(s), for example, by using varying (increasing) pulse width and / or amplitude within the stimulation period.

[0050]

[0054] In some embodiments, different electrodes may be used to deliver stimulation with different characteristics to different muscles. Furthermore, different stimulation may be delivered to different portions of muscles. For example, appropriate stimulation parameters may be selected to stimulate and cause contraction of the upper portion of the rectus abdominis, the lower portion of the rectus abdominis, the transverse abdominis, and / or the oblique abdominal muscles, and corresponding stimulation may be delivered specifically to these regions (e.g., via overlying skin electrodes). Electrode sizes and shapes may be selected from various alternatives to optimize stimulation and cause contraction of specific muscle(s) or portions thereof, and / or to avoid or minimize stimulation and contraction of other muscle(s) or portions thereof. (Note that as used herein, "optimize," "optimal," and similar terms do not require absolute optimum or "best" among all possible alternatives, but rather generally represent one or more preferred alternative(s) (e.g., for a particular purpose) among various available alternatives. Such preferred alternative(s) may include the "best" alternative for a particular purpose.)

[0055] The timing of delivery of the stimulus within the expiratory phase of breathing can vary. In some embodiments, delivery of the stimulus is triggered by the end of inspiration. In some embodiments, delivery of the stimulus is triggered by the start of exhalation (e.g., by the start of lung volume decline). For example, a change in magnitude or slope of a volume (or derived volume, such as tidal volume) detected by a sensor, or a rate of change of slope, can be used to detect the start of exhalation and / or the end of inspiration. In some embodiments, a peak detection or zero-crossing detection algorithm may be used for one or more such purposes. As described above, delivery of the stimulus can begin at a predetermined time after the end of inspiration or at a predetermined time after the start of exhalation. For example, delivery can begin between 0.5 and 2 seconds after the start of exhalation and continue for an appropriate amount of time to cause contraction of expiratory muscles, but allow sufficient time for such muscles to at least partially cease contracting before inspiration begins. In some embodiments, the stimulus lasts for between 1 and 1.5 seconds. In some embodiments, In some embodiments, stimulation delivery is timed to increase the force of expiratory muscle contraction during the last 0.5 to 1 second of exhalation. In some embodiments, a signal is provided to the stimulation device based on analysis of the subject's breathing to terminate stimulation prior to or at the onset of inspiration. Thus, in some embodiments, at least two signals are provided to the stimulation device (within a respiratory cycle), with a first signal causing stimulation delivery and a second signal terminating stimulation delivery within that respiratory cycle. It will be appreciated that the second signal may be a change in one or more characteristics of the first signal. For example, the first signal may include a waveform. Changes in the amplitude and / or frequency of the waveform may serve as the second signal. Different amplitudes and / or frequencies may encode multiple distinct commands to the stimulation device.

[0051]

[0056] A set of stimulation parameters, or a series of different sets of stimulation parameters, may be referred to as a "program" or "protocol." Different stimulation protocols may be selected, for example, to increase force production, account for different activity levels, and / or, in some embodiments of the invention, to increase muscle strength or endurance, enhance fatigue resistance, etc. In some embodiments, a protocol involves gradually changing at least some of the stimulation parameters over time. For example, stimulation may begin at a low intensity or frequency during a given session and increase in intensity or frequency, for example, over a predetermined period of time (which in some embodiments may be selected by the user), or based, at least in part, on an assessment of the subject's respiration or other parameters by the device itself.

[0052]

[0057] As described herein, in some aspects, the invention relates to using feedback from a respiratory sensor to deliver stimulation to a subject's lower chest and / or abdomen as the subject exhales, e.g., to assist the subject in exhaling. In some embodiments of the invention, at least some stimulation parameter(s) may be adjusted dynamically (e.g., on a breath-to-breath basis or over an average respiratory rate) based on input from one or more sensor(s). For example, the timing, duration, intensity, frequency, and / or location of stimulation (e.g., relative to the end of inspiration or the start of expiration) may be adjusted. In some embodiments, such adjustments are based, at least in part, on the tidal volume inspired prior to the particular exhalation at which stimulation is delivered. In some embodiments, the device analyzes the effect of stimulation on the subject's respiration and adjusts the stimulation. Thus, the invention may employ feedback to adjust, e.g., optimize, stimulation parameters.

[0053]

[0058] The stimulation can be generated, for example, using any of a wide variety of available stimulation generators or modifications thereof. In some embodiments, a constant current stimulator is used. In some embodiments, a constant voltage stimulator is used.

[0054]

[0059] In some embodiments, a commercially available abdominal muscle stimulator is used, and / or stimulation parameters employed by such a device are used, although in some embodiments, delivery of stimulation is limited to the expiratory phase of breathing. The stimulation device may, in some embodiments, be an electrical abdominal muscle stimulator in the form of a belt (and may be referred to as an abdominal tension belt). Exemplary devices that may be used to stimulate one or more abdominal muscles are described, for example, in U.S. Pat. Nos. 4,763,660, 6,341,237, U.S. Publication No. 20040039426, PCT Application Publication Nos. WO / 2000 / 041764, WO / 2006 / 121463, WO / 2006 / 113802, WO / 2010 / 136486, and the like. These and other references are described in the accompanying text. Abdominal muscle stimulators are commercially available, such as the "Flex Belt" or a device known as the "Slendertone FlexGo Abdominal Toning System." Some of these devices have been approved by the US Food & Drug Administration (FDA) for muscle conditioning purposes. See, for example, the FDA 510(k) devices under Product Code ngx. Beurer GmbH (Ulm, Germany) offers abdominal muscle stimulator belts, such as the model EM30 and EM35 abdominal toning belts.

[0055]

[0060] In some embodiments, the device of the present invention includes a RIP sensor or piezoelectric respiration sensor in signal communication with an abdominal muscle stimulator. In some embodiments, the sensor and abdominal muscle stimulator are directly connected via conductive wire or cable. In some embodiments, the sensor and abdominal muscle stimulator are both connected to a component that receives an input signal from the sensor and delivers an output signal to the abdominal muscle stimulator, causing the abdominal muscle stimulator to stimulate at least some abdominal muscles, for example, at least the rectus abdominis. The component can include appropriate electronics that analyze the signal received from the sensor, determine when exhalation is occurring, select appropriate stimulation parameters, and / or deliver appropriately timed signals to the abdominal muscle stimulator so that the abdominal muscle stimulator stimulates the abdominal muscles during exhalation.

[0056]

[0061] In some embodiments, magnetic stimulation of the expiratory muscles is optionally used in conjunction with electrical stimulation. For example, by delivering stimulation, e.g., magnetic stimulation, over the T10 spinous process, spinal nerve roots may be activated, for example, around the level of T8-T12. Stimulation may also, or alternatively, be delivered to other locations on the posterior chest in certain embodiments of the invention.

[0057]

[0062] In some embodiments of the invention, a device is at least partially implanted, e.g., in the chest or abdomen of a subject, and electrical and / or magnetic impulses are delivered internally, e.g., to the efferent nerve(s) supplying the expiratory muscles and / or to the muscles themselves.

