Two ad hoc registries have recently been launched aimed at studying the epidemiology of non-tuberculous mycobacteria (NTM) pulmonary disease

IRIDE (the Italian Registry of bronchiectasis) falls under EMBARC, which is a pan-European multicentre bronchiectasis database incorporating baseline data collection with annual follow-up data.  

IRENE (the Italian Registry of Vascular Lung Diseases) is the first registry in Europe dedicated to the collection of all cases of patients with NTM respiratory infections. This registry will play a key role as a platform for conducting observational or interventional studies in the near future, aimed at improving the chances of care and quality of life of patients.

Bronchiectasis and NTM-related respiratory infections are two rare pulmonary conditions sharing frequent failure diagnosis, lack of specific therapies, and a mutual cause-effect relationship.

NTM was the focus of the recent 2nd World Bronchiectasis Conference, held in Milan that included 350 participants from 38 countries.

What is bronchiectasis?

Bronchiectasis is a respiratory disease that has a prevalence of 168 cases per 100,000 inhabitants across Europe and which causes cough, mucus production and recurrent respiratory infections. The bronchi are dilated, in most cases irreversibly. This dilation makes it difficult to eliminate bronchial secretions that become dense and transform the bronchial surface into an ideal place for colonization and chronic infection by bacteria, fungi, and viruses.

In particular, it has been demonstrated that among the infecting agents, an important role is played by NTMs that cause recurring acute episodes. The presence of pathogenic microorganisms causes chronic inflammation that leads to further damage to the bronchial tissue with worsening of the bronchiectasis, a true vicious circle.

Infection by non-tuberculous mycobacteria

NTMs belong to the same genus of those responsible for tuberculosis from which they differ, however, for habitat, virulence and transmission of infection. At present, approximately 160 different species of NTM are known, 25 of which clinically relevant for humans. The agent most commonly responsible of pulmonary infections is Mycobacterium avium, which includes several subspecies and is therefore also referred to as Mycobacterium avium complex (MAC).

Other types of NTM causing lung disease are M. abscessus and M. fortuitum. These ubiquitous microorganisms, which are transmitted not by contamination but through the environment (soil and water), cause a chronically progressive and very debilitating respiratory disease capable of causing serious lung damage with a five year mortality rate greater than 25%. Pulmonary infections by NTM have prevalence in Europe of 6.5 cases per 100,000 inhabitants: therefore, represent a rare disease.

Individuals at risk of NTM-related lung disease

All subjects with chronic respiratory diseases (from cystic fibrosis to asthma to obstructive chronic bronchopneumopathy, pulmonary fibrosis) are at risk for NTM infection. Patients with bronchiectasis appear to be particularly predisposed to NTM infections: a meta-analysis has shown that approximately one in every ten patients has a NTM pulmonary infection (a total prevalence of 9.3%). However, the opposite is true as well, being that the presence of NTM in a non-bronchiectomy lung can in turn lead to the development of bronchiectasis. There is therefore a close, two-way relationship between bronchiectasis and NTM.

Diagnostic delays and lack of effective treatments

Both diseases are characterised by an important diagnostic delay due to the absence of specific symptoms and the lack of specific therapies. In the case of non-tuberculous mycobacterium, it has been assessed that if a patient visits the family physician due to the common symptoms, the suspected diagnosis is only raised in 10% of cases.

On average a further 4.4 assessments are needed by other healthcare providers before reaching the final diagnosis, which is regularly given five months after the first doctor consultation. This is due to the symptoms often being masked by the underlying condition. There are still no standardised treatments for either pathology.  

Bronchiectasis involves complex multidisciplinary management in a team coordinated by the pneumologist, which involves the collaboration of immunologists, microbiologists, infectologists, physiotherapists. Treatment for NTM pulmonary disease foresees use of antibiotics used for treatment of tuberculosis, but they are not specific to these bacteria. Treatment is usually multi-drug and long term, however it often does not lead to the resolution of the infection which tends to recur. Moreover, it is associated with several side effects, further complicating the patient's adherence to therapy.