Skip to main content
Download PDF

Comparative analysis of non-tuberculous mycobacterial lung disease and lung colonization: a case-control study

BMC Infectious Diseases volume 24, Article number: 1159 (2024) Cite this article

Abstract

Background

Non-tuberculous mycobacteria (NTM) are common opportunistic pathogens, and the most common infection site is lung. NTM are found commonly in the environment. Many patients have NTM lung colonization (NTM-Col). NTM lung disease (NTM-LD) have no specific sympotms, though it is hard to differentiate NTM-LD and NTM-Col under this circumstance. The aim of this study is to explore the differences between NTM-LD and NTM-Col for future clinical diagnosis and treatment.

Methods

We retrospectively enrolled patients who had a history of NTM isolated from respiratory specimens in Peking Union Medical College Hospital (PUMCH) from January 1st, 2013 to December 31st, 2022. Patients were classified into NTM-LD group and NTM-Col group. Demographic characteristics, clinical manifestations, laboratory tests and imaging findings of the two groups were compared. Comparative analysis was also performed in peripheral blood lymphocyte subsets among three groups.

Results

A total of 127 NTM-LD patients and 37 NTM-Col patients were enrolled. Proportion of patients with bronchiectasis was higher in NTM-LD group than in NTM-Col group (P = 0.026). Predominant NTM isolates were Mycobacterium avium complex (MAC). NTM-LD group had a higher proportion of Mycobacterium intracellulare (P = 0.004). CD4+ T cells counts was lower in NTM-LD group (P = 0.041) than in NTM-Col group. Imaging finding of bronchiectasis (P = 0.006) was higher in NTM-LD group than in NTM-Col group. Imaging findings of bronchiectasis (OR = 6.282, P = 0.016), and CD4+ T cell count (OR = 0.997, P = 0.012) were independent associated factors for differential diagnosis between NTM-LD and NTM-Col.

Conclusion

NTM isolates from both NTM-LD and NTM-Col patients were predominantly MAC, with a higher Mycobacterium intracellulare isolation rate in NTM-LD group. Imaging findings of bronchiectasis and lower peripheral blood CD4+ T cell count may be helpful to separate the diagnosis of NTM-LD from NTM-Col.

Peer Review reports

Introduction

Non-tuberculous mycobacteria (NTM) includes mycobacterial species other than Mycobacterium tuberculosis complex (MTBC) and Mycobacterium leprae [1]. NTM strains have certain heterogeneity [2]. Mycobacterium abscessus have a higher pathogenic potential, while Mycobacterium gordonae generally lack pathogenicity [3, 4]. NTM is widely present in soil, water, air, and also a common opportunistic pathogen isolated from the human respiratory tract [5]. Some people have colonized NTM flora within respiratory environment [6]. NTM lung disease (NTM-LD) is mainly found in hosts with pulmonary anatomical abnormalities or with immune or genetic disorders [7, 8]. Immunosuppressants, glucocorticoids, azithromycin, and proton pump inhibitors can increase the susceptibility to NTM-LD. Epidemiological survey studies in mainland China have shown that NTM-LD accounted for 6.8% of sputum anti-acid smear-positive patients, while NTM colonization (NTM-Col) or contamination accounted for 1.0% [9].

NTM isolated from airway secretions, along with symptoms such as fever and cough, and pulmonary imaging showing corresponding imaging findings such as bronchiectasis and cavitation, are commonly associated with NTM-LD. Not all NTM-LD cases present with typical clinical features, and infections with other pathogens can also present similar symptoms. The presence of NTM-Col can further complicate the diagnostic process [10,11,12]. On the other hand, although a portion of NTM-Col patients may develop NTM-LD, many will have spontaneous clearance of NTM from the sputum [13]. For these reasons, differential diagnosis between NTM-LD and NTM-Col would be helpful to doctors in clinical decision-making [14, 15]. However, this is still a challenge.

