a) Gerlinger et al. “KTP-532Laser-Assisted Endoscopic Nasal Sinus Surgery”. Clin Otolaryngol. 2003 April; 28(2):67-71;
b) Newman et al. “Applications Of The Diode Laser In Otolaryngology”. Ear Nose Throat J. 2002 December; 81(12):850-1;
c) Janda et al. “Comparison Of Laser Induced Effects On Hyperplastic Inferior Nasal Turbinates By Means Of Scanning Electron Microscopy”. Lasers Surg Med. 2002; 30(1):31-9;
d) Kamami Y V, “Laser-Assisted Outpatient Septoplasty Results On120Patients”. J Clin Laser Med. Surg. 1997; 15(3):123-9; and
e) Levine et al. “Lasers In Endonasal Surgery.”. Otolaryngol Clin North Am. 1997 June; 30(3):451-5.

Not surprisingly, none of these disclosures of surgical procedures, which focus on tissue ablation, removal or destruction, remotely suggests a treatment for rhinosinusitis or chronic rhinosinusitis in otherwise healthy and normal subjects. Accordingly, there is a need for less aggressive rhinosinusitis treatments avoiding the drawbacks of medications and which cause little or no damage to the sensitive tissues of the sino-nasal tract.

It is also known that electromagnetic radiation can be employed to destroy different types of bacteria, for example, Phoenix et al. in “The Phototoxicity Of Plenothiazinium Derivatives Against Escherichia Coli And Staphylococcus Aureus” FEMS Immunol Med. Microbiol. 2003 Oct. 24; 39(1): 17-22 teach that phenothiazinium derivatives like methylene blue and toluidine blue O can cause bacterial cell death in both gram negative (E. Coli) and gram positive (Staph aureus) bacteria by phototoxicity.

However, rhinosinusitis infections commonly comprise a diversity of bacterial and other microorganisms possibly including fungi and/or viruses which factors are not considered by Phoenix et al. Furthermore, Phoenix et al. provide no indication as to whether the responses of the two bacterial species selected for study, one of which is a gastrointestinal species, are likely to be exhibited by all of the diversity of bacterial species that can colonize the sino-nasal tract.

Teichert et al., in “Treatment of oral candidiasis with methylene blue-mediated photodynamic therapy in an immunodeficient murine model.” Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 February; 93(2): 155-60, described evaluating the efficacy in an immune-compromised murine model of using methylene blue-mediated photodynamic therapy. This is a narrow-focus treatment of a single target fungal organism, oral candidiasis, a pathogen commonly afflicting immune-compromised AIDS patients. The authors reported that methylene blue (“MB”) concentrations of 450 and 500 microgram/mL activated with diode laser light at 664 nm using a cylindrical diffuser at 275 J/cm fiber length at 400 mW for 687.5 seconds, were able to “totally eradicate”Candida albicansin an immunosuppressed murine model. Teichert et al. professed to be the first to use antimicrobial photodynamic therapy “PDT” in an animal model and to treat oral candiasis by using a methylene blue-mediated photodynamic therapy. Teichert et al. suggests methylene blue-mediated PDT of oral candidiasis as a potential treatment alternative to traditional antifungal drug therapy.

Teichert et al.'s teachings regarding the response of a single infective species in abnormal, immune-compromised mice do not solve the problem of providing a broad-spectrum treatment for a diverse human population most of whom may have normal immunity. Furthermore, Teichert et al.'s treatment is time-consuming having a duration of 687.5 seconds (page 156, right hand column), about 11.5 minutes, and is intended to be applied only to a specific acute care patient group, AIDS patients, rather than to segments of the population that may largely be in moderate to good health.

As an alternative to antibiotic or chemical agents, proposals have been made for the application of radiative energy to the treatment of bodily infections on internal organ surfaces with little attempt to discriminate between potentially hazardous ionizing radiation and relatively safe non-ionizing radiation.

For example, Ganz U.S. Pat. Nos. 6,491,618 and 6,464,625 disclose methods and apparatus employing ionizing radiation, for example, ultraviolet light or x-ray radiation for treating gastrointestinal ailments of a patient including gastritis, gastric ulcer, duodenal ulcer, gastric cancer, gastric lymphoma, ulcerative colitis, or Crohn's disease. Ionizing radiation brings a potential for DNA damage, mutagenicity, teratogenicity and carcinogenicity and is not desirable for the simple, safe treatment objectives of the present invention.

Biel U.S. Pat. No. 6,159,236 discloses a medical device including a tube and expandable member which emits light for photodynamic therapy of internal body surfaces such as the larynx or cheek in order to treat or detect pathologies such as cancer and microbiological pathogens? (what is said about them? nothing?). An integrated array of vertical cavity surface emitting lasers (VCSEL) can provide a light emitting source for photodynamic therapy (“PDT”) treatment. Light is transmitted through an expandable member or balloon, which is inflated by air or a fluid, possibly a proteinaceous light-diffusing gel. The expandable member conforms with the surface to be treated. Biel's balloon is undesirable for the objectives of the present invention which also do not relate to cancer detection or treatment.

Other biomedical applications of photothermal energy including external topical application especially for depilation, hair removal, for example, as disclosed in Azar and Shalev U.S. Pat. No. 6,187,001 and Azar U.S. Pat. No. 6,214,034. Kreindel U.S. Pat. No. 6,702,808 discloses use of light in combination with RF energy for treating hair, vascular lesions and other complex targets on the skin. Hair removal and similar largely cosmetic skin treatments are unrelated to the objectives of the present invention.

The specialist dental field contains proposals for photodynamic treatments of teeth and periodontal areas.

For example, Azar et al. United States Patent Application 20010024777 discloses a toothbrush-like apparatus for self use to effect photothermolysis of oral plaque bacteria sensitized by staining. The apparatus functions to direct light on to at least one tooth. In order to avoid coagulation of blood vessels, light wavelengths near oxyhemoglobin absorption peaks are avoided, e.g. by filtration.

Wilson et al. U.S. Pat. No. 5,611,793 discloses use of laser light in combination with a photosensitizing agent to disinfect or sterilize oral cavity2 tissues, wounds or lesions. Wilson et al.'s preferred photosensitizers are blue dyes and stains that will absorb red light. Disclosed applications include disinfecting and sterilizing dental tissues, gingival tissues and drilled-out carious lesions prior to filling, destroying cariogenic microbes on a tooth surface, treatment or prevention of chronic periodontitis and inflammatory periodontal diseases; treating oral candidiasis in AIDS patients, immunocompromised patients and patients with 8 denture stomatitis. These dental uses do not teach or suggest nondental9 applications of the disclosed methods. The application of stain to the teeth may be problematic and unacceptable to patients, discouraging the ordinary worker from adopting Wilson et al.'s methods.

None of the foregoing proposals provides an adequate solution to the problems of providing a safe treatment which is effective for chronic sino-nasal infections and which, preferably is suitable for treating a broad segment of the general population, many of whom may be in good health save for the sino-nasal infection. Nor do known treatments address problems of microorganisms that may be lodged in difficult-to-access locations in the nasal tract.

The foregoing description of background art may include insights, discoveries, understandings or disclosures, or associations together of disclosures, that were not known to the relevant art prior to the present invention but which were provided by the invention. Some such contributions of the invention may have been specifically pointed out herein, whereas other such contributions of the invention will be apparent from their context. Merely because a document may have been cited here, no admission is made that the field of the document, which may be quite different from that of the invention, is analogous to the field or fields of the present invention.

SUMMARY OF THE INVENTION

Pursuant to the invention, it would be desirable to have a simple, safe, broad-spectrum treatment for chronic sino-nasal infections suitable for use by a diversified patient population.

To solve the problem of providing a simple, safe, broad spectrum treatment for chronic sino-nasal infections suitable for use by a diversified patient population, the present invention provides, in one aspect, a method of controlling microorganisms in the sino-nasal tract of a subject, which method comprises applying visible spectrum electromagnetic energy to a microorganism-infected target site in the sino-nasal tract in a dosage effective to control the microorganisms without physiological damage to the tissue, blood vessels, or other anatomy. If desired, the visible spectrum electromagnetic energy can be supplemented with longer wavelength energy, for example heat, radio frequency (“RF”), microwave energy, or equivalents or combinations of the foregoing energy spectra.

The method can be effected by employing a handheld energy applicator instrument having an energy output port receivable in a nostril of the treatment subject. The applicator energy port can be inserted into the subject's nostril prior to the application of photothermal energy. The handheld applicator instrument, which is provided by another aspect of the invention, may comprise a handholdable body accommodating a light source, a light output head comprising the light energy output port and a light transmitting neck supporting the light output head on the handholdable body.

The electromagnetic energy employed can comprise pulses of photothermal energy or diffused diode laser light and is preferably applied without causing tissue ablation, coagulation or carbonization. Some useful embodiments of the invention employ a photosensitizing agent to the target site to sensitize the microorganisms prior to applying the electromagnetic energy. The photosensitizing agent may be a stain which is adsorbed by or adheres to a target microorganism and enhances the absorption of light energy by the organism. Electromagnetic energy having an energy peak overlapping with an absorption peak of the stain can advantageously be used for example orange or red light respectively may be used with a blue or green stain respectively.

If desired, nasal cleansing or irrigation may be employed as a pretreatment prior to the energy treatment of the invention. The pretreatment can comprise one or more of various cleansing or irrigation techniques to remove mucous, superficial colonies of microorganisms and detritus. Such cleansing pretreatment can enhance the efficacy of the radiation treatments or enable the applied radiation to reach deeper seated microorganisms.

The handheld energy applicator instrument can have an energy output port registrable with or receivable into a nostril of the treatment subject so that the energy port can be inserted into the subject's nostril prior to the application of photothermal energy. In cases where the target site is a sinus the method can comprise passing the electromagnetic energy applicator output through a nostril and positioning the applicator energy output to address the target sinus site.

The electromagnetic energy can comprises pulses of photothermal energy having a pulse width of not more than about 200 msec and an interval between pulses of from about 10 to about 2000 msec, along with an energy density at the output of from about 0.1 to about 50 Joule/cm². The energy application can be performed from about one to about twenty times per month, optionally from about two to about ten times per month, for a period of from about two weeks to about six months. If desired the energy application can be controlled to provide sufficient photothermal energy to effect a microorganism count reduction of at least about 50 percent, optionally about 80 percent without causing physiological damage, pain or discomfort to the patient or subject.

The microorganism population to which the inventive treatments are applied can comprise a heterogenous bacterial population, a fungal population, a viral population, or a mixed population comprising bacteria and fungus or virus or bacteria and fungus and virus.