[0058]

[0063] In some embodiments, the subject's breathing pattern is analyzed (e.g., using a spirometer) and / or one or more physical or neuromuscular characteristics, such as chest and / or abdominal dimension(s), expiratory and / or inspiratory muscle strength, sensitivity of the efferent and / or afferent nerve(s) supplying the muscle(s), etc., are assessed, e.g., prior to using the device. The analysis may be used, for example, to calibrate or select sensor(s) and / or stimulation device(s) based, at least in part, on the subject's individual breathing pattern and / or physical characteristics. Appropriate parameters or ranges of parameters for stimulation, number and / or location of electrodes, etc., may be selected (either automatically by the device itself or by a healthcare provider or other appropriately trained individual) to provide effective and well-tolerated stimulation. For example, the minimum electrical stimulation required to reliably induce effective contraction of one or more expiratory muscle(s) (e.g., the rectus abdominis muscle) or to achieve a desired level of reduction in EELV, and / or the maximum stimulation that can be delivered without causing undue discomfort, may be determined. In some embodiments, stimulation parameters (e.g., minimum current required) are used that are the minimum necessary to produce an observable (e.g., observable to the naked eye) contraction of a selected muscle or muscles in a particular subject. In some embodiments, stimulation parameters are used at a maximum level (e.g., maximum current) that the subject can reasonably tolerate. In some embodiments, the above minimum and maximum limits are not met. Stimulation parameters between are used. Thus, in some aspects, the present invention provides a respiratory assistance device that is customizable based on the individual characteristics of the subject.

[0059]

[0064] In some embodiments, the device is capable of detecting different breathing patterns, such as breathing patterns associated with coughing, tidal breathing, and breathing patterns associated with speech. In some embodiments, the device adjusts one or more stimulation parameters and / or signal conditioning procedures based, at least in part, on the detection of the different breathing patterns. For example, stimulation intensity and / or duration may be varied, at least in part, based on the breathing pattern. In some embodiments, stimulation is stopped during certain breathing types, such as breathing types associated with speech, and in at least some embodiments, stimulation is automatically resumed after the subject stops speaking. In some embodiments, the detection of different breathing patterns is performed using a statistical classifier, such as a maximum likelihood classifier or a Bayesian classifier. In some embodiments, the detection of different breathing patterns is performed using a threshold, e.g., a minimum amplitude of the sensor signal during inhalation, to distinguish between coughing and tidal breathing. In some embodiments, a set of breathing pattern “training examples” of different breathing types is acquired for a particular subject and used to generate a model or reference pattern that can later be used to assign breathing patterns to one or another category. In some embodiments, models or reference patterns are generated for subjects in various positions, e.g., lying, sitting, standing, walking. In some embodiments, an algorithm based on cross-correlation analysis of a subject's breathing pattern with one or more reference patterns of various breathing types in the subject may be used. For examples of using cross-correlation to detect and distinguish breathing patterns associated with coughing and tidal breathing, see Gollee, H., et al., Med Eng Phys. 29(7):799-807 (2007) and / or Gollee, H. et al., Technol Health Care. 16(4):273-81 (2008). Any of a variety of machine learning approaches known in the art may be used in various embodiments.In some embodiments, the apparatus includes or interfaces with an auxiliary sensor or device that detects subject movement that is not part of the respiratory cycle, such as walking, or voluntary movement during sleep, such as turning over in one's sleep. Such a sensor or device may include an accelerometer or may include electrodes placed on the arm or leg, for example. In some embodiments, input from the auxiliary sensor or device is used to determine the nature or intensity of the subject's physical activity, and in some embodiments, such information is used to adjust one or more stimulation or signal conditioning parameters. For example, in some embodiments, information regarding the subject's movement is used to determine whether input from a respiratory sensor contains artifacts resulting from movement that is not part of the respiratory cycle.

[0060]

[0065] It is also within the scope of the present invention to deliver inhibitory stimuli that inhibit contraction of one or more muscle(s) and / or inhibit conduction by one or more nerve(s). For example, it may be desirable to inhibit sensory impulses during at least a portion of the respiratory cycle. The period within the respiratory cycle during which the inhibitory stimuli are delivered may or may not overlap with the period during which stimuli that cause contractions are delivered. In some embodiments, contractions of at least some of the lower external intercostal muscles (located below the seventh intercostal space) are inhibited, while contractions of at least some of the lower internal intercostal muscles (located below the seventh intercostal space) are stimulated. Appropriate parameters may be selected to inhibit rather than induce contractions. Different sets of electrodes may be used for the different stimuli.

[0061]

[0066] For example, one, two, or more pulse generators and / or current or voltage sources may be provided to allow for convenient delivery of multiple stimuli.

[0062]

[0067] In some embodiments of the invention, at least some inspiratory muscles are stimulated (electrically or magnetically) while the subject is inhaling. In other embodiments, no such stimulation is provided (or any such stimulation is insufficient to cause contraction or a significant change in the force generated by such muscles). For example, the diaphragm is not stimulated and / or the external intercostal muscles are not stimulated (or any such stimulation is insufficient to cause contraction or a significant change in the force generated by such muscles). In at least some embodiments of the invention, stimulation is not delivered to the central nervous system. In at least some embodiments of the invention, stimulation is not delivered to the phrenic nerve.

[0063]

[0068] electrode

[0069] Various electrodes and electrode attachment means can be used in the devices of the present invention, for example, to sense and / or deliver electrical stimuli. For example, electrodes can be contained in pads that adhere to the skin. Electrodes can be disposable (intended for one-time to several uses) or intended for medium-term use (e.g., between one week and six months) or long-term use (e.g., six months or longer). Electrodes suitable for external (on-skin) or internal contact with the human body are known in the art. Electrodes can be "wet" electrodes, which require the use of a contact gel when used on the skin, or "dry" electrodes, which do not require a contact gel. In some embodiments, the electrodes are made at least in part from a conductive carbon material. In some embodiments, a conductive polymer is used. For example, a 3,4-ethylenedioxythiophene-based conductive polymer, such as PEDOT (poly(3,4-ethylenedioxythiophene)) or a PEDOT:PSS (poly(3,4-ethylenedioxythiophene)) poly(styrene sulfonate) composite, can be used to fabricate dry electrodes. Electrodes suitable for placement on the skin can be incorporated into adhesive patches or pads or attached to clothing (e.g., by sewing, snap or button fastenings, Velcro, or other fastening means). Electrodes can be independently positionable. In some embodiments, electrodes are interconnected or provided as an electrode array, e.g., arranged in a predetermined pattern relative to one another.

[0064]

[0070] Axelgard Manufacturing Co., Ltd. (Falbrook, CA) and PCP Medical, Inc. (Batavia, NY) supply a series of different electrodes that can be used in various embodiments of the present invention. For example, PALS®, UltraStim®, or ValuTrode® electrodes (Axelrod Manufacturing Co., Ltd.) may be used in various embodiments of the present invention.

[0065]

[0071] Mechanical Stimulation Devices

[0072] Devices that deliver mechanical stimulation to the lower anterior chest and / or abdomen may be implemented in a variety of ways. The mechanical stimulation typically delivers sufficient force to the subject's lower anterior chest and / or abdomen to cause an increase in intrathoracic pressure, which assists exhalation. For example, external pressure may be sufficient to push up abdominal contents and promote exhalation. As the external pressure is relaxed, for example, using gravity and / or elastic recoil forces, the abdominal contents may retract to their non-abdominal positions. It returns to the compressed position, allowing inspiration to occur.

[0066]

[0073] In some embodiments, the mechanical stimulation device includes an electroactive polymer (EAP). An electroactive polymer is a polymer that undergoes a change in size or shape when stimulated by an electric field. Examples of such polymers are described, for example, in U.S. Patent Nos. 6,249,076, 6,545,384, and 6,376,971. See also U.S. Patent No. 7,491,185 for discussion. The EAP can include a conductive polymer, an ionic polymer-metal composite (IPMC), or a reactive gel. Polyaniline, polypyrrole, polysulfone, and polyacetylene are exemplary EAPs contemplated for use (optionally, combinations thereof may also be used). The EAP may be in the form of fibers that can be woven directly into a garment or belt. The fibers may be interspersed within the garment or belt to extend circumferentially around the subject's lower anterior chest and / or abdomen in one or more substantially horizontal strips or rows, which may be separated by EAP-free regions.

