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`US 20110046432Al
`
`c19) United States
`c12) Patent Application Publication
`Simon et al.
`
`c10) Pub. No.: US 2011/0046432 Al
`Feb. 24, 2011
`(43) Pub. Date:
`
`(54) NON-INVASIVE TREATMENT OF
`BRONCHIAL CONSTRICTION
`
`(75)
`
`Inventors:
`
`Bruce J. Simon, Mountain Lakes,
`NJ (US); Joseph P. Errico, Green
`Brook, NJ (US); John T. Raffle,
`Austin, TX (US); Steven Mendez,
`Brookside, NJ (US)
`
`Correspondence Address:
`ELECTROCORE INC.
`51 Gilbralter Drive
`Suite 3C, Power Mill Plaza
`Morris Plains, NJ 07950-1254 (US)
`
`(73)
`
`Assignee:
`
`ElectroCore Inc., Morris Plains, NJ
`(US)
`
`(21) Appl. No.:
`
`12/859,568
`
`(22)
`
`Filed:
`
`Aug. 19, 2010
`
`Related U.S. Application Data
`
`(63)
`
`Continuation-in-part of application No. 12/408,131,
`filed on Mar. 20, 2009, which is a continuation-in-part
`of application No. 11/591,340, filed on Nov. 1, 2006,
`now Pat. No. 7,747,324.
`
`(60) Provisional application No. 60/736,001, filed on Nov.
`10, 2005, provisional application No. 60/736,002,
`filed on Nov. 10, 2005, provisional application No.
`60/772,361, filed on Feb. 10, 2006, provisional appli(cid:173)
`cation No. 60/814,313, filed on Jun. 16, 2006, provi(cid:173)
`sional application No. 60/786,564, filed on Mar. 28,
`2006.
`
`Publication Classification
`
`(51)
`
`Int. Cl.
`A61N 2104
`(2006.01)
`A61H 1100
`(2006.01)
`A61N 7100
`(2006.01)
`A61N 5106
`(2006.01)
`A61F 7100
`(2006.01)
`A61N 1136
`(2006.01)
`(52) U.S. Cl. ................... 600/14; 601/46; 601/2; 607/88;
`607/96; 607/42
`
`(57)
`
`ABSTRACT
`
`Devices, systems and methods are disclosed for treating bron(cid:173)
`chial constriction related to asthma, anaphylaxis or chronic
`obstructive pulmonary disease. The treatment comprises
`transmitting impulses of energy non-invasively to selected
`nerve fibers that are responsible for smooth muscle dilation.
`The transmitted energy impulses, comprising magnetic and/
`or electrical, mechanical and/or acoustic, and optical and/or
`thermal energy, stimulate the selected nerve fibers.
`
`NS Device 300
`
`Impulse
`Generator
`310
`
`Control
`Unit
`330
`
`POINer
`Source
`320
`
`LUMENIS EX1050
`Page 1
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 1 of 17
`
`US 2011/0046432 Al
`
`350
`
`FIG. 1
`
`NS Device 300
`
`lmpu!se
`Generator
`310
`
`Control
`Unit
`330
`
`Pmver
`Source
`320
`
`FIG. 2
`
`Current
`
`400
`
`! /-'\
`! /
`"''-
`~ ;
`
`rl
`
`I
`!
`
`'-~.._,,-j
`
`/
`
`Activity
`(
`,~,
`'•··----. __ /
`.// ""·
`~ /
`"-~,/
`Pulses
`4'10(
`
`F"\
`~-~
`~
`"--·
`
`Time
`
`420
`
`Current
`
`I
`
`410
`
`(----
`
`t I r·(cid:173)
`r~J
`,
`L -----------·---·----·------------·-
`
`I
`
`-
`
`Time
`
`LUMENIS EX1050
`Page 2
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 2 of 17
`
`US 2011/0046432 Al
`
`FIG. 3
`
`Linear Actuator 540
`
`r-----
`548
`
`46
`
`NS Device 500
`
`Impulse
`Generator
`510
`
`Control
`Unit
`530
`
`Pov1er
`Source
`520
`
`LUMENIS EX1050
`Page 3
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 3 of 17
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`US 2011/0046432 Al
`
`NS Device 800
`
`FIG. 4
`
`Impulse
`Generator -
`810
`
`lug
`Light- Emitting Earp
`86 0
`
`Control
`Unit
`830
`I
`Pov/er
`Source
`820
`
`854
`\
`
`Light
`rvlodulator
`850
`
`~
`L/~
`862
`
`Laser 840
`
`~·
`
`"-
`844
`
`LUMENIS EX1050
`Page 4
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 4 of 17
`
`US 2011/0046432 Al
`
`FIG. 5
`
`HR
`
`FIG. 6
`
`LUMENIS EX1050
`Page 5
`
`

