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The Treatment of Bronchiectasis
The Treatment of Bronchiectasis ARTHUR M. OLSEN O. THERON CLAGETT
'I'm] changes in the bronchi of patients with bronchiectasis are destructive and irreversible. The dilatations of the bronchi demonstrated by bronchography in cases of bronchiectasis are the result of injury to the elastic and muscular tissues of the bronchial wall. The important functions of bronchial contraction and ciliary activity are lost, and the patient's ability to cope with infected bronchial secretions is impaired. The surgical treatment of bronchiectasis is removal of the affected portions of the bronchial tree. This treatment must be reserved for patients whose disease process is so localized that excision of the involved bronchi can be accomplished without compromising pulmonary function. Medical treatment, on the other hand, is directed toward control and elimination of secondary infection, often present in ectatic bronchi. PROPHYLACTIC MEASURES
Much remains to be learned about the pathogenesis of bronchiectasis but this paper is not concerned with the controversial discussions of this problem. In the majority of cases bronchiectasis appears to have its origin in childhood. Aspirated foreign bodies, if neglected or overlooked, may result in serious suppurative disease. Also pneumonia or the pneumonitis accompanying acute infectious diseases of childhood may precede the development of bronchiectasis. Prompt recognition and early treatment of these conditions are most important. Bronchoscopy should always be considered for any pulmonary disease which does not resolve or respond rapidly to treatment. Primary tuberculosis with extensive mediastinal lymphadenopathy has been accused of causing bronchiectasis. Hence, antimicrobial therapy may well be indicated in such cases. Obviously, fever in the postoperative period after tonsillectomy or other surgical procedures on children should be investigated and pulmonary complications should be recognized and treated promptly. Bronchoscopy should be employed more liberally in the diagnosis and treatment of respiratory illnesses of children. 1019
1020
Arthur M. Olsen, O. Theron Clagett GENERAL MEASUHES
Good food, rest and clean air are essential to the patient with bronchiectasis. Of particular importance is avoidance of respiratory infections. Not only should individuals with bronchiectasis avoid exposure to acute upper respiratory infections but they also should stop work and go to bed during the early phases of any cold. Adequate humidification of the home and avoidance of respiratory irritants of all types are matters of great importance to these patients. A change to a warm, dry climate often seems beneficial to the patient but in many cases the benefits can be attributed to the decreased incidence of acute upper respiratory infection. Appropriate treatment for associated disease, such as sinusitis or asthma, may be most helpful. However, it is usually de<;irable to carry out surgical treatment for bronchiectasis rather than for sinusitis. Sinusi· tis often clears up after successful treatment for bronchiectasis. SURGICAL TREATMENT
Although some attempts had been made previously to treat bronchiectasis by various surgical procedures, the effective surgical treatment of bronchiectasis has developed largely during the last 20 years. Real progress in the surgical treatment of this lesion was not pOl:ll:lible until advances in anesthesia made operations within the open thorax feasible and safe from an anesthetic standpoint and until iodized oil provided a means of accurately determining the location and extent of bronchiectatic disease before operation. Improvements in surgical technique and in preoperative and postoperative care, the use of blood transfusions and the antibiotics have contributed greatly to the gratifying results that have been achieved in the surgical treatment of this disease. It seems that surgical resection of the involved portions of the lung il:l the treatment of choice for bronehiectasil:l when operation ean be carried out with reasonable risk and without too much 101:l1:l of pulmonary function. The greatest limiting factor to surgical treatment of bronehiectasil:l iH the not infrequent involvement of so much of the lung that it iH imp0l:lsible to remove all of the diseased tissue and still leave the patient with adequate respiratory capacity. Before any decision regarding surgical treatment of bronchiectasis il:l made, it is essential that bronchoscopic examination and complete bronchographic study be carried out. The importance of outlining every portion of the bronchial tree roentgenographically cannot be overestimated. It is disappointing to the patient and surgeon alike if investigation of persistent I:lymptoms after resection for bronchiectasis by further bronchograms discloses disease overlooked in previous bronchograms. Bronchiectasis occurs most commonly in the lower pulmonary lobel:l but any segment of any lobe or any combination of segments~ may. be involved, and the exact extent and location of the disease must be de-
'Treatment of Bronchiectasis
1021
