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Communications to the Editor |

Treatment Outcome in Mycobacterium avium Pulmonary Disease: A Correction and Comment FREE TO VIEW

Jerome Reich, MD, FCCP
Author and Funding Information

Affiliations: Portland, OR,  University of Calgary Calgary, AB, Canada

Correspondence to: Jerome Reich, MD, FCCP, 7400 SW Barnes Rd, A622, Portland, OR 97225; e-mail: Reichje@dnamail.com



Chest. 2005;127(5):1864-1866. doi:10.1378/chest.127.5.1864
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Huey Long (“Kingfish”), the famously corrupt, demagogic, depression-era governor of Louisiana, was interviewed by a high school senior, whose last question was, “Tell me, governor, is there a place for honesty in politics?” Long replied, reassuringly, in the affirmative, but as the student left the room, he winked at his surrounding cronies and commented, “In politics, boys, we use anything we can get!” We applied the same expediency rule in our treatment of pulmonary disease due to Mycobacterium avium.

Due to a misinterpretation of our data,1the authors of a recent review of the treatment of M avium pulmonary disease2 conveyed a misleadingly pessimistic view. They assumed (Stephen Field, MD, FCCP; personal communication; August 29, 2004) that individuals in whom surgery was an adjunct to medical therapy and those who had responded to drug treatment, as indicated by sputum conversion and radiographic improvement, but whose information had not been completed when we collated our data, were treatment failures. They excluded from consideration two patients whose primary treatment was surgery. Consequently, they considered that only 6 of 14 patients (43%) were treated successfully.

Sixteen of our patients were judged to be suitable for aggressive management, and 2 patients underwent surgery as the primary treatment. In Table 1 of the article by Reich and Johnson,1 case 17 was a 3-year-old child with unexplained right hilar adenopathy and middle lobe opacification. The diagnosis was established based on histology and the results of a culture of the resected middle lobe. This patient and patient 10 represent successful surgical treatment, evidenced by the absence of recurrence. Surgery was an adjunct to successful drug treatment, which was indicated by sputum conversion and radiographic improvement in cases 6, 9, 13, and 14. Each patient had localized disease, and their relative youth (mean age, 41 years) indicated a low surgical risk, which I judged to be lower than the risk of recurrence from residual disease. They had no recurrence after long-term follow-up. The title of column 8 in Table 1, “months observed since drug treatment was DC,” applied only to those individuals in whom treatment was completed. The patients in cases 7, 8, and 11 had each received ≤ 18 months of the planned 24 months of drug therapy when the data were collated. Each patient exhibited sputum conversion and radiographic improvement, and I classified them as treatment successes. I stand by the summary of successful outcomes in the 16 persons treated with intent to cure (short-term follow-up, 15 of 16 patients [94%]; long-term follow-up, 11 of 12 patients [92%]). We attributed our high success rate to the following two factors: fewer of our patients had moderate-to-far advanced disease than in compendia drawn from tertiary care settings; and none had experienced prior treatment failure. A decision to increase the dose of ethionamide stepwise may have contributed to success by reducing drug intolerance. We could not exclude the possibility that our favorable outcome reflected infection with a population of less virulent or more drug-susceptible organisms. With the advent of the newer macrolide agents, one would hope that aggressive treatment would be even more effective.

Primary disease is an infrequently cited pulmonary manifestation of M avium, which, when a plausible cause is sought, appears to be ascribable to a large, avian-sourced inoculum of organisms of low virulence in an immunologically naïve host.36 For example, our 3-year-old patient resided in a home in which a number of pet birds were housed.

