Fibro-cavitary NTM-PD remains predominant, but is now diagnosed more frequently in women. Fibro-cavitary disease is harder to cure than nodular-bronchiectatic disease. Adverse events are frequent and can necessitate cessation of treatment.

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Mycobacterium avium complex (MAC) bacteria, i.e. Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium chimaera and related species, can cause severe pulmonary disease (MAC-PD), especially in patients with chronic pulmonary diseases, like COPD and bronchiectasis [1, 2].Treatment of MAC-PD is difficult due to its long duration, frequent adverse events and comorbidities of the host. Reported cure rates vary by disease manifestation, with poorest cure rates in fibrocavitary disease [3]. The currently recommended treatment for MAC-PD is a combination of a rifamycin (R), ethambutol (E) and a macrolide (M), preferably azithromycin [4]. In severe disease, amikacin (A) can be added to improve treatment outcome, but there is no direct evidence to support its role [4].Clofazimine (C), an old anti-leprosy drug, may add efficacy to MAC-PD treatment regimens. In vitro, clofazimine shows synergy with amikacin and macrolides against MAC [5,6]. In retrospective studies, the outcomes of treatment regimens in which clofazimine replaces rifamycin are similar to those of the recommended REM regimen [7][8][9].In our nontuberculous mycobacterium (NTM) reference clinic, patients with severe MAC-PD have been receiving intensified treatment with the REMAC regimen since 2013. Here, we evaluate its outcome, as compared to a cohort that only received the REM regimen.We conducted a retrospective cohort study of adults (>18 years) with macrolide-susceptible MAC-PD diagnosed according to current guidelines [4], treated from January 2007 until January 2017 in our reference clinic (last check: March 2021). A waiver from the local ethical board has been given for this retrospective study. Patients were classified into two groups: the REM group and the REMAC group. Amikacin was given intravenously at a 15-mg•kg −1 initial dose with therapeutic drug monitoring and clofazimine was dosed at 100 mg once daily. We collected demographic and treatment related data from the electronic medical records. Disease was classified as fibrocavitary or nodular-bronchiectatic and followed up on basis of chest computed tomography reports and a second assessment by two expert pulmonologists (C. Magis-Escurra and W. Hoefsloot). Disease severity and thus indication for REMAC treatment was assessed by the multidisciplinary team (all authors) on the basis of symptoms, immune status, frailty, extent of radiological abnormalities and microbiology (i.e. sputum smear status and quantitative culture).Patients who received either amikacin or clofazimine, or who used amikacin for <2 weeks were excluded from the analysis. Primary outcome measurements were time until sputum culture conversion and cure rates. Outcomes were defined using the NTM-NET definitions [10], except that microbiological cure and culture conversion were defined by two, rather than three, consecutive negative cultures.

Pulmonary nodules with intermediate to high risk of malignancy should preferably be diagnosed with image guide minimally invasive diagnostics before treatment. Several technological innovations have been developed to endobronchially navigate to these lesions and obtain tissue for diagnosis. This review addresses these technological advancements in navigation bronchoscopy in three basic steps: navigation, position confirmation and acquisition, with a specific focus on cone-beam computed tomography (CBCT).For navigation purposes ultrathin bronchoscopy combined with virtual bronchoscopy navigation, electromagnetic navigation and robotic assisted bronchoscopy all achieve good results as a navigation guidance tool, but cannot confirm location or guide biopsy positioning. Diagnostic yield has seen improvement by combining these techniques with a secondary imaging tool like radial endobronchial ultrasound (rEBUS) and fluoroscopy. For confirmation of lesion access, rEBUS provides local detailed ultrasound-imaging and can be used to confirm lesion access in combination with fluoroscopy, measure nodule-contact area length and determine catheter position for sampling. CBCT is the only technology that can provide precise 3D positioning confirmation. When focusing on tissue acquisition, there is often more than 10% difference between reaching the target and getting a diagnosis. This discrepancy is multifactorial and caused by breathing movements, small samples sizes, instrument tip displacements by tool rigidity and tumour inhomogeneity. Yield can be improved by targeting FDG-avid regions, immediate feedback of rapid onsite evaluation, choosing sampling tools with different passive stiffnesses, by increasing the number biopsies taken and (future) catheter modifications like (robotic assisted-) active steering. CBCT with augmented fluoroscopy (CBCT-AF) based navigation bronchoscopy combines navigation guidance with 3D-image confirmation of instrument-in-lesion positioning in one device. CBCT-AF allows for overlaying the lesion and navigation pathway and the possibility to outline trans-parenchymal pathways. It can help guide and verify sampling in 3D in near real-time. Disadvantages are the learning curve, the inherent use of radiation and limited availability/access to hybrid theatres. A mobile C-arm can provide 3D imaging, but lower image quality due to lower power and lower contrast-to-noise ratio is a limiting factor. In conclusion, a multi-modality approach in experienced hands seems the best option for achieving a diagnostic accuracy >85%. Either adequate case selection or detailed 3D imaging are essential to obtain high accuracy. For current and future transbronchial treatments, high-resolution (CBCT) 3D-imaging is essential.

