Establishing a Diagnostic Test for Non-tuberculous Mycobacteria Lung Infection Using Non-tuberculous Mycobacteria Antigen Stimulation Test: From Immune Base, Standardized Setup to Validation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01676142
Recruitment Status : Unknown
Verified June 2011 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : August 30, 2012
Last Update Posted : August 30, 2012
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
  1. To compare TLR-2 expression of peripheral blood mononuclear cells and serum downstream cytokines in those with MAC or MAB pulmonary infection and those with MAC or MAB pulmonary colonization and controls.
  2. To investigate the response of TLR-2 expression and cytokines activation to NTM stimulation test in patients with MAC or MAB pulmonary infection and colonization and controls.
  3. To validate the NTM stimulation test for NTM pulmonary infection.

Condition or disease
To Set up NTM Stimulation Test Foar Diagnosing NTM Pulmonary Infectionon.

Detailed Description:

The increase of nontuberculous mycobacteria lung infection Nontuberculous mycobacteria lung infection (NTM-LD) becomes an important clinical concern [1] because the rate of NTM infection has increased over the past ten years [2-3]. According to a study in Taiwan, NTM-LD increased from 1.26 to 7.94 per 100,000 inpatients/year during 2000 to 2008 [2]. The reasons for this increase are not readily clear, but could be related to the growth in numbers of the acquired immunocompromised population and advances of technique for mycobacterial culture [4-7]. Among the NTM infection in Taiwan, Mycobacterium avium complex (MAC) and M. abscessus (MAB) were most frequently isolated [2].

The difficulty in early diagnosing and confirming true NTM-LD However, NTM exists in the environment ubiquitously, so the relevance (true disease patient number over the number of patients with disease or just colonization) is far less than 100% and varied in different NTM species. For example, previous studies have shown that the presence of M. kansasii and MAC had a clinical relevance around 47~70% and 35~42%, respectively [8-9]. As for MAB which is emerging pathogen worldwide, has a relevance of 33% [9]. According to contemporary NTM guidelines established by American thoracic society, NTM pulmonary infection is diagnosed by multiple criteria including microbiology of respiratory specimen and clinical findings as well as radiographic findings [1]. In microbiology criteria, two or more sets of positive sputum mycobacterial culture for the same NTM species within one year is needed.

Because NTM colonization is not uncommon in respiratory tract, diagnosis of true pulmonary NTM infection is a great challenge in clinical practice. Actually, microbiology tests for mycobacteria are neither timely nor efficient. Mycobacterial culture is time-consuming, which needed weeks to wait the results even though it's current gold standard for micro-organism identification [10]. The nucleic acid amplification method such as polymerase chain reaction could not discriminate true NTM infection and solely colonization because the micro-organism is present in both situations [11].

To early diagnose and then start treatment of NTM infection is important because NTM pulmonary infection might be rapid lethal infection in intensive care unit or in patients who had not received early proper treatment [6]. In addition, MAC or MAB which are most common in Taiwan are resistant to most of anti-tuberculosis regimen. Hence, more rapid and accurate diagnostic test should be developed [1-2, 6] The help of innate immunity in diagnosing NTM-LD The body inflammatory marker, represent our immune response, would be an indicator for differentiating true mycobacterial pulmonary infection from colonization while the first set of mycobacterial culture grew NTM [12-15]. Both interferon-gamma and tumor necrosis factor-alpha play critical roles in protective immunity to mycobacterial infections [16-17]. These responses are linked to engagement of Toll-like receptor 2 (TLR2) that is critical for mycobacterial infection [18]. However, the TLR-2 expression has not been evaluated between patients with NTM infection and colonization. According to the success of application of interferon-gamma release assay for tuberculosis detection [19], we understand the specific immune response is helpful to diagnose mycobacterial infection. We therefore focus on the expression of TLR-2 and associated downstream cytokines in our patients with MAC or MAB lung disease, which accounts the most of NTM infection [2].

The design in our study for diagnosis In order to investigate the help of host immune in diagnosing NTM pulmonary infection, we initially compare the baseline expression of TLR-2 and downstream cytokines in the MAC or MAB infected patients and colonized subjects. Then, we perform an in-vitro stimulation test using mycobacteria (MAC or MAB) for co-culturing with peripheral blood mononuclear cells of patients. The TLR-2 expression and cytokines activation will be examined after the stimulation test. We then analyze the expression difference between NTM-LD and colonization.

Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Establishing a Diagnostic Test for Non-tuberculous Mycobacteria Lung Infection Using Non-tuberculous Mycobacteria Antigen Stimulation Test: From Immune Base, Standardized Setup to Validation
Study Start Date : January 2011
Estimated Primary Completion Date : January 2014
Estimated Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

Patients with NTM pulmonary infection
Patients with other pathogen related lung infection
Patient with NTM pulmonary colonization

Primary Outcome Measures :
  1. Patients with non-tuberculous pulmonary infection [ Time Frame: 3 year ]

Secondary Outcome Measures :
  1. mortality [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
  1. Patients with NTM pulmonary infection: diagnosed by NTM guidelines by American Thoracic Society(ATS)
  2. Patients with NTM pulmonary colonization: Patients are not fulfilling the ATS diagnostic criteria but having at least one set of positive sputum for NTM (colonization).
  3. Patients have pulmonary infiltrates, not related by NTM: three sets of respiratory specimens that are negative for NTM.

Inclusion Criteria:

  • Age ≥ 18 years
  • A patient has at least 3 sets of respiratory specimen for mycobacterial culture.

Exclusion Criteria:

  • Age younger than 18 years.
  • Patients who have pregnancy.
  • Patients who have acquired immunodeficiency syndrome
  • Patients who have bleeding tendency which can not tolerate venous puncture such as hemophilia, thrombocytopenia.
  • In NTM infection group, patients having received anti-NTM treatment for one week will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01676142

Contact: Chin-Chung Shu, MD 886972653087

National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Chin-Chung Shu, MD    886972653087      
Principal Investigator: Chin-Chung Shu, MD         
Sponsors and Collaborators
National Taiwan University Hospital
Principal Investigator: Chin-Chung Shu, MD National Taiwan University Hospital

Responsible Party: National Taiwan University Hospital Identifier: NCT01676142     History of Changes
Other Study ID Numbers: 201012082RC
First Posted: August 30, 2012    Key Record Dates
Last Update Posted: August 30, 2012
Last Verified: June 2011

Additional relevant MeSH terms:
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections