Abstract:
An apparatus for inducing sputum samples for diagnosing pulmonary disorders, especially as it relates to detection of early stages of lung cancer. The apparatus is comprised of a pneumatic chest compression vest, a pneumatic pressure generator, and a mouthpiece connected to a nebulizer. Sputum samples are induced by applying an oscillating force to the chest via the pneumatic chest compression vest and pressure generator, while simultaneously providing an aerosolized solution (such as normal or hypertonic saline) via the nebulizer while the patient is standing. The sample is subsequently evaluated to ascertain a patient&#39;s risk of or the presence of a pulmonary disorder such as lung cancer.

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S)  
       [0001]    This application is a continuation of U.S. patent Application No. 09/387,312, filed Aug. 31, 1999 for “Method and Apparatus for Inducing Sputum Samples for Diagnostic Evaluation” by Nicholas P. Van Brunt and Donald J. Gagne. This application is related to U.S. patent application No.  09 / 387 , 319  for “Pneumatic Chest Compression Vest with Front Panel Bib” and U.S. Pat. Application No. 09/387,339 for “Chest Compression Vest with Connecting Belt”, which were filed on the same day, Aug. 31, 1999, and also assigned to American Biosystems, now doing business as Advanced Respiratory. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    The present invention relates to an apparatus and method for inducing sputum samples from a patient. In particular, the present invention relates to obtaining high quality sputum samples for diagnosing pulmonary disorders, especially lung cancer.  
           [0003]    Lung cancer has a survival rate of only 14% and is the leading cause of cancer death in the United States. The poor prognosis for lung cancer is related to both the lack of effective early detection methods, and the inability to precisely locate the diseased area of the lung to be treated. However, improved imaging techniques now allow much better tumor location capabilities, once detected, to allow specific treatment even at very early stages.  
           [0004]    A cooperative trial undertaken by Johns Hopkins Oncology Center, Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic utilized sputum induction as an early screening method to determine if a reduction in lung cancer deaths could be achieved. This study showed the resectability and survival rates among the study group were higher than among the control group, but the mortality rates were not reduced. This result led health policy groups to conclude that this type of screening method could not be justified.  
           [0005]    These findings discouraged further research using sputum cytology for early cancer detection. Recent findings in lung tumor biology research renewed interest in the use of noninvasive techniques for screening. Biomarkers which indicate phenotypic and genotypic abnormalities and track the transformation of bronchial epithelium into a malignant tumor have been found. Sputum samples are prime candidates for diagnosing cancer with biomarkers, because it is believed that exfoliated epithelial cells recovered in sputum samples may provide the earliest indicators of lung cancer. A number of molecular genetic techniques have provided evidence that biomarkers can be detected in sputum.  
           [0006]    Studies utilizing computer assisted, high-resolution image analysis have detected changes associated with cell transformation in normal appearing sputum samples, and also squamous cell carcinomas were detected in otherwise normal appearing epithelial cells. In addition, a number of monoclonal antibodies have been used to detect tumor-associated surface antigens on bronchial epithelial cells prior to the development of a pulmonary neoplasm. These types of studies strongly indicated that sputum cytology had the potential to improve the sensitivity, specificity, and predictive value for early diagnostic screening.  
           [0007]    The major flaw with these methods was that repeat samplings were required to ensure adequate samples for analysis which is costly and jeopardizes a timely diagnosis. Two methods have commonly been used to collect sputum. One method uses ultrasonic nebulizer treatments to provide a mild bronchial irritant which induces a cough and supplies moisture to facilitate mucus passage. The other method is an early morning cough technique to collect samples. Four independent studies were performed which utilized the two collection methods and tried to determine whether either or both would be adequate and, therefore, useful for early diagnostic screenings. The results, however, were inconclusive.  
           [0008]    Thus, a new method is needed to produce reliable samples while minimizing repeat sampling. This method could also be utilized to evaluate other pulmonary disorders and diseases such as asthma, chronic obstructive pulmonary disease (COPD), tuberculosis, Pneumocystis carinii pneumonia (PCP), inflammation, and infection by morphologic, immunochemical, fluorescence, molecular, or genetic techniques.  