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`Patent Application Publication
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`Feb. 24, 2011 Sheet 5 of 17
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`US 2011/0046432 Al
`
`FIG. 7
`
`FIG. 8
`
`LUMENIS EX1050
`Page 6
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`

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`Patent Application Publication
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`Feb. 24, 2011 Sheet 6 of 17
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`US 2011/0046432 Al
`
`FIG. 9
`
`FIG. 10
`
`:
`
`:
`
`:
`
`: :
`
`:
`
`:
`
`LUMENIS EX1050
`Page 7
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 7 of 17
`
`US 2011/0046432 Al
`
`FIG. 11
`
`FIG. 12
`
`LUMENIS EX1050
`Page 8
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`

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`Patent Application Publication
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`Feb. 24, 2011 Sheet 8 of 17
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`US 2011/0046432 Al
`
`FIG. 13
`
`FIG. 14
`
`LUMENIS EX1050
`Page 9
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`

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`Patent Application Publication
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`Feb. 24, 2011 Sheet 9 of 17
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`US 2011/0046432 Al
`
`FIG. 15
`
`Stimulation at 7 V
`
`electrode inserted
`
`l electrode removed
`
`0
`
`50
`
`1 00
`
`150
`
`200
`250
`Time (min)
`
`300
`
`350
`
`400
`
`450
`
`100
`
`95
`
`90
`
`85
`
`80
`
`75
`
`70
`
`65
`
`60
`
`55
`
`50
`
`---"O
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`+-'
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`0
`
`~ 0 ----->r-
`
`w
`u..
`
`LUMENIS EX1050
`Page 10
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 10 of 17
`
`US 2011/0046432 Al
`
`FIG. 16
`
`----- FEV
`------~----- Heart Rate
`----A- MAP/1.4
`
`90
`
`85
`
`a, 80
`"'O
`:::J
`+-'
`0..
`E
`<( 75
`
`70
`
`65+----r-----.,---r----.----.---.-----.----....----.-----.----.----r----,,..........,
`100
`150
`200
`250
`300
`350
`400
`450
`50
`0
`Time (min)
`
`LUMENIS EX1050
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`

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`Patent Application Publication
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`Feb. 24, 2011 Sheet 11 of 17
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`US 2011/0046432 Al
`
`FIG. 17
`
`Methacholine Challenge
`
`3.8
`
`3.6
`
`3.4
`
`3.2
`
`3
`
`....
`Gj
`LL 2.8
`
`2.6
`
`2.4
`
`2.2
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`2
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`
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`
`~-
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`~'),
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`~~
`
`LUMENIS EX1050
`Page 12
`
`

`

`> ....
`0 ... O'I ... (,H
`
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`....
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`N
`rJJ
`c
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`N
`
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`rJJ =(cid:173)
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`
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`('D
`
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`
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`('D = ..... t "e -....
`
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`
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`
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`
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`
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`
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`
`16
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`rn
`3-0
`15
`
`12% FEV 1 increase
`Efa1psed Time until
`
`45.0
`
`105 .. 0
`
`34 S
`
`59.3
`
`Aver.age
`
`90
`
`12% FEV1 increase
`Elapsed Time until
`
`30
`15
`
`SO
`
`150
`75
`
`191
`
`412
`43.B
`
`66
`5..: '
`61
`
`Peak FEV1 tncreas.e,
`Elapsed Time (min} to
`
`FEV1 from initial
`Peak % tnereese
`
`FEV1 % ?redicmd
`
`Historic.al
`
`FEV1 % Predicted
`
`lnitlaf
`
`01,{JQ2
`
`OH)01
`03°001
`Patient m
`
`96 0.
`
`5U
`
`Date m Im.is patient 044.)IH and 04-002
`
`49.2
`
`Ave.rage
`
`FEV1 from init!at
`Peak rE.V1 Increase
`Poak % increase Elapsed Tim& (min} to
`
`,.,,..,. ...
`
`15
`90
`itiO
`150
`75
`
`t9.2
`·19,7
`1313
`412
`
`43,9
`
`52
`66
`rn
`51
`01
`
`FEV~ Ci/~ Pt~dicteed
`
`Historical
`
`FEV 1 ;i'/i, Predicted
`
`tnitial
`
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`1\P44JP1J./
`
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`
`01,001
`···oiriin
`Patient m
`
`FIG. 18
`
`LUMENIS EX1050
`Page 13
`
`

