TITLE: Displacement Ventilation Assembly, Methods and Use for the Treatment of Sleep Apnea

CROSS REFERENCES TO RELATED APPLICATIONS

[0001] This is a Patent Cooperation Treaty Application which claims the benefit of United States Provisional Patent Application No. 61/132,900, filed on March 13, 2015, which is incorporated herein by reference in its entirety.

FIELD OF THE DISCLOSURE

[0002] The devices and methods disclosed herein relate to the delivery of medicaments. More particularly, the present disclosure relates to respiratory administration of medicaments for the treatment of breathing disorders, including breathing disorders associated with sleep apnea.

BACKGROUND OF THE DISCLOSURE

[0003] The following paragraphs are provided by way of background to the present disclosure. They are not however an admission that anything discussed therein is prior art or part of the knowledge of persons skilled in the art.

[0004] Breathing disorders are associated with a range of medical conditions, including sleep apnea, neurologic and cardio-pulmonary disease. These conditions may be treated using a variety of devices. Most commonly, such devices require pressurized ventilation support, referred to as Positive Airway Pressure (PAP). Typically these devices rely on a continuous positive pressure air source (CPAP) and delivery of air via a mask placed over mouth and/or nose of the patient. However patients experience significant discomfort when treated using PAP-devices, notably as a result of the unnatural sensation associated with exhalation against the continuous air pressure. Other discomforts experienced by patients are caused by nasopharyngeal dryness, direct facial contact with the mask and/or other parts of the air

l delivery system and perceptions by a patient's bed partner. In order to alleviate breathing discomfort, improved devices provide variations in air pressure. In these so-called bi-level devices (also known as Bi-PAP devices), the air pressure is varied as a function of the patient's breathing cycle. Upon inhalation the air pressure is higher, and upon exhalation the pressure is lower. While bi-level devices increase the patient's breathing comfort, the other aforementioned drawbacks remain unresolved, and of such significance that many patients with breathing deficiencies opt to abandon the use of their CPAP or bi-level devices, despite their proven efficacy, notably in the treatment of Obstructive Sleep Apnea (OSA). It is believed that prior to the present disclosure it was not known whether and how sufficient control of the breathing zone of a person could be achieved to permit delivery of a medicament, notably a medicament for the treatment of a breathing disorder, without the requirement for the use of a breathing mask through which the medicament is delivered.

[0005] Other treatments for sleep apnea-associated breathing disorders include nasal patches designed to increase end tidal airway pressure, pacemakers and reconstructive airway surgery, each requiring the patient to undergo a surgical procedure and/or acquire an implantable device, and oral devices, requiring the insertion of a device inside the patient's mouth while the patient is asleep. The efficacy of each of the aforementioned procedures and devices varies substantially and result in significant patient discomfort.

SUMMARY OF THE DISCLOSURE

[0006] The following paragraphs are intended to introduce the reader to the more detailed description that follows and not to define or limit the claimed subject matter of the present disclosure.

[0007] The present disclosure relates to devices and methodologies for the administration of medicaments to a person in need thereof. Accordingly, the present disclosure provides, in at least one aspect, at least one embodiment of a method of administering a medicament for the treatment of a breathing disorder, the method comprising:

providing an assembly comprising a reservoir containing a gaseous medicament for the treatment of a breathing disorder, the reservoir operably connected to a contact-free gaseous medicament disperser;

situating a person in need of receiving the gaseous medicament in a resting position in proximity of the medicament disperser;

delivering the gaseous medicament through the medicament disperser to displace ambient air and form a displacement zone encompassing a breathing zone of the person; and

allowing the gaseous medicament to freely diffuse from the displacement zone into ambient air.

[0008] In some embodiments, the gaseous medicament is delivered continuously to the person in resting position.

[0009] In some embodiments, the gaseous medicament is delivered intermittently to the person in resting position.

[0010] In some embodiments, the displacement zone is formed by dispersal of the gaseous medicament at a constant flow rate. In some embodiments, the displacement zone is formed by the dispersal of a gaseous medicament in the displacement zone at a constant flow rate of from about 0.1 m/s to about 4.0 m/s.

[001 1] In some embodiments, the displacement zone substantially encompasses the entire human body of the person in resting position.

[0012] In some embodiments, the displacement zone substantially encompasses the head of the person in resting position, but not the rest of the body. [0013] In some embodiments, the gaseous medicament is carbon dioxide or a perfluorocarbon, including perfluorooctylbromide (PFOB), and the person in need of receiving the gaseous medicament has been diagnosed with a breathing disorder, including a sleep apnea, or a respiratory condition.

[0014] In a further aspect, the disclosure provides in at least one embodiment an assembly for the treatment of breathing disorders, the assembly comprising:

a reservoir containing a gaseous medicament for the treatment of a breathing disorder operably connected to

a disperser for receiving the gaseous medicament from the reservoir and dispersing the gaseous medicament to ambient air and form a displacement zone comprising the gaseous medicament

[0015] The present disclosure in a further aspect provides, in at least one embodiment, an assembly comprising a reservoir containing a gaseous medicament for the treatment of a breathing disorder operably connected to a contact-free gaseous medicament disperser capable of displacing ambient air to form a displacement zone encompassing the breathing zone of a person in resting position, wherein the gaseous medicament can freely diffuse from the displacement zone into the ambient air.

[0016] Other features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description, while indicating some implementations of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those of skill in the art from the detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS [0017] The disclosure is in the hereinafter provided paragraphs described, by way of example, in relation to the attached figures. The figures provided herein are provided for a better understanding of the example embodiments and to show more clearly how the various embodiments may be carried into effect. The figures are not intended to limit the present disclosure. It is further noted that identical numbering of elements in different Figures is intended to refer the same element, possibly shown situated differently or from a different angle. Thus, by way of example only, element (105) in each FIG. 1 , FIG. 3, FIG. 4, FIG. 5, FIG. 8, FIG. 9, FIG 10 and FIG. 11 refers to a disperses

[0018] FIG. 1 is a schematic side view of an example assembly for the delivery of an inhaled medicament according to the present disclosure.

[0019] FIG. 2 depicts the chemical structure of perfluorooctylbromide.

[0020] FIG. 3 is a schematic side view of an example assembly for the delivery of an inhaled medicament according to the present disclosure, notably an assembly comprising an isokinetic flow rate.

[0021] FIG. 4 is a schematic side view of another example assembly for the delivery of an inhaled medicament according to the present disclosure.

[0022] FIG. 5 is a schematic side view of another example assembly for the delivery of an inhaled medicament according to the present disclosure.

[0023] FIG. 6 is a graph representing results obtained using the assembly for the delivery of an inhaled medicament of the present disclosure as further described in Example 1 using an animal model.

[0024] FIG. 7 is another graph representing results obtained using the assembly for the delivery of an inhaled medicament of the present disclosure as further described in Example 1 using an animal model. [0025] FIG. 8 is a schematic perspective view of an example of the disperser portion of the assembly of FIG. 1 , also showing a cross-section of the disperser.

[0026] FIG. 9 is a schematic side view of another example assembly for the delivery of an inhaled medicament according to the present disclosure.

[0027] FIG. 10 is a schematic perspective view of another example assembly for the delivery of an inhaled medicament according to the present disclosure.

[0028] FIG. 11 is a schematic partial side view of another example assembly for the delivery of an inhaled medicament according to the present disclosure.

