Chest
Volume 126, Issue 2, August 2004, Pages 566-581
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Review
Mycobacterium avium complex Pulmonary Disease in Patients Without HIV Infection

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Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater sources around the world, including hot water pipes. Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later. Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression. MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women. Preliminary data suggest that the interferon-γ pathways may be deficient in elderly women with MAC lung disease. Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal α1-antiproteinase gene and patients with certain chest wall abnormalities. Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high. A PubMed search identified 38 reports of the treatment of MAC lung disease. Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin. If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55%. The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.

Section snippets

Background

Mycobacteria that infect other species and mycobacterial saprophytes were identified soon after Koch's discovery of the tuberculosis bacillus, but were only widely recognized to be human pathogens in the 1950s.18 Various designations have been used to distinguish these other mycobacterial species from tuberculosis, including: paratubercle or pseudotubercle, anonymous, atypical, environmental, opportunistic, nontuberculous, and mycobacteria other than tuberculosis.31 NTM is the currently favored

Effects of Exposure to M avium on Tuberculin Skin Testing Results

Exposure to NTM can cause cross-reactions with tuberculin. Tuberculin skin testing was performed as part of the large international bacille Calmette-Guérin vaccination programs coordinated by the World Health Organization and the United Nations Children's Fund in the late 1940s and 1950s.56 In Northern countries, reactions to tuberculin were either strong or absent and correlated with the local prevalence of tuberculosis.57 In some geographic regions, primarily in warmer climates, a large

Epidemiology of MAC Lung Disease

As the prevalence of tuberculosis declined sharply after the introduction of effective chemotherapy in the 1950s, reports indicated an increase in the number of patients with tuberculosis-like illness due to NTM. Further instances of NTM disease were detected as more mycobacterial cultures were tested for drug susceptibility. In the 1950s, sputum from approximately 1 to 2% of patients admitted to sanatoria in Florida and Georgia grew NTM.6366 Fifteen cases of NTM pulmonary disease were detected

Clinical Features of MAC Lung Disease

Lung disease caused by MAC was first described in sanatorium patients with suspected tuberculosis.3464 Patients with MAC lung disease tended to be older, were more often white, and were more likely to have underlying lung disease than patients with tuberculosis.3669 Unlike tuberculosis, patients with MAC lung disease are not contagious, and family members and other contacts, including health-care workers and other patients in the health-care facilities, were usually not infected.3553

Male

Radiologic Features of MAC Lung Disease

Patients with underlying lung disease and MAC infection often have cavities apparent on the chest radiograph.366068 It has been suggested that MAC-related cavities tend to be thinner with less surrounding parenchymal opacification and more contiguous, but less distal bronchogenic, spread of opacification than in tuberculosis.8 In older women without underlying lung disease, MAC primarily involves the lingula and right middle lobe. Bronchiectasis is often evident. Often reticular changes, a

Microbiology of M avium

Unlike M tuberculosis, the NTM can grow at room temperature.66 Runyon and Timpe35 found that the NTM have little, if any, pathogenicity for guinea pigs, but group 1 (M kansasii) and group 3 (MAC) organisms are pathogenic for mice.35 The NTM demonstrate increased catalase activity and niacin negativity (compared to M tuberculosis).66 The cell wall of MAC is trilaminar with a basal peptidoglycan layer, an intermediate layer that is transparent as viewed by electron microscopy, and an outer layer

Predisposing Factors for MAC Lung Disease

Most patients in the earlier reports were male and had upper lobe cavitary disease. Patients with MAC lung disease tended to be older than patients with M tuberculosis or M kansasii, had a history of tobacco or alcohol consumption, and had underlying lung disease.686973 In the more recent reports, 2 most patients with fibronodular bronchiectasis were female and elderly. A Japanese study103 suggested that being thin was a risk factor for progression of disease in patients with fibronodular

Conclusion

MAC is an important pulmonary pathogen. It can complicate preexisting lung diseases and can cause lung disease in previously healthy people, usually thin, elderly women. Preliminary data suggest an important role for the IFN-γ pathways in the host defense against MAC and other mycobacteria. The newer macrolides, clarithromycin and azithromycin, have improved the results of therapy for MAC lung disease, but the failure rate remains high and work is needed to improve the outcome in MAC lung

ACKNOWLEDGMENT

The authors thank Ms. L.G. Field for editorial review.

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