`

`Patent Application Publication
`
`Feb. 24, 2011 Sheet 13 of 17
`
`US 2011/0046432 Al
`
`FIG. 19
`
`~!
`
`.....
`
`--·--------------·--'---
`
`~ · ~ ·
`
`'
`. ............................ c........
`'
`'
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`
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`. ................... , ..
`'
`'
`'
`
`BP
`
`.......................... , .................. .
`
`FIG. 20
`
`LUMENIS EX1050
`Page 14
`
`

`

`Patent Application Publication
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`Feb. 24, 2011 Sheet 14 of 17
`
`US 2011/0046432 Al
`
`FIG. 21
`
`··!······················:··················:····! AP2 \························································ L i:
`~
`
`: ........................ : .................... :········:························································:··········································:············:----:·-··
`
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`i
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`
`FIG. 22
`
`LUMENIS EX1050
`Page 15
`
`

`

`Patent Application Publication
`
`Feb. 24, 2011 Sheet 15 of 17
`
`US 2011/0046432 Al
`
`FIG. 23
`
`FIG. 24
`
`................... ,
`'
`
`···················,·
`.
`'
`
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`
`LUMENIS EX1050
`Page 16
`
`

`

`Patent Application Publication
`
`Feb. 24, 2011 Sheet 16 of 17
`
`US 2011/0046432 Al
`
`LO
`N
`(9
`LL
`
`}
`
`a.. !
`co
`l
`........................... t .................. ,., ... ,..
`
`i
`!
`
`LUMENIS EX1050
`Page 17
`
`

`

`Patent Application Publication
`
`Feb. 24, 2011 Sheet 17 of 17
`
`US 2011/0046432 Al
`
`i ______ _
`'
`
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`LUMENIS EX1050
`Page 18
`
`

