U.S. patent application number 13/688148 was filed with the patent office on 2013-04-18 for instrumented metered-dose inhaler and methods for predicting disease exacerbations.
This patent application is currently assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC.. The applicant listed for this patent is THE BRIGHAM AND WOMEN'S HOSPITAL, INC.. Invention is credited to Bruce D. Levy, Michael S. Singer.
Application Number | 20130092158 13/688148 |
Document ID | / |
Family ID | 39760303 |
Filed Date | 2013-04-18 |
United States Patent
Application |
20130092158 |
Kind Code |
A1 |
Levy; Bruce D. ; et
al. |
April 18, 2013 |
Instrumented Metered-Dose Inhaler and Methods for Predicting
Disease Exacerbations
Abstract
The present invention is directed to devices, systems, and
methods for monitoring inhaled drug usage to predict when an acute
attack or exacerbation of a disease, such as a respiratory disease,
is imminent. Instrumented inhalers that use modular designs with
standard components are disclosed, as are systems for monitoring
the instrumented inhalers. Also disclosed are methods for
determining whether or not a patient's inhaled drug usage pattern
indicates that an acute attack or disease exacerbation is imminent,
and notifying appropriate medical personnel of any usage patterns
indicative of an attack or disease exacerbation. If such an attack
or exacerbation is imminent, additional therapeutic agents may be
dispensed to the patient or other interventions made.
Inventors: |
Levy; Bruce D.; (West
Roxbury, MA) ; Singer; Michael S.; (Newton Centre,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE BRIGHAM AND WOMEN'S HOSPITAL, INC.; |
Boston |
MA |
US |
|
|
Assignee: |
THE BRIGHAM AND WOMEN'S HOSPITAL,
INC.
Boston
MA
|
Family ID: |
39760303 |
Appl. No.: |
13/688148 |
Filed: |
November 28, 2012 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12525540 |
Aug 1, 2009 |
8342172 |
|
|
PCT/US2008/052869 |
Feb 3, 2008 |
|
|
|
13688148 |
|
|
|
|
60899404 |
Feb 5, 2007 |
|
|
|
Current U.S.
Class: |
128/200.23 |
Current CPC
Class: |
A61M 2205/52 20130101;
A61M 15/008 20140204; G16H 20/10 20180101; A61M 2205/502 20130101;
A61M 11/04 20130101; A61M 2205/3306 20130101; A61M 2205/3592
20130101; A61M 15/009 20130101; A61M 2205/8206 20130101; G16H 50/20
20180101; A61M 15/0065 20130101; A61M 2205/3317 20130101; A61M
2205/3584 20130101; A61M 2205/3553 20130101; A61M 15/0028
20130101 |
Class at
Publication: |
128/200.23 |
International
Class: |
A61M 15/00 20060101
A61M015/00; A61M 11/04 20060101 A61M011/04 |
Goverment Interests
STATEMENT REGARDING FEDERALLY-FUNDED RESEARCH AND DEVELOPMENT
[0002] The United States Government may have a property interest in
this application by virtue of a research grant provided to the
inventors. The grant was provided by the Department of Defense and
is USAMRAA Grant No. DAMD17-02-2-0006.
Claims
1. A metered dose inhaler, comprising: a) an inhaler portion
including: i) a medication reservoir compartment constructed and
adapted to engage a medication canister; ii) a mouthpiece; iii) a
flow pathway opening into and connecting the medication reservoir
compartment and the mouthpiece so as to deliver a metered dose of a
medication from the medication reservoir compartment to the
mouthpiece when the inhaler portion is actuated to dispense a
metered dose of the medication; iv) a medication canister that fits
inside said medication reservoir compartment and acts as a movable
part such that when said medication canister is depressed, a dose
of drug is delivered into said flow pathway; v) a cap fitted to
said medication canister such that when said canister is depressed
to dispense a dose, the cap actuates a dose dispensing sensor
signaling that a dose has been dispensed; b) a wireless transmitter
connected to the dose-dispensing sensor, the wireless transmitter
being constructed and arranged to accept a signal from the
dose-dispensing sensor and transmit the signal to a remote station
thereby indicating that a dose has been dispensed.
2. The metered dose inhaler of claim 1, wherein said dose
dispensing sensor is an electrical switch.
3. The metered dose inhaler of claim 1, wherein said dose
dispensing sensor is in the form of a depressible button.
4. The metered dose inhaler of claim 1, wherein said canister
contains a supply of pressurized medication with a built-in
valve.
5. The metered dose inhaler of claim 1, wherein said canister
comprises a nozzle that, when said canister is present in said
medication reservoir compartment, bears against an opening into
said the flow pathway.
6. The metered dose inhaler of claim 5, wherein the wireless
transmitter is a cellular network wireless transmitter.
7. The metered dose inhaler of claim 1, further comprising a
microprocessor connected between the dose-dispensing sensor and the
wireless transmitter.
8. The metered dose inhaler of claim 7, wherein: a) the
microprocessor controls the wireless transmitter to transmit the
signal indicating that the dose has been dispensed at a
predetermined interval of time after the dose has been dispensed;
and b) the signal indicating that the dose has been dispensed
comprises the amount of the dose or number of times that the
inhaler portion was actuated, and the time that the dose was
dispensed.
9. The metered dose inhaler of claim 1, wherein said metered dose
inhaler communicates via a cellular telephone network and has a
telephone number associated with it.
10. The metered dose inhaler of claim 1, further comprising a
second, separate medication reservoir compartment.
