Health Impact of Non-Tuberculous Mycobacteria Pulmonary Disease (NTM-PD)

Official title

An Observational Cross-sectional Study Exploring Differences in Health Between People With Non-Tuberculous Mycobacteria Pulmonary Disease and People With Bronchiectasis Without NTM Pulmonary Infection.

Overview

Nontuberculous mycobacteria (NTM) are environmental organisms found in soil and water. The majority do not cause human disease. When they do, this is mostly as a chronic lung infection in people with long-term lung problems such as chronic obstructive pulmonary disease (COPD), bronchiectasis, or cystic fibrosis. The number of people with NTM pulmonary disease (PD) is increasing, and its management can be complex, requiring prolonged treatment with multiple, often toxic, drugs in someone who may already be frail. Non-drug approaches, such as airway clearance techniques, structured exercise, nutritional support and psychological care are used to help manage bronchiectasis and COPD. However, there is limited evidence about their benefit in people with NTM-PD. Also, it is not clear whether these patients' health needs are different from people with bronchiectasis alone. The investigators want to identify the most important symptoms encountered by people with NTM-PD and patient preferences for care. The study also aims to explore whether the need for non-drug measures differs between people with and without NTM-PD who have other underlying lung disease. The research will take place at one NHS centre and involve a single assessment of 40 people with NTM-PD not using specific antibiotics to treat their NTM and 40 people with bronchiectasis but no evidence for NTM. Following consent, and mainly using questionnaires, participants will be asked about their physical and mental health, and nutritional status. Exercise capacity, muscle strength and body muscle/fat composition will also be assessed using simple tests. The total time required will be a maximum of one hour. Recruitment to the study will last around six months. The results will help improve understanding of specific needs of people with NTM-PD and guide clinically relevant research in this area.

Detailed description

Nontuberculous mycobacteria are environmental organisms primarily found in soil and water, including locations such as lakes, rivers, agricultural zones, and some industrial sites. Environmental changes facilitate the transport of these organisms to many different settings, including external and internal living spaces. NTM are separate from the Mycobacterium tuberculosis complex (the cause of tuberculosis) and are not the mycobacteria that cause leprosy. With around 200 species, these organisms can be classified into slow growing mycobacteria (SGM ≥ 7 days) or rapid growing mycobacteria (RGM \< 7 days), based on their growth rate in solid culture medium. M. avium, M. kansasii, M. xenopi, and M. abscessus are the most common NTM species that can cause pulmonary disease. Unlike M. tuberculosis these mycobacteria are not pathogens, but in the right setting, they can infect humans and produce clinical disease. This is most often seen in people with pre-existing lung damage due to bronchiectasis, chronic obstructive pulmonary disease (COPD), or cystic fibrosis, and NTM infection results in worsening health, and the development of a chronic respiratory illness, NTM-PD.

This study is designed to explore the impact of non-tuberculous mycobacteria-pulmonary disease (NTM-PD) on patients' health, to explore what symptoms are of most concern to people with NTM-PD and to better characterise what non-pharmacological interventions might help this patient group.

The study questions guiding this research are:

1. What are the key clinical differences between people living with NTM pulmonary disease and people with bronchiectasis? 2. What symptoms are of most importance to people with NTM-PD and is this different to people with bronchiectasis? 3. Does the need for non-pharmacological intervention differ for people with NTM-PD compared to other patients with bronchiectasis without NTM-PD? This will be done by comparing the symptoms, investigation results and physiological measurement of people with NTM-PD to a group at risk of NTM-PD but without either NTM infection or disease, namely people with bronchiectasis but no evidence for NTM pulmonary infection. By identifying and analysing any differences between these groups, the study aims to increase the understanding of NTM-PD and so contribute to the development of more effective and evidence-based clinical practice.

This will be accomplished by integrating validated Patient-Reported Outcome Measures (PROMs) with radiological evaluation and respiratory assessments. Additionally, a self-reported questionnaire will be used to rank the most significant symptoms associated with NTM-PD, as well as the daily living activities affected, from the patients' perspective.

The findings could reveal key differences in clinical features and symptoms between these groups, helping to optimise non-pharmacological interventions, improve treatment plans for people with NTM-PD, and highlight areas for future research.

Primary outcome measures

• Health Related Quality of Life [Time frame: Baseline (during the past week)]

Secondary outcome measures (8)

• Nutritional Status [Time frame: Baseline (during the past 3 months)]
• Level of depression [Time frame: Baseline (during the past 2 weeks)]
• Breathlessness [Time frame: Baseline (Day of study visit)]
• Lung function test [Time frame: The most recent test done within the past 2 years.]
• Respiratory muscle strength [Time frame: Baseline (Day of study visit)]
• Physical Activity [Time frame: Baseline (Day of study visit)]
• Body composition [Time frame: Baseline (Day of study visit)]
• Lung condition [Time frame: The most recent CT scan done within the past 2 years.]