termined in every case before operation is considered. The most favorable conditions for use of resection are those in which the disease is welllocalized to a single lobe or at least to a single lung. In selected cases in young individuals resection of portions of each lung can be performed. The maximal amount of pulmonary tissue that can be removed without compromising pulmonary function dangerously is one entire lung or portions of two lungs which do not equal more than one entire lung. In general it can be stated that any patient between the ages of 4 and 40 years (and occasionally an older patient, who has well-localized bronchiectasis and whose general condition will permit operation) should be considered a candidate for surgical resection of the lungs. Resection of the portions of lung involved in bronchiectasis can be performed more easily and safely in most cases if the patient is carefully prepared for operation. In our experience it is best to defer operation until 4 to 6 weeks after use of radiopaque oil is employed for roentgenologic studies of the bronehial tree. This interval permits fairly complete evaeuation of the radiopaque oil from the bronchial tree and also provides a period for preoperative preparation. During this period the patient should practice postural drainage of the bronchial tree religiously, and in many cases antibiotics should be administered either parenterally or by inhalation so that the tracheobronchial tree will be as free of infection and seeretion as possible at the time of operation. The surgical techniques presently employed for the treatment of bronchiectasis have developed by a process of evolution. For earlier resections a lung tourniquet was used around the hilus of the lobe to be removed and mass ligatures were applied to the bronchovascular stump. This technique resulted in a high incidenee of bronchopleural fistulas and postoperative empyema. The development of hilar dissection and individual ligation of hilar structures by Blades provided us with a much better surgical technique and its use has reduced the postoperative pleural complieations. The development of teehniques for resection of segments of lobes involved by bronchiectasis provided means of accurately removing all bronchieetatic disease without sacrificing any normal lung. Use of these new techniques has extended materially the scope of pulmonary resection in the treatment of bronchiectasis. With the surgical techniques now available, the risk of operations for bronchiectasis in properly selected cases is only 1 or 2 per cent. The operation does not result in thoracic deformity, and little pulmonary disability results if the disease is reasonably well localized. In suitable eases the surgical treatment of bronchiectasis permanently relieves the patient of the chronic productive cough, foul breath and suppuration that has made him chronically ill and a social outcast. MEDICAL MANAGEMENT
The medical treatment of bronchiectasis is palliative and is directed toward the secondary infection which causes· the symptoms usually
1022
Arthur M. Olsen, O.
Theror~
Clagett
present in this disease. The objectives of this medical program are twofold: (1) adequate endobronchial drainage of the secretions which constantly accumulate in the affected portion of the bronehial tree and (2) eradication of bacterial invader" by chemotherapy. Drainage
The elimination of retained bronchial secretions may be facilitated in several ways. Postural or gravity drainage is helpful in many cases and all patients should give this method a thorough trial. Some patients benefit by elevating the foot of the bed. Others mu"t practically stand on their heads to achieve any significant bronchial drainage. Deliberate and forceful coughing often aids bronchial drainage and must be encouraged, especially in children. Bronchieetatic secretions are commonly thick and viscid and, therefore, are hard to cough up. Thinning of these secretions may be accomplished by the oral administration of expectorants such aH iodides, ammonium chloride or guaiacol, or even by increaHing the patient's intake of fluid. Inhalation of steam may be particularly helpful to the patient with bronchiectasis who has contraeted an acute upper respiratory infection. Therapeutic aerosols likewise play a valuable role in liquefying bronchiectatic secretions. Saline solution, sterile water or other substances used as diluents for antibiotics may exert a loosening effect on thick secretions. Wetting agents, such as triton A-20 may be helpful when added to solutions prepared for inhalation therapy. More recently the inhalation of proteolytic enzymes has been advocated, and in certain instances the method seems to be effective in liquefying thick secretions. Trypsin aerosol, 125,000 units of trypsin dissolved in 3 cc. of buffered diluent, may be administered with a standard nebulizer. Not more than two treatments daily are suggested. Similarly a solution containing 25,000 units of streptokinase and 6,250 units of streptodornase (5 cc.) has been used. Use of antihistaminic agents prior to the inhalation of these enzymes is recommended. Even so, patients frequently experience toxic reactions, such as fever, chills, thoracic pain, bronchospasm and sore throat, after taking these preparations by inhalation. Bronchoscopic examination is of importance in the diagnosis of bronchiectasis and is particularly necessary to exclude the presence of obstructing lesions within the bronchial tree. However, frequent bronchoscopic aspirations and bronchial lavage have limited value in providing for drainage of the bronchial tree. The instillation of iodized oil into the bronchial tree in the hope of displacing purulent secretions has been advocated. Only rarely do patients consider the benefits worth while. The expelling of purulent secretions from the bronchial tree is highly desirable. There is probably a correlation between the retention of such secretions and the development of pulmonary osteoarthropathy. Much can be done to help the patient with his problem of bronchial drainage.