11. A metered dose inhaler, comprising: a) a medication reservoir
compartment constructed and adapted to engage a medication
reservoir; b) a mouthpiece; c) a flow pathway opening to and
connecting the medication reservoir compartment and the mouthpiece
so as to deliver a metered dose of a medication from the medication
reservoir compartment to the mouthpiece when the inhaler is
actuated to dispense a metered dose of the medication; d) a
medication canister that fits inside said medication reservoir
compartment and acts as a movable part such that when said
medication canister is depressed, a dose of drug is delivered into
said flow pathway; e) a dose-dispensing sensor which is coupled to
said medication canister so as to be actuated when said medication
canister is depressed and, as a result, signal a wireless
transmitter; f) a wireless transmitter connected to the
dose-dispensing sensor, being constructed and arranged to accept a
signal from the dose-dispensing sensor and transmit a signal
indicating that a dose has been dispensed to a remote station.
12. The metered dose inhaler of claim 11, wherein said
dose-dispensing sensor is coupled to said medication canister by a
cap that is sized to accommodate the top end of the medication
canister.
13. The metered dose inhaler of claim 12, wherein said dose
dispensing sensor is an electrical switch.
14. The metered dose inhaler of claim 12, wherein said dose
dispensing sensor is in the form of a depressable button.
15. The metered dose inhaler of claim 11, wherein said medication
canister comprises a nozzle that, when said medication canister is
present in said medication reservoir compartment, bears against an
opening into said the flow pathway.
16. The metered dose inhaler of claim 15, wherein the wireless
transmitter is a cellular network wireless transmitter.
17. The metered dose inhaler of claim 11, further comprising a
microprocessor connected between the dose-dispensing sensor and the
wireless transmitter.
18. The metered dose inhaler of claim 17, wherein: a) the
microprocessor controls the wireless transmitter to transmit the
signal indicating that the dose has been dispensed at a
predetermined interval of time after the dose has been dispensed;
and b) the signal indicating that the dose has been dispensed
comprises the amount of the dose or number of times that the
inhaler portion was actuated, and the time that the dose was
dispensed.
19. The metered dose inhaler of claim 11, wherein said metered dose
inhaler communicates via a cellular telephone network and has a
telephone number associated with it.
20. The metered dose inhaler of claim 11, further comprising a
second, separate medication reservoir compartment.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. Ser. No.
12/525,540, which is U.S. national stage of international
application PCT/US2008/052869, filed Feb. 3, 2008, which claims the
benefit of U.S. Provisional Patent Application No. 60/899,404,
filed on Feb. 5, 2007.
FIELD OF THE INVENTION
[0003] The present invention is directed to a medical device for
monitoring the administration of drug to a patient by inhalation.
In addition, the invention includes systems and methods for
treating patients, particularly asthma patients, using remote
monitoring of drug usage to determine when an exacerbation is
imminent.
BACKGROUND OF THE INVENTION
[0004] Over twenty million Americans suffer from asthma or chronic
obstructive pulmonary disease (COPD). These diseases are
characterized by periods of relative normalcy punctuated by acute
attacks (exacerbations) that may be severe enough to require
hospitalization. Typically, an attack is preceded by a progressive
increase in a patient's use of "rescue" medication to alleviate
respiratory difficulties and a decrease in lung function, as
measured by peak expiratory flow rate. These changes usually occur
several days or weeks before an attack and can serve as a signal
for initiating preemptive treatment. Unfortunately, patients often
lack the time or resolve to keep accurate records of drug usage. As
a result, they may not become aware that their condition is
deteriorating until it is too late to prevent an attack requiring
urgent medical attention. Also, pediatric, elderly, or impaired
patients may lack the capacity for carefully monitoring changes in
drug use patterns.
[0005] Many different types of inhalation devices have been
developed and used by respiratory patients for delivering a
carefully controlled dosage of medication (see, e.g., U.S. Pat.
Nos. 6,223,746; and 6,532,955). Some of these devices have
microprocessors and sensors for counting the number of doses
administered (U.S. Pat. Nos. 6,138,669; and 5,593,390) or have
other adaptations to improve delivery characteristics (U.S. Pat.
No. 5,477,849). However, most continue to rely upon patients to
monitor their own drug use patterns.
[0006] To the extent that devices that can be used to detect and
monitor patient self-administration of inhaled drugs have been
described in the prior art (e.g., WO01/024690; U.S. Pat. No.
5,363,842), they are typically used to monitor patient compliance
with physician instructions, or to ensure that a patient receives
no more than a certain dose of a medication. Generally, there has
not been a focus on monitoring inhaled drug usage to recognize when
a patient's condition is likely to be deteriorating.
[0007] Moreover, in the existing devices, the mechanism for
detecting that a dose has been dispensed is usually within the
device, often in a position in which it can be easily fouled by
dirt or accumulated medication. The positioning of the detection
mechanism often makes the design of the devices relatively complex,
and increases the possibility of failure. Monitoring devices that
are more robust and more compatible with conventional types of
inhalers would be beneficial.
SUMMARY OF THE INVENTION
[0008] Aspects of the present invention provide devices, systems,
and methods for monitoring patient inhaled drug usage to predict
whether or not an acute attack or exacerbation of a chronic disease
or condition is imminent. As one example, the disclosed devices,
systems, and methods may be particularly useful in the treatment of
asthma.