[0029] FIG. 12 is another graph representing results obtained using the assembly for the delivery of an inhaled medicament of the present disclosure as further described in Example 1 using an animal model.

[0030] FIG. 13 is another graph representing results obtained using the assembly for the delivery of an inhaled medicament of the present disclosure as further described in Example 1 using an animal model.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0031] Various apparatuses and methods will be described below to provide an example of an embodiment of each claimed subject matter. No embodiment described below limits any claimed subject matter and any claimed subject matter may cover methods, apparatuses, devices, assemblies, processes or systems that differ from those described below. The claimed subject matter is not limited to apparatuses or methods having all of the features of any one apparatus, method, device, system, assembly or process described below or to features common to multiple or all of the apparatuses, methods, devices, systems, assemblies or processes described below. It is possible that an apparatus or method described below is not an embodiment of any claimed subject matter. Any subject matter disclosed in an apparatus, method or device described below that is not claimed in this document may be the subject matter of another protective instrument, for example, a continuing patent application, and the applicants, inventors or owners do not intend to abandon, disclaim or dedicate to the public any such subject matter by its disclosure in this document.

[0032] It should be noted that terms of degree such as "substantially", "about" and "approximately" as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of the modified term if this deviation would not negate the meaning of the term it modifies.

[0033] As used herein, the wording "and/or" is intended to represent an inclusive-or. That is, "X and/or Y" is intended to mean X or Y or both, for example. As a further example, "X, Y, and/or Z" is intended to mean X or Y or Z or any combination thereof.

[0034] All publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

[0035] As hereinbefore mentioned, the present disclosure relates to methods for the administration of medicaments to a person for the treatment of breathing disorders. The herein provided methods can be efficient for administering medicaments, including, in some embodiments, carbon dioxide and a perfluorocarbon. The assembly herein provided can be configured to disperse a gaseous medicament in such a manner that it can freely diffuse into the ambient air. The inventors have, surprisingly, found that the assembly providing freely diffusing gaseous medicaments, may be efficaciously administered to a person in a resting position. The assembly and methods notably may be used to treat breathing disorders, such as breathing disorders associated with sleep apnea. The methods and assemblies provided herein do not necessarily involve direct contact between the person in need of receiving the medicament and the delivery system, and thus the assembly does not require the use of a breathing mask. To the best of the inventors' knowledge, the current disclosure provides, for the first time, a methodology to deliver medicaments for the treatment of breathing disorders to a person in a resting position without requiring direct contact or facial contact between the person and the delivery device. The assembly and methods of the present disclosure do not necessarily involve positive air pressure and do not compromise respiration mechanics, notably exhalation. Furthermore the assembly and methods of the present disclosure do not cause, or only minimally cause nasopharyngeal dryness. Furthermore, the assembly is generally believed not to be deemed aesthetically undesirable to a bed partner. Moreover the assembly of the present disclosure does not necessarily involve the performance of surgery, the implantation of a device, or require the person suffering from a breathing disorder to wear an oral or nasal device. The assembly and methods of the present disclosure are believed to be comfortable to a person in need of receiving the medicament, and therefore substantial compliance with prescribed treatments may be attainable.

[0036] Accordingly, the present disclosure provides, in at least one aspect, at least one embodiment of a method of administering a medicament for the treatment of a breathing disorder, the method comprising:

providing an assembly comprising a reservoir containing the gaseous medicament for the treatment of a breathing disorder, the reservoir operably connected to a contact-free gaseous medicament disperser;

situating a person in need of receiving the gaseous medicament in a resting position in proximity of the medicament disperser; delivering the gaseous medicament through the medicament disperser to displace ambient air and form a displacement zone emcompassing a breathing zone of the person; and

allowing the gaseous medicament to freely diffuse from the displacement zone into the ambient air.

[0037] In some embodiments, the gaseous medicament is carbon dioxide or a perfluorocarbon and the person in need of receiving the medicament is a person diagnosed with a breathing disorder.

Definitions

[0038] The term "gaseous medicament", as used herein, refers to a chemical compound existent in a gas phase and/or capable of transitioning into a gas phase, in either case, provided in a gas phase within the breathing zone of a person in need thereof. The medicament may be a medicament that is existent in a gas phase in air under ambient conditions, e.g. carbon dioxide, or it may be dispersed in a manner that suspends the medicament in air, for example, as an aerosol, vapour, spray, fume, dust or mist.

[0039] The term "contact free", as used herein, refers to the absence of direct contact between the disperser of the gaseous medicament and the person in need of receiving the gaseous medicament, thus permitting the unhindered diffusion of dispersed gaseous medicament into the ambient air.

[0040] The term "perfluorocarbon", as used herein, refers to a class of compounds having the formula C _x F _y , wherein C represents the chemical element carbon, F represents the chemical element fluorine, and x and y are an integer > 1 , and y > x and wherein all carbon-hydrogen bonds have been replaced with carbon-fluorine bonds. The term perfluorocarbon further includes bromine derivatives having the formula C _x F _y Br _z wherein Br represents the chemical element bromine, x, y and z are integers > 1 , and y > x. Included, without limitation, within the term are perfluoroalkanes, e.g. linear carbon tetrafluoride (CF ₄ ), perfluoroethane (C ₂ F ₆ ), perfluoropropoane (C ₃ F ₈ ), perfluorobutane (C ₄ F-| ₀ ), perfluoropentane (C ₅ F ₁₂ ), perfluorohexane (CeF-i ), perfluoroheptane (C ₇ F ₁₆ ), perfluorooctane (CsF-is), pefluorononane (C ₉ F ₂₀ ) and perfluorodecane (C ₁₀ F ₂₂ ), branched perfluoralkanes (e.g. perfluoro-2- methylalkane), cyclic perfluoralkanes, e.g. perfluoro-1 ,3-dimethylcyclohexane, polycyclic perfluoroalkanes (e.g. perfluorodecalyn) and bromine derivatives wherein 1 ,2 or 3 carbon-fluorine bonds are replaced with carbon-bromine bonds including, without limitation, bromofluoromethane (CF ₃ Br),perfluoroethylbromide (C2F5B ₁ -), perfluoropropylbromide (C ₃ F ₇ Br), perfluorobutylbromide (C ₄ Fi ₉ Br), perfluoropentylbromide (CsF-n Br), perfluorohexylbromide (CeFi ₃ Br), perfluoroheptylbromide (C ₇ Fi ₅ Br), perfluorooctylbromide (CsF-i ₇ Br), pefluorononylbromide (CgF-igBr) and perfluorodecylbromide (CioF ₂ i Br)

[0041] The terms "perfluorooctylbromide", "perflubron" and "PFOB", which may be used interchangeably herein, refer to a chemical compound having the chemical formula CsF-^Br and the structure shown in FIG. 2.

[0042] The term "breathing zone", as used herein, refers to the three dimensional space immediately exterior to a person's mouth and nose comprising the person's inhalation and exhalation's air. The size and dimensions of the breathing zone may vary from person to person.

[0043] The term "displacement zone", as used herein, refers to a contiguous three-dimensional space in which the ambient air has been displaced with an atmosphere comprising a therapeutically effective concentration of a gaseous medicament, and in which the concentration of the gaseous medicament is higher than the concentration of the medicament in the ambient air encompassing the displacement zone. The gaseous medicament can be substantially homogenously distributed within the displacement zone, or a more or less stable three-dimensionally distributed concentration gradient of the gaseous medicament may exist within the displacement zone. With the term "more or less stable" it is meant that the three-dimensionally distributed gradient of the gaseous medicament within the displacement zone may exhibit temporary local deformations as a result of atmospheric disturbances, for example, as a result of cyclic or irregular breathing, or disturbances in the ambient air, but nevertheless remains substantially stable when considered over longer periods of time, for example over a period of at least 10 seconds, 30 seconds, 1 minute, 5 minutes, 10 minutes or one hour.

