4 Fishman AP, McClement J, Himmelstein A, et at: Effects of acute anoxia on the circulation and respiration in patients with chronic pulmonary disease studied during the "steady state." J Coo Invest 31 :770-781, 1952 5 Burrows B, Kettel LJ, Niden AH, et a1: Patterns of cardiovascular dysfunction in chronic obstructive lung disease. N Eng} J Med 286:912-918, 1972 6 Levine BE, Bigelow DB, Hamstra RO, et al: The role of long tenn continuous oxygen administration in patients with chronic airway obstruction with hypoxemia. Ann Intern Med 66:639-650,1967 7 Abraham AS, Cole RB, Bishop 1M: Reversal of pulmonary hypertension by prolonged oxygen administration to patients with chronic bronchitis. Circ Res 23: 147-157, 1968 8 Flick MR, Block AJ: Continuous in vivo measurement of arterial oxygen saturation by oximetry. Heart Lung 6:990993, 1977 9 Flick MR, Block AJ: Continuous in vivo monitoring of arterial oxygenation in chronic obstructive lung disease. Ann Intern Med 86:725-730, 1977 10 Koo KW, Sax DS, Snider GL: Arterial blood gases and pH during sleep in chronic obstructive pulmonary disease. Am J Med 58:663-670, 1975 11 Wynne jw, Block AJ, Hemenway J, et a1: Disordered breathing and oxygen desaturation during sleep in patients with chronic obstructive pulmonary disease. Chest 73( suppl) :301-303, 1978 12 Boysen PG, Wynne lW, Block AJ: Oxygen saturation in "blue bloaters." Lancet 1:936, 1978 13 Boysen PG, Block AJ, Wynne lW, et at: Nocturnal pulmonary hypertension in COPD (abstract). Chest 74: 331,1978 14 TiIkian AC, Guilleminault C, Schroeder JS, et a1: Hemodynamics in sleep-induced apnea: Studies during wakefulness and sleep. Ann Intern Med 85:714-719, 1976 15 Flenley DC: Clinical hypoxia: Causes, consequences, and correction. Lancet 1:542-546, 1978 16 Leggett RJ, Cooke NJ, Clancy L, et a1: Long-term domiciliary oxygen therapy in cor pulmonale complicating chronic bronchitis and emphysema. Thorax 31:414-418, 1976
The Other Mycobacteria Mycobacterium intraceUulare, M avium, M Jeansasii, M fortuitum, and other species of myco-
bacteria are well characterized microbiologically. Some are recognized as causing disease in man, but the clinical aspects are poorly understood. Although most of these organisms can be found in the natural environment (unlike the better known M tuberculosis ), the factors leading to infection and disease in man are enigmatic. The evidence indicates that infection with these mycobacteria is more common than with M tuberculosis in many areas of the United States and in some cases exceeds 70 percent of the population, as determined by skin test reactivity.I Disease, by contrast, is uncommon. Our understanding of the true incidence of disease is hampered by the fact that there is no nationwide system of reporting and collecting data. Definitive criteria
110 EDITORIALS
for the diagnosis of disease in distinction to infection alone or colonization have not been established. Since many strains of mycobacteria are ubiquitous in the environment, their presence in relationship to man is to be expected either as a saprophytic colonization (probably rather common) or as clinically insignificant tissue invasion resulting in infection without disease (very common and indicated by the host's positive delayed hypersensitivity reaction to the specific antigen). When a disease process exists in association with the finding of these mycobacteria, both of the preceding circumstances and the possibility of a direct cause must be considered. Their isolation from diseased tissues which are normally sterile indicates a definite cause-and-effect relationship, provided all other more likely pathogens have been excluded. Results of smear and culture of sputum require careful scrutiny even in the presence of compatible pulmonary disease. Our experience with human disease caused by these mycobacterial species has prompted our use of the following guidelines in determining when disease exists: 1. The organisms must be isolated repeatedly from the same source over a period of days or weeks. They are nearly always found in all properly collected specimens. 2. The organisms must be isolated in significant numbers. A quantitative culture method is essential. A disease process is usually associated with the isolation of more than a few colonies. 3. A compatible disease process as determined by roentgenogram or other diagnostic procedures must be present. Isolation of organisms from a person otherwise healthy usually has no significance. 4. Other pathogenic organisms have been excluded. M tuberculosis disease, for example, is the one most likely to have other mycobacterial species present as colonizers. Mixed infections causing disease can occur, but are uncommon. 5. When an underlying disease process is likely, pathologic examination is helpful to establish the role of a possible mycobacterial pathogen. The diagnosis is established when there are changes compatible with mycobacterial disease, particularly if acid-fast bacilli are present. Likewise, the isolation of the Mycobacterium on culture from tissue is strong evidence of disease. Even when disease clearly exists, controversy does not end. Whether to treat or not is a difficult decision ,- since most of these mycobacteria are resistant to a variable degree to drugs effective against M tubercuCHEST, 75: 2, FEBRUARY, 1979