[0009] One aspect of the invention provides an instrumented metered
dose inhaler with an inhaler portion and a sensor/transmitter
portion. The inhaler portion allows the patient to self-administer
an inhaled dose of a drug, such as a short-acting bronchodilator.
The sensor/transmitter portion, which is external to the inhaler
portion, registers that a dose has been dispensed and transmits
that information wirelessly to a remote station. In one embodiment,
the inhaler portion may be coupled to the sensor/transmitter
portion by a simple mechanical coupling. For example, in one
embodiment, a cap or lip may be fitted to the inhaler's medication
canister, such that when the medication canister is depressed to
dispense a dose, the cap or lip depresses and actuates an
electrical switch, thus indicating that a dose has been dispensed.
In some embodiments, the sensor/transmitter portion may be easily
added to a conventional inhaler, allowing existing inhalers to be
retrofit with instrumentation for monitoring.
[0010] Another aspect of the invention relates to a system for
predicting disease exacerbations based on inhaled drug usage
patterns. The system comprises one or more instrumented metered
dose inhalers described above and a monitoring system. The
monitoring system receives information regarding dispensed doses
from the one or more inhalers and associates that information with
patient records. Either or both of the inhalers and the monitoring
system may be adapted to analyze the information from the inhalers
to determine if any drug usage patterns indicate that an acute
attack or disease exacerbation is imminent.
[0011] Yet another aspect of the invention relates to methods for
predicting disease exacerbations based on inhaled drug usage
patterns. The methods involve collecting data on usage of a first
inhaled therapeutic agent by a patient essentially in real time as
doses of the first inhaled therapeutic agent are dispensed, for
example, using an instrumented metered-dose inhaler of the type
described above, analyzing the data, and notifying medical
personnel if any drug usage patterns indicate that an acute attack
or disease exacerbation is imminent. In some embodiments, a second
therapeutic agent or another form of intervention may be
administered if an acute attack or disease exacerbation is
imminent. The second therapeutic agent may be an inhaled
corticosteroid, an oral corticosteroid, a leukotriene modifier, a
long acting beta.sub.2 agonist or a methylxanthine.
[0012] Other aspects, features, and advantages of the invention
will be set forth in the description that follows.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The invention will be described with respect to the
following drawing figures, in which the same reference numerals
will refer to the same features throughout the figures, and in
which:
[0014] FIG. 1 is a perspective view of an instrumented metered-dose
inhaler according to one embodiment of the invention;
[0015] FIGS. 2-3 are front and side elevational views,
respectively, of the inhaler of FIG. 1;
[0016] FIG. 4 is a top plan view of the inhaler of FIG. 1, with the
medication canister disconnected and shown separately;
[0017] FIG. 5 is a side elevational view of the inhaler similar to
the view of FIG. 3, illustrating the actuation of the device to
dispense a dose of the drug;
[0018] FIG. 6 is a perspective view of an alternate embodiment of
the inhaler, in which the sensor/transmitter portion of the device
may be attached to a conventional inhaler;
[0019] FIG. 7 is an illustration of a system for monitoring patient
inhaled medication usage and disease progression according to
another embodiment of the invention;
[0020] FIG. 8 is an illustration of a method for detecting and
predicting disease exacerbations according to yet another
embodiment of the invention; and
[0021] FIG. 9 is an illustration of another method for detecting
and predicting disease exacerbations.
DETAILED DESCRIPTION OF THE INVENTION
[0022] FIG. 1 is a perspective view of an instrumented metered-dose
inhaler, generally indicated at 10, according to one embodiment of
the invention. The metered-dose inhaler 10 includes an inhaler
portion 12 and a sensor/transmitter portion 14.
[0023] For the purposes of the present application, the term
"metered dose inhaler" will include both inhalers that deliver a
liquid aerosol and dry powder inhalers. The illustrated inhaler 10
is configured for a liquid medication, such as albuterol, but other
embodiments of the inhaler 10 may be configured for other types and
sizes of inhalers.
[0024] The inhaler portion 12 of the illustrated embodiment is
essentially a standard, L-shaped inhaler with a medication
reservoir compartment 15 for a medication reservoir or canister 16,
and a mouthpiece 18 for inhalation. Between the compartment 15
housing the medication canister 16 and the mouthpiece 18 is a flow
pathway including a conventional flow chamber (not shown in the
figures) that disperses the medication and mixes it with air as it
is administered. FIG. 4 is a top plan view of the inhaler 10 with
the medication canister 16 removed from the compartment 15. The
opening 20 to the flow pathway is visible in FIG. 4.
[0025] In embodiments of the invention, the inhaler portion 12
typically has a movable part that moves between a dispensing
position, in which the inhaler portion 12 is actuated to dispense a
dose of medication, and a non-dispensing position, in which
medication does not flow from the medication reservoir compartment
15 to the mouthpiece 18. The movable part is typically biased
toward the non-dispensing position. The movement of the moveable
part may be linear, rotational, or of any other type. The movable
part is generally coupled to a valve or other structure that is
operable to release a flow of medication. In the illustrated
embodiment, the canister 16 acts as the movable part, although in
other embodiments of the invention, rods, levers, tabs, and hinged,
rotatable portions may all be used as moving parts.
[0026] The canister 16 is generally of a conventional type and
typically contains a supply of pressurized medication with a
built-in valve. The canister 16 is installed in its compartment 15
such that its nozzle 22 bears against the opening 20 to the flow
chamber. When the canister 16 is depressed downwardly, a dose of
the drug is aerosolized and propelled into the flow chamber, to be
inhaled by the patient through the mouthpiece 18. During the
process of dispensing a dose, air may be drawn into the inhaler
portion 12 and mixed with the medication in the conventional way.