[0044] The term "operably connected", as used herein, can have different meanings depending on the context in which the term is used. For example operably connected can have a mechanical or electric connotation depending on the context in which it is used, i.e. whether describing a physical layout or the transmission of signals or data, as the case may be. For example the term operably connected may indicate that two elements, parts or devices can be directly physically or electrically coupled or through one or more intermediate elements, parts or devices.

[0045] The term "therapeutically effective amount", as used herein, refers to the amount of a compound that, when administered to a subject for treating a disease, is sufficient to effect such treatment for the disease. The therapeutically effective amount will vary depending on the compound, the disease and its severity and the age, weight, etc., of the subject to be treated. General implementation of the assembly

[0046] Referring to FIG. 1 , the present disclosure provides an example implementation of an assembly (100) for the delivery of an inhaled medicament (not shown), comprising a reservoir (130) containing a gaseous medicament of which the flow is controlled by a valve (150), operably connected via two conduits (110) and (115) to a disperser (105) having several outlet portions (155) through which the gaseous medicament is dispersed in axial direction (shown in Figure 8) into a displacement zone (170), delineated from ambient air (175) by a boundary layer (165). The example implementation further comprises a second control valve (120) and a microphone (145). Also comprised and shown in the example implementation are a person in resting position (140) on a bed (135), and the breathing zone (160) delineated by a breathing boundary layer (161 ) of the person (140). Further shown is a support system (142) for the disperser (105) attaching the disperser to a ceiling (144).

[0047] The reservoir (130) comprising or containing the gaseous medicament may be any suitable reservoir. In certain embodiments, the gaseous medicament is contained in the reservoir (130) in a gas or vapour phase. Thus the reservoir (130) may, for example, be a gas cylinder comprising a pressurized gaseous medicament, such as pressurized carbon dioxide. In other embodiments, the gaseous medicament is contained in the reservoir (130) in a liquid phase or a solid phase, and the assembly comprises a system capable of effecting transition of the gaseous medicament from a liquid phase or solid phase to a gaseous phase. Such system may involve, for example, conducting, or bubbling, air through a liquid comprising the gaseous medicament thereby causing evaporation of the gaseous medicament and the formation of a vapour comprising the medicament. In other embodiments, the gaseous medicament is aerosolized, i.e. treated to form a colloid of fine solid particles of the medicament suspended in air.

[0048] In order to expel or discharge the gaseous medicament from the reservoir (130), the gaseous medicament may be pressurized, and the reservoir (130) may comprise an aperture and a control, e.g. a valve (150). In other embodiments, the gaseous medicament may be otherwise expelled or propelled from the reservoir (130), for example, the reservoir (130) may comprise a propellant to create movement of the medicament and transition to a gas phase. Whether the gaseous medicament is pressurized or whether the gaseous medicament is otherwise expelled or propelled from the reservoir (130), a pressure differential is employed as a driving force to conduct the gaseous medicament from the reservoir (130) to the disperser (105). [0049] The reservoir (130) may be any shape or form, and may be open or closed. In some examples, closed reservoirs are deemed most practical. The actual reservoir (130) used to contain the gaseous medicament may vary substantially and may be selected as desired.

[0050] The disperser (105) distributes or discharge the gaseous medicament, in gas phase, into the breathing zone (160), delineated by a boundary layer (161 ) of a person in a resting position (140), e.g. a horizontal resting position. Thus the breathing zone (160), and the quality of the air within the breathing zone (160), are controlled by the assembly and practice of methods of the present disclosure. In accordance herewith, the gaseous medicament is supplied to the disperser (105) from the reservoir (130) via one or more conduits (110 and 115). There exists a delineation between the breathing zone (160) and the displacement zone (170), comprising a breathing boundary layer (161 ). The breathing boundary layer (161 ) may be more or less diffuse (i.e. comprising a more or less steep concentration gradient of the inhaled and exhaled air), and it may be more or less regularly or irregularly shaped, depending inter alia on the breathing characteristics of the person (140). The breathing boundary layer (161 ) is further characterized by mixing of air or gas (turbulence mixing and/or diffusion mixing) and substantial local variations within the breathing boundary layer (161 ) in direction and rate of air or gas flow.

[0051] In general, the disperser (105) comprises an inlet portion (111), linking the disperser (105) to the conduit (110), and one or more outlet portions (155) projecting in the general direction of the person in resting position (140) when the assembly is operably installed, and through which the gaseous medicament exits the disperser (105) and enters the displacement zone (170) from the disperser (105). The dimensions and shape of the disperser (105) may vary substantially. In some embodiments, the disperser (105) comprises a surface area ((ab), as illustrated in FIG. 8) of approximately human sized dimensions, as shown, for example, in FIG. 1. Such a disperser can provide a displacement zone substantially encompassing a human body in its entirety while in resting position. In other embodiments, the disperser (105) has a surface area (ab) corresponding approximately in size with the dimensions of a human face, as shown in FIG. 10. Such a disperser can provide a displacement zone substantially encompassing the head of the person in resting position, but not the remainder of the body of the person.

[0052] The outlet portion (155) of the disperser (105) may vary substantially in shape and dimensions and can, in some embodiments, be a simple single aperture of varying shapes and dimensions, e.g. an aperture approximately circular or approximately square in shape, and in other embodiments, can comprise certain flow directing structures, such as generally extending axially from the aperture. In some embodiments, a single outlet portion (155) is provided. I n other embodiments, two or more outlet portions (155) are provided.

[0053] It is further noted that in some embodiments, an assembly may be constructed comprising two or more dispersers (105), which may be used to treat a single person. Such two or more dispersers (105) may be connected to the same reservoir (130) or to two or more separate reservoirs (130), and such two or more dispersers (105) may be used separately or simultaneously.

[0054] In some examples, in accordance herewith, the disperser (105) comprises a hollow body having an interior and an exterior wall, one or more inlet portions (111 ) permitting entry of the gaseous medicament from the reservoir (130), via one or more conduits (110 and 115), into the hollow interior, and an outlet portion (155) permitting exit of the gaseous medicament in axial direction into the displacement zone (170).

[0055] In one implementation, the disperser (105) is constructed to comprise a plenum or chamber in which the gaseous medicament is introduced via one or more conduits (110) and (115) and then dispersed from the plenum via a plurality of outlet apertures or perforations (155) into the displacement zone (170) and breathing zone (160) of the person (140). Referring to FIG. 8, shown therein is an exemplary implementation of a disperser (105) having a surface dimension (ab) comprising a hollow body (805), having an interior wall (810) and an exterior wall (820), a hollow interior (plenum) (840), an inlet portion (11 1 ) traversing the exterior wall (820) and the interior wall (810), and a plurality of apertures or outlets (155), traversing or perforating the interior wall (810) and the exterior wall (820). The gaseous medicament flows from the disperser via inlet portion (111 ) through the outlet portions (155). Flow of the gaseous medicament through the inlet portion (111 ) is signified by an arrow (830), and flow of the gaseous medicament through the outlet portions (155) in axial direction is signified by arrows (825).