In contrast to Mycobacterium tuberculosis, to which African Americans (AAs), in comparison with whites, exhibit a marked susceptibility, a noteworthy epidemiologic feature of pulmonary disease due to M avium, to which the authors allude, is its rarity in AAs. That genetic factors play a key role in resistance has been highlighted by several reports of a remarkably low incidence of M avium bacteremia in AAs with AIDS. Fordham et al7reported that disseminated M avium in patients with AIDS was far less common in undeveloped countries, chiefly Africa, in comparison with developed countries. Morrissey et al8 reported the absence of M avium bacteremia in AIDS patients in Uganda, despite the high prevalence of the organism in soil and water samples. It seems plausible that genetic sorting in sub-Saharan Africa has selected AAs possessing an inherent resistance to M avium. If this resistance resides in a propensity to develop a brisk granulomatous response, one might speculate that the increased susceptibility of AAs to sarcoidosis is a manifestation of the same propensity to develop a granulomatous response to undefined, possibly related, antigens. Evidence that this speculation is plausible is provided by the experiment of Hurley and Shelley,9 who reported that 5 of 50 healthy AAs developed persistent papules at the site of intradermal injections of first-strength purified protein derivative, which, at 4 weeks, demonstrated epithelioid granulomas that were indistinguishable from positive Kveim test results.

References

Reich, JM, Johnson, RE (1991) Mycobacterium avium-intracellulare pulmonary disease: incidence, treatment, and outcomes in a community setting.Am Rev Respir Dis143,1381-1385. [PubMed]
 
Field, SK, Fisher, D, Cowie, RL Mycobacterium aviumcomplex pulmonary disease in patients without HIV infection.Chest2004;126,566-581. [CrossRef] [PubMed]
 
Reich, JM Primary pulmonary disease due toMycobacterium avium-complex.Chest1992;101,1447-1448. [CrossRef] [PubMed]
 
Reich, JM Primary pulmonary disease due toMycobacterium avium-complex [letter].Chest1993;104,651
 
Magdorf, K, Ertel, M, Grassot, A, et al Tuberculin conversion and abnormal chest radiograph in an infant.Eur Respir J1996;9,1763-1765. [CrossRef] [PubMed]
 
Fergie, JE, Milligan, TW, Henderson, BM, et al IntrathoracicMycobacterium aviumcomplex infection in immunocompetent children: case report and review.Clin Infect Dis1997;24,250-253. [CrossRef] [PubMed]
 
Fordham von Reyn, C, Arbeit, RD, Tosteson, AN, et al The international epidemiology of disseminatedMycobacterium aviumcomplex infection in AIDS: International MAC Study Group.AIDS1996;10,1025-1032. [CrossRef] [PubMed]
 
Morrissey, AB, Aisu, TO, Falkinham, JO, III, et al Absence ofMycobacterium aviumcomplex disease in patients with AIDS in Uganda.J Acquir Immune Defic Syndr1992;5,477-478. [PubMed]
 
Hurley, HJ, Shelley, WB Sarcoid granulomas after intradermal tuberculin in normal human skin.Arch Dermatol1960;82,119-126. [CrossRef]
 
To the Editor:

We would like to thank Dr. Reich for his thoughtful comments and for providing additional information about the patients described in his previously published article.1 The major aim of our review was to focus interest on Mycobacterium avium lung disease, and it appears that we have been successful.

Surgery was part of the treatment plan for 6 of the 16 patients with M avium lung disease reported by Reich and Johnson.1Although there are no properly designed trials, surgery has been reported to convert sputum to negative in patients with localized lung disease who previously failed drug therapy.26 Dr. Reich described surgery as an adjunct to medication therapy, but inadequate pulmonary reserve precludes surgery in many patients with M avium lung disease; in those who undergo surgery, postoperative morbidity including hemorrhage, empyema, and bronchopleural fistula are common complications.,26 Moreover, lung involvement in many patients is too widespread for surgery to be a consideration. Our opinion is that surgery is a desperate and last-stage measure for the minority of patients who fail medical therapy but can tolerate lung resection as a life-saving procedure. We do not feel that surgery should be part of the routine management of these patients.

