Pulmonary therapy for sleep disordered breathing care

Abstract

Methods and / or devices to deliver pulmonary therapy to treat sleep disordered breathing are disclosed.

Description

PULMONARY THERAPY FOR SLEEP DISORDERED BREATHING CARECross-Reference to Related Applications

[0001] This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 63 / 543,067, filed October ?, 2023 and entitled “Pulmonary Therapy for Sleep Disordered Breathing Care,” the entire teachings of which are incorporated herein by reference.Background

[0002] Sleep disordered breathing (SDB) may dramatically affect a person’s entire health profile with significant comorbidities, such as cardiac disease. Sleep disordered breathing can include obstructive sleep apnea, which is commonly treated via interventions affecting the upper airway of the respiratory system.Brief Description of the Drawings

[0003] FIGS. 1 -2 are each a diagram schematically representing example methods and / or devices to deliver therapy to increase upper airway patency.

[0004] FIG. 3 is a diagram including at least some aspects of a functional physiologic model schematically representing example methods and / or devices to deliver therapy to increase upper airway patency.

[0005] FIGS. 4, 5, 6 are block diagrams schematically representing example agents, example delivery tools, and example delivery parameters, respectively, usable in example methods and / or devices to deliver therapy to increase upper airway patency.

[0006] FIG. 7 is a diagram schematically representing example methods and / or devices comprising application of electrical stimulation to deliver therapy to increase upper airway patency.

[0007] FIGS. 8, 9, 10 are each a diagram schematically representing example methods and / or devices comprising application of electrical stimulation therapy to deliver therapy to different nerve and / or muscle targets.

[0008] FIGS. 11 -12 are each a diagram including at least some aspects of physiologic model schematically representing example methods and / or devices to deliver pulmonary therapy to increase upper airway patency.

[0009] FIGS. 13A and 13C are each a block diagram schematically representing example control portions, respectively, and FIG. 13B is a block diagram schematically representing an example user interface.

[0010] FIG. 13D is a block diagram schematically representing an example patient care communication arrangement.

[0011] FIGS. 14A-14C are each a diagram schematically representing example methods and / or devices comprising application of sensing from and / or stimulating diaphragm-related tissue.

[0012] FIG. 15A is a diagram illustrating an example method of treating sleep disordered breathing including a stimulation protocol for activating diaphragm- related tissue.

[0013] FIG. 15B is a block diagram illustrating example respiratory parameters.

[0014] FIG. 15C is a diagram including a graph illustrating example respiratory parameters.

[0015] FIG. 15D is a block diagram illustrating an example stimulation engine.

[0016] FIGS. 16A-16F are diagrams illustrating example breathing patterns and / or stimulation protocols.

[0017] FIG. 17 is diagram schematically representing an example patient care arrangement, including various devices and / or communication pathways.Detailed Description

[0018] In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific examples in which the disclosure may be practiced. It is to be understood that other examples may be utilized and structural or logical changes may be made without departing from the scope of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense. It is to be understood that features of the various examples described herein maybe combined, in part or whole, with each other, unless specifically noted otherwise.

[0019] At least some examples of the present disclosure are directed to methods and / or devices to deliver therapy to treat sleep disordered breathing (SDB) such as, but not limited to, obstructive sleep apnea. In some such examples, delivering therapy may comprise delivering pulmonary therapy.

[0020] In some examples, the pulmonary therapy may comprise taking actions to decrease alveolar surface tension. In some such examples, the therapy may comprise delivering an agent to affect pulmonary surfactant within the lungs.

[0021] In some examples, delivering therapy may comprise causing ribcage expansion, which may be implemented with or without delivering an agent to affect pulmonary surfactant within the lungs. In some examples, the delivery of pulmonary therapy may be implemented in a coordinated manner (e.g. complementary) with one or more other therapy modalities (e.g. electrical stimulation) to treat sleep disordered breathing, as further described below.

[0022] It is generally well-established that pulmonary surfactant exogenously delivered into the lungs may decrease alveolar surface tension, and thereby alleviate respiratory distress syndrome (RDS) (e.g. infant RDS). See, for example, at least Jardine L, et al “Trial of Aerosolized Surfactant for Preterm Infants With Respiratory Distress Syndrome”, Arch Dis Child Fetal Neonatal Ed 2022; 107:F51 -F55 (doi: 10.1136 / archdischild-2021 -321645), which is hereby incorporated by reference in its entirety for its teaching. Such examples of pulmonary therapy also may be used to treat acute lung injury (ALI). In at least some of these diseases, natural production of pulmonary surfactant is impaired or absent and / or the lungs are otherwise damaged, impaired, etc. in a manner in which naturally occurring pulmonary surfactant is insufficient to achieve favorable levels of pulmonary surfactant which provide appropriate alveolar surface tension.

[0023] However, prior to the examples of the present disclosure, it has been previously unknown to cause an increase in pulmonary surfactant within the lungs to decrease alveolar surface tension to increase functional residual capacity in order to treat sleep disordered breathing (e.g. obstructive sleep apnea) such as (but not limited) reducing a frequency of apnea events and / or other measures ofreduced apneic burden. Moreover, at least some examples of the present disclosure comprise causing the increase in pulmonary surfactant in a coordinated or complementary manner with other pulmonary therapies (e.g. causing ribcage expansion) and / or other modalities (e.g. electrical stimulation, positive airway pressure, etc.) to treat sleep disordered breathing, as further described herein.

[0024] These examples and additional examples are further described below in association with at least FIGS. 1 -17.

[0025] As shown at 150 in FIG. 1 , in some examples, a method and / or device delivers therapy to increase upper airway patency. As further shown in FIG. 1 , in some examples the method and / or device may comprise delivering an agent to affect the lungs (at 162), applying electrical stimulation to a respiratory-related nerve and / or muscle (at 164), and / or applying an externally-generated airflow into the respiratory airway (at 166). More specific implementations of the examples (162, 164, 166) are further described below throughout examples of the present disclosure. As shown at 180 in FIG. 2, in some examples a method and / or device may comprise delivering an agent (e.g. drug) into the lungs via the externally- generated airflow.

[0026] As shown at 300 in FIG. 3, in some examples a method and / or device delivers an agent which increases pulmonary surfactant 324 in the lungs. As later described in more detail, the pulmonary surfactant may comprise an exogenously delivered pulmonary surfactant (e.g. 404 in FIG. 2) and / or an endogenous pulmonary surfactant (e.g. 406 in FIG. 2) secreted, by the patient’s own tissue, within the lungs caused by action of the agent. As shown in FIG. 3, the caused increase (arrow 325) of pulmonary surfactant (at 324) within the lungs causes a decreased (represented by arrow C) surface tension of the alveoli (at 320), which in turn may cause an increase (arrow F) in functional residual capacity (FRO) (340), as further described below.

[0027] In particular, as shown in FIG. 3, the example arrangement 300 schematically represents at least some aspects of a functional physiologic model (e.g. physiologic mechanisms, relationships, effects, etc.) by which methods and / or devices to deliver pulmonary therapy to decrease alveolar surface tensioncauses increased FRC, and the associated effects thereof. As further seen in FIG. 3, portion 302 schematically represents a balancing relationship 310 represented by a beam 312 resting upon a fulcrum 314 with alveolar surface tension 320 on a first end 313A of beam 312 and ribcage expansion 330 on the opposite second end 313B of beam 312. As further shown via portion 302 in FIG. 3, a decrease in alveolar surface tension 320 as represented by directional arrow C effectively lightens the metaphorical load at end 313A of the beam 312, which results in tilting upward of end 313A of the beam 312 as represented by directional arrow A, which in turn results in rotation (316) of the beam 312 in a direction representative of an increase (arrow F) of FRC 340. As further shown in portion 302 of FIG. 3, another physiologic aspect which may affect increases or decreases in FRC 340 comprises ribcage expansion 330. In particular, increasing (arrow D) ribcage expansion 330 causes an increased metaphorical load at end 313B of beam 312 resulting in downward motion (arrow B) of beam 312, which in turn results in rotation (316) of beam 312, which results in increased (arrow F) FRC 340 as represented in portion 304 of FIG. 3.

[0028] With reference to at least the functional physiologic model in FIG. 3, it will be further understood that the mechanism (and effect) of causing ribcage expansion 330 may be separate from, and independent of, the mechanism (and effect) of causing decreased alveolar surface tension 320. Accordingly, the representation of the ribcage expansion 330 in FIG. 3 of one possible mechanism does not necessarily indicate that action(s) have been implemented to cause such ribcage expansion 330. However, such actions and effects are described later in association with at least FIGS. 11-12 (and / or FIGS. 14A-16F) which schematically represent additional example methods and / or devices to deliver pulmonary therapy to treat sleep disordered breathing and / or to augment other therapy modalities to treat sleep disordered breathing.

[0029] With further reference to FIG. 3, the rotation 316 associated with up / down beam movements A and / or B shown in portion 302 of example arrangement 300 may cause an effect (directional arrow E) of increasing (F) FRC 340. Increasing the FRC 340 may increase upper airway patency 342 (e.g. via reducing upper airway collapsibility), which in turn may decrease sleep disordered breathing (e.g.obstructive sleep apnea burden 344) such as (but not limited to) the frequency of OSA events.

[0030] Without being bound by theory, when viewed as a functional physiologicphysics model, the caused increase in FRC 340 of the lungs causes caudal traction (even with a patient in a lying down position), which pulls the upper airway (e.g. oropharynx portion) of the patient inferiorly, which in turn causes stiffening of the upper airway (e.g. posterior and lateral pharyngeal walls), which corresponds to a reduced collapsibility of the upper airway. One example tissue of the oropharynx portion which may be pulled inferiorly comprises the thyroid cartilage. This reduced collapsibility corresponds to increasing or maintaining upper airway patency (342), which may alleviate obstructive sleep apnea.

[0031] In some examples, increasing FRC via at least some example methods and / or devices such as decreasing alveolar surface tension (and / or ribcage expansion) may benefit some patients even more than other patients. For instance, in some examples males may tend to exhibit more “lower” breathing (e.g. breathing which emphasizes use of their diaphragm) than females which may tend to exhibit more “upper” breathing (e.g. breathing which emphasizes use of their intercostal muscles / ribcage). Accordingly, even if both males and females (suffering from obstructive sleep apnea) exhibit an increased body mass index (BMI) corresponding with a significant amount of abdominal fat, the males may be disproportionately negatively affected by the abdominal fat because the abdominal fat tends to push the diaphragm (which the males tend to use more during breathing) superiorly, which in turn reduces the patient’s FRC. This reduction in FRC, in turn, increases upper collapsibility, which decreases upper airway patency, which may result in an increased apnea burden (e.g. greater frequency of OSA events).

[0032] However, at least some examples of the present disclosure which may cause an increase in FRC, such as via delivery of an agent to decrease alveolar surface tension (and / or electrical stimulation to increase ribcage expansion), may counteract the effects of the abdominal fat on the diaphragm, which may otherwise cause a decrease in FRC. As noted above, this beneficial effect of the example methods and / or devices may particularly favorably affect a male’sobstructive sleep apnea (such as males which tend to emphasize breathing via their diaphragm) at least because a mechanism (e.g. alveolar surface tension and / or ribcage expansion) different from the diaphragm may be used to increase functional residual capacity.

[0033] FIG. 4 is a block diagram schematically representing example agents 400 which may be used to decrease alveolar surface tension such as, but not limited to, increasing pulmonary surfactant within the lungs. As shown in FIG. 4, the agents 400 may comprise a pulmonary surfactant 402, which in some examples, the pulmonary surfactant 402 may comprise an exogenous type 404 and / or an endogenous type 406. In some examples, the agents 400 may comprise other types 408 of agents.

[0034] In some examples, the exogenous type 404 of pulmonary surfactant 402 comprises a pulmonary surfactant which is externally delivered into the lungs. In some such examples, the delivery is implemented via introduction into the airway via the oral and / or nasal cavities. In some examples, the exogenous type 404 of pulmonary surfactant 402 may be any type of surfactant configured to coat the lining of the alveoli in the lungs, thereby decreasing alveolar surface tension and / or increase the ease at which the alveoli expand during breathing. In some such examples, upon delivery within the lungs, the agent 400 may act to supplement any pulmonary surfactant naturally produced by the patient and / or act to cause increased secretion of pulmonary surfactant otherwise naturally produced by the patient’s body.

[0035] In some examples, the exogenous pulmonary surfactant may comprise a natural animal (e.g. bovine) derived lung surfactant, which may be obtained (e.g. isolated) via lung lavage. In some such examples, this lung surfactant extract may be lyophilized and reconstituted in a buffer supplied in a prefilled syringe. In some examples, by weight the example surfactant may comprise a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1 % phosphatidylinositol and 1 % sphingomyelin), 5% cholesterol, 1 % lipid-soluble surfactant-associated proteins (SP-B and SP-C), low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. Insome examples, this surfactant may comprise a SF-RI 1 surfactant and may be available as Alveofact® or otherwise available under the trade name Bovactant.

[0036] Various other example surfactants comprise Poractant alfa, Lucinactant, Calfactant, Beractant or commercially available surfactants.

[0037] In some examples, the surfactant may comprise an extract of natural porcine lung surfactant. In some examples, the surfactant may comprise Poractant alfa, which may be available under the name Curosurf®. In some examples, each milliliter of poractant alfa contains 80 milligram (mg) of surfactant (extract) that includes 76 mg of phospholipids and 1 mg of protein of which 0.2 mg is surfactant protein B (SP-B).

[0038] In some examples, the surfactant may comprise an extract of natural sheep lung surfactant. In some examples, the surfactant may be available under the name Varasurf®.

[0039] In some examples, the surfactant may comprise a synthetic pulmonary surfactant such as, but not limited to, Lucinactant (e.g. KL4), which is available under the trade name Surfaxin®. In some examples, the surfactant may comprise phospholipids and an engineered peptide, sinapultide, which is designed to mimic the actions of human surfactant protein B.

[0040] It will be understood that some other naturally-derived or synthetic surfactants may be suitable for use in example methods and / or devices.

[0041] In some examples, the endogenous type 406 of agent comprises a drug or other substance, which initiates or enhances secretion of pulmonary surfactant naturally produced by the patient, which in turn may decrease alveolar surface tension.

[0042] Whether delivered as an exogenous type 404 or endogenous type 406, delivery of pulmonary surfactant into the lungs may decrease alveolar surface tension, which may increase FRC of the lungs, which in turn may decrease upper airway collapsibility, as previously described. As further previously noted, increasing FRC corresponds to an increase in the volume of air retained in the lungs, which in turn may pull the upper airway inferiorly (e.g. via caudal traction), which effectively stiffens the upper airway, thereby reducing its collapsibility, which may maintain or increase the patency of the upper airway.

[0043] In some examples, an endogenous type 406 of agent may be delivered in same manner as an exogenous pulmonary surfactant with the agent causing lung tissue to secrete endogenous pulmonary surfactant via patient’s own tissues.

[0044] In some examples, the agent 400 (including associated preparation, delivery, mechanism of action, properties, etc.) may comprise at least some of substantially the same features and attributes as disclosed in Wilson D, et al, “The Future of Exogenous Surfactant Therapy”, Respiratory Care, September 2011 Vol. 56, No. 9, and / or as disclosed in Jardine L, et al “Trial of Aerosolised Surfactant for Preterm Infants With Respiratory Distress Syndrome”, Arch Dis Child Fetal Neonatal Ed 2022; 107:F51 -F55 (doi: 10.1136 / archdischild-2021 - 321645), both of which are hereby incorporated by reference in their entirety for their teachings.