To explore associated factors for differential diagnosis between NTM-LD and NTM-Col, we conducted a single-center, cross-sectional study to analyze clinical characteristics, laboratory tests, lymphocyte subsets and chest CT imaging manifestations of these two groups.

Methods

Study population

This study was approved by the institutional ethics committee of Peking Union Medical College Hospital (PUMCH). We retrospectively enrolled patients with positive NTM isolates from respiratory specimens in PUMCH from January 1st, 2013 to December 31st, 2022. Eligible respiratory specimens included sputum, bronchial lavage fluid, and bronchoalveolar lavage fluid. The real-time quantitative PCR was applied to detect the DNA of NTM, and then the gene chip method was further used for the identification of NTM species. Based on clinical diagnoses (see diagnostic criteria section), patients were classified into two groups: those with NTM-LD and those with NTM-Col. Exclusion criteria: (a) Disseminated NTM infection; (b) Clinical data is insufficient to confirm whether NTM is pathogenic, or there is a possibility of NTM specimen contamination.

In accordance with a 1:1 ratio with the NTM-LD group, random sampling of the healthy population is conducted, matching for age and gender. The healthy control group samples need to meet the following criteria: (a) No symptoms such as fever, cough, expectoration, and hemoptysis; (b) No active lesions in chest imaging; (c) Lymphocyte subsets results can be queried. Exclusion criteria: (a) Malignancies or severe organ injury; (b) any acute illness within the past three months; (c) Long-term use of steroids, immunosuppressive drugs or biological agents.

Diagnostic criteria

The diagnosis of NTM-LD must meet the following criteria: (a) respiratory or systemic symptoms; (b) radiologic nodular or cavitary opacities on chest radiograph, or a CT scan that shows bronchiectasis with multiple small nodules, with appropriate exclusion of other diagnoses; (c) microbiologic criteria, including (i) Positive culture results from at least two separate expectorated sputum samples. If the results are nondiagnostic, consider repeating sputum acid-fast bacillus (AFB) smears and cultures or (ii) Positive culture results from at least one bronchial wash or lavage or (iii) Transbronchial or other lung biopsy with mycobacterial histologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM [10, 14, 16].

NTM-Col is defined as follows: There are no respiratory or systemic symptoms caused by NTM-LD, nor any radiographic manifestations associated with NTM-LD, or symptoms and radiographic manifestations can be explained by underlying disease and there is no NTM-LD upon long-term follow-up. Meanwhile, individuals with NTM-Col must meet one of the following conditions: (a) A single sputum specimen with positive NTM culture or molecular biology test, and the identified species is not a commonly contaminated NTM species (Mycobacterium gordonii, Mycobacterium haemophilus and Mycobacterium mucogenicum); (b) At least two separate sputum samples are positive for NTM culture or molecular biology test and are identified as the same organism; (c) At least one bronchial la vage or bronchoalveolar lavage sample is positive for NTM culture or molecular biology test.

For patients with concurrent pneumonia, or those with difficulty to determine the status of NTM-LD or NTM-Col, two infectious disease specialists should make independent judgments. If their opinions were inconsistent, a third infectious disease specialist should be consulted for assessment.

Clinical information collection

Clinical information such as demographic data, clinical presentation and laboratory tests were extracted from medical records. The subject identification code list and case report form were filled out after extracting the information. The most recent lung CT image within three months before the positive culture was assessed using the modified Reiff scoring system [17, 18]. The system independently scores each lung lobe (the lingual segment of the left lung is regarded as a separate part) with a maximum total score of 18 points and a minimum score of 0 points. The scoring criteria for each lung lobe were as follows: no bronchiectasis 0 points, tubular bronchiectasis 1 point, variceal bronchiectasis 2 points, and cystic bronchiectasis 3 points. For patients who had previously undergone lobectomy, the score of the remaining n lung lobes (parts) was calculated and multiplied by 6/n. Cavities, nodules, consolidations, patchy cords, and ground-glass opacities were also evaluated separately by two infectious disease specialists and one radiologist.

