NTM and WHO'S AT RISK

ACCURATE AND EARLY IDENTIFICATION OF 
susceptible patients is important

Patients with a preexisting chronic respiratory problem and susceptibility factors are at a higher risk for getting NTM, including:

  • Patients with bronchiectasis, COPD, or asthma1
  • Slender, elderly women with Marfanoid body habitus (eg, Lady Windermere Syndrome)2,3
  • Patients who may be immunocompromised or have specific genetic disorders that cause structural lung damage that can impair airway and mucus clearance2,4

NTM may be more severe than you think

NTM lung disease is a chronic, debilitating condition that can significantly increase patient morbidity and mortality.5-9

The signs and symptoms of NTM lung disease often overlap with the underlying lung conditions that increase risk for NTM, like bronchiectasis, COPD, and asthma. This makes it difficult to diagnose NTM, potentially delaying a definitive diagnosis and compounding existing respiratory conditions.2,8,10,11

Among the almost 200 different species of NTM identified, the most common pathogens for lung disease in the US are Mycobacterium avium complex (MAC), Mycobacterium kansasii, and Mycobacterium abscessus.12-14

MAC accounts for more than 80% of all NTM lung disease cases in the US.14

NTM bacteria are most commonly classified by growth rate—either slowly growing (eg, MAC, Mycobacterium kansasii, Mycobacterium xenopi) or rapidly growing (eg, Mycobacterium abscessus, Mycobacterium fortuitum, Mycobacterium chelonae).5,12

Species that form colonies on culture in 7 days or fewer are termed “rapidly growing mycobacteria” whereas species that require more than 7 days are classified as “slowly growing mycobacteria.”5 Depending on the species, some slowly growing mycobacteria can take 4 or more weeks to form mature colonies.15

NTM increases morbidity

The effects of NTM:

  • Reduces patients’ quality of life16,17
  • Exacerbates the deterioration of lung function, compounding existing lung conditions8,18
  • Contributes to progressive, irreversible lung destruction16

  • In a study of 51 NTM patients, impairments in physical function resulted in a significant decline in quality of life17
    • This study defines quality of life as several parameters, including physical function, bodily pain, general health perceptions, energy or vitality, and mental health17
  • In a study between 2000 and 2008, patients with NTM isolates were approximately twice as likely as those with no isolates to experience exacerbations requiring hospitalization19

NTM increases mortality

NTM was associated with a 4.3-fold higher incidence of respiratory failure and an increase in mortality rates when compared to the general population.20,21

One study found that the overall 3-year cumulative death rate of NTM was 34% in 1282 patients.1,22

  • In a study of 316 patients with NTM respiratory isolates, the 5-year mortality rate was 35%21
  • A study using a data set of 2.3 million Medicare beneficiaries found that patients with NTM were 40% more likely to die over the 10-year study period than patients without NTM8
Download the NTM Fact Sheet

NTM can subvert macrophage defense and other mechanisms, leading to infection23-26

NTM are difficult-to-treat bacteria 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.7,24-28

NTM Mechanism of Disease

NTM is on the rise8

An increasing problem

  • NTM is rising, growing 8% each year. In 2018, it is estimated that 75,000–105,000 patients will be diagnosed with NTM lung disease in the US8,29,30
  • NTM infections are increasing among patients aged 65 and older, a population that’s expected to nearly double by 20308
  • NTM is now more prevalent than tuberculosis (TB) in the US.31 It has been found that while the prevalence of TB is low across the US, the prevalence of NTM is on the rise31,32

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.2,33,34 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 is generally not transmitted from person to person2,8,33,35,36
    • One US study across 25 states showed that NTM bacteria were found in nearly 8 out of 10 water samples33
  • 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 US29,37
  • Half of diagnosed NTM lung disease patients reside within 7 states: Florida, New York, Texas, California, Pennsylvania, New Jersey, and Ohio38
    • 1 in 7 NTM lung disease patients resides in Florida

The State of NTM

Click the map below to see how NTM affects your state29,37

  1. PREVALENCE
  2. COST
ANNUAL NTM CASE NUMBERS
  • <500
  • 500-1000
  • 1001-2000
  • 2001-3000
  • >3000
ANNUAL COST OF NTM
  • <$5 million
  • $5-20 million
  • $21-40 million
  • $41-90 million
  • >$90 million
PREVALENCE off on
  • High-risk areas
  • Coastal areas (70% of NTM cases)
click or tap
on your state

The above are estimates of NTM cases from 2010. Annual NTM costs are presented in constant 2014 dollars.

