Internal ultraviolet therapy

Abstract

To provide a UV light delivery device for providing an internal ultraviolet therapy.SOLUTION: A device includes a slender body that is separated by a proximal end and a distal end. The device also includes a UV light source that is constituted to be housed in a housing space. In some embodiments, the UV light source is constituted to emit light with a wavelength of 320-410 nm having significant intensity, and utilized in combination with an endotracheal tube or a nasopharyngeal airway.SELECTED DRAWING: Figure 1D

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 915,448, filed October 15, 2019, U.S. Provisional Application No. 62 / 992,861, filed March 20, 2020, U.S. Provisional Application No. 62 / 993,595, filed March 23, 2020, U.S. Provisional Application No. 63 / 000,788, filed March 27, 2020, and U.S. Provisional Application No. 63 / 012,727, filed April 20, 2020, all entitled Internal Ultraviolet Ray Therapy, the contents of which are incorporated herein by reference.

[0002] Field of Disclosure The present invention is directed to systems and methods for internal ultraviolet radiation therapy. [Background technology]

[0003] Background of the disclosure The following description contains information that may be useful in understanding the present invention. No admission is made that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0004] Infectious, immune-mediated, and inflammatory diseases continue to pose global challenges. Despite significant advances over the past few decades, treatment of these diseases remains suboptimal. For example, many patients suffer from upper respiratory tract infections and pneumonia while on a ventilator, which can lead to death. For example, patients on ventilator therapy are intubated with an endotracheal tube ("ETT") and may contract infections (e.g., pneumonia) through the ventilator system. Therefore, there is a need to reduce the rate of infections, such as viral infections, bacterial infections, etc., in the patient's somatic system, such as the respiratory system. Summary of the Invention

[0005] Disclosure Summary A UV light delivery system for performing internal UV light therapy is provided. The system includes a delivery tube adapted to be placed inside an endotracheal (ET) tube, a nasopharyngeal airway (NPA), or other similar device, and at least one UV light source within the delivery tube arranged to deliver UV light out of the delivery tube, the at least one UV light source configured to emit wavelengths between 335 nm and 350 nm. The delivery tube can be transparent or partially transparent.

[0006] The at least one UV light source can be a series of LED light sources. In some embodiments, the series of LED light sources can be configured to emit UV light with a peak wavelength between 335-350 nm, or between 338-342 nm. The UV light source can be configured to emit light between 335 nm and 350 nm at a threshold intensity sufficient to treat an infection.

[0007] The UV light source can be configured to deliver UV light along a substantial length of a delivery tube, which can be a catheter. The UV light source can be configured to only emit light at an intensity greater than 10% of its maximum intensity between 335 nm and 350 nm.

[0008] The system may also include a delivery tube adapted to be placed inside an endotracheal delivery (ET) tube, and at least one UV light source within the ET delivery tube arranged to emit UV wavelengths out of the ET delivery tube, the at least one UV light source configured to emit wavelengths between 335 nm and 350 nm. The UV light source may be configured for intermittent emission. The UV light source may be configured to emit wavelengths including at least one of UV-A and UV-B, or only UV-A.

[0009] The system may further include a power source connected to the UV light source.

[0010] The UV light source can be configured to treat infectious agents within the ET tube and within the larynx.

[0011] Also disclosed is a method of treating a patient for an infectious condition within the patient's body, the method including inserting a delivery tube inside the patient's respiratory cavity, emitting UV-A light in the 335-350 nm range from a UV light source disposed within the delivery tube, and emitting the UV wavelengths out of the delivery tube at a threshold intensity for a threshold duration.

[0012] The method may include a delivery tube that is a catheter equipped with an array of LED light sources having peak wavelengths between 339-346 nm. The respiratory cavity may be the trachea or nasopharynx.

[0013] The infectious condition may be selected from the group consisting of a bacterial infection, a viral infection, a fungal infection, pneumonia, and combinations thereof.

[0014] The threshold duration may include at least 20 minutes. The threshold intensity may include at least 13, 15, or 18 W / m2. The threshold intensity may include at least 1,100 microwatts / cm2. 2 , 1,100 microwatts / cm 2 , 2,000 microwatts / cm 2 , or 2,100 microwatts / cm 2 , 2,200 microwatts / cm 2 , or 2,300 microwatts / cm 2 The intensity may include:

[0015] The delivery tube can be inserted inside the endotracheal tube. Also, the delivery tube can be inserted inside the endotracheal tube while suctioning the endotracheal tube.

[0016] Additional features and advantages disclosed herein will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the principles disclosed herein. The features and advantages disclosed herein may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features disclosed herein will become more fully apparent from the following description and the appended claims, or may be learned by practice of the principles disclosed herein.

[0017] To describe the above disclosure and the manner in which its advantages and features may be obtained, a more particular description of the above principles will be made with reference to the illustrative examples shown in the accompanying drawings. These drawings represent only exemplary embodiments disclosed herein and therefore should not be considered limiting of its scope. These principles will be described and explained with further specificity and detail using the following drawings: [Brief description of the drawings]

[0018] [Figure 1A] 1 shows a cross-sectional view of an exemplary UV light-emitting device inserted into a patient's colon in accordance with principles disclosed herein. [Figure 1B] 1 illustrates a cross-sectional view of an exemplary UV light-emitting device inserted into a patient's vagina in accordance with principles disclosed herein. [Figure 1C] 1 shows a cross-sectional view of an exemplary UV light-emitting device inserted into a patient's trachea in accordance with principles disclosed herein. [Figure 1D] 1 illustrates a cross-sectional view of an exemplary UV light-emitting device inserted into a patient's nasopharynx in accordance with principles disclosed herein. [Diagram 2] 1 shows a schematic diagram of an exemplary UV light emitting device incorporating an LED according to principles disclosed herein. [Diagram 3] 1 shows a schematic diagram of an exemplary UV light emitting device incorporating a cold cathode according to principles disclosed herein. [Figure 4] 1 shows an exemplary schematic diagram of a UV spectrum according to principles disclosed herein. [Diagram 5] 1 illustrates a cross-sectional view of an exemplary UV light-emitting device inserted into the rectum and sigmoid colon of a patient according to principles disclosed herein. [Figure 6] 1 shows a cross-sectional view of an exemplary UV light-emitting device inserted into a patient's colon in accordance with principles disclosed herein. [Figure 7] 1 illustrates a cross-sectional view of a UV light-emitting device inserted into a patient's esophagus and stomach in accordance with principles disclosed herein. [Figure 8] 1 illustrates a cross-sectional view of an exemplary UV light-emitting device passing through a patient's digestive system in accordance with principles disclosed herein. [Figure 9] 1 illustrates a side view of an exemplary light source attachment according to principles disclosed herein. [Figure 10] 1 illustrates a side view of an exemplary light source attachment according to principles disclosed herein. [Figure 11] 1 shows an exemplary Foley catheter incorporating an exemplary UV light emitting device according to principles disclosed herein. [Figure 12A] 1 shows a growth curve of E. coli when an exemplary UV light emitting device disclosed herein is implemented. [Figure 12B] 1 shows a growth curve of E. coli when an exemplary UV light emitting device disclosed herein is implemented. [Figure 13] 1 shows an exemplary UV light-emitting device implemented in the colon of a mouse according to principles disclosed herein. [Figure 14] 14A and 14B show an exemplary UV light-emitting device as disclosed herein inserted into the vaginal canal of a rat, according to the principles disclosed herein. [Figure 15] Figure 15A shows a growth curve of a liquid culture containing E. coli when an exemplary UV light-emitting device as disclosed herein is implemented. Figure 15B shows an exemplary UV light-emitting device as disclosed herein implemented in a liquid culture containing E. coli. [Figure 16]1 shows a growth curve of a liquid culture containing E. coli upon implementation of an exemplary UV light emitting device disclosed herein. [Figure 17] 17A and 17B show growth curves of a liquid culture containing E. coli upon implementation of an exemplary UV light-emitting device disclosed herein. [Figure 18] 1 shows a growth curve of a liquid culture containing E. coli upon implementation of an exemplary UV light emitting device disclosed herein. [Figure 19] 1 shows a growth curve of a liquid culture containing E. coli upon implementation of an exemplary UV light emitting device disclosed herein. [Figure 20] 1 shows a growth curve of a liquid culture containing E. coli upon implementation of an exemplary UV light emitting device disclosed herein. [Figure 21] 1A and B show growth curves of a liquid culture containing E. coli when an exemplary UV light-emitting device disclosed herein is implemented. [Figure 22] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Figure 23] 23 shows the exemplary UV light emitting device of FIG. 22 attached to a gripping element 200 according to embodiments disclosed herein. [Figure 24] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Diagram 25] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Figure 26] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Figure 27] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Figure 28] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Figure 29] 1 illustrates an exemplary UV light emitting device according to embodiments disclosed herein. [Diagram 30]1 illustrates an exemplary process for performing internal ultraviolet light therapy according to embodiments disclosed herein. [Diagram 31] 1 illustrates an exemplary process for performing internal ultraviolet light therapy in conjunction with an ETT, according to embodiments disclosed herein. [Diagram 32] 1 shows a table showing the intensity and exposure duration of UVA light applied to bacterial cultures in one embodiment. [Diagram 33] 1 shows a table illustrating bacterial counts over time during UV light exposure in one example. [Diagram 34] 1 shows a growth curve illustrating bacterial count over time during UV light exposure using an exemplary system according to the present disclosure. [Figure 35A] Images over time of petri dishes containing bacteria exposed to UV light are shown compared to a control. [Figure 35B] 1 shows a growth curve illustrating the number of E. coli bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Figure 35C] 1 shows a growth curve illustrating the number of E. coli bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Figure 35D] 1 shows a growth curve illustrating the number of E. coli bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Figure 35E] 1 shows a growth curve illustrating the number of E. coli bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Fig. 35F] (Intentionally omitted.) [Figure 35G] 1 shows a growth curve illustrating the number of P. aeruginosa bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Fig. 35H] 1 shows a growth curve illustrating the number of Pseudomonas aeruginosa bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Fig. 35I] 1 shows a growth curve illustrating the number of Pseudomonas aeruginosa bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Fig. 35J] 1 shows a growth curve illustrating the number of Pseudomonas aeruginosa bacteria over time exposed to various intensities of UV light using an exemplary system according to the present disclosure. [Figure 35K] 1 shows growth curves comparing log reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system according to the present disclosure. [Figure 35L] 1 shows growth curves comparing log reduction at various intensities at 20 and 40 minutes, respectively, using an exemplary system according to the present disclosure. [Figure 35M] 1 shows growth curves illustrating the reduction in E. coli colony diameter at various intensities and treatment times using an exemplary system according to the present disclosure. [Figure 35N] 1 shows growth curves illustrating the reduction in P. aeruginosa colony diameter at various intensities and treatment times using an exemplary system according to the present disclosure. [Figure 36A] 1 shows a bar graph illustrating cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure. [Figure 36B] 1 shows a bar graph illustrating cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure. [Figure 36C] 1 shows a bar graph illustrating cell proliferation during exposure to UV-A light using an exemplary system according to the present disclosure. [Figure 36D] 1 shows a bar graph illustrating the absence of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure. [Figure 36E] 1 shows a bar graph illustrating the lack of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure. [Figure 36F] 1 shows a bar graph illustrating the lack of DNA damage to cells during exposure to UV-A light using an exemplary system according to the present disclosure. [Figure 37] 1 shows a bar graph illustrating the proliferation of virus-infected cells during exposure to UV light using an exemplary system according to the present disclosure. [Figure 38]1 shows a bar graph depicting cell number of infected cells 72 hours after UV light application using an exemplary system according to the present disclosure compared to a control. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Detailed Description definition Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Szycher's Dictionary of Medical Devices CRC Press, 1995 can provide a useful guide to many of the terms and phrases used herein. Those skilled in the art will recognize many methods and materials similar or equivalent to those described herein that could be used to practice the present invention. Indeed, the present invention is in no way limited to the methods and materials specifically described. For example, although the figures show the present invention primarily in the gastrointestinal tract, as shown throughout, the disclosed systems and methods can be used in other applications.

[0020] In some embodiments, characteristics such as dimensions, shapes, relative positions, and the like used to describe and claim particular embodiments of the invention should be understood as being modified by the term "about."