Statistical anaylsis

Statistical analysis were performed with SPSS 27.0 software. The Kolmogorov-Smirnov test was used to identify the normality of continuous data. Numerical variables with normal distributions were presented as mean ± standard deviation, and between-group comparisons were conducted using the t-test. Non-normally distributed continuous data were presented as median and interquartile range [IQR], and between-group comparisons were performed using the Mann-Whitney U test or Kruskal-Wallis H test. Categorical data were presented as frequency (percentage), and between-group comparisons were conducted using the chi-square test or Fisher’s exact test. Variables with P<0.05 in the univariate analysis were included in the binary logistic regression analysis (backward elimination method, stepwise removal of variables with P>0.1). P < 0.05 was considered statistically significant.

Results

Characteristics of the study population

Retrieving the medical database of PUMCH, a total of 1277 cases were identified from inpatients and outpatients from January 1st, 2013 to December 31st, 2022, which tested positive for mycobacterium culture or had a discharge diagnosis related to mycobacterium. After checking the clinical data, 164 eligible patients were enrolled. They were divided into two groups according to the diagnostic criteria: 127 patients with NTM-LD and 37 patients with NTM-Col. A total of 127 individuals were included in the healthy control group (Fig. 1).

Fig. 1
figure 1

Flowchart of the study. NTM-LD: NTM lung disease; NTM-Col: fi NTM colonization

Full size image

General characteristics of enrolled patients are shown in Table 1. The proportion of patients with NTM-LD combined with bronchiectasis was higher than that in the NTM-Col group (35.4% vs. 16.2%, P = 0.026). There were no statistically significant difference in other demographic characteristics or underlying diseases between the two groups. Both the NTM-LD group and the NTM-Col group showed a relatively higher prevalence in females and older patients (≥ 65 years old).

Table 1 General characteristics of NTM-LD group and NTM-Col group
Full size table

In the healthy control group, there were 53 males (41.7%), with an average age of 55 ± 15 years. There was no significant difference in age and gender distribution between the NTM-Col group and the healthy control group, which allowed for further pairwise analysis between the groups.

Clinical manifestations

NTM-LD was mainly characterized by a chronic course of illness, with a median duration of 20 months from onset to diagnosis. Symptoms included cough (113, 89%), sputum production (103, 81.1%), fever (75, 59.1%), shortness of breath (40, 31.5%), hemoptysis (34, 26.8%), fatigue (31, 24.4%), weight loss which was defined as ≥ 10% decrease of original weight (29, 22.8%), poor appetite (20, 15.7%), chest pain (16, 12.6%) and night sweats (7, 5.5%). As for physical signs, 15 patients (11.8%) exhibited signs of pleural effusion. There are 18 patients (14.2%) had wet rales, and 2 patients (1.6%) had dry rales.

Microbiological examination

Among the NTM-LD group, 37 cases (37/124, 29.8%) were acid-fast staining positive, with a total of 66 positive acid-fast staining instances (66/439, 15.0%); 118 cases (118/124, 95.2%) were positive in mycobacterial culture, with a total of 255 positive culture instances (255/434, 58.8%); molecular biology testing was positive in 110 cases (110/124, 88.7%), with a total of 179 positive instances (179/413, 43.3%). In the NTM-Col group, 1 case (1/34, 2.9%) was acid-fast staining positive, with a total of 1 positive acid-fast staining instance (1/137, 0.8%); mycobacterial culture showed positive results in 36 cases (36/37, 97.3%), with a total of 39 positive culture instances (39/110, 32.8%); molecular biology testing yielded positive results in 24 cases (24/35, 68.6%), with a total of 28 positive instances (28/95, 43.3%).

