Illustration of woman coughing while in bed. Several boxes of tissues are next to her.

The impact of NTM and who’s at risk

  • Nontuberculous mycobacterial (NTM) lung disease is a pulmonary infection that causes chronic, debilitating disease1,2
  • NTM lung disease has been associated with increased patient morbidity and all-cause mortality1,3-9
  • Bronchiectasis is a major risk factor for NTM lung disease10
    • 63% (1158/1826) of bronchiectasis patients had coexistent NTM lung disease or NTM isolation in an analysis of the US Bronchiectasis Research Registry11
    • See more data on the link between bronchiectasis and NTM
  • The index of suspicion for NTM lung disease remains low, taking ~20 months from the first NTM-related symptom or diagnostic procedure for patients to receive an NTM lung disease diagnosis12,13
    • Learn more about susceptibility factors and when to suspect NTM
Illustration of man bent over and coughing while holding his chest.

WHAT IS NTM LUNG DISEASE?

80% of NTM is MAC in the US

NTM lung disease is a pulmonary infection that can cause chronic, debilitating disease.1,2

80% of NTM is MAC in the US

Mycobacterium avium complex (MAC) accounts for more than 80% of all NTM lung disease cases in the United States.14

Read about

NTM microbiology and species of NTM

Despite increasing prevalence, the index of suspicion for NTM lung disease remains low. It can often be missed due to its nonspecific or overlapping symptoms in patients with underlying structural lung disease, making early identification a challenge and compounding existing respiratory conditions.5,12,15,16

Calendar with words '20 months'

It takes ~20 months from the first NTM-related symptom or diagnostic procedure for patients to receive an NTM lung disease diagnosis.13

INSPIRED BY ONE PATIENT’S STORY TRAPPED

Woman with heat lamps attached to her, sitting on a crowded public bus. Other passengers are frowning at her.
Transcript

[MUSIC PLAYING]

OK guys so--

[MUSIC PLAYING]

[MUSIC PLAYING]

Beth’s repetitive NTM symptoms made her feel trapped in an endless cycle of despair that took a toll on her personal and professional life. Watch “Trapped,” an animation inspired by Beth’s story.

The impact of NTM on patients—lung damage, MORBIDITY, AND MORTALITY

Multiple studies have shown that NTM lung disease increases morbidity and lung damage.1,3-5

  • Read more about 15 different studies that evaluated the association between NTM lung disease and morbidity, including research on radiographic progression, worsening lung function, and reduction in quality of life1,3-5

There is a large volume of evidence demonstrating the association between NTM lung disease and all-cause mortality.6-9

  • Read more about 13 different studies that evaluated the association between NTM lung disease and mortality, including studies that showed the increased risk of mortality in patients with NTM vs matched controls6-9
    Link to see more

    Bronchiectasis is a major risk factor for NTM10

    The incidence of bronchiectasis is increasing worldwide, with multiple studies showing that bronchiectasis and NTM lung disease are inextricably linked. The index of suspicion for NTM in your differential diagnoses should be elevated in bronchiectasis patients.10,11,26,36

    illustration of a lung with marks on it representing damage
    • Structural airway changes in patients with non-CF bronchiectasis predispose them to NTM infection10
    • Older female bronchiectasis patients with a low BMI are a high-risk group for NTM10
    • NTM lung disease is likely to exacerbate underlying bronchiectasis, making both conditions more difficult to manage5,16
    Exclamation point placed within a triangle.

    Macrolide monotherapy is commonly prescribed in bronchiectasis patients as a preventative measure for exacerbations, but it can be a key driver in the development of macrolide-resistant strains in NTM patients, leading to poor outcomes for NTM treatment.14,33,37

    Read more about macrolide resistance and its impact on patients with MAC lung disease:

    It is essential to rule out NTM lung disease in bronchiectasis patients before starting macrolide monotherapy in order to avoid creating macrolide-resistant lung disease.39

    Dr Julie Philley on bronchiectasis and NTM

    Dr Julie Philley in an examination room.
    Transcript

    [MUSIC PLAYING]

    I think you should have a higher index of suspicion for NTM when you see patients that have a chronic cough. They simply have acough that will not go away, and they've been treated with multiple antibiotics. I think other hallmark signs are fatigue, nightsweats, and hemoptysis.

