Video Diagnostic Precision and Initial Therapeutic DecisivenessReducing Diagnostic Delays: Driving Timely Multi-Drug Therapy (MDT) Initiation and Microbiological Monitoring Play Pause Volume Quality 1080P Fullscreen Captions Transcript Chapters Slides Diagnostic Precision and Initial Therapeutic DecisivenessReducing Diagnostic Delays: Driving Timely Multi-Drug Therapy (MDT) Initiation and Microbiological Monitoring Overview CLICK HERE FOR CME CREDIT Back to Symposium So thank you very much, uh, Professor Blasi, and, uh, uh, thank you all for, um, being, uh, in this, uh, webinar. Uh, my, uh, talk, uh, uh, is mainly on diagnostic precision and initial, uh, therapeutic, uh, deceiveness uh to reduce the diagnostic, uh, delay. I'm Stefano Liberti. Uh, I'm a full professor of, uh, respiratory medicine in Humanitas University. And I'm the director of the pulmonary department in the Humanitas Research Hospital in Milan. Uh, I have a very simple agenda for today. I would like to walk you through the concept of diagnostic precision in NTMPD to discuss with you actually therapeutic adhesiveness, and then to present a sort of a pathway in the field of NTMPD in order to avoid or reduce delay. In the different steps of the management of patients with NTMPD. The first chapter on diagnostic precision should start with the with some of the most recent data showing that there is a diagnostic delay in NTMPD. Uh, this is a study published a few years ago, uh, from a single center in Japan. Uh, this is a retrospective case control study rolling more than 180 patients with a suspicion of NTMPD according to the chest CT findings, and among them, uh, at the end of the story, 97 have been diagnosed with NTMPD. With an early diagnosis, uh, uh, within 6 months in 45 and a late diagnosis of 35 of more than 6 months in 35 patients. And as you can see by the graph, uh, the time to diagnose among all the suspected patients and among the 79 diagnosed patients with NTMPD is uh relevant. Uh, we are talking about 3.2. Uh, months, uh, uh, from uh the, uh, the, the time to diagnose, uh, in the 79 patients and uh 71 months uh in the entire study population. And, uh, uh, the authors also evaluated, uh, the multivariable analysis, uh, the factor associated with uh diagnosis and with the diagnostic delay. And, uh, the diagnostic delay, which means more than 6 months. Uh, the, um, uh, the, uh, lower cavity burden seems to predict the diagnostic delay, and this makes sense also from a clinical perspective, and this data led the authors to run another analysis looking at the longitudinal changes on the CT before diagnosis. Uh, and they found that the total CT score was less severe at the first visit in delay versus early diagnosis patients, but deteriorated prior to diagnosis, and this is the, the graph you are seeing on the uh on the right side of my slide. So diagnostic delay is there. I didn't mention data coming from other parts of the world. But, uh, since the last two decades, uh, several scientists uh published uh data on diagnostic delay in NTMPD across different countries. So it's a relevant problem. This problem is, uh, especially, is important not only in uh the secondary care centers in the pulmonary department, but it's extremely relevant in the community. Uh, I would like to, uh, discuss with you the flow chart published in the Primary Care Respiratory Medicine Journal in 2024, uh, about, uh, the multi-step diagnostic journey, uh, for a patient with NTMPD. Of course, the suspicion is the entry door for the physician to understand if the patient has some clinical features that are in line with the diagnosis of NTMPD and in this case, uh, physicians who should proceed with a screening for the presence of non-tuberculose mycobacteria in any respiratory samples now. The first step is for us to understand what are the host risk factors for infection and. Different papers from 2013, Claire Andre Jacques published one very important paper in Thorax at that time, are suggesting that COPD, bronchiectasis, thoracic skeletal abnormalities, low body weight. Immune monitoring drugs, steroids use, gastroesophageal reflux disease, hydrochloroquine treatment, and leflunomide treatment seems to be associated with the risk of NTM infection and TMPD. Uh, one particular mention, uh, is for chronic respiratory diseases like COPD and especially bronchiectasis. Um, a lot of literature came out, uh, also from the Embark registry and from other single center experience showing the importance of screening people for NTM among those with a chronic respiratory disease, not only cystic fibrosis, but also COPD and bronchiectasis. Uh, Michael Lobinger and, uh, other colleagues, uh, uh, in 200 in 2024, um, started a, uh, a very, um important project. Uh, this was a global online survey. Uh, among healthcare professionals, uh, looking at, uh, um, across, across the globe, so Europe, uh, US, uh, uh, Australia, New Zealand, uh, Japan, and other regions, uh, looking at, uh, um, physician practicing practices, uh, in, uh, screening people for NTM. Uh, you see that, uh, the, uh, majority of, uh, uh, patients with bronchiectasis, uh, uh, with, uh, uh, COPD, uh, with cystic fibrosis, uh, uh, but also those with frequent exacerbations of lung disease or recurrent pneumonia or previous TB seems to be the patients uh where physicians tend