What is MAC lung disease?

MAC lung disease is a slow-growing disease caused by a class of bacteria known as the Mycobacterium avium complex (MAC). This is a type of non-tuberculous mycobacteria (NTM) infection. MAC lung disease has over 200 causative agents, including Mycobacterium avium and Mycobacterium intracellulare. These bacterial species are closely related, and it is often difficult to distinguish the infections caused by them, so they are grouped as Mycobacterium avium complex (MAC) causative agents of MAC lung disease.¹

Where are MAC bacteria found?

MAC bacteria inhabit many natural environments such as rivers, lakes and organic-rich soil. Growth and survival are successful in these environments due to the rich nutrition the MAC bacterium gains from these areas. MAC bacteria also grow in household environments like water taps, showerheads and air conditioning systems.² This is achieved through MAC bacteria producing biofilm (a layer of growing bacteria and other microorganisms which can be infectious upon contact) over these objects. Similarly, MAC bacteria can produce biofilms on hospital equipment such as catheters, endoscopes and water systems. 

How is MAC transmitted?

MAC lung disease is often contracted through environmental exposure. As it is not contagious, it cannot be contracted from an infected person. The trasmission of MAC bacteria occurs through the inhalation of dust/aerosols contaminated with these bacteria or through the ingestion of contaminated water.² 

MAC transmission in the immunocompromised patients

Most individuals who breathe in or ingest these bacteria are not typically harmed, as their functioning immune system can easily clear them. However, those with underlying conditions such as chronic obstructive pulmonary disorder (COPD) or immunocompromising conditions will be more susceptible to MAC lung diseases.¹ For example, contracting M. avium will initiate a severe MAC infection or disease in HIV patients.² This is due to their inability to fight infection as the levels of antibodies in their blood are reduced. 

Why should the trends of MAC be studied?

In 2023, there were approximately 119000 cases of MAC lung disease, including 64% of these cases emerging from the United States, 8% in Europe and the UK and 28% from Asia (most notably Japan).³ These figures show that MAC lung disease is increasing, even in developed countries with strong healthcare infrastructures.⁴ Therefore, it is crucial to understand what is the cause behind this sudden rise in cases in order to effectively treat and prevent MAC.

Global burden of MAC lung disease

Epidemiologic Insights in the United States

The frequency of MAC cases ranges from 1.4 to 6.6 per 100,000 people, with states such as Hawaii reporting 44 people per 100,000. The incidence of rising cases in the U.S. is approximately 2.5-8% per year,² with women and the elderly being particularly at risk. 

Emerging trends that may explain the cause behind this rise are the ageing population contracting MAC lung disease more. This is due to a decline in their immune system, as the elderly are less able to fight off infection as well as reduced lung elasticity and structural changes in the lungs help to accommodate MAC bacterium growth. Cases of underlying health issues such as cystic fibrosis, COPD and bronchiectasis also increase vulnerability to MAC growth and infections.¹ A cystic fibrosis case study in the US (2010-2019) showed that over half of NTM pulmonary infections occurred in cystic fibrosis patients, with a higher frequency in the northeast regions.⁵

The most notable trend of MAC is Lady Windermere Syndrome (LWS). This involves distinct forms of MAC lung disease occurring exclusively in elderly women, who voluntarily suppress their cough reflex. They are not signs of any other underlying lung diseases.⁶ The predisoposing factor could be pulmonary structure, where the right middle lobe of the bronchi in the lungs is narrow and often receives poor ventilation.  The suppression of the cough reflex stops patients from clearing bacteria from their lungs, leading to subsequent infection.⁶ During the menopause, people assigned female at birth often experience a decline in levels of the hormone oestrogen. This can reduce the ability of white blood cells to effectively clear MAC bacteria from the lungs. Additionally, patients who try to stop coughing also prevent the removal of bacteria from the lungs. 

Epidemiology of MAC in asia

MAC lung diseases account for around 68% of pulmonary NTM infections in eastern Asia.⁷ Japan accounts for over 60% of NTM infections ⁸ whereas in South Korea and China, MAC infections due to M. intracellulare are more common (46% of cases) compared to M. avium (22% of cases).⁹

In Asia, specifically Singapore,  a different demographic of patients compared to other regions is observed. The median age of MAC patients in Singapore is around 70, with 62%  patients assigned male at birth.¹⁰ This trend is particularly interesting as it contrasts with the increasing cases in women from the USA. This alternative trend can be explained by the likelihood of men in Singapore (and other East Asian countries) previously or currently smoking, which research has proven to be fatal. Additionally, many men may have had increased exposure to environmental exposure compared to women, such as construction, manufacturing and agriculture activities. As water, dust and soil are heavily involved in these practices, this exposure can justify the trend of increase in male MAC patients in Singapore, China and Japan.¹⁰

Diagnostic challenges

Colonisation or disease?

One key challenge in the diagnosis of MAC is the differentiation between colonisation of MAC bacteria and actual disease. MAC bacteria are naturally found in the environment, in areas that are commonly in human contact (soil and water). Therefore, the presence of these bacteria in the body does not necessarily mean someone has MAC disease. Those with underlying health issues are often colonised with the MAC bacterium but often show no symptoms of disease. This causes challenges in diagnosis. 