:g'reatment of Bronchiectasis
1023
JIowever, he must realize that the responsibility for getting rid of the secretions is his. Efficient elimination of secretions is especially difficult to attain in children. Chemotherapy
The bacterial flora in chronic bronchopulmonary suppuratives is diversified and constantly changing. Certain bacteria such as Neisseria catorrhalis and nonhemolytic streptococci, may be considered normal inhabitants of the bronchial tree or usual flora. Many bacteria may be cultured from purulent bronchial secretions, and when a sufficient number are present, some organisms arc significant pathogens. Among the gram-positive organisms the most important are pneumococci, hemolytic streptococci and staphylococci (Micrococcus pyogenes). Gram-negative bacteria are found frequently after treatment with penicillin and include Escherichia coli, Aerobacter aerogenes, Hemophilus influenzae, Klebsiella, pseudomonas aeruginosa (Bacillus pyocyaneus) and Proteus vulgaris. The detection of these bacteria is often of considerable assistance in directing antibiotic therapy in bronchiectasis. However, bacteriologic identification of significant organisms is frequently a difficult task. Unless a pathogenic organism is found in considerable numbers and on more than one occasion, it may be unwise to plan a treatment program solely on the basis of the findings on eulture of sputum. It is also our opinion that primary pulmonary moniliasis is extremely rare, and the finding of Candida albicans in cultures of sputum is unlikely to have any particular significance. After antibiotics have been used extensively in the treatment of bronchopulmonary disease, monilia arc commonly found in bronchial secretions. All of the available antibiotics have been used in the treatment of bronchiectasis. Theoretically, treatment should be guided by the findings on bacteriologic examination of bronchial secretions. However, in actual practice it has been our policy to use penicillin first and then plan further antibiotic therapy after evaluation of results of this treatment and subsequent bacteriologic studies. All methods of administering antibiotics have been used, including the oral and parenteral routes, the aerosol method and the intratracheal instillation of solutions of antibiotics. The aerosol method of administering antibiotics deserves some comment. This method has been described in many publications and many variations in technique are employed. The method should be kept as simple as possible. A standard nebulizer* capable of producing an aerosol with an average particle size of 1 to 2 microns is desirable. Compressed oxygen or an electric motor and air compressor is usually necessary to provide the positive pressure required to nebulize 1 or 2 cc. of solution several times daily. In general, it is best to dispense with the masks, re* Examples: The De Vilbiss no. 40 (The De Vilbiss Company, Somerset, Pennsylvania) or the Vaponefrin (Vaponefrin Company, Upper Darby, Pennsylvania).
1024
Arthur M. Olsen, O. 7'heron Clagett
breathing bags and special hoods, which have been devised for aerosol therapy. However, special techniques are desirable for infants and children who are unable to use the standard nebulizer efficiently. Special large volume nebulizers* and tents are now available for continuous vaporization of antibiotic solutions. Although therapeutic aerosols have their limitations, their use does have certain advantages of getting the antibiotic to the actual site of bronchial infection. Inhalation of antibiotic aerosols does produce a high concentration of drugs in the bronchial secretion. Also it aids in thinning out viscous secretion. The inhalation of micronized or "dust" preparations of certain antibiotics (penicillin and streptomycin) has been recommended. In general, these dusts are less efficacious than aerosols and are likely to produce more local reactions. Supraglottic administration of solutions of antibiotics is of limited usefulness in the treatment of bronchiectasis. This method usually requires application of a local anesthetic to the hypopharynx, larynx and trachea or at least intratracheal instillation of cocaine. Some degree of skill and experience on the part of the physician are required, and the cooperation of the patient is essential. When properly used, supraglottic instillation may be a valuable adjunct to other methods of treatment. As said before, penicillin has been the drug of choice in the treatment of bronchiectasis. However, very little success has been attained with the usual doses of preparations for oral administration. Huge doses of aqueous or procaine penicillin are required if significant concentrations of penicillin are to be obtained in the sputum. At present, penethamate hydrochloride, the diethyl-aminoethyl ester hydriodide of penicillin G (Neo-Penil) is being used parenterally in the treatment of suppurative pulmonary disease. High concentrations of penicillin have been reported in the sputum when 500,000 units is injected once or twice daily. However, Neo-Penil is capable of producing severe reactions, especially in children, and the preparation should be used carefully. Penicillin may be administered effectively as an aerosol for the treatment of bronchiectasis. Penicillin G may be dissolved in distilled water, sterile saline solution or a specially prepared solution containing a detergent. Fifty thousand units of penicillin per cubic centimeter of solution is a satisfactory concentration and 500,000 units or more can be nebulized daily by the patient who is beginning his therapy. As the bronchorrhea is brought under control, the frequency of treatment and total dosage can be reduced. Penicillin aerosol can be used almost indefinitely by the patient if no signs of sensitivity to penicillin appear. Supraglottic instillations of penicillin solutions are sometimes used to replace or supplement aerosol treatment with penicillin. The same
* The
Mist-o-gen (Production Foundry Co., Oakland, California).
