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Background Near-patient access to appropriate tests is a major obstacle for the efficient diagnosis of tuberculosis (TB) and associated drug resistance. Methods We recently developed the “TB Concentration & Transport” kit for bio-safe, ambient-temperature transportation of dried sputum on Trans-Filter, and the “TB DNA Extraction” kit for DNA extraction from Trans-Filter for determining drug resistance by DNA sequencing. In the present study, we evaluated the compatibility of Kit-extracted DNA with Hain's line probe assays (LPAs), which are endorsed by National TB programmes for the detection of drug resistance in sputum collected from presumptive multidrug-resistant TB patients (n=207). Results Trans-Filter-extracted DNA was seamlessly integrated with the LPA protocol (Kit-LPA). The sensitivity of Kit-LPA for determining drug resistance was 83.3% for rifampicin (95% CI 52–98%), 77.7% for isoniazid (95% CI 52–94%), 85.7% for fluoroquinolones (95% CI 42–100%) and 66.6% for aminoglycosides (95% CI 9–99%), with a specificity range of 93.7% (95% CI 87–97) to 99.1% (95% CI 95–100) using phenotypic drug susceptibility testing (DST) as a reference standard. A high degree of concordance was noted between results obtained from Kit-LPA and LPA (99% to 100% (κ value: 0.83–1.0)). Conclusions This study demonstrates successful integration of our developed kits with LPA. The adoption of these kits across Designated Microscopy Centres in India can potentially overcome the existing challenge of transporting infectious sputum at controlled temperature to centralised testing laboratories and can provide rapid near-patient cost-effective “Universal DST” services to TB subjects residing in remote areas.

Exposure to organic dusts may cause airways inflammation in a large proportion of exposed persons. Most studies have relied on questionnaires and spirometry for diagnosis. To assess the possibility of determining the presence of inflammation using clinical diagnostic procedures, a study was undertaken among workers in a paper industry. Participants were 83 workers and 44 controls. Airborne endotoxin and (1-->3)-beta-D-glucan levels at the worksites were determined. The effects of this exposure were evaluated using a questionnaire, spirometry and measurements of airway responsiveness (methacholine) and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and C-reactive protein (CRP) in serum. The workers had a decreased baseline forced expiratory volume in one second (FEV1) and an increased airway responsiveness compared with controls. The concentrations of ECP and MPO were elevated compared with controls. There was a relation between exposure to endotoxin and (1-->3)-beta-D-glucan and airway responsiveness as well as ECP levels, when controlling for age, sex, smoking habits, atopy and asthma. The results suggest an increased prevalence of subjective respiratory symptoms, and an increased airway responsiveness among exposed workers. There was also a relationship between the serum concentration of eosinophil cationic protein and airway responsiveness. Taken together, the results suggest the presence of airways inflammation in the workers.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: a) Is noninvasive imaging capable of identifying PH? b) What is the role of imaging in establishing the cause of PH? c) How does imaging determine the severity and complications of PH? d) How should imaging be used to assess chronic thromboembolic PH before treatment? e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH., Competing Interests: Conflict of interest: M. Remy-Jardin received payment for lectures including service on speakers’ bureaus from Siemens Healthineers, Boehringer Ingelheim, Roche, and MSD, outside the submitted work. Conflict of interest: C.J. Ryerson disclosed no relevant relationships. Conflict of interest: M.L. Schiebler disclosed no relevant relationships. Conflict of interest: A.N.C. Leung disclosed no relevant relationships. Conflict of interest: J.M. Wild disclosed no relevant relationships. Conflict of interest: M.M. Hoeper is board member and consultant for Acceleron, Actelion, Bayer, Janssen, MSD, and Pfizer, received payment for lectures including service on speakers bureaus from Acceleron, Actelion, Bayer, Janssen, MSD, and Pfizer, outside the submitted work. Conflict of interest: P.O. Alderson disclosed no relevant relationships. Conflict of interest: L.R. Goodman disclosed no relevant relationships. Conflict of interest: J. Mayo received payment for lectures including service on speakers’ bureaus from Siemens Healthineers Canada, outside the submitted work. Conflict of interest: L.B. Haramati disclosed no relevant relationships. Conflict of interest: Y. Ohno received research grant from Canon Medical Systems, during the conduct of the study; has grants/grants pending with Bayer Pharma, outside the submitted work; received grants-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science and Technology; received research grant from Smoking Research Foundation; received research grant from Daiichi Sankyo. Conflict of interest: P. Thistlethwaite disclosed no relevant relationships. Conflict of interest: E.J.R. van Beek is board member of Aidence, Imbio, and QCTIS, is a consultant for InHealth and Mentholatum, outside the submitted work; is owner and founder of QCTIS; author and spouse are directors. Conflict of interest: S.L. Knight disclosed no relevant relationships. Conflict of interest: D.A. Lynch is a consultant for Parexel Imaging, Boehringer Ingelheim, Veracyte, Daiichi Sankyo, and AstraZeneca, received payment for lectures including service on speakers bureaus from Boehringer Ingelheim, outside the submitted work. Conflict of interest: G.D. Rubin disclosed no relevant relationships. Conflict of interest: M. Humbert is a board member and consultant for Acceleron, Actelion, Bayer, GSK, and Merck; has grants/grants pending with Acceleron, Actelion, and Bayer; received payment for lectures including service on speakers bureaus from Actelion, Bayer, GSK, and Merck, outside the submitted work., (© 2021 European Respiratory Society and RSNA. This article is a simultaneous joint publication in the European Respiratory Journal and Radiology. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.)