Other embodiments of the invention may use other types of
medication reservoirs and other methods of dispensing doses.
[0027] Generally speaking, if the patient's underlying condition is
asthma, the medication will be a bronchodilator, typically a
short-acting beta.sub.2 agonist, such as albuterol; bitolterol
mesylate; levalbuterol; metaproterenol sulfate; pirbuterol acetate;
and terbutaline sulfate. As will be described below in more detail,
if it appears that a patient is approaching an acute attack, there
are several second drugs that may be given in an attempt to avert
it or reduce its severity. These include long acting beta.sub.2
agonists (e.g., salmeterol; formoterol; bambuterol); inhaled
corticosteroids (e.g., beclomethasone; budesonide; flunisolide;
fluticasone; triamcinolone); leukotriene modifiers (e.g.,
montelukast; zafirlukast; zileuton); oral corticosteroids (e.g.,
prednisolone; prednisone; methylprednisolone); methylxanthines
(e.g., theophyline); IgE inhibitors (e.g., omalizumab); cromolyn;
and nedocromil. These drugs have all been used or suggested for use
for asthmatics and dosages, duration of administration, and
potential side effects are well known in the art. They may be used
in any pharmaceutically acceptable form including any
pharmaceutically acceptable salt form. The same or different drugs
may be used for other conditions. Situations in which a second drug
may be used will be described below in more detail.
[0028] As was described above, the inhaler 10 also includes a
sensor/transmitter portion 14. As shown in FIGS. 1-4, the general
arrangement of the inhaler 10 is such that the inhaler portion 12
is nested within and surrounded by the sensor/transmitter portion
14. One purpose of the sensor/transmitter portion 14 is to sense
that a dose of medication has been dispensed and to communicate
that fact to a remote monitoring station.
[0029] Many of the components of the sensor/transmitter portion 14
are contained within a housing 24, which may be plastic, metal, or
some other durable material that protects the components from
damage. However, protruding from the housing 24 and positioned so
as to be adjacent but external to the inhaler portion 12 is a
dose-dispensing sensor 26. In the illustrated embodiment, the
dose-dispensing sensor 26 is essentially an electrical switch in
the form of a depressable button. When the dose-dispensing sensor
26 is actuated (i.e., depressed), it establishes an electrical
signal indicating that a dose of medication has been dispensed. The
basic switch design is well known in the art and is described fully
in US 20050172958 (see especially FIGS. 3A and 3B). In essence, the
depression of the actuator moves a contact rod to a position where
the switch is closed to allow current flow. After compression, the
contact rod springs back to its original position opening the
circuit and preventing current flow.
[0030] The canister 16 is coupled to the dose-dispensing sensor 26
of the illustrated embodiment by means of a cap or lip 28 that is
sized to accommodate the top end of the canister 16 and is
releasably secured thereto by means of one or more set screws 30.
The cap or lip 28 is of sufficient diameter to overhang the
canister 16. Thus, as the canister 16 is depressed, the cap or lip
28 pushes down on and actuates the dose-dispensing sensor 26. This
simple mechanical coupling between the canister 16 and the
dose-dispensing sensor 26 is robust and simple to use. However, in
other embodiments, the dispensing of a dose may be sensed by other
means, including magnetic sensors (e.g., Hall Effect sensors) and
optical sensors.
[0031] The position of the dose-dispensing sensor 26 and the simple
means by which it is coupled to the canister 16 to sense when a
dose has been dispensed may have certain advantages. For example,
an off-the-shelf standard inhaler may be used as the inhaler
portion 12 of the inhaler 10. Additionally, the dose-dispensing
sensor 26 is not within the flow pathway, where it might be fouled
by medication particles or droplets. Moreover, the relatively large
size of the components may make the sensor/transmitter portion 14
easier to assemble, maintain, and repair. Furthermore, in the event
that the sensor/transmitter portion 14 should fail, the arrangement
of the inhaler 10 is such that the patient may continue to dispense
medication as normal; thus, mechanical or electrical failure would
not prevent a patient from getting his or her medication.
[0032] Also within the housing 24 and connected or coupled to the
dose-dispensing sensor 26 is a wireless transmitter 32, which is
shown schematically in the view of FIG. 3. The purpose of the
wireless transmitter 32 is to transmit a signal indicating that a
dose of medication has been administered to a remote monitoring
station. (As will be explained below in more detail, that signal
may, and usually will, contain additional information as well.)
[0033] The wireless transmitter 32 may be any sort of wireless
transmitter known in the art, provided that it provides the
capability to transmit from any place that the patient is likely to
be. In the illustrated embodiment, the wireless transmitter 32 may
be a conventional GSM cellular network transceiver, with associated
components. In other embodiments, the wireless transmitter 32 may
be adapted to transmit using substantially any frequency band or
transmission protocols (e.g., CDMA, WiFi, WiMax, etc.).
