Mycobacterial cavity on chest computed tomography: clinical implications and deep learning-based automatic detection with quantification

Purpose: CA 19-9 is a useful marker for the diagnosis of gastrointestinal cancer including pancreatic cancer. However, there are several previous studies about CA 19-9 elevation in benign lung diseases like emphysema, fibrosis and bronchiectasis. This study evaluates the clinical significance of serum CA 19-9 elevation in cases of pulmonary nontuberculous mycobacterial (PNTM) disease and cases of pulmonary tuberculosis (TB). Methods: Serum CA 19-9 levels in patients with PNTM (n=59) and pulmonary TB (n=36) were measured. Multivariate logistic regression analysis was performed to evaluate the factors related to CA 19-9 elevation in PNTM disease. The sequential changes in serum CA 19-9 before and after treatment were compared between pulmonary TB and PNTM disease. Results: The median CA 19-9 level was higher in patients with PNTM disease than in patients with pulmonary TB (PNTM: 13.80, TB: 5.85, P <0.001). Mycobacterium abscessus (OR 21.78, 95% CI: 1.68, 282.38; P =0.018) and extensive pulmonary lesions in more than three lobes (OR 11.03, 95% CI: 1.03, 117.89, P =0.047) were associated with elevated CA 19-9 levels in PNTM disease. CA 19-9 levels showed a tendency to decrease during successful treatment of PNTM disease but not in pulmonary TB. Conclusion: S erum CA 19-9 level was increased in substantial proportions of the patients with PNTM disease; in this setting, CA 19-9 may be a useful marker for monitoring therapeutic responses. Key words: Carbohydrate antigen 19-9; Nontuberculous mycobacteria; Tuberculosis; Biological marker Abbreviations : PNTM : Pulmonary nontuberculous mycobacterium TB : Tuberculosis CA 19-9 : Carbohydrate antigen 19-9.

Background Because of the low sensitivity of sputum smear and culture, diagnosis of nontuberculous mycobacterium (NTM) pulmonary disease, especially in patients with bronchiectasis, is often difficult. We investigated the usefulness of bronchoscopy for the diagnosis of NTM pulmonary disease including M. avium complex (MAC) and M. abscessus in patients with bronchiectasis and multiple pulmonary nodules on chest computed tomography (CT). Methods We reviewed 48 cases of patients who were performed bronchoscopic bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) under suspect of NTM pulmonary disease based on CT findings of bronchiectasis and multiple nodules from April 2002 to June 2003. Results Twenty five of the 48 patients (54%; 12 MAC, 14 M. abscessus) were diagnosed as NTM pulmonary disease on the basis of the American Thoracic Society diagnostic criteria for NTM pulmonary disease. Sixteen of the 21 patients (76%; 5 MAC, 11 M. abscessus) with 3 or more positive sputum cultures of NTM were confirmed tissue invasion by TBLB. Five of the 24 patients (21%; 4 MAC, 1 M. abscessus) who could not be diagnosed with sputum cultures were diagnosed by bronchoscopic BAL and TBLB. Conclusion Bronchoscopy is helpful for the diagnosis of NTM pulmonary disease and confirmation of tissue invasion by NTM, not only MAC but also M. abscessus, in patients with bronchiectasis and multiple nodules on chest CT scan.

ObjectiveTo investigate the early detection of pulmonary non-tuberculous mycobacterial (PNTM) disease by CT before the initiation of molecular-targeted therapeutic drugs in patients with rheumatoid arthritis (RA) and the efficacy and...

Study participants with rheumatoid arthritis (RA) have an elevated risk for nontuberculous mycobacterial pulmonary disease (NTM-PD), which limits the treatments for RA. Biomarkers for NTM-PD in study participants with RA are required. Patients with NTM-PD have been studied for small-molecule metabolites, although few have been performed for NTM-PD associated with RA. Therefore, we performed lipidomic profiling of NTM-PD in the urine specimens of study participants with RA to discover useful biomarkers. Urine specimens provided by 90 study participants with RA, with or without NTM-PD were subjected to lipidomic analysis. Univariate analysis found that the urinary concentrations of lysophosphatidic acid (LPA) 22:5 and phosphatidic acid (PA) 36:1 were altered in study participants with RA and NTM-PD (respective areas under the curves of receiver operating characteristic (AUROCs) were 0.977 and 0.811; P = 3.83 × 10−20 and 1.37 × 10−5), when compared with the levels in urine specimens of study participants with RA without NTM-PD. The partial least squares-discriminant analysis model created from these two phospholipids validated their ability to discriminate between the study participants with or without NTM-PD (AUROC: 0.988 [95% confidence interval 0.958–1.000]). Differences between the urinary levels of the phospholipids LPA and PA in study participants with RA and with or without NTM-PD were significant. Lipidomic profiling of urine samples should be effective in the process of evaluating biomarkers for NTM-PD associated with RA.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-19452-2.