`

`US 2011/0046432 Al
`
`Feb. 24, 2011
`
`1
`
`NON-INVASIVE TREATMENT OF
`BRONCHIAL CONSTRICTION
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`[0001] This application is a continuation-in-part applica(cid:173)
`tion of co-pending U.S. patent application Ser. No. 12/408,
`131, titled Electrical Treatment of Bronchial Constriction,
`filed Mar. 20, 2009, the entire disclosure of which is hereby
`incorporated by reference. This application is also related to
`commonly assigned co-pending U.S. patent Ser. Nos. 11/555,
`142, 11/555,170, 11/592,095, 11/591,768, 11/754,522,
`11/735,709 and 12/246,605, the complete disclosures of
`which are incorporated herein by reference for all purposes.
`
`BACKGROUND OF THE INVENTION
`
`[0002] The field of the present invention relates to the deliv(cid:173)
`ery of energy impulses (and/or fields) to bodily tissues for
`therapeutic purposes, and more specifically to non-invasive
`devices and methods for treating conditions associated with
`bronchial constriction. The energy impulses (and/or fields)
`comprise electrical and/or magnetic, mechanical and/or
`acoustic, and optical and/or thermal energy.
`[0003] There are a number of treatments for various infir(cid:173)
`mities that require the destruction of otherwise healthy tissue
`in order to affect a beneficial effect. Malfunctioning tissue is
`identified, and then lesioned or otherwise compromised in
`order to affect a beneficial outcome, rather than attempting to
`repair the tissue to its normal functionality. While there are a
`variety of different techniques and mechanisms that have
`been designed to focus lesioning directly onto the target nerve
`tissue, collateral damage is inevitable.
`[0004] Still other treatments for malfunctioning tissue can
`be medicinal in nature, in many cases leaving patients to
`become dependent upon artificially synthesized chemicals.
`Examples of this are anti-asthma drugs such as albuterol,
`proton pump inhibitors such as omeprazole (Prilosec ), spastic
`bladder relievers such as Ditropan, and cholesterol reducing
`drugs like Lipitor and Zocor. In many cases, these medicinal
`approaches have side effects that are either unknown or quite
`significant. For example, at least one popular diet pill of the
`late 1990's was subsequently found to cause heart attacks and
`strokes. Unfortunately, the beneficial outcomes of surgery
`and medicines are, therefore, often realized at the cost of
`function of other tissues, or risks of side effects.
`[0005] The use of electrical stimulation for treatment of
`medical conditions has been well known in the art for nearly
`two thousand years. It has been recognized that electrical
`stimulation of the brain and/or the peripheral nervous system
`and/or direct stimulation of the malfunctioning tissue, which
`stimulation is generally a wholly reversible and non-destruc(cid:173)
`tive treatment, holds significant promise for the treatment of
`many ailments.
`[0006] Electrical stimulation of the brain with implanted
`electrodes has been approved for use in the treatment of
`various conditions, including pain and movement disorders
`including essential tremor and Parkinson's disease. The prin(cid:173)
`ciple behind these approaches involves disruption and modu(cid:173)
`lation of hyperactive neuronal circuit transmission at specific
`sites in the brain. As compared with the very dangerous
`lesioning procedures in which the portions of the brain that
`are behaving pathologically are physically destroyed, electri(cid:173)
`cal stimulation is achieved by implanting electrodes at these
`
`sites to, first sense aberrant electrical signals and then to send
`electrical pulses to locally disrupt the pathological neuronal
`transmission, driving it back into the normal range of activity.
`These electrical stimulation procedures, while invasive, are
`generally conducted with the patient conscious and a partici(cid:173)
`pant in the surgery.
`[0007] Brain stimulation, and deep brain stimulation in par(cid:173)
`ticular, is not without some drawbacks. The procedure
`requires penetrating the sknll, and inserting an electrode into
`the brain matter using a catheter-shaped lead, or the like.
`While monitoring the patient's condition (such as tremor
`activity, etc.), the position of the electrode is adjusted to
`achieve significant therapeutic potential. Next, adjustments
`are made to the electrical stimulus signals, such as frequency,
`periodicity, voltage, current, etc., again to achieve therapeutic
`results. The electrode is then permanently implanted and
`wires are directed from the electrode to the site of a surgically
`implanted pacemaker. The pacemaker provides the electrical
`stimulus signals to the electrode to maintain the therapeutic
`effect. While the therapeutic results of deep brain stimulation
`are promising, there are significant complications that arise
`from the implantation procedure, including stroke induced by
`damage to surrounding tissues and the neurovasculature.
`[0008] One of the most successful modern applications of
`this basic understanding of the relationship between muscle
`and nerves is the cardiac pacemaker. Although its roots extend
`back into the 1800's, it was not until 1950 that the first
`practical, albeit external and bulky pacemaker was devel(cid:173)
`oped. Dr. Rune Elqvist developed the first truly functional,
`wearable pacemaker in 1957. Shortly thereafter, in 1960, the
`first fully implanted pacemaker was developed.
`[0009] Around this time, it was also found that the electrical
`leads could be connected to the heart through veins, which
`eliminated the need to open the chest cavity and attach the
`lead to the heart wall. In 1975 the introduction of the lithium(cid:173)
`iodide battery prolonged the battery life of a pacemaker from
`a few months to more than a decade. The modern pacemaker
`can treat a variety of different signaling pathologies in the
`cardiac muscle, and can serve as a defibrillator as well (see
`U.S. Pat. No. 6,738,667 to Deno, et al., the disclosure of
`which is incorporated herein by reference).
`[0010] Another application of electrical stimulation of
`nerves has been the treatment of radiating pain in the lower
`extremities by means of stimulation of the sacral nerve roots
`at the bottom of the spinal cord (see U.S. Pat. No. 6,871,099
`to Whitehurst, et al., the disclosure of which is incorporated
`herein by reference).
`[0011] Nerve stimulation is thought to be accomplished
`directly or indirectly by depolarizing a nerve membrane,
`causing the discharge of an action potential; or by hyperpo(cid:173)
`larization of a nerve membrane, preventing the discharge of
`an action potential. Such stimulation may occur after electri(cid:173)
`cal energy, or also other forms of energy, are transmitted to the
`vicinity of a nerve [F. RATTAY. The basic mechanism for the
`electrical stimulation of the nervous system. Neuroscience
`Vol. 89, No. 2, pp. 335-346, 1999; Thomas HEIMBURG and
`Andrew D. Jackson. On soliton propagation in biomem(cid:173)
`branes and nerves. PNAS vol. 102 (no. 28, Jul. 12, 2005):
`9790-9795]. Nerve stimulation may be measured directly as
`an increase, decrease, or modulation of the activity of nerve
`fibers, or it may be inferred from the physiological effects that
`follow the transmission of energy to the nerve fibers.
`[0012] The present disclosure involves medical procedures
`that stimulate nerves by non-invasively transmitting different
`
`LUMENIS EX1050
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`
`