to, um, screen uh for NTM. In terms of uh symptoms, for example, a patient with persistent cough, with weight loss, with a mop disease, with night sweats, with persistent fatigue, or even with increased or purulent sputum seems to be those symptoms that uh lead the physicians to prescribe uh a culture for NTM uh for uh screening for this disease. Uh, now, after the screening for NTM infection done both on sputum culture, uh, ear or bronchoscopy, and in the case of a consistent radiology, uh, then, uh, Uh, the pathway towards the diagnosis of NTMPD starts. So this flow chart is divided into a left pathway and a right pathway. The left pathway is more about the sputum culture screening process and the right pathway is more about the radiology-based screening process. This is important because there are different healthcare professionals that are. Interest uh in our, I would say I have the responsibility to screen for NTM. These are not just pulmonologists, but these are also, uh, radiologists, for example, internist, uh, general practitioner, uh, with a special rule for the clinical microbiology. And this is the major message of this flow chart is the fact that different healthcare professionals should be ready to start a diagnostic journey for. And uh uh this is published by primary care respiratory medicine, uh, mainly looking at the UK healthcare systems but can be generalized also across different healthcare systems and you see that the sputum culture, the use of a CT scan, uh, at the end of the story should be integrated in order to do a good referral for to a secondary care. To make uh to for the uh for the uh caring of people with NTMPD. Now, the secondary care for NTNPD is very important in this disease. Especially because uh the journey is longer. is tough. Treatment is. Even tougher than the diagnosis, so a multidisciplinary team in a secondary care is uh um is uh uh very, very important. However, there are um there is a waste of time. Uh, that is leading to the diagnostic, uh, delay I was previously mentioning. Now, where does time get lost? There are different. Moments during patient journey where we might have a delay, we might have a have a delay. Between symptoms onset and sampling, this is the recognition delay. There might be also a delay. After sampling to the diagnostic confirmation, and this could be a sampling delay for species identification and DSD or could be also a laboratory delay for a diagnostic confirmation to during a talk between the clinicians and the clinical microbiology. But there could be also a referral decision delay, so. There might be a delay for different healthcare professionals in sending the patient to a secondary care in order to start the treatment. Uh, and then there could be also a delay in response recognition. I think that all these different steps are important. There are multiple opportunities we have in order to avoid the final delay so we can work in more than one, ideally all of these different steps, uh, because the delay, the diagnostics delay is not just one delay. Uh, there is some literature that actually defined the concept of diagnostic delay, decision delay, treatment initcision delay, and response recognition delay, and I think that from a, from a healthcare perspective and from a standard operating procedures. Local standard operating procedures point of view, this is the right way to work when we are opening a secondary care on or when. Yearly, we are monitoring the performance of a secondary care, uh, taking care of people with NTMPD. The diagnostic precision has 3 dimensions. We know clinical, radiological, and microbiological, but the point is that clinical, radiological, and microbiological are not self-standing silos. Or boxes, but they are extremely integrated, so the probability that there is an active disease, an anti-MPD that is clinically relevant in order to propose a treatment to a patient, these three domains should be integrated and weighted one against the other one, not only once but also longitudinally. Uh, so I, I like to think about exploring the clinical, radiological, and macrological domains in this way more than in a, in a. Additive way as has been previously published. Now, uh, talking about the signs and symptoms, the clinical, uh, domain, I think, uh, that, uh, um, I, I mean, I really appreciated this paper published by Emily Ankel, uh, and, uh, and the, uh, colleagues in the United States who, uh, develop a symptom scale for NT-MPD. Uh, this has been based on a semi-structured interviews with adults with NTMPD across 4 US sites looking at the key symptoms from cough and shortness of breath to weight loss and chest congestion, and then they develop a conceptual framework on respiratory symptoms, fatigue, and other NTM symptoms. There was uh, uh, uh, the the, the development of this measurement and some psychometric testing, uh, 45 uh items, uh, uh, some cognitive interviews, uh, leading to psychometric testing. And then they came out with the final NTM symptom scale. Uh, as you can see here in my slide. respiratory symptoms, fatigue, related symptoms, emotional functioning, cognitive functioning, appetite, and sleep quality. Uh, this kind of, uh, uh, uh, NTM, uh, uh, symptom scale is depicting the complexity, uh, in the evaluation of the clinical domain to understand if there is uh