[0056] In one embodiment, the disperser (105) is constructed as having a surface area (ab) of approximately the same dimensions as the face of a person in resting position. The disperser can be mounted on the headboard of the bed (135) as further illustrated in the implementations (1000) and (1100) shown in FIG. 10 and FIG. 11 , respectively. It is noted that in FIG. 11 the length of the arrows 1105 represents the airflow rate at various points within the displacement zone (105).

[0057] The disperser (105) further may comprise a mixer to achieve mixing of the gaseous medicament with the ambient air. Such a mixer may in one embodiment comprise one or more apertures or vents in the interior and exterior wall of the body of the disperser (105) connecting the hollow interior of the disperser (105) to the ambient air. In other embodiments the mixer is a fan or ventilator.

[0058] Air or gas flow rates may vary, but are in some examples typically maintained at an equal rate from 0.1 m/s, or approximately 0.1 m/s, to 4.0 m/s, or approximately 4.0 m/s, at the outlet apertures or perforations (155). Air or gas may be delivered continuously or intermittently. Thus the flow rate within the displacement zone (170) may be approximately 0.1 m/s, 0.2 m/s, 0.3 m/s, 0.4 m/s, 0.5 m/s, 0.6 m/s, 0.7 m/s, 0.8 m/s, 0.9 m/s, 1 .0 m/s, 1 .1 m/s, 1 .2 m/s, 1 .3 m/s, 1 .4 m/s, 1 .5 m/s, 2.0 m/s, 2.5 m/s, 3.0 m/s, 3.5 m/s, or 4.0 m/s. Air or gas flow (i.e. volume of air per time unit) equally may vary but in some examples is typically maintained at an equal rate between from 0.1 or approximately 0.1 m ³ /s to 4.0 m ³ /s or approximately 1 .5 m ³ /s, and is equal in the outlet apertures (155) and the duct (110). Thus the air or gas flow may be approximately 0.1 m ³ /s, 0.2 m ³ /s, 0.3 m ³ /s, 0.4 m ³ /s, 0.5 m ³ /s, 0.6 m ³ /s, 0.7 m ³ /s, 0.8 m ³ /s, 0.9 m ³ /s, 1 .0 m ³ /s, 1 .1 m ³ /s, 1 .2 m ³ /s, 1 .3 m ³ /s, 1.4 m ³ /s, 1 .5 m ³ /s, 2.0 m ³ /s, 2.5 m ³ /s, 3.0 m ³ /s, 3.5 m ³ /s, or 4.0 m ³ /s. By establishing a continuous or intermittent air or gas flow, optionally within these ranges, the assembly of the present disclosure may be used to establish an isokinetic flow zone, as hereinafter further detailed.

[0059] The airflow within the displacement zone (170) may be determined by measuring the velocity, e.g. using a rotating vane or a hotwire anemometer and multiplying the surface area with the measured air velocity. Airflow may also be measured using a mass flow meter. Upon such measurements the airflow may be adjusted as desired.

[0060] Dispersal of the gaseous medicament into the displacement zone (170) and the breathing zone (160) of the person (140) is achieved upon exiting of the gaseous medicament, in a gas phase, from the disperser (105) through one or more outlet apertures or perforations (155). In order to form the displacement zone (170), the gaseous medicament exiting from the disperser (105) through the outlet portion (155) is preferably dispersed from the disperser (105) into the ambient air at a constant flow rate, and the constant flow rate is maintained for at least a period of time sufficiently long to displace the ambient air and form a displacement zone (170). It is noted that flow rates may vary with respect to geometrical points within the displacement zone (170). With the term "constant flow rate" it is meant that the flow rate at selected geometrical points within the displacement zone (170) is constant or approximately constant. [0061] In some embodiments, the displacement zone is formed by dispersal of the gaseous medicament at a constant flow rate at the outlet portion (155) of the disperser (105) of from about 0.1 m/s to about 4.0 m/s. In some embodiments, the gaseous medicament is dispersed at a constant flow rate at the outlet portion (155) of the disperser (105) of from about 0.1 m/s to about 1 .5 m/s.

[0062] In some embodiments, the displacement zone is formed by dispersal of the gaseous medicament at a constant flow rate wherein the flow rate within the displacement zone (170) varies in the range from about 0.1 m/s to 4.0 m/s. In some embodiments, the flow rate within the displacement zone (170) varies in the range from about 0.1 m/s to about 1 .5 m/s.

[0063] In some embodiments, the displacement zone is formed by dispersal of a gaseous medicament into the displacement zone (170) at a constant flow rate wherein the flow rate of the gaseous medicament is selected to establish a flow rate within the breathing zone (160) ranging from about 0.1 m/s to about 0.3 m/s.

[0064] The formed displacement zone (170) encompasses a contiguous three-dimensional space projecting in general axial direction from the disperser outlet portions (155) of the disperser (105) towards the person situated in resting position. The duration of the time period required to form the displacement zone (170) may vary somewhat, for example, as a function of the flow rate of the gaseous medicament, and disturbances in the ambient air, but generally at least several seconds of gaseous medicament dispersal at a constant flow rate are required to displace the ambient air and form the displacement zone (170). Once formed, the displacement zone (170) may be maintained for longer or shorter periods of time by maintaining flow of the gaseous medicament from the reservoir (130) through the disperser (105), as desired. Thus dispersal and flow of the gaseous medicament results in the formation of a displacement zone (170) encompassing a breathing zone (160) having a breathing boundary layer (161 ) within the displacement zone (170). The displacement zone (170) is further characterized by comprising a therapeutically effective amount of the gaseous medicament. Conversely the ambient air (175) does not comprise a therapeutically effective amount of the gaseous medicament.

[0065] It is also possible that a displacement zone (170) is initially formed in the absence of a person positioned in resting position within the displacement zone (170). The person (140) may then enter the formed displacement zone (170) and become situated in resting position. The entry into the displacement zone (170) of the person (140) can cause temporary disturbances to the concentration gradient of the gaseous medicament in the displacement zone (170), and it generally will then take a certain period of time, typically at least several seconds, after the person (140) is situated in resting position to form a more stable displacement zone (170).

[0066] In the example shown in assembly (100), the assembly does not comprise any structures substantially containing the air in the displacement zone (170). The displacement zone (170) is substantially open to the ambient air (175) and the air in the displacement zone (170) may freely diffuse from the displacement zone (170) into the ambient air (175). There is a delineation between the ambient air (175) and the displacement zone (170), comprising a boundary layer (165). The boundary layer (165) may be more or less diffuse, and it may be more or less regular or irregularly shaped, depending inter alia on the diffusion characteristics of the gaseous medicament. The boundary layer (165) is further characterized by more or less mixing of air or gas (turbulence mixing and/or diffusion mixing) and substantial local variations within the boundary layer (165) in direction and rate of air or gas flow.

[0067] Upon inhalation by the person (140) of the air within the displacement zone (170) the gaseous medicament is administered to the person's (140) airways and from there it may enter the person's (140) circulation to exert its therapeutic effect. In accordance herewith exhaled air, which may comprise a certain quantity of the gaseous medicament, may freely diffuse from the person's breathing zone (160) into the displacement zone (170), and equally freely diffuse from the displacement zone (170) in to the ambient air (175).