[0067]

[0074] In some embodiments, the mechanical stimulation includes pneumatically driven compression. For example, the device can include one or more compartment(s) or reservoir(s) into which gas (e.g., air) can be introduced or released. The one or more compartment(s) are positioned such that expansion of the compartment(s) due to introduction of gas compresses the anterior chest and / or lower abdomen. In some embodiments, gas is moved back and forth between two compartments. During exhalation, gas is introduced into the compartment positioned above the lower anterior chest and / or abdomen, thereby compressing these areas. The gas is released (e.g., into the other compartment) before or immediately after the start of inhalation. The compartment(s) may be secured to the subject's body using a harness, yoke, or corset assembly, or equivalent. The use of pneumatic artificial muscles at least partially surrounding the subject's lower chest and / or abdomen is also envisioned. Compressed gas or a compressor may be provided.

[0068]

[0075] In other embodiments, the mechanical force is provided by a motorized belt positioned around the subject's chest and / or abdomen that tightens and then relaxes during exhalation.

[0069]

[0076] The parameters of the mechanical stimulation may be selected to provide a steady or gradually increasing compressive force, and may avoid delivering a sudden jolt to the chest or abdomen, or an overly rapid and potentially uncomfortable change in compressive force experienced by the subject. The mechanical stimulation may, for example, last for between about 0.5 and 3 seconds in various embodiments.

[0070]

[0077] power supply

[0078] The device of the present invention can include a power supply that provides electrical energy to the stimulus generator. The energy may be obtained from a suitable energy source, such as an electrical energy transfer system that provides AC voltage or an energy storage device, such as one or more batteries. The power supply may be implemented as a discrete, stand-alone device or as an integral component of the device. The power supply can include one or more batteries, which can be provided as a battery pack. The batteries may be rechargeable. The device can be plugged into a standard electrical outlet, for example, for use while the subject is not ambulatory or remains near an outlet, and to allow the batteries to be recharged. The device may include a power cord that can be inserted into the device. In some embodiments, the battery pack (or power supply) is separable from the rest of the device to allow convenient charging of one battery or set of batteries while using the other(s). The power supply may include safety features such as current or voltage limiting circuits.

[0071]

[0079] controller

[0080] In some aspects, the device includes a controller that acts as a link between the one or more sensor(s) and the stimulation device. The controller may include a processor (e.g., a microprocessor), memory (e.g., both ROM and RAM), a means for accepting one or more input(s) (e.g., from one or more sensor(s)), and a means for providing one or more output(s) (e.g., to the stimulation device). In some embodiments, a microcontroller is used, in which the aforementioned functionality is provided by a chip comprising a single integrated circuit and multiple pins for input / output. The controller may analyze signal(s) received from one or more sensor(s) and determine whether and when to provide an output to the stimulation device. For example, the controller receives signal(s) from one or more sensor(s), analyzes the signal(s), and outputs a signal to the stimulation device in response to the signal(s). The stimulation device then delivers stimulation to the subject in response to the signal from the controller. Optionally, the controller selects stimulation parameters based, at least in part, on an analysis of the signal(s) received from the sensor(s). The analysis may consider signal(s) received over multiple respiratory cycles. For example, if the respiratory rate increases over time or exceeds a predetermined value, or if the duration of exhalation decreases over time, the controller may increase one or more parameters of the delivered stimulation to produce stronger muscle contractions. In some embodiments, the controller may vary one or more stimulation parameters of a given breathing type, e.g., tidal breathing, based on sensor feedback, e.g., to account for minor fluctuations. For example, in some embodiments, if the amplitude of the respiratory signal decreases over time, e.g., over at least a certain number of respiratory cycles, an increasing intensity of stimulation is provided.

[0072]

[0081] It will be appreciated that signal processing and analysis functionality may be provided, at least in part, by the sensor(s) themselves and / or by the stimulation device. For example, the sensor may include an analog-to-digital converter and / or may be designed to provide a signal to the controller (or to the stimulation device) only when a physical quantity measured by the sensor exceeds a predetermined value.

[0073]

[0082] Computer-readable instructions stored on a computer-readable medium for performing at least a portion of the signal analysis, stimulation parameter selection, and / or other function(s) of the device are an aspect of the present invention. The computer-readable instructions may be embodied in any tangible medium (e.g., a non-transitory storage medium) and / or may utilize any computer programming language in various embodiments. The computer-readable medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device. Examples of computer-readable media include a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (e.g., an EPROM or flash memory), a portable compact disc read-only memory (CD-ROM), a floppy disk, an optical storage device, or a magnetic storage devices, etc. The computer-readable medium may, in some embodiments, be paper or another suitable medium on which a program is printed or embodied, so that the program can be captured electronically, for example via optical scanning of paper or other medium (optionally employing optical character recognition), and then compiled, interpreted, or otherwise processed in a suitable manner, if necessary, and then stored in computer memory and / or executed by a computer processor. In the context of this document, a computer-readable medium may be any medium that can contain, store, convey, propagate, or transport data or computer-executable instructions.

[0074]

[0083] Clothing or belt

[0084] In some embodiments, at least one component of the device of the present invention is incorporated into clothing, by which is meant that the component is attached to the clothing as an integral part of the clothing. For example, the sensor, electrode(s), stimulation device, and / or an electrical cord connecting two or more component(s) are incorporated into the clothing. In some embodiments, the sensor, stimulation device, or both (or one or more of the component(s)) are attached to the clothing but are easily removable, for example, by fastening means selected to allow easy attachment and detachment.

[0075]

[0085] The garment may be an upper-body garment that the subject can wear by pulling it over the head and chest. It may typically fit tightly around the chest and, in some embodiments, be a form-fitting garment that extends to and fits around at least a portion of the abdomen (e.g., the midriff). In one aspect, the present invention provides a comfortable, unobtrusive garment having at least one sensor incorporated therein, the sensor operably connected to a device adapted to deliver stimuli to the subject, the stimuli being effective to assist the subject's breathing. The garment may be an undergarment suitable for wearing under a conventional shirt or blouse (if desired). For example, the garment may be a vest or "T-shirt." In some embodiments, the garment is sleeveless, while in other embodiments, sleeves (either short or long) are provided. In other embodiments, at least the device for delivering stimuli may be incorporated into a lower-body garment that the subject wears over their legs, such as a pair of briefs or a girdle, a pair of shorts, tights, pants, leggings, or the like. The lower body garment fits around at least the abdomen and, optionally, at least a portion of the lower chest of the subject, hi some embodiments, the garment is a bodysuit or leotard-like garment.

[0076]

[0086] In some embodiments, the sensor, the stimulus delivery device, or both are incorporated into a belt worn around the waist (i.e., the portion of the abdomen between the rib cage and buttocks). The belt may be wider than traditional belts used as clothing accessories and, in some embodiments, encompasses at least a portion of the lower rib cage and / or extends downward over at least a portion of the buttocks. The belt is typically made of a flexible material so that it can encircle the subject's waist. It will typically have fastening means such as one or more buckles, hooks, snaps, buttons, or Velcro fasteners. The belt may be flexibly adjustable around the abdomen.

[0077]

[0087] The sensor and stimulation device may be incorporated into the same garment or belt, or may each be incorporated into a different garment or belt. The device is incorporated into a belt wearable around the subject's waist, while the sensor device is incorporated into upper body clothing. The sensor and device may communicate via a direct electrical connection or wirelessly. In some embodiments, the belt or clothing includes multiple sites for potential attachment of electrodes, thereby allowing an individual (e.g., the subject or a healthcare provider or other caregiver) to adjust the number and / or location(s) of electrodes (for sensing and / or stimulation delivery).

