EP0105332A1

EP0105332A1 - Method and apparatus for the diagnosis of respiratory diseases and allergies

Info

Publication number: EP0105332A1
Application number: EP83901486A
Authority: EP
Inventors: Carl Peter Kremer, Jr.
Original assignee: Mallinckrodt Inc; Syntex USA LLC
Current assignee: Mallinckrodt Inc
Priority date: 1982-03-25
Filing date: 1983-03-22
Publication date: 1984-04-18
Also published as: GB8330116D0; SE8306464D0; IE54016B1; PT76434A; EP0105332A4; PT76434B; ATA901483A; ES520954A0; DE3338525T; AT396423B; IT8348001A0; JPS59500431A; SE8306464L; NL8320128A; SE449698B; IT1168853B; CH660118A5; WO1983003342A1; GB2128095B; AU561747B2

Abstract

Procédé et appareil consistent à enduire les voies respiratoires pulmonaires d'un patient, de façon sensiblement uniforme, avec une brume formée par aspiration d'un liquide. Les dimensions maximales des particules composant la brume sont limitées à environ 1,2 micron, les dimensions de la plupart des particules variant entre 0,056 micron et 1 micron, ce qui fait que la brume se comporte comme un gaz. Des conduites d'alimentation (21, 28, 29) permettent à un patient d'inspirer, pendant le processus normal de respiration, un mélange de brume et d'un gaz contenant de l'oxygène. Des soupapes (15, 17, 31) reliées aux conduites dévient la brume et le gaz expirés vers une voie d'évacuation. Si le liquide est étiquetté par radioactivité avant la production de la brume, le dépôt uniforme de la brume dans l'ensemble du poumon, sans une accumulation excessive dans les voies respiratoires principales et aux embranchements, permet d'obtenir un balayage des poumons avec des images à définition élevée.A method and an apparatus includes coating the pulmonary airways of a patient, substantially uniformly, with a mist formed by aspiration of a liquid. The maximum dimensions of the particles making up the mist are limited to approximately 1.2 microns, the dimensions of most particles varying between 0.056 microns and 1 micron, which means that the mist behaves like a gas. Supply lines (21, 28, 29) allow a patient to inhale, during the normal breathing process, a mixture of mist and an oxygen-containing gas. Valves (15, 17, 31) connected to the pipes divert the mist and the exhaled gas to an escape route. If the liquid is labeled by radioactivity before the production of the mist, the uniform deposition of the mist throughout the lung, without excessive accumulation in the main respiratory tract and at the branch lines, makes it possible to obtain a scan of the lungs with high definition images.

Description

Method and Apparatus for the Diagnosis of Respiratory Diseases and Allergies

Technical Field This invention relates to the diagnosis of respira¬ tory diseases and more specifically to a novel and im¬ proved method and apparatus utilizing an aerosolized radioactive isotope for ventilation of the lungs to en¬ able the production of multiple images of relatively high resolution and contrast to facilitate location of e boli, tumors and the like as well as other diseases affecting the respiratory tract without the danger of hyperdeposition and loss of image clarity.

Background Art Heretofore, diagnosis of respiratory diseases was principally effected by perfusion lung scans and venti¬ lation utilizing radioactive gases. The use of radio¬ active aerosols was also considered but it was found that with known systems excessive deposition or rainout occurred not only in the upper respiratory tract, the oral pharynx or the trachea but also at airway inter¬ sections. Moreover, uneven deposition of the mist was observed between the central and peripheral areas of the lung. Accordingly, when ventilation scans are deemed desirable, radioactive gases such as xenon and krypton are generally relied upon notwithstanding the relative¬ ly high cost entailed in producing the gas, patient in¬ convenience, extremely limited time in which to obtain even one image of the lung and the need for containment and disposition of the exhaled gas.

Disclosure of Invention

This invention overcomes the problems heretofore entailed in the diagnosis of lung diseases and provides a method and apparatus utilizing a radioactive mist which avoids the difficulties entailed with gases as well as the problems heretofore encountered with aero¬ sols. More specifically, it has been found that with the utilization of aerosols wherein the particle size is maintained below approximately 1.2 microns with by far the major portion of the particles being well below 1 micron, the mist behaves much the same as a gas and does not produce material rainout or hyperdeposition in the upper respiratory tract, pharynx or trachea. Moreover, there is substantially uniform deposition throughout the entire lung without accumulation at airway branching points and the patient can be in any position and is not required to hold his breath during the scanning opera- tion and ample time is available for multiple scans.