The composition of NTM species in the NTM-LD group and NTM-Col group is shown in Table 2. The proportion of MAC (Mycobacterium avium complex) isolates in the NTM-LD group was significantly higher than in the NTM-Col group (55.1% vs. 29.7%, P = 0.006). After further identification of MAC, there was a higher proportion of Mycobacterium intracellulare isolates in the NTM-LD group (38.6% vs. 13.5%, P = 0.004), while there was no significant difference in the proportion of Mycobacterium avium isolates between two groups (12.6% vs. 16.2%, P = 0.573).

Table 2 The composition of NTM species in the NTM-LD group and the NTM-Col group
Full size table

Laboratory examination

Routine laboratory tests

The laboratory test results for the NTM-LD group and NTM-Col group are shown in Table 3. The levels of hemoglobin and albumin were higher in the NTM-LD group. There were no significant differences in other routine laboratory tests between the two groups. Patients in both the NTM-LD group and the NTM-Col group did not exhibit a definitive trend of decreased blood cell count or impairment of liver and kidney function. Immunoglobulin levels were within the normal range for both groups, but elevated levels of high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and ferritin (Fer) were observed in both groups, indicating a high inflammatory state.

Table 3 Laboratory examination of patients in the NTM-LD group and NTM-Col group
Full size table

T-SPOT.TB

The T-SPOT.TB results for 76 NTM-LD patients and 22 NTM-Col patients are shown in Fig. 2. A total of 21 cases (27.6%) in the NTM-LD group tested positive for T-SPOT.TB. The median number of spot-forming cells (SFCs) for ESAT-6 was 80/106 peripheral blood mononuclear cell (PBMC) and was 64/106 PBMC for CFP-10. A total of 4 cases (18.2%)in the NTM- Col group tested positive for T-SPOT.TB. The median number of SFCs for ESAT-6 was 260/106 PBMC and was 116/106 PBMC for CFP-10. There were no significant differences in positivity rate or the number of SFCs between two groups. Within the MAC subgroup, there was also no statistically significant difference in the T-SPOT.TB positivity rate between NTM-LD and NTM-Col patients.

Fig. 2
figure 2

T-SPOT.TB results in the NTM pulmonary group and NTM colonization group. Abbreviations NTM: Non-tuberculous mycobacteria; NTM-LD: NTM lung disease; NTM-Col: NTM colonization; MAC: Mycobacterium avium complex

Full size image

Peripheral blood lymphocyte subsets

The lymphocyte subsets of NTM-LD group and NTM-Col group are shown in Table 4. The CD4+ T cell count of the NTM-LD group was lower than that of the NTM-Col group (441/µL vs. 626/µL, P = 0.041). There were no significant difference in the values or proportions of other lymphocyte subsets between these two groups. The NTM-LD group had widespread reduced counts of various lymphocyte subsets. The NTM-LD group had lower B cell (P ≤ 0.001), NK cell (P = 0.001), T cell (P = 0.01), CD4+ T cell (P ≤ 0.001), 45RA+ CD4+ T cell (P = 0.016), naïve CD4+ T cell (P = 0.023), CD8+ CD28+ T cell proportion (P = 0.013), and CD4/CD8 ratio (P ≤ 0.001) compared to healthy controls, but the CD8+ CD38+ T cell proportion of the NTM-LD group was higher than that of the healthy controls (P ≤ 0.001).

Table 4 Distribution of peripheral blood lymphocyte subsets in the NTM-LD group, NTM-Col group and control group
Full size table

Chest imaging characteristics and comparisons

The prevalence of bronchiectasis (74.8% vs. 51.4%, P = 0.006) and the severity which measured by modified Reiff score (2 vs. 1, P = 0.011) in the NTM-LD group is significantly higher than that in the NTM-Col group. We also evaluated other chest imaging performance relevant to NTM infection, including cavity, consolidation, patchy opacity, ground-glass opacity and nodule. There is no significant statistical difference in the occurrence rates of cavity (15/127, 11.8% vs. 3/37, 8.1%, P = 0.529), consolidation (39/127, 30.7% vs. 12/37, 32.4%, P = 0.843), patchy opacity (90/127, 70.9% vs. 28/37, 75.7%, P = 0.569), ground-glass opacity (44/127, 34.6% vs. 15/37, 40.5%, P = 0.514) and nodule (83/127, 64.5% vs. 27/37, 73%, P = 0.389) between the two groups.