The management of patients with nontuberculous mycobacterial (NTM) disease, especially pulmonary disease (PD), is neither intuitive nor simple. As is often lamented, treatment of NTM PD is typically more complicated and difficult than the treatment of tuberculosis (TB). Complexity begins with the requirement to select patients that meet established diagnostic criteria and who would benefit from therapy. Essentially all patients with NTM PD have respiratory comorbidities, typically bronchiectasis and/or chronic obstructive lung disease which also requires evaluation and treatment. Management of these comorbidities in the presence of NTM PD is critical but presents additional challenges such as symptomatic overlap with NTM PD that obfuscates NTM treatment responses. Likewise, the decision to begin a multidrug mycobacterial regimen must always involve careful risk-benefit assessment on an individual patient basis. In those instances that treatment for NTM PD is not started, continued monitoring and follow-up of patients are essential. For successful treatment outcomes, clinicians managing NTM PD patients must be familiar with the characteristics of individual NTM PD pathogens and especially the nuances and peculiarities of drug susceptibility patterns. For selected pathogens and antibiotics, the avoidance of acquired mutational drug resistance is imperative. Management requires close and ongoing patient monitoring to assess treatment response and drug toxicity. There are multiple impediments to successful NTM PD therapy so that even with optimal management strategies, treatment success can be elusive. In that context, however, adherence to basic management principles will maximize the chances for a successful treatment outcome. Specific recommendations for comprehensive NTM disease management are offered in this chapter.

This study aimed to analyze the differences in lymphocyte subsets and immune function between tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), thereby deepening the understanding of the pathogenesis of these diseases and providing important insights for clinical diagnosis, treatment, and prognosis evaluation. Patients with pulmonary imaging abnormalities admitted to the Tuberculosis Department of Shanghai Pulmonary Hospital from January 2023 to December 2023 were included. Based on diagnostic assessments, they were categorized into active tuberculosis (ATB), NTM-PD, and other pulmonary diseases (including inflammatory and neoplastic lung diseases). Flow cytometry was used to detect lymphocyte subset counts. (1) There were no significant differences in lymphocyte subset counts between the ATB and NTM groups; however, both groups showed marked differences when compared with the group of patients with other respiratory diseases. Specifically, the percentages and absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD19+ B cells were significantly lower in the ATB and NTM groups, whereas the levels of CD16+56+ natural killer (NK) cells were higher compared to those with other respiratory diseases.(2) Patients in the non-severe ATB (nSATB) group exhibited higher levels of CD3+ T cells and CD19+ B cells compared to those in the severe ATB (SATB) group.(3) Among patients with ATB, those with concomitant diabetes had lower CD8+ T cell counts and percentages, as well as a higher CD4/CD8 ratio, compared to those without diabetes.(4) In patients with NTM-PD, those with severe disease had lower percentages of CD16+56+ NK cells than those with non-severe NTM-PD.(5) No significant differences in lymphocyte subset parameters were observed between drug-resistant and drug-sensitive ATB patients, or between patients with rapidly growing and slowly growing NTM species. This study revealed the lymphocyte subset characteristics of patients with TB and NTM infections and identified potential associations between disease severity, diabetes comorbidities, and immune cell subsets with disease status. These findings provide a basis for further research on the immune mechanisms of infectious pulmonary diseases and contribute to the development of precision medicine strategies.