[0045] FIG. 5 is a block diagram schematically representing example delivery tools 600 for delivery agents 400 (FIG. 4). As shown in FIG. 5, the delivery tools 600 may comprise an airflow device 602, ingestible form 610, circulatory device 612 and / or other delivery tool 614. In some examples, the airflow device 602 may comprise an aerosol delivery device 604 and / or a positive airway pressure (PAP) delivery device 606 such as (but not limited to) a continuous positive airway pressure (CPAP) device. In some examples, the PAP delivery device 606 may comprise a nasal PAP delivery device (e.g. nCPAP). In some examples, in cooperation with the aerosol delivery device 604, the PAP delivery device 606 may be configured to transport an aerosolized form of an agent 400 via positive airway pressure from device 606 to increase pulmonary surfactant within the lungs. In this way, the delivered agent 400 may act to supplement any pulmonary surfactant naturally produced by the patient and / or act to cause increased secretion of pulmonary surfactant otherwise naturally produced by the patient’s body.

[0046] In some examples, the aerosol delivery device 604 may comprise an inhaler, such as a meter-dosed inhaler, a soft mist inhaler, nebulizer, smart inhaler (e.g. Teva ProAir Digihaler), and the like.

[0047] One example airflow device comprises an aerosol generator comprising a vibrating mesh nebulizer. In some examples, the aerosol generator may beinterposed between a nasal CPAP (nCPAP) gas flow and the nasal prongs through which the gas flow is discharged into the nostrils. In some examples, the airflow device may comprise a AeroFact® nebulizer-based airflow device.

[0048] With further reference to FIG. 5, in some examples the delivery tool may comprise an ingestible form 610 (e.g. pill, liquid) which may cause the patient’s body to secrete the endogenous type 406 of pulmonary surfactant 402 into the lungs. In some examples, a circulatory device 612 form of delivery may be used, such as delivering the agent 400 into the bloodstream or intramuscularly, such as via an injection needle. While less convenient, the circulatory device 612 also may comprise intravenous delivery of an agent configured to cause secretion of the endogenous type of pulmonary surfactant.

[0049] It will be understood that other forms 614 of delivery tools also may be used such as (but not limited to) wearable patches, fluid delivery devices, etc. such as those used by diabetics to provide regular delivery of the agents (400 in FIG. 4) to increase pulmonary surfactant within the lungs. In some such examples, the delivery of the agents may be performed just prior to and / or solely during a nightly treatment period (e.g. sleeping period) or according to other selectable time periods, days, weeks, etc. In some examples, this example of timing of delivery of the agents, or other timing, may be implemented via at least a timing parameter (e.g. 656 in FIG. 6) as later described herein.

[0050] In some examples, the aerosol (604) delivery of an exogenous type of the pulmonary surfactant may comprise selectable parameters 650, such as schematically represented in the block diagram of FIG. 6. As shown in FIG. 6, in some examples, the delivery parameters may comprise delivering the agent via aerosolization (652), which may be performed according to a selectable droplet size parameter 654. In some examples, the droplet size may comprise less than 3 micrometers as measured in units of mass median aerodynamic diameter (MMAD).

[0051] In some examples, the agent (e.g. exogenously delivered pulmonary surfactant in aerosol form) may be delivered according to a concentration parameter 660. In some such examples, the agent may be delivered in undiluted form, e.g. as an undiluted exogenous pulmonary surfactant in aerosolized form.In some such examples, the degree of dilution may be comprise greater than 0.3 milliliters-per-minute.

[0052] As further shown in FIG. 6, in some examples a timing parameter 656 may be used to cause the aerosolized delivery to occur according to a particular timing such as (but not limited to) during inspiration. In some examples, the aerosolized delivery may be synchronized relative to inspiration such the delivery coincides with at least a portion of an (or substantially an entire) inspiratory phase. Among other aspects, this timing may avoid wasting the pulmonary surfactant which may occur if delivered during an expiratory phase of the patient’s breathing.

[0053] In some such examples, in order to implement the desired timing parameter 656, the delivery may be implemented according to a sensing parameter 658 shown in FIG. 6. Sensing may be performed via an airflow sensor, which may be incorporated into (or added onto) an airflow delivery device, which may sense respiratory phase information such as inspiratory phase and / or expiratory phase, including the offsets, onsets, and duration of the respective phases. In some examples, the sensing may performed via a sensor separate from (e.g. independent from) the airflow delivery device. For instance, in some examples, the sensor may comprise an implantable sensor and / or external sensor, either of which may form part of a diagnostic or therapy device. Some example therapy devices may comprise any one or more of the therapy modalities described throughout examples of the present disclosure. In some examples, the delivery parameters may comprise other types 662 of parameters.

[0054] In some such examples, various sensing modalities may be used such as (but not limited to) pressure, impedance, electromyography (EMG), electroneurography (ENG), accelerometry, and / other sensing modalities. Any one or more of these sensing modalities may be used to sense the respiratory phase information by which the timing (656) of delivery may be implemented. In some examples in which sensing is implemented separately from an airflow device (which may comprise aerosolization), operation of the sensing and sensed data may be communicated to the airflow device and / or to a manager (e.g. control portion 3100 in FIGS. 13A-13C) in communication with the airflow device. Insome such examples, the airflow device and / or control portion 3100 may implement the timing of the delivery based on the sensed data.

[0055] In some examples, the timing parameter 656 also may be used to deliver the agent according to a selectable time period or recurring temporal window (e.g. nightly). The agent may be delivered during an entire nightly sleep period, just during a portion of the nightly sleep period, or just prior to a nightly sleep period.

[0056] With further reference to FIGS. 4-6, it will be understood that airflow device 602 may be used deliver an agent which causes lung tissue to secrete (or increase secretion of) endogenous pulmonary surfactant. This agent may be delivered with or without an exogenous pulmonary surfactant 404, which also may decrease alveolar surface tension.

[0057] As shown at 1502 in FIG. 7, in some examples a method and / or device 1500 comprises applying electrical stimulation to a respiratory-related nerve and / or muscle (see also 164 in FIG. 1 ). As further shown at 1512 in FIG. 7, in some examples, this electrical stimulation may comprise applying electrical stimulation to a muscle and / or nerve to cause contraction of the muscle to increase or maintain upper airway patency, which is sometimes herein referred to as “upper airway patency-related tissue”. In some such examples, the muscle may comprise a lingual muscle, which may comprise a genioglossus (muscle and / or other muscle) such as, but not limited to, tongue protrusor muscles which cause protrusion of the tongue, which in turn may increase and / or maintain upper airway patency. In one aspect, the protrusion moves a rear portion of the tongue away from at least a posterior pharyngeal wall (e.g. in the oropharyngeal region) of the upper airway to increase and / or maintain upper airway patency. In some examples, the nerve may comprise a nerve innervating at least a portion of the lingual muscle, which in some examples may comprise at least the hypoglossal nerve and / or other nerves.

[0058] In some examples, the muscle may comprise an infrahyoid muscle (IHM), such as an infrahyoid strap muscle while the nerve may comprise a nerve innervating the infrahyoid muscle. The nerve may sometimes be referred to as the IHM-innervating nerve. In some examples, the nerve may correspond to branches extending from the ansa-cervicalis nerve loop. In some examples, theexample methods and / or devices may comprise at least some of substantially the same features and attributes as those described in PCT Application PCT / US2022 / 030543 filed on May 23, 2022, entitled Multiple Target Stimulation Therapy For Sleep Disordered Breathing, published as WO 2022-246320 on November 24, 2022 and / or U.S. patent application Serial Number 17 / 926,010 filed on May 21 , 2021 and published as US 2023-0172479 on June 8, 2023, entitled Single or Multiple Nerve Stimulation To Treat Sleep Disordered Breathing, both of which are hereby incorporated by reference in their entireties for their teachings.

[0059] With this arrangement in mind, at 1550 of FIG. 8, an example method comprises applying electrical stimulation to a hypoglossal nerve and / or an IHM- innervating nerve, which causes contraction of the muscles innervated by such nerves. As noted above, the muscles (e.g. genioglossus, infrahyoid strap) may be directly stimulated in some examples, without or without stimulation of their respective innervating nerves.

[0060] As further shown at 1514 in FIG. 7, in some examples the example arrangement (e.g. method and / or device) 1500 comprises applying electrical stimulation to lower respiratory tissue, such as nerves and / or muscles.

[0061] As further shown at 1560 in FIG. 9, in some examples, the electrical stimulation is applied to the phrenic nerve and / or diaphragmatic tissue innervated by the phrenic nerve. In some such examples, with appropriate timing / application, this electrical stimulation may be used to increase FRO, which may increase upper airway patency. At least some additional details regarding example methods and / or devices comprising stimulation (and / or sensing of) the phrenic nerve and / or diaphragm muscle are further described in association with at least FIGS. 12 and 14A-16F. In some examples, the phenic nerve can be stimulated to increase muscle tone of the diaphragm , which can increase respiratory volume. Moreover, because stimulation of the phrenic nerve may cause ribcage expansion (e.g. pursuant to contraction of the diaphragm), the phrenic nerve also may be viewed as indirectly causing activation of at least the external intercostal muscles, which causes ribcage expansion. Accordingly, in atleast this way, stimulation of the phrenic nerve (and / or diaphragm) may be viewed as increasing ribcage expansion.

[0062] In some examples the method 1514 in FIG. 7 (e.g. applying electrical stimulation to lower respiratory tissue) may comprise applying electrical stimulation to nerves and / or muscles activating ribcage movement as further shown at 1570 in FIG. 10. Among other nerves and / or muscles, such nerves may comprise nerves originating from the thoracic region of the spinal cord, which in some examples, may comprise the anterior rami of thoracic spinal nerves. In another instance, activation of the exterior intercostal muscles (e.g. via direction electrical stimulation or via stimulation of those nerves innervating such muscles) may cause expansion of the rib cage, which in turn causes expansion of the lungs, and therefore increased FRO. In some such examples, the electrical stimulation may comprise tonic stimulation (e.g. less than full muscle contraction) which is applied according to a timing to maintain the expanded ribcage position, and therefore to maintain the expanded lung volume (e.g. expanded respiratory volume) over an extended period of time. In some such examples, the tonic stimulation may sometimes be referred to as causing and / or increase muscle tone via applying the electrical stimulation to the respective nerves and / or muscles noted above. In some examples, the electrical stimulation to cause ribcage expansion may be applied selectively to coincide with specific respiratory phases (e.g. expiratory phase) so as to help maintain end expiratory lung volume (EELV), i.e. increased FRC. However, the electrical stimulation may be applied at an energy (e.g. amplitude, etc.) so as to not substantially alter overall respiratory behavior by the patient.

[0063] Among other aspects, the expansion of the rib cage (and corresponding lung expansion) may increase FRC (e.g. end expiratory lung volume), which in turn may decrease upper airway collapsibility. At least some further details regarding the example methods and / or devices for ribcage expansion are further described in association with at least FIGS. 11-12.

[0064] It will be understood that at least some nerves (e.g. anterior rami of thoracic spinal nerves) which directly innervate the intercostal muscles (e.g. at least the external intercostal muscles) may promote ribcage expansion via onepathway, while some nerves (e.g. phrenic nerve) which directly innervate other muscles (e.g., diaphragm) may promote ribcage expansion via another pathway, and that both of these pathways may act in a complementary manner to promote ribcage expansion. Moreover, the delivery of an agent (e.g. pulmonary surfactant) (400 in FIG. 4 to decrease alveolar surface tension to increase FRO and the electrical stimulation of the ribcage (muscle and / or nerve) to increase FRC may be implemented in a complementary manner. For instance, in some examples, these different therapies may be implemented in sequence, concurrently at least part of nightly treatment period, intermittently, etc. Application of both of these therapy modalities may additively increase FRC or may be provide more a robust increase in FRC.

[0065] Moreover, as noted above, electrical stimulation of the phrenic nerve and / or diaphragmatic tissue may further increase FRC. Accordingly, with or without delivery of an agent for pulmonary therapy, the electrical stimulation of the ribcage (muscle and / or nerve) and the electrical stimulation of the phrenic / diaphragm may be performed sequentially, overlapping, intermittently, etc.

[0066] Moreover, any one or more of these modalities (e.g. 1514 in FIG. 7, 1560 in FIG. 9, 1570 in FIG. 10) may be performed in coordination with, complementary manner with other therapy modalities (e.g. 1512 in FIG. 7, 1550 in FIG. 8) with or without the example methods and / or delivery of agent to decrease alveolar surface tension as described throughout examples of the present disclosure.

[0067] As further shown at 1516 in FIG. 7, in some examples a method and / or device applies electrical stimulation to tissue causing an upper airway dilator reflex response. For example, electrical stimulation of various nerves such as (but not limited to) afferent fibers of the glossopharyngeal nerve and / or interior superior laryngeal nerve (iSLN) may cause an upper airway dilator reflex response. In some such examples, this therapy modality may be coordinated with and / or be complementary with any of other therapeutic modalities described herein particularly including (but not limited to) example methods and / or devices to deliver an agent to decrease alveolar surface tension to increase or maintain upper airway patency.

[0068] FIG. 11 is a diagram schematically representing example methods and / or devices 1900 via at least some aspects of a functional physiologic-physics model comprising at least some of substantially same features and attributes as the example arrangement in FIG. 3, except further comprising an example of applying electrical stimulation 1910 to increase ribcage expansion to increase upper airway patency, as previously described. The electrical stimulation may be applied to exterior intercostal muscles or nerves innervating such muscles such as intercostal nerves (and / or branches extending therefrom) originating in the thoracic region of the spinal cord.

[0069] This application of electrical stimulation (to increase ribcage expansion) may be performed with or without example methods (and / or devices) delivering of an agent to increase pulmonary surfactant 324. Moreover, this example of applying electrical stimulation to cause ribcage expansion also may be performed with or without one or more of the other therapy modalities described throughout the present disclosure.

[0070] As previously noted with regard to FIG. 3 and as shown in FIG. 11 , increasing (arrow D) ribcage expansion 330 causes an increased metaphorical load at end 313B of beam 312 resulting in downward motion (arrow B) of beam 312, which in turn results in rotation (316) of beam 312, which results in increased (arrow F) FRO 340 as represented in portion 304 of FIGS. 3 and 11.

[0071] FIG. 12 is a diagram schematically representing example methods and / or devices 1950 via at least some aspects of a functional physiologic-physics model comprising at least some of substantially same features and attributes as the example arrangement in FIG. 3 and 11 , except further comprising an example of applying electrical stimulation to the phrenic nerve and / or diaphragm to increase FRC, as previously described in association with at least 1514 in FIG. 7 and 1560 in FIG. 9.

[0072] This application of electrical stimulation of the phrenic nerve and / or diaphragm may be performed with or without example methods (and / or devices) delivering of an agent to increase pulmonary surfactant 324. Moreover, this example of applying electrical stimulation also may be performed with or withoutone or more of the other therapy modalities described throughout the present disclosure.

[0073] In a manner separate from and / or complementary to the ribcage expansion previously noted with regard to FIG. 3 and as shown in FIG. 11 , in the example shown in FIG. 12 arrow D represents an effect resulting from diaphragm activation 1960 (caused by electrical stimulation of the phrenic nerve and / or diaphragm), which causes an increased metaphorical load at end 313B of beam 312 resulting in downward motion (arrow B) of beam 312, which in turn results in rotation (316) of beam 312, which corresponds to increased (arrow F) FRO 340 as represented in portion 304 of FIG. 12.

[0074] FIG. 13A is a block diagram schematically representing an example control portion. In some examples, the control portion 3100 includes a controller (e.g. processor) 3102 and a memory 3104. In some examples, the control portion 3100 provides one example implementation of a control portion forming a part of, implementing, and / or managing any one of the devices, tools, functions, parameters, sensors, agent delivery devices, and / or methods, as represented throughout the present disclosure.