    The typical patient with NTM usually has structural lung disease. Many of these patients have underlying bronchiectasis, which, of course, is a disease where they have dilated floppy bronchial tubes, and this is an irreversible condition. As well, many other patients present with things like COPD, asthma, or other types of immunosuppression. They should prompt you to do a completeworkup for NTM.

    [MUSIC PLAYING]

    Multiple studies have investigated the high overlap between bronchiectasis and NTM5,10,26

      Link to see more

      See a patient case

      Female bronchiectatic patient with NTM

      COPD and NTM

      COPD is increasing around the world. In the United States, it affects 6.4% of adults. Studies have shown that COPD patients are particularly susceptible to NTM, with one population-based, case-controlled study reporting that COPD may increase the risk of NTM lung disease by 15.7 fold.36,53

      Read more about the connection of COPD to NTM and the negative outcomes that may result36:

      Patients with COPD and NTM experienced a

      
      increased risk of all-cause mortality 
      vs patients with COPD alone35

      Multiple NTM isolates in patients with COPD were associated with an accelerated decline in FEV1 compared to patients with a single or no NTM isolates (79.4 mL/year to 61.6/ 56.2 mL/year, respectively)20

      

      of COPD patients with NTM were hospitalized for exacerbations within the year prior to NTM diagnosis

      
      

      of COPD patients without NTM36

      COPD was identified as the most common underlying disease associated with NTM lung disease mortality, occurring in

      

      (719/2990) of NTM patient fatalities54

      See a patient case

      COPD patient with NTM

      Asthma and NTM

      The relationship between an NTM infection and asthma is complex. It has been demonstrated that the risk of NTM lung disease is increased in difficult-to-control asthmatic patients, particularly in those who are older, have more severe airflow limitations, and receive treatment with higher doses of ICS for a longer period of time.41

      Read more about the vulnerability of asthmatic patients to NTM infections41:

      One case-controlled study estimated that the prevalence of NTM infections among asthmatic patients was as

        41

      Asthma was associated with a

       

      risk of NTM compared to age-matched controls36

      Asthma was linked with a

       

      adjusted incidence of NTM lung disease in a population-based, retrospective study of >6 million people55

      Cystic fibrosis and NTM

      CF is a genetic disorder affecting ~30,000 people in the United States. The prevalence of NTM in patients with CF is varied; however, there has been a consistent increase since 2000. NTM are opportunistic bacteria that can impact morbidity and mortality in CF patients.56,57

      Read more about the impact of NTM on CF patients57:

      CF patients with chronic NTM infection had a higher rate of annual decline in predicted FEV1 at −2.33%/year (P<0.01) vs those with no NTM infection58

      In CF patients, NTM acquisition was associated with a

        

      on small airway function in both the SGM and RGM groups (median: 79/68 [P=0.013] and 64/51 [P=0.028], before/after acquisition, respectively)59

      Other comorbid conditions and NTM

      Other diseases or therapies that impair pulmonary clearance or suppress the immune system can increase the risk of NTM lung disease. There are also other comorbidities that have been associated with NTM.15,60

      These include but are not limited to:

      • Prior TB15
      • Chronic bronchitis50
      • Severe or chronic pneumonia51
      • Pneumoconiosis15
      • Lung cancer26

      Microbiology of NTM

      Among the almost 200 different species of NTM identified, the most common pathogens for lung disease in the US are MAC, Mycobacterium kansasii, and M abscessus.62,63

      MAC accounts for 80% of all NTM lung disease in the US, with its most common human pathogens including Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium chimaera.14,64

      NTM bacteria are regularly classified by growth rate62

      Slowly growing:

      • MAC
      • M kansasii
      • Mycobacterium xenopi

      Rapidly growing:

      • M abscessus
      • Mycobacterium fortuitum
      • Mycobacterium chelonae

      Species that form colonies on culture in ≤7 days are termed "rapidly growing mycobacteria" whereas species that require >7 days are classified as "slowly growing mycobacteria." Depending on the species, some slowly growing mycobacteria can take 4 or more weeks to form mature colonies.16,65

      NTM can subvert macrophage defense and other mechanisms, leading to infection66-68

      NTM are difficult-to-treat mycobacteria that can invade lung tissue and intracellular pulmonary compartments—specifically macrophages—where they can subvert normal cellular defense mechanisms, replicate, and cause chronic infections. Additionally, they may also live as planktonic mycobacteria and assembled in biofilm colonies in the mucus and alveolar walls in lung tissue.1,67-72

      NTM Mechanism of Disease

      NTM bacteria causing lung damage. A macrophage is in the background.
      Transcript

      [GENTLE ACOUSTIC MUSIC]

      Illuminating NTM-- nontuberculous mycobacterial lung disease.