activity in the NTMPD. In terms of microbiology, I think that there are some very clear messages and some other messages that is always important to remind ourselves. First, uh, not all positive cultures are created equally. So we are talking, uh, we are introducing the concept of probability. Uh, so there are some, uh, items that Give us a very low probability of an active disease like the presence of a single isolate low pathogenicity species smear negative from a microbiological point of view, and there are some other items that Are leading to a a higher disease probability, especially if there is a repeated isolation of the same species, uh, that are pathogenic, the smear is positive, there is an increasing macrological burden, and this is in line with the radiological findings and the clinical findings. So it's important for us to remind that as. Always in medicine, we are discussing, thinking about probability, especially in NTMPD. And this probability should be evaluated longitudinally in terms of weeks or even months, because the evolution of the clinical, microbiological, and radiological domain is very important to make the final decision about the activity or not activity of an NMPD. What does diagnostic precision mean? So I think that To be precise in the management of NTM, we should remind ourselves that we should not treat every NTM isolate. Um, we should, uh, not attribute every kind of deterioration, clinical or radiological deterioration, always to NTM, but always, uh, think that some other pathogens like Pseudomonas or Aspergillus might be there. Um, we don't want to start therapy, uh, without an adequate, uh, specimens in terms of, uh, characterization of the bug and the DST. We should always think about other co-infections. We should always think how to decrease the disease activity before starting an treatment through respiratory physiotherapy, bronchodilation, and several other management opportunities we have. So this is the kind of diagnostic precision we want, obtaining serial samples early. Have accurate specimens, especially the smear status, have a good susceptibility testing, and then try to integrate this data into the radiological items and the clinical aspects of the disease. What is the, what, what we can discuss about therapeutic diseases in NTM? So we mentioned the clinical, radiological and archaeological domains. We know that from the latest published guidelines, uh, uh, Chuck Daily, European Respiratory Journal in 2020, patients who meet the diagnostic criteria for NTM in these patients, uh, the authors suggested to initiate a treatment. Rather than do a watchful waiting, especially if the smear is positive and the um CT scan is showing cavitary lesions or the disease is very severe or deteriorating from a clinical or radiological point of view. Um, but, uh, uh, I would like to clarify a little bit of the concept of the watch, watchful waiting approach. So the watchful waiting. Could be appropriate or could be potentially harmful, so it's a very delicate period where both patients and physicians should be proactive. So there should be the, the appropriate observation. Um, could be, uh, reserved to patients with a limited disease, with mild symptoms, with a smear negative, no cavitary lesions with a stable imaging, stable microbiology, and also according to patient preferences. Now The watchful waiting could become a very harmful period. Leading to a delay in treatment initiation with potentially bad outcomes if a cavitation is there, if there is a smear positivity, if there is a clear radiological progression or significant symptom burden, if the disease extension is important, if there are also systemic manifestation of the disease such as weight loss, night sweat, or even if there is a declining in lung function. So the watchful waiting is a very tricky period that should be managed appropriately in people with NTM and should be reassessed dynamically. Um, the watchful waiting period should have. Regular visits of the patient according to an individual an individualized timing. Um, the timing is important, uh, for treatment decision, and I would say that timing is the 4th dimension together with the clinical, radiological, and microbiological. This is the way as I see this. The 3 boxes integrating the integrating together, harmonize, harmonize together with timing as a very important variables. And the timing is important to define the, the visits, the controls, and during which I should evaluate symptoms, culture burden, CT abnormalities, the appearing of cavitation, and also systemic symptoms like weight loss. So, time is the first dimension. Now, if we decided to treat, we should treat patients uh aggressively. Um, there are published guidelines for, especially for MAC. There's a, there is a consensus management recommendations for less common NTM pulmonary disease published. Uh, uh, we should, uh, Uh, treat based on the species, the susceptibility testing, uh, the, um, we should choose the right dose, route, frequency, but uh, The treatment initiation is not the end point because as soon as we start treatment, we should have clear in mind how to monitor the patient because monitoring is important as treatment initiation. Monitoring in terms of tolerability, in terms of adherence, in terms of clinical, radiological, and microbiological