WO2002055057A2 - Traitement de l'asthme et d'autres affections pulmonaires - Google Patents

Traitement de l'asthme et d'autres affections pulmonaires Download PDF

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Publication number
WO2002055057A2
WO2002055057A2 PCT/IE2002/000003 IE0200003W WO02055057A2 WO 2002055057 A2 WO2002055057 A2 WO 2002055057A2 IE 0200003 W IE0200003 W IE 0200003W WO 02055057 A2 WO02055057 A2 WO 02055057A2
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WO
WIPO (PCT)
Prior art keywords
air
water
humidified air
aerosol
humidified
Prior art date
Application number
PCT/IE2002/000003
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English (en)
Other versions
WO2002055057A3 (fr
Inventor
Conor Burke
Leonard W. Poulter
Original Assignee
Corcoran, Noel, M.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Corcoran, Noel, M. filed Critical Corcoran, Noel, M.
Priority to AU2002219473A priority Critical patent/AU2002219473A1/en
Publication of WO2002055057A2 publication Critical patent/WO2002055057A2/fr
Publication of WO2002055057A3 publication Critical patent/WO2002055057A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/083—Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/087—Measuring breath flow
    • A61B5/09—Measuring breath flow using an element rotated by the flow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/097—Devices for facilitating collection of breath or for directing breath into or through measuring devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/411—Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance

Definitions

  • the present invention relates to the treatment of diseases caused by airways inflammation; in particular asthma and Chronic Obstructive Pulmonary Disease; to methods of monitoring respiratory status in patients with such diseases; to devices for monitoring respiratory status and to devices for the prevention of and the treatment of acute respiratory distress.
  • the invention relates to methods and devices for use in acute asthma attacks.
  • the invention also relates to improved methods of and devices for air-conditioning in, for example, aircraft and buildings.
  • the diseases which can be treated or monitored by the invention include asthma, bronchitis, cigarette lung (bronchitis and emphysema), emphysema, cystic fibrosis, bronchiolitis and bronchiectasis.
  • Asthma is a disease characterised by intermittent airways obstruction. In western countries it affects 15% of the paediatric population and 7V ⁇ % of the adult population. It is caused by inflammation of the human airways and is associated with allergic reactions. Conventional treatment is by bronchodilators and anti-inflammatory drugs such as corticosteroids. Recent emphasis on the treatment of well asthmatics (i.e. those not in acute attacks) concentrates on the use of corticosteroids to prevent asthmatic attacks. Corticosteroids are also used as preventatives in other groups of patients with obstructive lung diseases such as those mentioned above, together with bronchodilators, oxygen and in the case of cystic fibrosis patients together with antibiotics.
  • Airway dehydration triggers bronchoconstriction in exercise, in virtually all patients with active asthma (1-5). Furthermore, eucapnic voluntary hyperventilation using dry air is similar to exercise and methacholine challenge in provoking bronchoconstriction in asthmatic subjects (6-9). More recently, epidemiological studies have demonstrated a high prevalence of asthma in Nordic skiers, who habitually inhale cold, dry air (10-11).
  • the present inventors have shown for the first time that there is a relationship between dehydration of the expired air, and bronchoconstriction in acute asthmatic subjects presenting to the emergency department.
  • the implication for this in the acute asthma setting is that asthmatics are worsening the bronchoconstriction with their tachypnoeic response, by drying their airways. This can be abolished by humidifying the inspired air, thus breaking this vicious cycle.
  • humidified air should be considered a simple, safe adjuvant to standard emergency room treatment of acute asthmatic subjects.
  • Humidified air, as a treatment for asthma has never been suggested in the medical literature.
  • It is a particular object to provide a portable device for the treatment or prevention of respiratory distress which can be carried by people suffering from airways diseases.
  • Many compounds are released by dehydrated epithelial cells and it is an object to prevent their release or to reverse the effects of an asthmatic stimulus to a cell.
  • Many compounds are released by dehydrated epithelial cells and it is an object to prevent their release or to reverse the effects of hypoosmality.
  • the humidified air is selected from an aerosol of water, water vapour or a mixture of the two.
  • the aerosol of water comprises droplets with a size in the range 0.1 to 30 microns in diameter, preferably 5 to 10 microns in diameter.
  • the humidified air is maintained at a temperature in the range 15°C to 100°C, preferably 20°C to 60°C , more preferably 35 °C to 39 °C, most preferably 37 °C.
  • the humidified air is fully saturated with water.
  • the weight (i.e. size) of the particle determines where it is deposited. Particles in the size range 1 to 30 microns in diameter are selectively deposited in the airways of the lung rather than in the mouth or in the alveloli; the airways being the site of the airways inflammation disease process.
  • the invention also provides a pharmaceutical composition comprising humidified air.
  • the humidified air is preferably fully saturated with water.
  • the humidified air is preferably selected from water vapour, an aerosol of water or a mixture of the two.
  • the aerosol of water comprises droplets in the size range 0.1 to 30 microns, preferably 5 to 10 microns in diameter.
  • the humidified air is preferably maintained at a temperature in the range 15°C to 100°C , preferably 20°C to 60°C , more preferably 35°C to 39°C , most preferably 37°C.
  • the pharmaceutical composition may further comprise one or more drugs selected from bronchodilators, anti-inflammatory drugs, decongestants, immune-modulators, antibiotics, cytokines or liposomes.
  • Such a pharmaceutical could allow the targeting of drugs in a focused therapy. It also has the advantage that freons are not necessary, as they are in many conventional nebulizers; there being moves in certain countries to ban the use of freons in nebulizers, on health and environmental grounds.
  • the invention relates to a method for treating acute respiratory distress comprising administering to the patient humidified air at a saturation level of at least 75%, more preferably at least 90% most preferably 100%.
  • the humidified air comprises an aerosol of water particles having a size in the range 0.1 to 30 microns in diameter, preferably 5 to 10 microns in diameter.
  • the humidified air is maintained at a temperature in the range 15 °C to 100°C, preferably 20°C to 60°C more preferably 35°C to 39°C, most preferably 37°C.
  • the invention provides a device for monitoring the relative humidity of expired air of a human subject comprising a collection means for collecting exhaled air from the subject , a means for measuring the humidity of the exhaled air and a means for displaying the humidity level of the exhaled air.
  • the collection means is adapted to collect the first 150mls of air exhaled by the subject, more preferably the device is adapted to discard the first 50mls of exhaled air and to collect the next lOOmls of air exhaled by the subject.
  • the collection means is provided with an in-line turbine to measure the flow-through of air and to activate shut-off valves to trap a defined volume of the exhaled air.
  • the object of the invention is to trap and analyse that airways air.
  • the device is adapted to measure the humidity of the air immediately it exits the mouth, or more preferably whilst still in the mouth. This is preferable because the humidity of the exhaled air will approximate to room conditions in a matter of seconds after exhalation.
  • the invention also provides a device for delivering humidified air to a human subject comprising a water reservoir, a means for forming humidified air from the water in the reservoir, a heating means for either heating the humidified air or the water in the reservoir to between 15 and 100°C and a mouthpiece adapted to deliver the humidified air to the subject.
  • the device is adapted to deliver fully saturated air at 15 to 100 °C.
  • the mouthpiece is provided with a non-return valve so that the subject can breath in humidified air and then exhale without interference to the flow or composition of the humidified air.
  • the means to heat the humidified air or the water in the reservoir comprises a powerpack and a heating element.
  • heated water from the water reservoir is fed by capillary action to a means to generate an aerosol.
  • the aerosol is fed to a breathing chamber for subsequent delivery to a mouthpiece.
  • the means to generate the aerosol may be selected from a jet nebulizer, an ultrasonic nebulizer or a vibrating disc nebulizer.
  • Figure 3 Panel A: Mean (SEM) FEN ! changes over time following a dry air tachypnoea challenge in asthmatic responders (filled squares), asthmatic nonresponders (open triangles), and control subjects (filled triangles).
  • Panel B Mean (SEM) relative humidity % changes over time following a dry air tachypnoea challenge in asthmatic responders (filled squares), asthmatic nonresponders (open triangles), and control subjects (filled triangles).
  • Panel C Mean (SEM) FEN X changes over time following a dry air tachypnoea challenge in asthmatic responders (filled squares), and in the same responder subjects following a humidified air tachypnoea challenge (open circles).
  • the Y-shaped circuit had inspiratory and expiratory limbs, and a subject connection with a dead space of 15mls.
  • the circuit had demand-flow, non-rebreathing performance characteristics. Dry air was fed into the system from a medical compressed air cylinder.
  • the subject connection was fitted with a differential pressure pneumotachograph, and a solid state mainstream infrared CO 2 sensor. The respiratory rate, end-tidal CO 2 , and tidal volume, were monitored continuously, and recorded at 30-second intervals by a CO 2 SMO+ respiratory profile monitor (Novametrics Medical Systems Inc.).
  • the dry air tachypnoea challenge caused a similar reduction in the humidity of the exhaled air from baseline values, in all groups (Fig. 3b).
  • the device comprises a mouth piece (1) into which the human subject blows.
  • the mouthpiece (1) is connected to a flow through chamber (2).
  • the flow-through chamber (2) is provided with an inline turbine (3) which measures the flow of air and activates a valve assembly (4) to trap a defined 100 mis of air.
  • the defined 100 mis of air is trapped in a collection means (5).
  • This chamber or collection means (5) is provided with a humidity monitor (6) which records the humidity and displays it on a display (7).
  • the flow-through chamber (2) is provided with an exhaust (8) to vent air other than the defined 100 mis which is exhaled by the patient.
  • a device for delivering humidified air to acute asthmatic patients is described in Figure 5.
  • the device comprises a water reservoir (11) which is provided with a heating element (12).
  • the water reservoir (11) is in communication with a breathing chamber (13).
  • a capillary tube (14) connects the water in the water reservoir (11) with the breathing chamber (13) and moves water by capillary action from the reservoir (11) into the breathing chamber (13).
  • the capillary tube (14) feeds the water to a oscillating washer or mesh (15) having a plurality of apertures.
  • the oscillation of the mesh (15) generates an aerosol of water particles.
  • the breathing chamber (13) is in communication with a mouth piece (16) for delivery of the aerosol to the mouth of a human subject.
  • the mouth piece (16) is provided with a suitable non-return valve (17) and an exit port (18) which allow exhaled air to exit the device. This allows humidified air to be breathed in and air to be exhaled normally.
  • the device is also provided with a power pack (17) to power the heating element (12) and the oscillating washer or mesh (15).
  • the aerosol can be generated in a number of ways. Conventional jet nebulizers blow a jet of air through the liquid to produce an aerosol. In ultrasonic nebulizers the ultrasonic vibration of a disk creates the aerosol. Alternatively the 5 aerosol can be generated by a dome-shaped metal plate with a plurality of holes, the plate being connected to an oscillator. When water is placed in contact with the moving plate, micro pumping action pours the liquid through the holes creating a fine particle aerosol.
  • the data demonstrates dehydration of expired air in patients with acute asthma in the emergency room.
  • airway air i.e. air mainly originating from the bronchi and bronchioles, the site of
  • asthmatics (20) is triggered by drying of the bronchial epithelium, due to airway water loss from the tracheobronchial tree, during the conditioning of large volumes of air (1-
  • the data demonstrates an increased respiratory rate, and increased minute volume in the asthma patients in the emergency room. This respiratory pattern is the most likely explanation for the dryer exhaled air in the asthma group.
  • the drier expirate of our asthmatic patients is not related to administration of oxygen, or any other therapy, as all our measurements were made prior to treatment.
  • the well preserved oxygen saturation of all our patients permitted the necessary measurements of respiratory rate, tidal volume, peak flow, and expiratory humidity, before treatment, without any risk to patients (see Methods). Since the control measurements were also made on patients in the emergency room at the same time, any factors such as anxiety relating to attendance in the emergency room do not explain the observed differences a novel in humidity between asthmatic and control subjects.
  • hypocapnia is a known bronchoconstrictor (28-30), by maintaining end-tidal CO 2 within normal limits without the confounding factor of CO 2 rebreathing in our subjects, we have effectively ruled out hypocapnia as contributing to the observed bronchoconstriction.
  • Humidification of the inspired air-oxygen mixture is not currently recommended in the guidelines for the treatment of acute asthma. Many patients receive some form of humidification such as bubble-through humidification of added oxygen at room temperature. This has limited effect on the overall humidity of the inspired mixture. For example, 40% oxygen in air, is made up of approximately three parts air to one part oxygen; therefore humidification of the oxygen alone, and only to room temperature, is of limited effect on the overall humidity of the inspired mixture. Full effective humidification, would require humidification of all inspired air and oxygen at 37°C. In summary, significant airway dehydration in acute asthma has been demonstrated. In addition, the laboratory results demonstrate the bronchoconstrictor potential of airway dehydration in clinically stable asthmatic subjects.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medical Informatics (AREA)
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  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
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  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Physiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Otolaryngology (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Vascular Medicine (AREA)
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Abstract

