Short summary

NTM disease is a heterogeneous disease entity with significant diagnostic difficulties. The prevalence of NTM disease is increasing globally and the morbidity and mortality related to NTM disease are both high despite treatment. Further study and characterization of NTM disease is thus warranted.

Rationale

Non-tuberculosis mycobacteria (NTM) are a heterogeneous group of bacteria that are ubiquitous in both natural and manmade environments. NTM are commonly found in water, sanitary facilities, soil, milk, and in animals and humans. Infection is transmitted from the environment via ingestion, inhalation, and dermal contact and rarely through person-to-person contact. More than 190 species have been identified.

The incidence of NTM disease in Denmark has been reported as 1.08/100,000 using data from 1997-2008. A more recent study reported the incidence of 1.2/100.000 from 1991-2015. This contrasts with the increases in NTM disease internationally where the incidences in the US and in Canada are up to 15.2/100,000 and 41.3/100,000 respectively

Treatment of NTM disease is complex and requires multiple drugs. Side effects are common and can be severe and include nephrotoxicity, hepatotoxicity, leukopenia, and thrombocytopenia. Treatment regimens are usually based on observational studies, and few randomized clinical trials exist. Surgical intervention in treatment resistant cavitary pulmonary-NTM (P-NTM) has also been suggested, although the data are sparse. There are no randomized clinical trials about optimal treatment duration and the recommendations are mostly based on the observational studies. The duration of antibiotic treatment is long, commonly lasting months to years, and often continued until 12 months after sputum culture conversion. A study on treatment of P- NTM in Canada showed a median duration of 14 months. The 5-year mortality rate is as high as 35% among patients with NTM disease. Patients with P-NTM also have a significantly lower quality of life. To obtain a better understanding of this increasing global health problem, and to improve treatment outcomes, there is a need to further investigate the epidemiology, risk factors, and treatments of NTM infections.

Hypothesis: Systematic evaluation of risk factors, CT-scans, immunological status, and host directed treatment may lead to substantially improved treatment outcomes and prognoses for patients with pulmonary and extrapulmonary NTM.

Description of the cohort

Patients will be enrolled from the centers responsible for treating NTM disease at Odense University Hospital and Aarhus University Hospital.

Inclusion criteria: Age >=18 years Diagnosed with culture verified NTM disease as defined by ATS/ERS/IDSA case definition in the regions of Southern and Central Denmark

Data and biological material

Blood samples, immunological biomarkers, sputum samples, data from the patient record.

Collaborating researchers and departments

Department of Pulmonary Medicine, Aarhus University Hospital

• Andreas F. Hvass, MD. PhD

Department of Pulmonary Medicine, Odense University Hospital

• Ingrid Titlestad, Consultant, PhD.

Department of Infectious Diseases, Odense University Hospital

• Isik S. Johansen, MD, DMSc, Professor
• Inge K. Holden, MD, MPH, PhD

Department of Medicine, Vejle Hospital, University Hospital of Southern Denmark

• Ole Hilberg, DMSc., Professor