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Last updated: 9/12/2024
Years published: 2015, 2018, 2024
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Leah Lande, MD, Division of Pulmonary and Critical Care Medicine, Lankenau Medical Center, Associate Program Director, Pulmonary and Critical Care Fellowship Program, Clinical Assistant Professor, Lankenau Institute for Medical Research, Clinical Assistant Professor of Medicine, Jefferson University Medical College, for assistance in the preparation of this report.
Nontuberculous mycobacterial (NTM) lung disease is a general term for a group of disorders characterized by exposure to specific bacterial germs known as mycobacteria. These germs are found in the water and soil and are common throughout the environment. They usually do not cause illness.
In NTM disorders, the severity of infection and the disease course can vary greatly from one person to another. The most common symptoms include a persistent cough, fatigue, weight loss, night sweats and occasionally shortness of breath (dyspnea) and coughing up of blood (hemoptysis). Less often, NTM infection can cause skin or soft tissue infections or infection and inflammation of the lymph nodes (lymphadenitis).
Most evidence indicates that these infections are not transmitted from one person to another but are acquired from the environment. NTM lung disease most commonly affects people with an underlying lung disease such as chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis, primary ciliary dyskinesia and alpha-1-antitrypsin disease, but individuals with no prior history of lung disease can also be affected.
Less severe infections may not require treatment. In other cases, the infection can become chronic requiring ongoing treatment.
The term โnontuberculousโ is used to differentiate these disorders from the mycobacterium that cause tuberculosis (i.e. mycobacterium tuberculosis complex). These disorders also exclude Mycobacterium leprae, the mycobacterium that causes leprosy.
Symptoms and severity of nontuberculous mycobacterial (NTM) lung disease can vary greatly from person to person, and the reason for this is not fully understood. Chronic lung infection is the most common complication affecting approximately 94% of people. Symptoms are usually nonspecific and resemble those of other lung or respiratory infections, including:
Recurrent respiratory infections may occur, which can lead to progressive lung damage, resulting in impaired lung function over time.
There are two main clinical presentations for NTM infection, which means that the symptoms and signs associated with this disorder are expressed in two specific ways. The two main forms of NTM Infection are:
Less common presentations of NTM Infection are:
Although pulmonary symptoms are the most common way NTM disease affects humans, these infections can also involve the skin, bones and lymph nodes. Specific symptoms vary depending on the exact areas of the body affected. An infection can be widespread (disseminated) throughout the body and, without proper treatment, can prove fatal. Disseminated NTM infection occurs almost entirely in individuals whose immune systemโs ability to fight infection is severely compromised or absent (immunocompromised individuals).
Nontuberculous mycobacterial (NTM) lung disease is caused by infection with bacteria called mycobacteria, which are found in many places in the environment. While most people exposed to these bacteria do not get sick, over 120 species of mycobacteria can cause disease in humans. The most common group is called the Mycobacterium avium complex (MAC), which includes three species: M. avium, M. intracellulare, and M. chimaera. These species account for about half of all NTM infections. Other species that can cause infection include M. abscessus, M. kansasii, M. fortuitum, M. xenopi, M. malmoense, M. szulgai, and M. simiae.
Itโs unclear why some people become sick when exposed to these bacteria while others do not. Certain risk factors might make infection more likely, but in some cases, no clear risk factor is identified. Two main theories suggest that abnormalities in the lungsโ ability to clear out mucus or a problem with the immune system may increase the risk of infection.
Different species and forms of NTM affect different groups of people. People with the cavitary form of infection often have a history of smoking, chronic obstructive pulmonary disease (COPD), or structural lung diseases such as bronchiectasis.
Those with the nodular bronchiectatic form of MAC or M. abscessus infection are often thin, middle-aged or older females who may have no history of smoking or lung disease. They may also have features like a sunken chest (pectus excavatum), abnormal spine curvature (scoliosis), mitral valve prolapse, or a single variant in the cystic fibrosis gene (CFTR).
People with cystic fibrosis (CF) and non-CF bronchiectasis are at higher risk for developing infections, particularly with MAC or M. abscessus. Infection with M. kansasii is more common in males and people with chronic pulmonary obstructive disease (COPD), immune suppression, HIV infection (AIDS), or cancer.
Certain immune system defects also increase the risk of NTM infection, including interferon gamma receptor deficiencies, STAT-1 deficiency, and GATA2 deficiency. Medications that suppress the immune system, like tumor necrosis factor (TNF) alpha antagonist drugs, can also raise the risk, as can genetic conditions like Marfan syndrome and hyper-IgE syndrome.