Interferon (IFN)-γ release assays (IGRAs) are probably the most accurate tests for the detection of latent Mycobacterium tuberculosis infection, but IGRAs are labour intensive and the transport of samples over longer distances is difficult. IFN-γ-induced protein (IP)-10 is expressed at 100-fold higher levels than IFN-γ, and IP-10 release assays have comparable performance to IGRAs. The aim of this study was to explore the diagnostic potential of a novel IP-10 release assay based on dried plasma spots (DPS). The presence of IP-10 and IFN-γ was determined in plasma and in DPS by ELISA. Diagnostic algorithms for plasma and DPS tests for IP-10 were developed on a training cohort comprising 60 tuberculosis (TB) patients and 59 healthy controls. Diagnostic accuracy was assessed in a validation cohort comprising 78 TB patients and 98 healthy controls. Plasma was measured in Spain and DPS samples were sent to Denmark using the conventional postal service for analysis. IP-10 was readily detectable in both plasma and DPS, and correlation was excellent (r(2) = 0.95). QuantiFERON-TB Gold In-Tube (QFT-TB) and IP-10 in DPS and plasma rendered comparable sensitivity (78%, 82% and 84%, respectively), specificity (100%, 97% and 97%, respectively) and indeterminate rates (p>0.55). The DPS-based IP-10 test has comparable diagnostic accuracy to the QFT-TB and samples can be sent via conventional mail over long distances for analysis without affecting the results.

In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry., Competing Interests: Conflict of interest: H-U. Kauczor reports grants, personal fees for lectures and non-financial support from Siemens, grants and personal fees for lectures from Philips, and personal fees for lectures from Boehringer Ingelheim and Bracco, outside the submitted work. Conflict of interest: A-M. Baird reports personal fees and non-financial support for meeting attendance from Roche and MSD, outside the submitted work; and is a board member for Lung Cancer Europe (LuCE); LuCE have received support from Abbvie, Amgen, BMS, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche and Takeda, and, as board member, A-M. Baird has participated on advisory boards for BMS, Takeda and Pfizer, with the fee paid directly to LuCE. Conflict of interest: T.G. Blum has nothing to disclose. Conflict of interest: L. Bonomo has nothing to disclose. Conflict of interest: C. Bostantzoglou has nothing to disclose. Conflict of interest: O. Burghuber reports grants from Boehringer Ingelheim, GSK, AstraZeneca, Menarini, Teva, Pfizer, Chiesi, Novartis and Federal State Department of Health, non-financial support (utilities and meeting facilities) from the Municipal Department of Health in Vienna and air liquid, during the conduct of the study; and personal fees for advisory board work and lectures from Boehringer Ingelheim, AstraZeneca, Chiesi, MSD, Menarini, Roche and GSK, outside the submitted work. Conflict of interest: B. Čepická is a member of the European Lung Foundation patient advisory group. Conflict of interest: A. Comanescu reports sponsorship from Merck Romania and Bristol-Myers Squibb România, during the conduct of the study; and patient advisory panel fees from Bristol-Myers Squibb, outside the submitted work. Conflict of interest: S. Couraud reports grants, personal fees and other from Roche, grants and personal fees from AstraZeneca, during the conduct of the study; and grants and personal fees from BMS, AstraZeneca, Lilly and Laidet Medical, grants, personal fees and other from Pfizer, Roche, Chugai, MSD and Boehringer Ingelheim, grants and non-financial support from Sysmex Innostics, grants from Novartis, Merck and Amgen, and personal fees from Exact Science, outside the submitted work. Conflict of interest: A. Devaraj has nothing to disclose. Conflict of interest: V. Jespersen has nothing to disclose. Conflict of interest: S. Morozov has nothing to disclose. Conflict of interest: I. Nardi Agmon has nothing to disclose. Conflict of interest: N. Peled reports consultancy for and honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Foundation Medicine, Guardant360, MSD, Novartis, NovellusDx, Pfizer, Roche and Takeda, outside the submitted work; and in addition, has patents WO2012023138, US20130150261 and WO/2015/059646 issued. Conflict of interest: P. Powell is an employee of the European Lung Foundation. Conflict of interest: H. Prosch reports grants from Siemens, outside the submitted work. Conflict of interest: S. Ravara has nothing to disclose. Conflict of interest: J. Rawlinson is a member of the patient advisory group of the ERS/European Lung Foundation (as a lung cancer patient) and a patient representative on the NHS England Screening advisory group; neither role is remunerated in any way. Conflict of interest: M-P. Revel has nothing to disclose. Conflict of interest: M. Silva has nothing to disclose. Conflict of interest: A. Snoeckx has nothing to disclose. Conflict of interest: B. van Ginneken reports grants and stock/royalties from Thirona, and grants and royalties from Delft Imaging Systems and MeVis Medical Solutions, outside the submitted work. Conflict of interest: J.P. van Meerbeeck has nothing to disclose. Conflict of interest: C. Vardavas has nothing to disclose. Conflict of interest: O. von Stackelberg has nothing to disclose. Conflict of interest: M. Gaga reports grants from Novartis, Chiesi, Elpen and Menarini, and personal fees from BMS and MSD, outside the submitted work., (This official statement of the European Society of Radiology (ESR) and the European Respiratory Society (ERS) is published jointly in European Radiology [DOI: 10.1007/s00330-020-06727-7] and the European Respiratory Journal [DOI: 10.1183/13993003.00506-2019]. The versions are identical aside from minor differences in typesetting and presentation in accord with the journal styles. ©European Society of Radiology and European Respiratory Society 2020.)