Furthermore, the isotope being in aerosol form can, upon being exhaled, be filtered out and safely stored until the radioactivity reaches a safe level for convenient disposition. Radioactive gases however cannot be fil- tered and great care is required for containment and storage, the latter requiring extended periods of time as compared to aerosols.

Another object of the invention resides in the pro¬ vision of a novel and improved method and apparatus for the diagnosis of lung diseases characterized by its sim¬ plicity, reliability, ease of operation and relatively low cost.

Still another object of the invention resides in the provision of novel and improved diagnostic apparatus which enables multiple photographic views of the lung to be recorded with little if any patient inconvenience. A still further object of the invention resides in the provision of a novel and improved method and appa¬ ratus for making image ventilation studies of the lung which affords greatly improved resolution and contrast. The invention utilizes a nebulizer wherein the maximum particle size is essentially limited to 1.2 ic- rons with a negligible quantity of particles larger than 1.2 microns. A unidirectional air inlet is coupled to the output of the nebulizer and the output is also cou¬ pled through a unidirectional flow valve and a T- or Y- connector to a mouthpiece or face mask through which the patient inhales the mist produced by the nebulizer. The third or discharge opening on the connector includes a unidirectional flow valve for the discharge of mist and air exhaled by the patient and a filter for the removal of the radioactive mist. The output from the filter is preferably fed to a suitable container for storage until the radioactivity decays to a safe level for disposal. Since the nebulizer is usually operated continuously by a compressed air supply, means are also provided at the output of the nebulizer to prevent the development of excess pressure during the exhaling periods.

The above and other objects and advantages of the invention will become more apparent from the following description and accompanying drawings forming part of this application.

Brief Description of Drawings

Figure 1 is a side elevational view in partially diagrammatic form of one embodiment of apparatus in accordance with the invention; and Figure 2.is. a side eleva.tional.vie -in partially diagrammatic form of a modification of the invention shown in Figure 1.

Best Mode for Carrying Out the Invention

While the desirability of utilizing radioactive aerosols or mists for the diagnosis of lung diseases had been suggested because of convenience and relatively low cost, the procedure has not heretofore been utilized be¬ cause of excessive deposition of the aerosols in large airways, posterior pharynx, trachea, stomach and the like. It was also generally considered that a satis- factory radioactive mist must merely not include parti¬ cles larger than 2 microns in mean mass aerodynamic di¬ ameter. With the invention now to be described, it has been found that particle sizes not only should not ex- ceed 1.2 microns but that the particles of the aerosol should be in the range of about .056 microns to about 1.2 microns with approximately 90% of the particles be¬ ing under 1 micron. Under these conditions, the aerosol behaves as a gas and the desired objectives can be achieved.

In preparation of the aerosol for the production of radioactive scans, either technetium-sulphur colloid or 99m technetiu -diethylene triamine penta- acetate functioned satisfactorily and have half lives of about 6 hours which provides adequate time for multi¬ ple image scans and yet a short enough half life to pro¬ vide for convenient disposal. Gases not only require the patient to hold his breath during an image scan which affords time for only a single scan but known satisfactory gases such as krypton has a half life of less than 30 seconds making it difficult to provide time for even the single scan and forms of tagged xenon have half lives of from 4 to 30 days making disposal diffi¬ cult. The radioactive technetium compounds referred to above are generally available in Nuclear Medicine De¬ partments for routine clinical diagnostic procedures and accordingly constitute a relatively inexpensive and available aerosol for the conduct of ventilation scans. Referring now to Figure 1 showing a partially dia- grammatic elevational view of one form of apparatus in accordance with the invention, the nebulizer is gener¬ ally denoted by the numeral 10 and includes a compressed gas inlet 11 and an outlet 12. The nebulizer may take any desired form though in the illustrated embodiment, the housing would include a suitable reservoir, an aspi¬ rator for producing the mist and the gas such as oxygen or air should be supplied at the rate of the order of 6 to 10 liters per minute. In the instant embodiment of the invention, a four-way connector generally denoted by the numeral 13 is coupled to the outlet 12 of the nebu¬ lizer 10 by the tubular leg 14. A unidirectional air inlet valve 15 is connected to a second tubular leg 16 of the four-way connector 13, a second unidirectional outlet valve 17 and particle filter 18 are connected to a third leg 19 of the four-way connector 13 and a fourth leg 20 of the connector 13 is connected to flexible tub- ing 21 having a bellows configuration for delivery of the aerosol to the patient. It is preferable to enclose the nebulizer 10 together with the four-way connector 13 within a container 22 formed of lead or other radiation shielding material since the nebulizer will contain a radioactive liquid.