losis and to other antimicrobial agents. Fortunately, M kansasii responds well to "standard" antituberculosis regimens. The M intraceUulare-avium-scrofula-
ceum complex of organisms represents another matter. The spectrum of disease varies widely. In many, there is little or no progression or very slow changes occurring over years, often with minimal symptoms. Underlying pulmonary disease is frequently present and difficult to differentiate in terms of progression or symptoms from those of the mycobacterial disease. Disease may progress and cause extensive damage or death in other patients. The organisms are resistant to most of the antituberculosis drugs when tested in vitro, and disease reponds poorly to "standard" regimens. Empirically chosen, multiple drug regimens of Bve and six antituberculosis drugs give better results but often are impracticable because of toxicity, unpredictable results, and the apparent benign circumstances of disease in some patients. Surgery is effective in selected patients. Unfortunately, all treatment modalities are in an uncertain state of understanding because of a lack of controlled treatment trials. It is clear that better and more specific drugs or methods are needed to treat disease. This can come about only with cooperative efforts since the number of patients and experience in anyone institution is limited. As the incidence of disease with M tuberculosis continues to diminish in the United States and the clinical awareness of disease caused by other mycobacteria increases, it is apparent that the major problems and areas of greatest concern in mycobacterial disease will be with these other mycobacteria which now are so incompletely understood.
PaulT. Davidson, M.D., F.C.C.P.· Denver
°From the Department of Medicine, National Jewish Hospital and Research Center. Reprint requeste: Dr. Davidson, 3800 East Colla Avenue, Denver 80206
REFERENCE 1 Edwards LB, Edwards PQ, Palmer CE: Sources of tuberculin sensitivity in human populations. A summing up of recent epidemiologic research. Acta Tuberc Scandinav (suppl) 47:77-97,1959
Selection of Diagnostic Procedures Meenee. Minee. Mo ••• 7 IEenee. n attempting to minimize the trauma and mor-
bidity associated with diagnostic procedures and at the same time improve the sampling yield, pul-
CHEST, 75: 2, FEBRUARY, 1979
monary physicians and surgeons have proven to be a resourceful and inventive group. Currently, we have available to us an array of diagnostic techniques that allow examination of the pulmonary structure. Based on the bridge principle that a "peek is worth two messes," directed sampling of airways' secretions and cells, pulmonary parenchymal juices and tissue, and mediastinal-pleural tissue is possible via bronchoscopic procedures, mediastinoscopic exami.. nation, minithoracotomy, and fluoroscopically guided needling. Regrettably, as yet the relative roles of these techniques in our diagnostic tool kit are unclear, although with each report of clinical experience, the merits of each procedure become further clarified. We can view the "inside" of the lung with the fiberoptic bronchoscope, and it was inevitable that methods would be devised for viewing it from the "outside" as well. To this end, the thoracoscopic procedure has recently been resurrected as a means for directed sampling of the pleural fluid and cells, as well as pleural and lung biopsy. Examination of the pleural cavity was used initially in the 19208 and 30s, especially in Europe, in association with therapeutic pneumothorax and the attendant "pneumonolysis" that was often necessary. With improvements in general anesthetic and thoracic surgical techniques, as well as the development of effective social and chemotherapeutic control of tuberculosis, the procedure fell into disuse in North America. Evolution of the thoracoscopic procedure for directed sampling has continued in Europe, where interest seems to have persisted and large series have been reviewed 1,2 Recently, on this side of the Atlantic, there has been a reawakening of interest in the thoracoscopic procedure as a means of diagnosing pleural and pulmonary disease.P" The technique for "peeking" used has varied greatly, and diverse instruments have been employed, including bron choscopes, trocar and telescopes, telescopes or bronchoscopes and chest tubes, flberoptic bronchoscopes, mediastinoscopes, and even sigmoidoscopes (I}. The only prerequisite is a reasonably free pleural space. Advantages cited include a high diagnostic yield (90+ percent), minimal morbidity, and reasonable simplicity. Minor limitations are that complete inspection of accessible pleural space is time-consuming; and, like all endoscopic procedures, considerable experience is required for the endoscopist to appreciate what is being viewed. Reported mortality has been negligible, although complications have included hemorrhage, persistent air leaks, empyema, and implantation of tumor. Elsewhere in this issue of Chest (see page 126), Rodgers and co-workers report their experience with