[0075] The control portion 3100 may include circuitry components and wiring appropriate for generating desired stimulation signals (e.g. converting energy provided by the power source into a desired stimulation signal), generating airflow delivery mechanisms and / or other agent delivery mechanisms. In some examples, the control portion 3100 may include telemetry components for communication with external devices. For example, the control portion 3100 may include a transmitter that transforms electrical power into a signal associated with transmitted data packets, a receiver that transforms a signal into electrical power, a combination transmitter / receiver (or transceiver), an antenna (e.g. an inductive telemetry antenna), etc.

[0076] In general terms, the controller 3102 of the control portion 3100 comprises an electronics assembly 3106 (e.g. at least one processor, microprocessor, integrated circuits and logic, etc.) and associated memories or storage devices. The controller 3102 is electrically couplable to, and in communication with, the memory 3104 to generate control signals to direct operation of at least some thedevices, tools, functions, parameters, sensors, agent delivery devices, and / or methods, as represented throughout the present disclosure. The control signals may be a software program stored on the memory 3104 (which may be stored on another storage device and loaded onto the memory 3104), and executed by the electronics assembly 3106, such as illustrated by 3109.

[0077] In response to or based upon commands received via a user interface (e.g. user interface 3240 in FIG. 13A), sensor signals, and / or via machine readable instructions, controller 3102 generates control signals as described above in accordance with examples of the present disclosure. In some examples, controller 3102 is embodied in a general purpose computing device while in some examples, controller 3102 is incorporated into or associated with at least some of the devices, portions of devices, user interfaces, instructions, information, engines, functions, actions, and / or method, etc. as described throughout examples of the present disclosure.

[0078] For purposes of this application, in reference to the controller 3102, the term “processor” shall mean a presently developed or future developed processor (or processing resources) that executes machine readable instructions contained in a memory. In some examples, execution of the machine readable instructions, such as those provided via memory 3104 of control portion 3100 cause the processor to perform the above-identified actions, such as operating controller 3102 to implement the various example methods and / or devices as generally described in (or consistent with) at least some examples of the present disclosure. The machine readable instructions may be loaded in a random access memory (RAM) for execution by the processor from their stored location in a read only memory (ROM), a mass storage device, or some other persistent storage (e.g. non-transitory tangible medium or non-volatile tangible medium), as represented by memory 3104. In some examples, the machine readable instructions may comprise a sequence of instructions, or the like. In some examples, memory 3104 comprises a computer readable tangible medium providing non-volatile storage of the machine readable instructions executable by a processor of controller 3102. In some examples, the computer readable tangible medium may sometimes be referred to as, and / or comprise at least a portion of, a computerprogram product. In some examples, hard wired circuitry may be used in place of or in combination with machine readable instructions to implement the functions described. For example, controller 3102 may be embodied as part of at least one application-specific integrated circuit (ASIC), at least one field-programmable gate array (FPGA), and / or the like. In some examples, the controller 3102 is not limited to any specific combination of hardware circuitry and machine readable instructions, nor limited to any particular source for the machine readable instructions executed by the controller 3102.

[0079] In some examples, control portion 3100 may be entirely implemented within or by a stand-alone device.

[0080] In some examples, the control portion 3100 may be partially implemented in one of the example devices (and / or methods) and be partially implemented in a computing resource (e.g. at least one external resource) separate from, and independent of, such example devices but in communication with the example devices. For instance, in some examples, control portion 3100 may be implemented via a server accessible via the cloud and / or other network pathways. In some examples, the control portion 3100 may be distributed or apportioned among multiple devices or resources such as among a server, an apnea treatment device (or portion thereof), and / or a user interface.

[0081] In some examples, control portion 3100 includes, and / or is in communication with, a user interface 3240 as shown in FIG. 13A.

[0082] FIG. 13B is a block diagram schematically representing a user interface. In some examples, user interface 3240 forms part of and / or is accessible via a device external to the patient and by which the example devices (and / or other medical device) may be at least partially controlled and / or monitored. In some examples, the external device which hosts user interface 3240 may be a patient remote, a physician remote, and / or a clinician portal. In some examples, user interface 3240 comprises a user interface or other display that provides for the simultaneous display, activation, and / or operation of at least some of the instructions, information, engines, functions, actions, and / or method, etc., as described in connection with FIGS. 1 -13A, as well as further described in connection with FIGS. 14A-16F. In some examples, at least some portions oraspects of the user interface 3240 are provided via a graphical user interface (GUI), and may comprise a display 3244 and input 3242.

[0083] Figure 13C is a diagram schematically illustrating at least some example arrangements of a control portion 3520 by which the control portion 3100 (FIG. 13A) can be implemented, according to one example of the present disclosure. In some examples, control portion 3520 is entirely implemented within or by a therapeutic medical device (TMD) 3525 (e.g. including implantable and / or external components) configured to implement the examples described throughout the present disclosure. Among other examples, the TMD 3525 may comprise one of the delivery tools (600 in FIG. 5) such as (but not limited to) an aerosol device 604 (e.g. inhaler, nebulizer) and / or circulatory device 612 (e.g. intravenous or needle). In some examples, control portion 3520 is entirely implemented within or by a remote control 3530 (e.g., a programmer) external to the patient’s body, such as a patient control 3532 and / or a physician control 3534. In some examples, the control portion 3100 is partially implemented in the TMD 3525 and partially implemented in the remote control 3530 (at least one of patient control 3532 and physician control 3534). In some examples, the control portion 3520 in FIG. 13C is at least partially implemented via a clinician portal (e.g., 3662 in FIG. 13D, 4260 in FIG. 17), which may or may not be in complementary relation with elements 3525 and 3519 of FIG. 13C.

[0084] FIG. 13D is a diagram 3600 which schematically represents some example implementations by which a medical device 3610 (e.g. TMD 3525 of FIG. 13C) may communicate wirelessly with other devices. In some examples, the medical device 3610 may comprise at least some implantable components and / or at least some external components. As noted above, in some examples the medical device 3610 (e.g. TMD 3525) may comprise one of the delivery tools (600 in FIG. 5).

[0085] As shown in FIG. 13D, in some examples, the medical device 3610 may communicate with at least one of patient app 3630 on a mobile device 3620, a patient remote control 3640, a clinician programmer 3650, and a patient management tool 3660. The patient management tool 3660 may be implemented via a cloud-based portal 3662, the patient app 3630, and / or the patient remotecontrol 3640, each of which may comprise a user interface (e.g., having a display, input) such as user interface 3240 in FIG. 13B. Moreover, each of the various devices (e.g. 3620, 3640, 3650, 3660 (e.g. 3662), which may communicate with medical device 3610, also may communicate with each other.

[0086] Among other types of data, these communication arrangements enable the medical device 3610 (and / or other devices of the arrangement of FIG. 13D) to track, communicate, display, adjust, manage, etc. any of the features of the example methods and / or devices of the various examples of the present disclosure. For instance, the medical device 3610 (e.g. TMD 3525) may track, communicate, display, adjust, manage, etc. usage information to the other devices FIG. 13D. In some such examples, usage information regarding at least one delivery tool (e.g. 600 in FIG. 5) such as (but not limited to) an aerosol device 604 (e.g. inhaler, nebulizer, etc.) and / or circulatory delivery tool 612 (e.g. intravenous, needle, etc.) may be tracked, communicated, displayed, adjusted, managed, etc. in relation to other devices such as those within the example arrangement of FIG. 13D. Similarly, in some examples, at least one of the delivery tools (e.g. 600 in FIG. 5) may comprise one of several therapeutic medical devices (e.g. 4285 of FIG. 17) which communicate patient care information (e.g. usage) with, and / or among, the various devices of the example arrangement 4200 of FIG. 17. In some such examples, the patient care information may comprise patient inputs, clinician inputs, patient habits, patient sleep behaviors, etc. in relation to the usage information.

[0087] In some such examples and referring to FIG. 17, this patient care information may be obtained or received via the patient app 4212, patient remote 4289, TMD 4285, one of devices 4250A, 4250B, 4250C, and / or resource 4230 in the example arrangement of FIG. 17. The TMD 4285 may comprise a delivery tool (e.g. 600 in FIG. 5) and / or the TMD 4285 may comprise a device for stimulation (4286 in FIG. 17) or sensing (4287 in FIG. 17) via method 164 in FIG. 1 and / or may comprise device implementing another therapeutic modality (e.g. at 166 in FIG. 1 ). In some such examples, the TMD 4285 may comprise one or more of the sensor 710, sensing circuit 752, stimulation element 720, and stimulation circuit 754 of FIG. 14A.

[0088] In some examples, at least some of the patient care information (e.g. patient inputs, clinician inputs, patient habits, patient sleep behaviors, etc. in relation to the usage information and / or other information) may be obtained or received via a third party monitoring device such as a sleep-related sensing system (e.g. Withings®) and / or other health-related sensing system (e.g. Apple® Health kit).

[0089] As further apparent from the later described example arrangement of FIG. 17, this patient care information may be communicated to a clinician (e.g. devices 4250A, 4250B, 4250C), whereby a clinician may make and communicate recommendations (regarding usage and / or therapy / sensing settings) to the patient and / or the therapeutic device such as (but not limited to) the delivery tool (e.g. 600 in FIG. 5) and / or other TM Ds (e.g. stimulation device, externally applied airflow device, etc.). In some examples, the clinician may implement modified or new therapy settings (re pulmonary therapy and / or other therapies described herein), whether such implementation is made remotely via the example arrangement of FIG. 17 or made via an in-person patient-clinician visit. In some examples, the recommendations and / or therapy settings may comprise whether and / or when to receive delivery of the agent (e.g. lung agent) to facilitate patient care (e.g. SDB care) with or without other SDB therapy modalities. In some such examples, the “when” to receive delivery of the agent may comprise which days, which times of day, frequency within a treatment session (e.g. nighttime sleep period), duration of delivery for each time that delivery occurs, overall volume delivered during a treatment session, duration of effectiveness for each delivery, etc. In some examples, the recommendation and / or therapy settings also may comprise which lung agent(s) to use.

[0090] In some examples, the example arrangements of FIGS. 13A-13D may comprise example implementations of and / or may comprise at least some of substantially the same features as the example arrangement 4200 of FIG. 17. Conversely, in some examples the example arrangement 4200 of FIG. 17 may comprise example implementations of, and / or may comprise at least some of substantially the same features as, the example arrangements of FIGS. 13A-13D.

[0091] FIGS. 14A-14C are each a diagram schematically representing example methods and / or devices comprising application of sensing from and / or stimulating diaphragm-related tissue.

[0092] In various examples, in order to treat SDB and / or other conditions, diaphragm-related tissue may be used to sense respiratory information and / or stimulated using a device, and which may be implemented with or without delivering an agent to affect pulmonary surfactant within the lungs and / or may include an implementation of stimulating respiratory-related tissue as described in connection with FIGS. -1 -17. As shown in FIG. 14A, diaphragm-related tissue 7117 may include the phrenic nerve 7118 and / or the diaphragm muscle 7119, which is innervated by the phrenic nerve 7118. Accordingly, stimulating the diaphragm-related tissue 7117 may cause contraction of the diaphragm muscle 7119 directly or via the phrenic nerve 7118. In some examples, the diaphragm- related tissue may be stimulated alone, or in addition to, other example target tissue such as (but not limited to) any of the target tissue, and / or in addition to delivering an agent to affect pulmonary surfactant within the lungs as described in connection with at least FIGS. 1 -13D and 17.

[0093] In some examples, a stimulation element 720 may be located at or in close proximity to such diaphragm-related tissue 7117 to apply stimulation thereto and cause contraction of the diaphragm muscle 7119. For example, FIG. 14A shows example target locations for activating the phrenic nerve 7118, as illustrated by target location I, and / or the diaphragm muscle 7119, as illustrated by target location II. In some examples the stimulation element 720 may include a stimulation lead and pulse generator. The stimulation lead, on which at least one stimulation electrode of the stimulation element is supported, may be implanted in a position extending between an implantable pulse generator (IPG) and a location at which the at least one stimulation electrode is in stimulating relation to the diaphragm-related tissue 7117 of the patient. In some examples, at least a portion of the pulse generator may be located external to the patient’s body and / or may wirelessly provide power, stimulation signals, and / or control signals to the implanted portions of the stimulation element, such as via the control portions and / or user interface as described in connection with FIGS. 13A-13D, and 17.

[0094] In some examples, the stimulation element 720 may comprise any of those described below. For example, the simulation element comprises at least one stimulation electrode. In some examples, the stimulation element 720 comprises a cuff electrode that at least partially encloses a portion of the phrenic nerve 7118. Whether in the format of a cuff electrode or other format, in some examples, the stimulation element 720 comprises a stimulation arrangement, such as a plurality of stimulation electrodes. In some examples, the stimulation element 720 comprises a paddle electrode or an axial electrode array. In some such examples, the diaphragm-related tissue 7117 may comprise a first diaphragm-related tissue (e.g. phrenic nerve 7118) and a second diaphragm- related tissue (e.g. diaphragm muscle 7119) and the stimulation electrode (e.g. paddle electrode or an axial electrode array) is co-extensive with the first diaphragm-related tissue and the second diaphragm-related tissue.

[0095] In some examples, a device (e.g. a therapy or medical device) can include or be in communication with the stimulation element 720. For example, a device can include stimulation circuit 754 which is in communication with a stimulation element 720 located within an environment, such as implanted in the body. In such embodiments, the device can be non-implanted or implanted at a different location from the stimulation element. In some examples, the device includes include stimulation circuit 754 and the stimulation element 720, and can be an implanted medical device (IMD). In some embodiments, the device further includes sensing circuit 752 and / or a sensor 710. For example, the device can include the stimulation circuit 754 and the sensing circuit 752, which are respectively in communication with the stimulation element and sensor 710 located within an environment. In other examples, the device can include the stimulation circuit 754, the stimulation element 720, the sensing circuit 752, and the sensor 710, and can be an IMD.

[0096] The sensor 710 may sense (e.g. detect) respiratory or other information associated with the environment and / or the stimulation element 720 may deliver (e.g. apply) stimulation to a target tissue, e.g. diaphragm-related tissue 7117 and / or other tissue. In some examples, the sensor 710 may comprise an electrode(s) and / or other elements for sensing. In some examples, thestimulation element 720 may comprise an electrode(s) for delivering a stimulation signal to the target tissue.

[0097] In some examples, the electrode(s) used for applying stimulation may also be used for sensing. Similarly, the electrode(s) used for sensing may also be used for applying stimulation, and as such also may comprise electrode(s). However, in some examples, the sensing electrode(s) are used solely for sensing and the stimulation electrode(s) are used solely for applying stimulation.

[0098] In some examples, other elements used for sensing may comprise a sensing element which does not depend on electrode(s) for sensing. For example, such other sensing elements may comprise a pressure sensor (e.g. differential pressure), an accelerometer, and / or other sensing elements.

[0099] In some examples, the electrode(s) and / or other sensing elements (e.g. accelerometer) may be used to sense one or more of motion, activity, body position (e.g. posture), respiration, heart rate, etc., at least some of which may be used to detect disordered breathing and / or other disease burdens. At least some further examples of other sensing elements and / or physiologic phenomenon sensed via such elements (and / or electrode(s).

[0100] In some example implementations, the sensor 710 may comprise both electrode(s) and other sensing element(s) , which may be operated independently from each other or in combination with each other.

[0101] In some examples, the sensor and stimulation element may take a wide variety of forms, and may be incorporated within a wide variety of different types of sensors and / or stimulation elements, at least some of which are described in association with U.S. Publication 2023 / 0172479, published on November 11 , 2022, and entitled “Single or Multiple Nerve Stimulation to Treat Sleep Disordered Breathing”, and U.S. Publication 2024 / 0252824, published on August 1 , 2024, and entitled “Multiple Target Stimulation Therapy for Sleep Disordered Breathing”, each of which are incorporated herein by reference in their entireties for their teachings.

[0102] In some examples, the sensor 710 and / or the stimulation element 720 can be implanted within the patient’s body. In other examples, one or both of the sensor 710 and the stimulation element 720 may be external to the patient’s body.