[0034] The sensor/transmitter portion 14 may also include storage
(e.g., random access memory, read-only memory, flash memory), and a
central unit, such as a microprocessor, connected to the other
components. An input/output (I/O) controller and appropriate
connection ports may also be included in order to facilitate the
process of programming the inhaler 10 or communicating with it at
short range. Although not shown in the illustrated embodiment, the
sensor/transmitter portion 14 may also be provided with a display
screen, one or more indicator lights, or another means for
communicating its status to the user. Additionally, to the extent
desired, the sensor/transmitter portion 14 may also include one or
more user inputs. The components of the sensor/transmitter portion
14 may be directly connected to one another, or data may be shared
among the components using a data bus or another similar
arrangement. Generally, the sensor/transmitter portion 14 would be
powered by one or more batteries, space for which is provided in
the housing 24.
[0035] It will be realized that although a microprocessor is one
type of central unit that may be used in the sensor/transmitter
portion 14 of the inhaler 10, other types of devices may be used.
For example, some or all of the functions described here may be
implemented in an application-specific integrated circuit (ASIC).
In general, any type of device capable of performing the functions
described in the present application may be used.
[0036] As was noted above, the wireless transmitter 32, and many of
the other processing components of the sensor/transmitter portion
14, may be conventional components from a cellular telephone.
Cellular telephones, or, to use a more general term, embedded
devices, increasingly have the performance and capabilities of
general-purpose computers. For example, U.S. Patent Application
Publication No. 20060066731 illustrates a cellular
telephone/embedded device architecture with significant processing
power and most, if not all, of the functions of a general-purpose
computer. These sorts of components are readily available, well
known, and also provide the possibility for bidirectional
communication in some circumstances.
[0037] In a relatively simple embodiment, an electrical signal from
the dose-dispensing sensor 26 would be registered and recorded by
the microprocessor or other central unit. Since the inhaler 10 may
be actuated to dispense doses of medication several times in
succession, a transmission reporting the dose(s) would generally be
sent some predetermined amount of time after the last dose was
administered. For example, a transmission reporting the dose(s) may
be sent one minute after the last dose was dispensed. (In medical
terms, a "dose" of a drug may comprise more than one puff or
inhalation from an inhaler; however, the inhaler 10 would generally
report in terms of the number of times that puffs were dispensed,
even though a dose may properly comprise two or more puffs or
actuations. Those units may be later be converted.)
[0038] The transmission itself may have any format or be encoded
for transmission in any manner. Depending on the embodiment, the
microprocessor or other central unit may add additional information
to the transmission, such as the date and time the dose(s) were
dispensed, and state information about the inhaler 10, such as the
amount of battery power remaining
[0039] Moreover, the inhaler 10 need not transmit only immediately
after a dose has been administered. For example, in some
embodiments, it may be advantageous to program the inhaler 10 to
power up and transmit a signal once a day, or at some other
predetermined interval, to confirm that it is still active and
functional. In those embodiments, if an inhaler 10 fails to report
in at its designated intervals, the patient may be contacted to
determine what his or her situation is.
[0040] As those of skill in the art will realize, it is
advantageous to have some means by which to identify each
individual inhaler 10 if multiple inhalers 10 are in use within the
same system. There are several ways in which that may be
accomplished. In the illustrated embodiment, the inhaler 10
communicates via a standard cellular telephone network and
therefore has a telephone number associated with it. Thus, any
communication from the inhaler 10 will have a unique telephone
number associated with it. In addition or alternatively, the
microprocessor could add a unique identifier, such as a serial
number, to the outgoing data transmission.
[0041] The inhaler 10 may also store a local copy of the dose
administration information, and may be configured and adapted to
display that information, either using output devices (e.g., a
display screen or indicator lights) provided as a part of the
sensor/transmitter module 14 of the inhaler 10 or through an
external display or device. Moreover, should a transmission fail,
the information may be stored for later transmission when service
once again becomes available.
[0042] The precise amount of storage space and computing power
provided as a part of the inhaler 10 and its sensor/transmitter
portion 14 may depend, at least in part, on the precise functions
that the inhaler 10 is tasked to perform. The above describes a
relatively simple embodiment; however, in some embodiments, pattern
analysis, detection, and two-way communication tasks may be
performed in whole or in part by the inhaler 10.
[0043] The form of the inhaler may vary considerably from
embodiment to embodiment.
[0044] For example, in the inhaler 10, the sensor/transmitter
portion 14 is essentially permanently attached to the inhaler
portion 12. In other embodiments, that may not be the case. For
example, FIG. 6 is a perspective view of an inhaler 100 according
to another embodiment of the invention. The inhaler 100 is
substantially similar to the inhaler 10 of FIGS. 1-5, and those
parts not described in detail here may be assumed to be the same or
substantially the same; however, in the inhaler 100, the
sensor/transmitter portion 114 is releasably connected to the
inhaler portion 112 by way of semi-rigid plastic straps 116, such
that the sensor/transmitter portion 114 may be detached from the
inhaler portion 112. This embodiment may be particularly useful in
retrofitting existing inhalers with a sensor/transmitter portion
114.
[0045] In some embodiments, the inhaler 10, 100 may be constructed
and arranged to contain a second therapeutic agent, as described
above, to be dispensed to the patient under certain conditions,
particularly when a disease exacerbation is detected. That second
agent may be stored, for example, in a separate medication
reservoir for inhalation. If the second therapeutic agent is in
tablet or caplet form, it may be stored in a compartment in the
inhaler 10, 100. Depending on the embodiment, the patient may be
able to open that compartment at will, or it may open only in
response to a signal sent by a medical professional authorized to
dispense the drug. In further embodiments, the inhaler 10, 100 may
be programmed to dispense a mixed dose of two inhaled medications
depending on the patient's particular condition. Alternately, the
patient may simply be provided with instructions regarding how to
titrate or apportion the doses of the first and second therapeutic
agents. In the simplest embodiments, the patient may be provided
with another inhaler or other dispensing device for the second
therapeutic agent. That inhaler may or may not be an inhaler 10,
100 according to the present invention.