According to the American Lung Association, more than 86,000 people are likely living with nontuberculous mycobacterial (NTM) lung disease in the U.S. Rates appear to be increasing, especially among females and older age groups. It is more frequently seen in Caucasians and Asians, as well as in people with weakened immune systems. However, the true rate of NTM infections is difficult to determine because many cases may go undiagnosed or misdiagnosed.
Diagnosing nontuberculous mycobacterial (NTM) lung disease involves identifying symptoms, reviewing medical history, conducting a clinical evaluation and performing various tests. However, this can be difficult since the symptoms are often nonspecific. A key part of the diagnosis is ruling out other diseases, such as tuberculosis or lung cancer.
The American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) have created guidelines for diagnosing NTM infections. These guidelines are most effective for diagnosing MAC, M. kansasii, and M. abscessus infections and require clinical, radiographic, and microbiologic criteria to be met.
Clinical Symptoms:
Radiographic Findings:
These findings can be detected through chest X-rays or high-resolution computed tomography (HRCT) scans, which provide detailed images of the lungs.
Microbiologic Evaluation:
Sputum cultures help detect bacteria in the lungs and a bronchoscopy may be necessary if adequate sputum samples canโt be obtained. A bronchoalveolar lavage (BAL) may also be performed during this procedure. In rare cases, a lung biopsy might be required, although itโs usually not needed.
NTM infections are classified as either rapidly growing or slowly growing. M. abscessus, M. chelonae, and M. fortuitum grow quickly, usually within a week in culture, while MAC and other slowly growing mycobacteria take longerโ10-14 days in liquid culture or 2-4 weeks in solid culture. Once growth is detected, nucleic acid probes can be used for rapid identification of certain species like M. tuberculosis, M. kansasii, and MAC.
Treatment
There is currently no cure for nontuberculous mycobacteria (NTM) lung disease, but treatment can help manage symptoms and improve quality of life. Treatment for NTM infections is complex and individualized. Not everyone diagnosed with NTM lung disease requires immediate treatment. Some infections grow slowly and may not progress, making a โwatchful waitingโ approach appropriate. In these cases, regular check-ups are important to monitor the progression of the disease and start treatment if symptoms worsen.
When treatment is necessary, it often involves a combination of antibiotics taken over an extended period, typically several months. The choice of antibiotics depends on the type of NTM infection and whether the bacteria have developed resistance. Progress is monitored through sputum samples, and the disease is considered cured only after 12 months of negative cultures. Updated guidelines emphasize the need for ongoing research and clinical trials to improve existing treatments and develop new therapies.
In 2020, updated guidelines were published by several leading medical organizations, including the American Thoracic Society (ATS), European Respiratory Society (ERS), and others. These guidelines confirm the standard treatment for M. avium infections, which consists of three medications: ethambutol, rifampicin, and a macrolide. For more serious infections, amikacin liposome inhalation suspension (ALIS), approved by the FDA in 2018, is recommended as an additional, less toxic treatment option when negative conversion is not achieved after six months.
For M. abscessus infections, the guidelines acknowledge the lack of an optimal treatment plan but recommend using at least three drugs, which may include a macrolide, amikacin, imipenem, cefoxitin and tigecycline. If the macrolides are effective for these bacteria, at least three drugs are used, while macrolide-resistant strains require at least four drugs. M. abscessus is difficult to treat, with success rates ranging between 41% and 46%. There is currently no antibiotic regimen that consistently leads to long-term recovery, emphasizing the need for new drugs and treatment strategies.
Antibiotic therapy for NTM lung disease can be difficult to maintain due to the long treatment duration and common side effects. These side effects may include digestive issues, hearing loss and liver problems, which can make it challenging to stay on the prescribed treatment. Close communication with healthcare providers is essential to manage side effects, adjust treatment plans, and prevent drug resistance.
In specific cases such as in individuals with localized bronchiectasis, cavitary disease, or coughing up blood that does not improve with treatment (refractory hemoptysis), surgical removal of the affected tissue may be recommended. However, determining the best candidates and timing for surgical therapy is unknown. In some cases, surgery may be considered when antibiotics alone are not effective. M. abscessus infections may require surgical removal of the infected portion of the lung, followed by continued drug treatment. Surgery may also be helpful for MAC patients who have localized infections, severe lung damage, or persistent bleeding. Minimally invasive techniques are often used, but the decision to pursue surgery depends on the overall health of the individual, the extent of the infection, and specific symptoms.