[0103] In some examples, the sensor 710 and / or sensing circuit 752 of FIG. 14A may comprise an example implementation of, and / or at least some of substantially the same features as, the sensing component 4287 of the therapeutic medical device (TMD) 4285 of FIG. 17. Meanwhile, the stimulation element 720 and / or stimulation circuit 754 of FIG. 14A may comprise an example implementation of, and / or at least some of substantially the same features as, the stimulation component 4286 of the therapeutic medical device (TMD) 4285 of FIG. 17. In some examples, the sensing component 4287 of the therapeutic medical device (TMD) 4285 of FIG. 17 may comprise an example implementation of, and / or at least some of substantially the same features as, the sensor 710 and / or sensing circuit 752 of FIG. 14A. Meanwhile, the stimulation component 4286 of the TMD 4285 of FIG. 17 may comprise an example implementation of, and / or at least some of substantially the same features as, the stimulation element 720 and / or stimulation circuit 754 of FIG. 14A.

[0104] In general terms, in a natural physiologic process of breathing (e.g. natural / intrinsic breathing), inspiration results from activation of a phrenic nerve to cause contraction of the diaphragm muscle, which induces a negative pressure in the lungs, resulting in air entering the lungs from the upper airway and external environment. Expiration follows inspiration, with expiration beginning immediately upon relaxation of the contracted diaphragm, which produces a force expelling air from the lungs. A breath includes both inspiration and expiration and it will be understood that a breath, as used herein in some examples, corresponds to a respiratory cycle with the term “breath” generally used henceforth (and / or in other portions of the present disclosure) for simplicity and consistency.

[0105] At least some example methods to treat sleep disordered breathing (SDB) comprise activating (e.g. stimulating) diaphragm-related tissue via a stimulation element to modulate a respiratory parameter. This activation may be performed in addition to any activation of diaphragm-related tissue occurring as part of normal / intrinsic breathing and / or may be performed in the temporary absence of (and / or diminished) normal / intrinsic breathing.

[0106] in some examples, some target tissues may be used to affect respiration in other ways and / or more generally. For instance, an immediate effect ofstimulation of the phrenic nerve 7118 includes activation of the diaphragm muscle 7119, whose contraction induces a negative pressure within the lungs, thereby resulting in inspiration of air (passing through the upper airway) and other structures.

[0107] It will be understood that some example devices and / or some example methods may engage the phrenic nerve solely for stimulation to treat various types of apnea (e.g. central, mixed, other). However, in some example devices and / or some example methods may engage the phrenic nerve solely for sensing or may engage the phrenic nerve for both sensing and stimulation. Further, in some examples, the phenic nerve can be stimulated to directly increase muscle tone of the diaphragm and / or indirectly increase muscle tone of the at least external intercostals to increase respiratory volume.

[0108] With this in mind, FIG. 14B schematically represents an example arrangement 6200 including example sensing patterns for the phrenic nerve and / or example stimulation protocols.

[0109] For example, FIG. 14B includes an example respiratory waveform 5010 obtained via sensing respiratory tissues (e.g. tissues in continuity with the lungs) and / or motion (e.g. chest) indicative of respiratory activity. The example respiratory waveform 5010 includes an inspiratory phase 5012 having duration INSP, an active expiratory phase 5014 having duration EA, and an expiratory pause phase 5016 having duration EP. Together, these phases comprise an entire respiratory cycle 5011 having a duration (e.g., respiratory period) of R. This respiratory cycle 5011 is repeated, as represented in successive frames A, B, C, D, E, and so on.

[0110] As further shown in FIG. 14B, an example respiratory waveform 5010 of respiratory activity obtained via sensing a phrenic nerve (e.g. 7119 in FIG. 14A) in which each instance 6212 of phrenic nerve activity generally coincides with the inspiratory phase (e.g. 5012) of a respiratory cycle. In some examples, the sensing is performed via ENG. Each instance 6212 of phrenic nerve activity includes an onset 6214 at which the phrenic activity begins and an offset 6216 at which the phrenic activity ceases, following by little to no neural activity as represented by segment 6215 during expiration takes place. Among other thingstranspiring during inspiration (or just before inspiration), the activation of the phrenic nerve causes contraction of the diaphragm to induce a negative pressure in the lungs, resulting in inspiration as air enters the lungs from the upper airway and external environment.

[0111] In some examples, the sensing of the phrenic nerve may comprise sampling at a rate between about 10 hertz (Hz) to about 5 kilohertz (kHz), and in some such examples, the sampling rate may be on the order of a few hundred Hz.

[0112] As shown in FIG. 14B, an amplitude of phrenic nerve activity generally increases from the onset 6214 to the offset 6216 at which time the amplitude abruptly decreases to zero or near zero. During a second phase (e.g. expiratory active phase and expiratory pause) of the respiratory cycle, the phrenic activity remains at or near zero, until the next onset 6214 of an inspiratory phase of a next respiratory cycle. Accordingly, the presence of phrenic nerve activity is directly indicative of inspiratory activity.

[0113] It will be understood that the phrenic activity waveform 6210 in FIG. 14B is just one example and that some small variations in amplitude (and / or duty cycle, timing, etc.) of the sensed phrenic nerve activity may exist when sensing at different portions of the phrenic nerve, among different patients, etc.

[0114] With this in mind, FIG. 14B further illustrates example respiratory activity waveforms 6330, 6350 obtained via sensing activity of a first phrenic nerve site and sensing activity of a first diaphragm muscle site, respectively. In some examples, the phrenic nerve activity of waveform 6330 is sensed via ENG while in some examples, the diaphragm muscle activity represented by waveform 6350 is sensed via EMG.

[0115] While some example devices and / or example methods may sense both activity of the phrenic nerve(s) and activity of the diaphragm muscle(s), some example devices and / or example methods may sense phrenic nerve activity without sensing diaphragm muscle activity and some example devices and / or example methods may sense diaphragm muscle activity (i.e., without sensing phrenic nerve activity).

[0116] In a manner consistent with the waveform 6210 in FIG. 14B of sensed phrenic activity, each instance 6332 of phrenic nerve activity in waveform 6330 of FIG. 14B generally coincides with the inspiratory phase (e.g. 5012 in FIG. 14B) of a respiratory cycle. Each instance 6332 of phrenic nerve activity as sensed at first phrenic site 6331 includes an onset 6334 at which the phrenic activity begins and an offset 6336 at which the phrenic activity ceases. Meanwhile, a non-active (e.g. rest or dormant) period 6337 extends between the instances 6332 of phrenic nerve activity. The peak amplitude of the phrenic nerve activity is represented as AMP 1 , while a duration D1 of each instance of phrenic nerve activity generally corresponds to a duration of an inspiratory phase (e.g. 5012 in FIG. 14B). As further shown in FIG. 14C, a total duration (D3) of a respiratory cycle includes the inspiratory phase (e.g. active phrenic nerve period 6332) and expiratory phase (e.g. non-active phrenic nerve period 6337). An inspiratory duty cycle may comprise a proportion of the duration D1 (e.g. time spent in inspiration as sensed phrenic activity) relative to the duration D3 (e.g. total time of a respiratory cycle).

[0117] In a manner consistent with the waveform 6330 of sensed phrenic activity, each instance 6352 of diaphragm muscle activity in waveform 6350 of the example arrangement 6300 of FIG. 14C generally coincides with each instance of 6332 of phrenic nerve activity (6330) and generally coincides with the inspiratory phase (e.g. 5012 in FIG. 14B) of a respiratory cycle. Each instance 6352 of diaphragm muscle activity as sensed at first diaphragm site 6351 includes an onset 6354 at which the diaphragm activity begins and an offset 6356 at which the diaphragm activity ceases. Meanwhile, a non-active period 6357 extends between the instances 6352 of diaphragm muscle activity. The peak amplitude of the diaphragm nerve activity is represented as AMP 2, while the duration D2 of each instance of diaphragm muscle activity generally corresponds to a duration of an inspiratory phase (e.g. 5012 in FIG. 14C). As further shown in FIG. 14C a total duration (D4) of a respiratory cycle includes the inspiratory phase (e.g. active diaphragm muscle period 6352) and expiratory phase (e.g. non-active diaphragm muscle period 6357). An inspiratory duty cycle may comprise a proportion of the duration D2 (e.g. time spent in inspiration as sensed diaphragm activity) relative to the duration D4 (e.g. total time of a respiratory cycle).

[0118] With further reference to FIG. 14B, one example arrangement comprises delivering stimulation to a stimulation target (STIM TARGET 6249). In some examples, a timing of the stimulation may be based on at least one parameter of the sensed phrenic activity (and / or diaphragm muscle activity per FIG. 14C), which comprises a respiration parameter. In some examples, the delivery of the stimulation signal is timed to generally coincide with the start, duration, and / or end of the sensed phrenic activity (e.g. waveform 6210 in FIG. 14B). In some such examples, each instance 6212 of phrenic nerve activity coincides with an inspiratory phase and because each stimulation period 6243 is intended to coincide with the inspiratory phase (in this example), each stimulation period 6243 coincides with a duration of the instance 6212 of phrenic nerve activity. In the particular example shown in FIG. 14B, an onset (B) of each instance of stimulation 6243 begins just prior to a start of an inspiratory phase (e.g. prior to onset 6214 of the sensed phrenic nerve activity). More generally speaking, the stimulation protocol 6220 in FIG. 14B comprises a series of stimulation cycles 6255, with each cycle 6255 including a stimulation period 6243 and a non-stimulation period 6245. During stimulation periods, stimulation is applied to target tissue for at least a portion of the periods. During non-stimulation periods, no stimulation is applied for the entire periods.

[0119] In some examples, an amplitude setting (and / or other parameters such as timing, duty cycle, etc.) of the stimulation signal may be based, at least on part, on the amplitude (and / or other parameters) of the sensed activity of the phrenic nerve and / or diaphragm muscle.

[0120] In some examples, the stimulation target 6249 (e.g. second target tissue) represented in FIG. 14B may comprise an upper airway patency-related tissue such as (but not limited to) a hypoglossal nerve (and / or genioglossus muscle). In some such examples, the sensed phrenic neural activity (or diaphragmatic activity) provides highly accurate respiratory information in view of its high fidelity relative to respiration, at least in part due to the phrenic nerve being dedicated to respiration versus other nerves which may be associated with multiple bodily functions. This high fidelity in turn may increase the effectiveness of delivery of the stimulation to treat SDB (e.g. obstructive sleep apnea).

[0121] In some examples, sensing respiration via the phrenic nerve (and / or the diaphragm muscle) may be used to detect central sleep apneas, which may be revealed in respiratory waveforms in which an inspiratory phase is absent for a time period corresponding to one or several breaths that would otherwise occur. In some examples, this detection of a central sleep apnea may be used as input to determining stimulation parameters / protocols. For instance, upon such detection of a central sleep apnea, a control portion may withhold (e.g. suspend) stimulation of upper airway patency-related nerves during such central sleep apneas. In another instance, upon such detection of a central sleep apnea, a control portion may adjust a timing (and / or an intensity (e.g. amplitude) of) stimulation of upper airway patency-related nerves during such central sleep apneas.

[0122] FIG. 15A is a diagram illustrating one example method 7300 of activating diaphragm-related tissue to modulate a respiratory parameter, while FIG. 15B is a block diagram illustrating some example respiratory parameters 7610. Both FIGS. 15A and 15B are more fully described later. However, as a brief introduction, as shown by FIG. 15B, at least some example respiratory parameters 7610 may include a periodic breathing parameter 7611 , an end expiratory lung volume (EELV) parameter 7612, FRO parameter 7613, an upper airway co I laps i b i I i ty parameter 7616, a tidal volume parameter 7618, a respiratory control gain (RCG) parameter 7620, a ventilation parameter 7621 , a carbon dioxide CO2 threshold parameter 7622, and / or an intrathoracic negative pressure parameter 7624, among other parameters 7625. At least some of these respiratory parameters 7611-7625 relate to respiratory functions, and therefore in some examples, may sometimes be referred to as respiratory function parameters. At least some of these respiratory functions, which may relate to various lung volumes, are further described later in association with at least FIG. 15C, which is addressed in context throughout the discussion of FIGS. 14A-16F. The respiratory parameters 7610 may be modulated individually and / or in different combinations by selectively applying stimulation to different target tissue according to stimulation parameters, such as those illustrated in connection with the stimulation portion 7500 of FIG. 15D.

[0123] Moreover, in some examples, performing pulmonary therapy (e.g. per the methods and / or devices of FIGS. 1 -13D, 17) also may modulate at least some of the respiratory parameters 7610 (individually and / or in different combinations), with such modulation occurring independently of, and / or in complementary relation with, at least the examples of sensing and / or stimulation of FIGS. 14A- 16F (which may comprise at least some example implementations of the methods 1514, 1560 of FIGS. 7,9). For instance, performing at least some of the features of the example pulmonary therapies may act to increase FRO 7613 / EELV 7612 (e.g. at 7222 in FIG. 15A) of respiratory parameters 7610 of FIG. 15B, which may cause a significantly therapeutic decrease in upper airway (UA) col lapsibi I ity 7616 (7226 in FIG. 15A) to promote upper airway patency. In some such examples, these actions (and / or effects) caused by performing pulmonary therapy (in the examples of FIGS. 1-13D, 17) may, in turn, cause a decrease in respiratory control gain (RCG) 7224 (FIG. 15A) according to the principles further described below, which may result in related or associated effects on CO2 threshold 7622, CO2 pattern 7261 , CO2 level 7260, etc. as further described below in association with at least FIGS. 15A-16F (e.g. particularly in association with the at least some of the examples of FIGS. 16D-16F) which are beneficial to treating SDB. Moreover, in at least some examples in which delivering pulmonary therapy (e.g. FIGS. 1 -13D, 17) are performed in complementary relation with at least some of examples of stimulating tissues (e.g. FIGS. 7-12) (or method 166 in FIG. 1 ), a beneficial synergistic effect may be achieved in increasing EELV 7612, FRC 7613 (e.g. 7222 in FIG. 15A), which may cause an even more therapeutically significant decrease in upper airway collapsibility 7616 in FIG. 15B (at 7226 in FIG. 15A), which may more extensively promote upper airway patency to further decrease (at least) obstructive sleep apnea.

[0124] With general reference to FIGS. 15A-15B, and with specific reference to FIG. 15C, FRC 7131 (parameter 7613 in FIG. 15B) generally comprises the volume of air present in the lungs and airway at the end of tidal expiration 7123 (e.g. the sum of expiratory reserve 7128 and residual volume 7129). In some examples, EELV 7130 (parameter 7612 in FIG. 15B) may generally correspond to FRC 7131 (e.g. such as when positive end-expiratory pressure (PEEP) isapplied) as shown in FIG. 15C. FIG. 15C is a graph 7150 illustrating example respiratory parameters (e.g., FRO 7131 , EELV 7130, among others) across a respiratory waveform, which includes inspiration and expiration phases as shown by the end tidal inspiration 7121 , end tidal expiration 7123, end max inspiration 7124, and end max expiration 7125.

[0125] FIG. 15A is a diagram 7300 illustrating an example method of treating SDB (e.g. OSA) via modulating at least one respiratory parameter. In some examples, at 7302 of FIG. 15A, a method includes activating diaphragm-related tissue, via a stimulation element. In some examples, method 7300 of treating SDB may comprise activating upper airway patency-related tissue via a stimulation element, as shown at 7301 , to modulate a respiratory parameter at 7304. The stimulation element used to activate (e.g. stimulate) the upper airway patency-related tissue may be different from the stimulation element(s) used to activate the diaphragm-related tissue.