[0078]

[0088] The garment or belt may be made at least in part from a stretchable material, including highly elastic fibers such as Spandex (also known as Lycra or elastane), Darlexx, or polyurethane, to promote a snug fit, and the fibers may be blended with other fibers, such as cotton or polyester. The garment or belt may be at least in part made from a woven, nonwoven, or mesh-like fabric or textile. In some embodiments, the garment or belt is at least in part made from an elastomeric material, such as a synthetic rubber material, e.g., polychloroprene (Neoprene). The garment or belt may have a Spandex- or nylon-containing lining on at least one side for contact with the skin, e.g., to improve comfort. In some embodiments, the garment or belt comprises multiple panels or sections, at least some of which comprise a stretchable material. The garment or belt may comprise padding or cushioning or the like, or may be made in part from a soft, flexible material that may serve to protect sensitive component(s) and / or improve the subject's comfort.

[0079]

[0089] Conductive strips may be woven into or attached to garments or belts, for example, as sensors and / or to transmit signals from the sensor(s) and / or to the stimulation device. Components such as sensors or electrode(s) may be attached to garments or belts, for example, by sewing, embroidering, embedding, gluing (e.g., using a suitable adhesive that is pressure-sensitive in some embodiments), weaving, enclosing at least a portion of the component between portions or layers of fabric, using drawstrings, tabs, slots, or grooves, tape, zippers, etc. In some embodiments, sensors and / or electrodes may be printed or stamped onto the fabric. The garments or belts may be washable. In some embodiments, the garments or belts are designed to allow the sensor(s) and / or electrode(s) for delivering stimulation to be positioned in a variety of different locations. For example, the garments or belts may include multiple snap or hook discs that would allow for attachment of sensors or electrodes thereto.

[0080]

[0090] As described above, various embodiments of the present invention may use electrically conductive or piezoelectric fibers as sensors. Such fibers may optionally be an integral part of a garment or belt. For example, a garment or belt may include one or more regions, optionally in the form of strips or bands, containing conductive or piezoelectric fibers or fabric portions. Such regions may optionally extend around the subject's chest or abdomen. They may be substantially straight or may be arranged in a zigzag, sinusoidal, or similarly shaped pattern.

[0081]

[0091] The garment or belt is comprised of two or more layers of fabric through which one or more electrical cords or cables can be "threaded" to connect the various components of the device. The garment or belt may contain one or more "channels" or "tunnels." The garment or belt may include one or more "pockets" or spaces between two or more fabric layers into which one or more components of the device may be placed. For example, a power supply, controller, compression compartment, electrical impulse generator, etc. may be placed in the pockets or between the fabric layers. The pockets may be connected by channels or tunnels within the garment or belt.

[0082]

[0092] In certain embodiments, the present invention provides a wearable abdominal muscle stimulation belt comprising sensors capable of sensing when a subject is exhaling. In some embodiments, the belt comprises two or more sensor(s). The sensors may be positioned such that a first sensor contacts the right upper quadrant of the anterior abdomen and a second sensor contacts the left upper quadrant of the anterior abdomen. The sensor(s) may detect strain and / or abdominal movement associated with respiratory activity. The sensor(s) may be positioned on the belt in a preferred orientation for sensitivity and / or specificity in sensing when a subject is exhaling. In some embodiments, the sensor(s) are piezoelectric sensors.

[0083]

[0093] Specifically, it is contemplated that any one or more sensor(s) or types of sensors described herein or other suitable sensor(s) may be attached to or incorporated into an abdominal muscle stimulation belt. It is also specifically contemplated to provide an abdominal muscle stimulation belt that includes means for attaching or incorporating one or more such sensor(s). It is also specifically contemplated to use an abdominal muscle stimulation belt with sensor(s) to stimulate at least one abdominal muscle in accordance with a subject's exhalation. It is specifically contemplated to provide a device that includes an abdominal muscle stimulation belt with sensor(s) and control means that processes signal(s) from the one or more sensor(s) and triggers delivery of electrical stimulation to one or more abdominal muscles when the subject is exhaling.

[0084]

[0094] In some embodiments, the belt is equipped with means for allowing attachment of one or more sensor(s) thereto such that the sensor(s) adequately contact the subject, enabling the sensor(s) to detect when the subject is exhaling. In some embodiments, the belt comprises one or more loops (similar to belt loops found on clothing such as pants), located on the surface of the belt that will contact the subject's skin when the belt is in use. In some embodiments, the sensors are in the form of bands or strips that can be attached to the belt by sliding them through the belt loops. In some embodiments, the sensor(s) comprise tabs (e.g., short strips of material attached to or protruding from the side of the sensor) that can fit into slots or slits in the belt. The tabs may be made, at least in part, from a reasonably rigid material, e.g., a plastic material. The inner surface of the belt may alternatively or additionally comprise one or more hooks, loops, eyelets, snaps, slots, slits, grooves, or other means or features that would allow secure fastening of the sensors. Thus, the present invention encompasses the use of an attachment system, where the stimulation device, e.g., an abdominal muscle stimulation belt, comprises a first element of the attachment system and the sensor comprises a second element of the attachment system, the first and second elements being compatible with each other such that the sensor may be fixedly attached to the belt. Examples of such attachment systems and respective elements include, for example, the "male" and "female" portions of a snap, a tab and a slit / slot, a hook and loop, a hook and hook, a hook and eyelet, a button and a buttonhole. (Note that hook and loop is intended to encompass the use of miniature hooks, loops, and / or eyelets, such as, for example, Velcro.) One or more of such attachment systems may be used. Such a mounting system may be used: The first element may be provided by the belt and the second element may be provided by the sensor, or vice versa.

[0085]

[0095] In some embodiments, the sensor(s) comprise an integral part of the belt, for example, one or more sensor(s) may be sewn or fixedly adhered to the side of the belt that will contact the subject when in use.

[0086]

[0096] The location of the integral sensor(s), attachment element(s), and / or electrodes may be selected so that the sensing element(s) do not spatially overlap the electrodes, hi some embodiments, the sensing elements and electrodes are spaced along the inside of the belt or garment.

[0087]

[0097] kit

[0098] The components of the device of the present invention may be provided separately or together, for example, in a single package or "kit," in which they may be individually packaged or otherwise separated. The kit or package contains at least the sensor (and optionally associated elements, such as a band for securing the sensor) and the stimulation device (e.g., an abdominal muscle stimulator), and optionally further includes one or more of electrode(s), electrode gel, a controller, a power supply, wires for connecting the component(s), instructions for use of the device, etc. In some embodiments, the kit or package includes the abdominal muscle stimulator (e.g., in the form of a belt) and a RIP sensor or piezoelectric sensor suitable for sensing respiration. In some embodiments, the sensor is incorporated into the garment or belt. Optionally, the kit or package contains notice (e.g., a label or package insert) indicating that the device has been cleared or certified by a regulatory agency, such as the FDA, for over-the-counter and / or prescription use. In some embodiments, the notice describes one or more indications for which the device is approved. For example, in some embodiments, the notice indicates that the device is approved for use in assisting breathing, reducing hyperinflation, and / or improving exercise tolerance in subjects with obstructive respiratory disease, e.g., COPD. In some embodiments, the notice indicates that the device is approved for use in assisting weaning from mechanical ventilation.

[0088]

[0099] Features and Uses

[0100] Without limiting the invention in any way, this section provides further information relating, at least in part, to various features and uses of embodiments of the device and methods of the invention. In some aspects, the device of the invention is used to treat a subject. The subject is typically a human, although it is contemplated that the subject may be a non-human animal, e.g., a non-human primate, or a domestic animal, e.g., a pet such as a dog or cat, for treatment and / or testing purposes. In some embodiments, the subject is male. In some embodiments, the subject is female. In some embodiments, the subject is an adult, e.g., a human at least 18 years of age, e.g., between 18 and 100 years of age. Many subjects with COPD may be adults aged 40 or older. Effective treatment of some embodiments of the invention reduces the severity of one or more symptoms, signs, or manifestations of a disease, disorder, or condition during at least a portion of the time the treatment is used by the subject.