      [BIRDS CHIRPING]

      Nontuberculous mycobacteria, or NTM, are ubiquitous in the environment and are opportunistic pathogens that can cause lungdisease. People with a history of bronchiectasis, COPD, or other lung conditions, slender elderly women with Marfanoid body habitus, as well as those who are immunocompromised or immunosuppressed, are at risk of developing NTM lung disease. Thesesusceptible individuals may have impaired airway or mucus clearance that aid the growth and survival of NTM.

      When NTM are inhaled, they can live intracellularly by invading macrophages and subverting their defenses by inhibiting theformation of phagolysosomes, which play a role in NTM destruction. This allows the bacteria to create a reservoir in the lungs. NTM can also live extracellularly, where free-floating bacteria form biofilm colonies in the lungs. Collectively, these mechanisms allow NTM to be resilient in the body.

      NTM lung disease may contribute to serious and permanent lung damage. Early diagnosis and appropriate treatment areimportant. Think NTM? Test for NTM. This information is intended for health care professionals only. For more information, visit NTMfacts.com.

      [GENTLE ACOUSTIC MUSIC]

      NTM lung disease is on the rise5

      Increasing prevalence

      • NTM lung disease is rising, growing 8% each year. In 2019, it was estimated that there were 95,000 to 115,000 diagnosed NTM lung disease patients in the United States5,13
      • In a 2012 study, NTM infections were increasing among patients aged 65 and older, a population that was expected to nearly double by 20305

      Stay up to date on NTM research, including NTM Articles

      Environmental factors

      • NTM are ubiquitous organisms found in water and soil, which are transmitted to humans by the inhalation of contaminated aerosols from the environment. Most people are not susceptible to developing an NTM infection. When susceptible hosts are exposed to the environmental sources, this could result in NTM infecting the host and causing lung disease. NTM are generally not transmitted from person to person5,15,42,43,73 8 out of 10 water samples
        • One US study across 25 states showed that NTM bacteria were found in nearly 8 out of 10 water samples43
        • NTM bacteria commonly live in households or establishments that utilize municipal water supplies5
      • NTM lung disease varies by geographic area: coastal regions, including Gulf States, have higher rates of infection, accounting for 70% of annual NTM cases in the United States74
      • Half of diagnosed NTM lung disease patients reside within 7 states: Florida, New York, Texas, California, Pennsylvania, New Jersey, and Ohio13
        • 1 in 7 NTM lung disease patients resides in Florida
      Test for NTM

      ATS=American Thoracic Society; BMI=body mass index; CCI=Charlson Comorbidity Index; CF=cystic fibrosis; CI=confidence interval; CPRD=Clinical Practice Research Datalink; CT=computed tomography; FEF25-75=forced expiratory flow of 25%-75%; FEV1=forced expiratory volume in 1 second; FVC=forced vital capacity; GBT=guideline-based treatment; GERD=gastroesophageal reflux disease; HIV=human immunodeficiency virus; HQOL/HRQL=health-related quality of life; ICS=inhaled corticosteroids; IDSA=Infectious Diseases Society of America; IQR=interquartile range; MAC=Mycobacterium avium complex; MAC-PP=persistent culture-positive MAC; MIC=minimum inhibitory concentration; NHIRD=National Health Insurance Research Database; NTM=nontuberculous mycobacteria; OR=odds ratio; RGM=rapidly growing mycobacteria; SF-36=36-Item Short-Form Health Survey; SGM=slowly growing mycobacteria; SGRQ=St George's Respiratory Questionnaire; TB=tuberculosis; TNF=tumor necrosis factor.