The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

Rationale: Health-related quality of life (HRQOL) is gaining importance among patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated whether the BACES score reflects HRQOL and associated factors in patients with NTM-PD. Methods: We used data from the nationwide NTM-KOREA prospective cohort of patients with NTM-PD who started antibiotic treatment. HRQOL and associated factors were measured, including symptoms, Quality of Life-Bronchiectasis (QOL-B) questionnaire, nutritional status using the Mini Nutritional Assessment-Short Form (MNA-SF) and prognostic nutritional index (PNI), physical activity, body composition, spirometry, handgrip strength, and 6-min walking distance. Associations between the BACES score and HRQOL and associated factors at enrollment were investigated in multivariate linear and logistic regression analyses. Results: We included 409 patients (median, 64 years; men, 27.6%). As the BACES score increased, the odds (adjusted odds ratio [95% confidence interval]) of cough (1.24 [1.04-1.48]), dyspnea (1.69 [1.28-2.27]), weight loss (1.78 [1.36-2.36]), malnutrition defined as MNA-SF score ≤ 7 (1.71 [1.21-2.45]), and PNI &amp;lt; 45 (2.14 [1.66-2.81]) also increased. The QOL-B respiratory symptom score (estimate −2.259, P=0.002) and 6-min walking distance (estimate −18.015, P&amp;lt;0.001) were negatively associated with the BACES score. Moreover, the odds of adipopenia (1.08 [1.03-1.13]), possible sarcopenia (2.15 [1.35-3.59]), and sarcopenia (2.37 [1.33-4.55]) increased in women, while adipopenia (1.15, [1.05-1.26] was associated with the BACES score in men. Conclusions: The BACES score can serve as a proxy for HRQOL and associated conditions at antimicrobial treatment initiation in patients with NTM-PD.

The evaluation of health-related quality of life (HRQOL) is gaining importance among patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We assessed whether the BACES score reflects HRQOL and associated factors in these patients. Data were collected from the nationwide NTM-KOREA prospective cohort of patients with NTM-PD who started antibiotic treatment and included symptoms, Quality of Life-Bronchiectasis (QOL-B) questionnaire, nutritional status using the Mini Nutritional Assessment-Short Form (MNA-SF) and Prognostic Nutritional Index (PNI), physical activity, body composition, spirometry, handgrip strength, and 6-min walking distance. Multivariate linear and logistic regressions were used for analysis. As the BACES score increased, so did the odds (adjusted odds ratio [95% confidence interval]) of cough (1.24 [1.04-1.48]), dyspnea (1.69 [1.28-2.27]), weight loss (1.78 [1.36-2.36]), and malnutrition, defined as MNA-SF score ≤ 7 (1.71 [1.21-2.45]), and PNI < 45 (2.14 [1.66-2.81]). The QOL-B respiratory symptom score (estimate: -2.259, P = 0.002) and 6-min walking distance (estimate: -18.015, P < 0.001) were negatively associated with the BACES score. Moreover, the odds of adipopenia (1.08 [1.03-1.13]), possible sarcopenia (1.80 [1.35-2.45]), and sarcopenia (2.09 [1.48-3.03]) increased in women. The BACES score can estimate HRQOL and associated conditions at antimicrobial treatment initiation in patients with NTM-PD.

A 45-year-old woman with scleroderma for 15 years duration, rheumatoid arthritis in the past five years, and interstitial pneumonia in the past two years had been followed at OPD. Although sputum had appeared and cough had increased since January 2002, there was no obvious abnormal findings on chest X-ray. Later, as a chest X-ray revealed an infiltrative shadow with cavity in the right lower lung field, we suspected pulmonary tuberculosis and performed the direct smear examination of sputum immediately. As acid-fast bacilli were positive (Gaffky 10) and the polymerase chain reaction (PCR) test was positive for only Mycobacterium avium, we diagnosed the case as pulmonary nontuberculous mycobacterial disease. This case was thought to be pulmonary nontuberculous mycobacterial disease complicated with interstitial pneumonia with collagen vascular disease as a secondary infectious type, and as the cause of the disease, the decrease of the local pulmonary defence mechanism due to pre-existing pulmonary lesions was suspected.

Background: In Japan, people are typically aware of tuberculosis (TB) as a respiratory infection, but awareness of nontuberculous mycobacteriosis is lacking. In 2014, the estimated incidence of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Japan exceeded that of TB. Furthermore, the risk of infection is increasing because of the lack of public awareness regarding the high incidence of NTM-PD. The purpose of this study was to determine and raise the public awareness of NTM-PD, chronic obstructive pulmonary disease (COPD), and pulmonary rehabilitation (PR) in Japan. Methods: A questionnaire survey was administered to 845 subjects who participated in and consented to a pulmonary age measurement event in Tokyo, Japan. The questions included items related to age, sex, smoking history, previous lung age measurement experience, and assessment of awareness of respiratory diseases such as NTM-PD and COPD, and PR awareness. Results: Awareness of NTM-PD was significantly lower (5.9%) than that of other diseases and independently of age. Of the subjects questioned, 10.3% had experienced PR and 18.6% were aware about PR. Those individuals who were aware of lung age measurement, PR, and other respiratory diseases were more likely to be aware of NTM-PD than those who were unaware. Conclusions: The general public is largely unaware of NTM-PD, regardless of age. In the future, more proactive educational activities targeting a wide range of age groups through different events such as lung age measurement are needed.