[0021] As used herein, "ETT" refers to an endotracheal tube, which is a flexible tube that is passed through a patient's mouth, into the trachea, and connected to a ventilator to help the patient breathe.

[0022] As used herein, "NPA" refers to a nasopharyngeal airway, which is a flexible tube placed through the nasal passages to the base of the tongue to help open the airway.

[0023] As used herein, the term "LED" refers to a light emitting diode, which is a semiconductor light source that emits light across a range of visible and non-visible light spectra. LEDs typically have an emission spectrum that includes a series of wavelengths that vary in intensity across their emission spectral range, and typically follow a bell-shaped or similarly shaped intensity curve across that wavelength range. A particular LED is typically characterized by the wavelength of its peak emission intensity, or the wavelength at which the LED emits its highest intensity radiation.

[0024] Thus, LEDs typically emit light over a range of wavelengths, and a particular LED may also be characterized with the range of wavelengths at which it emits above a threshold intensity (in some embodiments, a percentage of the LED's maximum intensity). For example, a given LED may emit light at at least 10% of its maximum emission intensity only between wavelengths of 335 nm and 345 nm. Below 335 nm and above 345 nm, the emission intensity of the LED may be less than 10% of the LED's peak intensity emission wavelength (herein "peak wavelength"), and in some cases may be too low to be suitable for treatment. Thus, for many treatment applications, only wavelengths between 335 nm and 345 nm will have a therapeutic impact on that particular LED.

[0025] Thus, the wavelength ranges described herein can be ranges of wavelengths that are therapeutically effective or significant for a particular therapeutic application, duration, and intensity of the luminescence delivered by the LED to a treatment site (or based on the output of the luminescence emitted by the LED). In some examples, the wavelength range can be a range of wavelengths emitted by an LED having an intensity that is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% of the peak luminescence intensity.

[0026] Thus, disclosed herein are emission spectral regions for various LED light sources that correspond to the regions where the LEDs emit a threshold intensity percentage of their maximum intensity. Examples of various LED spectral emission regions and peak intensity wavelengths of emission for commercially available LEDs are described in Filippo, et al, "LEDs: Sources and Intrinsically Bandwidth-Limited Detectors," the contents of which are incorporated by reference in their entirety.

[0027] Next, various embodiments of the present invention will be described. In the following description, specific details are provided to fully understand and enable the description of these embodiments. However, those skilled in the art will understand that the present invention may be practiced without the need for many of these details. Similarly, those skilled in the art will also understand that the present invention may include many other obvious features that are not described in detail herein. Furthermore, some well-known structures or functions may not be shown or described in detail below to avoid unnecessarily obscuring the relevant description.

[0028] The terms used below should be interpreted in their broadest reasonable manner, even when used in conjunction with detailed descriptions of certain specific embodiments of the invention. Indeed, certain terms may even be emphasized below. However, terms intended to be interpreted in a limiting manner are clearly and specifically defined as such in this Detailed Description section.

[0029] Although many specific embodiment details are described herein, these should not be construed as limitations on the scope of any invention or what may be claimed, but as descriptions of features that are specific to certain embodiments of a particular invention. Certain features described herein in the context of separate embodiments may also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment may also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, although features may be described above as functioning in a particular combination and may even be initially claimed as such, one or more features from a claimed combination may, in some cases, be separated from the combination, and the claimed combination may be directed to a subcombination or a variation of the subcombination.

[0030] Similarly, although operations may be depicted in the figures in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown, or in a sequential order, or that all of the operations shown be performed, to achieve desirable results. In certain situations, multitasking and parallel processing may be advantageous. Furthermore, the separation of various system components in the above embodiments should not be understood as requiring such separation in all embodiments, and it should be understood that the program components and systems described may generally be integrated together in a single software product or packaged in multiple software products.

[0031] overview UV light in the UV-A and UV-B ranges has traditionally been used to treat skin diseases, but has not been developed for the treatment of more widespread infections or inflammation within the human body. This disclosure describes a system for delivering therapeutic doses of UV light via a catheter, capsule, endoscope, tube, or port that can be used to manage internal infections and inflammatory conditions within a patient. The UV light sources disclosed herein are intended to provide a safe and effective alternative to antibiotics and anti-inflammatory / immunosuppressant drugs in various internal canals of a patient (e.g., colon, vagina, trachea).

[0032] In some examples, only UV-A light or only UV-B light may be emitted for a particular indication and treatment. For example, the UV light source may have a wavelength centered at or near 335 nm, 340 nm, or 345 nm, as disclosed herein. In other embodiments, the UV light source may emit a wavelength between 320 nm and 410 nm, and / or have a peak intensity of emission within that range. It is understood that a variety of wavelengths may be provided using the present systems and methods. In some examples, the wavelength range provided may be the longest possible wavelength that is therapeutically effective at a particular intensity and duration of application.

[0033] 1A illustrates an example of a UV light management system that includes a delivery tube 100 and several UV light sources 150, as well as a power source 120 for powering the system. Thus, as illustrated, a caregiver (e.g., a physician) can guide the delivery tube 100 to a patient's colon. Once guided to the patient's intended treatment target, the power source 120 can be energized to cause UV light to be emitted from the light sources 150 to the treatment target (e.g., the colon).

[0034] 1B shows an example of a UV light management system that includes a delivery tube 100, several UV light sources 150, and a power source 120 for powering the system. Thus, a caregiver (e.g., a physician) can guide the delivery tube 100 into the patient's vagina. Once in the patient's vagina, the delivery tube 100 can be energized by the power source 120 to emit therapeutic light (e.g., UV light) into the vaginal canal. The UV light sources disclosed herein are intended to provide a safe and effective alternative to antibiotics and anti-inflammatory / immunosuppressant drugs in the colonic and / or vaginal areas.

[0035] 1C illustrates an example of a UV light management system including a delivery tube 100, a UV light source 150, a power source 120, and a control system. The control system provides power and controls the duration and / or intensity of the treatment. Thus, as illustrated, a caregiver (e.g., a physician) can guide the delivery tube 100 to a patient's trachea during artificial ventilation. Once in the patient's trachea, the power source 120 is energized such that the power source 120 can provide power via the delivery tube 100 (e.g., a wired connection) to the light source 150 to emit therapeutic light (e.g., UV light) into the trachea and / or other respiratory tract.

[0036] For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet light therapy in combination with an endotracheal tube (ETT). Thus, a delivery tube 100 can be guided within the ETT during ventilation of the patient. In other embodiments, the delivery tube 100 can be connected to or incorporated into the ETT, or the ETT can have a light source 150 incorporated into the ETT. Thus, the light source 150 can be positioned within the tube 150 and / or the ETT such that the UV light source 150 irradiates respiratory tissue within the tracheal airway surrounding the ETT.

[0037] 1D illustrates an example of a UV light management system including a delivery tube 100, a UV light source 150, a power source 120, and a control system. The control system provides power and controls the duration and / or intensity of the treatment. Thus, as illustrated, a caregiver (e.g., a physician) can guide the delivery tube 100 to the patient's nasopharynx. Once in the patient's nasopharynx, the power source 120 is energized such that the power source 120 can provide power via the delivery tube 100 (e.g., a wired connection) to the light source 150 to emit therapeutic light (e.g., UV light) into the nasopharynx and / or other respiratory tract.

[0038] For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet light therapy in combination with a nasopharyngeal airway (NPA). Thus, a delivery tube 100 can be guided within a patient's NPA. In some embodiments, the delivery tube 100 can be sized and configured to fit the nasopharyngeal airway. In some embodiments, the delivery tube 100 can be flexible to accommodate the curvature of the nasopharyngeal airway. In other embodiments, the delivery tube 100 can be connected to or incorporated into the NPS, or the NPA can have a light source 150 incorporated into the NPA. Thus, the light source 150 can be positioned within the tube 150 and / or the NPA such that the UV light source 150 irradiates respiratory tissue within the nasopharynx surrounding the NPA.

[0039] Delivery System A delivery tube / rod 100 is provided for delivering therapeutic UV light to various parts of the body. The delivery tube / rod can include at least one UV light source 150. The delivery tube / rod 100 can be a catheter, an endoscope, a capsule (for swallowing or as a suppository), or any other medical device configured to house the UV light source 150.

[0040] In some examples, the UV delivery tube 100 may be configured as a catheter and guided inside the ETT or NPA during respiratory or other therapy for the patient. In some embodiments, the UV delivery tube / rod 100 may be configured as an endoscope that is inserted rectally or orally and guided to the appropriate area to deliver an anti-inflammatory or other therapeutic dose of UV light. In another embodiment, the UV delivery tube / rod 100 may be configured as a catheter that is inserted into an artery, urethra, vagina and urinary tract, ear canal, airway, etc. In yet another embodiment, the UV delivery tube / rod 100 may be configured as an indwelling urethral catheter that is inserted into the patient's bladder. In some embodiments, an inflatable balloon catheter may include a UV light source 150 to emit UV light inside an internal organ having a passageway, such as, for example, the vagina, rectum, gastroesophageal junction, stomach, biliary tract, or other suitable passageway. In some embodiments, the UV light source 150 may be configured as a caregiver's glove. This configuration can assist in delivering UV light to a patient's orifice (eg, mouth, rectum, vagina, or other orifice) for shorter duration treatments.

[0041] In some embodiments, the UV light source 150 is permanently attached to the delivery tube / rod 100. In other embodiments, the delivery tube / rod 100 is configured such that the UV light source 150 is configurable and can be attached and removed at the physician's preference. The delivery tube / rod 100 can include a hollow interior to allow for electrical connection to the UV light source 150. In alternative embodiments, the UV light source 150 may be wireless and capable of being coupled to the delivery tube / rod 100.

[0042] light source Depending on the delivery tube 100 or other delivery device, a variety of light sources 150 capable of emitting UV light can be utilized. For example, FIG. 2 illustrates an embodiment of a flexible delivery tube 100 (e.g., catheter, endoscope, etc.) that includes a series of LED light sources 150 distributed along the tube 100. In other embodiments, other suitable light sources 150 capable of emitting UV light can be utilized. Each of the light sources 150 is attached with an electrical connection and connected to the power source 120. LED light sources 150 can be advantageous because their small size and low power requirements allow them to be placed along the delivery tube 100.

[0043] Light source 150 may include a control system including circuitry, memory, and one or more processors for controlling the intensity and duration of the output of light source 150. The control system may include instructions executable by the one or more processors for controlling the output of light source 150. In some embodiments, the control system may be connected to light source 150 via a wired and / or wireless connection.

[0044] Thus, when the light source 150 is positioned along the delivery tube 100, the light source 150 can deliver UV light to a large delivery area within the patient's body, and therefore the treatment target area can be relatively large to treat inflammatory diseases that may affect a large portion of the colon.

[0045] FIG. 3 shows an example of a delivery tube 100 utilizing a cold cathode-based light source 150 connected to a power source 120. In this embodiment, the cold cathode light source 150 delivers light through a transparent, flexible delivery tube 100. This embodiment may include an inert gas that fills the delivery tube (or vacuum tube) 100. The delivery tube 100 may include, for example, a cold cathode fluorescent lamp. The delivery tube 100 may include any cathode luminescent material that is not electrically heated by a filament. For example, a cold cathode fluorescent lamp may utilize the discharge of mercury vapor to emit ultraviolet light.

[0046] In most embodiments, however, the gas used in the tube must be inert for safety. For example, neon gas vapor may be energized with a 12 volt power supply 120 to generate sufficient UV light. In other embodiments, other power supplies of varying voltages and / or currents are used to generate sufficiently intense light at the present wavelengths.

[0047] In some embodiments, the light source 150 can emit X-rays. In these embodiments, the system can include a vacuum tube or an X-ray tube.

[0048] The power source 120 may include an on / off switch or other control to turn the light source 150 on and off. In some embodiments, the power source will include the ability to turn on the UV light source at different intensities or adjust the intensity over time depending on the application of the treatment. The power source may vary depending on the type of UV light source 150. For example, the power requirements of an LED implementation may be less than the power requirements of a cold cathode implementation.