[0089]

[0101] Subjects suffering from respiratory diseases, for example, obstructive respiratory diseases such as COPD, can be diagnosed as known in the art. See, for example, the GOLD report. Increased airway resistance is evident by a decrease in forced expiratory volume in 1 second (FEV1), for example, as measured by spirometry or peak expiratory flow meter. COPD may be defined as a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1 / FVC) of less than 0.7. In some embodiments, the subject has stage II, III, or IV COPD as defined in the GOLD report, based on post-bronchodilator assessment of FEV1 / FVC and FEV1. For example, the subject may have FEV1 / FVC<0.70 and 30%≦FEV1<50% of predicted value (e.g., <50% of the value predicted for a healthy individual based on the individual's age, sex, and height), or FEV1 / FVC<0.70 and FEV1<30% of predicted value. In some embodiments, the subject has COPD symptoms that are not fully reversible with bronchodilator therapy, with an FEV1 / FVC in the lower 5% of healthy individuals in the subject's age group. Other spirometry-based definitions of airway obstruction (e.g., the British Thoracic Society definition) can be used. In some embodiments, the subject exhibits EFL, for example, as assessed using the NEP technique. For example, in some embodiments, the subject has an exhaled breath score of 1 or 2 using a 3-point scale, or a score of 0 to 4 using a 5-point scale, or an EFL of less than 50% using a continuous scale.

[0090]

[0102] In some aspects, use of an inventive respiratory support device reduces the objective or subjective effort required for a subject to exhale and / or inhale, e.g., when a subject (e.g., a subject with an obstructive respiratory condition, e.g., COPD) generally finds it easier to exhale and / or inhale when using the device than when not using the device (at the same activity level). As noted above, it should be understood that any one or more benefits provided by a device of the present invention may not be immediately apparent when a subject begins a session of using the device. For example, some time may be required for the stimulation provided by the device to result in the exhalation of air trapped in the subject's lungs. For example, the EELV may gradually decrease over a period of time after the start of the session. In some embodiments, one or more beneficial effects provided by a device of the present invention may persist for at least some time after the end of the session. For example, the effect may be evident for at least 15 minutes, e.g., between 15 and 30 minutes, after the session, or for up to 1, 2, 4, 6, or more hours after the end of the session. It should be understood that the effect may decrease over time during such a period. Thus, a beneficial effect is considered to occur if the subject experiences the effect during at least a portion of the session and / or if the subject experiences the effect after the session is completed.

[0091]

[0103] In some embodiments, use of an inventive respiratory support device results in a 5% to 75%, between 5% and 50%, or between 5% and 25% decrease in the subject's resting EELV (e.g., compared to the subject's resting EELV before the subject's first use of the device). In some embodiments, use of an inventive respiratory support system results in a 50 ml to 200 ml decrease in the subject's resting EELV (e.g., compared to the subject's resting EELV before the subject's first use of the device). In embodiments, use of an inventive device results in a 5% to 75% decrease and / or a 50 ml to 200 ml decrease in the subject's EELV during or immediately after a period of exercise, e.g., walking (e.g., compared to the subject's EELV after such exercise before the subject's first use of the device). In some embodiments, an inventive device used by a subject suffering from dynamic hyperinflation (e.g., due to a COPD exacerbation) results in a decrease in the subject's EELV that is within 125% of the EELV measured for the subject when not experiencing dynamic hyperinflation or a COPD exacerbation. In some embodiments, Use of the device of the present invention results in a decrease in the subject's EELV of no more than 150%, or in some embodiments, no more than 125% of the average predicted EELV of healthy matched subjects. As described above, the change in EELV may be present during a portion of a session using the device and / or may continue for a period of time after the session has ended. A "matched subject" will typically be reasonably matched for age, height (and / or other relevant dimension(s)), and, optionally, gender. Those skilled in the art will recognize or be able to obtain suitable standard ranges for normal EELV (or other lung volumes, vital capacities, or respiratory-related characteristics) in a subject. Assessment of EELV (or other lung volumes, vital capacities, or respiratory-related characteristics) can be performed using any of the methods described herein or other methods known in the art. Such measurements may be averaged over multiple breaths.

[0092]

[0104] Using the device of the present invention to stimulate abdominal muscles(s) may train these muscles(s), resulting in, for example, increased strength and / or endurance. Thus, the device may improve a subject's ability to exhale, independent of the direct effects of the stimulation itself. It is also contemplated that experimentation with the device may help train a subject on how to more effectively use their abdominal muscles when exhaling. For example, the device of the present invention may help a subject recognize the capabilities of their abdominal muscles and / or gain increased control over their contraction and / or their timing. Using the device of the present invention may teach a subject when to contract their abdominal muscles to exhale better. For example, the device may assist a subject with the proper timing of contraction relative to the onset of exhalation and / or the proper duration of contraction to promote one or more outcomes or goals, such as, for example, exhaling a selected volume, retaining only a selected volume in the lungs at end-exhalation, having a selected breathing rate or within a selected range of breathing rates, or efficiently utilizing respiratory muscle effort.

[0093]

[0105] In some embodiments, the device of the present invention may be used as a tool in biofeedback. Biofeedback generally refers to a process that allows an individual to learn how to change physiological activity, for example, for the purpose of improving health and / or performance, and may involve identifying various physiological functions using equipment that provides information about the activity of the system, with the goal of being able to manipulate them at will. This type of learning may occur naturally through use of the device of the present invention, may be facilitated by a trained biofeedback practitioner, and / or may be facilitated by a computer-based program. The computer program may communicate with the device and display, for example, waveforms associated with breathing, the time and / or location or intensity of stimulus delivery, and a comparison of breathing with and without stimulation. Information may be presented to the user on a display. Visual and / or auditory feedback and / or tactile feedback (e.g., electrical or mechanical) may be provided to the subject. The computer program may be written in a suitable computer language and stored on a computer-readable medium, and such a readable medium is an aspect of the present invention. The present invention provides a system comprising an apparatus of the present invention and a computer, the computer being programmed to execute instructions for providing biofeedback to a user based, at least in part, on input received from the apparatus and / or while the subject is using the device.

[0094]

[0106] In some embodiments, the device may be configured to, for example, (i) use stimulation parameters selected to stimulate contraction of one or more expiratory muscles during the respiratory cycle in which stimulation is delivered; and (ii) a second mode in which stimulation is delivered during at least some respiratory cycles that is below the level of stimulation that would be required to stimulate contraction of the expiratory muscle(s) under normal conditions of use (or in some embodiments, any effect on contraction would be negligible with respect to its effect on exhalation, as determined by one of ordinary skill in the art), but is sufficient to be felt by the subject. Stimulation as described in paragraph (ii) of the previous sentence may be referred to herein as "tactile stimulation," and the second mode may be referred to as "prompt mode." Generally, the tactile stimulation is sufficient to trigger an action potential in at least one sensory nerve, e.g., a sensory nerve supplying the skin, but, at least in some embodiments, not sufficient to trigger an action potential in a motor nerve supplying an expiratory muscle. In some embodiments, the tactile stimulation is delivered at a frequency of about 15 Hz or less. In some embodiments, when operating in the second mode, the tactile stimulation is delivered during at least 50%, 60%, 70%, 80%, 90%, 95%, or 100% of the respiratory cycle during which the stimulation is delivered. In some embodiments, stimulation parameters of the tactile stimulation are selected such that the stimulation, under normal use conditions, does not cause a detectable expiratory muscle contraction of non-contracted muscles (e.g., other than as a result of prompting the subject through sensory stimulation, as described herein below) and / or does not cause a detectable increase in the force or duration of contraction of non-contracted muscles (e.g., other than as a result of prompting the subject through sensory stimulation, as described herein below). In some embodiments, the "detectable effect" is visually observable with the naked eye. In some embodiments, the "detectable effect" is detectable by an appropriate sensor. In some embodiments, the "detectable effect" is detectable by electromyography (EMG). In some embodiments, the EMG is surface EMG. In some embodiments, the EMG is intramuscular EMG. In some embodiments, the parameters of the tactile stimulation are empirically determined for the subject.For example, in some embodiments, stimulation is selected at the minimum level required to be felt by the subject in at least 80%, 90%, 95% or more of the trials.