[0126] With continued reference to FIG. 15A, as previously noted, at 7301 the method may include activating the upper airway patency-related tissue, which may comprise a hypoglossal nerve (HGN) and / or its innervated muscles (e.g. genioglossus muscle), an infrahyoid muscle (IHM)-innervating nerve and / or its innervated muscles (e.g. infrahyoid strap muscles such as but not limited to the sternothyroid muscle), and / or other upper airway patency-related tissue (e.g. nerves and / or muscles) for treating SDB. For many patients, the activation of the upper airway patency-related tissue, at 7301 , may be sufficient to treat the SDB.

[0127] However, in some examples, method 7300 comprises activating diaphragm-related tissue (7302) in addition to activating upper airway patency- related tissue (7301 ). In some such examples, the diaphragm-related tissue may be activated during (e.g. generally concurrently with) activation of the upper airway patency-related tissue according to various stimulation protocols.

[0128] On the other hand, in some examples, method 7300 may comprise treating SDB via activating diaphragm-related tissue at 7302 (to modulate a respiratory parameter 7304) without activating (e.g. stimulating) an upper airway patency-related tissue (7301 ) for at least some portion of a treatment period.

[0129] The activation of the upper airway patency-related tissue at 7301 may cause modulation of a respiratory parameter(at 7304), which may comprise decreasing upper airway collapsibility parameter (7616 in FIG. 15B) as shown at 7226. In some such examples, decreasing upper airway collapsibility 7226 may comprise stiffening walls 7229 (e.g. posterior and / or lateral pharyngeal walls) of the upper airway and / or tongue protrusion 7330, as shown by arrows 7210C, 7210B, respectively. In some examples, decreasing upper airway collapsibility 7226 may comprise one aspect of promoting upper airway patency.

[0130] In some examples, tongue protrusion 7330 may be implemented via stimulating the hypoglossal nerve (HGN) and / or genioglossus muscle at 7301 , as represented via dotted line 7210B and the dotted box of tongue protrusion 7330. In some examples, stiffening walls 7229 (of the upper airway) may be implemented via stimulating an infrahyoid strap muscle (e.g. the sternothyroid muscle) and / or IHM-innervating nerve at 7301. As further described later in association with at least FIG. 15D, stimulating upper airway patency-related tissue also may comprise other target tissues and / or additional target tissues.

[0131] Regarding the aspect of decreasing upper airway collapsibility 7226 of method 7300 in FIG. 15A, in some examples, stiffening walls 7229 (FIG. 15A) can be implemented via modulating respiratory parameters such as but not limited to increasing EELV (at 7222), as further described later.

[0132] Further reference is now made to the remainder of FIG. 15A with particular attention to modulation of respiratory parameters (7304) via activation of diaphragm-related tissue (7302). In some such examples, modulating respiratory parameters (7304) may comprise decreasing (e.g. preventing or minimizing) periodic breathing 7221 , increasing EELV 7222, increasing tidal volume 7223, decreasing RCG 7224, and / or the previously described decreasing upper airway collapsibility 7226, as shown by arrows 7210A, 7210D, 7228A, 7228B, 7228C, 7228D, 7228E. It will be understood that these respiratory parameters (e.g. respiratory function parameters) are examples and that, in some examples, other respiratory function parameters may be modulated in addition to, and / or instead of, the respiratory function parameters shown in FIG. 15A.

[0133] In some examples, such stimulation of diaphragm-related tissue (7302) may cause an increase in EELV 7222. An increase in EELV 7222 may cause a decrease in upper airway collapsibil ity 7226 and a decrease in respiratory control gain (RCG) 7224, as shown by arrows 7228A, 7228B, 7228D, 7228E. In some examples, the decrease in RCG 7224 may be mechanically caused by the decrease in upper airway collapsibility 7226, as shown by arrow 7228D. For example, the diaphragm-related tissue may be activated (7302) to increase EELV 7130 (at 7222), which may reduce collapsibility of the upper airway (path 7228A; parameter 7616 in FIG. 15B), as shown at 7226 in FIG. 15A. Reducing collapsibility of the upper airway may prevent or mitigate OSA events.

[0134] Among other effects, increased EELV (at 7222 in FIG. 15A) corresponds to an increased mass within the lungs, which causes a pulling downward (i.e. caudal traction) of tissues defining the upper airway. This caudal traction effectively stiffens the walls of the upper airway, which reduces upper airway collapsibility (at 7226 in FIG. 15A) and thereby maintains upper airway patency (at 7330 in FIG. 15A) to prevent or minimize OSA events. For example, decreased upper airway collapsibility (7226) may result in fewer SDB events (e.g. lessen OSA). In some examples, in addition or alternatively, the decrease in RCG 7224 may be caused in response to or by the increase in EELV (7222), as shown by arrow 7228B. In one aspect, increases in EELV (7222) may result in greater air reserves, including CO2, and which may cause less sensitivity to fluctuations in CO2 levels. Further aspects relating to increasing EELV 7222 are described below in association with at least FIGS. 15D-16F. In some examples relating to increasing EELV (7222), the stimulation of diaphragm-related tissue (7302) is timed with respiration to coincide with at least a portion of the expiratory phase of the respiratory cycle, as further described later in association with at least FIG. 15D.

[0135] In some examples, stimulation of diaphragm-related tissue (7302) in example method 7300 of FIG. 15A may cause an increase in tidal volume, as shown at 7223. Among other effects, the increase in tidal volume 7223 may cause a decrease in RCG 7224, as represented by arrow 7228C. For example, the increase in tidal volume 7223 may increase ventilation (7621 in FIG. 15B) anddecrease (e.g. prevent or minimize) periodic breathing (at 7221 in FIG. 15A), which is further described later in association with FIG. 16A-16F. In some examples, increasing tidal volume 7223 may decrease a CO2 threshold 7622 (FIG. 15B) at which the body slows breathing or stops breathing in order to increase the CO2 level present to levels at which normal breathing occurs. By decreasing the CO2 threshold 7622, the patient may handle greater fluctuations in CO2 levels without entering into dysfunctional respiratory (e.g. breathing) patterns such as periodic breathing (7611 in FIG. 15B). At least some of these aspects regarding increasing tidal volume and related causes / effects are described in association with at least FIGS. 15D-16F. In some examples relating to increasing tidal volume (7223), the stimulation of diaphragm-related tissue (7302) is timed with respiration to coincide with at least a portion of the inspiratory phase of the respiratory cycle, as further described later in association with at least FIG. 15D.

[0136] For example and as described above, both the diaphragm-related tissue (at 7302) and the upper airway patency-related tissue (7301 ) may be activated to promote upper airway patency 7330 and, in some examples, may modulate at least one additional respiratory parameter, such as increasing EELV 7222, increasing tidal volume 7223, decreasing RCG 7224, and / or decreasing upper airway collapsibility 7226.

[0137] In some examples, respective respiratory parameters may be related to one in another in that modulation of a first respiratory parameter may cause modulation of a second respiratory parameter. In some examples, the first and second respiratory parameters may be exhibited together (e.g. at the same or near same time) whether or not they are respectively related to one another in cause and effect. In some examples, respective respiratory parameters may occur at different points in time without necessarily being related to one another in a cause and effect relationship.

[0138] With this in mind, a few introductory examples are provided while a fuller discussion of some respiratory parameters occur later in association with FIGS. 15D and 16A-16F. For instance, as illustrated by arrow 7228D in FIG. 15A, decreasing upper airway collapsibility (e.g. to promote upper airway patency)7330 may cause a decrease in RCG 7224. In some such examples, decreasing upper airway collapsibility (e.g. to promote upper airway patency) 7330 may reduce the frequency of SDB events, resulting in the decrease in RCG 7224. In some examples, stimulation of the diaphragm-related tissue (7302 in FIG. 15A) which is timed to cause an increase in tidal volume (at 7223), may additionally cause an increase in EELV 7222, albeit less of an increase than caused by stimulation of the diaphragm-related tissue that is timed to cause the increase in EELV 7222.

[0139] In some examples, stimulation of the diaphragm-related tissue which is timed to cause an increase in EELV 7222 may additionally cause an increase in tidal volume 7223, albeit less of an increase than caused by stimulation of the diaphragm-related tissue that is timed to cause the increase in tidal volume 7223.

[0140] Accordingly, stimulation of the diaphragm-related tissue (7302) may cause a combined effect on both increasing EELV (7222) and increasing tidal volume (7223).

[0141] In some examples, stimulation of the upper airway patency-related tissue (7301 ) may cause an increase in additional respiratory parameters, such as illustrated by arrow 7212D.

[0142] In some examples, the modulated respiratory parameter in method 7300 of FIG. 15A may include periodic breathing parameter (7611 in FIG. 15B), wherein stimulating diaphragm-related tissue (7302) may decrease periodic breathing, as represented at 7221 in FIG. 15A. Patients experiencing SBD, such as OSA-type SBD events, may sometimes exhibit periodic breathing behavior and / or otherwise unproductive breathing. This periodic breathing may include a repeating respiratory pattern of relatively fast and deep breaths (e.g. hyperventilation) followed by relatively slow and shallow breaths (e.g. hypoventilation). Among other causes, effects and / or characteristics, in periodic breathing a patient’s carbon dioxide (CO2) levels may significantly fluctuate in combination with ventilation (7621 in FIG. 15B) (i.e. movement of air in / out of lungs) becoming unstable. However, stimulating the diaphragm-related tissue (7302) in example method 7300 of FIG. 15A may decrease (e.g. prevent or minimize) periodic breathing (at 7221 ), which may stabilize ventilation and manage CO2 levels in amanner to treat sleep disordered breathing (SDB), such as (but not limited to) OSA-type SDB events.

[0143] With this in mind, FIG. 16A illustrates an example diagram 7203 of periodic breathing and includes a respiratory pattern 7220 shown in relation to a CO2 pattern 7261 of an example patient’s CO2 level 7260. The respiratory pattern 7220 comprises first grouping(s) 7230 of breaths 7212 (in which each breath 7212 is represented via a vertical line) and second grouping(s) 7240 of breaths 7241 (in which each breath 7241 is represented via a vertical line). As previously noted, each breath (e.g. 7212, 7241 ) includes both inspiration and expiration such that each “breath” corresponds to a respiratory cycle. As shown in FIG. 16A, the vertical length of the lines representing breaths 7212 (in groupings 7230) and of the lines representing breaths 7241 (in groupings 7240) correspond to a depth of the breath (e.g. longer lines representing deeper breaths, shorter lines representing shallower breaths). The spacing between the lines which represent breaths 7212, and the spacing between the lines which represent breaths 7241 , corresponds to a frequency (e.g. rate) of the breaths (e.g. lines are closer together for faster breathing; lines are farther apart for slower breathing). As further shown in FIG. 16A, in CO2 pattern 7261 the CO2 level 7260 varies along the respiratory pattern 7220 with a rising and falling CO2 level 7260 driving and resulting in a breathing response of faster / deeper breathing (groupings 7230 of breaths 7212) followed by slower, shallower breathing (groupings 7240 of breaths 7241 ), and so on.

[0144] It will be understood that the vertical length and / or spacing (e.g. D1 , D2) of the respective lines representing breaths 7212, 7241 are used to express a general physiological model and that for any given patient and / or any given episode(s) of periodic breathing, the particular depth or shallowness of breaths (e.g. represented via vertical line length) and / or the particular frequency of breaths (e.g. represented via space between adjacent vertical lines) may vary from that shown in FIGS. 16A, 16C.

[0145] A factor that may stimulate respiration is the concentration of CO2 in the blood. In some examples, periodic breathing may comprise and / or reflect swings in CO2 level 7260 that extend outside a healthy range. For example, periodicbreathing may be triggered by a disturbance 7211 , such as a SDB event. As part of and / or following the disturbance 7211 , a period 7217 may occur during which no breaths occur or during which “reduced airflow” breaths occur. This period 7217 may cause the CO2 level 7260 to increase and oxygen level to decrease. For example, in some instances and in response to the disturbance 7211 , as shown in FIG. 16A the CO2 level 7260 rises steadily to a peak segment 7262 which is above a first (e.g. ceiling) threshold 7254A of a target range (7254A, 7254B) of a CO2 level 7260. In response to the disturbance 7211 and the rise of the CO2 level 7260 at 7262, the patient may take relatively fast, deep breaths, as illustrated by the breaths 7212 (of first group 7230) extending past horizontal lines 7213, 7214 which represent a nominal breathing depth and with breaths 7212 at a frequency (e.g. spacing D1 ) faster than a nominal breathing frequency (see spacing D3 in of FIG. 16B). The fast and deep breaths, e.g. first group 7230 of breaths 7212, may be a part of a neurological arousal response to the disturbance7211 and / or response flowing from the rising CO2 level 7260 after the disturbance 7211. In some examples, the first group 7230 of breaths 7212 (e.g. faster, deeper breaths) may cause the CO2 level 7260 to decrease from its peak to a level which is below a second threshold 7254B (e.g. floor) of the target range (7254A, 7254B) of the CO2 level 7260. The CO2 level may decrease to a “negative” peak, as shown via segment 7264. As the CO2 level 7260 decreases, the patient may respond by taking relatively slow and shallow breaths, as illustrated by the second group 7240 of breaths 7241 which have a shallower depth (e.g. shorter vertical lines) and do not reach horizontal lines 7213, 7214. Breaths 7241 also occur at a frequency (e.g. higher spacing D2) which is less than the nominal breathing frequency (e.g. spacing D3 in FIG. 16B) but less than the frequency of breaths7212 (e.g. spacing D1 ). As the second group 7240 of shallower, slower breaths 7241 continues, the CO2 level 7260 eventually begins to increase again until it eventually reaches another peak such as second instance of segment 7262, with this increasing CO2 level 7260 again causing faster, deeper breathing as represented via another grouping 7230 of breaths 7212.

[0146] FIG. 16B illustrates an example respiratory pattern 7205 in which periodic breathing does not occur and / or was prevented via stimulation ofdiaphragm-related tissue according to examples of the present disclosure, such as method 7300 in FIG. 15A to minimize or prevent periodic breathing at 7221. As shown by FIG. 16B, breaths 7255 occur with a uniform depth as illustrated by the most or all of the vertical lines representing breaths 7255 having a length terminating at / near the horizontal lines 7213, 7214 and the breaths 7255 occurring with a uniform, consistent frequency as illustrated by the lines representing breaths 7255 exhibiting uniform spacing D3, which comprises a nominal breath frequency is greater than D1 and less than D2 in FIG. 16A. In one aspect, FIG. 16B also illustrates that CO2 level 7260 may generally fluctuate over time (e.g. long term minor fluctuations) within an acceptable range (e.g. between lines 7254A, 7254B) which does not induce periodic breathing. As noted elsewhere, it will be understood that changes in the CO2 level 7260 may occur within a breath with such changes also falling within the acceptable range (e.g. between lines 7254A, 7254B).

[0147] In contrast to the normal respiratory pattern 7205 in FIG. 16B, the periodic breathing in FIG. 16A comprises breaths which occur irregularly and / or with significantly varying depth, frequency, etc. which correspond to unstable ventilation (e.g. instability in ventilation). In some examples, periodic breathing may escalate, as illustrated in connection with FIG. 16C. For example, as shown in the respiratory pattern 7201 in FIG. 16C, the first groups 7230A, 7230B of breaths 7212A, 7212B (respectively) and the second group 7240A of breaths 7241A (respectively) generally correspond to similar groups (e.g. 7230, 7240) shown in FIG. 16A. However, as further shown in FIG. 16C, in some instances the periodic breathing may escalate as exhibited via subsequent first groups 7230C, 7230D of breaths 7212C, 7212D (respectively) and subsequent second groups 7240B, 7240C, 7240D of breaths 7241 B, 7241 C, 7241 D (respectively). In particular, in these subsequent first groups 7230C, 7230D, the breaths 7212C, 7212D occur at a frequency even higher (e.g. faster as represented via decreased spacing D5, D7) than the frequency (spacing D1 ) of breaths 7212A, 7212B of groups 7230A, 7230B and with breaths 7212C, 7212D occurring at even greater depths (e.g. longer vertical lines) than breaths 7212 of groups 7230A, 7230B. Meanwhile, the breaths 7241 B, 7241 C, 7241 D of subsequent second groups7240B, 7240C, 7240D occur at a frequency even lower (e.g. less often as represented via increased spacing D4, D6, D8) than the frequency of breaths 7241 A (spacing D2) of group 7240A and with breaths 7241 B, 7241 C, 7241 D (of groups 7240B, 7240C, 7240D) occurring at even shallower depths (e.g. shorter vertical lines) than breaths 7241 A, of group 7240A.