[0046] Instrumented metered-dose inhalers according to embodiments
of the present invention may be used simply to record when doses of
a medication are administered and to confirm that a patient is
complying with physician orders. However, such instrumented
metered-dose inhalers are most advantageously used not only to
perform those basic tasks, but also to predict, based on drug usage
patterns, when an acute attack or exacerbation is likely to
occur.
[0047] Studies show that increased use of short-acting inhaled
beta.sub.2 agonists among asthma patients is more common before an
exacerbation and before asthma-related death (Chan-Yeung, et al.,
Am. J. Respir. Crit. Care Med. 154: 889-93 (1996); Hessel, et al.,
Ann. Allergy Asthma Immunol 83:362-368 (1999); Cairns, Clin. Chest
Med. 27: 99-108 (2006)). Prospectively, albuterol use of greater
than 4 times a day was found to have a relative risk of 1.33 for an
exacerbation and nocturnal symptoms had a relative risk of 1.79
(Gibson, et al., Ann. Intern. Med. 123:488-492 (1995)). Thus, both
the amount of drug usage and the time of usage may be important
indicators of an impending exacerbation. Exacerbations usually
respond well to additional medication such as corticosteroids and,
if treatment is initiated early enough, it may be possible to avert
the attack or, at the least, reduce its severity. Unfortunately,
patients may not recognize warning signs either because drug usage
escalates gradually and they are preoccupied with other matters or,
in some cases, because their cognitive abilities are impaired,
e.g., due to age or illness.
[0048] Thus, aspects of the present invention provide systems and
methods for identifying exacerbation patterns--patterns of
medication use that would tend to indicate that a disease
exacerbation, or another other form of deterioration or
complication, is imminent--and notifying both a physician or other
medical professional and the patient. Additionally, as was noted
briefly above, systems and methods according to embodiments of the
invention may provide for bi-directional (i.e., two-way)
communication with the patient for diagnostic or interventional
purposes when exacerbations or complications occur.
[0049] FIG. 7 is a schematic illustration of a system, generally
indicated at 200, according to one embodiment of the invention. In
system 200, a plurality of inhalers 10 are shown, each presumably
belonging to a different patient. It should be understood that
although inhalers 10, 100 according to embodiments of the present
invention are shown as a part of system 200, other types of
instrumented inhalers may be used for at least some of the
functions and tasks described with respect to system 200. If the
inhalers that are used as part of system 200 have additional
features not found in the inhalers 10, 100 described here, those
features may be taken advantage of. For example, data from the
flowmeter of the inhaler disclosed in US 20050172958 may be taken
into account in determining whether or not an exacerbation pattern
exists.
[0050] Each of the inhalers 10, 100 communicates wirelessly with a
remote transceiver 202. In some embodiments, that remote
transceiver 202 may be a cell or base station in a cellular
telephone network.
[0051] The remote transceiver 202 is in communication with a
monitoring system 204. Although not shown in FIG. 7, the remote
transceiver 202 would generally be connected to a communications
network of its own, and may communicate with the monitoring system
204 indirectly through a number of intermediary systems and
elements. For example, traffic from the remote transceiver 202 may
pass through the proprietary network of a cellular communications
network and through a gateway to the Internet, through which it
reaches the monitoring system 204.
[0052] The monitoring system 204 itself is a system, or a plurality
of interconnected, interoperating systems, that are charged with
monitoring the transmissions from the inhalers 10, 100, performing
predictive analysis to determine when patients are experiencing
exacerbation patterns that might be indicative of forthcoming
exacerbations or complications, and distributing notifications
regarding patient status to the appropriate decisionmaking or
disease-management medical personnel. The monitoring system 204
also keeps the primary set of records associated with the system
200 and, for example, would usually be programmed with a database
that is capable of associating incoming traffic from particular
inhalers with patient information, including the patient's name,
physician or other attending medical professional, contact
information for the patient and relevant medical professionals,
pertinent medical history, name of the patient's preferred
pharmacy, and any other information deemed relevant. The database
may, for example, be indexed by the cellular telephone number of
the patient's inhaler 10, 100, or by some other kind of unique
identifier assigned to the patient or his or her inhaler 10,
100.
[0053] The monitoring system 204 communicates through a
communications network 206 to notification devices 210 associated
with the physicians or other medical professionals 208 attending
the patients. The notification devices 210 may be cellular
telephones, pagers, alphanumeric pagers, personal digital
assistants, smartphones, computers, or any other kind of device or
system capable of receiving notification messages directly or
indirectly from the monitoring system 204 and providing the medical
professionals 208 with those notifications. Depending on the
situation, particularly if there are relatively few inhalers 10,
100 to be monitored, one of the notification devices 210 could also
serve as the monitoring system 204.
[0054] The type of notification that is sent will depend on the
types of notification devices 210 that are in use, as well as the
preferences of the individuals using the system. As one example,
the monitoring system 204 may send e-mails to the attending
physicians, disease management nurses, or other responsible medical
professionals detailing the condition of each patient and whether
or not that patient is likely to be experiencing an exacerbation
pattern, either on a regular basis (e.g., daily), when a pattern
requiring immediate notification is detected, or both. This will be
described below in more detail.