L'invention concerne un traitement amélioré destiné à des patients souffrant de maladies liées à une inflammation des voies respiratoires. Ce traitement peut être administré en salle d'urgence ou pendant le transport et comprend un produit pharmaceutique, destiné au traitement desdits patients, qui est sûr, peu coûteux, simple à administrer et qui permet d'humidifier de façon maximale les voies respiratoires ou les bronches des poumons. L'invention concerne en outre un procédé amélioré permettant de contrôler l'état de l'asthme chez des asthmatiques et de traiter des crises d'asthmes aiguës. L'invention concerne également un dispositif portable que des personnes souffrant de maladie du système respiratoire peuvent emporter à des fins de traitement ou de prévention de troubles respiratoires. Selon l'invention, un dispositif de distribution d'air humidifié à un sujet humain comprend un réservoir d'eau (11), un moyen permettant de produire de l'air humidifié (15) à partir de l'eau contenue dans le réservoir, un moyen de chauffage (12) permettant de chauffer l'air humidifié ou l'eau dans le réservoir, entre 15 et 100 °C, ainsi qu'un élément buccal conçu pour distribuer l'air humidifié au sujet (16).
PCT/IE2002/000003 2001-01-12 2002-01-11 Traitement de l'asthme et d'autres affections pulmonaires WO2002055057A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002219473A AU2002219473A1 (en) 2001-01-12 2002-01-11 Treatment of asthma and other lung conditions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IE20010026 2001-01-12
IE2001/0026 2001-01-12