[0148] Within this context, FIG. 16C also illustrates the more abrupt and intense swings in CO2 level 7260 which both may precipitate, and result from, these breathing changes. For instance, the group 7230C of breaths 7212C (e.g. even faster, deeper breathing) is generally associated with, and / or is a response to, the elevated CO2 level 7260 represented by segment 7262C which comprises a relatively sharper, and higher peak than the segment 7262B of elevated CO2 level 7260. In one aspect, this relatively stronger response may result from the persistent variance of the CO2 level 7260 as the CO2 level 7260 swings back and forth above and below a target level / range (e.g. 7254A, 7254B). In some examples, this stronger breathing response (e.g. at 7230C) also may be a reaction from the significantly lower CO2 level 7260 associated with the even slower, shallower breaths 7241 B of group 7240B (spacing D4 greater than spacing D2), which occurred as the CO2 level 7260 significantly decreased as represented by segment 7264B.

[0149] Meanwhile, as further shown in FIG. 16C, the group 7240C of breaths 7241 C (e.g. even slower, shallower breathing as represented by spacing D6 being greater than spacing D4) is generally associated with, and / or is a response to, the rapidly decreasing (and decreased) CO2 level 7260 represented by segment 7264C which comprises a relatively sharper, and greater amplitude peak of decreased CO2 level 7260 than the segment 7264B of decreased CO2 level 7260.

[0150] As further shown in FIG. 16C, as the periodic breathing and associated swings in CO2 level 7260 worsens, the subsequent group 7230D of breaths 7212D may be even deeper and / or faster (e.g. spacing D7 less than D5, less than D1 ) and group 7240D may include even shallower and / or slower (e.g. spacing D8 greater than spacing D6, which is greater than D4, etc.) breaths 7241 D.

[0151] Accordingly, FIG. 16C illustrates a worsening pattern of swings of CO2 level 7260 both above and below threshold / target range, and the associated increasingly exaggerated periodic breathing pattern.

[0152] Stimulation of diaphragm-related tissue (7302) according to at least some examples of the present disclosure (e.g. method 7300 in FIG. 15A) may provide therapy for SDB by preventing occurrence of, or preventing escalation of, the periodic breathing by causing more regular uniform breathing of the patient in a frequency and / or depth of breaths, as shown in FIG. 16B.

[0153] FIG. 16D is a diagram of an example respiratory pattern in which a disturbance 7211 occurs and associated period 7273 (occurs as part of and / or following the disturbance 7211 ) generally lack breaths, in a manner similar as described in FIGS. 16A-16C. However, as represented in FIG. 16D, some example methods comprise applying stimulation 7274 (e.g. stimulation of diaphragm-related tissue 7302 in FIG. 15A) during at least a portion of period7273 to prevent or minimize periodic breathing (e.g. the patterns in FIGS. 16A, 16C) and instead cause or maintain generally uniform breathing. Stimulation7274 may be delivered upon sensing disturbance 7211 and / or receiving notification of a sensed disturbance 7211. In some examples, the stimulation 7274 may comprise one or more stimulation cycles with each stimulation cycle including a stimulation period and a non-stimulation period. Stimulation 7274 may extend during all or just part of period 7273. In some examples, stimulation is applied to diaphragm-related tissue as in the examples of at least FIGS. 15A-15B. However, in some examples, stimulation may be applied to additional or other target tissues such as at least those in various examples throughout the present disclosure.

[0154] With further reference to FIG. 16D, the delivery of stimulation 7274 of diaphragm-related tissue per examples of the present disclosure causes a group 7256 of breaths 7257 (dotted lines) which otherwise would not have occurred due to (and / or as part of) disturbance 7211. The stimulation-induced occurrence of breaths 7257 helps to maintain CO2 level 7260 within its target range (e.g. between level 7254A, 7254B) and avoid elevation of the CO2 level 7260 to higher levels (e.g. 7262 in FIG. 16A, 16C) and / or to lower CO2 level 7260 (e.g. segment7264) out of the target range (7254A, 7254B). After stimulation 7274 and the induced breaths 7257, normal breaths 7255 ensue at a regular, uniform depth and frequency (spacing D3) in a manner similar to that shown in FIG. 16B.

[0155] FIG. 16E is a diagram of an example respiratory pattern and example method 7208 of stimulating a diaphragm-related tissue. Method 7208 may comprise at least some of substantially the same features and attributes as method 7207 of FIG. 16D, except with stimulation 7284 being applied during period 7285 instead of during period 7273 (FIG. 16D). In particular, as shown in FIG. 16E, upon sensing the group 7230A of breaths 7212A and / or the elevated CO2 level 7260 (e.g. at / near segment 7262A), the example method 7208 applies stimulation 7284 during period 7285 which causes a group 7280 of stimulation- induced breaths 7282 (vertical dotted lines), which acts to increase the CO2 level 7260 back to its target range 7254A, 7254B. These stimulation-induced breaths 7282 prevent the decrease (segment 7264 in FIG. 16A, 7264A in FIG. 16C) in CO2 level 7260, and subsequent reactive CO2 swings (significant increase, significant decrease, etc.) exhibited in FIG. 16A, 16C during periodic breathing that would otherwise occur in the absence of such stimulation 7284. After the stimulation-induced breaths 7282, breaths 7255 of uniform depth and spacing (D3) may occur in a manner similar to method 7207 of FIG. 16D.

[0156] Accordingly, application of the stimulation 7284 (in method 7208 of FIG. 16E) interrupts behaviors which have become or may become periodic breathing (FIG. 16A, 16C). Moreover, in doing so, the stimulation also may modulate additional or other respiratory parameters such as decreasing or preventing RCG (RCG - 7620 in FIG. 15B) as shown at 7224 in FIG. 15A, as further described below. Aspects of method 7300 in FIG. 15A may decrease RCG (at 7224), which in turn may prevent or minimize periodic breathing (at 7221 in FIG. 15A).

[0157] In some examples, in the example method 7208 of FIG. 16E, in addition to application of stimulation 7284 of method 7208 in FIG. 16E, stimulation 7274 also may be applied in a manner similar to method 7207 in FIG. 16D.

[0158] FIG. 16F is a diagram illustrating an example method 7209 of stimulating diaphragm-related tissue to prevent and / or minimize periodic breathing. Method 7209 may comprise at least some of substantially the same features as method7207 of FIG. 16D and / or method 7208 of FIG. 16E, except with some stimulation 7295 being applied in intervals after an initial stimulation 7294 during period 7273 (like initial stimulation 7274 in FIG. 16D).

[0159] As in the example of FIG. 16D, in the example of FIG. 16F application of initial stimulation 7294 (of diaphragm-related tissue) in response to sensing disturbance 7211 provides a group 7290 of stimulation-induced breaths 7292A, which help to immediately minimize or prevent CO2 level 7260 from swinging above and below range (e.g. upper 7254A, lower 7254B), which helps to maintain breaths 7255 to be generally uniform in depth and spacing (e.g. D3). In addition, in example method 7209 additional stimulation 7295 may be applied at intervals (e.g. every 3 breaths, every 4 breaths, etc.) to cause stimulation-induced breaths 7292B (dotted lines). In some examples, each additional stimulation 7295 may correspond to a duration of a single breath or multiple breaths, in some examples. By spacing these stimulations 7295 (and ensuing stimulation-induced breaths 7292B) apart, the example method 7209 helps to ensure that breaths 7255, 7292B remain generally uniform in depth and spacing, which may help prevent a second disturbance 7211 and / or to quickly prevent periodic breathing if such a second disturbance were to occur.

[0160] With further reference to FIGS. 15A-15B, as further represented via arrow 7228G (FIG. 15A) in some examples, stimulating diaphragm-related tissue (7302) may cause an increase in the EELV (at 7222), which may contribute to preventing occurrence of, or preventing escalation of, periodic breathing at 7221 . For example, upon increasing the EELV (at 7222) in this manner, the patient may experience fewer respiratory disturbances (e.g. 7211 in FIG. 16A) caused by OSA events, such that periodic breathing may not occur at all or may be minimized (7221 ). In some such examples, the number of respiratory disturbances may be reduced to a frequency below a threshold frequency (e.g. AHI threshold).

[0161] Referring again to FIG. 15C, tidal volume 7127 (parameter 7618 in FIG. 15B) may comprise the amount of air moved through the lungs when a patient inhales and exhales during a single breath. In some examples, modulating the tidal volume parameter (7618 of FIG. 15B) may include increasing tidal volume as shown at 7223 in FIG. 15A, which may increase ventilation (7621 in FIG. 15B).In some examples, increasing tidal volume (at 7223 in FIG. 15A) may prevent occurrence of, and / or escalation of, periodic breathing (7221 of FIG. 15A). For example, increasing tidal volume (at 7223 in FIG. 15A) may decrease a CO2 level threshold (7622 in FIG. 15B; 7250 in FIG. 16A). As previously noted, a decrease in CO2 below threshold 7622 may cause a patient to slow their breathing or stop breathing in order to increase the CO2 level (e.g. 7260 in FIGS. 16A-16F) back up to or over the threshold 7622. Consequently, in some examples, by decreasing the CO2 level threshold 7622 (e.g. via increasing the tidal volume 7223), the patient may be able to handle greater fluctuations in their CO2 level 7260.

[0162] From the foregoing context of at least FIGS. 15A-16F, it will be understood that in some examples decreasing (e.g. preventing or minimizing) periodic breathing (7221 in FIG. 15A) may comprise an effect of, and / or cause of, decreasing RCG at 7224 in FIG. 15A. Moreover, as shown in at least FIG. 15A and discussed herein, other factors (increasing EELV, increasing tidal volume, etc.) may contribute to decreasing periodic breathing by those factors acting to decrease RCG at 7224 (FIG. 15A).

[0163] With further reference to 7304 of method 7300 in FIG. 15A, in some examples, modulating the respiratory parameter (7304) may include decreasing RCG at 7224 (parameter 7620 in FIG. 15B). Changes in RCG may include, or be associated with, a response of the patient to a varying CO2 level (e.g. 7260 in FIG. 16A-16C) such as (but not limited to) variances in CO2 level 7260 which may occur in periodic breathing (7221 in FIG. 15A; 7611 in FIG. 15B; and FIGS. 16A- 16F). As shown by and referring to FIG. 16A, a CO2 level 7260 may become low in a patient after the patient takes large (e.g. deep) breaths (e.g. 7212 in groups 7230). However, upon taking small breaths (e.g. 7241 in groups 7240) or not breathing, the CO2 level 7260 may increase and may become relatively high as represented by segment 7262 in FIG. 16A. When a CO2 level 7260 decreases below the CO2 level threshold 7250 (7622 in FIG. 15B) for the particular patient, the patient may slow their breathing (e.g. breaths 7241 in FIG. 16A) or stop breathing in order to increase the CO2 level 7260 back up to or over the threshold 7250. The threshold 7250 (7622 in FIG. 15B) at which the CO2 level 7260 causesthe patient to slow breathing or to stop breathing is associated with RCG (7620 in FIG. 15B). For example, RCG 7620 may, in part, affect a magnitude of a patient’s breathing response to swings (e.g. increases and decreases) in the CO2 level 7260 above and below threshold 7250. For example, the patient may exhibit swings between hyperventilation (e.g. hypernea) and hypoventilation (e.g. apneas and hypopneas).

[0164] However, via at least some examples of the present disclosure, stimulating diaphragm-related tissue (7302) may decrease RCG (at 7224), which in turn causes a patient’s breathing responses (e.g. breaths 7212, 7241 in FIG. 16A) to fluctuations in CO2 level 7260 to be more gradual and / or less pronounced, which in turn may induce a quicker return to a generally uniform respiratory pattern (e.g. FIG. 16B).

[0165] In some examples, modulating the respiratory parameter (7304 in FIG. 15A) may comprise a combination of increasing both EELV 7222 (parameter 7612 in FIG. 15B) and tidal volume 7223 (parameter 7618 in FIG. 15B) to prevent occurrence of or prevent escalation of periodic breathing 7221 in FIG. 15A (parameter 7611 in FIG. 15B). In this example, increasing both EELV and tidal volume may provide a combined effect that is greater than if just one of those respective respiratory parameters is increased (e.g. via stimulation of diaphragm- related tissue 7302 in FIG. 15A). In some of these examples, a combination of increasing EELV (at 7222 in FIG. 15A) and increasing tidal volume (at 7223 in FIG. 15A) may work together to reduce RCG (at 7224 in FIG. 15A).

[0166] With these various examples of FIGS. 15A-15C, 16A-16F in mind, for example and in accordance with the above, modulating at least one respiratory parameter (7304) may comprise at least one of: (i) preventing or mitigating reduction in EELV (e.g. EELV stays the same or has minimal reduction), and in some instances, increase FRC and / or EELV (e.g. FRC and / or EELV increases), (ii) preventing or mitigating a reduction in diaphragmatic electromyographic activity (EMG), (iii) increasing or maintaining upper airway patency, (iv) increasing ventilation, (v) preventing or mitigating an increase in RCG, and in some instances, decreasing RCG, and / or (vi) increasing tidal volume.

[0167] FIG. 15D is a block diagram illustrating an example stimulation portion 7500 which comprises some example stimulation parameters by which stimulation of a diaphragm-related tissue (and / or of an upper airway patency- related tissue) may be implemented in association with (or independent of) various examples of the present disclosure in FIGS. 14A-16F. In some examples, the stimulation portion 7500 may comprise an example implementation of, and / or at least some of substantially the same features and attributes as, the stimulation support portion (e.g., stimulation circuit 754 and stimulation element 720 of FIG. 14A) described throughout examples of the present disclosure and / or the control portion (e.g. FIGS. 13A-13C) of the present disclosure. Accordingly, the various functions and parameters of the stimulation portion 7500 may be implemented in a manner supportive of, and / or complementary with, the various functions, parameters, portions, etc. of such examples and / or various functions, parameters, portions, etc. relating to stimulation throughout examples of the present disclosure.

[0168] With reference to example method 7300 of FIG. 15A in association with FIG. 15D, in some examples, activating diaphragm-related tissue (7302) may be timed with respiration. Timing the activation (e.g. stimulation) with respiration may include identifying respiratory information, which is represented as respiratory information 7505 in FIG. 15D. The respiratory information 7505 may be sensed using one or more sensing modalities, which may be implemented as described in connection with at least FIGS. 9B-9C and 10 of U.S. Publication 2024 / 0216692, published on July 4, 2024, and entitled “Stimulating a Glossopharyngeal-Related Tissue for Upper Airway Patency”, which is incorporated herein it its entirety for its teaching. In some examples, identifying the respiratory information 7505 may include receiving sensed respiratory information 7505, such as from the same device which applies stimulation or from another device separate from the device applying stimulation. Activation (e.g. stimulation) being timed with respiration, as used herein, in some examples may refer to or include implementing the activation (e.g. stimulation) based on respiration, such as starting, stopping, and / or pausing each stimulation period of a stimulation cycle (of a series of stimulation cycles) relative to respiratoryinformation 7505. In some examples, such respiratory information 7505 may include, but is not limited to, parameters relating to a feature of the respiratory waveform 7508 (e.g. morphology), respiratory phase parameter(s) 7510, among other information.