           [0009]    A vest apparatus has been used by clinicians to facilitate mucus passage for patients with pulmonary disorders. The most widely used device is the ABI Vest Airway Clearance System by American Biosystems, the assignee of the present application. The apparatus compresses the chest at an alternating frequency faster than breathing which increases airflow velocity, creates cough-like shear forces, decreases the viscosity of mucus, and increases mucus mobilization. This apparatus, until now, has only been used therapeutically for patients with problems such as cystic fibrosis and asthma.  
         BRIEF SUMMARY OF THE INVENTION  
         [0010]    The invention discloses a method for inducing sputum from a patient, an apparatus for inducing and collecting those samples from the patient, and a method of evaluating patients for pulmonary disorders utilizing the sputum samples. The method of inducing the sputum sample includes applying an oscillating force to the chest of the patient while simultaneously providing the patient with a mouthpiece to maximize airflow velocity. In the preferred embodiment, the patient will be maintained in a standing position and also provided with a nebulizer that is connected via a port to the mouthpiece. The nebulizer produces an aerosolized solution, possibly a mild bronchial irritant, for the patient to inhale. In addition, the oscillating force is selected to maintain peak airflow velocities throughout the process.  
           [0011]    The method of screening patients for pulmonary disorders includes collecting a sputum sample which is induced by the oscillating force and the increased airflow velocity. The sample is subsequently analyzed and the patient is assessed as to the presence of or the risk of a pulmonary disorder, for example lung cancer. The apparatus for inducing the sputum sample from a patient includes a pneumatic chest compression vest and pneumatic pressure generator to provide the oscillating force to the chest of the patient, and a mouthpiece placed in the patient&#39;s mouth. In the preferred embodiment, a source of nebulized solution is coupled to the mouthpiece, and a support is also provided to maintain the patient in a standing position. In addition, the pneumatic chest compression vest is positioned and the parameters optimized in order to maintain peak airflow velocities. Intermittently during an approximate  12  minute treatment, the treatment is stopped, and the patient expectorates the induced sputum into sampling containers. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0012]    [0012]FIG. 1 is an illustration of a person using the preferred embodiment of the apparatus.  
         [0013]    [0013]FIG. 2 is an illustration of a person fitted with a chest compression apparatus.  
         [0014]    [0014]FIG. 3 is an illustration of a person with a mouthpiece coupled to a nebulizer for providing an aerosolized solution.  
         [0015]    [0015]FIG. 4 is an illustration of a person and a standing support.  
         [0016]    FIG. 5  is an illustration of a standing support. 
     
    
     DETAILED DESCRIPTION  
       [0017]    [0017]FIG. 1 is an illustration of person  10  undergoing treatment using the present process and apparatus. The apparatus includes pneumatic chest compression vest  12 , pneumatic pressure generator  14 , hoses  16 , mouthpiece  18  with nebulizer  20  and air supply tube  22 , and standing support  24 .  
         [0018]    Pneumatic chest compression vest  12  is worn around the upper torso of person  10 . Pneumatic pressure generator  14  is connected to pneumatic chest compression vest  12  by hoses  16 . Person  10  holds mouthpiece  18  in his or her mouth. Mouthpiece  18  is connected to nebulizer  20  which is supplied air by air supply tube  22  (which is connected to an air supply that is not shown). In a preferred embodiment, person  10  is kept in a standing position by standing support  24 .  
         [0019]    In operation, pneumatic pressure generator  14  maintains a positive pressure bias and delivers oscillated pneumatic pressure through hoses  16  to pneumatic chest compression vest  12 , which produces oscillating chest compressions on the chest of person  10 . Simultaneously, a mouthpiece is held in the mouth of person  10 . In a preferred embodiment, a solution, such as a mild bronchial irritant, contained in nebulizer  20  is inhaled by person  10 . Nebulizer  20  is connected to mouthpiece  18 . Mouthpiece  18  maintains the airways open to maximize airflow velocities and minimizes the amount of aerosolized solution lost in the air during treatment.  
