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• W2296626114 abstract "•Non-tuberculous mycobacteria (NTM) are an emerging cause of pulmonary infection among apparently immunocompetent persons worldwide.•NTM pulmonary disease afflicts persons with pre-existing structural pulmonary diseases (e.g. prior tuberculosis, chronic obstructive pulmonary disease, cystic fibrosis), but emerging data suggest that many persons without such diseases are genetically susceptible to pulmonary infection with NTM.•The diagnosis of NTM pulmonary infection relies on a combination of symptoms (which may be subtle), imaging (primarily high-resolution computed tomography), and microbiological findings (increasingly supplemented by molecular testing).•The treatment of NTM pulmonary disease is challenging and should be tailored to the particular patient, based on knowledge of the infecting species and appropriate antimicrobial susceptibility testing. Non-tuberculous mycobacteria (NTM) are emerging worldwide as significant causes of chronic pulmonary infection, posing a number of challenges for both clinicians and researchers. While a number of studies worldwide have described an increasing prevalence of NTM pulmonary disease over time, population-based data are relatively sparse and subject to ascertainment bias. Furthermore, the disease is geographically heterogeneous. While some species are commonly implicated worldwide (Mycobacterium avium complex, Mycobacterium abscessus), others (e.g., Mycobacterium malmoense, Mycobacterium xenopi) are regionally important. Thoracic computed tomography, microbiological testing with identification to the species level, and local epidemiology must all be taken into account to accurately diagnose NTM pulmonary disease. A diagnosis of NTM pulmonary disease does not necessarily imply that treatment is required; a patient-centered approach is essential. When treatment is required, multidrug therapy based on appropriate susceptibility testing for the species in question should be used. New diagnostic and therapeutic modalities are needed to optimize the management of these complicated infections. Non-tuberculous mycobacteria (NTM) are emerging worldwide as significant causes of chronic pulmonary infection, posing a number of challenges for both clinicians and researchers. While a number of studies worldwide have described an increasing prevalence of NTM pulmonary disease over time, population-based data are relatively sparse and subject to ascertainment bias. Furthermore, the disease is geographically heterogeneous. While some species are commonly implicated worldwide (Mycobacterium avium complex, Mycobacterium abscessus), others (e.g., Mycobacterium malmoense, Mycobacterium xenopi) are regionally important. Thoracic computed tomography, microbiological testing with identification to the species level, and local epidemiology must all be taken into account to accurately diagnose NTM pulmonary disease. A diagnosis of NTM pulmonary disease does not necessarily imply that treatment is required; a patient-centered approach is essential. When treatment is required, multidrug therapy based on appropriate susceptibility testing for the species in question should be used. New diagnostic and therapeutic modalities are needed to optimize the management of these complicated infections. Pulmonary disease due to non-tuberculous mycobacteria (NTM) has emerged as an increasingly prevalent clinical entity in the past two to three decades. Advances in imaging and microbiological techniques, particularly molecular techniques, have significantly enhanced our understanding of this disease, but many uncertainties remain, especially in epidemiology and clinical management. The aims of this concise and practical review are threefold: (1) to provide an update regarding the small proportion of the approximately 160 known species of NTM that are commonly associated with lung disease in humans;1Tortoli E. The new mycobacteria: an update.FEMS Immunol Med Microbiol. 