`

`US 2011/0046432 Al
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`Feb. 24, 2011
`
`2
`
`forms of energy to nerves. A medical procedure is defined as
`being non-invasive when no break in the skin ( or other surface
`of the body, such as a wound bed) is created through use of the
`method, and when there is no contact with an internal body
`cavity beyond a body orifice ( e.g, beyond the mouth or
`beyond the external auditory meatus of the ear). Such non(cid:173)
`invasive procedures are distinguished from invasive proce(cid:173)
`dures (including minimally invasive procedures) in that the
`invasive procedures insert a substance or device into or
`through the skin ( orother surface of the body, such as a wound
`bed) or into an internal body cavity beyond a body orifice. The
`following paragraphs give examples of non-invasive medical
`procedures, contrasting some of them with corresponding
`invasive medical procedures.
`[0013] For example, transcutaneous electrical stimulation
`of a nerve is non-invasive because it involves attaching elec(cid:173)
`trodes to the surface of the skin (or using a form-fitting con(cid:173)
`ductive garment) without breaking the skin. In contrast, per(cid:173)
`cutaneous electrical stimulation of a nerve is minimally
`invasive because it involves the introduction of an electrode
`under the skin, via needle-puncture of the skin.
`[0014] Another form of non-invasive electrical stimulation,
`known as magnetic stimulation, involves the generation (in(cid:173)
`duction) of an eddy current within tissue, which results from
`an externally applied time-varying magnetic field. The prin(cid:173)
`ciple of operation of magnetic stimulation, along with a list of
`medical applications of magnetic stimulation, is described in:
`Chris HOVEY and Reza Jalinous, THE GUIDE TO MAG(cid:173)
`NETIC STIMULATION, The Magstim Company Ltd,
`Spring Gardens, Whitland, Carmarthenshire, SA34 OHR,
`United Kingdom, 2006. As described in that Guide, applica(cid:173)
`tions of magnetic stimulation include the stimulation of
`selected peripheral nerves, as well as stimulation of selected
`portions of the brain (transcranial magnetic stimulation).
`Mechanisms underlying biological effects that result from
`applying such time-varying magnetic fields are reviewed in:
`PILLA, A. A. Mechanisms and therapeutic applications of
`time varying and static magnetic fields. In Barnes F and
`Greenebaum B (eds), Biological and Medical Aspects of
`Electromagnetic Fields. Boca Raton Fla.: CRC Press, 351-
`411 (2006).
`[0015] Diathermy includes non-invasive methods for the
`heating of tissue, in which the temperature of tissues is raised
`by high frequency current, ultrasonic waves, or microwave
`radiation originating outside the body. With shortwave,
`microwave and radiofrequency diathermy, the tissue to be
`treated is irradiated with electromagnetic fields having a car(cid:173)
`rier frequency of typically 13.56, 27.12, 40.68, 915 or 2450
`MHz, modulated at frequencies of typically 1 to 7000 Hz. The
`heating effects may be dielectric, wherein molecules in tis(cid:173)
`sues try to align themselves with the rapidly changing electric
`field, and/or induced, wherein rapidly reversing magnetic
`fields induce circulating electric currents and electric fields in
`the body tissues, thereby generating heat. With ultrasound
`diathermy, high-frequency acoustic vibrations typically in
`the range of 800 to 1,000 KHz are used to generate heat in
`deep tissue.
`[0016] Devices similar to those used with diathermy deliver
`electromagnetic waves non-invasively to the body for thera(cid:173)
`peutic purposes, without explicitly intending to heat tissue.
`For example, U.S. Pat. No. 4,621,642, entitled Microwave
`apparatus for physiotherapeutic treatment of human and ani(cid:173)
`mal bodies, to Chen, describes apparatus for performing acu(cid:173)
`puncture treatment with microwaves. U.S. Pat. No. 5,131,
`
`409, entitled Device for microwave resonance therapy, to
`Lobarev et al. discloses the transmission of an electromag(cid:173)
`netic wave that is propagated along a slotted transmission line
`in free space toward the patient's skin, for applications analo(cid:173)
`gous to laser acupuncture. U.S. Pat. No. 7,548,779, entitled
`Microwave energy head therapy, to Konchitsky, discloses the
`transmission of high frequency electromagnetic pulses non(cid:173)
`invasively to a patient's head, for purposes of treating head(cid:173)
