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

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

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

20 months to diagnosis icon

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

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

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

8 out of 10 water samples
  • 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
Macrolide monotherapy alert icon

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

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

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

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

of COPD patients without NTM36

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

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(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 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 Monthly

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

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.