[0068] In some embodiments, the disperser (105) comprises a displacement ventilation system, for example an airflow system, i.e. a system capable of providing a more or less continuous flow of air generally directed towards the breathing zone (160) of the person (140). In further embodiments, the airflow system comprises a laminar flow system. "Laminar flow system", as used herein, refers to a flow system capable of providing an isokinetic gas or airflow. The terms "isokinetic", "isokinetic flow rate" or "isokinetic flow", as may be interchangeably used herein, refer to certain movement characteristics of air or a gas, namely movement at an equal or approximately equal rate, i.e. if in a given geometric space or zone the airflow is isokinetic, then at every point in such geometric space or zone the air moves at an equal or approximately equal rate. In accordance herewith, in one embodiment, the disperser (105) is constructed in such a manner that the breathing zone (160) of the person (140), is encompassed by an isokinetic flow zone. This is further illustrated in the example implementation (300) shown in FIG. 3.

[0069] Example implementation of an assembly (300) (FIG. 3) comprises a disperser (105) capable of creating a displacement zone (170), substantially encompassing an isokinetic flow zone (185) delineated by an isokinetic flow zone boundary layer (186), and the isokinetic flow zone (185) substantially encompassing the breathing zone (160) of a person (140) situated in resting position on a bed (135). The relative length of the arrows (190) and (195) within the displacement zone (170) and the isokinetic flow zone (185) signifies the relative air or gas flow rate. Thus in this implementation, the assembly (300) is fabricated to comprise a disperser (105) which is constructed and operated in such a manner that an isokinetic airflow is achieved within the isokinetic flow zone (185)(as signified by arrows (190)), whereas outside the isokinetic flow zone (185), the flow rate may vary (signified by arrows (195)). There exists a delineation between the breathing zone (160) and the isokinetic flow zone (185), comprising a breathing boundary layer (161 ). The breathing boundary layer (161 ) may be more or less diffuse (i.e. comprising a more or less steep concentration gradient of the inhaled and exhaled air), and it may be more or less regular or irregularly shaped, depending inter alia on the breathing characteristics of the person (140) and the airflow characteristics. The breathing boundary layer (161 ) is characterized by mixing of air or gas (turbulence mixing and/or diffusion mixing) and substantial local variations within the breathing boundary layer (161 ) in direction and rate of air or gas flow.

[0070] In order to achieve an isokinetic airflow, it is beneficial to construct the disperser (105) in such a manner that turbulence at the outlet portions (155) is minimized. This may be achieved, for example, by constructing the disperser to comprise perforated screens, baffles, or veins, or a combination thereof, to conduct the flow of the gaseous medicament from the disperser via the outlet portions (155), optionally more or less equally shaped, into the displacement zone (170) and the breathing zone (160) of the person (140). The hollow interior or plenum (see: part (840) in FIG. 8) may further comprise one or a plurality of compartments which may comprise cloth, or other fibrous material, a foam or filter, e.g. a High Efficiency Particulate Arrestance (HE PA) filter, all of which can serve to minimize or reduce turbulence and facilitate the establishment of an isokinetic airflow.

[0071] In certain embodiments, the isokinetic flow rate zone (185) varies in geometric dimension from the displacement zone (as illustrated in example implementation of the assembly (300)). Thus in one embodiment, the isokinetic flow zone (185) may substantially comprise the headspace above a bed, while the displacement zone (170) may cover the entire bed. In other embodiments, the displacement zone (170) and the isokinetic flow zone (185) comprise substantially identical geometric dimensions. The isokinetic flow zone may vary substantially in geometric dimensions and shape, e.g. the isokinetic flow zone may be approximately conical, elliptical, cubical or any other shape, depending on, for example the exact design of the disperser. In some embodiments, the isokinetic flow zone (however shaped) (185) substantially comprises, at least the space projecting from the person's (140) facial surface in three dimensions into the displacement zone (170) along an approximately spherical geometric space having a radius of at least approximately 0.5 meter, at least approximately 0.75 meter, at least approximately 1 .0 meter, at least approximately 1 .25 meter, or at least approximately 1.50 meter, or at least the space projecting from the person's (140) facial surface in three dimensions into the displacement zone (170) along an approximately conical or elliptical geometric space of similar dimensions, but in any case encompassing the breathing zone (160). In further embodiments, the isokinetic flow zone (185) projects from the surface area of the head space of a bed, or the entire surface area of a bed in three dimensions up to a height of at least 0.5 meter, at least approximately 0.75 meter, at least approximately 1 .0 meter, at least approximately 1 .25 meter, or at least approximately 1 .50 meter of the surface area of the head space of the bed or the entire bed surface, respectively, again in any case encompassing the breathing zone (160), even if the person (140) moves position on the bed (135).

[0072] The dispersal pressure, i.e. the pressure at the edge of the outlet portion (155) of the disperser (105) that is used in accordance herewith is a pressure sufficient to form the displacement zone (170). In some embodiments, such pressure is a positive pressure, i.e. a pressure, exceeding ambient pressure, albeit only marginally in some embodiments, for example the dispersal pressure may vary between 1.001 and 1 .01 atmosphere, or the dispersal pressure may be approximately 1 .01 , 1 .02, 1 .03, 1 .04, 1 .05, 1.06, 1 .07, 1 .08, 1.09, 1 .10, 1 .1 1 , 1.12, 1 .13, 1 .14, 1 .15, 1 .16, 1 .7, 1 .18, 1 .19, 1 .20 atmosphere. In other embodiments, negative pressure may be employed. In such embodiments a negative pressure, created by an air suction device, e.g. a ventilator, would be used to generate an airflow and form the displacement zone (170).

[0073] The shape and size of the disperser (105) may vary, however it is constructed in such a manner that the gaseous medicament is dispersed into a displacement zone (170) encompassing the breathing zone (160) of a person (140).

[0074] The disperser (105) is further constructed in such a manner that the gaseous medicament is dispersed into a displacement zone (170) having three-dimensional geometric dimensions substantially exceeding the breathing zone (160) of a person (140), e.g. the volume of the displacement zone (170) is at least approximately 2, 3, 4, 5, 10, 25 or 100 times the volume of the breathing zone (160). In certain preferred embodiments, the disperser (105) is constructed in such a manner that it achieves a displacement zone (170) occupying or slightly exceeding the head space area of a bed, or a disperser (105) that achieves a larger displacement space (170) occupying, or slightly exceeding, for example, the space above of an entire bed, as illustrated in the example embodiment shown in FIG. 1.

[0075] The dispersed outlet apertures or perforations (155) are situated sufficiently proximal to the person (140) to form the displacement zone (170) in such a manner that it encompasses the breathing zone (160). In accordance herewith the disperser is situated in such a manner that no direct contact is necessarily made between the person in resting position (140) and the disperser (105). The person in resting position is not required to wear a breathing mask. The contact-free, breathing mask-free, feature of the assembly herein disclosed, permits comfort for the person in resting position (140). Furthermore the apertures or perforations (155) of the disperser (105) may be situated outside the breathing zone (160) of the person (140) in order to ensure that the displacement zone (170) encompasses the breathing zone (160), or facilitate the displacement zone (170) encompassing the breathing zone (160). [0076] The disperser may be provided as a stand-alone structure or attached to other fixed structures in proximity to the person (140). In the examples shown, the assembly includes a support system (142) that supports the disperser (105) and maintains the disperser in contact-free position with respect to the person (140). For example, the support system (142) may include a clamp (not shown) for attaching the disperser (105) to the bed, a cantilever (not shown) that mounts the disperser (105) to a wall or a suspension system that suspends the disperser from the ceiling (as illustrated in FIG. 1 ). Alternatively the support system may be fabricated within the ceiling or floor (not shown), and may have dimensions more or less identical to the ceiling or floor of a room in which one or more persons may be receiving treatment using the assembly. The disperser (105) may conveniently be situated above a person in resting position, as illustrated in the example implementation 100 of FIG.1. In yet other embodiments, the assembly may be portable. In general, the disperser (105) is situated in such a manner that, when in operation, the distance between the outlet portions (155) and the face of the person (140) in resting position is at least from about 20 cm to about 30 cm. In embodiments hereof, comprising a support system suspended from the ceiling, the distance between the outlet portions (155) of the disperser (105) and the face of the person (140) in resting position the distance may be approximately as long as the the distance from the ceiling to the face or the person (140), and could be, for example, between from about 3 meters to about 5 meters.