`aches, epilepsy, and depression, wherein the brain behaves as
`an antenna for receiving electromagnetic energy at certain
`wavelengths.
`[0017] Acupuncture (meridian therapy) may be non-inva(cid:173)
`sive if the acupuncture tool does not penetrate the skin, as
`practiced in Toyohari acupuncture and the pediatric acupunc(cid:173)
`ture style Shonishin. Other forms of acupuncture may also be
`non-invasive when they use the Teishein, which is one of the
`acupuncture needles described in classical texts of acupunc(cid:173)
`ture. Even though it is described as an acupuncture needle, the
`Teishein does not pierce or puncture the skin. It is used to
`apply rapid percussion pressure to the meridian point being
`treated, so its use may also be described as a form of acupres(cid:173)
`sure. Electroacupuncture is often performed as a non-invasive
`transcutaneous form of electrostimulation. Laser acupunc(cid:173)
`ture and colorpuncture are also non-invasive in that acupunc(cid:173)
`ture meridian points are stimulated at the surface of the skin
`with light, rather than mechanically or electrically. Although
`it is possible to compare the effectiveness of acupuncture
`treatment with the effectiveness of Western types of treat(cid:173)
`ments for recognized disorders such as asthma, it is always
`possible to ascribe any differences in effectiveness to differ(cid:173)
`ences in mechanisms. This is because acupuncture treats
`patients by stimulating acupuncture meridian points, not tis(cid:173)
`sue such as nerves or blood vessels as identified by modem
`western medicine. Furthermore, acupuncture endeavors to
`produce effects that are not contemplated by modern western
`medicine, such as the de qi sensation, and results using acu(cid:173)
`puncture may be confounded by the individualized selection
`of meridian points, as well as by the simultaneous treatment
`with herbal medicines. For example, acupuncture is not con(cid:173)
`sidered to be effective for the treatment of asthma [McCAR(cid:173)
`NEY R W, Brinkhaus B, Lasserson T J, Linde K. Acupuncture
`for chronic asthma (Review). The Cochrane Library 2009,
`Issue 3. John Wiley & Sons, Ltd.; Michael Y. SHAPIRA,
`Neville Berkman, Gila Ben-David, AvrahamAvital, Elat Bar(cid:173)
`dach and Raphael Breuer. Short-term Acupuncture Therapy
`Is ofNo Benefit in Patients With Moderate Persistent Asthma.
`CHEST 2002; 121:1396-1400; W GRUBER, E Eber, D
`Malle-Scheid, A Pfleger, E Weinhandl, L Dorf er, M S Zach.
`Laser acupuncture in children and adolescents with exercise
`induced asthma. Thorax 2002; 57:222-225], but even if were
`to have been shown effective, such effectiveness would, by
`definition, be attributable only to the stimulation of meridian
`points, as interpreted in terms of theories related to oriental
`medicine (e.g., restoration of Qi balance in Traditional Chi(cid:173)
`nese Medicine).
`[0018] Other forms of non-invasive medical procedures
`direct mechanical vibrations to selected organs or are used to
`massage muscles. For example, mechanical vibrations
`applied to the chest are used by physiotherapists to dislodge
`mucus in the lungs. [M. J. GOODWIN. Mechanical chest
`stimulation as a physiotherapy aid. Med. Eng. Phys., 1994,
`Vol. 16, 267-272; Harriet SHANNON, Rachael Gregson,
`Janet Stocks, Tim J. Cole, Eleanor Main. Repeatability of
`physiotherapy chest wall vibrations applied spontaneously
`
`LUMENIS EX1050
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`breathing adults. Physiotherapy 95 (2009) 36-42; McCAR(cid:173)
`REN B, Alison J A and Herbert RD (2006): Vibration and its
`effect on the respiratory system. Australian Journal of Phys(cid:173)
`iotherapy 52: 39-43]. It is believed that such vibration stimu(cid:173)
`lates the skeletal muscles involved in breathing, although
`vibration at 100, 105, or 120 Hz might also potentially excite
`intrapulminary receptors [A.P. BINKS, E. Bloch-Salisbury,
`R. B. Banzett, R. M. Schwartzstein. Oscillation of the lung by
`chest-wall vibration. Respiration Physiology 126 (2001) 245-
`249; Ikuo HOMMA. Inspiratory inhibitory reflex caused by
`the chest wall vibration in man. Respiration Physiology
`(1980) 39, 345-353]. Similarly, non-invasive mechanical
`ventilators use a face mask, an upper body shell known as a
`cuirass, or a Hayek Oscillator to force air in and out of the
`lungs, thereby avoiding the use of an invasive endotracheal