[0055] In some embodiments, the monitoring system 204 may also be
used to convey messages or instructions back to the inhalers 10,
100 and the respective patients. For example, as was described
above, in some embodiments, the patient may be instructed to take a
second therapeutic agent to manage an exacerbation or avert an
impending exacerbation. Those instructions could come from or
through the monitoring system 204. Additionally, the monitoring
system 204 could, if the inhalers 10, 100 are appropriately
equipped with a display and input mechanism, send questionnaires or
other queries for the users to answer, in order to assess whether
or not the pattern detected by the monitoring system 204 is
corroborated by other signs or symptoms. For example, patients
could be asked to take an asthma questionnaire, in which case the
questions may be sent by the monitoring system 204 to the inhaler
10, 100 of the patient in question. Alternatively, appropriate
questionnaires and other contingency protocols and instructions may
be stored in the inhalers 10, 100 and activated by a communication
from the monitoring system 204.
[0056] In describing the elements and functions of system 200, it
may thus be said that the inhalers 10, 100 transmit their data to a
remote station, that data is processed, and appropriate
notifications are made if the patient's condition or pattern of
medication usage so warrants. However, the term "remote station" is
a general one, and may encompass any one of or all of the elements
202, 204, 210 that receive and process signals from the inhalers
10, 100. The precise nature of the elements that receive and
process signals from the inhalers 10, 100 may vary from embodiment
to embodiment; the illustration of FIG. 7 is but one example. Those
of skill in the art will also realize that although certain tasks
and capabilities have been ascribed to certain elements of system
200, as a practical matter, at least some functions of system 200
may be equally well performed by a number of elements in system
200. For example, some of the tasks ascribed to the monitoring
system 204, such as the detection of exacerbation patterns, may be
equally well performed by the inhalers 10, 100 themselves in some
embodiments.
[0057] As was noted above, one function of system 200 is to detect
exacerbation patterns. The description above points out two such
specific exacerbation patterns for albuterol: use greater than 4
times a day, and nocturnal use of the drug when the patient in
question would normally be sleeping. More generally, exacerbation
patterns may involve any or all of the following: increased
frequency of use (e.g., more actuations per 24 hour period or per
72 hour moving window); increased nocturnal frequency (e.g.,
between 10 PM and 6 AM) in a patient who would normally be
sleeping; and increased stacking of doses (e.g., more than two
successive actuations in less than 10 minutes). Additionally,
seasonal usage may be taken into account. For example, a patient's
usage on a weekly basis may be determined, seasons during which the
patient tends to experience exacerbations could be identified, and
interventions may be planned for the next season.
[0058] Although absolute thresholds may be used in determining
whether or not a particular patient is experiencing an exacerbation
pattern, it may be more advantageous to establish which usage
patterns qualify as exacerbation patterns for each individual
patient. That could be done, for example, by tracking the patient's
usage prior to a known exacerbation (e.g., an emergency room or
physician visit for acute treatment) and using that data to
establish what usage patterns qualify as exacerbation patterns. In
some embodiments, the inhalers 10, 100 may auto-calibrate (or be
calibrated by the monitoring system 204) for the patient's baseline
drug usage by averaging the patient's drug usage over a defined
period of time, and defining an exacerbation pattern to be any
pattern that deviates from the average by more than a certain
amount. As an example, an increase in the frequency of
administration of a short acting beta.sub.2 agonist of 20-100%
measured over a period of 3 to 10 days would generally be
considered an exacerbation pattern, and may also be grounds for
administering the second therapeutic agent, as described above.
[0059] The above gives a broad overview of the types of
exacerbation patterns that may be detected. However, not all
exacerbation patterns are necessarily equally well correlated to
disease exacerbations; some exacerbation patterns may be more
strongly indicative of an impending exacerbation, and some
exacerbation patterns may be indicative of a more severe
exacerbation. Systems and methods according to embodiments of the
present invention may take these differences into account.
[0060] FIGS. 8 and 9 are flow diagrams illustrating two similar
methods of detecting and predicting disease exacerbations according
to embodiments of the invention. Method 300 of FIG. 8 illustrates a
scenario in which the inhaler 10, 100 does not have significant
processing capabilities, and thus, does not perform any pattern
analysis tasks. Method 400 of FIG. 9 illustrates an opposite
scenario in which the inhaler 10, 100 does have significant
processing power. As those of skill in the art will realize,
methods 300 and 400 represent opposite ends of a spectrum, and
methods according to embodiments of the invention may apportion
functions or tasks to different components of the system in many
different ways. Moreover, both methods illustrate only routine
cycles of use; other calibration, reporting, and interactive tasks,
particularly those described above, may be included in the
methods.
[0061] Method 300 begins at 302 and continues with task 304, in
which the inhaler 10, 100 detects whether or not a dose of
medication has been administered. If a dose has been administered
(task 306: YES), method 300 continues with task 308; if a dose has
not been administered (task 306: NO), method 300 returns to task
304. The inhaler 10, 100 may remain in this loop for a long period
of time, and may be programmed to power down into a "standby" or
"sleep" mode accordingly, shutting down the transmitter or other
components until needed in order to conserve power.
[0062] When a dose has been administered (task 306: YES), the
inhaler 10, 100 powers up and transmits an appropriate report to
its remote station, as described above. Typically, that report
would reach the monitoring system 204, which would timestamp and
store the information in its database before proceeding with task
310, in which the patient's usage patterns are tracked and analyzed
to determine whether an exacerbation pattern exists.
