Pub Date : 2024-07-16DOI: 10.1136/thorax-2024-221493
Gang Wang, Erik Melén
{"title":"Reinforcing the benefits of children's physical activity on lung health.","authors":"Gang Wang, Erik Melén","doi":"10.1136/thorax-2024-221493","DOIUrl":"10.1136/thorax-2024-221493","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1136/thorax-2023-221148
Leticia Kawano-Dourado, Tejaswini Kulkarni, Christopher J Ryerson, Pilar Rivera-Ortega, Bruno Guedes Baldi, Nazia Chaudhuri, Manuela Funke-Chambour, Anna-Maria Hoffmann-Vold, Kerri A Johannson, Yet Hong Khor, Sydney B Montesi, Lucilla Piccari, Helmut Prosch, María Molina-Molina, Jacobo Sellares Torres, Iazsmin Bauer-Ventura, Sujeet Rajan, Joseph Jacob, Duncan Richards, Lisa G Spencer, Barbara Wendelberger, Tom Jensen, Melanie Quintana, Michael Kreuter, Anthony C Gordon, Fernando J Martinez, Naftali Kaminski, Victoria Cornelius, Roger Lewis, Wendy Adams, Gisli Jenkins
Background: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD).
Methods: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure.
Results: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results.
Conclusion: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.
{"title":"Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.","authors":"Leticia Kawano-Dourado, Tejaswini Kulkarni, Christopher J Ryerson, Pilar Rivera-Ortega, Bruno Guedes Baldi, Nazia Chaudhuri, Manuela Funke-Chambour, Anna-Maria Hoffmann-Vold, Kerri A Johannson, Yet Hong Khor, Sydney B Montesi, Lucilla Piccari, Helmut Prosch, María Molina-Molina, Jacobo Sellares Torres, Iazsmin Bauer-Ventura, Sujeet Rajan, Joseph Jacob, Duncan Richards, Lisa G Spencer, Barbara Wendelberger, Tom Jensen, Melanie Quintana, Michael Kreuter, Anthony C Gordon, Fernando J Martinez, Naftali Kaminski, Victoria Cornelius, Roger Lewis, Wendy Adams, Gisli Jenkins","doi":"10.1136/thorax-2023-221148","DOIUrl":"10.1136/thorax-2023-221148","url":null,"abstract":"<p><strong>Background: </strong>Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD).</p><p><strong>Methods: </strong>Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure.</p><p><strong>Results: </strong>The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results.</p><p><strong>Conclusion: </strong>By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1136/thorax-2024-221375
Olivier Taton, Pierre Alain Gevenois, Alain Van Muylem, Benjamin Bondue, Sébastien Van Laethem, Dimitri Leduc
Rationale: Endoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised that endoscopic lung volume reduction increases its strength by modifying its shape.
Objectives: To investigate changes in both diaphragm shape and strength induced by the insertion of endobronchial valves.
Methods: In 19 patients, both the diaphragm shape and strength were investigated respectively by 3D Slicer software applied on CT scans acquired at functional residual capacity and by transdiaphragmatic pressure measurements by bilateral magnetic stimulation of the phrenic nerves before and 3 months after unilateral valves insertion.
Measurements and main results: After lung volume reduction (median (IQR), 434 mL (-597 to -156], p<0.0001), diaphragm strength increased (transdiaphragmatic pressure: 3 cmH2O (2.3 to 4.2), p<0.0001). On the treated side, this increase was associated with an increase in the coronal (16 mm (13 to 24), p<0.0001) and sagittal (26 mm (21 to 30), p<0.0001) lengths as well as in the area of the zone of apposition (62 cm2 (3 to 100), p<0.0001) with a decrease in the coronal (8 mm (-12 to -4), p<0.0001) and sagittal (9 mm (-18 to -2), p=0.0029) radii of curvature.
Conclusions: Endoscopic lung volume reduction modifies the diaphragm shape by increasing its length and its zone of apposition and by decreasing its radius of curvature on the treated side, resulting in an increase in its strength.