Strollo SE, et al. Ann Am Thorac Soc. 2015;12(10):1458-1464.

Adjemian J, et al. Am J Respir Crit Care Med. 2012;186(6):553-558.

These estimates are based on national and state-specific NTM case numbers and associated costs, taken from annual inpatient and outpatient visit costs, prescription medications, and previous national NTM studies using Medicare and national survey data.29

Adapted with permission from the American Thoracic Society. Copyright © 2016 American Thoracic Society.

The Annals of the American Thoracic Society and the American Journal of Respiratory and Critical Care Medicine are official journals of the American Thoracic Society.

NTM and your practice

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Identifying the NTM patient

Patients with a preexisting chronic respiratory problem and susceptibility factors are at a higher risk for getting NTM:

  • Bronchiectasis, COPD, or asthma1
  • Slender, elderly women with Marfanoid body habitus (eg, Lady Windermere Syndrome)2,3
  • May be immunocompromised2
  • Other conditions or specific genetic disorders that cause structural lung damage that can impair airway and mucus clearance4

NTM are opportunistic bacteria. Most people are not susceptible to developing NTM lung disease. NTM is generally not transmitted from person to person. When susceptible hosts are exposed to the environmental sources, this could result in NTM infecting the host and causing lung disease.2,33,35,36 Patients who are already vulnerable with underlying lung conditions are at increased risk.2,39

Patients with susceptibility factors for NTM, such as underlying structural lung disease, who present with pulmonary (eg, chronic cough) and nonspecific systemic symptoms (eg, malaise or fever) should be assessed for NTM.2,40

Characteristics strongly
associated with NTM

Bronchiectasis & NTM

The incidences of bronchiectasis are increasing worldwide, with up to 50% of patients with bronchiectasis having an NTM infection.42,43 Bronchiectasis increases susceptibility for NTM, and NTM infections are also likely to exacerbate the underlying bronchiectasis, making both conditions more difficult to treat.8

Studies indicate that NTM is common in patients with non-CF bronchiectasis. For patients with non-CF bronchiectasis, it is likely that structural changes in the airways predispose them to colonization by NTM. Alterations in the host’s immune response may also play a pivotal role in the development of infection.42

In these patients, MAC is the most frequently isolated species.5 While age and sex characteristics vary, female patients with a low BMI have emerged as a high-risk group for NTM lung disease in patients with non-CF bronchiectasis. Therefore, regular screening for NTM in this patient population is strongly recommended.42

View bronchiectasis patient profile >

COPD & NTM

COPD is increasing around the world and affects 8% of adults across the US. These patients are particularly susceptible, as a population-based, case-controlled study reported that COPD may increase the risk of an NTM lung infection by 15.7 fold.1

In a study of COPD patients with NTM, 52.8% were hospitalized for exacerbations within the previous year, as opposed to COPD patients without NTM, where only 15.6% were hospitalized.1

Another retrospective study has shown that the isolation of NTM from sputum specimens of COPD patients has been linked to an increased number of COPD exacerbations. The exacerbations in the group without NTM isolates requiring hospitalizations (0.47 ± 1.24) tended to be lower than that of the multiple- (0.82 ± 1.08) and single- (0.88 ± 1.20) NTM isolate groups (P=0.046). Additionally, repeated NTM isolates in patients with COPD were associated with an accelerated decline in lung function compared to patients with no NTM isolates (79.4 mL/year to 56.2 mL/year in FEV1, respectively).19

View COPD patient profile >

Asthma & NTM

Asthma was associated with a 7.8-fold higher risk of NTM.1 The relationship between an NTM infection and asthma is complex. It has been demonstrated that the risk of NTM lung disease has 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.11,40

A study has suggested that patients with poorly controlled asthma represent a very high-risk group for NTM lung disease. It’s believed that NTM infections associated with asthma may be under-recognized and should be part of the differential diagnosis in difficult-to-treat patients.40

This case-controlled study evaluated 22 patients with difficult-to-treat asthma referred to a tertiary academic referral center and subsequently found to have infection with NTM. Each case was matched with 2 control subjects (next 2 consecutive patients referred for asthma management).40

  • Case subjects with NTM typically40:
    • Were older
    • Had a longer disease duration (asthma)
    • Had more severe airflow obstruction with significantly lower forced vital capacity (FVC)
    • Had a longer duration of ICS use
    • Had a larger percentage of oral steroid use

Recognizing host susceptibility factors that increase risk for NTM is critical to early identification and evaluation of NTM

Recognizing susceptible patient types

Keep patients like these top of mind

Nodular Bronchiectatic

Do you have patients like this in your practice?