[0063] In determining whether an exacerbation pattern exists, any
of the criteria or methods described above may be employed, and any
other medically reasonable criteria may also be employed. Other
criteria may be found in the literature. More generally, additional
guidance regarding patient monitoring and monitoring systems may be
found in Tovar et al. (Ann. Pharmacother. 38(1):126-133 (2004));
Marosi et al. (J. Asthma 38(8):681-690 (2001)); Martin et al. (J.
Allergy Clin. Immumol. 103(3 Pt. 1):535-536 (1999)) and, especially
US 20050172958.
[0064] Task 310 need not always be performed every time incoming
data is received. Rather, it may be delayed or performed on a
regular schedule (e.g., every 4-6 hours, every day, etc.). However,
the more often task 310 is performed, the more likely it is that an
exacerbation pattern will be detected quickly if present, and the
more likely it will be that the patient receives timely
intervention. Method 300 continues with task 312, a decision
task.
[0065] If no exacerbation pattern is detected (task 312: NO), the
monitoring system 204 may simply wait for the next packet of
incoming data from an inhaler 10, 100. In terms of FIG. 8, method
300 returns to task 304. If an exacerbation pattern is detected
(task 312: YES), method 300 continues with task 314, in which
appropriate notifications (e.g., by e-mail to a physician or
disease management nurse) are made.
[0066] As shown in FIG. 7, illustrating system 200, many inhalers
10, 100 may be in the field at any one time, and many may be in
communication with the monitoring system 204 at any one time. Thus,
method 300 may be executed may times concurrently or in parallel.
If method 300 is executed multiple times and several patients have
exacerbation patterns for which notifications are to be sent to the
same physician or other destination, the notifications may be
concatenated to the extent practicable. If multiple patients are
covered by a single notification, their situations may prioritized
so that the most serious or potentially serious condition is most
readily seen. Patients whose usage is normal may also be included
in the notifications, for the sake of completeness. For example, a
physician may receive an e-mail similar to the following:
TABLE-US-00001 PHYSICIAN: Jane Q. Doe, M. D. CONDITION PATIENT
REASON/COMMENT RED John Smith Usage up 50% in last 3 days ORANGE
Jane Jones Known seasonal problem YELLOW David James Administered
dose at 2:43 AM GREEN Larry Zeller Within normal limits
[0067] Although e-mail is given as one specific example of a mode
of notification, notifications may also be posted to a public or
private World Wide Web site, entered directly into an electronic
medical records system, or delivered in any other convenient
fashion. Additionally, a notification signal may be sent back to
the inhaler 10, 100, in order to notify the patient that a possible
problem has been detected. Method 300 terminates at task 316.
[0068] Method 400 of FIG. 9 is similar in many respects to method
300, and the description of method 300 above is thus applicable to
method 400 unless otherwise indicated. Method 400 begins at task
402 and continues with tasks 404 and 406, which are substantially
similar to tasks 304 and 306 of method 300.
[0069] However, in method 400, if a dose has been administered
(task 406: YES), method 400 continues with task 408, in which the
patient's usage pattern is analyzed. As was described above, in
method 400, the inhaler 10, 100 is assumed to have substantial
processing power, and thus performs at least some analysis tasks.
Task 408 of method 400 generally corresponds with task 310 of
method 300, although the inhaler 10, 100 may perform only a portion
of the "full" analysis, depending on its capabilities.
[0070] Following task 408, method 400 continues with task 410, a
decision task. In task 410, if an exacerbation pattern is detected
(task 410: YES), method 400 continues with task 412; if not (task
410: NO), method 400 may return to task 404. (It should be noted
that the inhaler 10, 100 will report that a dose has been
administered regardless of whether or not an exacerbation pattern
was detected in most embodiments. In those embodiments, it may be
desirable or advantageous to report that no exacerbation pattern
was detected in order to save time and processing power on the
monitoring system 204. However, in other embodiments, the
monitoring system 204 may confirm the results reached by the
inhaler 10, 100 regardless of the outcome of task 408.)
[0071] Tasks 412 is somewhat similar to task 308 of method 300; the
inhaler 10, 100 reports to the monitoring system 204. However, in
task 412, the inhaler 10, 100 may also report the results of any
analysis that was performed, in addition to the bare fact that a
dose was dispensed. Method 400 continues with task 414, which is
essentially the same task 314 of method 300, and terminates and
returns at task 416.
[0072] Any method according to an embodiment of the present
invention may be encapsulated in one or more sets of
machine-readable instructions that are interoperable with a machine
or machines to perform the tasks of the method. Machine-readable
media include magnetic and optical media, as well as FLASH drives,
read-only memory, and any other sort of machine-readable storage
medium known in the art.
[0073] As was described above, devices, systems, and methods
according to embodiments of the invention will be of particular use
to patients with respiratory diseases, such as asthma and chronic
obstructive pulmonary disease. However they may also be used for
patients with cystic fibrosis, non-cystic fibrosis bronchiectasis,
forms of interstitial lung disease, reactive airways disease,
occupational lung disease, congestive heart failure, and in
patients that have received a solid organ transplant or bone marrow
transplant.
[0074] All references cited herein are fully incorporated by
reference. Having now fully described the invention, it will be
understood by one of skill in the art that the invention may be
performed with a wide range of modifications and changes and under
a broad range of conditions, without affecting the spirit or scope
of the invention or any embodiment thereof.
* * * * *