Eligibility criteria

Inclusion criteria

\- Age: 18 years or older, able to provide informed consent.

NTM-PD Group:

• Participants will be adults diagnosed with confirmed NTM-PD based on the British Thoracic Society (BTS) guidelines.
• The participant should not be on any antimicrobial therapy (at least two weeks before participation) and should not have previously received or be currently on antimicrobial therapy for NTM-PD.

\* BTS guidelines:

• Clinical (both required):
• Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or a high-resolution CT scan that shows multifocal bronchiectasis with multiple small nodules.
• Appropriate exclusion of other diagnoses.
• Microbiological:
• A minimum of two positive expectorated sputum culture results of the same NTM species from samples collected on separate days within 12 months before recruitment.

OR

• Positive culture results from at least one bronchial wash or lavage. OR
• Transbronchial or other lung biopsy with mycobacterial histopathological features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histopathological features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture-positive for NTM.

Bronchiectasis Group:

• Diagnosed with bronchiectasis, as confirmed in medical records based on clinical assessment, and radiological findings.
• Never had a history of positive culture result for NTM pulmonary infection.
• The latest NTM-negative result must be within the past 12 months from the study's start date or no earlier than 2024.

Exclusion criteria

\- Age: Under 18 years of age, or unable to provide informed consent.

NTM-PD Group:

• No confirmation of NTM-PD diagnosis.
• Diagnosed with a reinfection of NTM-PD.
• Started antimicrobial therapy for NTM-PD.

Bronchiectasis Group:

• No diagnosis of bronchiectasis or diagnosis of bronchiectasis with NTM-PD.
• Diagnosed with other chronic respiratory diseases considered primary conditions, rather than bronchiectasis.
• Participants with a history of NTM pulmonary infection.
• NTM-negative results obtained before 2024.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 1 center

• Royal Free London NHS Foundation Trust — London

Publications

• Sulaiman N, Martins B, Moreira-Sousa D, Aguiar A, Hurst JR, Brown J, Duarte R, Lipman M. Optimising non-pharmacological interventions in people with non-tuberculous mycobacterial pulmonary disease: a systematic review. ERJ Open Res. 2025 Dec 22;11(6):00533-2025. doi: 10.1183/23120541.00533-2025. eCollection 2025 Nov. PMID 41438867
• Ratnatunga CN, Lutzky VP, Kupz A, Doolan DL, Reid DW, Field M, Bell SC, Thomson RM, Miles JJ. The Rise of Non-Tuberculosis Mycobacterial Lung Disease. Front Immunol. 2020 Mar 3;11:303. doi: 10.3389/fimmu.2020.00303. eCollection 2020. PMID 32194556
• Winthrop KL, Marras TK, Adjemian J, Zhang H, Wang P, Zhang Q. Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in a Large U.S. Managed Care Health Plan, 2008-2015. Ann Am Thorac Soc. 2020 Feb;17(2):178-185. doi: 10.1513/AnnalsATS.201804-236OC. PMID 31830805
• Chalmers JD, Polverino E, Crichton ML, Ringshausen FC, De Soyza A, Vendrell M, Burgel PR, Haworth CS, Loebinger MR, Dimakou K, Murris M, Wilson R, Hill AT, Menendez R, Torres A, Welte T, Blasi F, Altenburg J, Shteinberg M, Boersma W, Elborn JS, Goeminne PC, Aliberti S; EMBARC Registry Investigators. Bronchiectasis in Europe: data on disease characteristics from the European Bronchiectasis registry PMID 37105206
• Kunst H, Wickremasinghe M, Wells A, Wilson R. Nontuberculous mycobacterial disease and Aspergillus-related lung disease in bronchiectasis. Eur Respir J. 2006 Aug;28(2):352-7. doi: 10.1183/09031936.06.00139005. Epub 2006 Apr 12. PMID 16611651
• Lipman M, Kunst H, Loebinger MR, Milburn HJ, King M. Non tuberculous mycobacteria pulmonary disease: patients and clinicians working together to improve the evidence base for care. Int J Infect Dis. 2021 Dec;113 Suppl 1:S73-S77. doi: 10.1016/j.ijid.2021.03.064. Epub 2021 Mar 26. PMID 33781905
• Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, Leitch A, Loebinger MR, Milburn HJ, Nightingale M, Ormerod P, Shingadia D, Smith D, Whitehead N, Wilson R, Floto RA. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017 Nov;72(Suppl 2):ii1-ii64. doi: 10.1136/thoraxjnl-2017-210927. No abstract available. PMID 29054853

Identifiers

NCT: NCT07192705 · 178013 · IRAS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