Abstract: A method and corresponding device are described for combating microbes and infections by delivering intermittent high doses of nitric oxide to a mammal for a period of time and which cycles between high and low concentration of nitric oxide gas. The high concentration of nitric oxide is preferably delivered intermittently for brief periods of time that are interspersed with periods of time with either no nitric oxide delivery or lower concentrations of nitric oxide. The method is advantageous because at higher concentration, nitric oxide gas overwhelms the defense mechanism of pathogens that use the mammalian body to replenish their thiol defense system. A lower dose or concentration of nitric oxide gas delivered in between the bursts of high concentration nitric oxide maintains nitrosative stress pressure on the pathogens and also reduces the risk of toxicity of nitric oxide gas.

Abstract: Methods and devices for treating excess mucus accumulation in mammals by administering gaseous inhaled nitric oxide or nitric oxide releasing compounds as a mucolytic agent or expectorant are provided. Delivery of gaseous nitric oxide can be made nasally or orally and is preferably substantially coincident with inhalation of the mammal or based on a synchronous parameter of the mammal's respiratory cycle. Varying therapeutic profiles may be used for the delivery of gaseous nitric oxide depending on the severity of the excess mucus accumulation. Parameters for the therapeutic profiles may include flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways.

Abstract: Methods and devices for treating excess mucus accumulation in mammals by administering gaseous inhaled nitric oxide or nitric oxide releasing compounds as a mucolytic agent or expectorant are provided. Delivery of gaseous nitric oxide can be made nasally or orally and is preferably substantially coincident with inhalation of the mammal or based on a synchronous parameter of the mammal's respiratory cycle. Varying therapeutic profiles may be used for the delivery of gaseous nitric oxide depending on the severity of the excess mucus accumulation. Parameters for the therapeutic profiles may include flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways.

Abstract: A method and corresponding device are described for combating microbes and infections by delivering intermittent high doses of nitric oxide to a mammal for a period of time and which cycles between high and low concentration of nitric oxide gas. The high concentration of nitric oxide is preferably delivered intermittently for brief periods of time that are interspersed with periods of time with either no nitric oxide delivery or lower concentrations of nitric oxide. The method is advantageous because at higher concentration, nitric oxide gas overwhelms the defense mechanism of pathogens that use the mammalian body to replenish their thiol defense system. A lower dose or concentration of nitric oxide gas delivered in between the bursts of high concentration nitric oxide maintains nitrosative stress pressure on the pathogens and also reduces the risk of toxicity of nitric oxide gas.

Abstract: Gas packages for the delivery of therapeutic gases, and in particular gaseous nitric oxide (gNO) are provided herein. The gas packages comprise one or more of a gas reservoir, interface layer, sealing layer, and holding container. The interface layer regulates discharge of the therapeutic gas from the gas reservoir to the external environment. The sealing layer and/or holding container prevent evolution of the gas until the sealing layer is compromised or the holding container is opened.

Abstract: Gas packages for the delivery of therapeutic gases, and in particular gaseous nitric oxide (gNO) are provided herein. The gas packages comprise one or more of a gas reservoir, interface layer, sealing layer, and holding container. The interface layer regulates discharge of the therapeutic gas from the gas reservoir to the external environment. The sealing layer and/or holding container prevent evolution of the gas until the sealing layer is compromised or the holding container is opened. The gas packages and methods for using them are useful for the treatment, alleviation, and prevention of various disease and non-disease, medical and non-medical, conditions in humans and animals.

Abstract: A method of topically treating the respiratory tract of a mammal with nitric oxide exposure includes the steps of providing a source of nitric oxide containing gas and delivering the nitric oxide containing gas nasally to the upper respiratory tract of the mammal. Also provided are several designs for a nasal delivery device for the controlled nasal deliver the nitric oxide containing gas.

Abstract: A method and corresponding device are described for combating microbes and infections by delivering intermittent high doses of nitric oxide to a mammal for a period of time and which cycles between high and low concentration of nitric oxide gas. The high concentration of nitric oxide is preferably delivered intermittently for brief periods of time that are interspersed with periods of time with either no nitric oxide delivery or lower concentrations of nitric oxide. The method is advantageous because at higher concentration, nitric oxide gas overwhelms the defense mechanism of pathogens that use the mammalian body to replenish their thiol defense system. A lower dose or concentration of nitric oxide gas delivered in between the bursts of high concentration nitric oxide maintains nitrosative stress pressure on the pathogens and also reduces the risk of toxicity of nitric oxide gas.

Abstract: A method and corresponding device are described for combating microbes and infections by delivering intermittent high doses of nitric oxide to a mammal for a period of time and which cycles between high and low concentration of nitric oxide gas. The high concentration of nitric oxide is preferably delivered intermittently for brief periods of time that are interspersed with periods of time with either no nitric oxide delivery or lower concentrations of nitric oxide. The method is advantageous because at higher concentration, nitric oxide gas overwhelms the defense mechanism of pathogens that use the mammalian body to replenish their thiol defense system. A lower dose or concentration of nitric oxide gas delivered in between the bursts of high concentration nitric oxide maintains nitrosative stress pressure on the pathogens and also reduces the risk of toxicity of nitric oxide gas.