Airway clearance techniques can help improve lung health by removing mucus and reducing the risk of infection. These techniques may include chest physical therapy, nebulized saline (saltwater mist), postural drainage, and oscillation vests. Good hygiene practices, staying up to date on vaccinations, and avoiding lung irritants can also help prevent new infections.
Although NTM bacteria are found in the environment, certain precautions can help reduce the risk of re-infection:
Maintaining overall health is essential for managing NTM lung disease. Regular exercise can improve lung function and overall well-being, while a balanced diet supports the immune system. Avoiding lung irritants, especially smoking, is critical, as smoking worsens lung conditions.
Living with a chronic lung condition like NTM can be emotionally challenging, often leading to feelings of depression and anxiety. It is important to address these mental health challenges and seek support from healthcare providers, support groups, or counseling services.
Developing new treatments for NTM infections, particularly those that are less toxic and require shorter durations, is a top priority in research. Recent attention has focused on repurposing tuberculosis drugs like bedaquiline and linezolid for NTM infections. However, more specific treatments are needed to address the growing public health concerns posed by NTM.
The 2020 guidelines highlight the critical need for ongoing research into new therapies, greater collaboration between clinicians and researchers and investment in clinical trials. Improving treatment outcomes for NTM lung disease will require sustained research efforts and better education about the disease and its treatment options.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Conyers LE & Saunders BM. Treatment for non-tuberculous mycobacteria: challenges and prospects. Frontiers Microbiol., 02 June 2024. Sec. Infectious Agents and Disease 15 -2024. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1394220/full
Lande L, George J, Plush T. Mycobacterium avium complex pulmonary disease: new epidemiology and management concepts. Curr Opin Infect Dis. 2018 Apr;31(2):199-207. https://www.ncbi.nlm.nih.gov/pubmed/29346118
Haworth CS, Banks J, Capstick T, et al. British Thoracic Society Guidelines for the Management of Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD). Thorax 2017;72:ii1โii64. https://thorax.bmj.com/content/thoraxjnl/72/Suppl_2/ii1.full.pdf
Honda JR, Knight V, Chan ED. Pathogenesis and risk factors for nontuberculous mycobacterial lung disease. Clin Chest Med. 2015;36:1-11. https://www.ncbi.nlm.nih.gov/pubmed/25676515
Philley JV, Griffith DE. Treatment of slowly growing mycobacteria. Clin Chest Med. 2015;36:79-90. https://www.ncbi.nlm.nih.gov/pubmed/25676521
Reves R, Schluger NW. Update in tuberculosis and nontuberculous mycobacterial infections 2013. Am J Respir Crit Care Med. 2014;189:894-898. https://www.ncbi.nlm.nih.gov/pubmed/24735031
Johnson MM, Odeall JA. Nontuberculous mycobacterial pulmonary infections. J Thorac Dis. 2014;6:210-220. https://www.ncbi.nlm.nih.gov/pubmed/24624285
Mirsaeidi M, Farshidpour M, Ebrahimi G, Aliberti S, Falkinham JO. Management of nontuberculous mycobacterial infection in the elderly. Eur J Intern Med. 2014;25:356-363. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067452/
Kartalija M, Ovrutsky AR, Bryan CL, et al. Patients with nontuberculus mycobacterial lung disease exhibit unique body and immune phenotypes. Am J Respir Crit Care Med. 2013;187:197.https://www.ncbi.nlm.nih.gov/pubmed/23144328
Lim J, Lvu J, Choi CM. Non-tuberculous mycobacterial diseases presenting as solitary pulmonary nodules. Int J Tuberc Lung Dis. 2010;14:1635-1640. https://www.ncbi.nlm.nih.gov/pubmed/21144251
Glassroth J. Pulmonary disease due to nontuberculous mycobacteria. Chest. 2008;133:243-251. https://www.ncbi.nlm.nih.gov/pubmed/18187749
Griffith DE, Aksamit T, Brown-Elliot BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Resp Crit Car Med. 2007;175:367-416. https://www.ncbi.nlm.nih.gov/pubmed/17277290
Field SK, Cowie RL. Lung disease due to the more common nontuberculous mycobacteria. Chest. 2006;129:1653-1672. https://www.ncbi.nlm.nih.gov/pubmed/16778288
INTERNET
Akram SM, Attia FN. Mycobacterium avium Complex. [Updated 2023 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431110/ Accessed Sept 12, 2024.
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