{"title":"Improvements of the shape and strength of the diaphragm after endoscopic lung volume reduction.","authors":"Olivier Taton, Pierre Alain Gevenois, Alain Van Muylem, Benjamin Bondue, Sébastien Van Laethem, Dimitri Leduc","doi":"10.1136/thorax-2024-221375","DOIUrl":"10.1136/thorax-2024-221375","url":null,"abstract":"<p><strong>Rationale: </strong>Endoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised that endoscopic lung volume reduction increases its strength by modifying its shape.</p><p><strong>Objectives: </strong>To investigate changes in both diaphragm shape and strength induced by the insertion of endobronchial valves.</p><p><strong>Methods: </strong>In 19 patients, both the diaphragm shape and strength were investigated respectively by 3D Slicer software applied on CT scans acquired at functional residual capacity and by transdiaphragmatic pressure measurements by bilateral magnetic stimulation of the phrenic nerves before and 3 months after unilateral valves insertion.</p><p><strong>Measurements and main results: </strong>After lung volume reduction (median (IQR), 434 mL (-597 to -156], p<0.0001), diaphragm strength increased (transdiaphragmatic pressure: 3 cmH<sub>2</sub>O (2.3 to 4.2), p<0.0001). On the treated side, this increase was associated with an increase in the coronal (16 mm (13 to 24), p<0.0001) and sagittal (26 mm (21 to 30), p<0.0001) lengths as well as in the area of the zone of apposition (62 cm<sup>2</sup> (3 to 100), p<0.0001) with a decrease in the coronal (8 mm (-12 to -4), p<0.0001) and sagittal (9 mm (-18 to -2), p=0.0029) radii of curvature.</p><p><strong>Conclusions: </strong>Endoscopic lung volume reduction modifies the diaphragm shape by increasing its length and its zone of apposition and by decreasing its radius of curvature on the treated side, resulting in an increase in its strength.</p><p><strong>Trial registration number: </strong>NCT05799352.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1136/thorax-2024-221967
Timothy J Davies
In 2015 the WHO set ambitious targets to tackle the global epidemic of Mycobacterium Tuberculosis (TB), including increased detection, reduced mortality, and decreased economic burden of disease, however, the WHO update from September 2023 reports that none are on track for their 2025 milestones (https://reliefweb.int/report/world/global-tuberculosis-report-2023). This situation is not new- globally all three of the 2020 milestones were missed despite some country specific successes. However, the pandemic has had a major impact, stalling, or outright reversing pre-pandemic progress. For example, overall incidence estimates had declined year-on-year between 2010 and 2020 from 11.4 million (95% CI, 8.94,14.10) to 10 million (95% CI, 9.40,10.70). However, in 2021 and 2022, global incidence estimates increased to 10.3 million (95% CI, 9.64,11.00) and 10.6 million (95% CI, 9.87,11.40) respectively. Similar trends were seen in mortality, although the initial increase was in 2020 with 1.37 million estimated deaths compared with 1.32 million in 2019, with the number returning back to pre-pandemic levels (1.30 million, 95% CI 1.18 to 1.43) in 2022. The timing discrepancy reflects the delayed onset of the disease post infection, compared with the more immediate effects of reduced access to treatment. Shockingly, they estimate that 500 000 excess TB deaths occurred compared with if pre-pandemic trends had been maintained. As it stands, the total reduction in incidence rate and TB deaths in 2022 compared with 2015 were 8.7% and 19% respectively, a long …
{"title":"Journal club","authors":"Timothy J Davies","doi":"10.1136/thorax-2024-221967","DOIUrl":"https://doi.org/10.1136/thorax-2024-221967","url":null,"abstract":"In 2015 the WHO set ambitious targets to tackle the global epidemic of Mycobacterium Tuberculosis (TB), including increased detection, reduced mortality, and decreased economic burden of disease, however, the WHO update from September 2023 reports that none are on track for their 2025 milestones (https://reliefweb.int/report/world/global-tuberculosis-report-2023). This situation is not new- globally all three of the 2020 milestones were missed despite some country specific successes. However, the pandemic has had a major impact, stalling, or outright reversing pre-pandemic progress. For example, overall incidence estimates had declined year-on-year between 2010 and 2020 from 11.4 million (95% CI, 8.94,14.10) to 10 million (95% CI, 9.40,10.70). However, in 2021 and 2022, global incidence estimates increased to 10.3 million (95% CI, 9.64,11.00) and 10.6 million (95% CI, 9.87,11.40) respectively. Similar trends were seen in mortality, although the initial increase was in 2020 with 1.37 million estimated deaths compared with 1.32 million in 2019, with the number returning back to pre-pandemic levels (1.30 million, 95% CI 1.18 to 1.43) in 2022. The timing discrepancy reflects the delayed onset of the disease post infection, compared with the more immediate effects of reduced access to treatment. Shockingly, they estimate that 500 000 excess TB deaths occurred compared with if pre-pandemic trends had been maintained. As it stands, the total reduction in incidence rate and TB deaths in 2022 compared with 2015 were 8.7% and 19% respectively, a long …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1136/thorax-2023-220032
Renata L Riha, Ankur Singh, Elizabeth A Hill, Hazel Evans, David O'Regan
Background In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment. Method Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024. Results Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes. Conclusions This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population.