endpoints, uh, in terms also of um culture conversion, and then after the end of the treatment, still, the monitoring is important during the post-treatment surveillance. So, treatment initiation and monitoring are equally important. Uh, once you make a diagnosis of NTMPD, uh, Koso Morimoto published, uh, last year in 2025 in the annals of the ATS, uh, this very helpful, uh, checklist for regular outpatient clinic visits. I would like you to, to, uh, to read. Because it's it's telling us the importance of the holistic management of patients, looking at nutritional status, airway clearance, the management of comorbidities, the education, uh, the evaluation of treatment risk, the self-management plan, a plan decided not only with the patient but also with the caregivers and with the families. Uh, the explanation of the need for treatment duration, side effects, goals, and I think this checklist, uh, I'm using this in my clinic is very, very helpful. From a, from a microbiological point of view, we should remind ourselves that also time to positivity together with the species DST and smear is important. Time to positivity is important for treatment initiation, but it's also important during the monitoring after you start the treatment. And time to positivity should be written down in any uh microbiological report for NTM because it's very important. There are plenty, plenty. There are several uh good uh experiences published in the literature supporting time to positivity in uh in the management of people with NTM. Now, I'm uh going through the last uh section of my presentation. Um, now, I mentioned the concept of having more than one delay in the management of patient with NTMPD. Now, I would like to give you a solution, or maybe I would like to discuss with you possible solutions on how to handle, uh, and to reduce the possible delay during the patient journey. Uh, the. Suspicion is. Crucial because everything starts from there. And as I mentioned at the beginning of my presentation, the suspicion should be not only something belonging to pulmonary physicians, but also to radiologists, internists, microbiologists, even emergency medicine physicians. Uh, the samples should be adequate, um, collected. And there should be an agreement with your clinical microbiologist on timing for talking, timing for meeting, timing for discussing the data, and the clinical microbiology should be part of the multidisciplinary team in the NTMPD. Uh, the, uh, stratification, uh, in terms of disease severity and disease activity, uh, is leading to the decision for a treatment or for a watchful waiting, uh, and in this case, uh, the multidisciplinary team, uh, might, uh, in a, in a secondary care center might reduce this kind of uh delay or might improve the accuracy. Uh, of the, uh, of the, uh, proposals we are giving to the patient, and then, uh, the majority of the delay I see in my clinical practice is after treatment initiation. It's related to when, how to monitor a patient, when to perform a CT scan, when to perform a bronchoscopy. And I think that good standard operating procedures and uh a daily, uh, a daily meeting with the NTMPD physicians in your unit uh might help in reducing the delay during this phase of the, uh, of the, of the management. However. Every kind of solutions are good, in order to avoid the gaps between the different actions. The point is that this kind of solutions should be individualized in each single center according to the type of centers, the countries, legislations, uh, uh, local data, and several other factors. So I don't have a solution for all the NTM centers worldwide, uh, but uh with this kind of scheme, I would like to, uh. Walk you through. Uh, I mean, I would like to suggest you to try to. Find solutions to avoid the delay in each different uh moment uh of the NTMPD management. Um, As I mentioned, uh, it would be interesting to have a sort of uh general opinion uh about the possible uh uh delay that might occur in your clinical practice, um, and these are some options the delay in recognition, the delay in respiratory sampling, the delay in species identification NDST, in patient decision, in drug access, or in monitoring. And I think uh that uh there could be a good heterogeneity across different countries in terms of, in terms of uh possibilities. Now, my take-home messages are, first of all, just to remind us that NTM isolation is not an NTM pulmonary disease, so we need to do our best to identify the cons the level of activity of the disease in order to propose ourselves and the patients a possible treatment. The diagnostic precision should be should accelerate the appropriate treatment, not to delay. So be precise in the diagnostic is extremely relevant. Then the disease activity and the trajectory, uh. Once the NTMPD is established. Are those who determine the urgency in suggesting the treatment initiation, and then when the treatment is indicated, we should not fail in selecting the best multi-drug regimen that is effective from day one. And then monitoring. The serial microbiology is part of the therapy, as I mentioned, monitor. Published September 2, 2026 Created by Related Presenters Professor Stefano Aliberti, MD Professor in Respiratory MedicineHumanitas UniversityChief, Pulmonary DepartmentIRCCS Humanitas Research HospitalMilan, Italy