EDITORIALS 111
The Other Mycobacteria Mycobacterium intraceUulare, M avium, M Jeansasii, M fortuitum, and other species of myco-
bacteria are well characterized microbiologically. Some are recognized as causing disease in man, but the clinical aspects are poorly understood. Although most of these organisms can be found in the natural environment (unlike the better known M tuberculosis ), the factors leading to infection and disease in man are enigmatic. The evidence indicates that infection with these mycobacteria is more common than with M tuberculosis in many areas of the United States and in some cases exceeds 70 percent of the population, as determined by skin test reactivity.I Disease, by contrast, is uncommon. Our understanding of the true incidence of disease is hampered by the fact that there is no nationwide system of reporting and collecting data. Definitive criteria
110 EDITORIALS
for the diagnosis of disease in distinction to infection alone or colonization have not been established. Since many strains of mycobacteria are ubiquitous in the environment, their presence in relationship to man is to be expected either as a saprophytic colonization (probably rather common) or as clinically insignificant tissue invasion resulting in infection without disease (very common and indicated by the host's positive delayed hypersensitivity reaction to the specific antigen). When a disease process exists in association with the finding of these mycobacteria, both of the preceding circumstances and the possibility of a direct cause must be considered. Their isolation from diseased tissues which are normally sterile indicates a definite cause-and-effect relationship, provided all other more likely pathogens have been excluded. Results of smear and culture of sputum require careful scrutiny even in the presence of compatible pulmonary disease. Our experience with human disease caused by these mycobacterial species has prompted our use of the following guidelines in determining when disease exists: 1. The organisms must be isolated repeatedly from the same source over a period of days or weeks. They are nearly always found in all properly collected specimens. 2. The organisms must be isolated in significant numbers. A quantitative culture method is essential. A disease process is usually associated with the isolation of more than a few colonies. 3. A compatible disease process as determined by roentgenogram or other diagnostic procedures must be present. Isolation of organisms from a person otherwise healthy usually has no significance. 4. Other pathogenic organisms have been excluded. M tuberculosis disease, for example, is the one most likely to have other mycobacterial species present as colonizers. Mixed infections causing disease can occur, but are uncommon. 5. When an underlying disease process is likely, pathologic examination is helpful to establish the role of a possible mycobacterial pathogen. The diagnosis is established when there are changes compatible with mycobacterial disease, particularly if acid-fast bacilli are present. Likewise, the isolation of the Mycobacterium on culture from tissue is strong evidence of disease. Even when disease clearly exists, controversy does not end. Whether to treat or not is a difficult decision ,- since most of these mycobacteria are resistant to a variable degree to drugs effective against M tubercuCHEST, 75: 2, FEBRUARY, 1979
losis and to other antimicrobial agents. Fortunately, M kansasii responds well to "standard" antituberculosis regimens. The M intraceUulare-avium-scrofula-
ceum complex of organisms represents another matter. The spectrum of disease varies widely. In many, there is little or no progression or very slow changes occurring over years, often with minimal symptoms. Underlying pulmonary disease is frequently present and difficult to differentiate in terms of progression or symptoms from those of the mycobacterial disease. Disease may progress and cause extensive damage or death in other patients. The organisms are resistant to most of the antituberculosis drugs when tested in vitro, and disease reponds poorly to "standard" regimens. Empirically chosen, multiple drug regimens of Bve and six antituberculosis drugs give better results but often are impracticable because of toxicity, unpredictable results, and the apparent benign circumstances of disease in some patients. Surgery is effective in selected patients. Unfortunately, all treatment modalities are in an uncertain state of understanding because of a lack of controlled treatment trials. It is clear that better and more specific drugs or methods are needed to treat disease. This can come about only with cooperative efforts since the number of patients and experience in anyone institution is limited. As the incidence of disease with M tuberculosis continues to diminish in the United States and the clinical awareness of disease caused by other mycobacteria increases, it is apparent that the major problems and areas of greatest concern in mycobacterial disease will be with these other mycobacteria which now are so incompletely understood.