2006; 48: 159-178Crossref PubMed Scopus (0) Google Scholar, 2Tortoli E. Microbiological features and clinical relevance of new species of the genus Mycobacterium.Clin Microbiol Rev. 2014; 27: 727-752Crossref PubMed Scopus (24) Google Scholar (2) to elucidate the clinical approach to these pulmonary infections; and (3) to focus attention on areas of NTM pulmonary disease in which further research is urgently required. Over the past two decades, improving microbiological techniques have enhanced the recovery of NTM from the respiratory tract, and there has been a growing appreciation of their clinical significance. Perhaps driven by these phenomena, but also in addition to them, there seems to have been a genuine increase in the prevalence of pulmonary disease due to these organisms.3Kendall B.A. Winthrop K.L. Update on the epidemiology of pulmonary nontuberculous mycobacterial infections.Semin Respir Crit Care Med. 2013; 34: 87-94Crossref PubMed Scopus (0) Google Scholar Interestingly, the increase in proportion of pulmonary disease caused by NTM seems to be associated with a simultaneous decrease in the incidence of tuberculosis.4Brode S.K. Daley C.L. Marras T.K. The epidemiologic relationship between tuberculosis and non-tuberculous mycobacterial disease: a systematic review.Int J Tuberc Lung Dis. 2014; 18: 1370-1377Crossref PubMed Scopus (0) Google Scholar However, obtaining an accurate picture of the epidemiology of NTM disease is compromised by the fact that these infections are not reportable in most of the world. Much of the available epidemiological data on pulmonary NTM therefore come from sentinel surveillance and microbiology laboratory-based studies, with the attendant limitations of those study designs.5Prevots D.R. Marras T.K. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review.Clin Chest Med. 2015; 36: 13-34Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Furthermore, describing the epidemiology of NTM pulmonary disease is complicated by several challenges: (1) case ascertainment (e.g., patients are variably symptomatic, and the diagnosis often depends on computed tomography, which is not universally available and/or used); (2) the presence of the organism in the environment, which clouds the significance of a positive culture in an individual patient; (3) a disease definition based on scant evidence; and (4) reporting of the disease is not required or performed in many jurisdictions, resulting in spotty population-based data. As a result of these challenges, many authors focus on reporting disease prevalence (defined as the proportion of individuals in a given setting/region with disease according to a standardized definition, often but not always based on the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines).6Griffith D.E. Aksamit T. Brown-Elliott B.A. Catanzaro A. Daley C. Gordin F. et al.An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases.Am J Respir Crit Care Med. 2007; 175: 367-416Crossref PubMed Scopus (1963) Google Scholar Another commonly used measure is isolate incidence (number of individuals with NTM newly isolated from a respiratory source during a time period, without regard to disease status). NTM disease incidence (defined as the number of persons with a new diagnosis of NTM pulmonary disease by a standardized definition) is rarely reported because it is challenging to meaningfully describe given uncertainties in timing of disease onset and variable timing and rate of ascertainment after onset. In Ontario, Canada, the annual prevalence of NTM isolation from respiratory specimens (without considering whether true disease was present) has recently ranged from 14.1 to 22.2 per 100 000 population.7Al Houqani M. Jamieson F. Chedore P. Mehta M. May K. Marras T.K. Isolation prevalence of pulmonary nontuberculous mycobacteria in Ontario in 2007.Can Respir J. 2011; 18: 19-24Crossref PubMed Google Scholar, 8Marras T.K. Mendelson D. Marchand-Austin A. May K. Jamieson F.B. Pulmonary nontuberculous mycobacterial disease, Ontario, Canada, 1998–2010.Emerg Infect Dis. 2013; 19: 1889-1891Crossref PubMed Scopus (0) Google Scholar In one study, the prevalence of disease was estimated to be 9.8 per 100 000 in 2010.8Marras T.K. Mendelson D. Marchand-Austin A. May K. Jamieson F.B. Pulmonary nontuberculous mycobacterial disease, Ontario, Canada, 1998–2010.Emerg Infect Dis. 2013; 19: 1889-1891Crossref PubMed Scopus (0) Google Scholar With the exclusion of Mycobacterium gordonae, Mycobacterium avium complex (MAC) was found to be the most common species both isolated from the respiratory tract and associated with clinical lung infection, followed by Mycobacterium xenopi and the rapidly growing mycobacteria (RGM). In Oregon, USA, the estimated prevalence of pulmonary NTM disease was 8.6 per 100 000.9Winthrop K.L. McNelley E. Kendall B. Marshall-Olson A. Morris C. Cassidy M. et al.Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease.Am J Respir Crit Care Med. 2010; 182: 977-982Crossref PubMed Scopus (0) Google Scholar A population-based study in the same state highlighted increasing pulmonary NTM incidence from 4.8 per 100 000 in 2007 to 5.6 per 100 000 in 2012.10Henkle E. Hedberg K. Schafer S. Novosad S. Winthrop K.L. Population-based incidence of pulmonary nontuberculous mycobacterial disease in Oregon 2007 to 2012.Ann Am Thorac Soc. 2015; 12: 642-647Crossref PubMed Scopus (0) Google Scholar In other parts of the country, using laboratory surveillance complemented by electronic medical record review within four health systems, the prevalence of pulmonary disease due to NTM was estimated to be 1.4 to 6.6 per 100 000.11Prevots D.R. Shaw P.A. Strickland D. Jackson L.A. Raebel M.A. Blosky M.A. et al.Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems.Am J Respir Crit Care Med. 2010; 182: 970-976Crossref PubMed Scopus (0) Google Scholar In 2007, using data from ICD-9 coding (International Classification of Diseases ninth revision), a disease prevalence of approximately 47 per 100 000 was observed among adults aged ≥65 years in the USA, although there was quite marked variance in the regional prevalence of NTM pulmonary disease in different parts of the country.12Adjemian J. Olivier K.N. Seitz A.E. Holland S.M. Prevots D.R. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries.Am J Respir Crit Care Med. 2012; 185: 881-886Crossref PubMed Scopus (119) Google Scholar The available information from Central and South America has been limited, with significant potential for selection bias that calls the generalizability of the data into question.13Pedro Hda S. Pereira M.I. Goloni Mdo R. Ueki S.Y. Chimara E. Nontuberculous mycobacteria isolated in Sao Jose do Rio Preto, Brazil between 1996 and 2005.J Bras Pneumol. 2008; 34: 950-955Crossref PubMed Scopus (0) Google Scholar The estimated prevalence of NTM lung disease, as reported, was around 1 per 100 000 or even less. MAC was generally the most common species isolated, followed by Mycobacterium kansasii and the RGM.13Pedro Hda S. Pereira M.I. Goloni Mdo R. Ueki S.Y. Chimara E. Nontuberculous mycobacteria isolated in Sao Jose do Rio Preto, Brazil between 1996 and 2005.J Bras Pneumol. 2008; 34: 950-955Crossref PubMed Scopus (0) Google Scholar, 14de Mello K.G. Mello F.C. Borga L. Rolla V. Duarte R.S. Sampaio E.P. et al.Clinical and therapeutic features of pulmonary nontuberculous mycobacterial disease, Brazil, 1993–2011.Emerg Infect Dis. 2013; 19: 393-399PubMed Google Scholar In Europe, due to varying study methodologies and differences in underlying populations studied, the reported prevalence of isolation of NTM from respiratory specimens and the reported prevalence of such disease have been discrepant. For example, in the UK, Greece, and the Netherlands, NTM isolation rates of approximately 2.9 per 100 000, 7.0 per 100 000, and 6.3 per 100 000, respectively, have been found, and the prevalence of NTM pulmonary disease has been estimated to be 1.7 per 100 000, 0.7 per 100 000, and 1.4 per 100 000, respectively.15Henry M.T. Inamdar L. O’Riordain D. Schweiger M. Watson J.P. Nontuberculous mycobacteria in non-HIV patients: epidemiology, treatment and response.Eur Respir J. 2004; 23: 741-746Crossref PubMed Scopus (0) Google Scholar, 16Gerogianni I. Papala M. Kostikas K. Petinaki E. Gourgoulianis K.I. Epidemiology and clinical significance of mycobacterial respiratory infections in Central Greece.Int J Tuberc Lung Dis. 2008; 12: 807-812PubMed Google Scholar, 17van Ingen J. Bendien S.A. de Lange W.C. Hoefsloot W. Dekhuijzen P.N. Boeree M.J. et al.Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, the Netherlands.Thorax. 