Multivariate analysis of factors associated with differential diagnosis between NTM-LD and NTM-Col

Based on the univariate analysis, which showed statistical significance for variables such as hemoglobin (HGB) concentration, albumin (ALB) concentration, bronchiectasis signs on chest imaging, and CD4+ T cell count, a multivariable logistic regression analysis was conducted. No clear collinearity was found among the variables. The multivariable analysis revealed that imaging findings of bronchiectasis (OR = 6.282, 95%CI: 1.417–27.845, P = 0.016) and CD4+ T cell count (OR = 0.997, 95%CI: 0.995–0.999, P = 0.012) were independent factors associated with differential diagnosis between NTM-LD and NTM-Col (Table 5).

Table 5 Logistic analysis of factors associated with differential diagnosis between NTM-LD and NTM-Col
Full size table

Discussion

In our study, we found that bronchiectasis was more common in the NTM-LD group than that in the NTM-Col group. Previous studies have found that bronchiectasis is a risk factor for NTM-LD [9, 19, 20]. Furuuchi et al. found that the severity of bronchiectasis [HR = 1.32(1.14–1.53), P = 0.001] and decreased lymphocyte count (< 1000/µL) [HR = 2.33(1.29–4.22), P = 0.005] were independent risk factors for recurrence after NTM-LD treatment [21]. Additionally, NTM infection itself may also cause bronchiectasis [22, 23]. Garcia et al. found that NTM-LD group had a higher proportion and more severe bronchiectasis lesions compared to NTM-Col group (17.5% vs. 0%, P = 0.016). Low body mass index, fever at admission, pulmonary infiltrates, and cavitary lesions were also identified as independent factors associated with NTM-LD [24]. Our study further supports the association between bronchiectasis and NTM-LD. Screening and following up of bronchiectasis will contribute to prevention of NTM-LD [25].

Immunodeficiency is also a risk factor for NTM-LD. The NTM-LD patients in our study had clear evidence of immune dysfunction, showing an overall reduction in lymphocyte subsets. The numbers of B cells, NK cells, T cells, and CD4+ T cells of NTM-LD group in our study were lower than those in healthy controls group, indicating potential compromised innate and acquired immune responses in NTM-LD patients. Previous studies have supported the reduction and dysfunction of CD4+ T cells in patients with NTM-LD. Wobma et al. found that a reduced number of CD4+ T cells is a risk factor for NTM disease in children after stem cell transplantation [26]. Han et al. found increased expression of the co-inhibitory molecules programmeddeath-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-3 (TIM-3) in peripheral blood circulating CD4+ T cells of MAC lung disease patients [27].

Our study found that a decreased count of CD4+ T cells is an independent risk factor for separating the diagnosis of NTM-LD from NTM-Col. There is few research comparing lymphocyte subsets between patients with NTM-LD and NTM-Col. Pan et al. found that peripheral blood CD4+ T cells and CD8+ T cells in NTM-LD patients had higher expression of TIM-3 molecule on their surface than in individuals with NTM-Col. Surface TIM-3 on these cells has been shown to be associated with cell apoptosis and attenuation of specific cytokines. The number of TIM-3-expressing T cells was found to be higher in patients with lower BMI, advanced disease, and higher bacterial load, and decreased after treatment [28, 29]. The reduction of CD4+ T cells may increase susceptibility to NTM-LD, but it cannot be ruled out the possibility that disease itself leads to of CD4+ T cells depletion. In addition, the number of CD4+ T cells in peripheral blood does not solely reflect pulmonary lymphocyte infiltration. Further researches are needed. Additionally, the proportion of CD8 + CD38+ T cells was higher in the NTM-LD group compared to healthy controls, indicating the presence of activated CD8+ T cell subset, although their specific roles require further study.