[0077] In other embodiments, the disperser (105) may be situated to the side of the person (140) in resting position (as illustrated in assembly (400) of the example implementation shown FIG. 4).

[0078] In other embodiments, the disperser may be situated below the person (140) (as illustrated in assembly (500) of the example embodiment shown in FIG. 5). In this example, the support system (142) may have a base (143) upon which the support system (142) and disperser (105) rests. [0079] One or more conduits (shown in assembly (100) in the example implementation shown in FIG.1 ; assembly (400) in the example implementation shown in FIG. 4; and assembly (500) in the example implantation shown in FIG. 5) (110) and (115)) are operably connecting the reservoir (130) with the disperser (105). The conduits may vary in length and width and maybe constructed of any suitable conduit construction material, such as gas impermeable tubing or piping. Furthermore the conduits may comprise one or more flow controllers (e.g. a valve (120)) to control the flow of the gaseous medicament from the reservoir (130) to the disperser (105).

[0080] In other embodiments, an air suction device, or structure to effect transport of the gaseous mixture from the disperser to such structure, is placed opposite of the disperser (105) in order to facilitate airflow and the formation of a displacement zone (170). Thus referring to FIG. 9, shown therein is implementation (900) comprising an air suction device (910) and a disperser (105). The disperser (105) is situated to disperse the gaseous medicament longitudinally across the surface area of the bed (135) and the air suction device is situated at the opposite end of the bed to facilitate the airflow discharged from the disperser (105). The air suction device may for example be a fan, ventilator or air duct operably connected to a space with lower pressure. In alternate embodiments, the disperser (105) and the air suction device are situated opposite each other in a cross sectional fashion relative to the bed (135), and the gaseous mixture is delivered across the head area or the entire surface of the bed.

[0081] In further embodiments, the assembly may comprise a temperature controller to control the temperature of the gaseous medicament. The temperature controller may be constructed so that a range of temperatures may be set. Referring to the example implementations of FIG. 4 (assembly (400)), FIG. 5 (assembly (500)) and FIG. 9 (assembly (900), there is shown a temperature controller (180) to control the temperature of the gaseous medicament. Such a temperature controller may be an air conditioner, vent, ventilation device or fan. In accordance herewith, in example implementations hereof where the disperser (105) is situated above the person (140), to cool the gaseous medicament so that the temperature of the gaseous medicament upon exiting the disperser is lower than the ambient temperature. For example the temperature controller may be set in such a manner that the temperature of the gaseous medicament upon exiting the disperser (105) is between approximately 1 °C and 15 °C lower than the ambient temperature, e.g. approximately 1 °C, 2 °C, 3 °C, 4° C, 5° C, 6° C, 7 °C, 8 °C, 9 °C, 10 °C, 11 °C, 12 °C, 13 °C, 14 °C , or 15 °C lower than the ambient temperature. It is further noted that depending on the selection and design of the reservoir (130) and the gaseous medicament, the gaseous medicament may be cooling upon release as a result of expansion of the gaseous medicament. Thus, for example, pressurized carbon dioxide will cool upon release from a pressure cylinder. Thus in certain embodiments the cooling effect may be achieved without a separate temperature controller for controlling the temperature of the gaseous medicament. In accordance herewith in certain embodiments hereof where the disperser (105) is situated below the person (140) (as shown in the assembly 500 in the example implementation shown in FIG. 5), the gaseous medicament is heated so that the temperature of the gaseous medicament upon exiting the disperser is higher than the ambient temperature. For example the temperature controller may be set in such a manner that the temperature of the gaseous medicament upon exiting the disperser (105) is between approximately 1 °C and 15 °C higher than the ambient temperature, e.g. approximately 1 °C, 2 °C, 3 °C, 4° C, 5° C, 6° C, 7 °C, 8 °C, 9 °C, 10 °C, 11 °C, 12 °C, 13 °C, 14 °C , or 15 °C higher than the ambient temperature.

[0082] It is noted that in embodiments hereof wherein an air introducer for introducing ambient air into the disperser (105), such as a fan, vent, heater or ventilation device is included, such fan, vent, heater or ventilation device may serve the purpose of cooling or heating the gaseous medicament, but furthermore may also be used to control the airflow and to mix ambient air with the gaseous medicament, thus minimizing the requirements for the amount of gaseous medicament used.

[0083] In further embodiments, a device monitoring the person (140) in resting position, such as a microphone or a body based telemetry device, may be included. Referring to the example implementations of FIG.1 (assembly (100); FIG. 4 (assembly (400) and FIG. 5 (assembly (500)), there is shown a microphone (145) to monitor the person (140) in resting position, e.g. to monitor the breathing pattern of the person in resting position and detect abnormal sounds, e.g. snoring sounds, or to monitor sounds associated with restless sleep. The monitoring device (145) may be operably connected to an output device (not shown), e.g. one or more computer terminals, laptops, tablets, cellular phones, speakers, electronic storage devices, or a radio or other communication device capable of communicating with another device, or computing unit. The signals received from the monitoring device by the output device may be used to control the assembly (e.g. assembly (100); (400); (500) or (900)), either manually by e.g. a physician, or automatically, thus creating a feedback system. The hereinafter described intermittent administration of the gaseous medicament to the person in resting position (140) may be achieved and controlled by such feedback system.

[0084] It is further noted that movement of ambient air in which the assembly is placed may impact and temporarily deform the dimensions of the displacement zone (170), and/or the isokinetic flow zone (185) and/or the breathing zone (160) and or create turbulences therein. Thus it is may be beneficial to limit ambient air movement inside the room or space in which an assembly (e.g. assembly ((100); (400); (500) or (900)), or another assembly in accordance herewith, is situated and operated. This may be achieved by placing the assembly in a windowless room or space, or by closing windows, if any are present, in the room or space, and by eliminating other sources of air drafts or flows, and/or limit the activity of any ventilation or other airflow systems present in the room or space. It is further noted that in rooms or spaces where it is impractical to restrict movement of ambient air, the airflow and airflow rate may be increased in order to minimize deformation of the dimensions of the displacement zone (170)), and/or the isokinetic flow zone (185) and/or the breathing zone (160) and or created turbulences therein.

Gaseous medicaments

[0085] The gaseous medicament used in accordance herewith may be any medicament deliverable in a gas phase in a breathing zone of a person in need of the medicament in order to treat a breathing disorder.

[0086] The gaseous medicament may be formulated with other chemical compounds which may be therapeutically effective, or included in the formulation for other purposes, including, without limitation, to enhance stability of the gaseous medicament, to enhance dispersal of the gaseous medicament, or to enhance delivery to the airways of the gaseous medicament, or to dilute the gaseous medicament. Thus a gaseous medicament formulation may comprise a carrier (e.g. a carrier gas such as air, or air supplemented with oxygen (which may be separately supplied) or a diluent, or other delivery enhancing compositions, for example nano-particles. The air may be supplied from a separately contained air source or drawn from the ambient air, as a noted above.