[0095]

[0107] In some embodiments, when in prompt mode, sensory stimuli, e.g., tactile stimuli, are provided to serve as cues for the subject regarding the timing of breathing and / or respiratory muscle contraction. For example, in some embodiments, the sensory stimuli, e.g., tactile stimuli, provide cues regarding the appropriate initiation, duration, or termination of breathing or expiratory muscle contraction, or one or more phases, for the subject to achieve a specific target, e.g., regarding exhaled volume or duration of exhalation. In some embodiments, the sensory stimuli serve as cues prompting the subject to initiate and / or maintain exhalation and / or to initiate, maintain, or increase expiratory muscle contraction. For example, the subject may be instructed to continue exhaling and / or to continue contracting their expiratory muscles as long as they continue to feel the stimuli. In some embodiments, the target is for the subject to exhale for at least a specific period of time and / or to exhale at least a specific volume. In some embodiments, the target is at least partially predetermined prior to the start of a particular training session. For example, in some embodiments, the target is for the subject to exhale for at least a selected minimum time. In some embodiments, the minimum time may be calculated on an individual basis as a percentage increase in the subject's existing exhalation time when the device is not being used. In some embodiments, the target is selected based, at least in part, on the subject's recent respiratory activity as detected by the device. For example, if the subject's exhalation phase and / or exhaled volume decrease in length over each of at least a certain number of consecutive respiratory cycles (e.g., at least three respiratory cycles), the device may prompt the subject to increase the duration of their next exhalation.

[0096]

[0108] The prompt mode can be used for any of a variety of purposes in various embodiments. For example, in some embodiments, the prompt mode is used to help a subject, e.g., a subject with an obstructive respiratory disorder, acquire a more effective breathing pattern. In some embodiments, the prompt mode is used as an exercise aid. In some embodiments, the device can operate in a mode in which sensory stimulation is delivered during some respiratory cycles and stimulation of sufficient intensity to cause enhanced expiratory muscle contraction is delivered during at least some of the other respiratory cycles. In some embodiments, the device determines whether the subject has met a target, and in some embodiments, selects a course of action based, at least in part, on whether the subject has met the target. In some embodiments, the device determines whether the subject's breathing is trending in an unfavorable direction, and in some embodiments, selects a course of action based, at least in part, on whether the subject's breathing is trending in an unfavorable direction. The course of action may be, for example, if the subject fails to meet the target and / or if the subject's breathing is trending in an unfavorable direction, delivering stimulation sufficient to cause increased expiratory muscle contraction during the next exhalation, or delivering sensory stimulation (or no stimulation) if the subject has met the target. For example, stimulation causing increased expiratory muscle contraction may be delivered if the subject is unable to meet the target or if the subject's breathing is trending in an unfavorable direction. In some embodiments, the unfavorable direction is a direction indicating an increase in the length of the subject's expiratory phase. In some embodiments, the unfavorable direction is a direction suggesting that the subject is developing hyperinflation or that hyperinflation is worsening. In various embodiments, any reasonable period of time may be selected to determine whether the subject's breathing exhibits a trend. For example, in some embodiments, a trend is detected by analyzing the subject's breathing over a period of between 5 and 100 breaths, or over a period of between 30 seconds and 5 minutes.

[0097]

[0109] In some embodiments, the sensory stimulus includes electrical stimulation. The intensity, nature, and / or other characteristics of the sensory stimulus may be selected and / or customized appropriately for a particular subject. For example, an electrical stimulus that does not induce enhanced expiratory muscle contraction but is reliably perceived by the subject may be selected based on experimentation. In some embodiments, the sensory stimulus is provided using any one or more electrodes. In some embodiments, the electrodes deliver either tactile stimulation or stimulation sufficient to stimulate contraction, depending, for example, on the mode in which the device is operating. In some embodiments, one or more electrodes are provided solely for the purpose of delivering tactile stimulation. In some embodiments, the sensory stimulus includes auditory or visual stimulation. For example, in some embodiments, the device includes or is interfaced with a unit that functions as a sensory stimulus, is capable of emitting one or more sounds, is equipped with one or more lights (e.g., light-emitting diodes), or the like. In some embodiments, the device provides information regarding the extent to which the subject has achieved a particular respiratory cycle, time interval, or session target.

[0098]

[0110] In some embodiments, the device may be capable of operating in a manner that stimulates one or more abdominal muscles to contract synchronously with inspiration during at least a portion of the inhalation phase. In this case, the abdominal muscles would work against the action of the diaphragm. Without wishing to be bound by theory, it is envisioned that working the abdominal muscles against resistance in this manner may be more efficient, for example, leading to greater or more rapid muscle strength gains, compared to stimulation at random times relative to the timing of the respiratory cycle or stimulation during exhalation. In some embodiments, this type of functionality may be provided as one of multiple modes of the device for use by individuals with reduced respiratory function who require respiratory assistance. In some embodiments, this type of functionality may be provided as, for example, It may be provided for use by individuals not requiring respiratory assistance, e.g., individuals with normal respiratory function, for abdominal tightening or strengthening purposes. In some embodiments, the subject's training program or monitoring may be provided, at least in part, over the internet.

[0099]

[0111] In some embodiments, use of the device of the present invention reduces the severity of at least one symptom of COPD or other respiratory disease. As described above, such an effect may be present during a portion of the session and / or may continue for a period of time after the session has ended. Such improvement may be assessed using various instruments known in the art. For example, the Modified Medical Research Council (MMRC) Dyspnea Scale, the Baseline Dyspnea Index (BDI), the Borg Dyspnea Score, and / or the Oxygen Utilization Chart (OCD) may be used. See also the GOLD report and the ATC / ERS guidelines for various approaches to symptom assessment. In some embodiments, use of the respiratory support device of the invention improves a subject's exercise tolerance. For example, a subject may exhibit improved performance in a 6-minute walk test (e.g., an increase in the distance the subject can walk in 6 minutes), a round-trip walk test, and / or a cardiopulmonary exercise test. For a discussion of the 6-minute walk test, see, for example, the ATS Statement: Guidelines for the Six-Minute Walk Test (2002). In some embodiments, use of the devices of the present invention provides a clinically meaningful benefit to a subject (e.g., a subject suffering from an obstructive respiratory disease, such as COPD) within the reasonable judgment of, for example, a healthcare provider, e.g., a physician, optionally a physician specializing in pulmonary medicine and / or experienced in treating subjects with obstructive respiratory diseases, such as COPD. In some embodiments, the benefit is evident based on measurement of one or more respiratory parameters or derived parameters. For example, in some embodiments, peak expiratory flow (PEF), expiratory volume (VE), inspiratory volume (VI), respiratory rate (RR), inspired and expired minute ventilation (MVI and MVE), and / or inspiratory volume (IC) are measured over one or more time periods and compared between the subject's unassisted breathing and device-assisted breathing.In some embodiments, the ratios of MVE and / or VE to MVI and VI, respectively, are compared between device-assisted and unassisted breathing to assess changes in hyperinflation over a selected period of time after the start of the session, e.g., 1-2 minutes, where an increase in MVE or VE to MVI or VI, respectively, indicates a decrease in hyperinflation. In some embodiments, IC is compared between device-assisted and unassisted breathing to assess changes in hyperinflation, where a greater IC for the subject during device-assisted breathing indicates a decrease in hyperinflation. While COPD is of primary interest herein, it should be understood that the devices and methods of the present invention may be used to treat, among other things, other obstructive pulmonary diseases, other conditions in which hyperinflation occurs, and that such methods of treatment are aspects of the present invention. In some embodiments, the subject has respiratory muscle weakness. Such weakness can result from a variety of causes. For example, individuals with chronic illnesses and / or who have experienced periods of prolonged physical inactivity (e.g., bed rest) may experience respiratory muscle weakness, at least in part, due to, for example, muscle atrophy. Individuals suffering from congenital or acquired neurological or neuromuscular conditions such as amyotrophic lateral sclerosis (ALS), or myopathic conditions such as myotonic dystrophy, may benefit from the use of the device of the present invention.