Treatment of Bronchiectasis
1025
preparation and concentration of penicillin is suitable and 10 cc. may be instilled as a single daily treatment. To be effective the patient must be able to retain the solution for 30 minutes or more. Streptomycin or dihydrostreptomycin may be administered alone or ill combination with penicillin as an aerosol or by supraglottic instillation. A concentration of 200 mg. per cubic centimeter of solution is suggested. The use of streptomycin is reserved for individuals whose response to penicillin is not satisfactory or whose sputum cultures reveal large numhers of gram-negative bacteria. It has been our policy to use streptomycin as an adjunct to penicillin therapy and for limited periods only. Gramnegative bacteria quickly become resistant to streptomycin and its usefulness is limited. The broad-spectrum antibiotics have been given almost exclusively by mouth and they may be effective in eradicating bronchial infection and reducing the volume of sputum. Tetracycline hydrochloride may be ~iven in a dosage of 0.25 grams every 6 hours for 4 or 5 days at a time. A satisfactory preparation of oxytetracycline for aerosol administration i:i available but it is not as well tolerated as penicillin. Other antibiotics have limited usefulness in the treatment of bronchiectasis. Erythromycin and carbomycin have no advantage over penicillin. Neomycin and polymyxin B are used only in dire circumstances because of their toxicity. LIMITATIONS OF MEDICAL MANAGEMENT
As previously stated medical treatment is directed toward the conrol of the secondary infection associated with bronchiectasis and its ever changing bacterial flora. Thus, we are treating a complication rather than the disease itself. As far as chemotherapy is concerned, we not only must use antibiotics which are effective against the bacteria present but also must get the drug to the infection. In cases of chronic bronchiectasis with much pulmonary fibrosis and poor blood supply, it is indeed difficult to combat the infection. Antibiotics have greatly altered the prognosis in eases of bronchiectasis in which surgical procedures cannot be used. However, the effectiveness of drug therapy is limited by sensitivity to the drugs or the toxic effects of the drugs on one hand and by the development of resistant bacteria on the other. It has been estimated that 1 or 2 per cent of individuals become allergic to penicillin. It should be noted that pneumococci and hemolytic streptococci rarely become resistant to penicillin. However, 60 to 70 per cent of all strains of Staphylococcus aureus (Micrococcus pyogenes) are already resistant to penicillin. Emergence of gram-negative bacteria which are resistant to streptomycin occurs frequently after prolonged therapy. The gastrointestinal complications of use of broad-spectrum antibiotics are well known and certainly limit the usefulness of these drugs t
1026
Arthur M. Olscn, O. Thcron Clagctt
in the management of bronchiectasis. Of greater importance is the emergence of resistant bacteria in cultures of bronchial secretions. Many strains of Micrococcus pyogenes are resistant before therapy is even attempted. Proteus vulgaris and Pseudomonas aeruginosa are frequently isolated in the sputum cultures of patients who have had much treatment with tetracycline derivative::;. The destruetion of the sensitive bacteria then seems to predispose to the luxuriant growth of these resistant bacteria. Staphylococcic enterocolitis has been reported, and Barach, Bickerman and Beck have recently reported fatalities in debilitated individuals treated intensively with broad-spectrum antibiotics with emergence of resistant bacteria. Hence, we advise that the use of broadspectrum antibiotics be limited to 4 or 5 days out of each month or for the preoperative preparation of patients. SUMMARY
Surgical excision is the treatment of choice for bronchiectasis. Unfortunately, many patients have disease which is so diffuse that surgical procedures cannot be considered. Medical management is palliative and is direeted toward drainage of the affected region and eradication of infection by chemotherapy. Penicillin continues to be our most valuable drug and is most effeetively administered as an aerosol. Aerosols which contain wetting agents or possibly proteolytic enzymes may likewise aid in the problem::; of bronchopulmonary drainage. The value of antibiotic therapy of infeetion in bronchiectasis is limited by the toxic effects of the drugs and by the emergence of resistant bacteria. The problems of bacterial resistance are of particular importance when broad -spectrum antibiotics are used. Their continued use tends to favor the emergence of bacteria resistant to all clinically useful antibiotics. Hence, they should be used for short period::;. Despite the limitations of antibiotic therapy, the outlook in eases of bronchiectasis has been considerably improved. The patient is usually able to control those symptoms which would make him socially undesirable and chronically ill. REFERENCES 1. Barach, A. L., Bickerman, H. A. and Beck, G. J.: Antibiotic Therapy in Infections of the Respiratory Tract. Arch. Int. Med. 90: 808-849 (Dec.) 1952. 2. Blades, Brian: Individual Ligation Technique for Lower Lobe Lobectomy. J. Thoracic Surg. 10: 84-98 (Oct.) 1940.