{"title":"Sleep-disordered breathing in children and adults with intellectual disability: mind the gap!","authors":"Renata L Riha, Ankur Singh, Elizabeth A Hill, Hazel Evans, David O'Regan","doi":"10.1136/thorax-2023-220032","DOIUrl":"https://doi.org/10.1136/thorax-2023-220032","url":null,"abstract":"Background In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment. Method Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024. Results Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes. Conclusions This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1136/thorax-2023-220558
Christian A Merlo, Teja Thorat, Maral DerSarkissian, Lisa J McGarry, Catherine Nguyen, Yuqian M Gu, Joe Healy, Jaime L Rubin, M Alan Brookhart
Background Ivacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US. Methods Data from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator ( CFTR ) gating mutation (excluding R117H ); age-matched comparator cohort included people with a F508del and a minimal function CFTR mutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations. Findings Over a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio [HR] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV1: 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMI z -scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m2 and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733). Interpretation Our analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term. Data are available on reasonable request. The data supporting the findings of this study are available from the US CFFPR at . The US CFFPR collects and manages its own data and maintains processes for researchers to request summarised data. Restrictions may apply to the availability of these data, which were used under the licence agreement for this study.
背景 伊伐卡夫托(IVA)已被证明可改善囊性纤维化(CF)患者的肺功能和其他临床疗效。十年来,IVA在现实世界中的应用使人们能够对这种治疗方法的长期疗效进行研究。这项回顾性纵向队列研究调查了 IVA 对美国 CF 患者死亡率和健康状况的影响。方法 对美国 CF 基金会患者登记处 2010 年 1 月至 2019 年 12 月的数据进行了分析。IVA治疗队列包括具有CF跨膜传导调节器(CFTR)门控突变(不包括R117H)的患者;年龄匹配的比较队列包括具有F508del和最小功能CFTR突变且之前未接受过CFTR调节剂治疗的患者。利用倾向评分生成的标准化死亡率加权法对各队列的基线特征进行了平衡。研究结果包括总生存率、肺移植、1 s内预测用力呼气容积百分比(ppFEV1)、体重指数(BMI)、肺部恶化(PEx)、门诊就诊次数和住院次数。研究结果 在最长 7.9 年的随访中,IVA 治疗组群(N=736)的死亡率(危险比(HR)(95% CI):0.22(0.09 至 0.45))、肺移植率(HR:0.11(95% CI 0.02 至 0.28))、PEx(比率:0.49(95% CI 0.42 至 0.55))和全因住院率(比率:0.50(95% CI 0.43 至 0.56))以及肺功能(ppFEV1 平均差异:8.46(95% CI 7.34 至 9.75))和 BMI/BMI z 分数(平均差异分别为 1.20(95% CI 0.92 至 1.71)kg/m2 和 0.27(95% CI 0.25 至 0.40))均优于参照队列(N=733)。解释 我们的分析表明,IVA 可在约 8 年的随访期内为 CF 患者带来持续的临床益处。这些研究结果加强了现有的实际证据,即 IVA 可以长期延缓疾病进展并减轻 CF 的医疗负担。如有合理要求,可提供相关数据。支持本研究结果的数据可从美国CFFPR获取,网址为 。美国 CFFPR 收集和管理自己的数据,并为研究人员申请汇总数据提供程序。根据本研究的许可协议,这些数据的提供可能会受到限制。
{"title":"Long-term impact of ivacaftor on mortality rate and health outcomes in people with cystic fibrosis","authors":"Christian A Merlo, Teja Thorat, Maral DerSarkissian, Lisa J McGarry, Catherine Nguyen, Yuqian M Gu, Joe Healy, Jaime L Rubin, M Alan Brookhart","doi":"10.1136/thorax-2023-220558","DOIUrl":"https://doi.org/10.1136/thorax-2023-220558","url":null,"abstract":"Background Ivacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US. Methods Data from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator ( CFTR ) gating mutation (excluding R117H ); age-matched comparator cohort included people with a F508del and a minimal function CFTR mutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations. Findings Over a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio [HR] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV1: 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMI z -scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m2 and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733). Interpretation Our analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term. Data are available on reasonable request. The data supporting the findings of this study are available from the US CFFPR at <https://www.cff.org/researchers/patient-registry-data-requests>. The US CFFPR collects and manages its own data and maintains processes for researchers to request summarised data. Restrictions may apply to the availability of these data, which were used under the licence agreement for this study.