The treatment methods and apparatus or instruments of the invention provide novel, simple, safe and effective broad spectrum treatments for chronic rhinosinusitis or other low-level infections of the sino-nasal tract. The inventive treatment methods can be quickly and easily carried out in a doctor's or dentist's office, clinic or other medical facility, by a physician or other practitioner, or could be effected by consumers. Systemic or topical drugs are not required and accordingly problems of antibiotic resistance are avoided. Nor is it necessary to employ damaging radiation, such as ionizing radiation which might induce long-term adverse effects.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

Some embodiments of the invention, and of making and using the invention, as well as the best mode contemplated of carrying out the invention, are described in detail below, by way of example, with reference to the accompanying drawings, in which like reference characters designate like elements throughout the several views, and in which:

FIG. 1 is a sectional and partially schematic view of a photothermal treatment instrument according to one embodiment of the invention suitable for treating the sino-nasal tract;

FIG. 2 is a side elevational view of a photic treatment instrument according to another embodiment of the invention which is also suitable for treating the sino-nasal tract;

FIG. 3 is a partial view of one embodiment of sinus applicator suitable for use with the photothermal treatment instrument shown inFIG. 1;

FIG. 4 is a partial view of another embodiment of sinus applicator suitable for use with the photothermal treatment instrument shown inFIG. 4;

FIG. 5 is a plan view of one embodiment of nasal swab suitable for applying a photosensitizer to the nasal cavities;

FIG. 6 is a plan view of another embodiment of sinus swab suitable for applying a photosensitizer to the sinus cavities; and

FIG. 7 is an anatomical vertical section through a human head illustrating some target treatment sites for the methods of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The following more detailed description of the invention is intended to be read in the light of, and in context with, the preceding summary and background descriptions but without being limited by the preceding descriptions.

In one aspect the invention provides a method of treating low-level infections in the nasal or sinus cavities, the method comprising application to target tissue surfaces in the nasal or sinus cavities, via the nostrils, of sufficient photothermal energy to effect a colony microorganism count reduction of at least about 50 percent. Some useful embodiments of the invention effect a microorganism count reduction of at least about 80 percent, or at least about 90 percent and such a reduction can be effected in a single treatment. The treatments may be repeated, as necessary, to control the microorganism population.

To achieve a desired reduction in microorganism count, the treatment energy can be applied in a dosage which is a multiple of the LD₅₀for a target organism, for example, a multiple in the range of about 1 to about 3 times the LD₅₀, for example about two times the LD₅₀which should provide a reduction of about 90 percent.

The photothermal energy can be produced in any suitable manner, for example by operating a flashlamp to generate a pulsed electromagnetic output comprising both visible light and thermal energy. The energy pulse or pulses produced, or flashes, can be directed to a desired target surface in any suitable manner, for example by reflecting the energy through a window in a housing. The angular divergence of the pulses can be controlled to control the depth of penetration into mucous target tissue, if desired, with wider beams penetrating less deeply, for example by suitable choice of the shape of the reflector and other light guiding surfaces between the source and the target site.

Referring toFIG. 1 of the drawings, thephotothermal treatment instrument10 there illustrated is designed to be held and operated in one hand, either the left or the right hand and comprises a partially tapered, generallycylindrical body12, serving as a handle, from which projects, in the axial direction aneck14 carrying anoutput head16 intended to be inserted into a patient's or user's nostril. As shown,neck14 can curve or bend away from the axis ofcylindrical body12 to facilitate operation of the instrument whileoutput head16 is inserted in the nostril.

With advantage,neck14 can be releasably attached tobody12 by a joint15 which can be a push or screw fit, with or without snap engagement or other suitable connection. If desired joint15 may permit relative rotation betweenneck14 andbody12.Neck14 stably supportslight output head16 onbody12, maintaininglight output head16 in a desired position abovebody12 whenbody12 is gripped and held in a generally upright position. Thus,light output head16 can readily be carefully positioned by a physician or other medical practitioner, or self-administrator, to juxtaposelight output head16 to the treatment subject's nostrils.Photothermal treatment instrument10 can be gripped, manipulated and operated with one hand to inject photothermal energy into the nasal cavity for treating nasal and septal surfaces and, employing extended light guides such as are shown inFIGS. 3 and 4, sinus surfaces.

Cylindrical body

12 houses alight source18 andcontroller unit20 forlight source18 operated by an on-off switch22.Neck14 is traversed by alight pipe24 which guides light fromlight source18 tooutput head16. As shown,light source18 is powered from anexternal power supply26, via apower cord28. However, it will be understood that rechargeable or other batteries (not shown) can be housed inbody12, if desired, as either a supplement to or an alternative toexternal power supply26.

Body

12 ofphotothermal treatment instrument10 can be comfortably gripped in one hand and switch22 can be operated to activatelight source18 viacontroller unit20.Light source18, when activated, generates light and heat which are transmitted alonglight guide24 throughneck14 to be output fromoutput head16 on to a treatment target site, as will be described in more detail hereinbelow.Body12, except as may otherwise be apparent herein, can have any suitable cross-section for example, circular, but other cross-sectional shapes, such as oval, rectangular or polygonal that can conveniently be accommodated in a user's hand, may be employed if desired.

As may be understood fromFIG. 1,body12 and its internally accommodated light-generating components can be constructed in a generally similar manner tohousing12 and the light-generating components housed therein disclosed in Azar et al. Pub. No. US 2001/0024777, particularly in FIG. 3 and at paragraphs [0075] to the entire disclosure of which patent publication is hereby incorporated herein by reference thereto. However, in the currently described embodiments of the present invention, the energy delivered, the light delivery system and the target sites are, or can be, quite different from Azar's intended destruction of sensitized plaque bacteria on the teeth.

Incoherentlight source18 inbody12 can include alamp reflector30 and alamp32 disposed withinreflector30.Lamp32 is electrically connected tocontroller unit20 vialeads34 and is powered frompower supply26 in response to actuation ofswitch22 under the control ofcontroller unit20. If desired,lamp32, and optionally also,reflector30 can be user removable and replaceable inbody12 to enable the user to replacelamp32 with a lamp having different energy output characteristics during a treatment procedure. For this purpose,body12 may have an access opening and cover therefor (neither one shown).

Lamp reflector

30 can have any suitable shape to collect light fromlamp32 and reflect the collected light intolight pipe24, via aproximal opening34. The lamp shape may, for example, be ellipsoidal, quasi-ellipsoidal, parabolic, quasi-parabolic, spherical, quasi spherical or the like.

If desired, one or more filters, such as are shown at36 and38, can be provided in the light path betweenlamp32 andproximal opening34 to limit the spectrum of the output light. Preferably, filters36,38 are selectively removable frombody12, for example throughslots39 by graspingtabs40 which project externally ofbody12, to enable a user to select desired filtration characteristics.

Filters

36,38 and any other optical components in the light path fromlamp32 to the target site are preferably heat-transmissive to permit heat fromlamp32 to be applied to the target site along with light, duly filtered, if desired. By inserting or removing one or more of

filters

34,36, a user may vary the filtration, for example, between zero filtration and a high degree of filtration provided by a low bandpass and a high bandpass filter with adjacent cutoff frequencies which provide an output with a particularly narrow waveband, if desired. Some useful frequency ranges such as blue, blue-green or orange with or without limited ultraviolet, are described hereinbelow.Suitable filters34 and/or36, or possibly even three filters, that can be employed to provide desired outputs, as described herein, will be apparent to those skilled in the art. If desired, without limitation, filters34,36 may comprise: a single blue filter, for example a filter having a transmission spectrum wherein at least about 90 percent of the energy lies between about 400 to about 500 nm; a single blue-green filter, for example a filter having a transmission spectrum wherein at least about 90 percent of the energy lies between about 400 to about 600 nm; an orange filter transmitting at least about 70 percent of the incident infrared energy, which may optionally transmit at least about 90 percent of the energy at wavelengths of about 600 nm and longer; or an ultraviolet filter transmitting no more than 10 percent of incident UVC, and optionally, no more than about 40 percent of incident UVA and UVB.

Alternatively, the ultraviolet filter may transmit no more than about 10 percent of incident UVA, UVB and UVC radiation. In other embodiments of the invention, filters,34,36 can comprise an ultraviolet filter as described and one of the blue, blue-green or orange filters, as described.

Lamp

32 can be any suitable lamp providing an incoherent broadband light output with an appropriate energy-versus-wavelength output spectrum for the purposes of this invention.Lamp32 may for example be an arc discharge lamp, a flash lamp, such as a xenon or quartz xenon flash lamp, or other suitable lamp and may have a peak energy output around 500 nm or at other suitable wavelength. Such a lamp will generally deliver heat energy as well as light. For treatments limited to blue-rich light, other light sources may be employed forlamp32, including sources delivering little or no heat energy and having peak energy outputs at shorter wavelengths.

As indicated above,photothermal treatment instrument10 can be designed forlamp32 to be readily changed by a user. In this case,photothermal treatment instrument10 can includemultiple lamps32 having different output characteristics enabling the user to vary the energy output during a treatment procedure. The outputs can be comparable with or equivalents of the outputs obtainable with

filters

34,36 and may be suitably modified with filters, if desired. It will be understood that a suitable filter or filters can be selected for use with a particular lamp and changed when the lamp is changed, if desired.

Lamp

32, when utilized inphotothermal treatment instrument10 can be such as to provide an output capable of photothermolysis of stained or unstained bacteria, and other microorganisms resident on or populating mucous tissues in desired target areas, preferably without significant tissue damage.

Controller unit

20 includes suitable circuitry to operateflash lamp32 with desired pulse characteristics, as will be described. The circuitry (not shown) can include a triggering unit, a capacitor unit and electronic timing circuitry for timing the flash frequency.

Neck

14 is preferably rather short and curved or angled, along its length, about an axis transverse to its length, as illustrated, so thatlight output head16 can be partially inserted in the nasal cavity withbody12 conveniently downwardly disposed. Alternativelyneck14 can be rectilinear. The length ofneck14 is preferably kept to a minimum effective for convenient and ergonomic operation.Light pipe24 can be a reflectively lined tubular passage, fiber optic or other suitable light-conveyance device andneck14 can be formed of a suitable structural material, preferably a heat- and light-insulating material.