'I'm] changes in the bronchi of patients with bronchiectasis are destructive and irreversible. The dilatations of the bronchi demonstrated by bronchography in cases of bronchiectasis are the result of injury to the elastic and muscular tissues of the bronchial wall. The important functions of bronchial contraction and ciliary activity are lost, and the patient's ability to cope with infected bronchial secretions is impaired. The surgical treatment of bronchiectasis is removal of the affected portions of the bronchial tree. This treatment must be reserved for patients whose disease process is so localized that excision of the involved bronchi can be accomplished without compromising pulmonary function. Medical treatment, on the other hand, is directed toward control and elimination of secondary infection, often present in ectatic bronchi. PROPHYLACTIC MEASURES
Much remains to be learned about the pathogenesis of bronchiectasis but this paper is not concerned with the controversial discussions of this problem. In the majority of cases bronchiectasis appears to have its origin in childhood. Aspirated foreign bodies, if neglected or overlooked, may result in serious suppurative disease. Also pneumonia or the pneumonitis accompanying acute infectious diseases of childhood may precede the development of bronchiectasis. Prompt recognition and early treatment of these conditions are most important. Bronchoscopy should always be considered for any pulmonary disease which does not resolve or respond rapidly to treatment. Primary tuberculosis with extensive mediastinal lymphadenopathy has been accused of causing bronchiectasis. Hence, antimicrobial therapy may well be indicated in such cases. Obviously, fever in the postoperative period after tonsillectomy or other surgical procedures on children should be investigated and pulmonary complications should be recognized and treated promptly. Bronchoscopy should be employed more liberally in the diagnosis and treatment of respiratory illnesses of children. 1019
1020
Arthur M. Olsen, O. Theron Clagett GENERAL MEASUHES
Good food, rest and clean air are essential to the patient with bronchiectasis. Of particular importance is avoidance of respiratory infections. Not only should individuals with bronchiectasis avoid exposure to acute upper respiratory infections but they also should stop work and go to bed during the early phases of any cold. Adequate humidification of the home and avoidance of respiratory irritants of all types are matters of great importance to these patients. A change to a warm, dry climate often seems beneficial to the patient but in many cases the benefits can be attributed to the decreased incidence of acute upper respiratory infection. Appropriate treatment for associated disease, such as sinusitis or asthma, may be most helpful. However, it is usually de<;irable to carry out surgical treatment for bronchiectasis rather than for sinusitis. Sinusi· tis often clears up after successful treatment for bronchiectasis. SURGICAL TREATMENT
Although some attempts had been made previously to treat bronchiectasis by various surgical procedures, the effective surgical treatment of bronchiectasis has developed largely during the last 20 years. Real progress in the surgical treatment of this lesion was not pOl:ll:lible until advances in anesthesia made operations within the open thorax feasible and safe from an anesthetic standpoint and until iodized oil provided a means of accurately determining the location and extent of bronchiectatic disease before operation. Improvements in surgical technique and in preoperative and postoperative care, the use of blood transfusions and the antibiotics have contributed greatly to the gratifying results that have been achieved in the surgical treatment of this disease. It seems that surgical resection of the involved portions of the lung il:l the treatment of choice for bronehiectasil:l when operation ean be carried out with reasonable risk and without too much 101:l1:l of pulmonary function. The greatest limiting factor to surgical treatment of bronehiectasil:l iH the not infrequent involvement of so much of the lung that it iH imp0l:lsible to remove all of the diseased tissue and still leave the patient with adequate respiratory capacity. Before any decision regarding surgical treatment of bronchiectasis il:l made, it is essential that bronchoscopic examination and complete bronchographic study be carried out. The importance of outlining every portion of the bronchial tree roentgenographically cannot be overestimated. It is disappointing to the patient and surgeon alike if investigation of persistent I:lymptoms after resection for bronchiectasis by further bronchograms discloses disease overlooked in previous bronchograms. Bronchiectasis occurs most commonly in the lower pulmonary lobel:l but any segment of any lobe or any combination of segments~ may. be involved, and the exact extent and location of the disease must be de-
'Treatment of Bronchiectasis
1021