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuberculosis (TB) control efforts are limited by ineffective characterisation of tuberculosis infection (TBI) -a heterogeneous spectrum of pre-clinical infection states, invisible to tools of routine clinical screening, that are associated with variable risk of progression to TB disease. In this prospective study, we use positron emission tomography-CT (PET-CT) as a high-resolution imaging modality to characterise and classify structural and metabolic features observed in 16 asymptomatic household TB contacts with normal chest radiographs. We identify four feature patterns that associate with distinct clinical and microbiological outcomes, supporting potential utility of PET-CT for objective classification of TBI phenotypes.
{"title":"A structural and metabolic framework for classifying pre-clinical tuberculosis infection phenotypes using 18F-FDG PET-CT: a prospective cohort analysis following <i>M. tuberculosis</i> exposure.","authors":"Jee Whang Kim, Sonam Vadera, Meedya Sharifpour, Amrita Bajaj, Anver Kamil, Pranabashis Haldar","doi":"10.1136/thorax-2024-221470","DOIUrl":"https://doi.org/10.1136/thorax-2024-221470","url":null,"abstract":"<p><p>Tuberculosis (TB) control efforts are limited by ineffective characterisation of tuberculosis infection (TBI) -a heterogeneous spectrum of pre-clinical infection states, invisible to tools of routine clinical screening, that are associated with variable risk of progression to TB disease. In this prospective study, we use positron emission tomography-CT (PET-CT) as a high-resolution imaging modality to characterise and classify structural and metabolic features observed in 16 asymptomatic household TB contacts with normal chest radiographs. We identify four feature patterns that associate with distinct clinical and microbiological outcomes, supporting potential utility of PET-CT for objective classification of TBI phenotypes.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14DOI: 10.1136/thorax-2023-221052
David Abelson, James Di Michiel, Clayton Frater, Mark Pearson, Robert Russo, Martin Wechselberger, Alice Cottee, Lucy Morgan
Background: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health.
Methods: Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared.
Measurements and main results: In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18o ex-smokers, 47o non-smokers (p=0.036)), but not to actual speed on helical path (r=0.26 (p=0.46); median 13.6 mm/min ex-smokers vs 13.9 mm/min non-smokers (p=1.0)).
Conclusion: For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.
{"title":"Mucus clears from the trachea in a helix: a new twist to understanding airway diseases.","authors":"David Abelson, James Di Michiel, Clayton Frater, Mark Pearson, Robert Russo, Martin Wechselberger, Alice Cottee, Lucy Morgan","doi":"10.1136/thorax-2023-221052","DOIUrl":"10.1136/thorax-2023-221052","url":null,"abstract":"<p><strong>Background: </strong>Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health.</p><p><strong>Methods: </strong>Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared.</p><p><strong>Measurements and main results: </strong>In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18<sup>o</sup> ex-smokers, 47<sup>o</sup> non-smokers (p=0.036)), but not to actual speed on helical path (r=0.26 (p=0.46); median 13.6 mm/min ex-smokers vs 13.9 mm/min non-smokers (p=1.0)).</p><p><strong>Conclusion: </strong>For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}