They may have an NTM infection

Nodular bronchiectatic patient

Gender: Female

Age: 70

Weight: 120 lb

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Patient History: patient with 3 years of productive cough, with yellow, brown, and occasionally blood-tinged sputum and chest pain; patient mentioned she was previously diagnosed with bronchiectasis. Primary care physician (PCP) ordered an acid-fast bacilli (AFB) smear, which showed a positive result. As symptoms progressed, NTM was suspected and patient was referred to a pulmonologist

Physical Examination: tall, slender, scoliosis, pectus excavatum; auscultation: mitral valve prolapse, wheezing, and crackles

X-Ray/CT Scan: showed nodular opacities with local bronchiectasis and local cystic bronchiectasis

AFB Smear: positive, but negative polymerase chain reaction (PCR) assay for M tuberculosis

Culture: Mycobacterium avium isolated from 3 sputum samples

Susceptibility Testing: susceptible to clarithromycin

Treatment & Follow-Up: NTM was treated with a multidrug regimen three times a week (TIW) according to the ATS/IDSA Statement

  • Monthly patient visits and sputum cultures
  • Improved clinical symptoms; sputum production became minimal
  • Patient was treated for 6 months and sputum AFB culture was negative last month

Therapy should continue until this patient remains culture-negative for 12 months

Fibrocavitary

Are you currently treating patients like this?

They may have an NTM infection

Fibrocavitary patient

Gender: Male

Age: 55

Weight: 180 lb

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Patient History: patient with one year of progressive cough with greenish sputum; treated for pneumonia with multiple antibiotics without symptomatic improvement. Patient is currently a smoker and has severe COPD. Positive sputum culture showed AFB and confirmed infection with Mycobacterium intracellulare. Patient was referred to an infectious disease (ID) specialist with experience treating NTM

Physical Examination: overweight, wheezing, and cracklings on auscultation

X-Ray/CT Scan:

  • Chest CT scan showed thin-walled cavity in right upper lobe
  • Severe emphysematous changes
  • Stable calcified nodule in right upper lobe and mediastinal lymphadenopathy
  • X-ray and CT scan showed cavitary lesions

AFB Smear: positive

Culture: 3 positive samples identified Mycobacterium intracellulare

Susceptibility Testing: susceptible to clarithromycin

Treatment & Follow-Up: NTM was treated with a multidrug regimen daily according to the ATS/IDSA Statement

  • Monthly patient visits and sputum cultures
  • Symptoms improved; sputum production was reduced
  • Sputum continued to be positive for 6 months and an additional agent was added to therapeutic regimen. Four months later, his sputum was still AFB-positive but showed reduced mycobacterial burden

Therapy should continue under close monitoring with a goal to achieve sputum conversion to negative

Recurring Lung Infections

Do you hear stories like this in your practice?

These patients may have an NTM infection

Patients with recurring infections

Gender: Female

Age: 70

Weight: 180 lb

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Patient History: patient with dry cough for the past 4 years; diagnosed with anemia, asthma, hyperlipidemia, with family history of TB. Treated previously for pneumonia and TB. Patient was referred to pulmonologist and was diagnosed with NTM. After treatment initiation, ocular toxicity was detected and treatment was stopped

Physical Examination: overweight, wheezing, and cracklings on auscultation

X-Ray/CT Scan: nodular opacity and bronchiectasis

AFB Smear: reported positive in 2 sputum samples

Culture: Mycobacterium avium isolated from 3 sputum samples

Treatment & Follow-Up: treatment was stopped due to potential side effects. Patient is currently stable with symptoms closely monitored

  • Patient visits every 3-6 months
  • Patient did not achieve culture conversion

Patient should be monitored closely for worsening symptoms