[0049] UV area FIG. 4 illustrates UV ranges that may be implemented by the disclosed devices and methods. For example, the light source may emit light only in the UV-A and UV-B ranges, but not in the UV-C range. In other examples, the systems and methods may emit light in all three UV ranges, or may emit light in the visible spectrum. In some examples, only UV-A or only UV-B light may be emitted for specific indications and treatments. As previously mentioned, the light source may have a wavelength of maximum intensity centered at 335 nm, 340 nm, or 345 nm, or a range thereabout. In other embodiments, the light source 150 may emit light at wavelengths between 320 nm and 410 nm, between 250 nm and 400 nm, or other suitable ranges discussed herein.

[0050] In some embodiments, the wavelength range applied may be the longest wavelength range that is therapeutically effective for a particular application (given the intensity and duration of the therapeutic application). For example, the shorter the wavelength, the more likely the treatment will damage the patient's body cells or tissues. Therefore, it is safest to apply the longest wavelength that is effective.

[0051] In some embodiments, a light source centered at 345 nm or 340 nm (or surrounding wavelengths) may be optimal, since smaller / shorter wavelengths are more harmful as they approach the UV-C region. For example, the shorter the wavelength, the more energy it has and the more likely it is to damage the patient's tissue and DNA. In some embodiments, the longest wavelengths that still provide sufficient antibacterial effects and are the safest wavelengths that are still effective may include one or more of the following: 335, 336, 337, 338, 339, 340, 341, 342, 342, 344, 345, 346, 347, 348, 349, or 350 nm. Thus, the light source 150 disclosed herein can emit light having one or more of the foregoing wavelengths at therapeutically significant intensities.

[0052] In some embodiments, the light source may be an LED having a peak wavelength of 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm 354 nm, 355 nm. In some embodiments, the peak wavelength of the LED may have an error of + / - 3 nm, 2 nm, or 1 nm. In some embodiments, the LED may emit light of significant intensity in a range of + / - 4, 5, or 6 nm around its peak intensity emission wavelength. Thus, in some embodiments, the wavelength range of the LED or other light source may be 340-350 nm (e.g., a wavelength range that includes wavelengths with significant emission intensity).

[0053] Treatment regimen The procedures herein can be utilized to treat a number of different inflammatory and infectious diseases. Thus, different amounts or durations of dosages of UV radiation can be administered depending on: (1) the type of disease, (2) the type of light source, (3) the light source power, (4) the UV range of the light source, and (5) the severity of the infection or inflammation. For example, in some embodiments, the administration time is determined by the capsule digestion rate, and other factors (e.g., light source power, UV range, etc.) can be manipulated to vary the dosage.

[0054] In other examples, the light therapy can be provided by a caregiver for 10, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 60, 90, 120, or 160 minutes, any range between 10 and 160 minutes, or any other suitable time. Additionally, the methods of the present invention can include administering therapy for a threshold duration of at least 10, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 60 minutes. The light source intensity can be at least 1,000 microwatts / cm. 2 , 1,100 microwatts / cm 2 , 2,000 microwatts / cm 2 , 2,100 microwatts / cm 2 , 2,200 microwatts / cm 2 , 2,300 microwatts / cm 2 , 2,400 microwatts / cm 2 , 2,500 microwatts / cm 2 , 2,600 microwatts / cm 2 , 2,700 microwatts / cm 2 , 2,800 microwatts / cm 2 , 2,900 microwatts / cm 2 , 3,100 microwatts / cm 2 , 3100 microwatts / cm 2 , 3,200 microwatts / cm 2 , 1,000 to 5,000 microwatts / cm2 or other suitable intensities depending on factors related to the therapeutic effect, such as the area to which it is applied. We have used UV-A light at up to 5,000 microwatts / cm 2 It has been determined that light can be safely applied in intensities up to 100 nm. In some embodiments, the light will be emitted continuously, while in other embodiments, the light will be incorporated into a pulsed regimen.

[0055] The light source 150 can be at various distances from the target depending on the intensity and the target microorganism. For example, in some embodiments, the light source 150 can be 2000 microwatts / cm 2 In some embodiments, the intensity is 1000-5000 microwatts / cm, and in some embodiments, the intensity is 1000-5000 microwatts / cm. 2 and the distance to the target tissue may be 0-1 cm, 0-1.5 cm, 0-2 cm, 0-2.5 cm, 0-3.0 cm, 0-3.5 cm, 0-4.0 cm, or other similar suitable ranges based on the light intensity and the target pathogen. In other embodiments, the required timing, distance, wavelength, and intensity may vary for different targets, such as viruses.

[0056] Control System In some embodiments, a control system is utilized to control the intensity and duration of the wavelengths emitted from the UV light source. An example of an LED control system is described, for example, in U.S. Patent No. 8,350,497, entitled "Method and apparatus for outputting light in a LED-based lighting system," the contents of which are incorporated herein by reference in their entirety.

[0057] Thus, in some cases, light source 150 may be connected to a control system that controls the power provided to light source 150 and the output of light source 150. The control system may include various electronic circuitry for controlling the output of light source 150, including LEDs, based on the requirements of the individual light source 150. In some embodiments, where light source 150 includes multiple LEDs of different wavelength ranges, the control system may determine which LEDs to supply current to, and therefore the wavelengths emitted by light source 150. EXAMPLES

[0058] The following examples are provided to better illustrate the claimed invention and are not intended to be construed as limiting the scope of the invention. To the extent that specific materials or steps are mentioned, they are for illustrative purposes only and are not intended to limit the invention. Those skilled in the art may develop equivalent means or reactants without the exercise of inventive capacity and without departing from the scope of the invention.

[0059] gastrointestinal tract 5-6 show an application for treating diseases of the colon and / or rectum. For example, FIG. 5 shows that a delivery tube 100 including a light source 150 can be inserted into the colon through the anus by a caregiver. The delivery tube 100 can then be guided to the treatment site, e.g., the colon, a portion or a large portion of the intestine (see, e.g., FIG. 6), or through the mouth into the stomach (see, e.g., FIG. 7). The power source (or light source) 120 can then be turned on to illuminate the treatment site with UV light.

[0060] In some embodiments, this may be utilized to treat various inflammatory diseases, including diseases such as ulcerative colitis and Crohn's disease, IBD, infectious diseases, etc. As shown, depending on the size, location, and type of disease, the delivery tube 100 may include various amounts of light sources 150 that may be embedded or included in a particular portion or length of the delivery tube 100.

[0061] 7 shows an embodiment in which an endoscope or other delivery tube 100 is inserted through the oral cavity, down the esophagus and into the stomach. In this example, stomach infections or inflammatory diseases can be treated with a UV light source 150.

[0062] Colonoscopy FIG. 13 shows an example where a UV light emitting device is used for colonoscopy in mice. Colonoscopy and application of UV were performed safely. Parameters included 1,100 microwatts / cm. 2 The study included 10 and 30 minutes of UV exposure at 100 nm intensity followed by a standard colonoscopy 72 hours later.

[0063] GI treatment may include the following exemplary applications: 1. Treatment of chronic inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, as well as acute / chronic pouchitis 2. Treating non-IBD-related proctitis 3. Treatment of IBD-related or non-IBD-related fistulas 4. Treatment of inflammatory strictures 5. Treatment of Microscopic Colitis 6. Treating infectious diarrhea using UV light-emitting capsules 7.Treatment of refractory Helicobacter pylori and MALT lymphoma 8. Treatment of esophageal lichen planus and pemphigus vulgaris 9. Treatment of refractory Clostridium difficile 10. Treatment of colonic incompetence, tropical sprue, celiac disease, small intestinal bacterial overgrowth, post-bone marrow transplant appendicitis, pseudopolyps (similar to nasal polyps), and radiation enteritis 11.Treatment of Barrett's Esophagus with or without Dysplasia 12. Treating Hepatic Encephalopathy with Daily UV Light Capsules 13. Treatment of blind loop syndrome in Roux-en-Y patients by placing an ILT (intracorporeal phototherapy) catheter through an intragastric PEG 14. Treatment of perianal fistulas with transparent drainage lines capable of emitting UV light 15. Reduced infection rates associated with percutaneous feeding or suction tubes 16. Treatment of gastrointestinal cancer confined to the mucosa and submucosa 17. Treatment of hepatic and biliary infections, inflammation, and cancers limited to the mucosa and submucosa

[0064] capsule In some embodiments, the delivery device is shaped as a capsule instead of a delivery tube / rod 100. In such embodiments, the capsule is inserted into the patient orally or anally. The capsule can emit light for a period of time. For example, the capsule can include a lubricious transparent or translucent polymer or other biocompatible coating to allow passage of the capsule. In some examples, the capsule can include a light source 150 and a power source 120. The power source 120 can include, for example, a small battery. In some embodiments, the capsule can be placed and secured in an internal organ to provide long-term light exposure.

[0065] In some embodiments, the capsule is configured such that the UV light 150 is positioned to emit light in all directions from the capsule, thus as the capsule passes through the digestive system, it emits UV light in all directions until the capsule is excreted.

[0066] FIG. 8 shows an embodiment of the system utilizing a delivery device as a capsule 800 that may be swallowed by the patient. The capsule 800 may include a light source 150 and a power source 120 for powering the light source 150. In some embodiments, the capsule or a portion thereof may be made of a transparent material to allow light to be emitted through the capsule. The capsule may include a tracking device to assess the location of the capsule within the gastrointestinal tract. The capsule delivery system may be clipped to a hollow organ for continuous or intermittent controlled delivery.

[0067] In some embodiments, the capsule may be the size of a pill or smaller and may be orally ingestible. The capsule may include a timer to turn the UV light source on and off when the capsule reaches or is most likely to reach a particular portion of the digestive tract. For example, the capsule may include a simple timer that turns the capsule on after 30 minutes, 1 hour, or 2 hours. For example, the capsule may not turn on the light source 150 until the capsule reaches the digestive tract to treat IBS or other infectious or inflammatory conditions.

[0068] Photoconductive Delivery Tube In certain embodiments, the light source 150 may be disposed inside the delivery tube 100 (e.g., an LED), while in other embodiments the light source 150 may be disposed outside or in conjunction with the proximal end of the delivery tube 100. Thus, in some embodiments, the delivery tube 100 may be made from optical fiber or other light-conducting material to propagate light from the light source 150 up the delivery tube 100 so that the light can be emitted to the treatment site.

[0069] 9 and 10, a UV light management system can include a delivery rod 940, a UV light source 950, and a light source attachment 900 configured to be mounted between the UV light source 950 and the delivery rod 940. The delivery rod 940 can include a borosilicate segment 930 to filter out UV-C from the light spectrum, followed by a segment made of pure silica (quartz) 900 to extend the transmission distance of UVA / B with minimal loss.

[0070] For example, using only pure quartz segments results in significant UV-C light emission (e.g., 4,300 microwatts / cm 2It has been shown that UV-A and UV-B light are generated at the tip of the delivery rod 940, but when a pure quartz rod is used with a short segment of borosilicate (e.g., a borosilicate filter) between the UV light source 950 and the delivery rod 940, UV-A and UV-B are detected at the same levels without the borosilicate segment, and only 10 microwatts / cm of UV-C light is emitted at the tip of the delivery rod 940. 2 , meaning that the UV light is reflected back into the body of the delivery rod 940 so that it is delivered throughout the entire delivery rod 940. The UV light source 950 can be configured to be connected to a power source (not shown) that provides power to the UV light source 950.

[0071] The delivery rod 940 can be a fiber optic rod / catheter. In some exemplary embodiments, the delivery rod 940 is made by using industrial diamonds to score the rods, whereby glass cutter oil is used and bilateral pressure is applied to break them off clear (not opaque). The tip of the delivery rod 940 can be rounded by a drill (e.g., a 500 RPM drill) using a premium diamond polishing pad (e.g., a 120-200 grit premium diamond polishing pad) and sandpaper (e.g., 400 grit sandpaper). The body of the delivery rod 940 can then be polished with a 120-200 grit premium diamond polishing pad so that non-UV-C light (e.g., UV-A and UV-B) can be emitted throughout the body of the delivery rod 940. Alternative chemical opacifiers can be used for custom opacification of the rods.

[0072] The light source attachment 900 may include a body 920 and a fastening mechanism 910 (e.g., a screw, set screw, fastener, nail, etc.) that attaches the body 920 to a housing (e.g., a rod, catheter, handle, etc.). The body 920 may include a front end opening 970 configured to connect to a light source (or power source) and a rear end opening 980 configured to connect to a rod (or catheter).