Abstract: Topical exposure of nitric oxide gas to wounds such as chronic non-healing wounds may be beneficial in promoting healing of the wound and in preparing the wound bed for further treatment and recovery. Nitric oxide gas may be used, for example, to reduce the microbial infection and burden on these wounds, manage exudate secretion by reducing inflammation, upregulate expression of endogenous collagenase to locally debride the wound, and regulate the formation of collagen. High concentration of nitric oxide ranging from about 160 to 400 ppm may be used without inducing toxicity in the healthy cells around a wound site. Additionally, exposure to the high concentration for a first treatment period reduces the microbial burden and inflammation at the wound site and increase collagenase expression to debride necrotic tissue at the wound site.

Abstract: A method of reducing pathogens in blood by exposure to a nitric oxide containing gas in an extracorporeal circuitry is provided. The method includes: obtaining blood from a mammal or a blood source, separating the blood into plasma and blood cells, exposing the plasma to nitric oxide containing gas, combining the exposed plasma with the blood cells, reducing nitric oxide content in the recombined blood, and returning the blood to the mammal or blood source.

Abstract: Topical exposure of nitric oxide gas to wounds such as chronic non-healing wounds may be beneficial in promoting healing of the wound and in preparing the wound bed for further treatment and recovery. Nitric oxide gas may be used, for example, to reduce the microbial infection and burden on these wounds, manage exudate secretion by reducing inflammation, upregulate expression of endogenous collagenase to locally debride the wound, and regulate the formation of collagen. High concentration of nitric oxide ranging from about 160 to 400 ppm may be used without inducing toxicity in the healthy cells around a wound site. Additionally, exposure to the high concentration for a first treatment period reduces the microbial burden and inflammation at the wound site and increase collagenase expression to debride necrotic tissue at the wound site.

Abstract: A device and method is disclosed for delivering NO to a patient. The device utilizes a single controller that controls two separate flow controllers to deliver an oxygen-containing gas and a NO-containing gas to the patient to provide NO-containing gas at a flow profile that is proportional or quasi-proportional to a flow profile of the oxygen-containing gas throughout patient inspiration. The controller further comprises logic for setting a nitric oxide delivery profile comprising at least two different concentrations of nitric oxide containing gas and for automatically switching between the at least two different concentrations of nitric oxide containing gas on a timed basis.

Abstract: The administration of gaseous nitric oxide as a biocidal moiety is proffered as a de novo treatment in the control and eradication of biofilms. The present invention relates to the use or methods of application of exogenous nitric oxide gas (gNO) as a stand alone biocidal agent or in cohort with any or all adjunct vehicles in the control of biofilms generated by microbial organisms, i.e., bacteria, protozoa, amoeba, fungi etc. Further, the present invention introduces the concept of utilization and methods of application of gaseous nitric oxide in control and eradication of biofilm forming microorganisms. Noteworthy areas of application are offered as examples. They include, and are not limited to, air and/or water heating/cooling distribution systems in facilities such as hospitals and laboratories, surfaces of medical devices, household surfaces, dental plaque, dental and/or medical water treatment lines, industrial pipelines, water treatment and distribution facilities and fluids sterilization.

Abstract: A method of topically treating the respiratory tract of a mammal with nitric oxide exposure includes the steps of providing a source of nitric oxide containing gas and delivering the nitric oxide containing gas nasally to the upper respiratory tract of the mammal. Also provided are several designs for a nasal delivery device for the controlled nasal deliver the nitric oxide containing gas.

Abstract: A method of topically treating the respiratory tract of a mammal with nitric oxide exposure includes the steps of providing a source of nitric oxide containing gas and delivering the nitric oxide containing gas nasally to the upper respiratory tract of the mammal. Also provided are several designs for a nasal delivery device for the controlled nasal deliver the nitric oxide containing gas.

Abstract: A system controls and manages administration of a therapeutic gas, such as NO, O2, or the like, to a patient. The system includes an equalizing valve and a reservoir.

Abstract: Topical exposure of nitric oxide gas to wounds such as chronic non-healing wounds may be beneficial in promoting healing and preparing the wound bed for further treatment and recovery. Nitric oxide gas may be used to reduce the microbial infection, manage exudates secretion by reducing inflammation, upregulate expression of endogenous collagenase to locally debride the wound, and regulate the formation of collagen. High concentration of nitric oxide ranging from 160–400 ppm may be used without inducing toxicity in the healthy cells around a wound site. Exposure to the high concentration for a first treatment period reduces the microbial burden and inflammation, and increases collagenase expression to debride necrotic tissue at the wound site. After a first treatment period, a second treatment period at a lower concentration of nitric oxide, preferably ranging from 5–20 ppm may be used to restore the balance of nitric oxide and induce collagen expression aiding in the wound closure.

Abstract: A system controls and manages administration of a therapeutic gas, such as NO, O2, or the like, to a spontaneously breathing, non-ventilated patient such that concentrated NO is as low as reasonably possible while delivering the desired amount of NO to the distal portions of the lungs. The system includes an entrainment cell that provides remote, turbulent mixing with low temporal latency and can be used with a nasal cannula or a mask. The entrainment cell uses room air to dilute the therapeutic gas; however, supplementary gases can also be used. A baffle can be included to promote mixing and a flow sensor can also be used if desired. Multiple ports can be included in the entrainment cell. An equalizing valve is also disclosed.

Abstract: Therapeutic gas, such as NO, is delivered to a patient in accurately controlled amounts by a system that uses a closed loop feedback system in which the amount of therapeutic gas delivered is a precise fraction of the total gas delivered to the patient. Ratiometric feedback is used in the control loop.