[0169] The respiratory phase parameter 7510 may include parameters regarding inspiratory phase 7512 (e.g. inspiration), expiratory phase 7514 (e.g. expiration), and / or a transition 7518 between inspiration and expiration. In some examples, the respiratory information 7505 may include respiratory rate, respiratory rate variability, rate times volume, among other parameters.

[0170] For example, via inspiratory phase parameter 7512, stimulation of diaphragm-related tissue (7302 in FIG. 15A) may be applied to coincide with all (or a part of) an inspiratory phase of the respiratory cycle. In some such examples, the activating of diaphragm-related tissue 7302 is timed to occur during each inspiratory phase (and not during the expiratory phase) for each respective respiratory cycle of a selectable number of respiratory cycles.

[0171] As previously described, in some examples stimulating diaphragm- related tissue during the inspiratory phase may increase tidal volume (at 7223 in FIG. 15A). In some examples, activating diaphragm-related tissue (7302 in FIG. 15A) during an inspiratory phase may modulate a tidal volume parameter and a RCG parameter. In some such examples, the tidal volume may increase, and the RCG may decrease. In addition, and in some examples, activating the diaphragm-related tissue 7117 during inspiratory phases may modulate the EELV parameter, such as EELV increasing (7222).

[0172] In some examples, via expiratory phase parameter 7514, stimulation may be timed with respiration so as to be applied during (e.g. coincide with all (or part of)) an expiratory phase of a respiratory cycle such as (but not limited to) during each expiratory phase (and not the inspiratory phase) for each respective respiratory cycle of a selectable number of respiratory cycles. In some such examples, this stimulation may cause supra-threshold contraction of the diaphragm muscle. Stimulating diaphragm-related tissue during the expiratory phase may increase EELV (at 7222 in FIG. 15A). As previously described, among other effects, this increase in EELV may induce caudal traction, whichmay stiffen walls (e.g. lateral and / or posterior pharyngeal wall) at 7229 in FIG. 15A to decrease upper airway collapsibility (at 7226 in FIG. 15A).

[0173] In some examples, activating the diaphragm-related tissue (7302 in FIG. 15A) during expiratory phases may modulate an EELV parameter and a RCG parameter. In some such examples, the activation (e.g. stimulation) causes an increase in the EELV (7222 in FIG. 15A) and a decrease in the RCG (7224 in FIG. 15A). In addition, and in some examples, activating the diaphragm-related tissue (7302 in FIG. 15A) during expiratory phases may modulate the tidal volume parameter, such as causing an increase in the tidal volume (7223 in FIG. 15A).

[0174] In some examples, via transition parameter 7518 in FIG. 15D, stimulation (7302 in FIG. 15A) may be applied during (e.g. coincide with all (or part of)) the transition between the inspiratory phase 7512 and expiratory phase 7514. In some examples, stimulation may be applied during (e.g. coincide with all of, or a part of) a combination of at least a portion of the inspiratory phase and at least a portion of expiratory phase of the respiratory cycle. It will be understood that in some such examples the stimulation period does not extend through the entire inspiratory phase and does not extend through the entire expiratory phase, but rather the stimulation period extends over some latter portion of the inspiratory phase and over at least some initial portion of the expiratory phase. In some such examples, the stimulation of the diaphragm-related tissue (7302 in FIG. 15A) during such transition 7518 is implemented without activating the diaphragm- related tissue during the entire expiratory phase (or a substantial majority of each expiratory phase) for each respective respiratory cycle.

[0175] In some examples, activating the diaphragm-related tissue (7302 in FIG. 15A) during (e.g. coincide with) a transition(s) 7518 between the inspiratory phase and the expiratory phase may increase an EELV parameter (7222 in FIG. 15A, 7612 in FIG. 15B), hinder increases in RCG parameter (7620 in FIG. 15B), e.g. decrease the RCG parameter at 7224 in FIG. 15A, and / or increase a tidal volume parameter (7618 in FIG. 15B) at 7223 in FIG. 15A. With further reference to transition parameter 7518 in FIG. 15D, in some examples, the stimulation may be selectively applied at the end of inspiration and overlapping with a start of expiration. In some such examples, the stimulation does not occur during abeginning and / or middle portion of the inspiratory phase 7512. In some of these examples, the stimulation does not occur during a middle portion and / or an end portion of the expiratory phase 7514.

[0176] Because activating diaphragm-related tissue (7302 in FIG. 15A) may increase application of intrathoracic negative pressure (parameter 7624) in addition to what might already be occurring naturally, in some examples the activation is applied at times and / or at magnitudes to achieve the target effect (e.g. increase EELV, decrease RCG, etc.) but without causing an undesired increase in intrathoracic negative pressure at times and / or magnitudes that might otherwise increase upper airway collapsibil ity . For example, when stimulating the diaphragm-related tissue (7302 in FIG. 15A) during the expiratory phase, and particularly near or during an end of the expiratory phase 7514, example methods may apply the stimulation at a tonic level (7532 in FIG. 15D) and / or at a selectable magnitude at which the effect of decreasing upper airway collapsibility (due to caudal traction) caused by increased EELV is greater than the effect of increasing upper airway collapsibility due to increase negative intrathoracic pressure caused by activating the diaphragm-related tissue. In some such examples, the decrease in upper airway collapsiblity (due to increase EELV caused by stimulating diaphragm-related tissue) may be strengthened, such as at end of an expiratory phase (e.g. during expiratory pause just prior to inspiration), via simultaneously stimulating upper airway tissue to increase upper airway patency during this same time frame. In some such examples, increasing the upper airway patency during this time frame may be implemented via tongue protrusion (7330 in FIG. 15A) caused by stimulating the hypoglossal nerve (and / or genioglossus muscle) and / or via stiffening the upper airway walls (7229 in FIG. 15A) via stimulating other nerves / muscles (e.g. IHM-innervating nerve, sternothyroid muscle, etc.) as described elsewhere in examples of the present disclosure.

[0177] As discussed elsewhere, general initiation, termination, pausing of a stimulation therapy protocol (e.g. a series of stimulation cycles) also may be timed with respiration, among other physiologic parameters.

[0178] With further reference to the stimulation portion 7500 in FIG. 15D, in some examples, example methods may use multiple stimulation elements. Forexample, stimulation may be applied to a first portion of the body via a first stimulation element and to a second portion of the body of the patient via a second stimulation element. In some examples, the first and second portions of the body may include the left and right sides of the patient such that the stimulation may be applied in a bilateral manner (parameter 7520 in FIG. 15D). In some examples, the respective first and second portions of the body correspond to different areas of one diaphragm-related tissue (7117 in FIG. 14A) on just one side (e.g. just the left side or just the right side) of the patients’ body. In some examples, the first portion of the body corresponds to a diaphragm-related tissue 7117 on a left side of the patient’s body and the second portion of the body corresponds to a diaphragm-related tissue 7117 on a right side of the patient’s body. In some examples, the stimulation may be applied, via at least one of the first and second stimulation elements, on one of a left side and an opposite right side of a body of the patient.

[0179] In some examples, the diaphragm-related tissue (7117 in FIG. 14A) comprises a first phrenic nerve 7118 and a second phrenic nerve 7118. In some such examples, a first stimulation element may be located on a first side of a body of the patient and at or in close proximity to the first phrenic nerve 7118, and a second stimulation element may be located on an opposite second side of the body and at or in close proximity to the second phrenic nerve 7118.

[0180] In some examples, the diaphragm-related tissue 7117 (FIG. 14A) comprises a first portion of the diaphragm muscle 7119 (e.g. a left diaphragm) and a second portion of the diaphragm muscle 7119 (e.g. a right diaphragm). In some such examples, a first stimulation element may be located on a first side (e.g. left side) of a body of the patient and at or in close proximity to the first portion of the diaphragm muscle 7119, and a second stimulation element may be located on an opposite second side (e.g. right side) of the body and at or in close proximity to the second portion of the diaphragm muscle 7119.

[0181] In some examples, the to-be-stimulated diaphragm-related tissue 7117 may be located on just one side (e.g. the same side) of the patient, such as two different portions of the diaphragm muscle 7119 being located on just one side of the patient (e.g. whether the left side or the right side). In some examples, thediaphragm-related tissue 7117 may comprise two different portions of a phrenic nerve 7118 being located on just one side (e.g. the same side) of the patient (e.g. whether the left side or right side).

[0182] In some examples, stimulation of diaphragm-related tissue (7302 in FIG. 15A) is applied for a selectable number of respiratory cycles, with the number of respiratory cycles being selected to reduce a frequency of SDB events. In some examples, after the stimulation for a selectable number of respiratory cycles to reduce the frequency of SDB events, this activation may be suspended at least until the frequency of SDB events again rises to an unacceptable level, at which time further activation of the diaphragm-related tissue may be implemented. In some such examples, the suspension(e.g. selective omission of activation) may be implemented for a selectable number of respiratory cycles . Stated differently, in some examples, the selectable number of respiratory cycles may be on an order of ones, such as a range of between one and ten breaths, one and five breaths, five and ten breaths, three and seven breaths, among other ranges. In some examples, the selectable number of respiratory cycles may be on an order of tens, such as a range between ten and fifteen breaths, ten and twenty breaths, fifteen and twenty breaths, among other ranges. In some examples, the selectable number of respiratory cycles may be on the order of both ones and tens, such as a range between five and fifteen breaths, five and twenty breaths, among other ranges. Accordingly, in some such examples, stimulating the diaphragm-related tissue (7302 in FIG. 15A) to modulate a respiratory parameter (7304) may be implemented in a manner which, without generally entraining breathing (in some examples), the patient’s respiratory response may be conditioned such that the SBD events may be reduced over time, using fewer stimulations of the diaphragm-related tissue, and / or with longer times between stimulation of the diaphragm-related tissue.

[0183] After the suspension of the activation of the diaphragm-related tissue for a selectable time period and / or selectable number of respiratory cycles, the activation of the diaphragm-related tissue may be resumed when needed again to reduce the frequency of SDB events.

[0184] In some examples, the selectable number of respiratory cycles may be determined based on correlation between a selectable activation pattern and a reduction in frequency of SDB events relative to a criteria. In some examples, the selection activation pattern may include a stimulation pattern and / or the selectable number of respiratory cycles. The criteria may include a threshold frequency of SDB events, as further described herein. In some examples, the correlation may be obtained from a database containing historical averages for a plurality of patients and / or may be determined using observations for the particular patient. In some such examples, modulation of the respiratory parameter (7304 in FIG. 15A) may comprise hindering an increase in RCG (7224 in FIG. 15A) to prevent occurrence of or minimize periodic breathing (7221 ). In some examples, an increase in RCG may be prevented (7224) via tonic stimulation (e.g. while preventing full contraction of the diaphragm).

[0185] In some examples, the stimulation may be selectively applied as a ramped stimulation (e.g. starts at a low amplitude and increases) that starts at the beginning of the inspiratory phase 7512 at a relatively-low intensity (e.g. a first value) and ramps up to a relatively-high intensity (e.g. a second value greater than the first value) at the end of the inspiratory phase 7512, with the stimulation stopping during the expiratory phase 7514 to prevent sudden negative intrapleural pressure at or just prior the start of a next inspiratory phase. In some such examples, the ramped stimulation may prevent the sudden negative intrapleural pressure. Recoil, which causes exhalation, may be reduced if the ramped stimulation is still present at the start of exhalation as the diaphragm may still be pulling on the lungs to prevent the recoil.

[0186] In some examples, unless otherwise noted, per supra-threshold parameter 7530 of stimulation portion 7500 in FIG. 15D, stimulation applied to the diaphragm-related tissue 7302 (FIG. 15A) in example methods may comprise an energy (e.g. amplitude, current, pulse width, etc.) to cause a supra-threshold contraction of the diaphragm muscle 7119.

[0187] Per parameter 7532 of stimulation portion 7500 in FIG. 15D, in some examples, activating the diaphragm-related tissue 7117 as timed with the respiratory information may comprise implementing the activation of diaphragm-related tissue 7117 as a tonic stimulation (7532), which causes the diaphragm muscle 7119 to exhibit tone but not a full contraction (e.g. a supra-threshold contraction). In some examples, a tonic stimulation 7532 may include delivering, to the diaphragm-related tissue 7117, a stimulation signal at a subthreshold intensity level during the treatment period, whether during a selectable number of respiratory cycles and / or according to other protocols. In some such examples, the tonic stimulation 7532 is applied to diaphragm-related tissue (e.g. 7302 in FIG. 15A) for each respective respiratory cycle of the selectable number of respiratory cycles.

[0188] In some examples, activating the diaphragm-related tissue 7117 as a tonic stimulation 7532 may modulate the EELV parameter (7612 in FIG. 15B) and the RCG parameter (7620 in FIG. 15B). In some examples, the EELV may increase (at 7222 in FIG. 15A; 7612 in FIG. 15B) and the RCG may decrease (at 7612 in FIG. 15B). In addition, and in some examples, activating the diaphragm- related tissue 7117 during expiratory phases may modulate the tidal volume parameter, such as tidal volume increasing (at 7223 in FIG. 15A; 7618 in FIG. 15B). In some examples, tidal volume may not increase because expiration may be reduced. In some examples, both EELV and tidal volume may increase as both expiration and inspiration contribute to tidal volume.

[0189] In some examples, stimulation of the diaphragm-related tissue (7302 in FIG. 15A) may be applied based on a disease burden parameter 7540, as shown in stimulation portion 7500 of FIG. 15D. In some examples, the disease burden parameter 7540 may comprise a frequency of SDB events such as, but not limited to, a number of SDB events per hour (e.g. apnea-hypopnea index (AHI)). In some examples, the diaphragm-related tissue is activated (7302 in FIG. 15A) in response to an SDB event. For example, at least one SDB event may be identified and in response, activation of the diaphragm-related tissue 7117 is implemented. In some examples, the activation of the diaphragm-related tissue is implemented solely in response to the identified at least one SDB event.

[0190] In some examples, per disease burden parameter 7540, the diaphragm- related tissue 7117 is activated in response to a frequency of a number of SDB events meeting a criteria. The threshold may include a threshold frequency. Forexample, SDB events may be tracked for the patient over a treatment period (e.g. night), and in response the frequency over the treatment period being greater than the threshold (e.g. the number of SDB events in period of time exceeding the threshold), the diaphragm-related tissue 7117 may be activated. For example, clinically, a patient with an AHI of 5 events per hour or less may be considered well-controlled enough to not invoke activation of the diaphragm-related tissue 7117, particularly where the activation of the diaphragm-related tissue 7117 is a secondary treatment to a primary treatment of stimulating upper airway patency- related tissue (e.g. HGN). Conversely, if stimulation is being applied to the upper airway patency-related tissue of the patient, and the patient still exhibits SDB events (e.g. frequency outside the criteria), the diaphragm-related tissue 7117 may be activated. In some examples, the stimulation may be applied during the current treatment period, such as to provide on-demand therapy to reduce frequency of SDB events.

[0191] In some examples, the on-demand therapy may include selectively activating the diaphragm-related tissue (7302 in FIG. 15A) for a selectable number of stimulation cycles and discontinuing the activation after the selectable number of stimulation cycles, such as stimulation cycles that coincide with respiratory cycles as described above. In some examples, the activation of the diaphragm-related tissue 7302 may be discontinued for another selectable number of stimulation cycles. In some examples, the selective activation and selective discontinued activation of the diaphragm-related tissue 7302 may be repeated. For example, after the activation of the diaphragm-related tissue 7302 and the discontinuing of the activation, the activation of diaphragm-related tissue 7302 may be re-initiated (e.g. reactivated) in response to a frequency of another number of SDB events meeting the criteria (and which may occur after the other selectable number of stimulation cycles). As an example, stimulation may be applied to diaphragm-related tissue 7302 for a first selectable number of stimulation cycles in response to a frequency of a first number of SDB events meeting a criteria and then discontinued for at least a second selectable number of stimulation cycles, and applied for a third selectable number of stimulation cycles in response to a frequency of a second number of SDB events meetingthe criteria and which is after the second selectable number of stimulation cycles. In some examples, the cycling of stimulation and resting (e.g. not stimulating) may be independent of SDB event detection.