[0073] The light source attachment 900 may be made of aluminum for heat conduction and to reduce light intensity degradation. The diameters of both the front end opening 970 and the rear end opening 980 may vary, for example, to fit a particular catheter, tube, rod, etc. The light source attachment 900 may also include a convex lens 930 between the front end opening 970 and the rear end opening 980 configured to reduce light loss. This convex lens may include a semi-convex heat resistant lens that reduces light loss and focuses the light.

[0074] catheter In some examples, the delivery device can be a catheter tube 100 that can be insertable into an artery, urethra, or other part of a patient's body. For example, the catheter tube 100 can include a hollow portion that allows a guidewire to pass through. Thus, a caregiver can guide the guidewire to a treatment site and then pass the catheter over the guidewire to guide the catheter to or beyond the treatment site.

[0075] Secondly, similar to the endoscope embodiment, the catheter tube 100 can include any of a variety of light sources 150 suitable for administering UV treatment inside the artery. In some examples, this embodiment can use smaller light sources 150, such as LEDs.

[0076] In another embodiment disclosed herein, the delivery device may be a catheter tube 100 that is inserted into the bladder as an indwelling urethral catheter (e.g., as shown in FIG. 11) so that the UV light can sterilize the urinary tract infection. In another embodiment, the delivery device may be part of a balloon that is inserted into the rectum to treat the rectum with UV light.

[0077] vagina In yet another example, the delivery device may be incorporated into a vaginal rod to treat an infection within the patient's vagina.

[0078] FIG. 22 illustrates an exemplary UV light emitting device according to embodiments disclosed herein that may be utilized for intravaginal delivery of UV light in some examples. The UV light emitting device may include a delivery tube / rod 100. In some examples, the delivery tube / rod 100 includes a four sided elongated body 101. The four sided elongated body 101 may include a UV light source 150 on each of the four sides. The UV light sources 150 may be staggered on each side of the delivery tube / rod 100. The delivery tube / rod 100 may include a proximal end 102 and a distal end 103. The four sides of the elongated body 101 converge into a rounded surface 105 toward the distal end 103. The distal end 103 of the delivery tube / rod 100 is configured for insertion into a patient, as described above. In contrast, the opposing proximal end 102 is configured for maneuverability of the delivery tube / rod 100.

[0079] FIG. 23 illustrates an example of the UV light emitting device of FIG. 22 with a gripping element 200. The gripping element 200 can be configured as a handle. The gripping element 200 can be attached to the delivery tube / rod 100 at the proximal end 102. The gripping element 200 can be designed to be ergonomically sufficient for a physician or healthcare provider. The gripping element 200 can also include an input component 201 configured to receive user input. The input component 201 can be connected to an internal processor that alters the functionality of the delivery tube / rod 100 and the UV light sources 150. In some embodiments, the delivery tube / rod 100 includes between 2 and 20 UV light sources. The delivery tube / rod 100 illustrated herein includes three UV light sources 150 on each of the four sides, for a total of 12 UV light sources 150. It should be understood that other configurations incorporating the features disclosed herein are possible.

[0080] FIG. 24 illustrates an exemplary UV light-emitting device 300 according to embodiments disclosed herein. The UV light-emitting device 300 can include a gripping element 350. The gripping element 350 can be designed to be ergonomically sufficient for a physician or healthcare provider. The gripping element 350 can also include an input component 351 configured to receive user input. The input component 351 can be connected to an internal processor that alters the functionality of the delivery tube / rod 300 and the UV light sources 330. The delivery tube / rod 300 illustrated herein includes two UV light sources 330 on each of the four sides, for a total of eight UV light sources 330. It should be understood that other configurations incorporating the features disclosed herein are possible.

[0081] In some embodiments, the delivery tube / rod 100 can include a rotational base at its distal end 103. The rotational base can enable rotation of the delivery tube / rod 100 such that the light emitted from the UV light source 150 is uniform. When a rotating delivery tube / rod 100 is used to treat a patient, the uniform UV emissivity is likely to aid in the treatment of microbial growth. In some examples, the delivery tube / rod 100 also includes a stepper motor. The stepper motor can enable rotation of the rotational base.

[0082] In some embodiments, the UV light sources 150 are distributed along the entire length of the delivery tube / rod 100 and at the distal end 103 to achieve broader coverage of the UV light sources 150.

[0083] In some embodiments, the delivery tube / rod 100 is configured to illuminate and deliver UV light uniformly throughout the entire delivery tube / rod 100. In some embodiments, the delivery tube / rod 100 is configured to emit light waves only in the UV-A and / or UV-B ranges, and not in the UV-C range. For example, the peak wavelength of the UV light source 150 can include 340 nm. In other broader embodiments, the delivery tube / rod 100 (and light source 150) can deliver wavelengths between 320 nm and 410 nm. It should be understood that the disclosed delivery tube / rod 100 can be used to provide a variety of wavelengths and combinations of various wavelengths. Wavelengths in other ranges can include, for example, 250 nm to 400 nm. In some embodiments, the vertical illumination length extends between 8 and 10 cm around the delivery tube / rod 100.

[0084] The delivery tube / rod 100 may be made of any suitable structure (e.g., rigid or flexible), including various polymers that are biocompatible or have biocompatible coatings. FIG. 25 illustrates an exemplary UV light emitting device 400, according to embodiments disclosed herein. In some embodiments, the delivery tube / rod 100 may include an outer layer of a transparent material to allow UV light from the light source 430 to radiate out of the delivery tube / rod 100. In some embodiments, the delivery tube / rod 100 may include an outer surface made from, for example, silicon, silica, polyurethane, polyethylene, Teflon / PTFE, borosilicate, or other suitable material. In some embodiments, the delivery tube / rod 100 is constructed using copper with a borosilicate outer layer. For optimal cooling, exposed area, and uniformity, the delivery tube / rod 100 may include multiple light emitting diodes (LEDs) staggered on a copper rod. In some examples, eight LEDs may be provided on the delivery tube / rod. The spacing of the light sources 430 is such that allows for optimal vertical illumination length. In some embodiments, the vertical illumination length extends between 8-10 cm around the delivery tube / rod 100.

[0085] By using copper to manufacture the body of the delivery tube / rod 100, the delivery tube / rod 100 can withstand reaching high temperature levels. The copper acts as a heat sink and prevents the delivery tube / rod 100 from reaching uncomfortable temperatures. Applicant also proposes to operate the light source 150 at a specific current to optimize the temperature of the delivery tube / rod 100. In some embodiments, the light source 150 is operated within the range of 60-100 mA. Within the proposed range, the temperature of the delivery tube / rod 100 will not rise above 40° C., thus achieving the goal of implementing a suitable cooling solution.

[0086] 26-29 show various examples of UV light delivery systems with a controller 450. The controller 450 can include one or more processors, memory, and a battery or other power source. The memory can include instructions associated with various treatment regimens that can be applied using various intensities and / or durations as disclosed herein. For example, the memory can include data structures that, when executed by the processor, power the light source 150 at a given intensity or timing. The controller can be utilized in any of the embodiments disclosed herein, including vaginal, GI, and ETT-based UV light delivery devices.

[0087] 30, a process for performing internal ultraviolet light therapy is provided. The process includes, in step 2501, providing a UV light delivery device. The UV light delivery device includes an elongated body including a proximal end and a distal end. The elongated body includes a receiving space. The UV light delivery device also includes a UV light source configured to be coupled to the receiving space. In some embodiments, the method also includes, in step 2503, rotating the elongated body such that the two UV light sources are configured to uniformly emit UV light outwardly.

[0088] The process may also include, in step 2504, emitting wavelengths between 320 nm and 410 nm with peak wavelengths of 340, 341, 342, 343, 344, 345, and 346 nm from the two UV light sources. In some embodiments, the process also includes emitting radiation from the two UV light sources out of the elongated body. In some embodiments, the elongated body includes four sides. Each of the four sides of the elongated body includes a receiving space such that a corresponding UV light source 150 is staggered in the elongated body.

[0089] The elongated body includes a receiving space and a corresponding UV light source at a proximal end. The elongated body is partially coated with borosilicate glass. In some embodiments, the elongated body is made of copper.

[0090] respiratory system In some embodiments, the systems and methods disclosed herein may be utilized to deliver UV light to the body passages of a patient's respiratory system. For example, in some embodiments, the delivery tube 150 may be guided into an endotracheal tube (ETT) while the patient is being ventilated. Alternatively, the delivery tube 150 may be guided into a nasopharyngeal airway (NPA) of the patient. These applications may be utilized to treat or prevent infections, including viral infections, bacterial infections, pneumonia, and other infections.

[0091] In some embodiments, the delivery tube 100 may be inserted into the ETT while the ETT is being aspirated. In other embodiments, the systems and methods herein may be utilized to improve the treatment of empyema by equipping a chest tube with a delivery tube to deliver intracorporeal phototherapy.

[0092] For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet light therapy in combination with an endotracheal tube (ETT). Thus, a delivery tube 100 can be guided within the ETT during ventilation of the patient. In other embodiments, the delivery tube 100 can be connected to or incorporated into the ETT, or the ETT can have a light source 150 incorporated into the ETT. Thus, the light source 150 can be positioned within the tube 150 and / or the ETT such that the UV light source 150 irradiates respiratory tissue within the tracheal airway surrounding the ETT.

[0093] For example, as disclosed herein, systems and methods have been developed for providing internal ultraviolet light therapy in combination with a nasopharyngeal airway (NPA). Thus, a delivery tube 100 can be guided within a patient's NPA. In other embodiments, the delivery tube 100 can be connected to or incorporated into the NPA, or the NPA can have a light source 150 incorporated into the NPA. Thus, the light source 150 can be positioned within the tube 150 and / or the NPA such that the UV light source 150 irradiates respiratory tissue within the nasopharyngeal airway surrounding the NPA.

[0094] In some embodiments, the UV light source 150 in the delivery tube 100 can be a series of LEDs. For example, the delivery tube 100 can be a flexible catheter that connects to an ETT or NPA and can have LEDs located on or within the catheter to emit UV light out of the delivery tube 100 to treat the patient's respiratory tract and / or the interior of the ETT or NPA. The LEDs can be connected with a wired connection to a power source. In other embodiments, the light source 150 can be other suitable light sources 150 other than LEDs.

[0095] In this example, the LEDs may have a maximum emission intensity wavelength of 335, 336, 337, 338, 339, 340, 341, 342, 342, 344, 345, 346, 347, 348, 349, 350 nm, or any wavelength range between 335 and 350 nm. In other embodiments, the LEDs may emit wavelengths between 320 nm and 410 nm, 250 nm and 400 nm, or any other suitable range discussed herein.

[0096] 31 shows a flow chart illustrating an embodiment of a treatment regimen for treating a patient's respiratory tract and surrounding tissue with UV light. For example, a catheter or other delivery tube 150 equipped with a UV light source may be provided 3100 and guided 3102 into the ETT. The UV light source may then be energized 3104 for various treatments.

[0097] In some examples, a delivery catheter equipped with an LED having a wavelength of maximum emission intensity centered at 339, 340, 341, 342, 343, 344, 345, or 346 nm can be energized for at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 60, 80, or 90 minutes (or other suitable time frame within or outside these ranges) once, twice, or three times per day. The applied intensities are based on the power of the LEDs and the distance from the LED light source to the tracheal tissue or other respiratory tract tissue, and are 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300 uW / cm 2 , or other suitable intensities between or outside these ranges.

[0098] Other therapeutic applications and treatment regimens The procedures herein can be utilized to treat several different inflammatory and infectious diseases. Thus, different amounts or durations of dosages of UV radiation can be administered depending on: (1) the type of disease, (2) the type of light source, (3) the light source power, (4) the UV range of the light source, and (5) the severity of the infection or inflammation. For example, in some embodiments, the administration time is determined by the capsule digestion rate, and other factors (e.g., light source power, UV range, etc.) can be manipulated to vary the dosage. In other examples, the endoscope can be delivered by the physician / surgeon for 1 hour, 30 minutes, 2 hours, or other suitable time.