Light output head

16 comprises a funnel- or frustoconical-shapednozzle70 which is designed to be a close fit within a subject's nostril and hasouter flanks72 extending aroundlight pipe24. Desirably, flanks72 are configured and otherwise designed to comfortably seat against the subject's nostril. The external configuration ofnozzle70 can be similar to what is known for inhalers used to administer sprays, mists and the like. Reflectively linedlight pipe24 can be of constant cross-section along its length. Alternatively, in one useful embodiment of the invention,light pipe24 can have a distally increasing cross-section (not shown) toward anoutlet port74 to provide a flared or divergent output beam76, spreading the photothermal energy for good coverage of the irregular configuration of the surfaces of the lower and upper nasal cavities. However, a cylindrical or other appropriate shape of the internal surfaces oflight pipe24 may be useful, in some cases to provide a pencil beam for more localized treatment of the nasal cavity or to better treat the upper nasal cavity. Desirably,nozzle70 has a circular cross-section, although other suitable shapes may be employed, and is provided in a range of sizes to fit different nasal anatomies, including e.g. smaller for children and larger for adults, in a manner known generally to the art. Depending upon its size,nozzle70 can have anoutlet74 with a diameter in the range of from about 1 to about 10 mm, desirably from about 3 to about 7 mm.

Nozzle

70 can be detachably attached toneck14 enabling different sizes and possibly shapes ofnozzle70 to be used interchangeably. Also,disposable nozzles70 can be utilized, permitting a new, sterilized nozzle to be used for each treatment. Such adisposable nozzle70 may have a centrally depending, internally reflective tubular portion extending intolight pipe24, if desired, for hygienic purposes. Another alternative is forneck14 to be detachably attached tobody12 ofphotothermal treatment instrument10 enabling alternative applicators such as the sinus applicators shown inFIGS. 3 and 4 to be utilized in place ofneck14 andnozzle70. Optionally,neck14 can be rotatable onbody12.

It will be appreciated thatoutput port74 and the other components ofphotothermal treatment instrument10 can have any structure which will provide suitable energy pattern areas on a desired target site with sufficient energy intensity to provide effective microorganism control.

In many desirable embodiments, but not necessarily all embodiments, the energy output fromlamp32 travels entirely through air or breath from

filter

34 or36, or fromlamp32 if no filter is employed, to target surfaces or materials within the subject's nasal or sinus cavities.

For application of radiant heat energy or, preferably heat and light energy, to the target site,lamp32 can be selected to be a thermal emitter having a heat transmissive glass, e.g. quartz glass, borosilicate glass or other suitable enclosure or bulb. To avoid undue attenuation of the heat energy before it reaches the target site,photothermal treatment instrument10 can be formed with a clear path fromlamp32 to the target site which is free of heat attenuating elements that are strong infrared absorbers, for example, infrared-blocking glass lenses or filters. For example, the light path throughphotothermal treatment instrument10 fromlamp32 to the target site may be entirely through air, or other gas or vacuum, and through heat and light transmitting members, desirably members formed of quartz glass or an equivalent. Thus, for delivery of heat as well as light to thetarget29, filters36,38, or other radiation transmissive elements between the energy source and the target, if employed, may be formed of a suitable glass such as an orange or red glass with good infrared transmissivity, e.g. quartz glass or a more exotic glass such as an infrared transmitting chalcogenide or chalcohalide glass, as is known to those skilled in the art.

Materials.Photothermal treatment instrument10 can be manufactured of any suitable materials as will be apparent to those skilled in the art for example, moldable thermoplastic or thermosetting polymers and/or resins and may be of rigid construction. However, the invention also includes embodiments whereneck14 orlight output head16, or both, are flexible and, optionally, resilient. For example,neck14 could be flexible to facilitate orientation or location oflight output head16. Another option isneck14 ornozzle70, or both, to be deformable, permitting the user to change the orientation ofnozzle70 with respect tobody12 or to better conformnozzle70 to the subject's anatomy or possibly, to modify the shape of the output photothermal beam.

Disposability. As described above,output head16 and alsoneck14 can be removably attachable tobody12 which houseslight source18 and associated electrical equipment. By makingoutput head16 and/orneck14 of economical construction, for example plastic moldings, they can be rendered disposable. Thus anew head16, optionally with anew neck14, can be employed for each new patient, or each new treatment, avoiding need for sterilization of a component for reuse. However, if desired,neck14 and optionally alsooutput head16 could be sterilized and reused for multiple treatments. Wherephotothermal treatment instrument10 is dedicated to a single patient or consumer, sterilization may not be necessary.

The embodiment ofphotic treatment instrument110 for nasal applications as shown inFIG. 2 is generally similar to theFIG. 1 embodiment but has a morecompact body112 for convenience bearing alight output head116 similar tolight output head16.Photic treatment instrument110 can be usefully embodied in an end user product with lower maximum photothermal energy output, for example a low cost unit for personal use.Instrument110 is activated by acontrol button122 and power is supplied through apower line128.Instrument110 can employ a scaled down version of the photothermalenergy output device18 ofFIG. 1, if desired. Alternatively, either

instrument

10 or110 may be equipped with adiode laser118 controlled by asuitable controller120 in which caselight pipe24 can be replaced by a fiber opticlight connection124 andlight output head116 can employ asuitable diffuser126 which preferably projects the light forwardly and spreads the laser beam over a wider area, for example with a beam angle of between about 10° and about 170° optionally between about 30° and about 120°.

Referring now toFIGS. 3 and 4,

sinus applicators

140,142 can be provided to access a patients' sinus cavities via their nostrils and to output photothermal energy into one or more target sinus cavities.

Sinus applicators

140,142 have relatively thin

elongated shafts

144,146 respectively, to extend into and through the nasal cavity and terminate in relatively

small nozzles

148,150 with

small outlets

152,154, respectively, intended to direct light into a sinus cavity to be treated when the sinus applicator is suitably positioned.

Sinus applicators

140,142 are also provided with internal light pipes (not shown) which may be flared, if desired, at their distal ends to provide a flared light output beam.

In another alternative embodiment, electrical rather than photothermal energy is transmitted fromhandheld body12 throughneck14 tolight output head16 where the energy is converted to light, simplifying the construction ofneck14. For this purpose, a suitable, relatively smaller embodiment oflamp32, e.g. a bulb-shaped embodiment, can be provided inlight output head16, within or adjacent tonozzle70 displacing most or all oflight pipe24. Such asmaller lamp32 can be supplied with electricity via conductors such as34, extending throughneck14 fromcontroller unit20.

Chemical Sensitization. Some, but not all, preferred embodiments of the invention employ a chemical sensitization agent as a pre-treatment to sensitize target microorganisms to the effects of the applied photothermal radiation and enhance microbial kill rates. Some suitable sensitizers include dyes such as methylene blue and oxygen gels containing, for example peroxide. Other suitable agents are described in more detail hereinbelow.

Such sensitizers are conveniently applied in liquid form employing applicators such as are shown inFIGS. 5 and 6. Nasal swab80 shown inFIG. 5 comprises anelongated support82 to one end of which is secured asterile pad84 of cotton, foam or other suitable absorbent material. Nasal swab80 may for example be a calcium alginate fiber haemostatic swab. Sinus swab86 is similar to nasal swab80, with the difference of having anelongated support88 which is curved or angled at one end. Also pad90 may be a little smaller than pad86, to better adapt sinus swab86 to apply fluid to the sinus or sinus passages. If desiredsupport88 of sinus swab86 can be flexible to facilitate accessing the sinuses with sensitizer fluid-impregnated pad90. In use, pad86 or90 is dipped in a source of suitable topical pre-treatment fluid, for example a sensitizer, while manually gripped by the

respective support

82 or88, is manually inserted through the nostril and contacted with a desired target surface to apply the fluid to the target surface.

Photosensitizing Agents

As described in more detail hereinbelow, photosensitizing agents such as stains, liquid compositions colored with dyes or pigments, may be employed to enhance the treatment process. Desirable aspects of the invention employ a combination of stain and energy dosage which is effective, of convenient duration and aesthetic. A benefit of the invention is that, unlike dental applications where whiteness of the teeth may be paramount to the subject, the sino-nasal surfaces to which the treatments of the invention are applied in most cases conceal, or substantially conceal applied stains. Biocompatible photosensitizing stains showing strong absorbance of one or more peak wavelengths output by the light source or other source of electromagnetic radiation are particularly useful in enhancing the efficacy of the energy treatments or in rendering lethal energy dosages that might otherwise be innocuous. However, excess and displaced stain may be problematic and unaesthetic if the stain exhibits itself to the subject after treatment, for example, after blowing their nose.

To control such problems while benefiting from the lethality and efficacy that use of a suitable stain can bring, the stain can be employed in relatively low concentrations, for example a concentration of less than 1%, referring to methylene blue. In practice, concentrations of less than 0.1%, for example 0.08% or lower, are desirable to avoid aesthetic problems over an extended time period. In general, again referring to methylene blue, some useful microorganism lethality can be obtained with concentrations of 0.01% or greater, although extended energy exposures may be necessary at such concentrations. Some particularly useful embodiments of the invention employ concentrations of methylene blue in the range of from about 0.02 to about 0.08%. Concentrations of methylene blue in the range of from about 0.03 to about 0.06% are also believed to be particularly effective. It will be appreciated that other stains may employ different concentrations according to their efficacy as known or as determined by routine experimentation.

In one embodiment, the invention employs a low or the minimal effective dosage of stain which is sufficient to obtain a useful or desired reduction of harmful microbes. Optionally, the dosage may be selected to leave a residual population, perhaps 10 or 20% to promote the proliferation of healthy microflora.

Such modest stain concentrations may be relatively aesthetic, providing only modest, or short-lasting coloration, yet have little, if any lethal effect when used alone. However they can provide a surprising enhancement of the efficacy of the energy treatment, reducing the effective dosage and thence the risks of physiological damage or the treatment duration.

Some specific photosensitizers which may be used in practicing the invention, as alternatives to methylene blue, include, for example, photosensitizers selected from the group consisting of stains, dyes, pigments, arianor steel blue, toluidine blue, tryptan blue, crystal violet, azure blue cert, azure B chloride, azure2, azure A chloride, azure B tetrafluoroborate, thionin, azure A eosinate, azure B eosinate, azure mix sicc., azure II eosinate, haematoporphyrin HCl, haematoporphyrin ester, aluminum disulfonated phthalocyanine and chlorins. Other photosensitizing agents may also be used, as will be apparent to those skilled in the art, including, for example, suitable biocompatible oxidizing agents such as dilute hydrogen peroxide or other biocompatible oxidizing agents.

Desirably, photosensitisers such as the haematoporphyrins which are not well taken up by Gram negative organisms, if selected for use, are employed in treating microorganism colonies that are rich in Gram positive bacteria. Various dyes such, for example, as aluminum disulfated phthalocyanine, toluidine blue, azure B chloride or methylene blue can, without limitation, be employed for treating Gram negative organisms. In embodiments of the invention practiced utilizing an He Ne laser desirably, tryptan blue or crystal violet are not employed.