2009; 64: 502-506Crossref PubMed Scopus (0) Google Scholar For this continent, recent data have also revealed marked geographic variability in the species isolated from patients.18Hoefsloot W. van Ingen J. Andrejak C. Angeby K. Bauriaud R. Bemer P. et al.The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study.Eur Respir J. 2013; 42: 1604-1613Crossref PubMed Scopus (0) Google Scholar MAC was isolated more frequently in Northern Europe (44% among all NTM) than in Southern Europe (31% of all NTM), with M. avium being the predominant subspecies. M. xenopi was more frequently isolated in Southern Europe (21% of all NTM isolates) than in Northern Europe (6% only). In Africa, there has been recent enthusiasm to search for NTM in patients with suspected pulmonary tuberculosis.19Aliyu G. El-Kamary S.S. Abimiku A. Brown C. Tracy K. Hungerford L. et al.Prevalence of non-tuberculous mycobacterial infections among tuberculosis suspects in Nigeria.PLoS One. 2013; 8: e63170Crossref PubMed Scopus (0) Google Scholar, 20Asiimwe B.B. Bagyenzi G.B. Ssengooba W. Mumbowa F. Mboowa G. Wajja A. et al.Species and genotypic diversity of non-tuberculous mycobacteria isolated from children investigated for pulmonary tuberculosis in rural Uganda.BMC Infect Dis. 2013; 13: 88Crossref PubMed Scopus (0) Google Scholar While these studies have not categorically classified NTM lung disease, their findings suggest that a proportion of patients with suspected tuberculosis (3.7–15%) might actually have NTM disease instead of tuberculosis. Likewise, other studies have suggested that a significant proportion of patients with suspected multidrug-resistant tuberculosis (18% in each of two studies) might have NTM pulmonary disease instead.21Newman M.J. Addo K.K. Aboagye S. Bonsu F.A. Caulley P. Hesse I.F. et al.Culture and sensitivity of mycobacterial isolates from cases of pulmonary tuberculosis classified as treatment failures in a teaching hospital.West Afr J Med. 2007; 26: 131-133PubMed Google Scholar, 22Maiga M. Siddiqui S. Diallo S. Diarra B. Traore B. Shea Y.R. et al.Failure to recognize nontuberculous mycobacteria leads to misdiagnosis of chronic pulmonary tuberculosis.PLoS One. 2012; 7: e36902Crossref PubMed Scopus (0) Google Scholar In Asia, there has been no population-based study regarding the epidemiology of NTM pulmonary isolates and NTM pulmonary disease to enable in-depth understanding of the size of the problem. The available data come from studies undertaken in some countries and geographical areas of Eastern Asia, notably Japan, South Korea, India, China, Thailand, and Taiwan.23Simons S. van Ingen J. Hsueh P.R. Van Hung N. Dekhuijzen P.N. Boeree M.J. et al.Nontuberculous mycobacteria in respiratory tract infections, eastern Asia.Emerg Infect Dis. 2011; 17: 343-349Crossref PubMed Google Scholar A recent study from Japan estimated the national prevalence of NTM lung disease to be 33 to 65 per 100 000 in 2005, with most of the cases due to MAC.24Morimoto K. Iwai K. Uchimura K. Okumura M. Yoshiyama T. Yoshimori K. et al.A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan.Ann Am Thorac Soc. 2014; 11: 1-8Crossref PubMed Scopus (0) Google Scholar The leading role of MAC in the pulmonary isolates of NTM was also observed in most of the other countries in Eastern Asia.23Simons S. van Ingen J. Hsueh P.R. Van Hung N. Dekhuijzen P.N. Boeree M.J. et al.Nontuberculous mycobacteria in respiratory tract infections, eastern Asia.Emerg Infect Dis. 2011; 17: 343-349Crossref PubMed Google Scholar The other frequently isolated species included RGM and M. kansasii. Mycobacterium scrofulaceum and Mycobacterium szulgai were also occasionally found in respiratory specimens. A study from Taiwan reported an estimated prevalence of 7.94 per 100 000 inpatients in 2008, with the disease occurring largely in elderly subjects.25Lai C.C. Tan C.K. Chou C.H. Hsu H.L. Liao C.H. Huang Y.T. et al.Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000–2008.Emerg Infect Dis. 2010; 16: 294-296Crossref PubMed Scopus (0) Google Scholar In some Asian countries where the mainstay of tuberculosis diagnosis is the acid-fast smear, there are concerns that a number of patients diagnosed with tuberculosis, especially putative drug-resistant tuberculosis, might actually have NTM pulmonary disease (30.7% of isolates that tested resistant to isoniazid and rifampicin and 4% of tuberculosis retreatment cases in one study from China, similar to the African data mentioned previously).26Jing H. Wang H. Wang Y. Deng Y. Li X. Liu Z. et al.Prevalence of nontuberculous mycobacteria infection, China, 2004–2009.Emerg Infect Dis. 2012; 18: 527-528Crossref PubMed Scopus (16) Google Scholar, 27Khann S. Mao E.T. Rajendra Y.P. Satyanarayana S. Nagaraja S.B. Kumar A.M. Linkage of presumptive multidrug resistant tuberculosis (MDR-TB) patients to diagnostic and treatment services in Cambodia.PLoS One. 2013; 8: e59903Crossref PubMed Scopus (0) Google Scholar For example, a study from China demonstrated that 3.4% of smear-positive sputum specimens grew NTM, primarily MAC.28Shao Y. Chen C. Song H. Li G. Liu Q. Li Y. et al.The epidemiology and geographic distribution of nontuberculous mycobacteria clinical isolates from sputum samples in the eastern region of China.PLoS Negl Trop Dis. 2015; 9: e0003623Crossref Scopus (8) Google Scholar In Australia and New Zealand, there have been a few robust population-based studies to address the epidemiology of pulmonary NTM isolation and disease.29Thomson R.M. Changing epidemiology of pulmonary nontuberculous mycobacteria infections.Emerg Infect Dis. 2010; 16: 1576-1583Crossref PubMed Scopus (112) Google Scholar, 30Haverkort F. National atypical mycobacteria survey, 2000.Commun Dis Intell Q Rep. 2003; 27: 180-189PubMed Google Scholar, 31Freeman J. Morris A. Blackmore T. Hammer D. Munroe S. McKnight L. Incidence of nontuberculous mycobacterial disease in New Zealand, 2004.N Z Med J. 2007; 120: U2580PubMed Google Scholar The most recent data have suggested a rising disease incidence/prevalence (it is often challenging to distinguish the two) that reached 3 per 100 000. MAC has consistently been the most commonly isolated pulmonary NTM species associated with pulmonary disease.29Thomson R.M. Changing epidemiology of pulmonary nontuberculous mycobacteria infections.Emerg Infect Dis. 2010; 16: 1576-1583Crossref PubMed Scopus (112) Google Scholar Thus the available data, especially those derived from population-based studies undertaken in countries in North America, Europe, and Australia, have suggested a continuing rise in the prevalence of pulmonary NTM isolates and NTM disease in these continents. Studies from some countries and geographical areas in Eastern Asia, such as Japan, South Korea, and Taiwan, have echoed this phenomenon.5Prevots D.R. Marras T.K. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review.Clin Chest Med. 2015; 36: 13-34Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar The increasing prevalence of pulmonary disease due to NTM is especially notable among the elderly, particularly in the context of aging populations in many countries.11Prevots D.R. Shaw P.A. Strickland D. Jackson L.A. Raebel M.A. Blosky M.A. et al.Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems.Am J Respir Crit Care Med. 2010; 182: 970-976Crossref PubMed Scopus (0) Google Scholar The gender predominance is frequently confounded by the differential prevalence of smoking-associated lung damage between men and women.5Prevots D.R. Marras T.K. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review.Clin Chest Med. 2015; 36: 13-34Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar NTM are ubiquitous organisms found in environmental sources that include drinking and natural water, as well as soil and dust. Human subjects can inhale or ingest NTM in water, aerosols, or dust. NTM are quite resistant to water disinfectants in common use, such as chlorine.32Thomson R.M. Carter R. Tolson C. Coulter C. Huygens F. Hargreaves M. Factors associated with the isolation of nontuberculous mycobacteria (NTM) from a large municipal water system in Brisbane, Australia.BMC Microbiol. 2013; 13: 89Crossref PubMed Scopus (0) Google Scholar This resistance likely contributes to reports describing frequent NTM detection in potable water within Australia and the USA.32Thomson R.M. Carter R. Tolson C. Coulter C. Huygens F. Hargreaves M. Factors associated with the isolation of nontuberculous mycobacteria (NTM) from a large municipal water system in Brisbane, Australia.BMC Microbiol. 