[0099] Below are examples of treatment regimens and their applications: Thus, the devices and methods disclosed herein can be adapted to treat these different conditions. Urology and Nephrology: 1. To sterilize blood from patients with known bacteremia, fungemia, or viremia during dialysis to eradicate or reduce the microbial load. Alternatively, a light needle can be placed in the fistula and turned on even outside the dialysis window. Ex vivo sensitivity analysis is performed for narrower wavelength but more intense ILT. 2. Sterilization of indwelling urinary catheters in catheter-dependent patients 3. Treatment of bladder and urethral cancer localized to the mucosa and submucosa 4.Treatment of intractable cystitis / urinary tract infections 5. Adding UV phototherapy to peritoneal dialysis catheters to reduce the risk of peritonitis and even long-term peritoneal sclerosis. Cardiology 1. To sterilize blood in patients with known bacteremia, fungemia, or viremia with LVAD to eradicate or reduce microbial load. Alternatively, a light needle can be placed in the fistula and turned on outside the dialysis window. Ex vivo sensitivity analysis can be performed for narrower wavelength but more intense UV therapy. 2. Refractory bacterial and fungal endocarditis is treated with direct UV light exposure of the valve, sometimes with intravenous administration of a photosensitizer. Dentistry 1. Treatment of gingivitis. 2. Treatment of leukoplakia and oral lichen planus. 3. Treatment of cancer limited to the mucosa and submucosa Hematology / Oncology 1. Treating intestinal graft-versus-host disease. In this case, wavelengths of X-rays are emitted, killing lymphocytes. This can be used in patients with end-stage Crohn's disease awaiting small intestine transplants or palliative care. ENT 1.Treatment of chronic sinusitis. 2. Treatment of chronic otitis. 3. Treatment of acute otitis media in patients requiring myringotomy. 4. Treating nasal polyps (there is evidence that UV light can shrink nasal polyps - see attached paper). 5. Treating bad breath. 6. Treating recurrent tonsillitis / pharyngitis. 7. Treatment of cancer limited to the mucosa and submucosa surgery 1. To improve the treatment of abscesses by equipping drains with UV light technology. 2. Use with a surgical drain to avoid mixed infection. 3. To speed up the anastomotic healing process. 4. Helps prevent adhesions. Neurosurgery 1.Intrathecal fiberoptic delivery of UV light in the treatment of refractory meningitis. 2. Treatment of refractory shunt infections. 3. Treatment of prion diseases with intrathecal or subarachnoid UV therapy. 4-Treatment of JC virus associated with progressive multifocal leukoencephalopathy by reducing the viral load. Gynecology 1. Treating bacterial or fungal vaginosis. 2. Treatment of rectovaginal / colonic fistula. 3. Treatment of cancer limited to the mucosa and submucosa Rheumatology 1. Intra-articular ILT for the treatment of inflammatory and infectious large arthritis. Vaginal therapy 1. Figures 14A and 14B show an example of a UV light-emitting device being used for vaginal treatment of mice.

[0100] Experimental Data The following set of experimental data is provided to better illustrate the presently claimed invention and is not intended to be construed as limiting its scope.

[0101] Example 1: E. coli 12A and 12B show experimental data illustrating an embodiment in which the UV light emitting device disclosed herein is used to prevent the growth of E. coli. As shown, the control group to which no UV light was applied continued to grow, while the test group to which UV light was applied by the UV light emitting device showed a continuous decrease in E. coli counts over time. UV light has been shown to prevent the growth of E. coli and kill the bacteria over time.

[0102] Figure 15B shows an example where a UV light emitting device disclosed herein is used with a liquid culture containing E. coli. Results of this experiment and similar experiments with other bacteria and the fungus Candida albicans are shown, for example, in Figure 15A, and in Figures 16, 17A-17B, 18-20, 21A, and 21B. All results show a significant reduction in the growth of E. coli and other infectious pathogens in liquid samples where UV-A and UV-B light was emitted onto the liquid sample by a UV light emitting device disclosed herein.

[0103] Example 2: Bacteria In another example, two exemplary devices according to the present disclosure were used in UVA experiments to treat bacteria. The first device was a borosilicate rod (3 mm outer diameter) that was repeatedly etched with a mixture of dilute sulfuric acid, sodium bifluoride, barium sulfate, and ammonium bifluoride, and a reflective coating was added to the end of the rod that allowed UVA to be emitted from the side. This process resulted in a UVA (peak wavelength 345 nm) side-emitting rod, as confirmed by a spectrometer (Ocean Optics; Extech). The second device was integrated with a narrowband LED with a peak wavelength (345 nm).

[0104] The UVA rod was inserted into the liquid medium. A mercury lamp (Asahi Max 303, Asahi Spectra Co., Tokyo, Japan) was used as the light source. The second UVA-emitting device was a small light-emitting diode (LED) array (peak wavelength 345 nm) attached to a heat sink (Seoul Viosys, Gyeonggi-Do, Korea). This device was used in the plating experiments described below.

[0105] Stock cultures of Escherichia coli, E. coli GFP, Pseudomonas aeruginosa, Streptococcus pyogenes, Staphylococcus epidermis, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, Clostridioides difficile, and Candida albicans were grown in the appropriate liquid media and conditions as indicated in the table shown in Figure 32. American Type Culture Collection (ATCC) strains and one clinical isolate were grown in the appropriate solid and liquid media according to the instructions suggested by ATCC for each organism (Manassas, VA, USA). Using sterile technique, the vial containing the microbial strain was opened and the entire pellet was rehydrated with approximately 500 μL of liquid broth.

[0106] The resuspended pellet was aseptically transferred to a tube containing 56 mL of the same liquid broth used to resuspend the cells. A few drops from the primary broth tube were used to inoculate solid microbial agar to isolate single colony forming units (CFUs). The liquid and solid cultures were incubated at the specified temperatures, atmospheric conditions, and times as described in FIG.

[0107] First, liquid cultures were prepared from a single CFU of each microorganism to ensure the purity of the strains during UVA therapy. Only fresh pure liquid cultures were used during the experiment. One single colony was added to a 10 mL sterile tube containing 5 mL of liquid medium, followed by thorough vortexing to homogenize the microbial cells. The liquid cultures shown in Figure 32 were incubated until they reached 0.5 in the McFarland turbidimetric assay. After meeting the standard turbidity, the microbial cultures were thoroughly mixed for 1 min and 1000 μL of the liquid culture was transferred to two 1.7 mL microcentrifuge sterile tubes to be used as treatments and controls. 100 μL aliquots of each tube were serially diluted and plated on solid microbial media to determine the CFU / mL count at baseline, as shown in Figure 33.

[0108] Prior to UVA phototherapy, several sterile 1.7 mL tube caps were prepared by using a heated glass rod to poke a small hole in the top, the shape and size of the rod that would be used to transmit the UVA light.

[0109] Aseptically, the original caps from the liquid cultures in the 1.7 mL tubes were replaced with sterile caps with holes. A UV light emitter rod (sterilized with 70% ethanol) was placed in the hole made in the top of each cap. An identical rod was also placed in the control tube. Light was transmitted through a glass rod inserted into the tube using a MAX-303 xenon light source (Asahi Spectra USA, Inc., Torrance, CA). UV bandwidth and irradiance peak were evaluated (Flame UV-VIS fiber optic spectrometer, Ocean Optics). UV intensity was measured with SDL470 and UV510 UV light meters (Extech, NH, USA) Extech. Absence of UVC was confirmed using an SDL470 UV light meter (Extech, NH, USA). Figure 32 describes the intensity and exposure period of UVA light applied to the bacterial cultures.

[0110] After the treatment time was completed, the rods were removed from the treatment and control tubes and the liquid cultures were closed using new sterile caps without holes. Both the treatment and control groups were homogenized by vortexing. A 100 μL aliquot of each tube was then serially diluted and plated on solid microbial media to determine the number of CFU / mL after UVA treatment as shown in the table in Figure 33. This process was repeated until all time points listed in Figure 33 were achieved.

[0111] After each time point (baseline and post-UVA treatment), 100 μL of liquid microbial culture (treated and control) was serially diluted in sterile 1xPBS (EMD Millipore, Billerica, MA). The final serial dilution factors were 1:10 (100 μL microbial culture and 900 μL sterile 1xPBS), 1:100, 1:1000, 1:10,000, and 1:100,000. 100 μL of each dilution was plated in duplicate on solid agar plates and incubated for the time, temperature, and atmospheric conditions described in Figure 32. After incubation, colonies were counted using a Scan 300 automated colony counter (Interscience, Woburn, MA, USA) and corrected for volume and dilution factor to define the number of CFU / mL.

[0112] The second device used in these experiments incorporates a small light-emitting diode (LED) array (peak wavelength 345 nm, bandwidth 10 nm) mounted on an aluminum heat sink (Seoul Biosys, Gyeonggi-Do, Korea). In the first experiment, the system was placed 1 cm above the surface of a culture plate with a thick lawn of E. coli, emitting approximately 2000 μW / cm. 2 The light source was then placed in a separate experiment at 10 2 CFU / mL was applied to liquid cultures of E. coli and P. aeruginosa.

[0113] In both conditions, UVA was irradiated at 500, 1000, 2000, and 3000 μW / cm 2Intensities of 100 μg / mL and 1 cm for 20 and 40 min were tested in separate series of experiments to generate dose-response curves. After incubation, colonies were counted using a Scan 300 automated colony counter (Interscience), colony size was measured, and the number of CFU / mL was defined after correction for volume and dilution factor.

[0114] result Exposure to UVA was associated with a significant reduction in various pathogenic microorganisms, including Candida albicans (P = 0.007) and Clostridium difficile (P = 0.01), as shown in the table shown in Figure 33. UVA light exposure time of 20 min (intensity 1300-3500 μW / cm 2 ) showed a reduction in most microorganisms compared to the control group (P<0.05), except for Klebsiella pneumoniae (P=0.17), Enterococcus faecalis (P=0.1), and Streptococcus pyogenes (P=0.64). When compared to the untreated control, UVA light exposure times of 40 and 60 minutes were effective against all microorganisms tested (P<0.05, Figure 33). Notably, the bactericidal and fungicidal effects showed a dose-dependent response to UVA light, with greater microbial reductions associated with longer exposure times, as shown in Figure 33.

[0115] UVA light therapy was also applied to a clinically isolated strain of E. coli obtained from the human urinary tract. UVA light was tested in a set of five consecutive experiments, exposing the bacterial culture to 1100-1300 μW / cm for 20, 40, 60, and 80 minutes. 2 Compared to baseline, the number of CFU / mL observed in bacterial cultures exposed to UVA light was reduced at all time points evaluated, including 20 minutes (P=0.03), 40 minutes (P=0.0002), 60 minutes (P<0.0001), and 80 minutes (P<0.0001), as shown in FIG.

[0116] Finally, experiments were performed to test the effect of LED narrowband UVA (peak wavelength of 345 nm) on E. coli and P. aeruginosa. In these experiments, this particular wavelength of UVA caused a significant reduction in bacterial cells, as shown in Figures 35A-35N. For example, Figure 35A shows a photograph of bacterial colonies in a petri dish and the disappearance pattern of colonies around the site of application of the LED light at 20 and 40 minutes.

[0117] Figures 35B-35F show graphs showing colony forming units (CFU) of E. coli over time when irradiated with UV-A light with a peak wavelength of 345 nm at various intensities. As shown, most of the bacteria were eliminated by 40 minutes at an intensity of 2000 uW (Figure 35D), and most of the bacteria were eliminated by 20 minutes at an intensity of 3000 uW (Figures 35E and 35F). When the same light was irradiated at intensities of 500 uW and 1000 uW, there was a significant reduction in CFU by 40 minutes, but only by about half (Figures 35C and 35B).

[0118] Figures 35G-35J show graphs showing the time course of colony forming units (CFU) of Pseudomonas aeruginosa when exposed to various intensities of UV-A light with a peak wavelength of 345 nm. As shown, treatments with intensities of 1000 uW, 2000 uW, and 3000 uW showed significantly greater reductions in CFU compared to the control (Figures 35H, 35I, and 35J), and by 20 minutes at intensities of 2000 uW and 3000 uW, most of the bacteria were eliminated (Figures 35I and 35J).

[0119] Figures 35K-L show growth curves comparing the log reduction of P. aeruginosa at various intensities at 20 and 40 minutes, respectively. Figure 35M shows growth curves showing the reduction in E. coli colony diameter at various intensities and treatment times. Figure 35N shows growth curves showing the reduction in P. aeruginosa colony diameter at various intensities and treatment times.