[0100]

[0112] In some embodiments, the subject is suffering from, for example, a COPD exacerbation, injury, surgery, infection (e.g., pneumonia, sepsis), temporary paralysis (e.g., paralysis from a cause that would reasonably be expected to result in the subject being weaned from a ventilator within a maximum of 3-6 months of onset), stroke, and / or hypotension, cardiovascular disease (e.g., heart attack, heart failure), shock, altered mental state, respiratory arrest, drug intoxication (e.g., alcohol, barbiturates), or other conditions. The subject is undergoing mechanical ventilation due to one or more central nervous system depressants, such as an acid-based hypnotic or an opiate), general anesthesia, acute lung injury (e.g., due to trauma, adult respiratory distress syndrome, smoke inhalation, or chemical lung injury), seizure (e.g., status epilepticus), coma, or any other reason. The respiratory support device of the present invention can serve as a bridge to help wean the subject from mechanical ventilation. In some embodiments, the device is used while the subject remains on mechanical ventilation, e.g., when it is deemed appropriate (e.g., within sound medical judgment) to attempt to wean the patient from the ventilator. In some embodiments, the subject is experiencing difficulty being weaned from mechanical ventilation; e.g., the subject may have failed one or more weaning attempts or experience significant difficulty adapting to weaning due to ongoing respiratory symptoms. The subject may have failed one or more spontaneous breathing attempts, e.g., one or more spontaneous breathing attempts performed using a T-piece, for example, while the subject remained intubated or during trial extubation (e.g., the subject may have required reintubation after being extubated). In some embodiments, the subject is undergoing mechanical ventilation or has recently been extubated (e.g., extubated up to 4 weeks ago) and has been undergoing mechanical ventilation for at least 1-4 weeks, e.g., 4-24 weeks, e.g., in an intensive care unit. In some embodiments, the device may be used to provide muscle stimulation while the subject remains intubated, but the ventilator does not provide ventilatory support while the device is in use, or provides only partial ventilatory support while the device is in use. Partial ventilatory support by the ventilator may include, for example, pressure support, delivery of at least a minimum number of breaths per minute (e.g., synchronized with the subject's respiratory efforts), or a combination thereof. Use of the device may, for example, help strengthen respiratory muscles (e.g., regaining muscle strength that may have been lost due to disuse) and / or assist the subject in learning or relearning effective breathing patterns.In some embodiments, the device is used during at least some period when the ventilator is providing full ventilatory support, in addition to or instead of periods when weaning is appropriate, e.g., before weaning becomes appropriate. Use of the device by a subject receiving full ventilatory support can be beneficial, for example, to reduce muscle ataxia that would otherwise likely occur. When operating in this manner, the device may provide stimulation synchronous with exhalation, based at least in part on signals received from the ventilator, and need not, but may, sense the subject's breathing.

[0101]

[0113] In some embodiments, the device may be used to assist breathing by a subject who uses, or is a candidate for, non-invasive ventilatory support, e.g., ventilatory support delivered via a mask. In some embodiments, the non-invasively delivered ventilatory support includes continuous positive airway pressure (CPAP). In some embodiments, a subject using the device may have a reduced need for, or reduced utilization of, non-invasive ventilatory support, e.g., compared to a control subject. As used herein, a subject may be considered a "candidate" for a particular treatment if, within sound medical judgment, there is at least a reasonable likelihood that the subject will benefit from the particular treatment, e.g., a likelihood sufficient to warrant serious consideration of use of the treatment or to justify a trial of the treatment.

[0102]

[0114] In some embodiments, the device may be used to support breathing by subjects who use, or are candidates for, supplemental oxygen (e.g., at least once a week, e.g., daily). In some embodiments, subjects using the device may have a reduced need for, or reduced use of, supplemental oxygen, e.g., compared to control subjects.

[0103]

[0115] In some embodiments, the subject has one, more, or all of the expiratory muscles In some embodiments, the subject does not have partial or complete paralysis. For example, the subject has not suffered a spinal cord injury (e.g., partial or complete spinal cord transection) or brain injury that causes such paralysis. In some embodiments, the subject does not have partial or complete paralysis of the diaphragm. In some embodiments, partial paralysis is characterized by reduced function of the affected muscle, but not complete loss of function. In some embodiments, the subject has normal phrenic nerve function. In some embodiments, the subject does not have paraplegia. In some embodiments, the subject does not have tetraplegia. In some embodiments, the subject does not have quadriplegia.

[0104]

[0116] The device of the present invention may be used by individuals who do not suffer from an obstructive respiratory disease or who may be asymptomatic, undiagnosed, and / or have an early stage of the disease that does not warrant treatment. In some embodiments, the subject is apparently healthy. In some embodiments, the subject has one or more diseases other than an obstructive respiratory disease. The device may be used, for example, to tone, condition, and / or strengthen abdominal muscle(s). Without wishing to be bound by theory, at least some individuals who desire to tone, condition, and / or strengthen abdominal muscles may find certain embodiments of the device of the present invention more comfortable and / or pleasant than abdominal muscle stimulation devices that deliver stimulation regardless of whether the subject is inhaling or exhaling. Patients with obstructive respiratory diseases may benefit from the tone, condition, and / or strengthening of expiratory muscle(s) that may occur as a result of using the device of the present invention. Over time, the subject's expiratory muscle(s) may become stronger and / or more fatigue-resistant.

[0105]

[0117] In some embodiments, the device may be used by a subject who is, or is reasonably expected to be, primarily or essentially completely bed- or chair-bound, e.g., due to illness or injury, for an extended period of time, e.g., a period of time sufficient to have a reasonable, within reasonable medical limits, likelihood of resulting in abdominal muscle dysfunction (e.g., loss of tone, strength, and / or muscle strength). In some embodiments, the period of time is at least two weeks, e.g., at least two to four weeks. Use of the device may, for example, reduce or prevent muscle dysfunction. In some embodiments, the subject is not mechanically ventilated and has not recently (e.g., within the past four weeks) been mechanically ventilated. In some embodiments, the subject has been mechanically ventilated within the past four weeks. In some embodiments, the subject has never been mechanically ventilated.

[0106]

[0118] The present invention encompasses embodiments that include the use of the respiratory assist device of the present invention in conjunction with additional pharmacological or non-pharmacological therapy for obstructive respiratory disorders. Such additional therapy may include the administration of any compound(s) used in the art or potentially useful for treating subjects with obstructive respiratory disorders, such as COPD. In some embodiments, use of the respiratory assist device of the present invention allows for a reduction in the use of pharmacological therapy. For example, patients may avoid or reduce the use of systemic corticosteroids. In some embodiments, subjects may receive training on how to use the device. In some aspects, the training includes breathing exercises. In some embodiments, the device of the present invention is used by subjects participating in a pulmonary rehabilitation program. In some embodiments, the device of the present invention is used by subjects engaged in an exercise training program (endurance (aerobic) and / or strength training). The device may be used during and / or between sessions.