Landmark studies on automatic CT quantification of the pathophysiological factors in obstructive pulmonary diseases http://ow.ly/YEKhv.

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and quality assurance plan. The establishment of a central registry, including biobank and image bank, and preferably on a European level, is strongly encouraged., (Copyright ©ERS/ESR 2015.)

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness. [ABSTRACT FROM AUTHOR]

Background In the last decade, a fundamental shift in the treatment of cystic fibrosis (CF) took place due to the introduction of CF transmembrane conductance regulator (CFTR) modulators. Adequate medication adherence is a prerequisite for their effectiveness, but little is known about adherence to CFTR modulators. We aimed to assess the extent of medication adherence to CFTR modulators in patients with CF and assess which characteristics are associated with adherence. Methods A systematic review following PRISMA guidelines was performed. Studies needed to report adherence to CFTR modulators. Main outcomes were: 1) level of medication adherence and 2) associations of demographic and/or clinical characteristics with adherence. Results In total, 4082 articles were screened and 21 full-text papers were assessed for eligibility. Ultimately, seven studies were included. Most studies were retrospective and focused on adherence to ivacaftor or lumacaftor–ivacaftor with only one focusing on elexacaftor–tezacaftor–ivacaftor. The majority used pharmacy refill data with adherence determined with the proportion of days covered (PDC) or the medication possession ratio (MPR). One study additionally used electronic monitoring and patient self-reported adherence. Adherence was 0.62–0.99 based on pharmacy data (PDC or MPR), 61% via electronic monitoring and 100% via self-report. Age <18 years appeared to be associated with good adherence, as was a higher lung function. Conclusions Despite the wide variety of adherence methods used, adherence to CFTR modulators is suboptimal, based on objective measures such as pharmacy refill data or electronic monitoring. CFTR modulator adherence measurement and definitions requires more standardisation with a preference for objective and granular methods. [ABSTRACT FROM AUTHOR]

Introduction Exertional dyspnoea is the primary diagnostic symptom for chronic cardiopulmonary disease populations. Whilst a number of exercise tests are used, there remains no gold standard clinical measure of exertional dyspnoea. The aim of this review was to comprehensively describe and evaluate all types of fixed-intensity exercise tests used to assess exertional dyspnoea in chronic cardiopulmonary populations and, where possible, report the reliability and responsiveness of the tests. Methods A systematic search of five electronic databases identified papers that examined 1) fixed-intensity exercise tests and measured exertional dyspnoea, 2) chronic cardiopulmonary populations, 3) exertional dyspnoea reported at isotime or upon completion of fixed-duration exercise tests, and 4) published in English. Results Searches identified 8785 papers. 123 papers were included, covering exercise tests using a variety of fixed-intensity protocols. Three modes were identified, as follows: 1) cycling (n=87), 2) walking (n=31) and 3) other (step test (n=8) and arm exercise (n=2)). Most studies (98%) were performed on chronic respiratory disease patients. Nearly all studies (88%) used an incremental exercise test. 34% of studies used a fixed duration for the exercise test, with the remaining 66% using an exhaustion protocol recording exertional dyspnoea at isotime. Exertional dyspnoea was measured using the Borg scale (89%). 7% of studies reported reliability. Most studies (72%) examined the change in exertional dyspnoea in response to different interventions. Conclusion Considerable methodological variety of fixed-intensity exercise tests exists to assess exertional dyspnoea and most test protocols require incremental exercise tests. There does not appear to be a simple, universal test for measuring exertional dyspnoea in the clinical setting. [ABSTRACT FROM AUTHOR]