There are some limitations of this study. Firstly, it is a single-center retrospective observational study with a relatively small sample size, especially in the NTM-Col group, which may lack statistical power to detect existing differences. Secondly, the NTM-Col group in our study only enrolled individuals with multiple positive microbiological results or those with identified NTM species excluding commonly contaminated NTM species; some individuals with NTM-Col who had only one positive microbiological test may not have been enrolled in the study.

Conclusion

In conclusion, NTM isolates from both NTM-LD and NTM-Col patients were predominantly MAC, Mycobacterium chelonae/Mycobacterium abscessus complex, and Mycobacterium kansasii, with a higher Mycobacterium intracellulare isolation rate in the NTM-LD group. Imaging findings of bronchiectasis and lower peripheral blood CD4+ T cell count may be helpful to separate the diagnosis of NTM-LD from NTM-Col.

Data availability

Data is provided within the manuscript.

References

  1. Johansen MD, Herrmann JL, Kremer L. Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus. NAT REV MICROBIOL. 2020;18(7):392–407.

    Article  CAS  PubMed  Google Scholar 

  2. Shulha JA, Escalante P, Wilson JW. Pharmacotherapy approaches in Nontuberculous Mycobacteria infections. MAYO CLIN PROC. 2019;94(8):1567–81.

    Article  CAS  PubMed  Google Scholar 

  3. Kumar K, Daley CL, Griffith DE, Loebinger MR. Management of Mycobacterium avium complex and Mycobacterium abscessus pulmonary disease: therapeutic advances and emerging treatments. EUR RESPIR REV 2022, 31(163).

  4. Agizew T, Basotli J, Alexander H, Boyd R, Letsibogo G, Auld A, Nyirenda S, Tedla Z, Mathoma A, Mathebula U, et al. Higher-than-expected prevalence of non-tuberculous mycobacteria in HIV setting in Botswana: implications for diagnostic algorithms using Xpert MTB/RIF assay. PLoS ONE. 2017;12(12):e189981.

    Article  Google Scholar 

  5. Loret JF, Dumoutier N. Non-tuberculous mycobacteria in drinking water systems: a review of prevalence data and control means. INT J HYG ENVIR HEAL. 2019;222(4):628–34.

    Article  Google Scholar 

  6. Okoi C, Anderson ST, Mulwa S, Worwui A, Antonio M, Gehre F, Adetifa I. Pulmonary non-tuberculous mycobacteria in colonisation and disease in the Gambia. SCI REP-UK. 2022;12(1):19523.

    Article  CAS  Google Scholar 

  7. Cowman S, van Ingen J, Griffith DE, Loebinger MR. Non-tuberculous mycobacterial pulmonary disease. EUR RESPIR J 2019, 54(1).

  8. Binder AM, Adjemian J, Olivier KN, Prevots DR. Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis. AM J RESP CRIT CARE. 2013;188(7):807–12.

    Article  Google Scholar 

  9. Tan Y, Deng Y, Yan X, Liu F, Tan Y, Wang Q, Bao X, Pan J, Luo X, Yu Y, et al. Nontuberculous mycobacterial pulmonary disease and associated risk factors in China: a prospective surveillance study. J Infect. 2021;83(1):46–53.

    Article  CAS  PubMed  Google Scholar 

  10. Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ, Andrejak C, Bottger EC, Brozek J, Griffith DE, Guglielmetti L et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. EUR RESPIR J 2020, 56(1).

  11. Ku JH, Henkle E, Aksamit TR, Barker A, Brunton AE, Winthrop KL. Treatment of Nontuberculous Mycobacterial (NTM) Pulmonary infection in the US Bronchiectasis and NTM Registry: treatment patterns, adverse events, and adherence to American Thoracic Society/Infectious Disease Society of America Treatment Guidelines. CLIN INFECT DIS. 2023;76(2):338–41.