PaulT. Davidson, M.D., F.C.C.P.· Denver
°From the Department of Medicine, National Jewish Hospital and Research Center. Reprint requeste: Dr. Davidson, 3800 East Colla Avenue, Denver 80206
REFERENCE 1 Edwards LB, Edwards PQ, Palmer CE: Sources of tuberculin sensitivity in human populations. A summing up of recent epidemiologic research. Acta Tuberc Scandinav (suppl) 47:77-97,1959
Selection of Diagnostic Procedures Meenee. Minee. Mo ••• 7 IEenee. n attempting to minimize the trauma and mor-
bidity associated with diagnostic procedures and at the same time improve the sampling yield, pul-
CHEST, 75: 2, FEBRUARY, 1979
monary physicians and surgeons have proven to be a resourceful and inventive group. Currently, we have available to us an array of diagnostic techniques that allow examination of the pulmonary structure. Based on the bridge principle that a "peek is worth two messes," directed sampling of airways' secretions and cells, pulmonary parenchymal juices and tissue, and mediastinal-pleural tissue is possible via bronchoscopic procedures, mediastinoscopic exami.. nation, minithoracotomy, and fluoroscopically guided needling. Regrettably, as yet the relative roles of these techniques in our diagnostic tool kit are unclear, although with each report of clinical experience, the merits of each procedure become further clarified. We can view the "inside" of the lung with the fiberoptic bronchoscope, and it was inevitable that methods would be devised for viewing it from the "outside" as well. To this end, the thoracoscopic procedure has recently been resurrected as a means for directed sampling of the pleural fluid and cells, as well as pleural and lung biopsy. Examination of the pleural cavity was used initially in the 19208 and 30s, especially in Europe, in association with therapeutic pneumothorax and the attendant "pneumonolysis" that was often necessary. With improvements in general anesthetic and thoracic surgical techniques, as well as the development of effective social and chemotherapeutic control of tuberculosis, the procedure fell into disuse in North America. Evolution of the thoracoscopic procedure for directed sampling has continued in Europe, where interest seems to have persisted and large series have been reviewed 1,2 Recently, on this side of the Atlantic, there has been a reawakening of interest in the thoracoscopic procedure as a means of diagnosing pleural and pulmonary disease.P" The technique for "peeking" used has varied greatly, and diverse instruments have been employed, including bron choscopes, trocar and telescopes, telescopes or bronchoscopes and chest tubes, flberoptic bronchoscopes, mediastinoscopes, and even sigmoidoscopes (I}. The only prerequisite is a reasonably free pleural space. Advantages cited include a high diagnostic yield (90+ percent), minimal morbidity, and reasonable simplicity. Minor limitations are that complete inspection of accessible pleural space is time-consuming; and, like all endoscopic procedures, considerable experience is required for the endoscopist to appreciate what is being viewed. Reported mortality has been negligible, although complications have included hemorrhage, persistent air leaks, empyema, and implantation of tumor. Elsewhere in this issue of Chest (see page 126), Rodgers and co-workers report their experience with
EDITORIALS 111