termined in every case before operation is considered. The most favorable conditions for use of resection are those in which the disease is welllocalized to a single lobe or at least to a single lung. In selected cases in young individuals resection of portions of each lung can be performed. The maximal amount of pulmonary tissue that can be removed without compromising pulmonary function dangerously is one entire lung or portions of two lungs which do not equal more than one entire lung. In general it can be stated that any patient between the ages of 4 and 40 years (and occasionally an older patient, who has well-localized bronchiectasis and whose general condition will permit operation) should be considered a candidate for surgical resection of the lungs. Resection of the portions of lung involved in bronchiectasis can be performed more easily and safely in most cases if the patient is carefully prepared for operation. In our experience it is best to defer operation until 4 to 6 weeks after use of radiopaque oil is employed for roentgenologic studies of the bronehial tree. This interval permits fairly complete evaeuation of the radiopaque oil from the bronchial tree and also provides a period for preoperative preparation. During this period the patient should practice postural drainage of the bronchial tree religiously, and in many cases antibiotics should be administered either parenterally or by inhalation so that the tracheobronchial tree will be as free of infection and seeretion as possible at the time of operation. The surgical techniques presently employed for the treatment of bronchiectasis have developed by a process of evolution. For earlier resections a lung tourniquet was used around the hilus of the lobe to be removed and mass ligatures were applied to the bronchovascular stump. This technique resulted in a high incidenee of bronchopleural fistulas and postoperative empyema. The development of hilar dissection and individual ligation of hilar structures by Blades provided us with a much better surgical technique and its use has reduced the postoperative pleural complieations. The development of teehniques for resection of segments of lobes involved by bronchiectasis provided means of accurately removing all bronchieetatic disease without sacrificing any normal lung. Use of these new techniques has extended materially the scope of pulmonary resection in the treatment of bronchiectasis. With the surgical techniques now available, the risk of operations for bronchiectasis in properly selected cases is only 1 or 2 per cent. The operation does not result in thoracic deformity, and little pulmonary disability results if the disease is reasonably well localized. In suitable eases the surgical treatment of bronchiectasis permanently relieves the patient of the chronic productive cough, foul breath and suppuration that has made him chronically ill and a social outcast. MEDICAL MANAGEMENT
The medical treatment of bronchiectasis is palliative and is directed toward the secondary infection which causes· the symptoms usually
1022
Arthur M. Olsen, O.
Theror~
Clagett
present in this disease. The objectives of this medical program are twofold: (1) adequate endobronchial drainage of the secretions which constantly accumulate in the affected portion of the bronehial tree and (2) eradication of bacterial invader" by chemotherapy. Drainage
The elimination of retained bronchial secretions may be facilitated in several ways. Postural or gravity drainage is helpful in many cases and all patients should give this method a thorough trial. Some patients benefit by elevating the foot of the bed. Others mu"t practically stand on their heads to achieve any significant bronchial drainage. Deliberate and forceful coughing often aids bronchial drainage and must be encouraged, especially in children. Bronchieetatic secretions are commonly thick and viscid and, therefore, are hard to cough up. Thinning of these secretions may be accomplished by the oral administration of expectorants such aH iodides, ammonium chloride or guaiacol, or even by increaHing the patient's intake of fluid. Inhalation of steam may be particularly helpful to the patient with bronchiectasis who has contraeted an acute upper respiratory infection. Therapeutic aerosols likewise play a valuable role in liquefying bronchiectatic secretions. Saline solution, sterile water or other substances used as diluents for antibiotics may exert a loosening effect on thick secretions. Wetting agents, such as triton A-20 may be helpful when added to solutions prepared for inhalation therapy. More recently the inhalation of proteolytic enzymes has been advocated, and in certain instances the method seems to be effective in liquefying thick secretions. Trypsin aerosol, 125,000 units of trypsin dissolved in 3 cc. of buffered diluent, may be administered with a standard nebulizer. Not more than two treatments daily are suggested. Similarly a solution containing 25,000 units of streptokinase and 6,250 units of streptodornase (5 cc.) has been used. Use of antihistaminic agents prior to the inhalation of these enzymes is recommended. Even so, patients frequently experience toxic reactions, such as fever, chills, thoracic pain, bronchospasm and sore throat, after taking these preparations by inhalation. Bronchoscopic examination is of importance in the diagnosis of bronchiectasis and is particularly necessary to exclude the presence of obstructing lesions within the bronchial tree. However, frequent bronchoscopic aspirations and bronchial lavage have limited value in providing for drainage of the bronchial tree. The instillation of iodized oil into the bronchial tree in the hope of displacing purulent secretions has been advocated. Only rarely do patients consider the benefits worth while. The expelling of purulent secretions from the bronchial tree is highly desirable. There is probably a correlation between the retention of such secretions and the development of pulmonary osteoarthropathy. Much can be done to help the patient with his problem of bronchial drainage.