    Article  CAS  PubMed  Google Scholar 

  12. Griffith DE, Eagle G, Thomson R, Aksamit TR, Hasegawa N, Morimoto K, Addrizzo-Harris DJ, O’Donnell AE, Marras TK, Flume PA, et al. Amikacin Liposome Inhalation suspension for treatment-refractory lung Disease caused by Mycobacterium avium Complex (CONVERT). A prospective, Open-Label, Randomized Study. AM J RESP CRIT CARE. 2018;198(12):1559–69.

    Article  CAS  Google Scholar 

  13. Kwon BS, Lee JH, Koh Y, Kim WS, Song JW, Oh YM, Lee SD, Lee SW, Lee JS, Lim CM, et al. The natural history of non-cavitary nodular bronchiectatic Mycobacterium avium complex lung disease. RESP MED. 2019;150:45–50.

    Article  Google Scholar 

  14. Feng JY, Chen WC, Chen YY, Su WJ. Clinical relevance and diagnosis of nontuberculous mycobacterial pulmonary disease in populations at risk. J FORMOS MED ASSOC. 2020;119(Suppl 1):S23–31.

    Article  PubMed  Google Scholar 

  15. Phillips MS, von Reyn CF. Nosocomial infections due to nontuberculous mycobacteria. CLIN INFECT DIS. 2001;33(8):1363–74.

    Article  CAS  PubMed  Google Scholar 

  16. Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, Leitch A, Loebinger MR, Milburn HJ, Nightingale M, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017;72(Suppl 2):ii1–64.

    Article  PubMed  Google Scholar 

  17. Baratella E, Roman-Pognuz E, Zerbato V, Minelli P, Cavallaro M, Cova MA, Luzzati R, Lucangelo U, Sanson G, Friso F, et al. Potential links between COVID-19-associated pulmonary aspergillosis and bronchiectasis as detected by high resolution computed tomography. FRONT BIOSCI-LANDMRK. 2021;26(12):1607–12.

    Article  CAS  Google Scholar 

  18. Chiu CC, Wang CJ, Lee WI, Wong KS, Chiu CY, Lai SH. Pulmonary function evaluation in pediatric patients with primary immunodeficiency complicated by bronchiectasis. J MICROBIOL IMMUNOL. 2020;53(6):1014–20.

    Google Scholar 

  19. Aksamit RT, O’Donnell EA, Barker A, Olivier NK, Winthrop LK, et al. Adult patients with bronchiectasis: a First look at the US Bronchiectasis Research Registry. Chest: J Circulation Respiration Relat Syst. 2017;151(5):982–92.

    Article  Google Scholar 

  20. Pan SW, Su WJ, Chan YJ, Ho ML, Feng JY, Shu CC, Wang JY, Wang HC, Yu CJ, Chen YM. Disease Progression in patients with Nontuberculous Mycobacterial Lung Disease of Nodular Bronchiectatic (NB) Pattern: the roles of Cavitary NB and Soluble programmed death Protein-1. CLIN INFECT DIS. 2022;75(2):239–47.

    Article  PubMed  Google Scholar 

  21. Furuuchi K, Fujiwara K, Uesgi F, Shimoda M, Seto S, Tanaka Y, Yoshiyama T, Yoshimori K, Kurashima A, Ohta K, et al. Posttreatment Lymphopenia is Associated with an increased risk of redeveloping Nontuberculous Lung Disease in patients with Mycobacterium avium Complex Lung Disease. CLIN INFECT DIS. 2021;73(1):e152–7.

    Article  CAS  PubMed  Google Scholar 

  22. Fujita J, Ohtsuki Y, Shigeto E, Suemitsu I, Yamadori I, Bandoh S, Shiode M, Nishimura K, Hirayama T, Matsushima T, et al. Pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex. RESP MED. 2003;97(8):933–8.