Some useful combinations of photosensitizer agent and light wavelength include toluidine blue irradiated with optical or photothermal energy including a peak or peaks at or near a wavelength of about 630 nm and aluminum disulfonated phthalocyanine irradiated with optical or photothermal energy including a peak or peaks at or near a wavelength of about 660 nm.

Kits. If desired, embodiments ofphotothermal treatment instrument10 can be supplied as kits comprising one or both of

photothermal treatment instrument

10 and110 and, optionally, one or more other similar photothermal treatment instruments adapted for treatment of other sites or for providing different treatments pursuant to the invention herein. Such kits can also include one or more replacement or alternative light output heads16 together with a suitable selection ofnozzles70,

sinus applicators

140 and142 and optionally one or more

interchangeable filters

34,36. For example, one embodiment of useful rhinosinusitis kit can comprise a

photothermal treatment instrument

10 or110 together with at least twonozzles70, or nozzle-light pipe combinations, and one each of

sinus applicators

140 and142. Preferably a multiplicity ofdisposable nozzles70 is included, for example a stock of between about 4 and 100nozzles70. If desired one or more swabs such as nasal swab80 and sinus swab86 is included, for example a stock of from about 4 to about 100 of each swab. In addition, a stock of suitable photosensitizer agent can be included, for example from about 0.5 to about 100 ml of methylene blue or other suitable agent as described herein. Bulk supply kits can be supplied to professionals such as physicians and medical facilities whereas individual kits comprising only one or two items of each or a selection of the foregoing components can be suitable for marketing to consumers.

Energy sources. A variety of energy sources can be employed for the photothermal treatment instruments of the invention including for example pulsed light, pulsed heat and light, and continuous or pulsed LED or laser sources. If a laser is utilized, it is preferably a low intensity or relatively low intensity laser provided with a diffuser to spread the output radiation. The energy system desirably outputs energy over a target area or in a target pattern which is neither a thin pencil, which would make coverage of the target difficult, nor an area so wide as to render the received radiation too weak to be effective.

One embodiment of the invention (not illustrated) employs, as an alternative to the type of light source employed by Azar et al. and described hereinabove, an electromagnetic energy source such as the incoherent pulsed light sources disclosed in Eckhouse et al. U.S. Pat. No. 6,514,243, the entire disclosure of which is hereby incorporated herein by reference thereto. Eckhouse et al. employ, for removal of hair from the skin by means of electromagnetic follicle destruction, a gas filled flashlamp, such as a xenon-filled linear flashlamp ILC Technologies model no. L5568. Xenon-filled flashlamps having suitable characteristics can be employed as photothermal energy sources in the present invention, for example (?see brochure)

Character of Energy Output. Depending upon the nature of the organism or organisms to be controlled, the applied energy delivered fromoutput head16 to the target site can be either heat energy alone or light energy alone but is preferably a mix of heat and light energy. The energy should be applied in a quantity and at a wavelength effective to obtain a desired reduction of the colony microorganism or microorganisms to be controlled. In one embodiment of the invention about 80 percent of the applied energy reaching the target site can be heat and about 20 percent can be light. These quantities can of course vary substantially for example within the ranges of from about 60 to about 90 percent heat and about 10 to about 40 percent light.

Preferably the light energy employed includes visible wavelengths and optionally it may include a minor proportion of ultraviolet light in the wavelengths for UVA or UVB or both. However it is usually desirable to avoid UVC wavelengths which may induce DNA or other damage to human tissue. Another embodiment of the invention substantially excludes all wavelengths of ultraviolet, or has minimal or modest ultraviolet, for treatments where the potential carcinogenicity, or other potentially harmful effects of ultraviolet light are unacceptable.

As described elsewhere herein, particularly in relation to

filters

34,36 the invention can employ pulses of photothermal energy rich in blue light, having for example at least 70 percent or even at least 90 percent of the pulse energy in visible wavebands is contained in a relatively narrow blue waveband of from about 400 to 500 nm or a blue-green waveband of from about 400 to about 600 nm.

As described above, utilization of Azar et al.'s apparatus for destroying sensitized, e.g. selectively stained, oral bacteria within dental plaque, is preferably effected, according to Azar, by employing energy filtered to exclude the absorption peaks of oxyhemoglobin at wavelengths of 418 nm, 542 nm and 577 nm and neighboring wavelengths, to avoid undesired coagulation of blood vessels (paragraph [0066]). Blood vessel coagulation can be understood to be a risk of Azar's procedure, intended for consumers, which employs staining in the dental area where gingivitis and associated bleeding, is common. In contrast, the present invention can, in some embodiments, include energy at the oxyhemoglobin absorption wavelengths to be excluded by Azar et al. Indeed, as described hereinabove, photothermal energy rich in polychromatic blue light in the waveband of 400-500 nm or polychromatic blue-green light in the waveband of 400-600 nm can be particularly useful for the treatment of bacteria colonies resident on or in nondental upper respiratory mucous tissues. where. It is contemplated that coagulation of blood vessels will not usually occur, or will not be a problem, with the treatments of the invention described herein.

While the invention is not limited by any particular theory, it is contemplated that light may often be effective to reduce superficial colonies of microorganisms at the target, i.e. microorganisms that are essentially on the surface of the target. Light may also incapacitate microorganisms up to a depth of about 1 to about 1.5 mm. However, light may not adequately penetrate deeper layers of tissue. Accordingly employment of near infrared or longer wavelength heat energy that can penetrate the superficial layers and reduce microorganisms in lower layers of the tissue is contemplated as an advantageous but optional, feature of the present invention. Preferably, such heat energy is applied simultaneously with the light energy and from a common source.

Pursuant to one embodiment of the invention, a microorganism control treatment can comprise an application of photothermal energy, e.g. one or two pulses, rich in blue light to control superficial microorganisms and a separate application of photothermal energy, e.g. one or two pulses, of orange or other longer frequency radiation to control deeper microorganisms.

By employing light energy in conjunction with mild heat energy, many microorganisms can be effectively destroyed photochemically, possibly avoiding the need to use more intense heat to raise the tissue temperature to the coagulation temperature of the microorganism. Such an embodiment of the invention can be employed where a patient has particularly sensitive, or previously damaged tissue, or there is a particular concern to avoid tissue damage. Furthermore, mild heating can increase the local blood flow, facilitating the elimination of bacteria or other microorganisms.

The applied energy can be selected to include wavelengths, in addition to visible light wavelengths, that both elevate the temperature of the target to cause thermal damage to colonies of microorganisms resident at the target and also to accelerate destructive photochemical reactions. The energy can be selected to include wavelengths absorbed by the mucous tissue at the target which is impacted by the applied radiation.

Pursuant to the invention, it is desirable to destroy microorganisms resident on or in the target tissue without damage to, or with only minimal damage to, the tissue itself and without causing the patient pain, soreness or other undesired reaction. To this end in one embodiment of the invention the tissue temperature can be raised to a temperature in the range of from about 50° C. to about 70° C., preferably to about 60° C., for example in the range of from about 57° C. to about 63° C. The temperature of the target tissue can be determined in known manner or by employing a thermosensor (not shown) carried by thephotothermal treatment instrument10 and operated during, or preferably, promptly after application of a photothermal treatment.

If desired the instrument can be calibrated by performing a number of treatments with different durations, intensities and targets and detecting the resultant target temperatures. Using this information settings and protocols can be provided for future procedures that will yield appropriate target temperatures with reasonable confidence, without the need for real time temperature determinations.

The period of elevated temperature is preferably of the order of about 1 minute for example from about 5 seconds to 5 minutes or in the range of from about 20 seconds to 2 minutes, or from about 40 to about 80 seconds. A desired period of elevated temperature may be achieved by application of one or more energy pulses, up to no more than about ten pulses within the period, each pulse being of brief duration, as described herein, and each being followed by a quiescent interval providing for tissue relaxation.

One example of effective heat energy is the infrared energy of a CO₂laser at a wavelength of about 10,540 nm which wavelength is very efficiently absorbed by water and may be employed, preferably in conjunction with other frequencies, as described herein. If laser energy is utilized for the practice of the invention, it can be diffused, using a diffuser to spread the energy over a desired tissue area and avoid tissue damage, and, preferably is also, supplemented with other frequencies.

Pulsed or continuous energy. Some other useful embodiments of the invention employ pulsed rather than continuous energy sources to provide high peak power and efficient photochemical activation of harmful chemical species in the microorganisms or in treatment materials such as oxygen gels, if the latter are employed. Other embodiments can employ continuous energy sources, if desired.

In the application of heat, use of a pulsed source can be helpful as pulsing allows for thermal relaxation of the tissue in the troughs between peaks preventing localized overheating of and damage to tissue.

Useful pulsed radiation for practicing the invention can have a pulse width of not more than about 200 msec, for example from about 10 to about 100 msec. In one useful embodiment of the invention the pulse width is about 25-35 msec. If multiple pulses are applied at one time, there is desirably a delay, providing a tissue relaxation interval between pulses of the order of from about 10 to about 2000 msec, desirably from about 20 to about 100 msec, for example about 40 or 50 msec, to permit tissue relaxation and prevent tissue damage.

The pulse energy delivered to the target sites should be sufficient to be effective in controlling microorganisms without causing tissue damage such as to be normally perceived by the patient or that would be harmful to the patient. For example, energies of from about 0.1 to about 5 J/cm², preferably from about 0.5 to about 3.0 J/cm²may be employed.

Typically, individual light flashes can have durations in the range of about 0.1 to about 10 msec and irradiates internal sino-nasal surfaces with incoherent light. The light can be band-limited by suitable filtration, if desired and longer duration flashes up to about 2000 msec may be employed, if desired. The output energy density at outlet port73, or other suitable energy output port, can be from about 0.1 to about 50 Joule/cm². Some embodiments of the invention can employ energy densities of from about 3 to about 20 joules/cm², for example from about 7 to about 12 joules/cm². Other useful embodiments of the invention can employ energies of from about 0.1 to about 5 J/cm², preferably from about 0.5 to about 3.0 J/cm². The peak energy waveband can be selected to be at, to include, or to overlap the bacterial stain sensitization peaks, for good efficiency.

The duration and energy density are desirably controlled to heat stained bacteria and other microorganisms to a destruction temperature such as their temperature of coagulation, while avoiding tissue or other physiological damage. Using energy densities within this range, even a single flash can, in many cases, effectively cause photothermal heating and coagulation of selectively stained sino-nasal bacteria.

Optionallyphotothermal treatment instrument10 may have settable controls to provide different predetermined dosages, which controls may be labeled. For example, a duration controller may be provided for selecting the pulse duration or pulse width e.g. from about 10 to about 50 msec, and a pulse number selector may select the number of pulses output for a single actuation ofphotothermal treatment instrument10, for example from 1-10 pulses, at a predetermined relaxation interval, for example of from about 10 to about 100 msec.