[0192] With further reference to FIG. 15D, the stimulation portion 7500 also may comprise a patient comfort parameter, an arousal index, and an upper airway collapse pattern. In some examples, the stimulation may be modulated based on at least one of: (i) respiratory phase parameter (7510), (ii) a disease burden (e.g. AHI) parameter 7540, (iii) the patient comfort parameter, (iv) the patient sleeping position, and (v) the upper airway collapse pattern; and may be synchronized relative to the sensed respiratory phase parameter 7510.

[0193] As further shown in FIG. 15D, the stimulation portion 7500 also comprises a closed loop parameter 7550 by which the stimulation is applied to diaphragm-related tissue (7302 in FIG. 15A) based on sensed physiologic information such as (but not limited) to sensed respiratory information 7505, as described above. In some examples, the stimulation portion 7500 also comprises an open loop parameter 7552 by which the stimulation is applied to diaphragm- related tissue (7302 in FIG. 15A) without using (e.g. independent of) sensed physiologic information such as (but not limited) to sensed respiratory information 7505.

[0194] As further shown in FIG. 15D, in some examples stimulation portion 7500 comprises target tissue parameter 7553 by which a particular target tissue to be stimulated may be selected. At least some previously-described target tissues comprise diaphragm-related tissue (7302) and upper airway patency-related tissue (7304) such as (but not limited to) the hypoglossal nerve, genioglossus muscle, infrahyoid-muscle (IHM)-innervating nerve, and / or infrahyoid muscles (e.g. infrahyoid strap muscles). In some examples, other and / or additional target tissues comprise a glossopharyngeal nerve and / or an internal superior laryngeal nerve (iSLN) as further described below. In particular, in some such examples, stiffening walls 7229 (of the upper airway) may be implemented via stimulating an efferent nerve fiber(s) of a glossopharyngeal nerve to cause contraction (e.g. tonal and / or supra-threshold) of the pharyngeal walls (e.g. at least partially defining the upper airway). In some examples, stiffening walls 7229 (of the upperairway) may be implemented via stimulating an afferent nerve fiber(s) of a glossopharyngeal nerve (GPN) and / or stimulating an afferent nerve fiber(s) of an iSLN to induce an overall upper airway reflex response, which necessarily increases upper airway patency. In some such examples, stimulation of these target tissues (e.g. glossopharyngeal nerve, iSLN) may be implemented according to at least some of substantially the same features as described in U.S. Patent Publication 2024 / 0216692, published July 4, 2023, and entitled Stimulating A Glossopharyngeal-Related Tissue For Upper Airway Patency, which is hereby incorporated by reference in its entirety for its teaching.

[0195] FIG. 17 is a block diagram schematically representing an example arrangement 4200, deployable in an example method of (or as an example system for) to facilitate SDB patient care such as within (but not limited to) a patient management arrangement.

[0196] In some examples, the example arrangement 4200 may comprise a resource 4230, which comprises a computing resource (including stored programming) provided via a third party (third party service provider) to help provide and support at least some aspects of the example methods throughout the present disclosure such as (but not limited to) delivering pulmonary therapy for SDB care, which may comprise delivering an agent to affect the lungs and / or other therapies (e.g. FIG. 1 ). In some examples, resource 4230 may comprise at least a portion or, and / or an example implementation of, the control portion 3100 (FIG. 13A) and user interface 3240 (FIG. 13B). In some examples, the third party providing resource 4230 may comprise a device manufacturer, device supplier, or third party contracted by a device manufacturer. The resource 4230 may be hosted via the internet, World Wide Web, and / or other network communication link. Via a wireless communication protocol as represented by directional arrows 4227 and / or wired communication protocol, the resource 4230 may communicate with, and / or support communication among various other parties through devices 4240 such as (but not limited to) a medical clinic 4250A, a sleep center 4250B, clinician device(s) 4250C (e.g. programmer 4262 and / or portal 4260), therapeutic medical device (TMD) 4285, patient remote 4289, and / or patient devices 4210.

[0197] In some examples, the wireless communication protocol or pathway may comprise modalities such as (but not limited to) various forms of radiofrequency communication and / or other forms of wireless communication, such as (but not limited to) magnetic induction telemetry, Bluetooth (BT), Bluetooth Low Energy (BLE), near infrared (NIF), near-field protocols, Wi-Fi, Ultra-Wideband (UWB), ultrasonic waves, and / or other short range or long range wireless communication protocols suitable for use in communicating between implanted components and external components in a medical device environment and / or between external devices in a medical device environment.

[0198] Each of the entities associated with the respective devices 4250A, 4250B, 4250C may work together in at least some aspects to help coordinate care for the patient(s). Each entity may provide a particular form of expertise in patient care, such examples in which one entity may comprise a medical clinic (4250A), while another entity (associated with a different device 4250B) may comprise a sleep center, and some other entities comprise a clinician (4250C). Yet other entities may comprise providers which support patient care in some manner. There may be greater or fewer than the various devices (e.g. care entities) 4250A, 4250B, 4250C shown in FIG. 17 which form at least part of a care team.

[0199] Each of the devices 4250A, 4250C, 4250C comprise a computing resource, such as workstation or other computing device which may be stationary or mobile. In some examples, at least one of the respective devices comprises a user interface (GUI) to facilitate display a workflow, inputs, outputs, etc. relative to perform a method which implements a pulmonary therapy for SDB care via the examples of FIGS. 1 -16F. The user interface may comprise one example implementation of, and / or comprise at least some of the features and attributes of, the user interface 3540 described in association with at least FIG. 13C (and FIGS. 13A-13B, 13D). Accordingly, it will be further understood that the various devices 4250A, 4250B, 4250C of FIG. 17 may comprise a control portion, or comprise an example implementation of one part of a control portion, such as control portion 3100, 3520 (FIGS. 13A, 13C).

[0200] As part of this arrangement, the devices may display at least some usage information as part of preparing and / or executing such methods, as well as managing a patient including recommending or implementing further actions, etc. At least some of this actions may comprise receiving patient information, inputting usage information, and / or sending patient information to the resource 4230 and / or to other devices in arrangement 4200 via resource 4230 or directly.

[0201] In some examples, among other functions and features, the portal 4260 of devices 4250A, 4250B, 4250C, etc. may comprise a patient management app 4270 by which the particular care provider (e.g. medical clinic, sleep center, clinician, etc.) may manage patient care among a group of patients, for an individual patient, etc. In some such examples, this patient care may comprise implementing the previously described example methods and / or devices of FIGS. 1 -17.

[0202] The patient management app 4270 also may enable communicating with other entities (e.g. 4250A, 4250B, 4250C) regarding SDB care of the patients associated with devices 4210. In some examples, the clinician devices 4250A, 4250B, etc. may communicate with each other via at least resource 4230 (e.g. network communication link, internet, web, etc.) as represented via arrows 4227.

[0203] In some examples a clinician device 4250C comprises a programmer 4262 for programming, etc. the therapeutic medical device (TMD) 4285. For example, the programmer 4262 may periodically communicate with the TMD 4285 (or external medical device) wirelessly (e.g. inductive telemetry) to initially configure and / or later modify the configured stimulation therapy settings, sensing settings, therapy management settings, etc. of the TMD 4285, as well as send / receive patient information to and from the TMD 4285. However, in some examples, the programmer 4262 which may perform tasks or operations (relating to SDB patient care, maintenance) etc. in addition to programming stimulation- related aspects and / or sensing-related aspects of the TMD 4285.

[0204] As shown in FIG. 17, example arrangement 4200 also may comprise an array 4202 of computing devices 4210, each of which host a patient app 4212 relating to patient care. The devices 4210 may sometimes be referred to as patient devices, patient computing devices, and the like. The patient app 4212may provide patient education and / or enable communication with resource 4230, and / or communicate (via resource 4230 and / or directly) with any one of the devices 4250A, 4250B, 4250C. Via such communication, the patient app 4212 may receive, send, display, store, and / or communicate patient information, usage information, etc. In some examples, the patient app 4212 is one vehicle via which a patient may participate in a SDB patient care management arrangement according to the various examples of the present disclosure. In some such examples, at least some of the patient devices 4210 may comprise a mobile computing device, such as a mobile phone, tablet, smartwatch, etc. which has a user interface 3240 (FIG. 13B) to provide for operation of, and display of, the patient app 4212.

[0205] As shown in FIG. 17, in some examples the example arrangement 4200 may comprise a therapeutic medical device (TMD) 4285, which include implantable components and / or external components. In some examples, the TMD 4285 may be adapted for treating sleep disordered breathing (SDB) and / or other patient conditions (e.g. cardiac, etc.). A patient remote control 4289 may communicate with the TMD 4285 via a wireless communication protocol either directly or indirectly via an intermediary communication element (e.g. antenna, other). In some examples, such wireless communication may take the form of inductive telemetry. In some examples, the TMD 4285 may comprise an implantable pulse generator (IPG) for generating stimulation therapy signals to be delivered to the patient via a stimulation element (e.g. electrode) within the patient.

[0206] In general terms, the patient remote control 4289 enables a patient to have limited control over their stimulation therapy, such as turning the stimulation therapy on / off, pause, and / or increasing or decreasing the amplitude of stimulation within a lower and upper limit set by a clinician (and / or device manufacturer, supplier, etc.). In some examples, the patient remote control 4289 also tracks patient usage of these controls to enable a clinician, the patient, and others to learn about the patient’s usage, therapy effectiveness, patient adherence, etc. In some examples, the patient remote control also may receivesome information from the TMD 4285 regarding stimulation metrics, sensing metrics, therapy metrics, usage metrics, etc.

[0207] In some examples, the patient remote control 4289 is in communication with the patient app 4212 such that patient app 4212 on device 4210 may receive the patient usage information from the patient remote control 4289, as well as whatever therapy, sensing, etc. information was communicated from the TMD 4285 to the patient remote control 4289. In some examples, the communication between the patient remote control 4289 and the patient app 4212 (on patient device 4210) may occur wirelessly 4229 via a number of wireless communication protocols such as, but not limited to, a Bluetooth® wireless communication protocol. In some examples, the communication between patient remote control 4289 and patient app 4212 (on patient device 4210) may occur via a wired connection.

[0208] As noted here and elsewhere, the patient app 4212 may communicate this information (received from the patient remote control 4289) to one or more of the devices 4250A, 4250B, 4250C via resource 4230 to facilitate patient management according to examples of the present disclosure. In some examples, the patient app 4212 also may obtain some patient information through the patient’s use of the app 4212 which also may be communicated to the devices 4250A, 4250B, 4250C separately from, or integrated with, the patient usage information and therapy information from the patient remote control 4289 and / or TMD 4285.

[0209] As further shown in FIG. 17, in some examples a TMD 4285 may comprise a stimulation component 4286 and / or sensing component 4287. In some examples, the stimulation component 4286 comprises a stimulation engine to generate a stimulation signal to be applied to a tissue (e.g., nerve, muscle, etc.). In the examples in which the TMD 4285 comprises an implantable pulse generator (IPG), the tissue to be stimulated may comprise any of the tissue described throughout various examples of the present disclosure. In some such examples, the tissue may comprise tissue to maintain or restore upper airway patency, such as but not limited to a hypoglossal nerve, infrahyoid-muscle (IHM)- innervating nerve, and / or other nerves / muscles which may directly or indirectlypromote upper airway patency. In some such examples, the stimulation component 4286 also may comprise circuitry for generating and delivering the stimulation signal. In some examples, the stimulation component 4286 of the TMD 4285 also may comprise a stimulation element, such as an electrode through which the stimulation signal may be applied to the target tissue. In some examples, the stimulation component 4286 and / or sensing component 4287 can include an implementation of, and / or include at least some of substantially the same features and attributes and the sensing circuit 752, sensor 710, stimulation circuit 754, and / or stimulation element 720 as previously described in connection with FIG. 14A.

[0210] In some examples, the sensing component 4287 comprises a sensing engine to receive a sensing signal obtained relative to a tissue (e.g., muscle, organ, etc.). In the examples in which the TMD 4285 comprises an IPG for treating sleep disordered breathing (SDB), the tissue to be sensed may be related to respiration, oxygenation, cardiac functions, upper airway patency, and the like. In some such examples, the sensing component 4287 also may comprise circuitry for receiving and processing the sensing signal. In some examples, the sensing component 4287 of the TMD 4285 also may comprise a sensing element, such as an electrode or other element through which the sensing signal is obtained. In some examples, the sensing element may comprise an accelerometer for determining sleep information, respiratory information, posture information, physical control information. The accelerometer may be implantable, and in some examples, may be incorporated within a device including a stimulation generating element, such as an implantable pulse generator.

[0211] In some examples, the stimulation component 4286 and / or sensing component 4287 may be on-board the TMD 4285, which in some examples may comprise a microstimulator which houses stimulation circuitry, power element, and / or communication element.

[0212] In some examples, at least a portion of the stimulation component 4286 and / or sensing component 4287 may be separate from, and independent of, a housing of the TMD 4285 with one or both components 4286, 4287 being in wired or wireless communication with the TMD 4285.

[0213] Although specific examples have been illustrated and described herein, a variety of alternate and / or equivalent implementations may be substituted for the specific examples shown and described without departing from the scope of the present disclosure. This application is intended to cover any adaptations or variations of the specific examples discussed herein.

Claims

CLAIMS1 . A method comprising: delivering pulmonary therapy to treat sleep disordered breathing.

2. The method of claim 1 , wherein the sleep disordered breathing comprises obstructive sleep apnea.

3. The method of claim 1 , wherein the delivering pulmonary therapy comprises taking actions to increase alveolar surface tension.

4. The method of claims 1 , 2, or 3, wherein delivering the pulmonary therapy comprises delivering an agent to affect pulmonary surfactant within the lungs.

5. The method of claim 4, wherein the delivering an agent comprises: delivering the agent exogenously into the lungs.

6. The method of claim 5, wherein the agent comprises a pulmonary surfactant.

7. The method of claim 5, wherein the agent is to cause secretion of pulmonary surfactant from the patient’s lung tissue.

8. The method of claim 5, 6, or 7, wherein delivering the agent comprises: delivering the agent into the lungs via an externally-generated airflow, an inhaler, or intravenously via injection.

9. The method of claims 1 , 2, 3, 4, 5, 6, 7, or 8, wherein delivering pulmonary therapy comprises causing ribcage expansion.

10. The method of claim 9, wherein delivering pulmonary therapy comprises applying electrical stimulation to a nerve and / or muscle activating ribcage expansion.11 . The method of claims 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 comprising: applying electrical stimulation to a respiratory-related nerve and / or muscle to treat sleep disordered breathing; and / or applying an externally-generated airflow into the respiratory airway, an inhaler, or intravenously via injection.

12. The method of claim 11 , wherein the applying electrical stimulation to a respiratory-related nerve and / or muscle comprises: applying electrical stimulation to muscle and / or nerve increasing upper airway patency; applying electrical stimulation to lower respiratory tissue; and / or applying electrical stimulation to tissue causing an upper airway dilator reflex response.

13. The method of claim 12, wherein the applying electrical stimulation to muscle and / or nerve increasing upper airway patency comprises: delivering electrical stimulation therapy to a hypoglossal nerve, and / or an infrahyoid muscle (IHM)-innervating nerve.

14. The method of claim 12 or 13, wherein the applying electrical stimulation to lower respiratory tissue comprises: delivering electrical stimulation therapy to a phrenic nerve and / or a diaphragm; and / or delivering electrical stimulation therapy to a nerve and / or muscle activating ribcage movement.

15. A device to perform the method of claims 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, or 15.

Images