2013; 13: 89Crossref PubMed Scopus (0) Google Scholar, 33Donohue M.J. Mistry J.H. Donohue J.M. O’Connell K. King D. Byran J. et al.Increased frequency of nontuberculous mycobacteria detection at potable water taps within the United States.Environ Sci Technol. 2015; 49: 6127-6133Crossref PubMed Scopus (0) Google Scholar The ability of NTM to persist in urban water supplies may therefore be contributing to the increasing prevalence of pulmonary NTM disease in many countries. The relationships between environmental conditions, exposure, and development of disease are poorly understood and bear further study. The early concepts of NTM in the respiratory tract described a dichotomous scenario of colonization versus invasion.34Wolinsky E. Nontuberculous mycobacteria and associated diseases.Am Rev Respir Dis. 1979; 119: 107-159PubMed Google Scholar In all likelihood the situation is more complicated than a simple dichotomy and is more of a spectrum, as modeled in Figure 1. The outcome of respiratory exposure to NTM likely depends on a complex interplay between exposure-related factors (particle size, number of organisms, duration) and host-related factors (immune status, genetic background, presence of localized or generalized lung damage). Most of this interplay is poorly understood at present, but some recent data have begun to reveal certain of the key factors at work. The microbial factors and the host susceptibility factors are discussed in the subsections below. The pathogenicities of the various NTM species vary widely. Figure 2 shows the most important species that cause pulmonary disease. These pathogens include slowly growing mycobacteria, notably Mycobacterium malmoense, M. szulgai, M. kansasii, and M. xenopi, as well as the RGM, especially Mycobacterium abscessus (subsp. abscessus and bolletii).17van Ingen J. Bendien S.A. de Lange W.C. Hoefsloot W. Dekhuijzen P.N. Boeree M.J. et al.Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, the Netherlands.Thorax. 2009; 64: 502-506Crossref PubMed Scopus (0) Google Scholar, 35Bodle E.E. Cunningham J.A. Della-Latta P. Schluger N.W. Saiman L. Epidemiology of nontuberculous mycobacteria in patients without HIV infection, New York City.Emerg Infect Dis. 2008; 14: 390-396Crossref PubMed Google Scholar MAC account for the plurality of pulmonary isolates as well as disease worldwide.12Adjemian J. Olivier K.N. Seitz A.E. Holland S.M. Prevots D.R. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries.Am J Respir Crit Care Med. 2012; 185: 881-886Crossref PubMed Scopus (119) Google Scholar, 24Morimoto K. Iwai K. Uchimura K. Okumura M. Yoshiyama T. Yoshimori K. et al.A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan.Ann Am Thorac Soc. 2014; 11: 1-8Crossref PubMed Scopus (0) Google Scholar, 25Lai C.C. Tan C.K. Chou C.H. Hsu H.L. Liao C.H. Huang Y.T. et al.Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000–2008.Emerg Infect Dis. 2010; 16: 294-296Crossref PubMed Scopus (0) Google Scholar, 35Bodle E.E. Cunningham J.A. Della-Latta P. Schluger N.W. Saiman L. Epidemiology of nontuberculous mycobacteria in patients without HIV infection, New York City.Emerg Infect Dis. 2008; 14: 390-396Crossref PubMed Google Scholar, 36Al-Mahruqi S.H. van-Ingen J. Al-Busaidy S. Boeree M.J. Al-Zadjali S. Patel A. et al.Clinical relevance of nontuberculous mycobacteria.Oman. Emerg Infect Dis. 2009; 15: 292-294Crossref PubMed Scopus (0) Google Scholar Interestingly, the clinical relevance of NTM isolation from respiratory specimens appears to vary by geographic region, presumably due to variability in both environmental microbial distribution and the prevalence of host risk factors. Aside from pathogenicity of the NTM species, the quantitative exposure to mycobacteria appears to be associated with the likelihood of progression to clinical respiratory disease.37Johnson M.M. Odell J.A. Nontuberculous mycobacterial pulmonary infections.J Thorac Dis. 2014; 6: 210-220PubMed Google Scholar However, the critical exposure dose remains unknown, and almost certainly varies by host susceptibility. At an extreme end of the spectrum, hot tub lung caused by NTM (which afflicts immunocompetent hosts) occurs in the setting of indoor hot