Publications (2)

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WO2002055057A2 true WO2002055057A2 (fr) 2002-07-18
WO2002055057A3 WO2002055057A3 (fr) 2002-09-19

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009105445A1 (fr) * 2008-02-18 2009-08-27 Virginia Commonwealth University Délivrance efficace de nanoparticules et d’aérosols pharmaceutiques de taille micrométrique au poumon par croissance par condensation optimisée
EP2827773A4 (fr) * 2012-03-19 2015-11-11 Richard C Fuisz Procédé et système pour amplifier et mesurer des substances à analyser dans des gaz respiratoires

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4441505A (en) * 1982-01-11 1984-04-10 Kinetics Measurement Corp. Sensing device for human lung exhalation/inhalation air flow measurement
US4753245A (en) * 1985-03-26 1988-06-28 Icor Ab Apparatus for measuring the oxygen uptake of a person
FR2635674A1 (fr) * 1988-08-29 1990-03-02 Duwald Vincent Procede et dispositif de depistage de la ventilation pulmonaire
US5005582A (en) * 1990-06-28 1991-04-09 Vladimir Serikov Non-invasive method for measuring lung tissue volume and pulmonary blood flow and a probe to carry out the method
EP0650051A2 (fr) * 1993-10-25 1995-04-26 Kyoto Dai-ichi Kagaku Co., Ltd. Méthode pour la collection d'air expirés et collecteur automatique d'air expiré
US6126613A (en) * 1999-02-08 2000-10-03 Edwards; Raymond A. Device and method to measure inhalation and exhalation air flows

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4441505A (en) * 1982-01-11 1984-04-10 Kinetics Measurement Corp. Sensing device for human lung exhalation/inhalation air flow measurement
US4753245A (en) * 1985-03-26 1988-06-28 Icor Ab Apparatus for measuring the oxygen uptake of a person
FR2635674A1 (fr) * 1988-08-29 1990-03-02 Duwald Vincent Procede et dispositif de depistage de la ventilation pulmonaire
US5005582A (en) * 1990-06-28 1991-04-09 Vladimir Serikov Non-invasive method for measuring lung tissue volume and pulmonary blood flow and a probe to carry out the method
EP0650051A2 (fr) * 1993-10-25 1995-04-26 Kyoto Dai-ichi Kagaku Co., Ltd. Méthode pour la collection d'air expirés et collecteur automatique d'air expiré
US6126613A (en) * 1999-02-08 2000-10-03 Edwards; Raymond A. Device and method to measure inhalation and exhalation air flows

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009105445A1 (fr) * 2008-02-18 2009-08-27 Virginia Commonwealth University Délivrance efficace de nanoparticules et d’aérosols pharmaceutiques de taille micrométrique au poumon par croissance par condensation optimisée
US8479728B2 (en) 2008-02-18 2013-07-09 Virginia Commonwealth University Effective delivery of nanoparticles and micrometer-sized pharmaceutical aerosols to the lung through enhanced condensational growth
EP2827773A4 (fr) * 2012-03-19 2015-11-11 Richard C Fuisz Procédé et système pour amplifier et mesurer des substances à analyser dans des gaz respiratoires

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Publication number Publication date
AU2002219473A1 (en) 2002-07-24
WO2002055057A3 (fr) 2002-09-19

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