BackgroundThe number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly increasing globally, especially in the older population. However, there is a dearth of evidence regarding the impact of aging on the treatment outcomes of NTM-PD.MethodsWe analyzed consecutive patients who satisfied the diagnostic criteria for Mycobacterium avium complex (MAC)-PD and received antibiotic treatment between January 2009 and December 2020 at a tertiary referral hospital in Korea. The main outcomes were (1) long-term treatment success, defined by negative culture conversion for more than 12 months; and (2) adverse drug reactions (ADRs). Multivariable logistic regression model was used to evaluate the association between age and main outcomes.ResultsA total of 614 patients (median age, 65 years, interquartile range [IQR] 57–73 years; men, 35.3%) were included. Median treatment duration (530 days, IQR 290–678 days; P for trend < 0.001) and long-term treatment success (P for trend = 0.026) decreased, whereas ADRs (P for trend < 0.001) increased significantly with age. Multivariable analyses demonstrated that age ≥ 80 years was an independent factor associated with ADRs (adjusted odds ratio [aOR] 3.29; 95% confidence interval [CI] 1.05–10.28) and worse treatment outcome (aOR 0.42; 95% CI 0.19–0.91).ConclusionsAging is associated with worse treatment outcome and frequent ADRs of patients with MAC-PD. Individualized treatment with reduced-intensity may be a reasonable alternative for older adults.

Usefulness of bronchial sputum aspirate specimens for the diagnosis of Non-tuberculous mycobacterial pulmonary disease.

Introduction. Disease caused by non-tuberculous mycobacteria (NTM) is an emergent problem. Because NTM pulmonary disease and tuberculosis (TB) have similar clinical presentations, many cases of NTM may be misdiagnosed as TB before laboratory identification of the NTM species.Hypothesis/Gap Statement. Clinical laboratories should always perform differentiation between Mycobacterium tuberculosis complex (MTBC) and NTM to guide patients' correct treatment.Aim. To describe the characteristics and to identify mycobacterial isolates presumptively classified as MTBC by macroscopic characteristics in culture media that tested negative in GenoType MTBDRplus.Methodology. All cultures from February 2019 to December 2021 showing MTBC macroscopic characteristics were processed by GenoType MTBDRplus. MTBC-negative cultures underwent species identification by immunochromatography, line probe assays and PRA-hsp65. Patients' data were obtained from Brazilian surveillance systems.Results. Only 479 (3.1%) of 15 696 isolates presumptively identified as MTBC were not confirmed by GenoType MTBDRplus and were then subjected to identification. A total of 344 isolates were shown to be NTM, of which 309 (64.5%) and 35 (7.3%) were identified to the species and genus levels, respectively. Of the 204 NTM isolates with MTBC characteristics, the most frequent species were M. fortuitum (n=52, 25.5%), M. abscessus complex (MABC; n=27, 13.2%) and M. avium complex (MAC; n=26, 12.7%). Regarding the GenoType MTBDRplus results from NTM isolates, there were diverse hybridisation profiles with rpoB gene's different wild-type (WT) probes. Seventy-six (16.1%) of the 473 patients were classified as having NTM disease, the most frequent being MAC (n=15, 19.7%), MABC (n=13, 17.1%), M. kansasii (n=10, 13.2%) and M. fortuitum (n=6, 7.9%).Conclusion. Because the signs and symptoms of pulmonary TB are similar to those of pulmonary mycobacteriosis and treatment regimens for TB and NTM are different, identifying the disease-causing species is paramount to indicate the correct management. Thus, in the laboratory routine, when an isolate presumptively classified as MTBC is MTBC-negative, it is still essential to perform subsequent identification.