[0087] In some embodiments, the medicament that is used is carbon dioxide or a perfluorocarbon, including without limitation, PFOB. The perfluorocarbon is preferably a medical grade perfluorocarbon.

[0088] The assembly and methods of the present disclosure may be used to administer carbon dioxide or a perfluorocarbon to treat any breathing disorder, including, without limitation, any sleep associated breathing disorder causing sleep disturbances or irregularities. Thus the assembly and methods may be used to treat any primary breathing disorder associated with sleep apnea, such as central sleep apnea, obstructive sleep apnea, and Cheyne Stokes breathing. The assembly and methods may further be used to treat breathing disorders resulting from a medical condition, such as a pulmonary disease, obstructive lung disease, chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, cystic fibrosis, or a systemic disease, e.g. cardiovascular disease, hypoventilation syndrome due to obesity or diabetes.

[0089] In accordance herewith, the gaseous medicament is administered in a therapeutically effective amount. In embodiments hereof where carbon dioxide is used, carbon dioxide may be provided in an amount substantially in excess (e.g. at least 10X in excess) to the amount of carbon dioxide present in ambient air, which typically comprises between from about 0.03% to about 0.05% carbon dioxide (or between about 300 ppm and 500 ppm). Thus in some embodiments, carbon dioxide is used in an amount that results in a displacement zone and/or an isokinetic flow zone comprising 0.5% or approximately 0.5%, at least 1 .0% or approximately 1 .0%, at least 2.0%, or approximately 2.0%, at least 3.0% or approximately 3.0%, or at least 4.0% or approximately 4.0% carbon dioxide. Higher amounts may also be used, e.g. amounts resulting in the displacement zone and/or isokinetic flow zone comprising at least 6.0%, 8.0%, 10.0%, 12.0% or approximately 4.0%, 6.0%, 8.0%, 10%, 12% carbon dioxide. The carbon dioxide used is preferably a medical grade carbon dioxide.

[0090] In yet further embodiments, minute amounts of carbon dioxide may be delivered, i.e. amounts in small excess of the amount carbon dioxide present in ambient air e.g. 0.05%, 0.06%, 0.07%, 0.08%, 0.09% or 0.1 %.

[0091] In certain embodiments, the amount of oxygen present in the airflow may be adjusted above the ambient amount (approximately 21 %; or 2, 100 ppm), e.g. the amount of oxygen may be increased to 21 .5%, 22.0% or 22.5%, or decreased to 20.5%, 20%, 19.5%, 18.5%, 18%, 17.5%, 17%, 16.5% or 16%. In certain embodiments, e.g. in embodiments where patients with CPOD are treated, oxygen may be provided in high concentrations e.g. in the range from approximately 90% - 94%.

[0092] In further preferred embodiments, mixtures of a perfluorocarbon and carbon dioxide may be used, e.g. mixtures of PFOB and carbon dioxide as, shown in Example 1 . In such mixtures the perfluorocarbon and carbon dioxide may act additively or synergistically.

[0093] In accordance herewith the person in need of receiving the gaseous medicament may be situated in resting position in proximity to the disperser. A resting position includes a horizontal position, e.g. lying on a bed, or an inclined position. The person may be awake or sleeping while the gaseous medicament is administered. The gaseous medicament may be administered continuously, or intermittently. In both cases however, the duration of administration is for a time period sufficiently long in duration to allow the formation of a displacement zone encompassing a breathing zone of a person in resting position, as hereinbefore described. Notably where the assembly is used to treat sleep associated breathing disorders the gaseous medicament may be administered for the entire period, or substantially the entire period, a person is sleeping. Intermittent administration may be achieved by regular or irregular cyclical administration of the gaseous medicament.

[0094] In some embodiments, the gaseous medicament is delivered continuously to the person in resting position. Thus the person for the approximate duration of the period that he is in resting position can receive the gaseous medicament. The person can be asleep and approximately for the duration of the entire period the person is asleep, the gaseous medicament can be continuously delivered.

[0095] In some embodiments, the gaseous medicament is delivered intermittently to the person in resting position. Thus, for example, the gaseous medicament can be delivered for a period of approximately 30, 20, 10 or 5 minutes every hour. In other embodiments, the gaseous medicament is pulsed, for example for a period of approximately at least 5 seconds, 10 seconds, 30 seconds, 45 seconds, one minute or two minutes followed by a time period, which may be varying in duration, and equal in duration, or shorter in duration, or longer in duration than the pulse period, during which no gaseous medicament is delivered. Pulse periods in accordance herewith are minimally sufficiently long in duration to allow the formation of a displacement zone encompassing a breathing zone of a person in resting position, as hereinbefore described.

[0096] Further provided in accordance with at least one aspect of the present disclosure, in at least one embodiment, is an assembly for the treatment of breathing disorders, the assembly comprising:

a reservoir containing a gaseous medicament for the treatment of a breathing disorder operably connected to

a disperser for receiving the gaseous medicament from the reservoir and dispersing the gaseous medicament to ambient air and form a displacement zone comprising the gaseous medicament.

[0097] Referring to FIG.1 as illustrated in example implementation 100, the assembly comprises a reservoir (130) comprising a gaseous medicament (not shown) of which the flow is controlled by a valve (150), operably connected via two conduits (110) and (115) to a disperser (105) having one or more outlet portions (155). The example implementation further comprises a second control valve (120) and a microphone (145). Also shown for illustrative purposes in the example implementation of FIG. 1 is a person in resting position (140) on a bed (135) and the breathing zone (160) of the person (140).

[0098] In other embodiments of the assembly, the disperser is situated to the side of the person (140) in resting position (as illustrated and exemplified by assembly (400) of this embodiment shown FIG. 4. [0099] In yet other embodiments, the disperser is situated below the person (140) (as illustrated and exemplified by assembly (500) of this embodiment shown in FIG. 5).

[00100] Further included herein, is a use of an assembly to treat a breathing disorder, the assembly comprising:

a reservoir containing a gaseous medicament for the treatment of a breathing disorder operably connected to

a disperser for receiving the gaseous medicament from the reservoir and dispersing the gaseous medicament to ambient air and form a displacement zone comprising the gaseous medicament.

[00101 ] Hereinafter are provided examples of specific embodiments for performing the methods of the present disclosure, as well as embodiments representing the compositions of the present disclosure. The examples are provided for illustrative purposes only, and are not intended to limit the scope of the present disclosure in any way.

EXAMPLES

Example 1 - Treatment of breathing disorders in a rat model system using displacement ventilation

[00103] The present example shows treatment of breathing irregularities in rats by delivery of carbon dioxide and PFOB and a combination thereof.

The experiments were designed to be a reasonable model for displacement ventilation.