`tube.
`[0019] The mechanical larynx is another example of a non(cid:173)
`invasive mechanical device, which is placed under the man(cid:173)
`dible so as to produce vibrations that the patient uses to create
`speech. Similarly, a hearing aid directs mechanical vibrations
`(acoustical or sound vibrations) to the eardrum. Because it is
`placed in a natural orifice (the ear canal or external auditory
`meatus), the hearing aid is considered to be non-invasive.
`Extracorporeal shock wave lithotripsy is another non-inva(cid:173)
`sive mechanical treatment, which is used to break-up kidney
`stones by focusing onto the stones a high-intensity acoustic
`pulse that originates from outside the body.
`Imaging procedures that require the insertion of an
`[0020]
`endoscope or similar device through the skin or into a cavity
`beyond a natural orifice ( e.g., bronchoscopy or colonoscopy)
`are invasive. But capsule endoscopy, in which a camera hav(cid:173)
`ing the size and shape of a pill is swallowed, is non-invasive
`because the capsule endoscope is swallowed rather than
`inserted into a body cavity. Such a swallowed capsule could
`also be used to perform non-invasive stimulation of tissue in
`its vicinity from within the digestive tract. Similarly, admin(cid:173)
`istration of a drug or biologic through a transdermal patch is
`non-invasive, whereas administration of a drug or biologic
`through a hypodermic needle is invasive. The acts of taking a
`drug or biologic orally or through inhalation are not consid(cid:173)
`ered to be medical procedures in the strict sense (so the issue
`of invasiveness does not arise), because those acts are func(cid:173)
`tionally indistinguishable from the normal acts of eating,
`drinking, or breathing substances that may be metabolized or
`otherwise disposed ofby the body.
`[0021] Radiological procedures, such as X-ray imaging
`(fluoroscopy), magnetic resonance imaging and ultrasound
`imaging, are non-invasive unless a transducer is inserted into
`a body cavity or under the skin ( e.g., when an ultrasound
`transducer is inserted into the patient's esophagus). However,
`a non-invasive radiological procedure may be a component of
`a larger procedure having invasive components. For example,
`a component of the procedure is invasive when the formation
`of an image or delivery of energy relies on the presence of a
`contrast agent, enhancer, tissue-specific label or radioactive
`emitter that is inserted into the patient with a hypodermic
`needle.
`In the present application, the non-invasive delivery
`[0022]
`of energy is intended ultimately to dilate bronchial passages,
`by relaxing bronchial smooth muscle. The smooth muscles
`that line the bronchial passages are controlled by a confluence
`ofvagus and sympathetic nerve fiber plexuses. Spasms of the
`bronchi during asthma attacks and anaphylactic shock can
`
`often be directly related to pathological signaling within these
`plexuses. Anaphylactic shock and asthma are major health
`concerns.
`[0023] Asthma, and other airway occluding disorders
`resulting from inflammatory responses and inflammation(cid:173)
`mediated bronchoconstriction, affects an estimated eight to
`thirteen million adults and children in the United States. A
`significant subclass of asthmatics suffers from severe asthma.
`An estimated 5,000 persons die every year in the United
`States as a result of asthma attacks. Up to twenty percent of
`the populations of some countries are affected by asthma,
`estimated at more than a hundred million people worldwide.
`Asthma's associated morbidity and mortality are rising in
`most countries despite increasing use of anti-asthma drugs.
`[0024] Asthma is characterized as a chronic inflammatory
`condition of the airways. Typical symptoms are coughing,
`wheezing, tightness of the chest and shortness of breath.
`Asthma is a result of increased sensitivity to foreign bodies
`such as pollen, dust mites and cigarette smoke. The body, in
`effect, overreacts to the presence of these foreign bodies in the
`airways. As part of the asthmatic reaction, an increase in
`mucous production is often triggered, exacerbating airway
`restriction. Smooth muscle surrounding the airways goes into
`spasm, resulting in constriction of airways. The airways also
`become inflamed. Over time, this inflammation can lead to
`scarring of the airways and a further reduction in airflow. This
`inflammation leads to the airways becoming more irritable,