The outlet end of the tubing 21 is connected to a third unidirectional valve 23 which may be contained within a second container 24 also formed of lead or other radiation shielding material. The outlet of the one-way valve 23 is coupled to one leg 25 of a Y- con¬ nector 26 disposed within the container 24 and the sec¬ ond leg 27 of the Y- connector is coupled to a flexible tube 28 similar to that of the tube 21. A mouthpiece 29 for the patient is secured to the end of the tube 28 so that the patient can conveniently inhale the mist generated by the nebulizer 10 together with air entering the one-way valve 15. While a simple mouthpiece 29 has been illustrated, a suitable facemask may replace the mouthpiece if so desired. The unidirectional flow valve 23 may take any desired form and may preferably be ad¬ justed to prevent flow during the presence of atmos¬ pheric pressure on the downstream side of the valve and provide for free flow when the downstream pressure is reduced during the time the patient is in the process of inhaling.

When utilizing aerosols for ventilation scans, the patient may inhale and exhale several times in order to be certain that the radioactive mist has been uniformly deposited throughout the entire lung. During the exhal¬ ing periods, the patient will exhale through the mouth¬ piece or face ask, as the case may be, and through the tube 28. Since the one-way valve 23 will prevent re¬ verse flow of mist, the exhaled aerosol will pass out¬ wardly through the leg 30 of the Y- connector 26, a one¬ way valve 31 and a filter 32 and the exhaled air and/or gas will be discharged through the tube 33. The filter 32 retains the aerosol exhaled by the patient and con¬ tains the filtered aerosol until the level of radio¬ activity has decreased to a safe level for convenient disposal. During the exhaling period, the valve 23 will remain closed and it is therefore desirable to prevent development of excessive pressure within the tube 21 caused by compressed air entering the inlet 11 of the nebulizer 10. For this purpose, the tubing 21., being in the form of a bellows, will tend to expand and thus limit the pressure. If desired, the one-way valve 17 may be utilized and adjusted to act as a relief valve to limit the maximum pressure in the tube 21. When the re¬ lief valve 17 is utilized, an aerosol filter 18 is pro¬ vided to filter out and contain the aerosol and the re¬ maining gas is discharged through the pipe 34. If de- sired, pipes 33 and 34 may be coupled together and fed to a holding container which will retain the gaseous material until the radioactivity has decreased to a level permitting normal disposal.

The nebulizer 10 may take any desired form pro- vided however that the aerosol particles generated thereby are within the ranges set forth above. One such nebulizer which will generate a mist meeting the requirements outlined above is illustrated and described in.United States Patent No. 4,116,387. Figure 2 illustrates a modified embodiment of the invention wherein a large particle trap is included in the event the specific nebulizer 10 utilized may have an excess number of large particles.

In the figures, like numerals have been used to de¬ note corresponding elements in each figure.

In Figure 2, it will be observed that the leg 20 extending from the four-way connector 13 is curved up¬ wardly and receives the vertical leg of an elbow 35 hav¬ ing a plurality of inclined baffles 36. The horizontal output leg of the elbow 35 is then coupled to the bel¬ lows-shaped tubing 21 for delivery of the mist to a patient.

The baffle arrangement contained within the. albow „ 35 provides a circuitous path for the mist with the re¬ sult that the larger particles which because of their greater mass will tend to collide with one of the baf- fles and be removed from the remainder of the aerosol. These larger particles upon reconversion to a liquid will automatically drain back into the nebulizer and enter the liquid reservoir therein. If desired, a sep¬ arate drain may be employed for returning this liquid directly to the reservoir or to an individual receiver. The method and apparatus for the production of lung scans utilizing an aerosol has been found to be exceedingly effective not only from the standpoint of reduced costs and convenience for the patient but vast- ly improved image scans have been obtainable which greatly facilitate diagnosis of precise difficulties in¬ volving the entire lung.