         [0020]    The process and apparatus move the mucus, which contains exfoliated cells from the lungs, up the airway and force person  10  to cough during the treatment. The treatment is stopped, person  10  removes mouthpiece  18 , coughs, and collects sputum in a cup (not shown) that is provided. Treatment is then resumed. The sputum sample is subsequently evaluated as to risk of or the presence of pulmonary disorders such as lung cancer. The combination of mouthpiece  18  with nebulizer  20  and chest compressions while in a standing position provides an optimal method for obtaining quality sputum samples.  
         [0021]    [0021]FIG. 2 is an illustration of person  10  wearing pneumatic chest compression vest  12 . This illustration demonstrates how person  10  having torso T, rib cage R, and collar bones C, is fitted into pneumatic chest compression vest  12 . Pneumatic chest compression vest  12  is composed of an inelastic, flexible shell  30  (which has front panel section  32  and wrap-around belt section  34 ), flexible liner  36  (shown in phantom) attached to the inner surface of front panel section  32  to form a flexible air bladder, suspenders  38 , and air couplings  40 . A preferred embodiment of pneumatic chest compression vest  12  is described in detail in the previously mentioned related applications, which are incorporated by reference.  
         [0022]    Front panel section  32  is shaped to cover the person&#39;s chest from the bottom of rib cage R to near collar bones C, the region of the person&#39;s chest that encompasses the lungs. Front panel section  32  has central bib portion  32 A which is about 11.75 inches in height, but can range from about 9.0 inches to about 13.0 inches, and a pair of side portions  32 B and  32 C which are about 7.25 inches in height but can range from about 6.0 inches to about 9.0 inches. The width of front panel section  32  is about 21 inches. Side portions  32 B and  32 C allow front panel section  32  to extend under the person&#39;s arms. Preferably, these sections are made from 8 mil polycarbonate plastic which reduces stretching.  
         [0023]    Flexible liner  36  covers essentially all of the inner surface of front panel section  32  and is sealed around its edges to front panel section  32 . The flexible liner  36  is preferably made from  4  mil polyethylene. Together, front panel section  32  and flexible liner  36  define an air bladder which is inflated against the person&#39;s chest to apply compressive force to the chest and lungs. The compressions are focused on the region of the chest that encompasses the lungs, which effectively moves mucus from all lobes of the lungs. Air is supplied to the air bladder through a pair of ports in front panel section  32  into which air couplings  40  are inserted. Hoses  16  connect pneumatic pressure generator  14  to air couplings  40  and to the air bladder formed by front panel section  32  and flexible liner  36 .  
         [0024]    Belt section  34  is attached to side section  32 B of front panel  32  and is long enough to wrap around torso T of person  10  and extend across the other side section  32 C and bib section  32 A. Belt section  34  has a series of longitudinally spaced belt holes  42  extending along its length. As shown in FIG. 2, two of the belt holes  42  are aligned with the ports of front panel section  32  so that air couplings  40  are inserted into belt holes  42  and into the air ports. As a result, belt section  34  is held in place around torso T and is connected to bib section  32 A by air couplings  40 . Other belt holes  42  on belt section  34  are used for attachment of suspenders  38 .  
         [0025]    In one embodiment, belt section  34  has a height of about 7.25 inches and a length (in the horizontal direction) of about 42 inches. Belt holes  42  are about 1.4 inches in diameter and are spaced on about 2 inch centers. Depending on the circumference of the person&#39;s chest, belt section  34  will wrap around the chest so that different belt holes  42  will be aligned with the air ports of front panel section  32 . This allows pneumatic chest compression vest  12  to fit securely around person  10 .  
         [0026]    Pneumatic pressure generator  14  produces oscillatory pneumatic pressure and a positive pressure bias which is delivered through hoses  16  to the air bladder defined by front panel section  32  and liner  36 . In one embodiment, the oscillatory pneumatic pressure that is delivered to the air bladder is at a frequency of between about 5 and about 25 pressure cycles per second. The oscillatory frequency preferably ranges between about 12 and about 15 pressure cycles per second, with the preferred frequency being approximately the chest resonant frequency. The force created on the chest of person  10  compresses a bronchial airway slightly. The force on the mucus (F) is related to a diameter of the airway (d) by the following equation, F=1/d 4 . Therefore, even a slight narrowing of the airway, as caused by pneumatic chest compression vest  12 , causes the force on the mucus during the outflow portion of the oscillation to increase as the fourth power of the diameter reduction. During the inflow portion of the oscillation, the airway is not compressed, and therefore, the force on the mucus is less. This results in the mucus being pushed up and out of the airway more than it is pushed back down the airway.  