In the treatment section of our review, we discussed that previous authors had used various definitions for treatment success. To allow comparison between the results of the different investigators, we had to define success and apply that definition in a similar fashion to the various reports. Most medication trials did not include surgery as a routine part of their treatment regimen. We defined the inability to complete medication therapy, failure of sputum to convert to negative with medication therapy, relapse during or after treatment was completed, death, and the need for surgery as failures of medication therapy.7

We were not sure how to categorize the two patients who underwent surgery prior to medication therapy, so we limited the analysis to the other 14 individuals reported by Reich and Johnson.1 Three of 14 patients were reported as “treatment not completed,” and 4 patients required surgery despite drug therapy.1 Dr Reich’s present communication now clarifies the status of the three patients described as “treatment not completed.” The other seven patients converted to negative, but one patient relapsed.1 Consistent with our interpretation of the other treatment reports, we categorized the 6 of Dr. Reich’s 14 patients who were able to complete drug therapy, whose sputum converted to negative, and did not relapse, as drug treatment successes. Changing the status of these three patients to treatment successes in our Table 4, which includes the patients treated with regimens that included ethambutol and/or rifampin, changes the overall success rate from 37.7 to 38.1%.

Dr. Reich’s comments about possible racial differences in the susceptibility to M avium are provocative, but there are only very preliminary studies of the immune changes that may predispose to infection with this organism.8 Patients with HIV infection have a constellation of T-cell immune defects, but elderly women with fibronodular bronchiectasis have much more subtle immune changes, yet both groups of patients are susceptible to disease with M avium.,8Moreover, studies in Uganda may not be applicable to African Americans whose ancestry is primarily West African. We would caution that there are many other possible explanations for the apparently different racial susceptibilities to M avium. Tuberculosis is much more prevalent in the developing world and kills many AIDS patients before their CD4+ counts fall low enough for disseminated M avium disease to develop. Moreover, a greater proportion of the population in the developing world has been exposed to tuberculosis and/or have been vaccinated with bacille Calmette Guérin and have some immunity to mycobacterial disease, at least before their CD4+ counts fall very low, that may confer partial protection from M avium.10 Life expectancy is much lower in the developing world than in North America. The larger elderly population in the developed world is more susceptible to M avium, which may also help to explain some of the apparent differences in prevalence of this condition.

References
Reich, JM, Johnson, RE Mycobacterium avium-intracellulare pulmonary disease: incidence, treatment, and outcomes in a community setting.Am Rev Respir Dis1991;143,1381-1385. [PubMed]
 
Corpe, RF Surgical management of pulmonary disease due toMycobacterium avium-intracellulare.Rev Infect Dis1981;3,1064-1067. [CrossRef] [PubMed]
 
Moran, JF, Alexander, LG, Staub, EW, et al Long-term results of pulmonary resection for atypical mycobacterial disease.Ann Thorac Surg1983;35,597-604. [CrossRef] [PubMed]
 
Nelson, KG, Griffith, DE, Brown, BA, et al Results of operation inMycobacterium avium-intracellularelung disease.Ann Thorac Surg1998;66,325-330. [CrossRef] [PubMed]
 
Pomerantz, M, Madsen, L, Goble, M, et al Surgical management of resistantMycobacterial tuberculosisand other mycobacterial pulmonary infections.Ann Thorac Surg1991;52,1108-1112. [CrossRef] [PubMed]
 
Shiriaishi, Y, Nakajima, Y, Takasuna, K, et al Surgery forMycobacterium aviumcomplex lung disease in the clarithromycin era.Eur J Cardiothorac Surg2002;21,314-318. [CrossRef] [PubMed]
 
Field, SK, Fisher, D, Cowie, RL Mycobacterium avium complex pulmonary disease in patients without HIV infection.Chest2004;126,566-581. [CrossRef] [PubMed]
 
Vankayalapati, R, Wizel, B, Samten, B, et al Cytokine profiles in immunocompetent persons infected withMycobacterium aviumcomplex.J Infect Dis2001;183,478-484. [CrossRef] [PubMed]
 
Trnka, L, Dankova, D, Svandova, E Six years’ experience with the discontinuation of BCG vaccination: 4. Protective effect of BCG vaccination against theMycobacterium avium intracellularecomplex.Tuber Lung Dis1994;75,348-352. [CrossRef] [PubMed]
 
Romanus, V, Hallander, HO, Wahlen, P, et al Atypical mycobacteria in extrapulmonary disease among children: incidence in Sweden from 1969 to 1990, related to changing BCG-vaccination coverage.Tuber Lung Dis1995;76,300-310. [CrossRef] [PubMed]
 

