NTM isolation and disease in Asia have several features. First, a substantial percentage (31%) of patients from whom pulmonary NTM were isolated had clinically relevant NTM disease. This finding is similar to the 33% and 25% found in studies in Canada and the Netherlands, respectively (2,3
). In Asia, NTM may cause substantial pulmonary disease; differences in clinical relevance exist among species (), as previously observed (2
Second, MAC was the main cause of pulmonary NTM infection (68% of cases) in Asia. In a key article in 2002, Marras and Daley reviewed the prevalence of pulmonary NTM disease in the world (3
). They noted a predominance of MAC among the causative agents of pulmonary NTM disease in Asia. Data from Asia were, however, scarce, and their conclusion was mainly based on 1 study (6
). Our study supports their conclusion of the predominance of MAC in Asia, which is consistent with its predominance in other parts of the world, namely, North America and most parts of Europe (3
Third, we found that in some regions in Asia, RGM are a major cause of pulmonary NTM disease. This finding contrasts with studies of NTM in other parts of the world (3
). In a surveillance study from the Netherlands for instance, RGM caused only 3% of all pulmonary NTM infections (2
). In the United States, this percentage is ≈5% (36
). In the present review, RGM was found to generally cause 14% of pulmonary NTM infections, but in 3 countries (India, Taiwan, South Korea) this percentage rose to >30% of infections. The fact that RGM were frequently found in pulmonary samples () could reflect higher environmental exposure of RGM in Asia and, hence, higher isolation frequency. The predominance of RGM species may be the result of laboratory practices as well. Ethnic factors may also contribute to susceptibility to different species; i.e., Asian persons could be more susceptible to RGM infection.
Contrary to the high frequency of isolation of RGM species, M. malmoense
and M. xenopi
, frequently seen in other parts of the world, were not seen as causative species in any of the studies from Asia. M. xenopi
has been associated with hot water systems (1
); as a result, it might be expected to be more rare in Asia, where the water delivery infrastructure is less developed than that in Europe and North America.
A fourth feature of pulmonary NTM disease in Asia—compared with Europe and North America—was the relatively high percentage of patients with a history of TB. This finding might merely reflect the higher incidence of TB in Asia, or it could reflect higher clinician awareness in Asia, such that physicians order Mycobacterium
spp. cultures in former TB patients with coughing and hence find a relatively higher number of NTM isolates. Alternatively, it could reflect a true predilection of NTM for patients with structural lung disease (1
) associated with a higher susceptibility to mycobacterial infection in general. The role of TB in the pathogenesis of pulmonary NTM disease is controversial; structural lung damage by a TB infection renders the host vulnerable to NTM disease (1
), but there are also clues that exposure to TB infers cross-protection to NTM disease (37
Our study has some limitations. The major limitation is the language restriction. The inclusion of languages other than English would probably have increased precision. For instance, during our literature search we came across 5 articles, published as abstracts in PubMed, on NTM infections in Japan. Although certain aspects of these data were already published in the English-language articles we included, we did not have the means to include these non–English-language studies. Nevertheless, our study illustrates the distribution of NTM infections from different geographic areas in Asia and will increase knowledge of the distribution and relevance of NTM species in Asia.
Another limitation is the long time span of the included studies. Because they ranged from 1969 to 2008, they used different decontamination, culture, and identification methods. Data should therefore be considered with caution because of the variety of laboratory procedures used by the several authors to isolate and identify NTM. First, different sample decontamination protocols may determine the yield of NTM by selecting for certain NTM species and inhibiting others (38
). Second, the introduction of more sensitive liquid media probably increased NTM isolation and perhaps selected for specific species (26
). Finally, and foremost, the major differences in identification methods used in the studies introduce important biases. Because the taxonomy of NTM has been changing in recent years (37,39,40
), the different NTM identification methods used in the various studies might have influenced our results; use of molecular tools to identify the historical isolates would probably result in different, more detailed, identifications, especially among the MAC, the M. simiae
group, and the RGM (37,39,40
). We did note increased use of molecular tools for NTM identification over time (), which will, over the next few years, provide us with a more up-to-date overview of NTM species distribution in Asia.
In conclusion, despite the limitations of language and species identification methods, we have described the scale of human pulmonary NTM infections in eastern Asia. MAC bacteria were not only the most prevalent NTM found in pulmonary samples, but they were also the most common cause of pulmonary NTM disease in this geographic region. Distinct epidemiologic and clinical characteristics of pulmonary NTM disease in Asia were found: many patients had a history of TB, and RGM were a frequent cause of pulmonary NTM infections. These distinct characteristics of pulmonary NTM disease in this part of the world are not well reflected in the current ATS criteria on NTM infections and could be incorporated in future guidelines.