:g'reatment of Bronchiectasis
1023
JIowever, he must realize that the responsibility for getting rid of the secretions is his. Efficient elimination of secretions is especially difficult to attain in children. Chemotherapy
The bacterial flora in chronic bronchopulmonary suppuratives is diversified and constantly changing. Certain bacteria such as Neisseria catorrhalis and nonhemolytic streptococci, may be considered normal inhabitants of the bronchial tree or usual flora. Many bacteria may be cultured from purulent bronchial secretions, and when a sufficient number are present, some organisms arc significant pathogens. Among the gram-positive organisms the most important are pneumococci, hemolytic streptococci and staphylococci (Micrococcus pyogenes). Gram-negative bacteria are found frequently after treatment with penicillin and include Escherichia coli, Aerobacter aerogenes, Hemophilus influenzae, Klebsiella, pseudomonas aeruginosa (Bacillus pyocyaneus) and Proteus vulgaris. The detection of these bacteria is often of considerable assistance in directing antibiotic therapy in bronchiectasis. However, bacteriologic identification of significant organisms is frequently a difficult task. Unless a pathogenic organism is found in considerable numbers and on more than one occasion, it may be unwise to plan a treatment program solely on the basis of the findings on eulture of sputum. It is also our opinion that primary pulmonary moniliasis is extremely rare, and the finding of Candida albicans in cultures of sputum is unlikely to have any particular significance. After antibiotics have been used extensively in the treatment of bronchopulmonary disease, monilia arc commonly found in bronchial secretions. All of the available antibiotics have been used in the treatment of bronchiectasis. Theoretically, treatment should be guided by the findings on bacteriologic examination of bronchial secretions. However, in actual practice it has been our policy to use penicillin first and then plan further antibiotic therapy after evaluation of results of this treatment and subsequent bacteriologic studies. All methods of administering antibiotics have been used, including the oral and parenteral routes, the aerosol method and the intratracheal instillation of solutions of antibiotics. The aerosol method of administering antibiotics deserves some comment. This method has been described in many publications and many variations in technique are employed. The method should be kept as simple as possible. A standard nebulizer* capable of producing an aerosol with an average particle size of 1 to 2 microns is desirable. Compressed oxygen or an electric motor and air compressor is usually necessary to provide the positive pressure required to nebulize 1 or 2 cc. of solution several times daily. In general, it is best to dispense with the masks, re* Examples: The De Vilbiss no. 40 (The De Vilbiss Company, Somerset, Pennsylvania) or the Vaponefrin (Vaponefrin Company, Upper Darby, Pennsylvania).
1024
Arthur M. Olsen, O. 7'heron Clagett
breathing bags and special hoods, which have been devised for aerosol therapy. However, special techniques are desirable for infants and children who are unable to use the standard nebulizer efficiently. Special large volume nebulizers* and tents are now available for continuous vaporization of antibiotic solutions. Although therapeutic aerosols have their limitations, their use does have certain advantages of getting the antibiotic to the actual site of bronchial infection. Inhalation of antibiotic aerosols does produce a high concentration of drugs in the bronchial secretion. Also it aids in thinning out viscous secretion. The inhalation of micronized or "dust" preparations of certain antibiotics (penicillin and streptomycin) has been recommended. In general, these dusts are less efficacious than aerosols and are likely to produce more local reactions. Supraglottic administration of solutions of antibiotics is of limited usefulness in the treatment of bronchiectasis. This method usually requires application of a local anesthetic to the hypopharynx, larynx and trachea or at least intratracheal instillation of cocaine. Some degree of skill and experience on the part of the physician are required, and the cooperation of the patient is essential. When properly used, supraglottic instillation may be a valuable adjunct to other methods of treatment. As said before, penicillin has been the drug of choice in the treatment of bronchiectasis. However, very little success has been attained with the usual doses of preparations for oral administration. Huge doses of aqueous or procaine penicillin are required if significant concentrations of penicillin are to be obtained in the sputum. At present, penethamate hydrochloride, the diethyl-aminoethyl ester hydriodide of penicillin G (Neo-Penil) is being used parenterally in the treatment of suppurative pulmonary disease. High concentrations of penicillin have been reported in the sputum when 500,000 units is injected once or twice daily. However, Neo-Penil is capable of producing severe reactions, especially in children, and the preparation should be used carefully. Penicillin may be administered effectively as an aerosol for the treatment of bronchiectasis. Penicillin G may be dissolved in distilled water, sterile saline solution or a specially prepared solution containing a detergent. Fifty thousand units of penicillin per cubic centimeter of solution is a satisfactory concentration and 500,000 units or more can be nebulized daily by the patient who is beginning his therapy. As the bronchorrhea is brought under control, the frequency of treatment and total dosage can be reduced. Penicillin aerosol can be used almost indefinitely by the patient if no signs of sensitivity to penicillin appear. Supraglottic instillations of penicillin solutions are sometimes used to replace or supplement aerosol treatment with penicillin. The same
* The
Mist-o-gen (Production Foundry Co., Oakland, California).