[0120] When examining the effect of light intensity on the reduction of E. coli and P. aeruginosa, a dose-response effect was observed on both bacterial load and colony size (Figures 35B-35N). The ideal UVA intensity to affect bacteria appears to be 2000-3000 μW / cm2 using narrowband LEDs with a peak wavelength of 345 nm, and in some examples may depend on the type and species of bacteria or pathogen, as well as other factors disclosed herein.

[0121] Example 3: Safety Data Three experiments were performed to evaluate the safety of UVA on mammalian cells. In the first experiment, HeLa cells in culture were exposed to UVA. HeLa cells were plated in DMEM cell culture medium (Gibco, Waltham, MA) plus 10% bovine calf serum (Omega Scientific, Tarzana, CA) and 1x antibiotic-antimycotic (100x Gibco) in 60x15mm cell culture dishes (Falcon) and grown at 37°C (5% CO2) for 24 hours to reach 1,000,000–1,800,000 cells per plate. At this point, the cells were incubated with UVA LED light (1800 μW / cm 2 ) for 0 (control), 10, or 20 min. After 24 h, cells were removed with 0.05% trypsin EDTA (1x) (Gibco), stained with trypan blue (trypan blue 0.4% ready to use (1:1) (Gibco)), and quantified with an automated cell counter (Biorad T20, Hercules, CA). In a similar experiment, LED UVA light was applied at a higher intensity (5000 μW / cm 2 ) for 20 min. Again, HeLa cells were quantified 24 h after UVA exposure.

[0122] The safety of UVA was also examined in two types of human respiratory cell lines. These included alveolar (ATCC A549) and primary ciliated tracheal epithelial cells (HTEpC) (PromoCell, Heidelberg, Germany). For each cell line, 250,000 cells were plated and grown in DMEM for 48 h until there were approximately 750,000 cells per plate. At this point, the cells were exposed to UVA (2000 μW / cm 2 ) for 0 (control) or 20 (treatment) minutes, and cell counts were taken 24 hours later.

[0123] The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA of UVA-treated cells were also analyzed. 8-OHdG is widely accepted as a sensitive marker of oxidative DNA damage and oxidative stress. DNA was extracted using the AllPrep DNA / RNA / Protein Mini kit (Qiagen) according to the manufacturer's instructions. The levels of 8-OHdG were detected using the EpiQuik™ 8-OHdG DNA Damage Quantification Direct Kit according to the manufacturer's instructions (Epigentek, Farmingdale, NY). For optimal quantification, the input DNA amount was 300 ng, as basal 8-OHdG is generally less than 0.01% of total DNA (Epigentek, Farmingdale, NY).

[0124] Wild-type 129S6 / SvEv mice (n=20, female=10) and BALB / cJ mice (n=10, female=5) were used for UVA light safety testing. All animals were anesthetized prior to treatment. Prior to UVA light treatment, animals were placed in an induction chamber containing isoflurane anesthetic gas (1-5%). The carrier gas for isoflurane was compressed oxygen (100% oxygen). Once the respiratory rate slowed (approximately 1 breath per second), animals were removed from the induction chamber and kept under sedation using nose cone anesthesia (1-2% isoflurane). Depth of anesthesia was confirmed by lack of response to toe pinch.

[0125] Under anesthesia, a customized rod (D=4mm, L=40mm) was introduced through the anus to the splenic flexure. In the control group, the same procedure was applied with an identical but non-illuminated rod. The light source and measurement equipment were the same as those described in the liquid culture experiments.

[0126] In the first experiment, five BALB / cJ mice were given a 30-min colonic UVA exposure (2,000 μW / cm 2 ) and were compared with five mice treated with an unlit optical rod using the same technique.

[0127] In the second experiment, ten 129S6 / SvEv mice were given 20 min of colonic UVA exposure (3,000–3,500 μW / cm) per day. 2 ) on two consecutive days and compared with 10 mice (5 males) treated with unlit rods.

[0128] Colonoscopy before and after UVA phototherapy A rigid pediatric cystoscope (Olympus A37027A) was used to evaluate the intestinal mucosa before and after 7 days of UVA exposure. Endoscopy was performed in anesthetized animals. Sedation methods were as previously described.

[0129] The anus was first lubricated with an aqueous gel (Astroglide®, BioFilm, Inc., Vista, CA, USA). The endoscope was then inserted to the splenic flexure and the colon was insufflated using room air injected through the endoscope port. All endoscopic examinations were recorded and interpreted in a blinded manner by two gastroenterologists experienced in animal model endoscopy. Endoscopic images were analyzed based on perianal examination, bowel wall transparency, mucosal bleeding, and focal lesions.

[0130] On day 14, control and treated mice were euthanized and whole colon Swiss roll preparations were made as suggested by Bialkowska et al. Briefly, the entire colon was removed and rinsed in modified Bouin's fixative (50% ethanol / 5% acetic acid in dH2O). Using scissors, the colon was opened longitudinally along the mesenteric line and briefly rinsed in a Petri dish containing 1xPBS. The luminal side was identified and Swiss rolling of the open tissue was performed. Once the entire length of the colon had been rolled, the colon was carefully transferred into a tissue processing / embedding cassette. The cassette was kept in 10% buffered formalin overnight at room temperature, after which paraffin sections of the colon were cut, stained with hematoxylin and eosin (H&E) and evaluated by a blinded pathologist (SS).

[0131] Bacterial count data between groups were not normally distributed and were compared using nonparametric tests (Mann Whitney U test). Other quantitative data were compared by t test using GraphPad Prism 7 (GraphPad, San Diego, CA).

[0132] result Overall, based on cell proliferation over time, LED UVA appeared to be safe in the mammalian cells tested (HeLa, alveolar A549, and primary tracheal cells). Cell proliferation continued in all plates despite UVA exposure, with 1.5-2x the number of cells per plate compared to controls, indicating continued robust replication. For HeLa cells, UVA had no effect on viable cell counts after 24 hours (approximately 2000 μW / cm) compared to unexposed controls, as shown in Figure 36A. 2 of UVA for 10 and 20 min, P = 0.99 and P = 0.55, respectively. 2 ) did not affect the proliferation of HeLa cells, as shown in the bar graph depicted in Figure 36B. Similar findings were observed at 2000 μW / cm, as shown in Figure 36C. 2 , and alveolar cells at 20 min (P = 0.99). Finally, the growth of ciliated epithelial cells was also increased by UVA irradiation at approximately 1000 μW / cm 2and about 2000 μW / cm 2 After 20 minutes of exposure to light, there was no effect.

[0133] Furthermore, exposure to UVA did not cause DNA damage in any of the cell lines analyzed, and the levels of 8-oxo-2'-deoxyguanosine (8-OHdG) in cells treated with narrowband LED UVA were similar to controls without UVA exposure (P<0.05) as shown in Figure 36D (HeLa cells), Figure 36E (alveolar cells), and Figure 36F (tracheal cells). Higher LED UVA intensities (5000 μW / cm2) reduced DNA damage in any of the cell lines analyzed. 2 ), levels of 8-OHdG appeared to be elevated ( P = 0.07), but the percentage of 8-OHdG remained well below the generally accepted threshold of 0.01% of total DNA.

[0134] UVA light exposure is not associated with endoscopic or histological damage To evaluate the safety of UVA therapy on internal organ cells and tissues, two different wild-type mouse strains were exposed to intracolonic broad-spectrum UVA light using an optical rod designed to uniformly laterally emit broad-spectrum UVA. Only the left side of the colon up to the splenic flexure was exposed to UVA light, so the unexposed right side served as an autologous control. In the first experiment, five mice under anesthesia were given a 30-minute colonic UVA exposure (2,000 μW / cm2) and compared to five mice treated with the same technique but without the optical rod.

[0135] In the second experiment, 10 mice (129S6 / SvEv, male = 5) received 20 min of colonic broad-spectrum UVA exposure (3,000–3,500 μW / cm) per day. 2 ) on two consecutive days and compared with 10 mice (male = 5) treated with unlit rods. No perforation, bleeding, or death was observed in any experiment. Colonoscopy images of mice show no changes before and after UVA exposure.

[0136] In both experiments, endoscopic evaluation of mice before and after UVA treatment revealed no macroscopic evidence of mucosal erythema, fragmentation, ulceration, or bleeding. As assessed by a blinded pathologist (SS), full-thickness colon specimens exposed to broad-spectrum UVA showed no chronic / acute inflammation, cystitis, crypt abscesses, granulomas, ulcers, or dysplasia compared to control and untreated colon segments.

[0137] RNA virus experiment data Additionally, experimental data was obtained using the disclosed system and method to treat various RNA viruses with UVA light. As a result, the data shows that UV-A light emitted from an LED with a peak wavelength of 340 nm can kill RNA viruses, such as Coxsackievirus. For example, Hela cells infected with Coxsackievirus survived when this UV-A treatment was applied, but did not survive when UV-A light treatment was not applied after infection. Furthermore, the experimental data showed that only 15% of the UV-A light was lost after passing through the ET tube.

[0138] In late December 2019, an outbreak of novel coronavirus disease (SARS-CoV-2 or COVID-19, previously known as 2019-nCoV) was reported in the city of Wuhan, China. COVID-19 is a viral infection that replicates efficiently in the upper respiratory tract. As part of its mechanism of action, the virus infects ciliated airway epithelial cells, which then slough off, compromising alveolar function. Secondary bacterial infections have also been noted, and either of these processes can lead to further inflammation, acute respiratory distress syndrome (ARDS), and ultimately death. It is estimated that 10-15% of infected individuals will have a severe clinical course, and approximately 5% will progress to a critical condition requiring mechanical ventilation due to respiratory or other organ failure. The case fatality rate of COVID-19 is estimated to range from 0.5% to 9.5%, although this estimate is confounded by the prioritization of testing symptomatic patients and a time lag of up to 14 days before symptom onset. Deaths are believed to be due to respiratory failure in the setting of ARDS and / or secondary infections, including ventilator-associated pneumonia (VAP).

[0139] Ventilator-associated pneumonia (VAP) can develop in intensive care unit (ICU) patients receiving mechanical ventilation for at least 48 hours and is common in COVID-19 patients. The incidence of VAP ranges widely from 5% to 67%, depending on the diagnostic criteria used and the patient population studied. Causative bacteria include Enterobacteriaceae (25%), Staphylococcus aureus (20%), Pseudomonas aeruginosa (20%), Haemophilus influenzae (10%), and Streptococcus pyogenes (13). Multidrug-resistant bacteria are more prevalent in late-onset cases. Mortality from early-onset VAP is approximately 6%, whereas mortality from late-onset VAP is 10%.

[0140] There is currently no cure for COVID-19, and traditional means to reduce secondary infections in mechanically ventilated patients have thus far proven insufficient. A safe and effective broad-spectrum antiviral and antibacterial approach in these patients should potentially reduce viral load, secondary infections and VAP, time on mechanical ventilation, and deaths due to respiratory failure.

[0141] As disclosed herein, ultraviolet (UV) light has antimicrobial properties. UVC (110-280 nm) is widely used for industrial sterilization (16), but has been shown to have deleterious effects on human DNA. External UVA (320-400 nm) and UVB (280-320 nm) devices have been approved by the FDA for human diseases such as psoriasis, eczema, and cutaneous lymphoma. These wavelengths penetrate mucosal and submucosal tissues. Of the three spectra, UVA appears to cause the least damage to mammalian cells. There are currently no studies showing the effect of internal application of UVA light on bacterial or viral infections. Advances in light-emitting diodes (LEDs) have made it possible to apply narrow-band UVA to internal organs.

[0142] Thus, experimental data are disclosed that demonstrate the efficacy of broadband and / or narrowband UVA for the treatment of common bacterial pathogens known to be associated with VAP. Additionally, data are disclosed that demonstrate the efficacy of specific wavelengths of UVA against group B coxsackievirus and coronavirus 229E. Finally, additional data demonstrate the safety of UVA exposure to mammalian cells and epithelial cells in vivo.