Non-specificity of symptoms 

The symptoms associated with many MAC infections and diseases are non-specific. These vague symptoms include persistent coughing, fatigue and weight loss, which can be easily mistaken for a variety of other complications. This can cause a delayed diagnosis or a misdiagnosis.  Elderly women can show no underlying diseases or health issues, which would place them in a low-risk group for MAC lung disease.⁶ These cases make MAC lung diseases difficult to diagnose and can lead to a lack of proper diagnosis and treatment. 

Inefficient lab diagnostics methods

Using microscopy to identify MAC bacteria from patient samples or growing bacteria in the lab is a helpful method of investigating MAC bacteria and confirming diagnosis in patients. However, MAC takes 2-6 weeks to grow. Moreover, growth cultures can be negative in the early stages of disease. This time lag interferes with efficient diagnosis and hinders treatment plans for the patient.¹¹

Molecular testing is also key for identifying various diseases, as it is much more efficient than slow microscopy and culture-based techniques. Molecular diagnostics such as polymerase chain reactions are less accessible for MAC as it is not as frequent as tuberculosis. rRNA sequencing can be used to identify the genetic makeup of the bacteria and confirm that it is MAC; however, this is not a routine diagnostic method in many countries. Therefore, reliance is heavy on slower culture-based techniques, which increases the waiting time for patients to be diagnosed and treated.¹¹

Treatment of MAC lung disease

Non-drug-based treatments

For those with minimal symptoms and changes, antibiotic treatment may not be needed. Instead, routine check-ups involving breathing tests and mucus cultures are provided. Airway clearance therapies include a range of breathing treatments using a nebuliser and other devices, which help to remove bacteria-filled mucus from the airways of the lungs.

Antibiotic treatment

If the above measures do not help to clear MAC infections, antibiotics are prescribed. A routine using multiple antibiotics (for 12 months) is typically carried out in order to reduce the chances of resistance to antibiotics. The key drug in this multi-drug regimen is clarithromycin, a type of macrolide antibiotic.¹² This drug helps to stop bacteria from forming proteins, which in turn stops the growth and survival of MAC bacteria in the lungs. Rifampin may also be used to stop the bacteria from producing genetic material. As these antibiotics target a separate cellular component of MAC bacteria, they can effectively clear these bacteria. However, a major concern in antibiotic usage is the resistance to macrolides that patients may experience with overuse. This can happen if macrolides alone are used, and so it is important to have a multi-drug regimen, as multiple antibiotics can fight the disease better than one.¹²

Public health, economic implications and future direction

With delayed and misdiagnosis being common, MAC lung disease can cause a significant burden to the healthcare systems and economy if treatment is long-term. Those who are asymptomatic may be treated too late, and this results in worse outcomes and prolonged disease. This reduces their quality of life and, in turn, increases the length of hospital stays and requires more health workers and medical equipment to treat MAC cases.¹³ This means more antibiotics, more imaging (CT scans) and more monitoring in the lab. Other factors, such as patients and carers taking days off work or retiring earlier, must also be considered, as this brings financial strain on patients, their families and employers.

Thorough data collection and registration are essential to track frequency and trends accurately. In many countries, MAC lung disease is not notifiable.¹⁴ Tuberculosis has a structured system for reporting disease, whereas NTM infections do not have such a system. This is a key reason why MAC diseases are on the rise. 

Improving the diagnostic methods will help to accurately detect infections much earlier and reduce misdiagnosis and less effective treatments. Encouraging prevention strategies is key to help reduce the amount of MAC cases and increase public awareness.¹³ This can be achieved through investment in vaccine development to overcome antibiotic resistance¹⁴. A broad approach is therefore needed, consisting of surveillance, innovation, and public health preparedness in order to effectively control global MAC lung disease.¹³

Summary

Mycobacterium avium complex (MAC) lung disease is a slow-growing respiratory infection caused mainly by M. avium and M. intracellulare, found in soil, water, and biofilms in both household and hospital environments. It is not contagious but is transmitted through inhaling or ingesting contaminated dust or water, primarily affecting people with weakened immune systems, chronic lung diseases, or structural lung abnormalities.

Global incidence is rising—about 119,000 cases in 2023, with most from the U.S., Japan, and parts of Asia. In the U.S., elderly women (often linked to “Lady Windermere Syndrome”) are at higher risk, while in East Asia, older men are more commonly affected due to smoking and occupational exposure.

Diagnosis is challenging due to non-specific symptoms, difficulty distinguishing colonization from disease, and slow culture growth times. Molecular tests exist but are not widely used. Treatment involves long-term multidrug antibiotic regimens (often macrolides with rifampin) and airway clearance therapies, but antibiotic resistance is a growing concern.

The disease imposes a significant healthcare and economic burden due to delayed diagnosis, prolonged treatment, and reduced patient quality of life. Improved surveillance, faster diagnostics, public awareness, and vaccine development are key to controlling MAC lung disease globally.