Figures

Tables

References

Reich, JM, Johnson, RE (1991) Mycobacterium avium-intracellulare pulmonary disease: incidence, treatment, and outcomes in a community setting.Am Rev Respir Dis143,1381-1385. [PubMed]
 
Field, SK, Fisher, D, Cowie, RL Mycobacterium aviumcomplex pulmonary disease in patients without HIV infection.Chest2004;126,566-581. [CrossRef] [PubMed]
 
Reich, JM Primary pulmonary disease due toMycobacterium avium-complex.Chest1992;101,1447-1448. [CrossRef] [PubMed]
 
Reich, JM Primary pulmonary disease due toMycobacterium avium-complex [letter].Chest1993;104,651
 
Magdorf, K, Ertel, M, Grassot, A, et al Tuberculin conversion and abnormal chest radiograph in an infant.Eur Respir J1996;9,1763-1765. [CrossRef] [PubMed]
 
Fergie, JE, Milligan, TW, Henderson, BM, et al IntrathoracicMycobacterium aviumcomplex infection in immunocompetent children: case report and review.Clin Infect Dis1997;24,250-253. [CrossRef] [PubMed]
 
Fordham von Reyn, C, Arbeit, RD, Tosteson, AN, et al The international epidemiology of disseminatedMycobacterium aviumcomplex infection in AIDS: International MAC Study Group.AIDS1996;10,1025-1032. [CrossRef] [PubMed]
 
Morrissey, AB, Aisu, TO, Falkinham, JO, III, et al Absence ofMycobacterium aviumcomplex disease in patients with AIDS in Uganda.J Acquir Immune Defic Syndr1992;5,477-478. [PubMed]
 
Hurley, HJ, Shelley, WB Sarcoid granulomas after intradermal tuberculin in normal human skin.Arch Dermatol1960;82,119-126. [CrossRef]
 
Reich, JM, Johnson, RE Mycobacterium avium-intracellulare pulmonary disease: incidence, treatment, and outcomes in a community setting.Am Rev Respir Dis1991;143,1381-1385. [PubMed]
 
Corpe, RF Surgical management of pulmonary disease due toMycobacterium avium-intracellulare.Rev Infect Dis1981;3,1064-1067. [CrossRef] [PubMed]
 
Moran, JF, Alexander, LG, Staub, EW, et al Long-term results of pulmonary resection for atypical mycobacterial disease.Ann Thorac Surg1983;35,597-604. [CrossRef] [PubMed]
 
Nelson, KG, Griffith, DE, Brown, BA, et al Results of operation inMycobacterium avium-intracellularelung disease.Ann Thorac Surg1998;66,325-330. [CrossRef] [PubMed]
 
Pomerantz, M, Madsen, L, Goble, M, et al Surgical management of resistantMycobacterial tuberculosisand other mycobacterial pulmonary infections.Ann Thorac Surg1991;52,1108-1112. [CrossRef] [PubMed]
 
Shiriaishi, Y, Nakajima, Y, Takasuna, K, et al Surgery forMycobacterium aviumcomplex lung disease in the clarithromycin era.Eur J Cardiothorac Surg2002;21,314-318. [CrossRef] [PubMed]
 
Field, SK, Fisher, D, Cowie, RL Mycobacterium avium complex pulmonary disease in patients without HIV infection.Chest2004;126,566-581. [CrossRef] [PubMed]
 
Vankayalapati, R, Wizel, B, Samten, B, et al Cytokine profiles in immunocompetent persons infected withMycobacterium aviumcomplex.J Infect Dis2001;183,478-484. [CrossRef] [PubMed]
 
Trnka, L, Dankova, D, Svandova, E Six years’ experience with the discontinuation of BCG vaccination: 4. Protective effect of BCG vaccination against theMycobacterium avium intracellularecomplex.Tuber Lung Dis1994;75,348-352. [CrossRef] [PubMed]
 
Romanus, V, Hallander, HO, Wahlen, P, et al Atypical mycobacteria in extrapulmonary disease among children: incidence in Sweden from 1969 to 1990, related to changing BCG-vaccination coverage.Tuber Lung Dis1995;76,300-310. [CrossRef] [PubMed]
 
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