One useful embodiment of energy application protocol employs a xenon flashlight and an orange filter, transmission about 600-700 nm, with two photothermal energy pulses of about 35 msec, with a 50 msec interval, at an energy density of about 2.5 J/cm². An energy waveband output through an orange filter is strongly absorbed by methylene blue-stained organisms. Different filters may be used with different stains to provide good absorption, for example a green filter may be used with a pink stain.

Another useful embodiment employs light at 760 nm from a laser diode at an energy of 50 milliwatts/cm²for a duration of 30 seconds.

If employed, the heat energy may be provided by any suitable source, for example infrared radiation, convection, conduction or in situ induction by RF or microwave energy or the like. If desired, RF or microwave energy may be applied to obtain useful therapeutic results in conjunction with light and/or a heat source. It will be understood that RF or microwave or equivalent energy fluxes can be employed to provide useful microorganism control effects by mechanisms other than local heating, for example by electroporation (cell membrane pore formation) or cell membrane rupture. Some, but not all, useful embodiments of the invention employ light, optionally in combination with another energy source.

The electromagnetic energy can be applied in any suitable wavelength mode, waveband mode or combination of wavelength and/or waveband modes which is or are effective to provide control of one or more target microorganism species without causing unacceptable pain, trauma or other side effects. A suitable source or combination of sources can be provided to generate or introduce the desired energy or energy mix in situ.

For example, any combination of two or more of light energy, heat energy, radio frequency (“RF”) and microwave energy may be employed in the inventive treatments, if desired. Some useful treatment embodiments of the invention apply light energy together with heat energy and may optionally also apply RF or microwave energy. In alternative embodiments, a light energy mode is employed together with a heat energy mode, a microwave or RF mode or with a heat energy mode and a microwave or RF mode. Useful embodiments include heat energy modes wherein the heat energy is generated by RF or microwave radiation. Alternatively, the heat energy mode may comprise infrared radiation.

The invention includes embodiments wherein two or more energy modes are applied essentially simultaneously. By “essentially simultaneously” is meant that the two energy modes are applied simultaneously, or are applied in rapid succession, one after the other, such that significant cooling of the target does not occur between the first and second applications of energy.

Each energy mode source or applicator can be any suitable device as known to those skilled in the art. Combination devices and methods such as disclosed in Kreindel U.S. Pat. No. 6,702,808, the entire disclosure of which is hereby incorporated herein by this specific reference thereto, can also be employed. The invention includes novel uses of such devices and novel combinations and modifications of such devices adapting or combining them for the purposes of the invention, as will be apparent to those skilled in the art in light of the disclosure herein.

By way of example, the energy applicator device can include a light source to emit optical energy, one or more electrode pairs for generation of RF energy and/or microwave elements for generation of microwave energy. Optionally, the light source may also provide an effective intensity of heat energy. Pulsed RF energy applied by the electrodes can be applied to the target tissue either directly or through a conductive substance.

Usefully, the frequency of the RF energy can be in a range of from about 300 kHz to about 100 MHz, the output power can be from about 5 to about 200 W, pulse duration from about 1 to about 500 msec and the pulse rate can be from about 0.1 to about 10 pulse per second. Frequencies, or frequency ranges, in spectral locations assigned by governmental entities for industrial, scientific and/or medical purposes are particularly useful, including for example in the United States, FCC-assigned frequencies of about 13.56 MHz, 27.12 MHz and 40.68 MHz.

The optical energy employed with such an RF energy mode can have an intensity of from about 5 to about 100 Joules/cm2 and a pulse duration of from about 1 to 200 msec. The individual or combined energy dosages desirably are selected to avoid long-term physiological damage or unacceptable discomfort pain or other immediate adverse effects.

Visible light, if employed, may have a single wavelength, multiple wavelengths or a waveband and this or these are preferably selected according to the absorbency of the target organism or organisms, and are typically in the range of 500 to 1200 nm. Other energy modes, if employed, may also have a single wavelength, multiple wavelengths or a waveband or wavebands.

Microwave energy for use in the invention can be of any suitable frequency for example in a range of from about 100 MHz to about 50,000 MHz, the output power can be from about 0.01 to about 10 watts/ml of target volume, optionally from about 0.1 to about 2 watts/ml. Frequencies, or frequency ranges, in spectral locations assigned by governmental entities for industrial, scientific and/or medical purposes are particularly useful, including for example in the United States, FCC-assigned frequencies of about 915 MHz, 2,450 MHz, 5,800 MHz and 24,125 MHz.

Selection of a suitable energy mode or mix of energy modes to provide an effective treatment can be made on the basis of the teachings herein with the assistance of knowledge in the art, if desired. For example, useful guidance regarding antimicrobial energy treatments may be found, inter alia, in the food processing arts, for example in disclosures such as the USFDA Center for Food Safety and Applied Nutrition publication “Kinetics of Microbial Inactivation for Alternative Food Processing Technologies”, dated Jun. 2, 2000, the entire disclosure of which is hereby incorporated herein by this specific reference thereto. Of particular interest is the section headed “Microwave and Radio Frequency Processing” and section 3.3 thereof.

RF and microwave energy fluxes are useful for their rapid and uniform effect and ability to penetrate subepithelially to reach microorganisms harbored in tissue crevices, folds, pockets and the like and organisms overlaid with other material, e.g. coatings or other microorganisms. Suitable guides and screens or other protective structure can be provided to introduce the desired energy flux to the target area while protecting the subject anatomy from incidental harm. The intensity and duration and other characteristics of the energy flux can be selected with these objectives in mind, without undue experimentation, and pursuant to the principles described in more detail herein for application of light or heat.

The invention includes treatment methods employing a mix of energy modes selected to provide comprehensive therapy at a target site by killing or otherwise controlling a broad spectrum of undesired microorganisms resident at the target site wherein effective energy dosages are applied so as to reach not only superficially resident microorganisms, but also deeper layers or volumes of the target site that are believed to harbor undesired microorganisms. When safely introduced to the target site, RF or microwave energy fluxes are believed useful to this end for their relatively uniform or distributed effects in solid materials especially high water solids such as tissue or other anatomical structures.

Colony count. In one embodiment of the invention, the photothermal treatment is applied in a manner such as to obtain a desired reduction of colony count of a target microorganism or microorganisms, for example a broad spectrum bacterial infection or infection by an antibiotic-resistant strain or strains of bacteria. Pursuant to this embodiment of the invention, parameters such as the intensity and spectrum of the applied energy and the duration of treatment are controlled to obtain a desired colony count reduction of the target microorganism.

The colony count reduction in a given energy dosage may for example be at least 70%, or preferably at least about 90%. A 90% reduction can generally be effected by applying twice the LD₅₀for a given target organism or an average of the LD₅₀'s for a spectrum of target organisms. The bacterial colony count can be determined by taking a biopsy of the target site using a suitable biopsy implement such for example as a scraper, swab or the like and cultivating the biopsied tissue through serial dilutions and determining the colony counts by known methods. Determinations of colony count reduction can be employed to calibrate the energy output ofphotothermal treatment instrument10 to output one or more specific dosages determined to elicit a particular response in a patient or group or class of patients. Optionallyphotothermal treatment instrument10 may have settable controls to provide different predetermined dosages, which controls may be labeled. For example, a duration controller may be provided for selecting the pulse duration or pulse width e.g. from about 10 to about 50 msec, and a pulse number selector may select the number of pulses output for a single actuation ofphotothermal treatment instrument10, for example from 1-10 pulses, at a predetermined relaxation interval, for example of from about 10 to about 100 msec.

As described, the inventive treatments can be performed to obtain a desired temperature elevation of target tissue for a predetermined period of time or to obtain a desired microorganism colony count reduction. The treatments can also be performed to elevate the target tissue to a selected temperature or temperature range for a duration sufficient to obtain a desired colony count reduction in a target or sample microorganism or spectrum of microorganisms.

Chemical supplementation. If desired, various chemical means can be used to supplement the effect of the radiation or to sensitize the target microorganisms to the radiation, for example, stains or oxidants. Given the diversity and virulence of the colonies of organisms commonly responsibly for rhinitis and sinusitis, use of such a sensitizer is often desirable in the practice of the invention described herein. The treatment may, for example, be a photochemotherapeutic treatment, effected for example by employing an oxygen gel or other suitable material containing a biocompatible oxidant, e.g. hydrogen peroxide, in a concentration of from about 0.5 to about 5% by weight of the gel. The oxidant chemically sensitizes the bacteria or other microorganisms to the effects of the applied radiation.

Alternatively, the target organisms may be stained, e.g. with a food dye, a known bacterial stain, or other suitable stain which is adsorbed by or adheres to a target microorganism and enhances the absorption of light energy by the organism. Employing staining, desirably the stain color is selected to correspond with the applied light wavelengths, to enhance the effect, for example by using a blue or green stain with applied orange or red light and a red or orange stain with applied green or blue-green light.

Esthetic considerations can make staining problematic in the anterior oral cavity, especially in the vicinity of the teeth because the unsightly colored appearance of the tissues or teeth, induced by staining is likely to be visible to others during normal conversation and may linger for days. However, staining of the back of the tongue is less likely to be problematic and careful application of modest quantities of stain to the nasal and sinus cavities, pursuant to the present invention, is unlikely to be apparent to others. Accordingly, staining which enhances the lethal efficacy to microorganisms of applied radiation can be advantageous in the practice of the invention.

Such gels, stains or other topical target treatment compositions, for example local anesthetics, can advantageously be applied employing swabs ??, or other suitable means.

Target sites. The method and instruments of the invention, used separately or together, can be employed to treat a variety of target sites, including sino-nasal target sites, to control microorganisms infecting the target site. Exemplary target sites include either or both nostrils, the left or right lower nasal cavity, the left or right upper nasal cavity, the sinuses, especially those sinuses that are accessible via the nasal cavity and, if accessible, the frontal, ethmoidal, sphenoidal and maxillary sinuses. Various suitable instruments, including the instruments described herein, for treating one or more target sites, as well as other suitable target sites, will be apparent to those skilled in the art in light of the disclosure herein.

The sinuses are nominally air-filled bony cavities located in the face and skull adjacent to the nose. There are eight paranasal sinuses, which occur as “paired” structures. The right and left frontal sinuses are located in the forehead region; the maxillary sinuses are in the cheek area; the ethmoid sinuses are located between the eyes just behind the bridge of the nose; and the sphenoid sinuses lie deep in the center of the skull. Each sinus is connected to the nose by a small opening called an ostium, and has a size which may be as large as a walnut. The frontal sinuses are situated beneath the bone of the forehead and just in front of the bone overlying the brain.