[0107]

[0119] In some embodiments, beneficial effects resulting from use of a device described herein by a subject or group of subjects may be demonstrated by comparison with a control subject or group of control subjects. In some embodiments, the control subjects are appropriately matched controls who are not using and / or will not use the device. One of ordinary skill in the art will be able to select appropriate matched control subjects. In some embodiments, matched subjects are matched for the indication for use of the device (e.g., COPD, weaning from mechanical ventilation, etc.). In some embodiments, matched subjects are also matched for the severity of their condition and, optionally, for one or more demographic variables, such as age, gender, etc. In some embodiments, a historical control subject or group of subjects is used. In some embodiments, a subject serves as their own control. For example, in some embodiments, the subject's condition during use of the device is compared to the subject's condition when not using the device, and / or the subject's condition after regular use of the device over a period of weeks or months is compared to the subject's condition that existed before they began using the device. In some embodiments, beneficial effects resulting from use of a device described herein may be demonstrated in a clinical trial.

[0108]

[0120] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. The scope of the invention is not intended to be limited to the above description, but rather is as set forth in the appended claims. In the claims, articles such as "a," "an," and "the" may mean one or more than one, unless indicated to the contrary or otherwise clear from the context. A claim or description including "or" between one or more members of a group is deemed satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process, unless indicated to the contrary or otherwise clear from the context. The invention includes embodiments in which exactly one member of a group is present in, employed in, or otherwise relevant to a given product or process. It is to be understood that the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive language, etc. from one or more of the recited claims are introduced into another claim. For example, any claim that relies on another claim can be modified to include one or more elements, limitations, clauses, or descriptive language found in any other claim that relies on the same base claim. Furthermore, where a claim recites a product (e.g., an apparatus or device), it is understood that methods of using the product and methods of making the product according to any of the methods disclosed herein are included within the scope of the present invention, unless otherwise indicated or unless it would be apparent to one of ordinary skill in the art that a contradiction or inconsistency would arise. A method of treating a subject can include providing a subject in need of such treatment (e.g., a subject having a disease or disorder affecting the respiratory system, such as COPD, and / or suffering from hyperinflation), diagnosing the subject as having such a disease or disorder, selecting the subject for treatment, and / or offering or prescribing a device of the present invention to the subject, or providing instructions regarding the use of the device, e.g., instructions for using the device for one or more purposes.

[0109]

[0121] When elements are presented as lists, it is understood that each subgroup of the elements is also disclosed, and that any element(s) can be removed from the group. The present invention provides all such embodiments. Also, when the invention or aspects of the invention are generally referred to as comprising particular elements, features, etc., it is also understood that certain embodiments of the invention or aspects of the invention consist of or consist essentially of such elements, features, etc.

[0110]

[0122] The term "approximately" or "about" in reference to a number generally includes numbers that fall within ±10%, in some embodiments within ±5%, in some embodiments within ±1%, and in some embodiments within ±0.5%, of that number, unless otherwise stated or otherwise clear from the context (unless such number would unacceptably exceed 100% of possible values). When ranges are recited, endpoints are included. Furthermore, unless otherwise indicated or otherwise clear from the context or the understanding of one of ordinary skill in the art, it is understood that values ​​expressed as ranges can assume any specific value or subrange within the stated range in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless clearly dictated otherwise by the context. Additionally, any particular embodiment, aspect, element, feature, etc. of the invention may be explicitly excluded from any one or more of the claims.

Claims

1. (a) a sensor suitable for sensing when a subject is exhaling; (b) a device adapted to deliver electrical stimulation to at least some expiratory muscles of the subject, the electrical stimulation being synchronized with an expiratory phase of the subject's respiratory cycle and effective to cause or increase contraction of the expiratory muscles to increase expiratory flow rate during at least a portion of exhalation; Equipped with A device configured to deliver the electrical stimulus in response to a signal received from the sensor.

2. 10. The device of claim 1, The electrical stimulation causes contractions of the subject's lower chest or abdomen.

3. 10. The device of claim 1, The electrical stimulation is triggered by the onset of the expiratory phase of the subject's respiratory cycle and is effective to cause or increase contraction of the expiratory muscles during at least a portion of the expiratory phase of the subject's respiratory cycle.

4. 4. The device of claim 3, The device is further adapted to discontinue the delivered electrical stimulation prior to the onset of inspiration.

5. 4. The device of claim 3, The electrical stimulation is effective to assist the subject in exhaling.

6. 10. The device of claim 1, The subject exhibits a higher than normal EELV, and the electrical stimulation is effective to result in a decrease in the subject's end-expiratory lung volume (EELV) compared to the subject's EELV in the absence of the electrical stimulation.

7. 10. The device of claim 1, The instrument, wherein the sensor comprises a strain gauge.

8. 10. The device of claim 1, The device, wherein the sensor comprises a respiratory inductive plethysmography sensor or a piezoelectric sensor.

9. 10. The device of claim 1, The device, wherein the sensor is incorporated into an adhesive patch suitable for placement on the subject's skin.

10. 10. The device of claim 1, The sensor is physically connected to the device.

11. 10. The device of claim 1, The sensor communicates wirelessly with the device.

12. 10. The device of claim 1, The device further comprises a power supply.

13. 10. The device of claim 1, The apparatus further comprising a control unit that allows a subject to turn said device on or off.

14. 10. The device of claim 1, The device comprises a controller that analyzes a subject's breathing pattern or activity level and adjusts one or more stimulation parameters selected from frequency, amplitude, duty cycle, pulse shape, and pulse width based at least in part on the analysis.

15. 4. The device of claim 3, The device comprises: (a) within 0.01 seconds to 0.25 seconds after the start of the expiratory phase; or (b) within 0.5 seconds to 2 seconds after the start of the expiratory phase the device being adapted to deliver the electrical stimulus to

16. 10. The device of claim 1, The apparatus, wherein the sensor, the device, or both are incorporated into clothing or a belt.

17. 10. The device of claim 1, The electrical stimulation comprises a pulse train delivered between 1 Hz and 200 Hz, with a stimulation amplitude between 30 mA and 500 mA, with a pulse width between 10 μs and 1000 μs, for a duration between 0.1 seconds and 2 seconds.

18. 10. The device of claim 1, The instrument, wherein the sensor is a pressure-based airflow sensor or a temperature airflow sensor.

19. 10. The device of claim 1, The subject is also receiving non-invasive ventilatory support.

20. 20. The device of claim 19, The subject is provided with a device wherein the non-invasive ventilatory assistance is delivered to the subject via a mask.

21. 10. The device of claim 1, The subject is also receiving supplemental oxygen.

22. 10. The device of claim 1, A device adapted to detect a breathing pattern associated with speaking or coughing and adjust one or more electrical stimulation parameters based at least in part on the detection of the breathing pattern.

23. 23. The device of claim 22, The one or more electrical stimulation parameters are selected from the group consisting of stimulation intensity, duration, and combinations thereof.

24. 23. The device of claim 22, When the device detects a breathing pattern associated with speech, the device stops delivering the electrical stimulation.

25. 25. The apparatus of claim 24, When the device detects that the subject has stopped speaking, the device resumes delivering the electrical stimuli.

26. 10. The device of claim 1, The device further comprises an auxiliary sensor that detects movement of the subject that is not part of a respiratory cycle.

27. 27. The apparatus of claim 26, The device is adapted to adjust one or more electrical stimulation parameters based at least in part on the detection of the movement.

28. (a) a sensor suitable for sensing when a subject inhales; and (b) a device adapted to deliver electrical stimulation to at least some abdominal muscles of the subject, the electrical stimulation being synchronized with an inspiratory phase of the subject's respiratory cycle and effective to cause or increase contraction of the abdominal muscles so as to increase muscular strength of the abdominal muscles; Equipped with A device configured to deliver the electrical stimulus in response to a signal received from the sensor.

29. The device according to claim 28, The abdominal muscles include expiratory muscles.

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