         [0027]    The positive pressure bias that is provided to pneumatic chest compression vest  12  is about 7 inches of water (0.25 P.S.I. or 13 mm IIg). The pressure compresses the chest to create an outward airflow bias which creates the force to move the mucus. The pressure setting and frequency of force are selected for a maximum airflow velocity of greater than about 50 ml/cycle while maintaining comfort. This, in turn, maximizes the force on the mucus to increase mobilization.  
         [0028]    Ideally, the treatment lasts for about 12 minutes but can last as long as about 20 minutes. A timer stops the treatment once it reaches about 12 minutes, but it can be restarted.  
         [0029]    The apparatus also includes mouthpiece  18  which is illustrated in FIG. 3. This illustration demonstrates how mouthpiece  18  is used and how nebulizer  20  is connected to it. FIG. 3 shows person  10  with mouth M, mouthpiece  18 , nebulizer  20 , nebulizer port  50 , and air supply tube  22 .  
         [0030]    The mouthpiece  18  extends into mouth M of person  10 . Nebulizer  20  is coupled to mouthpiece  18  via nebulizer port  50 . Nebulizer  20  is connected to an air supply via air supply tube  22 .  
         [0031]    In operation, the air supply provides a low airflow to nebulizer  20  through air supply tube  22 . The airflow aerosolizes a solution, such as a mild bronchial irritant like hypertonic saline, contained in nebulizer  20  and allows person  10  to inhale the solution. The solution provides moisture to facilitate mucus mobilization, and some solutions may also help induce a cough.  
         [0032]    Mouthpiece  18  extends about 1.5 inches into mouth M and holds open mouth M while depressing the tongue of person  10  to maximize airflow velocity. Preferably, mouthpiece  18  has an 8 inch long, 1 inch diameter extension outside mouth M beyond nebulizer  20 , which limits the amount of aerosolized solution lost to the room during treatment. In a preferred embodiment, mouthpiece  18  is PVC plastic and has a generally oval cross-section and is about 1.5 inches wide by about 0.6 inches high. This size permits an airflow velocity of about 90 ml/cycle during the treatment.  
         [0033]    In order to maximize inducement of sputum, person  10  should be kept in a standing position. FIG. 4 illustrates person  10  with feet F, legs L, and hands H using standing support  24 . This figure shows how person  10  is positioned on standing support  24 . As shown in FIGS. 4 and 5, standing support  24  includes seat  60 , telescoping support  62 , handlebars  64 , height adjustment means  66 , and platform  68 .  
         [0034]    Person  10  leans against seat  60 . Feet F of person  10  rest on platform  68 . Hands H of person  10  grip handlebars  64 . Seat  60  sits on top of and is connected to support  62 . Handlebars  64  are connected near the top of support  62 . Support  62  rests on top of and is connected to the center of platform  68 . Height adjustment means  66  is on support  62 , and permits telescoping adjustment of the height of support  62  and then locks support  62  at the adjusted height. Any known height adjustment structure, such as those commonly used to adjust chair heights, can be used.  
         [0035]    In operation, person  10  is positioned against standing support  24  as described above. Height adjustment means  66  is set so that legs L of person  10  are straight. This maintains person  10  comfortably in a standing position which is the most effective body position for the treatment, because it produces the highest airflow velocities.  
         [0036]    Once a sputum sample has been collected using the present method and apparatus, the sample is prepared for cytological evaluation, then analyzed and assessed. In one embodiment, a sample can be assessed as to a person&#39;s risk for lung cancer.  
         [0037]    The evaluation can also include other pulmonary disorders and diseases, such as asthma, COPD, tuberculosis, PCP, inflamation and infection, which can be diagnosed using morphologic, immunochemical, fluorescence, molecular, or genetic techniques.  
         [0038]    Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.