    Article  Google Scholar 

  23. Choi S, Potts KJ, Althoff MD, Jimenez G, Bai X, Calhoun KM, Cool CD, Chan ED. Histopathologic analysis of surgically resected lungs of patients with non-tuberculous mycobacterial lung disease: a retrospective and hypothesis-generating study. YALE J BIOL MED. 2021;94(4):527–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Garcia B, Wilmskoetter J, Grady A, Mingora C, Dorman S, Flume P. Chest computed Tomography features of Nontuberculous Mycobacterial Pulmonary Disease Versus Asymptomatic colonization: a cross-sectional cohort study. J THORAC IMAG. 2022;37(3):140–5.

    Article  Google Scholar 

  25. Lommatzsch ST. Infection prevention and chronic disease management in cystic fibrosis and noncystic fibrosis bronchiectasis. THER ADV RESPIR DIS. 2020;14:1022326984.

    Article  Google Scholar 

  26. Wobma H, Chang AK, Jin Z, Baker C, Garvin J, George D, Satwani P, Foca M, Bhatia M. Low CD4 count may be a risk factor for non-tuberculous mycobacteria infection in pediatric hematopoietic cell transplant recipients. PEDIATR Transpl. 2021;25(4):e13994.

    Article  CAS  Google Scholar 

  27. Han SA, Ko Y, Shin SJ, Jhun BW. Characteristics of circulating CD4(+) T cell subsets in patients with Mycobacterium avium Complex Pulmonary Disease. J CLIN MED 2020, 9(5).

  28. Pan SW, Shu CC, Lee CC, Feng JY, Chan YJ, Chen YM, Su WJ. Role of Soluble T-Cell Immunoglobulin Mucin Domain-3 in differentiating Nontuberculous Mycobacterial Lung Disease from Pulmonary colonization. ARCH BRONCONEUMOL. 2022;58(7):547–53.

    Article  PubMed  Google Scholar 

  29. Wang PH, Wu MF, Hsu CY, Pan SW, Shu CC, Cheng SL. The Trend of TIM3 expression on T cells in patients with Nontuberculous Mycobacterial Lung Disease: from Immune Cell Dysfunction to Clinical Severity. FRONT IMMUNOL. 2021;12:738056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-C-013 and 2022-PUMCH-A-043).

Author information

Author notes

  1. Shi Chen and Jingjing Zhong contributed equally to this work.

Authors and Affiliations

  1. Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Shi Chen, Jingjing Zhong, Lifan Zhang, Guiren Ruan, Baotong Zhou, Xiaochun Shi & Xiaoqing Liu

  2. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Qiwen Yang & Xinuo Song

  3. Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Lifan Zhang, Xiaochun Shi & Xiaoqing Liu

  4. Clinical Epidemiology Unit, International Epidemiology Network, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Lifan Zhang & Xiaoqing Liu

Authors
  1. Shi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingjing Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiwen Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinuo Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lifan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guiren Ruan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baotong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaochun Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaoqing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XCS and XQL conceived, designed, and supervised this research. QWY, XNS, GRR and BTZ assisted with revisions of protocol. SC and JJZ collected data. SC and LFZ analyzed and performed interpretation of data. SC and JJZ wrote the first draft of the manuscript. XCS and XQL provided comments and modifications to the final version. All authors approved the final manuscript to be published.

Corresponding authors

Correspondence to Xiaochun Shi or Xiaoqing Liu.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics review board of the Peking Union Medical College Hospital (I-23PJ103) and performed with the appropriate participants’ informed consent in compliance with the Helsinki Declaration, according to Ethics in Good Clinical Practice as addressed by Declaration of Helsinki and Greek Regulations.

Consent for publication

Not applicable.

Clinical trial number

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Zhong, J., Yang, Q. et al. Comparative analysis of non-tuberculous mycobacterial lung disease and lung colonization: a case-control study. BMC Infect Dis 24, 1159 (2024). https://doi.org/10.1186/s12879-024-10067-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-024-10067-y

Keywords

BMC Infectious Diseases

ISSN: 1471-2334

Contact us