Treatment of Bronchiectasis
1025
preparation and concentration of penicillin is suitable and 10 cc. may be instilled as a single daily treatment. To be effective the patient must be able to retain the solution for 30 minutes or more. Streptomycin or dihydrostreptomycin may be administered alone or ill combination with penicillin as an aerosol or by supraglottic instillation. A concentration of 200 mg. per cubic centimeter of solution is suggested. The use of streptomycin is reserved for individuals whose response to penicillin is not satisfactory or whose sputum cultures reveal large numhers of gram-negative bacteria. It has been our policy to use streptomycin as an adjunct to penicillin therapy and for limited periods only. Gramnegative bacteria quickly become resistant to streptomycin and its usefulness is limited. The broad-spectrum antibiotics have been given almost exclusively by mouth and they may be effective in eradicating bronchial infection and reducing the volume of sputum. Tetracycline hydrochloride may be ~iven in a dosage of 0.25 grams every 6 hours for 4 or 5 days at a time. A satisfactory preparation of oxytetracycline for aerosol administration i:i available but it is not as well tolerated as penicillin. Other antibiotics have limited usefulness in the treatment of bronchiectasis. Erythromycin and carbomycin have no advantage over penicillin. Neomycin and polymyxin B are used only in dire circumstances because of their toxicity. LIMITATIONS OF MEDICAL MANAGEMENT
As previously stated medical treatment is directed toward the conrol of the secondary infection associated with bronchiectasis and its ever changing bacterial flora. Thus, we are treating a complication rather than the disease itself. As far as chemotherapy is concerned, we not only must use antibiotics which are effective against the bacteria present but also must get the drug to the infection. In cases of chronic bronchiectasis with much pulmonary fibrosis and poor blood supply, it is indeed difficult to combat the infection. Antibiotics have greatly altered the prognosis in eases of bronchiectasis in which surgical procedures cannot be used. However, the effectiveness of drug therapy is limited by sensitivity to the drugs or the toxic effects of the drugs on one hand and by the development of resistant bacteria on the other. It has been estimated that 1 or 2 per cent of individuals become allergic to penicillin. It should be noted that pneumococci and hemolytic streptococci rarely become resistant to penicillin. However, 60 to 70 per cent of all strains of Staphylococcus aureus (Micrococcus pyogenes) are already resistant to penicillin. Emergence of gram-negative bacteria which are resistant to streptomycin occurs frequently after prolonged therapy. The gastrointestinal complications of use of broad-spectrum antibiotics are well known and certainly limit the usefulness of these drugs t
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Arthur M. Olscn, O. Thcron Clagctt
in the management of bronchiectasis. Of greater importance is the emergence of resistant bacteria in cultures of bronchial secretions. Many strains of Micrococcus pyogenes are resistant before therapy is even attempted. Proteus vulgaris and Pseudomonas aeruginosa are frequently isolated in the sputum cultures of patients who have had much treatment with tetracycline derivative::;. The destruetion of the sensitive bacteria then seems to predispose to the luxuriant growth of these resistant bacteria. Staphylococcic enterocolitis has been reported, and Barach, Bickerman and Beck have recently reported fatalities in debilitated individuals treated intensively with broad-spectrum antibiotics with emergence of resistant bacteria. Hence, we advise that the use of broadspectrum antibiotics be limited to 4 or 5 days out of each month or for the preoperative preparation of patients. SUMMARY
Surgical excision is the treatment of choice for bronchiectasis. Unfortunately, many patients have disease which is so diffuse that surgical procedures cannot be considered. Medical management is palliative and is direeted toward drainage of the affected region and eradication of infection by chemotherapy. Penicillin continues to be our most valuable drug and is most effeetively administered as an aerosol. Aerosols which contain wetting agents or possibly proteolytic enzymes may likewise aid in the problem::; of bronchopulmonary drainage. The value of antibiotic therapy of infeetion in bronchiectasis is limited by the toxic effects of the drugs and by the emergence of resistant bacteria. The problems of bacterial resistance are of particular importance when broad -spectrum antibiotics are used. Their continued use tends to favor the emergence of bacteria resistant to all clinically useful antibiotics. Hence, they should be used for short period::;. Despite the limitations of antibiotic therapy, the outlook in eases of bronchiectasis has been considerably improved. The patient is usually able to control those symptoms which would make him socially undesirable and chronically ill. REFERENCES 1. Barach, A. L., Bickerman, H. A. and Beck, G. J.: Antibiotic Therapy in Infections of the Respiratory Tract. Arch. Int. Med. 90: 808-849 (Dec.) 1952. 2. Blades, Brian: Individual Ligation Technique for Lower Lobe Lobectomy. J. Thoracic Surg. 10: 84-98 (Oct.) 1940.