[0143] Example 4: Coxsackievirus Obtaining coxsackievirus samples and infecting cells Recombinant Coxsackievirus B expressing enhanced green fluorescent protein (EGFP-CVB) plasmid (pMKS1) was linearized using ClaI restriction enzyme (ER0142, Thermo Fisher), and the linearized plasmid was purified using standard phenol / chloroform extraction and ethanol precipitation. Viral RNA was then generated using the mMessage mMachine T7 transcription kit (AM1344, Thermo Fisher). The viral RNA was then transfected into HeLa cells (~80% confluency) using Lipofectamine 2000 (11668027, Thermo Fisher). When the cells showed ~50% cytopathic effect, the cells were scraped off and the cell / medium suspension was collected. The mixture was then subjected to three rounds of rapid freeze-thaw cycles and centrifuged at 1000xg for 10 min to clear the medium of cell debris. The supernatant was used as the passage 1 virus stock. The passage 1 virus stock was then overlaid onto separate HeLa cells (approximately 80% confluency) to expand the stock to a passage 2 virus stock, which was used in subsequent experiments.

[0144] UVA treatment of HeLa cells infected with group B coxsackieviruses. HeLa cells were used for four different experiments using enhanced green fluorescent protein (EGFP)-expressing group B coxsackievirus (EGFP-CVB). In the first experiment, HeLa cells (253,000 per plate) (n = 12 plates) were cultured for 24 h. Half of the EGFP-CVB aliquot was irradiated with LED UVA (2000 μW / cm 2 , peak wavelength 340 nm) for 20 min and the other was not. HeLa cells were then infected (MOI=0.1) with either the virus exposed to UVA or the virus not exposed to UVA. After 6 h, the supernatant was removed and the cells were washed twice with 1x sterile PBS (pH=7.0). Fresh DMEM medium was added. The plate infected with the virus exposed to UVA was then exposed to UVA (2000 μW / cm) for an additional 20 min. 2) for 24 hours. Dead cells in the supernatant were collected and quantified after 24 hours. Six plates (three UVA-treated and three UVA-untreated) were assessed for viable cells. Of the remaining six plates, the three plates that were initially exposed to UVA with a peak wavelength of 340 nm were exposed to UVA (2000 μW / cm) for an additional 20 minutes. 2 After a further 24 hours, the remaining plates were counted for dead and live cells.

[0145] Pretreatment of HeLa cells with UVA against group B coxsackievirus infection In the second experiment, HeLa cells (235,000 cells) were plated and then incubated in DMEM for 24 hours. Plates were then treated with either an unexposed control (n=3) or with LED UVA (2000 μW / cm 2 After a further 24 hours, all plates were infected with EGFP-CVB (MOI=0.1). After a further 24 hours, cells were counted as described above.

[0146] Pretreatment of group B coxsackieviruses with UVA for infection of HeLa cells In the third experiment, HeLa cells were cultured for 24 h and then infected with EGFP-CVB (MOI = 0.1). Immediately before infection, half of the EGFP-CVB aliquot was irradiated with LED UVA (2000 μW / cm 2 Half were exposed to a 300 nm UV-bright light (peak wavelength 340 nm) and the other half were left unexposed. After 24 hours, viable cell counts were taken.

[0147] Long-term UVA treatment of HeLa cells during ongoing infection with group B coxsackieviruses. In this experiment, 250,000 HeLa cells were plated. After 24 hours, the cells were divided into three groups. In the first group, the cells were infected with EGFP-CVB (MOI=0.1). These cells served as positive infection controls. In group 2, HeLa cells were infected with EGFP-CVB (MOI=0.1) treated with UVA (2000 μW / cm2, 20 min, peak wavelength 340 nm), and after 6 hours, the infected cells were exposed to UVA (2000 μW / cm2) and then to UVA (2000 μW / cm2). 2 Group 3 was not infected with EGFP-CVB but was treated with UVA five times at the same time points used in group 2. This was a non-infected positive control to demonstrate the safety of UVA. Imaging and cell counts were obtained in all conditions.

[0148] UVA treatment of group B coxsackievirus-infected alveolar (A549) cells In preliminary experiments with alveolar cells, we determined that the ideal time point for cell death due to infection was 48 hours post-infection. In this study, 200,000 alveolar cells were plated and counted 48 hours later (754,000 cells). The alveolar cells were then infected with EGFP-CVB (MOI=0.1). 24 hours after infection, the alveolar cell plates were exposed to LED UVA (2000 μW / cm 2 The cells were exposed to infrared radiation (peak wavelength 340 nm) for 0 minutes (control) or 20 minutes (treatment), and this was repeated every 24 hours for three days. Imaging and cell numbers were then measured 96 hours after infection.

[0149] result Pretreatment of HeLa cells with group B coxsackieviruses only with UVA does not reduce infection. In this experiment, half of the plate containing HeLa cells was treated with EGFP-CVB and the other half was treated with a 340 nm peak wavelength and approximately 2000 μW / cm 2The mice were treated with group B Coxsackievirus followed by 20 min exposure to LED UVA light. The effect on infectivity at 24 h did not differ between groups.

[0150] UVA pretreatment of HeLa cells prior to infection with group B coxsackievirus does not attenuate the effects of the virus In this experiment, half of the plate with HeLa cells was left untreated, and the other half was exposed to a 340 nm peak wavelength and approximately 2000 μW / cm 2 We pretreated HeLa cells with 100% LED UVA for 20 min without further UVA treatment. Both groups were spiked with EGFP-CVB. Both groups were equally infected, suggesting that treating HeLa cells prior to infection had no effect on infection rates.

[0151] UVA treatment after infection with group B coxsackievirus attenuated viral effects on HeLa cells. In this study, UVA was applied after HeLa cells were infected with EGFP-CVB. Treated cells received approximately 2000 μW / cm with a peak wavelength of 340 nm at 6 h postinfection. 2 1000 cells were exposed to LED UVA and then cell counts were taken at 72 hours post-infection and exposed twice daily for two more days. This was compared to infected but untreated controls. In the treated group, UVA light prevented cell death from EGFP-CVB, increasing cell count to 339,333 ± 60,781 at 72 hours as shown in the bar graph depicted in Figure 37, whereas the untreated control showed no viable cells remaining on the plate at 48 and 72 hours. Importantly, a third group of HeLa cells, not infected but exposed to UVA for the same time interval, showed normal cell growth with cell count of 2,413,333 ± 403,773 after 72 hours.

[0152] Effect of UVA treatment on alveolar (A549) cells infected with group B coxsackieviruses. In alveolar cells infected with EGFP-CVB, cell death was much less than that seen in HeLa cells. At 96 hours post-infection, cells in the control group showed clear and extensive infection. Alveolar cells treated with LED UVA at a peak wavelength of 340 nm also showed infection, but visual assessment suggested a lower infection rate and much fewer cells emitting viral EGFP signal. Also, the number of viable cells appeared to be higher in the UVA-treated group when compared to the untreated group.

[0153] Example 5: Coronavirus In another example, coronavirus-infected ciliated tracheal epithelial cells (HTeCs) were treated with UV light as disclosed below.

[0154] Ciliated tracheal epithelial cells (Promocell, Heidelberg, Germany) were plated (135,000 cells per plate) in three groups. One group was infected with coronavirus 229E (Cov-229E) (50 uL per plate). The other group was infected with coronavirus 229E at a peak wavelength of 340 nm (2000 μW / cm) immediately before infection. 2 ) LED UVA for 20 min. The third group received neither infection nor UVA. After infection, cells were treated daily with 20 min of UVA (4 cm distance, 2000 μW / cm at the plate surface). 2 Plates were imaged at 16, 72, and 96 hours and cell counts were obtained at 72 and 96 hours post-infection.

[0155] UVA to rescue already infected (coronavirus 229E-infected) ciliated tracheal epithelial cells In this experiment, plates of ciliated tracheal epithelial cells (HTeCs) were infected with Cov-229E as described above. After 24 hours, the plates were divided into two groups. Group 1 was allowed to continue the infection. Group 2 was exposed to UVA with a peak wavelength of 340 nm (4 cm distance, 2000 μW / cm at the plate surface). 2) for 20 min. After 48 h, the plates were imaged and the viable cell count was determined.

[0156] UVA for close-range treatment of coronavirus-infected ciliated tracheal epithelial cells Another experiment was carried out on an intratracheal device using UVA technology, with 20 minutes of light per day at a lower intensity (1300 μW / cm at the surface of the plate from a distance of just 1 cm). 2 ), which is the expected distance between the tracheal tissue and the optical catheter in a patient being ventilated from inside the endotracheal tube.

[0157] Coronavirus load in UVA-treated or non-UVA-treated cells Total protein extraction from cell samples was performed using the AllPrep DNA / RNA / Protein Mini Kit (Qiagen). Proteins were loaded onto a Bolt 4-12% Bis-Tris gel (NW04122 Thermo Fisher) and transferred onto a Biotrace NT nitrocellulose membrane (27376-991, VWR). Total proteins were stained with Ponceau S solution (P7170, Sigma-Aldrich). The membrane was then blocked with blocking solution (Tris-buffered saline containing 3% bovine serum albumin (A7030, Sigma-Aldrich) and 0.1% Tween 20 (P1379, Sigma-Aldrich)). The membrane was then incubated overnight at 4 °C with rabbit anti-coronavirus spike protein antibody (1:1000; PA5-81777, Thermo Fisher) or mouse anti-MAVS (mitochondrial antiviral signaling) antibody (1:200; SC-166583, Santa Cruz Biotechnology) diluted in blocking solution. After washing with Tris-buffered saline + 0.1% Tween 20 (TBS-T), the membrane was overlaid with either horseradish peroxidase (HRP)-conjugated goat anti-rabbit IgG antibody (1:300; 95058-734, VWR) or HRP-conjugated goat anti-mouse IgG antibody (1:300; 5220-0286, SeraCare). The membrane was then washed with TBS-T and subsequently exposed to enhanced chemiluminescence solution (RPN2235, GE Healthcare). Immunoreactive protein bands were imaged using a ChemiDoc imaging system (Bio-Rad Laboratories, Hercules, CA USA).

[0158] LED UVA light preserves ciliated tracheal epithelial cells infected with coronavirus 229E Ciliated tracheal epithelial cells were pretreated with coronavirus 229E and exposed daily to LED UVA (2000 μW / cm 2; peak wavelength 340 nm) for 20 min were compared to control cells (no UVA, no infection) and cells infected with coronavirus but without UVA exposure. Direct visualization showed clear changes in cell morphology (no UVA) with infection. However, control cells and infected cells treated daily with UVA showed similar morphology. After 96 hours, the supernatant was removed and viable cells (attached to the plate) were counted. There was no difference in tracheal cell numbers between control and UVA-treated infected cells. However, there was a significant decrease in viable cells among infected cells compared to UVA-treated cells (P=0.005), as shown in the bar graph in Figure 38.

[0159] Interestingly, LED-UVA treated infected cells showed a decrease in Cov-229E spike (S) protein (~130 kDa) when compared to untreated infected cells. Furthermore, Cov-229E infected and UVA treated cells showed increased levels of MAVS when compared to Cov-229E infected but not UVA treated cells.

[0160] Therefore, the present experimental data confirms that UV-A light can kill coronavirus 229E after it infects lung epithelial tissue, and validates its use in combination with ET tubes or other devices to irradiate lung tissue as a treatment for coronavirus-infected patients.

[0161] Computer and Hardware Implementations of the Disclosure At the outset, it should be understood that the disclosure herein may be implemented by any type of hardware and / or software, including pre-programmed general-purpose computing devices. For example, the system may be implemented using a server, a personal computer, a portable computer, a thin client, or any suitable device or devices. The disclosure and / or its components may be a single device at a single location, or multiple devices at a single location or multiple locations, which are connected together using any suitable communication protocol, via any communication medium, such as electrical cable, fiber optic cable, or wirelessly.

[0162] It should also be noted that the present disclosure is illustrated and discussed herein as having a number of modules performing certain functions. It should be understood that these modules are merely illustrated generally based on their functions for clarity purposes only, and do not necessarily represent specific hardware or software. In this regard, these modules may be hardware and / or software implemented to substantially perform the specific functions discussed. Furthermore, these modules may be combined together within the present disclosure, or may be divided into additional modules based on the specific functions desired. Thus, the present disclosure should not be construed as limiting the present invention, but should be understood as merely illustrating an example embodiment thereof.

[0163] A computing system may include clients and servers. Clients and servers are generally remote from each other and typically interact through a communications network. The relationship of client and server arises by virtue of computer programs running on the respective computers and by virtue of having a client-server relationship to each other. In some implementations, a server sends data (e.g., HTML pages) to a client device (e.g., for the purposes of displaying the data to a user interacting with the client device and receiving user input from the user). Data generated at the client device (e.g., results of user interaction) can be received from the client device at the server.