tubs, with presumed exposure to large numbers of organisms due to a combination of high organism burden in the water and concentration of aerosols within closed indoor spaces.37Johnson M.M. Odell J.A. Nontuberculous mycobacterial pulmonary infections.J Thorac Dis. 2014; 6: 210-220PubMed Google Scholar The relationship between quantitative mycobacterial exposure and disease in other settings is not well understood. A number of diseases associated with structural lung damage have been cited as predisposing to NTM pulmonary infection. Chronic obstructive pulmonary disease (COPD) has frequently been associated with NTM lung disease.12Adjemian J. Olivier K.N. Seitz A.E. Holland S.M. Prevots D.R. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries.Am J Respir Crit Care Med. 2012; 185: 881-886Crossref PubMed Scopus (119) Google Scholar, 15Henry M.T. Inamdar L. O’Riordain D. Schweiger M. Watson J.P. Nontuberculous mycobacteria in non-HIV patients: epidemiology, treatment and response.Eur Respir J. 2004; 23: 741-746Crossref PubMed Scopus (0) Google Scholar, 38Marras T.K. Mehta M. Chedore P. May K. Al Houqani M. Jamieson F. Nontuberculous mycobacterial lung infections in Ontario, Canada: clinical and microbiological characteristics.Lung. 2010; 188: 289-299Crossref PubMed Scopus (22) Google Scholar, 39Andrejak C. Thomsen V.O. Johansen I.S. Riis A. Benfield T.L. Duhaut P. et al.Nontuberculous pulmonary mycobacteriosis in Denmark: incidence and prognostic factors.Am J Respir Crit Care Med. 2010; 181: 514-521Crossref PubMed Scopus (0) Google Scholar Pneumoconioses such as silicosis have also been traditionally mentioned as risk factors,40Sonnenberg P. Murray J. Glynn J.R. Thomas R.G. Godfrey-Faussett P. Shearer S. Risk factors for pulmonary disease due to culture-positive M. tuberculosis or nontuberculous mycobacteria in South African gold miners.Eur Respir J. 2000; 15: 291-296Crossref PubMed Scopus (0) Google Scholar, 41McGrath E.E. Bardsley P. An association between Mycobacterium malmoense and coal workers’ pneumoconiosis.Lung. 2009; 187: 51-54Crossref PubMed Google Scholar although the relative importance of these conditions is diminishing as their prevalence diminishes worldwide. Although the available evidence is limited, there is some suggestion that tobacco smoke and alcohol (whose mechanism may not be related to impairment of local host defenses) may be cofactors in the development of pulmonary involvement by NTM in the human host.42Gitti Z. Mantadakis E. Maraki S. Samonis G. Clinical significance and antibiotic susceptibilities of nontuberculous mycobacteria from patients in Crete, Greece.Future Microbiol. 2011; 6: 1099-1109Crossref PubMed Google Scholar, 43Matveychuk A. Fuks L. Priess R. Hahim I. Shitrit D. Clinical and radiological features of Mycobacterium kansasii and other NTM infections.Respir Med. 2012; 106: 1472-1477Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Cystic fibrosis (CF) has frequently been associated with NTM respiratory colonization and disease, and NTM infection has been increasingly relevant in CF patients as medical advances have prolonged the life-spans of these patients.44Leung J.M. Olivier K.N. Nontuberculous mycobacteria: the changing epidemiology and treatment challenges in cystic fibrosis.Curr Opin Pulm Med. 2013; 19: 662-669Crossref PubMed Scopus (0) Google Scholar NTM have been isolated from between 4% and 32% of respiratory specimens obtained from CF patients.45Rodman D.M. Polis J.M. Heltshe S.L. Sontag M.K. Chacon C. Rodman R.V. et al.Late diagnosis defines a unique population of long-term survivors of cystic fibrosis.Am J Respir Crit Care Med. 2005; 171: 621-626Crossref PubMed Scopus (0) Google Scholar, 46Adjemian J. Olivier K.N. Prevots D.R. Nontuberculous mycobacteria among patients with cystic fibrosis in the United States: screening practices and environmental risk.Am J Respir Crit Car" @default.
• W2296626114 created "2016-06-24" @default.
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• W2296626114 date "2016-04-01" @default.
• W2296626114 modified "2023-10-16" @default.
• W2296626114 title "Update on pulmonary disease due to non-tuberculous mycobacteria" @default.
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