The purpose or purposes of the sinuses is or are not yet fully understood and are variously described as being to lighten the skull, to improve vocal resonance and/or to produce liquid mucus that drains downwardly from the respective sinus cavity to the nasal cavity and throat and thence to the stomach. Pursuant to the latter theory the mucous fluid moistens the nasal cavity as it travels, preventing undue dryness inside of the nose and trapping and removing dust, dirt, pollutants and microbiologic organisms, preventing them from reaching and infecting or contaminating the lungs. Instead, in a healthy, functioning sino-mucal system such potentially harmful foreign matter is carried to the stomach and destroyed by gastrointestinal digestive factors.

In people with good upper respiratory tract health, tiny hair cells, called cilia, move the mucus layer toward the back of the nose and throat, where the material is ultimately swallowed. Mucus produced in the frontal sinus usually drains through the frontal recess, then through the ethmoid sinus, and ultimately into the nasal cavity. The size and nature of the connection between the frontal sinus and the nasal cavity is highly variable between individuals, making the performance of surgery to mitigate persistent chronic sinus conditions in this area a challenging task fraught with risk of damage to delicate anatomical structures.

Each ethmoid sinus comprises many chambers of 7 to 10 cells each, or smaller, that collectively make up the sinus. Ethmoid cells are composed of very thin-walled bone and lined with mucous membrane. Each cell has its own opening that ultimately leads into the nasal cavity. The ethmoid structure is highly variable and unique, like a fingerprint. The variability complicates the surgeon's task, as does the ethmoid sinuses' adjacency to the eyes and brain. The maxillary sinuses are two air-filled cavities within the maxilla, the bone that forms the cheek and upper jaw located above the teeth, below the eye, and just to the side of the nose. Each maxillary sinus is comprised of a single air-filled chamber lined with a mucus-producing membrane. The mucus travels from the maxillary sinus through an opening, or ostium, until it reaches the nose. Deep within the skull behind the ethmoid sinuses are the sphenoid sinuses, small cavities approximately the size of a large grape. The right and left sphenoid sit next to each other, separated by a thin “septum” or plate of bone. The sphenoid sinuses discharge mucus into the back part of the nose through an opening, or ostium in close proximity to the optical cortex and major vessels that carry blood to and from the brain lie. Sinus disease, as well as surgery in the sphenoid area, carry special risks which may be mitigated by employing the methods and devices of the invention.

The relatively simple sinus applicators illustrated inFIGS. 3,4 and6 and alternative instruments, as will be apparent to those skilled in the art, are useful in many embodiments of the invention, as described hereinabove. however, more complex instruments may be employed, if desired. For example, a functional endoscope or microcatheter may be employed to access a desired target sinus site via the nasal cavity, and, if necessary via an ostium and may be operated, to apply a sensitizing agent followed by photic, laser or photothermal energy to the sinus site to destroy or debilitate infective microorganisms as described herein.

Dental regions of the anatomy are subject to special considerations regarding bacterial or other infections. Unique organisms may be implicated in the diseases of the teeth and the periodontal region and the distinctive nature of pathologies such as caries and gum disease, along with aesthetic and other considerations, render the treatment and prognosis of dental region infections to lie largely in the province of the profession of dentistry.

Target conditions. Target conditions that can be treated by the methods and instruments of the invention include low level or chronic infections of microorganisms comprising bacteria, fungi, viruses and any other microorganisms that may be present at the target site. The invention is particularly useful for treating persistent chronic rhinitis and sinusitis conditions that persist for extended periods, for example longer than four or six weeks. It will be understood that target conditions may comprise any or all of bacterial, fungal or viral population and that most target conditions will comprise a diversity of species although in some cases one or two or a small number of species may predominate. The invention is contemplated as being particularly useful for treating conditions that include species unresponsive to conventional treatments for example resistant bacteria, fungi and viruses. Target conditions to be treated by means of the invention may include one or more of any of the species of microorganism specifically named herein, an in particular those organisms named in the discussion of background art.

Thus, for example, nasal microbial populations including significant proportions of fungal and viral microbes can be treated with a photosensitizing blue or violet dye, e.g. gentian violet, and a suitable dosage of bright light from a photothermalor laser source e.g. a laser diode.

The inventive treatments are broad spectrum and are contemplated to be active or effective against each of the foregoing classes of microorganisms, namely bacteria, fungi and viruses. In particular the photothermal treatments of the invention are contemplated to be effective against antibiotic-resistant bacteria and anerobic bacteria. Furthermore, the treatments of the invention can be controlled to be effective against nonplaque bacteria and the invention includes treatments limited to control of nonplaque bacteria and other microorganisms. An ability of the invention to effectively treat antibiotic-resistant bacteria is especially advantageous. It is believed that the lethal modalities of photothermal energy bombardment and photic sensitization will be relatively unlikely to be overcome by adaptive organisms developing resistant strains.

Some of the conditions that can be treated by the nasally applied methods of the invention include stuffy or runny nose, viral infections such as colds of the upper respiratory tract, influenza, sinusitis, congestion and other low-level chronic infections of the nose and sinuses as well as more serious streptococcal or other bacterial or viral infections of the nose and sinuses. The invention is particularly, although not exclusively, useful for the treatment of infections having, or likely to have, bacterial, viral and fungal components, which may respond only poorly to other treatments.

Methods of Treatment. The microorganism control treatments and instruments of the invention are particularly suited for professional use, for example by doctors, dentists, suitably licensed medical practitioners or technicians or medical assistants, to treat patients in the practitioners' offices or other medical facility. However, the invention is not so limited and can be practiced in any suitable location, including hospitals and homes. Suitable treatment protocols may vary according to the severity and persistence of the infection, the responsiveness of an individual patient and the persistence of patient-perceived symptoms. Suitable treatment protocols can comprise diagnosis of a condition and its proximate cause, target site cleaning and preparation, application of a photochemical sensitizer or other useful agent, if desired and an individual procedure for application of photic or photothermal energy as described herein. With advantage, energy application can be performed on one or more infected target surfaces to a desired detectable conclusion, such as a tissue temperature elevation or microorganism colony count reduction.

The protocol may be repeated as infrequently as biweekly (every two weeks) or even monthly, or may be weekly or twice-weekly, depending upon the judgment of the physician. Also, the protocol may be continued indefinitely, e.g. for two or more years, or more desirably for no more than about one year.

In one preferred embodiment, treatments are performed approximately weekly or biweekly until symptoms are adequately relieved as determined by the treatment subject or their medical advisor. Other desirable embodiments of the invention comprise more frequent such procedures continued for shorter periods, for example from one to five times per week, desirably once or twice per week, for periods of from about two to about sixteen weeks preferably from about four to eight weeks for example for five or six weeks.

Individual treatment procedures can comprise one or two shots of energy applied for example to each nostril or to one or more target sinuses or to both the nostrils and one or more sinuses. Each individual procedure can have a duration of from about 10 seconds to about 10 minutes, preferably from about 30 seconds to about 2 minutes, per target site referring to the time that a treatment instrument is disposed to direct energy toward the target surface. The instrument may emit energy substantially throughout that time period or may emit one or more pulses of energy at intervals during the time period.

Preparatory steps of the energy treatment protocol can comprise verifying the patient's condition, for example as being a chronic rhinitis or sinusitis sufferer, and diagnosis of the character of the infection for example by sampling or taking a biopsy and employing microscope examination or other laboratory tests to determine the presence or concentration of one or more infectious species. The treatment protocol can, if appropriate be adapted according to the results of the diagnosis, for example to specifically target one or more organisms identified.

Usefully, nasal irrigation may be employed prior to the energy treatment if desired, is known in the art. For example with the head tilted forward to a point where the nasal passages are near horizontal, saline, isotonic or other suitable fluid can be flushed through the nose to remove mucous and detritus, employing a syringe or other suitable dispenser and a source of irrigation fluid. Optionally, the energy treatments described herein can be supplemented by subject-applied nasal irrigations at suitable intervals, e.g. commencing at least twelve hours after an energy treatment, once or twice a day. A resiliently squeezable handheld bottle with a dispenser tube and nozzle, or other suitable self-applicator may be used for this purpose.

Such nasal irrigation or cleansing can be effected in a variety of ways employing a gravity flow, pressurized or other suitable device to apply a cleansing fluid to flush the nasal passages. The cleansing fluid may be clean water, or more desirably saline, isotonic or other suitable electrolyte-containing aqueous medium. Efficient nasal irrigation may assist with partial removal of mucous and other matter from the sinuses or sinus passageways. If desired, specialist techniques for clearing or cleansing the sinuses may be employed in the pretreatment some suitable ones of which are described hereinbelow.

A number of useful devices and procedures for cleansing or clearing the nasal passages that may be employed in the sino-nasal pretreatments of the invention are disclosed in “Nuances of Nasal and Sinus Self-Help” by Susan F. Rudy, Susan F. Rudy and Trafford Publishing (2004), the entire disclosure of which, including in particular Chapters 6, 7 and 8 at pages 61-89 relating to gravity-flow, low-pressure and electrically powered devices for nasal cleansing, is incorporated herein by this specific reference thereto.

Some suitable gravity flow devices include: neti pots, in styles such as gravy boat, tea pot or rhino horn and which may be made of ceramic, metal, plastic; bags and douches. Some suitable low pressure devices include: aspiration devices; syringes and squeeze bottles in a variety of sizes; and pressurized sterile canisters of saline or other electrolyte solution. The latter may be advantageous in the clinic or medical office, enabling a single disposable product to be employed to nasally irrigate a patient or for a pretreatment, providing an efficient way of assuring each patient of a sterile treatment and avoiding cross-contamination from one patient to another.

Squeeze bottles suitable for nasal irrigation are available with capacities of from about 4 oz. to about 14 oz. from a number of suppliers including Kenwood Laboratories, Hydromed, Inc., Respironics, Inc., New York Sinus Center and others. Some bottles are prefilled with isotonic fluid. Some suppliers provide dry mixes that can be made up with water into suitable treatments fluids.