ObjectivesTo determine if cone beam CT-guided navigation bronchoscopy (CBCT-NB) is a cost-effective diagnostic procedure in patients with a pulmonary nodule (PN) with an intermediate risk for lung cancer.Materials and methodsTwo decision analytical models were developed to compare the long-term costs, survival and quality of life. In the first model, CBCT-NB was compared with CT-guided transthoracic needle biopsy (TTNB) in TTNB eligible patients. In the second model, CBCT-NB was compared with direct treatment (without pathology proven lung cancer) in patients for whom TTNB is not suitable. Input data were gathered in-house, from literature and expert opinion. Effects were expressed in quality-adjusted life years (QALYs). Sensitivity analyses were used to assess uncertainty.ResultsCBCT-NB can be cost-effective in TTNB eligible patients with an incremental cost-effectiveness ratio of €18 416 in an expert setting. The probabilistic sensitivity analysis showed that in 69% and 90% of iterations CBCT-NB remained cost-effective assuming a willingness to pay (WTP) of €20 000 and €80 000 per QALY. CBCT-NB dominated in the treatment strategy in which TTNB is not suitable. The probabilistic sensitivity analysis showed that in 95% of iterations CBCT-NB remained the dominant strategy, and CBCT-NB remained cost-effective in 100% of iterations assuming a WTP limit of €20 000. In the comparison between CBCT NB and TTNB, the deterministic sensitivity analysis showed that the diagnostic properties and costs of both procedures have a large impact on the outcome.ConclusionsCBCT-NB seems a cost-effective procedure when compared with TTNB and when compared with a direct treatment strategy in patients with an intermediate risk PN.

Background Peripheral pulmonary nodules are often detected as multiple nodules in one patient. Computed tomography (CT) guided transthoracic biopsy (TTNB) is the most widely implemented method for minimal invasive biopsy of pulmonary nodules, but generally only one nodule is sampled per procedure. Navigation bronchoscopy is an endobronchial procedure with very low complication rates, and uses high-end image guidance which allows for the sampling of multiple nodules in one session, while also allowing inspection of the central airways and endobronchial ultrasound (EBUS) guided staging in one session. This report presents a unique case with three different synchronous primary tumors treated with three different treatment modalities that highlights the added value of cone-beam CT guided navigation bronchoscopy (CBCT-NB) in the diagnostic work-up of suspected early-stage lung cancer. Case Description This case describes an asymptomatic patient with no history of prior lung cancer referred because of a shadow seen on a screening X-ray. CT and positron emission tomography (PET) showed two nodules for which a navigation procedure was performed. Both nodules were sampled, and on inspection, a third occult endobronchial lesion was also found. Pathology revealed three separate primary tumors, which were treated with three different treatment modalities: surgery, radiotherapy and endobronchial cryoablation. Current follow-up at 12 months shows no signs of recurrence. Conclusions This case highlights that synchronous primary malignancies do occur and require a patient tailored approach to minimize treatment related morbidity and optimize survival. To this goal, image guided navigation bronchoscopy allows for a full and complete diagnostic evaluation and can be combined with a staging EBUS in one single session.