While the invention is particularly useful for the production of image scans of the lung, it is of course useful for medication of the lung in the treatment of disease. For instance, the method and apparatus would be useful for treatment of the lung with antimicrobials, antifungals, tagged anticancer drugs and the like. The method and apparatus is also useful for provocative al- lergy testing to determine the body reaction, for in¬ stance, to histamines and antigens such as ragweed and the like.

O While only certain embodiments of the invention have been illustrated and described, it is apparent that alterations, changes and modifications may be made without departing from the true scope and spirit there- of.

Claims

Cl ims

1. The method for diagnosing lung diseases comprising the steps of producing a mist by aspirating a radio- actively tagged liquid wherein the particles form- ing said mist do not exceed 1.2 microns in diameter with the major portion of the particles being with¬ in the general range of .056 microns to 1 micron, intermixing said mist with a gas containing oxygen and feeding said mixture to a patient for exclusive- ly inhaling and exhaling said mixture in the course of the natural breathing process, whereby said mist will substantially uniformly pervade the entire lung area and deposit substantially uniformly throughout all lung passageways and producing radioactive image scans of the lung.

2. The method according to claim 1 including the step of filtering out large particles from said mixture ^• after production of said mist.

3. The method according to claim 1 including the step of providing unidirectional flow of said mixture in the direction of said patient and conducting the ex¬ haled mixture through a second unidirectional path.

4. Apparatus for producing a mist to be inhaled by a patient and having gaseous properties to facilitate pervasion of the entire lung with substantially uni¬ form deposition throughout all the airways therein comprising means including an outlet for aspirating a liquid utilizing gas pressure to produce a mist having particles within the range of .056 microns . to 1.2 microns with the major portion of the parti¬ cles being less than 1 micron, a conduit including pressure limiting means connected at one end to said outlet, a unidirectional flow valve communicating

ith said conduit for the admission of ambient air, a second unidirectional flow valve connected to the other end of said conduit, a second conduit connect¬ ed to said second flow valve and terminating in an outlet to facilitate inhaling of the mist by the pa¬ tient, and a third unidirectional flow valve con¬ nected to said second conduit and arranged to per¬ mit flow in a direction opposite to said first and second valves whereby said patient upon inhaling will draw mist from said aspirating means and upon exhaling, the exhaled mist and gas will be dis¬ charged through said third flow valve.

5. Apparatus according to claim 4 including large par¬ ticle intercepting means interposed between the out- put of said aspirating means and said first conduit.

6. Apparatus according to claim 4 wherein said gas pressure is in the range of 6 to 10 liters per min¬ ute and said pressure limiting means comprises an undulating bellow-like wall on said first conduit.

7. Apparatus according to claim 4 wherein said pres¬ sure limiting means comprises a pressure relief valve communicating with the outlet of said aspi¬ rating means.

8. Apparatus according to claim 4 wherein said mist is radioactive and said third flow valve includes a filter for removal of the radioactive mist while permitting discharge of the gas such as air or oxy¬ gen combined with the mist.

9. .Apparatus according to claim 8 wherein said pres- sure limiting means comprises a pressure relief valve and a filter for the removal of the radio¬ active mist while permitting discharge of the gas such as air or oxygen combined with the mist.

10. The method of diagnosing diseases comprising the steps of producing a mist by aspirating a liquid capable of producing image scans involving the use of radioactivity wherein the particles forming said mist do not exceed 1.2 microns in diameter with the major portion of the particles being within the gen¬ eral range of .056 microns to 1 micron, intermixing said mist with a gas, feeding said mixture to a cavity within a patient whereby said mist will be uniformly distributed throughout said cavity and deposited on surfaces therein and producing image scans of said surfaces.

11. Apparatus for producing a mist to be inhaled by a patient and having gaseous properties to facilitate pervasion of the entire lung with substantially uni¬ form deposition throughout all the airways therein comprising means including an outlet for aspirating a liquid utilizing gas pressure to produce a mist having particles within the range of .056 microns to 1.2 microns with the major portion of the parti¬ cles being less than 1 micron, a conduit connected at one end to said outlet, a unidirectional flow valve communicating with said conduit .for.„the .admis- sion of ambient air, means coupled to said conduit to facilitate inhaling of the mist by the patient, and a second unidirectional flow valve connected to said conduit and arranged to permit flow in a direc¬ tion opposite to said first flow valve whereby said patient upon inhaling will draw mist from said aspi¬ rating means and upon exhaling, the exhaled mist and - gas will be discharged through said second flow valve.