A wide range of electrically powered irrigators, including portable units, is available and may be employed in the nasal pretreatment procedures of the invention. Such irrigators apply irrigation fluid under pressure, optionally with pulsing, typically at a pressure in the range of about 5 to about 80 psi. In such devices, irrigation fluid may be electrically pumped from a bulk reservoir having a capacity of from about 80 ml to about 2 liters and is supplied via a short hose to a wand which has a suitable applicator tip which may be removable and optionally disposable. Different tips, wands or adapters may be provided to serve different purposes, for example, stream, spray, adjustable between the two, bulbous tip, straw-like tip, fanciful adapter tips for oral irrigators and so on. Some devices, provide for adjustable pressure, in various ranges from about 5 to about 100 psi. Other options include pulsing features providing a pulsed output in the range of from about 1,000 to 3,000 pulses per minute. Suppliers of such equipment include WaterPik Technologies, Hydro Med. Inc. (Sherman Oaks, Calif.) Panasonic, Conair (Trumbull, Conn.), Sinus Pharmacy (Carpenteria, Calif.) and others.

In general, such nasal irrigation devices are used with the head tilted forward, and possibly also to one side, the with irrigation fluid being applied to one nostril and draining out of the other. Aspiration devices may draw congesting material from one nostril, while closing or partially closing the other, as necessary.

Usefully also, nasal cleansing can be practiced by the treatment subject, or patient on a routine basis, for example daily or twice daily between office visits for the primary, radiative treatments of the invention. It will be appreciated that the cleansing and clearing effected by such nasal cleansing treatments will usually be temporary. As mentioned, nasal cleansing may also effect some clearing of the sinuses or sinus passageways.

Desirable devices for professional use in a medical office, clinic or other treatment facility intended for multiple applications of irrigation fluid to a number of treatment patients or subjects desirably have means to control transmission of infectious agents from one patient to another. Removable and disposable applicator nozzles or other fittings can be useful in this respect. In addition, means to control possible runback of fluid from the patient are desirable. Such means may comprise a one-way valve to prevent runback being delivered to a subsequent patient. In one useful embodiment of such runback control means the one way valve is provided in a disposable applicator tip or adjacent conduit, which is also disposable. Optionally, the device can also include a manually operable shutoff valve just upstream of the point of connection of the disposable tip enabling the disposable tip to be easily removed and replaced, without loss of pressure, so that fluid discharge can be quickly resumed. Such shutoff valve may be manually operable and resiliently biased to a closed position or otherwise structured to close automatically. Other suitable structural measures for controlling runback will be apparent to those skilled in the art.

Nasal or sinus cleansing pretreatments such as described above can be helpful in enhancing the performance of the electromagnetic radiative treatments of the invention by improving the access of the radiation to deeper seated organisms that may be resident subepithelially or interstitially in cracks, crevices or folds of the tissues or other anatomical structures.

To perform a desired protocol on a patient to treat one of the described target conditions employingphotothermal treatment instrument10, the medical practitioner initially determines the desired energy output of thephotothermal treatment instrument10 by selecting anappropriate lamp32 and filter or filters34,36. In addition, the practitioner sets controls for power output and duration of energy output to values selected to be appropriate for the target-condition, if such controls are present or manually controls the instrument to output energy for a desired time period at a desired distance from the target.

The patient is prepped as necessary for example, by clearing or cleaning the nose or sinuses by more or less mechanical processes such as blowing or removal with a suitable implement. For some particularly useful embodiments of the invention, a sensitizer such as a dye is then applied, in liquid form using a swab or spray.

Some illustrative examples of. sino-nasal treatment protocols according to the invention will now be described, by way of example, and without limitation.

EXAMPLE 1Nasal Treatment Using Diode Laser Energy

In one example of a nasal treatment protocol, a patient attending a doctor's office presents symptoms of chronic sinusitis, complaining of a feeling of congestion, having nasal mucous an affected voice and headaches ranging from mild to severe. The following treatment protocol is performed.

1. The nose is cleaned of accumulated mucous and related detritus employing tissues and blowing or saline irrigation or both.

2. One or more endoscopic cultures is or are taken from the mucous membrane lining the affected area or areas of the nose, employing a small surgical scraper, to monitor what organisms are growing. This information is used to monitor the effectiveness of the treatment, and to adjust the dosage or frequency of treatment accordingly.

3. The affected nasal or sinus areas are coated with a concentration of about 0.5 mg/ml methylene blue, a blue-spectrum dye, employing an alginate swab (?check brochure).

4. A quiescent interval of from 1 to 20, preferably from about 5 to about 10 minutes prior to photothermal treatment is allowed for absorption of the applied stain.

5. The practitioner then applies a suitable dosage of radiation, employing diodelaser energy applicator110 fitted with nasal tip?? to provide a desired energy dosage to the internal surfaces of the nasal cavity. The energy applicator is carefully fitted to each nostril in turn and oriented to direct the output upwardly into the upper nasal cavity. An energy dosage of light at a wavelength of about 760 nm emanating from a laser diode at an energy of 50 milliwatts/cm2 for a duration of 30 seconds. is then output while the practitioner holds the applicator in position. Dosage is selected to reduce the heterogenous microbe population by about 50-90% leaving a residual colony to permit and encourage growth of normal microflora. A suitable dosage can be determined by in vitro testing, by culturing nasal samples before and. after treatments or by both methods. Each diode laser energy treatment of a target nasal area is effected for from about 5 to about 15 minutes depending upon the judgment of the practitioner, for example for from about 10 to about 12 minutes, completing a nasal treatment of both sides of the nose in about 3040 minutes.

6. Steps 1-5 are repeated every two weeks until symptoms abate. If appropriate, the treatment in step 5 is modified according to the results of the biopsy in step 2. For example??

EXAMPLE 2Sinus Treatment Using Diode Laser Energy

The protocol of Example 1 is repeated employing a sinus applicator tip in place of the nasal tip. Each affected or targeted sinus is treated by inserting the sinus applicator tip through the nasal cavity and positioning the sinus applicator outlet as closely adjacent to the entrance to the respective sinus cavity as possible. A desired energy dosage is then output while the practitioner holds the applicator in position. of Such treatment can be effective in managing microbial blockage of the sinus drainage ducts bringing significant relief to some patients.

The foregoing sinus treatment is preceded by, or alternatively, followed by, the nasal treatment of Example 1. The whole protocol, with application of radiation to all subject nasal and sinus target areas is completed within about 50-70 minutes.

EXAMPLE 3Nasal and Sinus Treatments with Pulsed Photothermal Energy

The protocols of Examples 1 and 2 are repeated employing pulsed energy from a photothermal applicator equipped with a xenon flashlight having an orange filter, transmission about 600-700 nm. Two photothermal energy pulses of about 35 msec each, with a 50 msec interval, at an energy density of about 2.5 J/cm²are applied to each nostril and target sinus area. In this case with much shorter duration energy treatments, the whole protocol is completed in about 10-20 minutes, or possibly less.

EXAMPLE 4Determination of Lethal Sensitization of Oral Pathogens

Suitable stain dosages for providing lethal sensitization of oral pathogens are determined in vitro by the following procedure. An objective is to determine the minimum duration of light exposure and minimum agent dilution required to achieve at least a 50% reduction in bacteria counts. Experimental tests are performed on two common pathogens using a continuously working, high intensity, red filtered halogen lamp. Red light from the filtered halogen lamp is transmitted through a flexible light guide to radiate downwardly onto petri dishes containing samples of live bacteria of speciesPorphyromonas GingivalisandPrevotella Intermediausing the protocols described below.

Bacteria.Prevotella Intermediais isolated from patient sample material, identified in the laboratory using standard diagnostic test systems (Remel Inc., Lenexa, Kans., USA) and is maintained by twice-weekly subculture in thioglycollate medium (Becton Dickinson and Co, Sparks, Md., USA).P. gingivalisATCC 33277 obtained from Remel Inc., is maintained by a twice-weekly subculture on CDC anaerobe blood agar (Becton Dickinson and Co, USA) and in thioglycollate medium (Becton Dickinson and Co, USA).

Light Source. The source for light energy is a continuously working, high intensity halogen lamp having a built-in 250-Watt quartz halogen light source, model I-250 supplied by Medithon, New York, N.Y., USA. Such lights are customarily employed for ear, nose or throat procedures. The light is transmitted through a flexible light guide and filtered to maintain maximum energy output at wavelengths in the vicinity of about 650 nm using a broadband red filter (Edmund Optics Inc., Barrington, N.J., USA). The light output power density measured at 3 cm distance from the end of the light guide with filter is about 50 milliwatts/cm2.

Photosensitizer. 1% methylene blue solution (Faulding Pharmaceutical Co, Paramus, N.J., USA) is used as a photosensitizer. Serial dilutions with water of initial solution with respective concentrations of 0.1%, 0.075%, 0.05%, 0.025% and 0.01% are prepared from the initial solution using sterile 10-ml bottles of normal saline and sterile syringes.

Lethal photosensitization ofP. Intermedia. Petri dishes containing CDC anaerobe blood agar (Becton Dickinson and Co, USA) are inoculated with 0.5 ml of broth containing 5×10⁵CFU/ml and left closed at room temperature for about 10 minutes to let the broth penetrate the agar media. The inoculated plates are then exposed to 1 ml of methylene blue solution at concentrations 0.1%, 0.075%, 0.05%, 0.025% and 0.01% respectively for at least 60 seconds and then exposed to the red filtered light source for time intervals of 1 min, 5 min, 10 min and 20 min respectively. Only plates with concentrations of 0.01%, and 0.025% are used in the experiment with 20 min light exposure. Four plates are used for each experiment. Four inoculated plates that are not exposed to methylene blue or to the light source are used as controls. The controls are covered to protect them from ambient light. In order to examine the ability of light to cause killing of bacteria, inoculated plates are exposed to the red-filtered light at the same time intervals, without previous exposure to methylene blue, in the same groups of four plates. To study the ability of methylene blue alone to induce bacterial death, groups of four inoculated plates are exposed to the methylene blue solution at specified concentrations without subsequent exposure to the red-filtered high intensity light. A total of 108 subcultures is used for the experiment. Plates are incubated in anaerobic conditions in the jars using anaerobic pack kits (BBL GasPak Plus, Becton Dickinson and Co, Sparks, Md., USA) at 37° C. for 24 hours. Samples of the resulting culture growth are taken from each plate with sterile 1:L standard loop, dispensed in 1 ml of sterile NS and placed at the same media. Cultures are incubated at anaerobic conditions at 37° C. for another 24 hours, and after that the resulting colony count is performed on each plate.

Lethal photosensitization ofP. Gingivalis. Serial dilutions of theP. gingivalisculture are prepared from the initial culture preserved on plates using 1:L sterile standard loop (Becton Dickinson and Co, USA) and sterile NS. AVitek calorimeter (Hach Company, Loveland, Colo., USA) is used to achieve a final concentration of about 5×10³CFU/ml from an initial 0.5 standard McFarland suspension of 10⁸CFU/ml. Plates containing CDC anaerobic blood agar (Becton Dickinson and Co, USA) are inoculated with the resulting suspension using sterile 10:L standard loops (Becton Dickinson and Co, USA). The plates are then exposed to the methylene blue solution at different concentrations and thereafter to the red-filtered high-intensity light source at different time intervals using the algorithm described forP. Intenmedia. Plates are also incubated at 37° C. in the tightly closed jars supplied with anaerobic pack kits (BBL GasPak Plus, Becton Dickinson and Co, USA) for 24 hours, and the resulting colony count is performed on each plate.