BackgroundThe respiratory illness caused by SARS‐CoV‐2 infection continues to present diagnostic challenges. Our 2020 edition of this review showed thoracic (chest) imaging to be sensitive and moderately specific in the diagnosis of coronavirus disease 2019 (COVID‐19). In this update, we include new relevant studies, and have removed studies with case‐control designs, and those not intended to be diagnostic test accuracy studies.ObjectivesTo evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X‐ray and ultrasound) in people with suspected COVID‐19.Search methodsWe searched the COVID‐19 Living Evidence Database from the University of Bern, the Cochrane COVID‐19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID‐19 publications through to 30 September 2020. We did not apply any language restrictions.Selection criteriaWe included studies of all designs, except for case‐control, that recruited participants of any age group suspected to have COVID‐19 and that reported estimates of test accuracy or provided data from which we could compute estimates.Data collection and analysisThe review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using the QUADAS‐2 domain‐list. We presented the results of estimated sensitivity and specificity using paired forest plots, and we summarised pooled estimates in tables. We used a bivariate meta‐analysis model where appropriate. We presented the uncertainty of accuracy estimates using 95% confidence intervals (CIs).Main resultsWe included 51 studies with 19,775 participants suspected of having COVID‐19, of whom 10,155 (51%) had a final diagnosis of COVID‐19. Forty‐seven studies evaluated one imaging modality each, and four studies evaluated two imaging modalities each. All studies used RT‐PCR as the reference standard for the diagnosis of COVID‐19, with 47 studies using only RT‐PCR and four studies using a combination of RT‐PCR and other criteria (such as clinical signs, imaging tests, positive contacts, and follow‐up phone calls) as the reference standard.Studies were conducted in Europe (33), Asia (13), North America (3) and South America (2); including only adults (26), all ages (21), children only (1), adults over 70 years (1), and unclear (2); in inpatients (2), outpatients (32), and setting unclear (17).Risk of bias was high or unclear in thirty‐two (63%) studies with respect to participant selection, 40 (78%) studies with respect to reference standard, 30 (59%) studies with respect to index test, and 24 (47%) studies with respect to participant flow.For chest CT (41 studies, 16,133 participants, 8110 (50%) cases), the sensitivity ranged from 56.3% to 100%, and specificity ranged from 25.4% to 97.4%. The pooled sensitivity of chest CT was 87.9% (95% CI 84.6 to 90.6) and the pooled specificity was 80.0% (95% CI 74.9 to 84.3). There was no statistical evidence indicating that reference standard conduct and definition for index test positivity were sources of heterogeneity for CT studies.Nine chest CT studies (2807 participants, 1139 (41%) cases) used the COVID‐19 Reporting and Data System (CO‐RADS) scoring system, which has five thresholds to define index test positivity. At a CO‐RADS threshold of 5 (7 studies), the sensitivity ranged from 41.5% to 77.9% and the pooled sensitivity was 67.0% (95% CI 56.4 to 76.2); the specificity ranged from 83.5% to 96.2%; and the pooled specificity was 91.3% (95% CI 87.6 to 94.0). At a CO‐RADS threshold of 4 (7 studies), the sensitivity ranged from 56.3% to 92.9% and the pooled sensitivity was 83.5% (95% CI 74.4 to 89.7); the specificity ranged from 77.2% to 90.4% and the pooled specificity was 83.6% (95% CI 80.5 to 86.4).For chest X‐ray (9 studies, 3694 participants, 2111 (57%) cases) the sensitivity ranged from 51.9% to 94.4% and specificity ranged from 40.4% to 88.9%. The pooled sensitivity of chest X‐ray was 80.6% (95% CI 69.1 to 88.6) and the pooled specificity was 71.5% (95% CI 59.8 to 80.8).For ultrasound of the lungs (5 studies, 446 participants, 211 (47%) cases) the sensitivity ranged from 68.2% to 96.8% and specificity ranged from 21.3% to 78.9%. The pooled sensitivity of ultrasound was 86.4% (95% CI 72.7 to 93.9) and the pooled specificity was 54.6% (95% CI 35.3 to 72.6).Based on an indirect comparison using all included studies, chest CT had a higher specificity than ultrasound. For indirect comparisons of chest CT and chest X‐ray, or chest X‐ray and ultrasound, the data did not show differences in specificity or sensitivity.Authors' conclusionsOur findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID‐19. Chest X‐ray is moderately sensitive and moderately specific for the diagnosis of COVID‐19. Ultrasound is sensitive but not specific for the diagnosis of COVID‐19. Thus, chest CT and ultrasound may have more utility for excluding COVID‐19 than for differentiating SARS‐CoV‐2 infection from other causes of respiratory illness.Future diagnostic accuracy studies should pre‐define positive imaging findings, include direct comparisons of the various modalities of interest in the same participant population, and implement improved reporting practices.