[0164] Embodiments of the inventive subject matter described in this application can be implemented in a computing system that includes a back-end component (e.g., a data server), or includes a middleware component (e.g., an application server), or includes a front-end component (e.g., a client computer having a graphical user interface or web browser through which a user can interact with embodiments of the inventive subject matter described herein), or includes any combination of one or more such back-end, middleware, or front-end components. The components of the system can be interconnected by any form or medium of digital data communication (e.g., a communications network). Examples of communications networks include local area networks ("LANs") and wide area networks ("WANs"), internetworks (such as the Internet), and peer-to-peer networks (such as ad-hoc peer-to-peer networks).

[0165] Implementations of the subject matter and operations described herein can be implemented in digital electronic circuitry, or computer software, firmware, or hardware, including structures disclosed herein and equivalents of those structures, or a combination of one or more of them. Implementations of the subject matter described herein can be implemented as one or more computer programs, i.e., as one or more modules of computer program instructions encoded on a computer storage medium for execution by or to control the operation of a data processing apparatus. Alternatively, or in addition, the program instructions can be encoded into an artificially generated propagated signal, e.g., into a machine-generated electrical, optical, or electromagnetic signal that is generated to encode information for transmission to a receiving apparatus suitable for execution by a data processing apparatus. The computer storage medium can be, or can be included in, a computer readable storage device, a computer readable storage substrate, a random or serial access memory array or device, or a combination of one or more of them. Furthermore, although a computer storage medium is not a propagated signal, a computer storage medium can be a source or destination of computer program instructions encoded into an artificially generated propagated signal. Also, the computer storage medium can be, or can be contained in, one or more separate physical components or media (eg, multiple CDs, disks, or other storage devices).

[0166] The operations described herein may be implemented as operations performed by a "control system" on data stored in one or more computer-readable storage devices or received from other sources.

[0167] The term "control system" encompasses any type of apparatus, device, and machine for processing data, including, by way of example, a programmable processor, a computer, a system on a chip, or a plurality or combination thereof. The apparatus may include special purpose logic circuitry, such as a field programmable gate array (FPGA) or an application specific integrated circuit (ASIC). In addition to hardware, the apparatus may also include code that creates an execution environment for the computer program of interest, such as code that configures processor firmware, a protocol stack, a database management system, an operating system, a cross-platform runtime environment, a virtual machine, or one or more combinations thereof. The apparatus and execution environment may implement a variety of different computing model infrastructures, such as web services, distributed computing, and grid computing infrastructures.

[0168] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted, declarative or procedural, and can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. A computer program may correspond to a file in a file system, but this is not necessarily the case. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program, or in multiple associated files (e.g., files that store one or more modules, subprograms, or code portions). A computer program can be deployed to be executed on one computer or on multiple computers located at one site or distributed across multiple sites and interconnected by a communication network.

[0169] One or more programmable processors can execute the processes and logic flows described herein to execute one or more computer programs and perform actions by operating on input data to generate output. The processors and logic flows can also be implemented as, in addition to being performed by, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0170] Processors suitable for executing computer programs include, by way of example, both general-purpose and special-purpose microprocessors, as well as one or more processors of any kind of digital computer. Generally, a processor receives instructions and data from a read-only memory or a random-access memory, or both. The basic elements of a computer are a processor for performing actions according to instructions, and one or more memory devices for storing instructions and data. Generally, a computer also includes one or more mass storage devices, such as magnetic, magneto-optical, or optical disks, for storing data, or is operatively coupled to receive data from or transfer data to these mass storage devices, or both. However, a computer need not include such devices. Furthermore, a computer can be embedded in another device, such as a mobile phone, a personal digital assistant (PDA), a mobile audio or video player, a game console, a global positioning system (GPS) receiver, or a portable storage device (e.g., a universal serial bus (USB) flash drive), to name just a few. Devices suitable for storing computer program instructions and data include all types of non-volatile memory, media, and memory devices, including, for example, semiconductor memory devices such as EPROM, EEPROM, and flash memory devices, magnetic disks such as internal hard disks or removable disks, magneto-optical disks, and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

[0171] conclusion The various methods and techniques described above provide multiple means of implementing the present invention. Of course, it should be understood that not all of the described objectives or advantages can necessarily be achieved according to any particular embodiment described herein. Thus, for example, one skilled in the art will recognize that a method can be implemented to achieve or optimize one or a group of advantages taught herein without necessarily achieving other objectives or advantages taught or suggested herein. Various alternatives are mentioned herein. It should be understood that some embodiments specifically include one, another, or several features, while others specifically exclude one, another, or several features, and still others reduce a particular feature by including one, another, or several advantageous features.

[0172] Moreover, one skilled in the art will recognize the applicability of various features from different embodiments. Similarly, the various elements, features, and steps discussed above, as well as other known equivalents of each such element, feature, or step, can be used in various combinations by one skilled in the art to perform methods according to the principles described herein. Among the various elements, features, and steps, some are specifically included and others are specifically excluded in various embodiments.

[0173] Although the present application has been disclosed in the context of particular embodiments and examples, it will be understood by those skilled in the art that the embodiments of the present application extend to other alternative embodiments and / or uses beyond the specifically disclosed embodiments, as well as modifications and equivalents thereof.

[0174] In some embodiments, the terms "a" and "an" and "the" and similar referents used in the context of describing certain embodiments of the present application (particularly in the specific context of the claims below) can be construed to cover both the singular and the plural. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of individually referring to each separate value falling within the range. Unless otherwise indicated herein, each separate value is incorporated herein as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "etc.") provided with respect to certain embodiments herein is intended only to better illustrate the application and does not pose a limitation on the scope of the application as otherwise claimed. No language in this specification should be construed as indicating any non-claimed element essential to the practice of the application.

[0175] Certain embodiments of the present application have been described herein. Variations to those embodiments will become apparent to those skilled in the art upon reading the foregoing description. It is contemplated that those skilled in the art can use such variations as appropriate and can implement the present application in ways other than as specifically described herein. Accordingly, many embodiments of the present application include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the present application unless otherwise indicated herein or clearly contradicted by context.

[0176] Particular implementations of the subject matter have been described. Other implementations are within the scope of the following claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. Additionally, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results.

[0177] All patents, patent applications, patent application publications, and other materials, such as articles, books, specifications, publications, documents, articles, and / or the like, referenced herein are incorporated by reference in their entirety and for all purposes, but excluding any prosecution file history associated therewith, any that is inconsistent or contradictory with this document, or any that may have a limiting effect on the broadest scope of the claims now or in the future associated with this application document. By way of example, in the event of an inconsistency or contradiction between the explanation, definition, and / or use of a term associated with any of the incorporated materials and that associated with this document, the explanation, definition, and / or use of the term in this document shall control.

[0178] Finally, it should be understood that the embodiments of the present application disclosed herein are illustrative of the principles of the embodiments of the present application. Other modifications that may be used are within the scope of the present application. Thus, by way of example, and not of limitation, alternative configurations of the embodiments of the present application may be utilized in accordance with the teachings herein. Thus, the embodiments of the present application are not limited to the exact ones shown and described.

Claims

1. 1. A system for performing internal ultraviolet light therapy, comprising: A delivery tube; at least one UV light source within the delivery tube arranged to deliver UV light out of the delivery tube, the at least one UV light source configured to emit wavelengths between 335 nm and 350 nm; The system comprising:

2. The system of claim 1 , wherein the delivery tube is adapted to be placed inside an endotracheal (ET) tube.

3. The system of claim 1 , wherein the light source is an array of LED light sources.

4. The system of claim 1 , wherein the array of LED light sources is configured to emit UV light having a peak wavelength between 335-350 nm.

5. The system of claim 1 , wherein the array of LED light sources is configured to emit UV light having a peak wavelength between 338-342 nm.

6. The system of claim 1 , wherein the UV light source is configured to deliver UV light around the delivery tube.

7. The system of claim 1 , further comprising a power source connected to the UV light source.

8. The system of claim 1 , wherein the UV light source is configured to deliver UV light along a substantial length of the delivery tube.

9. The system of claim 2 , wherein the ET tube is configured to be connected to a ventilator.

10. 2. The system of claim 1, wherein the UV light source has a majority of its light intensity in the spectral region between 335 nm and 350 nm.

11. The system of claim 1 , wherein the UV light source is configured to emit only light at a threshold intensity between 335 nm and 350 nm.

12. 10. The system of claim 1, wherein the UV light source is configured to emit light only at an intensity greater than 10% of its maximum intensity between 335 nm and 350 nm.

13. The system of claim 1 , wherein the delivery tube is adapted to be placed in a nasopharyngeal airway.

14. 1. A system for performing internal ultraviolet light therapy, comprising: A delivery tube; a UV light source connected to the delivery tube and configured to emit wavelengths between 335 nm and 350 nm; Memory, a control system coupled to the memory and comprising one or more processors, the control system being configured to execute machine executable code to cause the UV light source to emit wavelengths; The system comprising:

15. The system of claim 14 , further comprising a power source connected to the UV light source.

16. 15. The system of claim 14, wherein the control system is further configured to execute machine executable code to cause the UV light source to emit a wavelength for at least 20 minutes, 40 minutes, or 60 minutes.

17. 20. The system of claim 17, wherein the UV light source is configured to treat bacteria in an ET tube and in the larynx and trachea of ​​a patient.

18. 20. The system of claim 17, wherein the UV light source comprises an array of LED light sources.

19. The system of claim 17 , wherein the delivery tube is disposed inside an ET tube.

20. The system of claim 17 , wherein the delivery tube is integral with an ET tube.

21. The control system further executes the machine executable code to control the UV light source to emit at least 1,100 microwatts / cm ２ , 100 microwatts / cm ２ , 2,000 microwatts / cm ２ , or 2,100 microwatts / cm ２ , 2,200 microwatts / cm ２ , 2,300 microwatts / cm ２ , 2,400 microwatts / cm ２ , 2,500 microwatts / cm ２ , 2,600 microwatts / cm ２ , 2,700 microwatts / cm ２ , 2,800 microwatts / cm ２ , 2,900 microwatts / cm ２ , or 3,000 microwatts / cm ２ 20. The system of claim 17, configured to emit wavelengths having a threshold intensity comprising:

22. The control system further executes the machine executable code to control the UV light source to provide at least 13, 15, or 18 W / m ２ 20. The system of claim 17, configured to emit wavelengths having a threshold intensity comprising:

23. 1. A method of treating a patient for an infectious condition in the patient, comprising: Inserting a delivery tube into a cavity within a patient's body; emitting UV-A light in the range of 335-350 nm from a UV light source disposed within said delivery tube and emitting UV wavelengths out of said delivery tube at a threshold intensity for a threshold duration; The method comprising:

24. 24. The method of claim 23, wherein the delivery tube is a catheter equipped with an array of LED light sources having peak wavelengths between 339-346 nm.

25. 24. The method of claim 23, wherein the body cavity is a respiratory cavity.

26. 26. The method of claim 25, wherein the respiratory cavity is the trachea.

27. 26. The method of claim 25, wherein the respiratory cavity is the nasopharynx.

28. 24. The method of claim 23, wherein the infectious condition is selected from the group consisting of a bacterial infection, a viral infection, a fungal infection, and combinations thereof.

29. 24. The method of claim 23, wherein the infectious condition is pneumonia.

30. 24. The method of claim 23, wherein the threshold duration comprises at least 20 minutes.

31. The threshold intensity is at least 13, 15, or 18 W / m ２ 24. The method of claim 23, comprising:

32. The threshold intensity is at least 1,100 microwatts / cm ２ , 100 microwatts / cm ２ , 2,000 microwatts / cm ２ , or 2,100 microwatts / cm ２ , 2,200 microwatts / cm ２ , 2,300 microwatts / cm ２ , 2,400 microwatts / cm ２ , 2,500 microwatts / cm ２ , 2,600 microwatts / cm ２ , 2,700 microwatts / cm ２ , 2,800 microwatts / cm ２ , 2,900 microwatts / cm ２ , or 3,000 microwatts / cm ２ The method of claim 23, comprising an intensity of

33. 27. The method of claim 26, wherein the delivery tube is inserted inside an endotracheal tube.

34. 27. The method of claim 26, wherein the delivery tube is inserted inside an endotracheal tube while the tube is being suctioned.

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