Typical results obtainable from experiments such as those described in Example 2 are shown in Table 1 below, which describes the data as the means of four values, two each from each species, along with their standard deviations. The results for the two species were broadly comparable. Statistical analyses can be carried out using single-factor analysis of variance.

TABLE 1

Survival of Bacteria Exposed to Blue Stain and Red light
Percent of living bacteria

Methylene

Exposure to Red Light

blue %	0	1 min	5min	10min	20 min

0	N/A	70 +/− 6	75 +/− 7	73 +/− 8	N/A
0.01%	70 +/− 11	73 +/− 6	69 +/− 7	55 +/− 6	51 +/− 4
0.025%	75 +/− 14	67 +/− 4	47 +/− 6	48 +/− 8	49 +/− 5
0.05%	68 +/− 12	53 +/− 10	32 +/− 7	32 +/− 9	N/A
0.075%	51 +/− 10	45 +/− 5	26 +/− 5	25 +/− 5	N/A
0.1%	35 +/− 9	39 +/− 12	28 +/− 9	24 +/− 4	N/A

Column 1 of Table 1 reports the concentration of stain employed in each culture as a percent of methylene blue, “methylene blue %”. The remaining column headings describe the duration of red light exposure in each test.

Results. It may be seen from the data in Table 1 that a statistically significant reduction in bacterial colony count, with a survival rate of 50% or less can be achieved at concentrations of methylene blue of 0.05% and higher when the red light exposure is 10 or 20 minutes. No statistically significant difference is noted between the exposure for 10 and 20 minutes in either species or with any concentration of methylene blue. Exposure of both cultures to red-filtered high-intensity light source may produce statistically significant increased killing with duration as read at the time intervals of 1 min, 5 min and 10 min, with methylene blue concentration of 0.05%, and at the time intervals of 5 and 10 min with methylene blue concentration of 0.025%. Methylene blue concentrations of 0.075% and 0.1% show significant bactericidal effect even without light exposure. Some statistically significant bacterial killing can also be at a 0.01% concentration without light exposure in theP. gingivalisculture. With light exposure for 1 min both 0.075% and 0.1% concentrations of methylene blue produced statistically significant bacterial count reduction in both cultures. Little, if any statistically significant reduction in bacterial counts is noted with the exposure of either culture to the red-filtered high-intensity light source without the exposure to methylene blue.

Conclusion. The results of the study show that red-filtered high-intensity light, used in combination with methylene blue solution at a concentration of 0.01% or higher, can produce a bactericidal effect on both species examined, when a time of exposure less than 10 minutes and an accumulated energy level of 30 J/cm²are employed. Significant reduction in bacteria counts can also be achieved with combination of light exposure for 5 min and methylene blue concentration of 0.025% and light exposure for 1 min and methylene blue concentration of 0.05% and higher. Methylene blue can produce bactericidal effect onP. gingivalisat concentration of 0.1%. Exposure to red light with wavelength of 650 nm alone does not appear to produce significant killing ofP. intermediaorP. gingivalis.

Furthermore, as may be seen from the data in Table 1 that a desired level of lethal photosensitization, namely killing of 50% or more of the bacteria population, of the studied oral pathogens can be achieved under the following conditions:

- 1. Illumination with red halogen light for 5 minutes or more using 0.05% methylene blue stain; or
- 2. Exposure to red halogen light for 20 minutes in the presence of a concentration of 0.025% or 0.01% methylene blue stain. It may be understood that some useful conditions to avoid tissue damage and destruction of commensal organisms, while obtaining useful kill rates of target bacteria are, for example, 8-12 min at 0.01%, 4-6 min at 0.025% and equivalent combinations of concentration and exposure.

The useful conditions that are apparent from Table 1 and the accompanying discussion can be understood to be exemplary of a range of possible effective conditions that may be apparent, or may be determined with modest experimentation, and which may vary according to the particular stain employed, the prevalent species of microorganism and the wavelength and energy density of the applied light. For example, it is contemplated that use of a pulsed xenon photothermal light source as described herein can significantly reduce the exposure periods required for desired lethality.

Neither exposure to the halogen light for 20 minutes in the absence of a photosensitizer, in this case methylene blue, nor concentrations of methylene blue of 0.001% or 0.025%, without halogen light, appeared to be effective in killing bacteria

Reduction of bacteria treated with 0.05% methylene blue alone, without exposure to light, is found to be insignificant. However, concentrations of 0.075% and 0.1% methylene blue are found to be significantly bactericidal, for the test species, even in the absence of red halogen light.

The data shows that lethal photosensitization of two common oral pathogens can be obtained employing high intensity red-filtered halogen light in the presence of dilute methylene blue verifying the value of chemical photosensitization and suitable applied light as a treatment alternative to chemical antibiotics which may induce resistance. Though not demonstrated by the tests described here, unlike chemical antibiotics, combinations of halogen light and suitable stains may also destroy non-bacterial organisms such as fungi and viruses.

In a still further embodiment, the invention provides methods and apparatus wherein the bacterial populations at the target are quantitatively monitored by species or strain on a relative or absolute basis. The treatment protocol or dosage can then be varied according to the data obtained regarding the increase or decrease of one or more bacterial populations with time. Thus, for example, treatment may be continued until a desired low level of one or more undesired or pathological bacteria is reached. In one embodiment of the invention treatment is conducted to eliminate most but not all micro-organisms, for example to destroy or kill from about 50 to about 90 percent of a target species or heterogenous population of species, so as to permit desirable organisms, associated with health to survive. Possibly, treatment may be continued until a desired increase in level of a bacterium associated with health is reached.

If desired the treatment apparatus can include a power unit having user-settable controls to provide a desired photothermal output enabling the operator to select a desired pulse energy, pulse duration, number of pulses and so on, preferably, using an electronic display to give a visual indication of the settings. Also, the power unit may provide a number of treatment selections each representing a particular combination of pre-set output characteristics suitable for a particular purpose, for example, for treating a specific bacterial strain, a specific patient condition or other suitable parameters. The programming of same can be managed by a microprocessor and suitable software if desired included in or operatively connected with the power unit.

While the invention has been described in the context of a handpiece intended for manipulation by a human user, the invention also includes robotic or remote operation of any of the devices described herein or modifications thereof designed for remote or robotic operation with either manual simulations or electronic actuation of the operator movements that would otherwise be required to conduct the procedure.

Many embodiments of the invention are suitable for, and the invention includes, the practice or use in a doctor's or dentist's office, or clinic of, photothermal and other treatments with photic or thermal energy of halitosis, and other oral or other bodily cavity infections with bacteria or other microorganisms on an out-patient or other basis. Self-administration and home use applications by a parent, nurse, caregiver or the like of embodiments of the invention will also be apparent to those skilled in the art and are embraced by the invention.

Consumer Product. The products and processes of the invention are suitable for use by consumers either for self-application or for one person to apply to another. If desired, particularly, although not exclusively, for consumer use,photothermal treatment instrument10 can have a limited energy output intended to prevent user injury or abuse which may limit the maximum pulse intensity and/or the number of pulses that can be emitted in a given time period. For example the instrument may have a delay which prevents further operation for a period of from about 10 to about 30 minutes after a given number of pulses has been generated, for example from about 5 to about 10 pulses. Such a feature may prevent consumers or others overdosing and causing tissue damage.

Possible mechanism of action. While the invention is not limited by any particular theory, it will be understood by those skilled in the art that heat acts destructively on microorganisms by raising the temperature of their immediate environment. In contrast, a probable mechanism for the bactericidal properties of light is that of catalytic liberation of highly reactive species such as superoxides and free radicals which destroy sensitive molecules for example DNA in the bacteria.

If desired the photoactivated energy treatments described herein, optionally employing photosensitizers such as stains, can be employed as an adjunct to or alternative to nasal or sinus surgery.

The invention furthermore includes rhinosinusitis treatment methods and apparatus for practicing same employing a herein described inventive light-utilizing therapy augmented by a conventional rhinitis or sinusitis treatment. Such conventional rhinosinusitis treatments include not only the nasal irrigation therapies described herein but also, as alternatives or adjuncts to such irrigation therapies, application of one or more chemically or pharmaceutically active agents such as an anti-infective, anti-inflammatory or mucolytic agent as is known or becomes known in the art.

The active agent may be administered in any suitable manner, for example by spray, drops or vapors, as an aerosol, or optionally with the assistance of a nebulizer. If desired, the active agent may be administered in solution, optionally as a unit dosage, employing a surfactant. Also, if desired, the droplet or particle size may be controlled or selected for efficacy, for example as described and claimed in Osbakken et al. (supra), the entire disclosure of which is hereby incorporated herein by this specific reference thereto. Any of the known or novel sinusitis treatments and apparatus, including the illustrated nebulizer, disclosed or referenced by Osbakken et al. may be employed as such adjunctive treatments to the light-utilizing therapies described herein. Such adjunctive treatment may be effected at any appropriate time in relation to the light-utilizing therapy, for example immediately prior thereto, from 1 to 6 hours prior thereto and/or on an ongoing daily, twice daily or more frequent basis between light-based treatments.

Though described in relation to the treatment of nasal and nasally accessed sinus cavities, it will be understood that the principles of the invention can be applied to the treatment of target sites, and especially mucous tissues, in other externally accessible bodily cavities.

Treatment of nonhuman mammals. While the invention has been described in relation to the control of microorganisms in nondental cavities of the upper respiratory tract in humans, it will be understood that the principles of the invention can also be applied to non-human mammals including for example, horses, cattle, sheep and other husbanded animals, pets such as dogs and cats, laboratory animals for example mice, rats and primates, animals employed for sports, entertainment, law enforcement, draft usage, zoological or other purposes.

Disclosures Incorporated. The entire disclosure of each and every United States patent and patent application, each foreign and international patent publication, of each other publication and of each unpublished patent application that is referenced in this specification or elsewhere in this patent application, is hereby incorporated herein, in its entirety, by the respective specific reference that has been made thereto.

While illustrative embodiments of the invention have been described above, it is, of course, understood that many and various modifications will be apparent to those of ordinary skill in the relevant art, or may become apparent as the art develops. Such modifications are contemplated as being within the spirit and scope of the invention or inventions disclosed in this specification.