`which may cause an increase in coughing and increased sus(cid:173)
`ceptibility to asthma episodes.
`[0025] Two medicinal strategies exist for treating this prob(cid:173)
`lem for patients with asthma. The condition is typically man(cid:173)
`aged by means of inhaled medications that are taken after the
`onset of symptoms, or by injected and/or oral medication that
`are taken chronically. The medications typically fall into two
`categories; those that treat the inflammation, and those that
`treat the smooth muscle constriction. The first is to provide
`anti-inflammatory medications, like steroids, to treat the air(cid:173)
`way tissue, reducing its tendency to over-release the mol(cid:173)
`ecules that mediate the inflammatory process. The second
`strategy is to provide a smooth muscle relaxant ( e.g. an anti(cid:173)
`cholinergic) to reduce the ability of the muscles to constrict.
`It has been highly preferred that patients rely on
`[0026]
`avoidance of triggers and anti-inflammatory medications,
`rather than on the bronchodilators as their first line of treat(cid:173)
`ment. For some patients, however, these medications, and
`even the bronchodilators are insufficient to stop the constric(cid:173)
`tion of their bronchial passages, and more than five thousand
`people suffocate and die every year as a result of asthma
`attacks.
`[0027] Anaphylaxis likely ranks among the other airway
`occluding disorders of this type as the most deadly, claiming
`many deaths in the United States every year. Anaphylaxis (the
`most severe form of which is anaphylactic shock) is a severe
`and rapid systemic allergic reaction to an allergen. Minute
`amounts of allergens may cause a life-threatening anaphylac(cid:173)
`tic reaction. Anaphylaxis may occur after ingestion, inhala(cid:173)
`tion, skin contact or injection of an allergen. Anaphylactic
`shock usually results in death in minutes if untreated. Ana(cid:173)
`phylactic shock is a lifethreatening medical emergency
`because of rapid constriction of the airway. Brain damage sets
`in quickly without oxygen.
`[0028] The triggers for these fatal reactions range from
`foods (nuts and shellfish), to insect stings (bees), to medica(cid:173)
`tion (radio contrasts and antibiotics). It is estimated that 1.3 to
`
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`13 million people in the United States are allergic to venom
`associated with insect bites; 27 million are allergic to antibi(cid:173)
`otics; and 5-8 million suffer food allergies. All of these indi(cid:173)
`viduals are at risk of anaphylactic shock from exposure to any
`of the foregoing allergens. In addition, anaphylactic shock
`can be brought on by exercise. Yet all are mediated by a series
`of hypersensitivity responses that result in uncontrollable
`airway occlusion driven by smooth muscle constriction, and
`dramatic hypotension that leads to shock. Cardiovascular
`failure, multiple organ ischemia, and asphyxiation are the
`most dangerous consequences of anaphylaxis.
`[0029] Anaphylactic shock requires advanced medical care
`immediately. Current emergency measures include rescue
`breathing; administration of epinephrine; and/or intubation if
`possible. Rescue breathing may be hindered by the closing
`airway but can help if the victim stops breathing on his own.
`Clinical treatment typically consists of antihistamines (which
`inhibit the effects of histamine at histamine receptors) which
`are usually not sufficient in anaphylaxis, and high doses of
`intravenous corticosteroids. Hypotension is treated with
`intravenous fluids and sometimes vasoconstrictor drugs. For
`bronchospasm, bronchodilator drugs such as salbutamol are
`employed.
`[0030] Given the common mediators of both asthmatic and
`anaphylactic bronchoconstriction, it is not surprising that
`asthma sufferers are at a particular risk for anaphylaxis. Still,
`estimates place the numbers of people who are susceptible to
`such responses at more than 40 million in the United States
`alone.
`[0031] Tragically, many of these patients are fully aware of
`the severity of their condition, and die while struggling in vain
`to manage the attack medically. Many of these incidents
`occur in hospitals or in ambulances, in the presence of highly
`trained medical personnel who are powerless to break the
`cycle of inflammation and bronchoconstriction (and life(cid:173)
`threatening hypotension in the