Experimental Methodology

[00104] All data was collected using the Buxco Research Systems Biosystem XA software and Buxco Research Systems whole body plethysmography system designed for rat use (model number: PLY 3213). The plethysmograph is designed such that the animals are not restrained, sedated or surgically manipulated. The gaseous inflow passes through a perforated diffuser that ensures uniform distribution of the medicinal gas within the breathing zone of the animal. The plethysmograph was used to monitor rat pulmonary function before and after ovalbumin (OVA) allergen challenge as well as before and after treatment. Each experiment began by placing an OVA-sensitized rat (male pathogen free Brown Norway rats (BN/RijHsd), acquired from Harlan laboratories) inside the plethysmograph. Once placed inside the plethysmograph chamber, the rat was allowed 15 to 20 minutes to acclimatize and calm down before a 30 minute baseline recording period began. Following the baseline recording, the rat was removed from the plethysmograph chamber and given an aerosolized OVA challenge to elicit an allergic asthma response. Once the OVA challenge was complete, the rat was placed back into the plethysmograph chamber. When the late-phase response had plateaued, treatment was administered for 10 minutes. Treatments consisted of C0 ₂ alone (at 4%/8%/12%), or PFOB alone, or C0 ₂ (at 4%/8%/12%) and PFOB, or medical air. Following treatment, the rat was monitored for an additional 30 minutes while still in the plethysmograph.

[00105] The C0 ₂ with PFOB treatment consisted of nebulized PFOB with C0 ₂ enriched gas mixture (4%/8%/12% C0 ₂ , 21 % 0 ₂ , balanced N ₂ ; Praxair Nl CDOXR1 C). The C0 ₂ enriched gas was delivered through the bias flow machine and then routed through a vibrating mesh nebulizer (AeroNeb Go) nebulising perflubron prior to entering and flowing into the plethysmograph chamber through the top port. The same gas mixtures were used for the C0 ₂ alone treatment. The medical air treatment consisted of a gas mixture of 21 % 0 ₂ and balanced N ₂ (Praxair 1002).

[00106] Four 5-minute periods (baseline, late-phase, 0-5 minutes post- treatment, 10-15 minutes post-treatment) were extracted from the ACQKnowledge file of each individual rat containing recordings of the breathing pattern of the rat for the duration of the experiment, as measured by the Buxco system. The 5 minute baseline period was extracted from the time where the rat breathing looks the most normal during the 30 minute baseline recording. The late-phase period is taken from the last 5 minutes of the rat late-phase asthmatic response, before the set-up for the treatment began. The 0-5 minute post-treatment period was taken immediately following treatment cessation. The 10-15 minute post-treatment period was taken 10 minutes following treatment cessation.

[00107] Each 5-minute period was analyzed for each rat using ACQKnowledge, a program that provides precise (to 1/10,000 sec) time measurements and allows the user to define the start and end of a breath. For each experiment, the average duration (sec.) of a regular baseline breath was used to determine the time interval of an apnea for each animal. An apneic event was defined as an interval equivalent to one or more breaths, during regular baseline breathing, measured from the end of expiration to the beginning of the next inspiration. This interval was used to determine the total number and duration (sec.) of apneas during each 5-minute period. Apneas occurring at the beginning or end of a period were not recorded.

[00108] For each experiment, the apnea measurements were analyzed by calculating the total number of apneas and the total duration of apneas for each 5-minute period (baseline, late-phase, 0-5 minutes post-treatment, 10-15 minutes post-treatment). Comparisons were made within each treatment (C0 ₂ alone (at 4%/8%/12%), or PFOB alone, or C0 ₂ (at 4%/8%/12%) and PFOB, or medical air) using a one-way analysis of variance (ANOVA) followed by a Dunnett's post-hoc analysis to analyze differences in apneic events between each of the 5-minute periods analyzed. For each treatment, two ANOVA tests were performed; one ANOVA between the baseline, late-phase, and 0-5 minute post-treatment periods and one ANOVA between the baseline-late- phase and 10-15 minute post-treatment periods.

[00109] In a separate experiment, the rats were monitored during the treatment period and response to treatment determined at 1 minute intervals. Comparisons were made between treatment groups using a one-way ANOVA followed by a Dunnett's post-hoc analysis to analyze differences in apneic events for each 1 minute interval, between medical air and the 8% C02, PFOB alone, and 8% C02 and PFOB treatments.

Results

[001 10] During the late-phase, the number and duration of apneic events increased in all treatment groups (FIG. 6 and FIG. 7). FIG. 6 shows the effect of C0 ₂ alone (12%, 8%), PFOB alone, as well as the combination of C0 ₂ (12%, 8%, 4%) and PFOB in significantly reducing the number of apneas from the late-phase asthmatic response in the 0-5 minute post-treatment period. For the 10-15 minute post-treatment period, only the 12% C0 ₂ and PFOB combination was able to maintain a significant reduction from late-phase in the number of apneas. FIG. 7 shows the effect of C0 ₂ alone (12%, 8%) and the combination of C0 ₂ (12%, 8%, 4%) and PFOB in significantly reducing the duration of apneas from the late-phase in the 0-5 minute post-treatment period. For the 10-15 minute post-treatment period both the 12% C0 ₂ as well as the combination of 12% C0 ₂ and PFOB maintained a significant reduction from late-phase in the duration of apneas.

[001 1 1 ] The rapidity of the response to C0 ₂ and PFOB, expressed as the number and duration of apneic events, is shown in FIG. 12 and FIG. 13, respectively. A significant suppression of apneas was observed with PFOB at 1 minute for both number and duration of apneic events. This response persisted for the full 10 minutes of the exposure. C0 ₂ gas alone significantly reduced the number and duration of apneas at 7 minute and 1 minute, respectively, and a majority of subsequent time periods. The results of the combination of 8% C0 ₂ and PFOB are also shown in FIG. 12 and FIG. 13.

[001 12] FIG. 6. Total number of apneas. Data represents the average recorded values over each five minute period ± SEM of at least n=6 per treatment group. The baseline is pre-allergen challenge, the late-phase represents the height of the peak of the late-phase response, and the post- treatment periods are taken immediately (0-5 min) and 10 minutes (10-15 min) following cessation of treatment. P-values show significant difference from late-phase as calculated by a one-way analysis of variance followed by a Dunnett's post-hoc analysis; * p<0.05, #p<0.01 .

[001 13] FIG. 7. Total duration of apneas. Data represents the average recorded values over each five minute period ± SEM of at least n=6 per treatment group. The baseline is pre-allergen challenge, the late-phase represents the peak of the late-phase response, and the post-treatment periods are taken immediately (0-5 min) and 10 minutes (10-15 min) following cessation of treatment. P-values show significant difference from late-phase as calculated by a one-way analysis of variance followed by a Dunnett's post- hoc analysis; * p<0.05, #p<0.01 . [001 14] FIG. 12. Total number of apneas. Data represents the average ± SEM recorded values over the ten minute treatment period of at least n=6 per treatment group. The baseline (B), late-phase (LP), and post-treatment (PT) responses are averaged over five minute periods. The treatment period is shown at minute intervals. The increasing concentration of C0 ₂ in the chamber as it progressively displaces the ambient chamber environment is shown at the base of the graph. P-values show significant difference from medical air as calculated by a one-way analysis of variance followed by a Dunnett's post-hoc analysis; * p<0.05, #p<0.01 .

[001 15] FIG. 13. Total duration of apneas. Data represents the average ± SEM recorded values over each five minute period of at least n=6 per treatment group. The baseline (B), late-phase (LP), and post-treatment (PT) responses are averaged over five minute periods. The treatment period is shown at minute intervals. The increasing concentration of C0 ₂ in the chamber as it progressively displaces the ambient chamber environment is shown at the base of the graph. P-values show significant difference from medical air as calculated by a one-way analysis of variance followed by a Dunnett's post-hoc analysis; * p<0.05, #p<0.01 .