Previous studies have reported that NTM is more likely to infect older females [2,11]. According to this study, female patients in the NTM group accounted for 78.1%, with an average age of 58.4±11.7 years, suggesting that estrogen played a protective role against NTM [11,12]. The guidelines have shown that NTM is particularly prone to structural lung diseases, such as COPD and bronchiectasis [9,13]. This study showed that up to 76.6% of NTM patients had bronchiectasis, which was significantly higher compared with the patients with PTB, while COPD was more commonly detected in the PTB group. In systemic complications, upper airway disease showed a relatively high rate in the NTM group, although with no statistical difference in our data, which might be attributed to that it is more associated with bronchiectasis [13].
Patients with mycobacteriosis often lack specificity in clinical manifestations [6]. Fever and night sweats were not particularly common, while as systemic symptoms, they were more commonly detected in patients with PTB than NTM. Reflecting systemic inflammation, the levels of CPR and ESR were significantly higher in the PTB patients compared with the NTM patients in this study.
Nowadays, interferon-gamma release assays (IGRAs) are essential tools for detecting infections with mycobacterium tuberculosis, including latent tuberculosis infection. IGRAs, including both QFT and T-SPOT.TB, enable the direct observation of the response of a patient's blood cells to specific antigens derived from mycobacterium tuberculosis [14,15]. In this study, negative test for QFT was found in 81.3% of NTM patients, and it was proved to be an independent risk factor for predicting NTM, which could be used as an important reference index for differential diagnosis.
The gold standard for diagnosis of NTM infections is referred to the result of tuberculosis culture and strain identification, and a least two batches of sputum samples are required to confirm a diagnosis of pulmonary NTM [16,17]. As NTM is widely distributed in the environment, sputum samples may be contaminated during collection and examination, resulting in false positive results. BALF culture may be more sensitive than sputum culture in diagnosing nodular bronchiectatic NTM-LD [18]. We found that the positive rate of BALF tuberculosis culture was higher than the sputum culture. Because electronic bronchoscopy is relatively sterile, the result of BALF samples is also more reliable than sputum.
Meanwhile, definite diagnosis of NTM-LD cannot simply rely on isolated and cultured NTM from the respiratory tract. To make a diagnosis of NTM-LD, etiology, clinical symptoms and imaging findings are indispensable [19]. Chest HRCT is an important imaging examination for the diagnosis of NTM-LD. Our data showed that the chest HRCT manifestations of AFB smear-positive cases of mycobacteriosis were mainly multiple nodules and plaques in both lungs. The involvement of the right middle and the left lingular lobes might be some of the characteristics that distinguished NTM from PTB in the present study, and cystic change was found to be an HRCT morphological feature of NTM, which was more commonly detected in NMT patients.
In the clinical practice, for patients with cough and expectoration, especially with hemoptysis and the characteristics of mycobacteriosis in chest CT, AFB smear of sputum and other respiratory tract specimens would be the primary and relatively fast examinations to make a clear diagnosis. Patients with positive AFB smear results may be directly diagnosed as PTB and received a long-term anti-tuberculosis treatment, in the absence of specimen culture and strain identification. According to Chang’s study, of the patients with AFB smear-positive sputum but no PTB, 18.5% were later diagnosed with NTM-LD, and 32% were afflicted with NTM colonization [20]. Once NTM-LD is misdiagnosed as PTB and given chemotherapy, there will be not only a high risk of adverse reactions, but also a long course of treatment, poor efficacy, and a heavy economic burden [7,8]. Despite the recent advances in the BACTEC MGIT (Mycobacteria Growth Indicator Tube) 960 System (BD, Franklin Lakes, NJ, USA), which greatly shortens the time required for culturing mycobacteria from 6-8 weeks to 2-4 weeks, the time required to confirm a diagnosis is still significant [21]. Therefore, how to determine the NTM-LD by some rapid and effective clinical features will directly affect the administration of anti-tuberculosis treatment and the prognosis of the disease for patients with AFB smear-positive results. Based on this situation, we analyzed all the clinical characteristics in AFB smear-positive patients to find the independent risk factors for NTM and then established a model to predict NTM, showing a prominent high level of sensitivity and specificity. Moreover, through the internal and external verifications of the model, we suggested that the model showed the practicality and effectiveness in the clinical practice.
In conclusion, female patients, bronchiectasis, negative test for QFT, and the right middle lobe affected were independent risk factors for fast prediction of NTM-LD in AFB smear-positive patients. Through the verification of the model, it showed prominent practicability and effectiveness in clinical practice. When patients show all the above-mentioned characteristics, it is strongly suggests the possibility of NTM infection, and it is necessary to wait for the mycobacterial culture results and meanwhile to conduct the identification and drug susceptibility test of mycobacterium, by which incorrect anti-tuberculosis treatment-related adverse reaction and the appearance of drug-resistant tuberculosis might be reduced, and the unnecessary economic burden could also be lessened. Our findings might have important clinical significance for improving the early diagnosis rate of NTM-LD and the prognosis of the disease.
However, there are some limitations in this study. First, the test of QFT may not be conducted in every hospital or center. This study lacked the identification of NTM species, and did not distinguish the positive degree of AFB from + to 4+. In addition, the total number of cases observed in this study was insufficient, and the data were acquired from a single center, which might have certain impact on the representative of the results. Even though we have drawn some firm conclusions, then established and validated a fairly effective model. We will further verify it in subsequent clinical practice and in more centers.