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Clarus Leung,1 Jean Bourbeau,2 Don D Sin,1 Shawn D Aaron,3 J Mark FitzGerald,4 François Maltais,5 Darcy D Marciniuk,6 Denis O’Donnell,7 Paul Hernandez,8 Kenneth R Chapman,9 Brandie Walker,10 Jeremy D Road,4 Liyun Zheng,1 Carl Zou,1 James C Hogg,1 Wan C Tan1 On behalf of the CanCOLD Collaborative Research Group1Centre for Heart Lung Innovation, St Pauls Hospital, The University of British Columbia, Vancouver, BC, Canada; 2Research Institute McGill University Health Centre, McGill University, Montreal, Quebec, Canada; 3The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; 4Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, Canada; 5Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada; 6Respiratory Research Centre, University of Saskatchewan, Saskatoon, Canada; 7Department of Medicine, Queen’s University, Kingston, Canada; 8Department of Medicine, Dalhousie University, Halifax, Canada; 9Toronto General Hospital Research Institute, University of Toronto, Toronto, Canada; 10Department of Medicine, University of Calgary (BW), Alberta, CanadaCorrespondence: Wan C TanCentre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Rm 166, 1081 Burrard Street, Vancouver, B.C, V6Z 1Y6, CanadaTel +1-604-682-2344 ext 62749Fax +1-604-806-9274Email wan.tan@hli.ubc.caPurpose: To determine the spirometric-based prevalence of COPD across different regions in Canada and to evaluate the site heterogeneity of risk factors.Patients and Methods: In this cross-sectional, population-based study, random samples of non-institutionalized adults aged ≥ 40 years were generated by random digit dialling. Participants answered an interviewer-administered questionnaire and performed spirometry before and after bronchodilator administration. COPD was defined as post-bronchodilator FEV1/FVC < 0.70 (fixed ratio, FR) and as FEV1/FVC < 5th percentile (lower limits of normal, LLN). Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD. I2 and Tau2 analyses were used to evaluate heterogeneity.Results: Out of 5176 (95%) participants, 4893 (47% male with mean age 56.6 years (95% confidence interval, 56.0– 57.2)) had spirometry that satisfied ATS criteria. The population prevalence of COPD was 16.2% (95% CI, 14.5– 17.8) by FR and 11.2% (95% CI, 9.7– 12.6) by LLN. Male predominance in prevalence was shown by FR but not by LLN criteria. Patient characteristics associated with an increased risk of COPD included: age (OR 1.56; 95% CI 1.33– 1.84); history of physician-diagnosed asthma (OR 3.30; 95% CI 2.42– 4.49); and childhood hospitalization for respiratory illness (OR 1.81; 95% CI 1.17– 2.80). In terms of smoking-related risk factors, current smoking status had the highest odds ratio (OR 3.49; 95% CI 2.55– 4.80). Variance in prevalence among sites was significantly reduced by adjusting for risk factors in Tau2 analyses. Higher odds of exposure for each risk factor was found in more severe COPD, suggesting that a higher risk could be linked to the development of severe disease.Conclusion: This study reports the population prevalence of COPD in nine urban cities which collectively represent the majority of the Canadian population and demonstrates that heterogeneity in prevalence among sites is substantially explained by variation in associated risk factors for COPD.Keywords: prevalence, heterogeneity, COPD

Tze Pin Ng,1 Qi Gao,1 Xinyi Gwee,1 Denise QL Chua,1 Wan C Tan2 1Gerontology Research Programme, Department of Psychological Medicine, National University of Singapore, Singapore; 2Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaCorrespondence: Tze Pin NgGerontology Research Programme, Department of Psychological Medicine, National University of Singapore, NUHS Tower Block, 9 th Floor, 1E Kent Ridge Road, 119228, SingaporeTel +65-67723478Fax +65-67772191 Email pcmngtp@nus.edu.sgObjective: The anti-oxidant and anti-inflammatory actions of phytochemicals and the smooth muscle relaxant actions of theophylline present in tea may confer pulmonary protection and reduce COPD risk. We investigated tea consumption (black, oolong, or green) association with COPD risks in a population-based cohort study of older adults aged ≥ 55.Methods: GOLD criteria was used to identify prevalent and incident cases of COPD (FEV1/FVC < 0.70) among 4617 participants and 920 participants free of COPD at baseline who were assessed at follow-up 4.5 years later.Results: Prevalent cases of COPD consumed less tea than their non-COPD counterparts. Estimated odds ratio (OR) and 95% confidence intervals (95% CI) of association with prevalent COPD, adjusted for age, sex, ethnicity, housing type, smoking, alcohol, physical activity and BMI declined across tea consumption levels (p-trend=0.048), and was lowest for ≥ 3 cups/day (OR=0.77, 95% CI=0.61– 0.96). The cumulated incidence of COPD declined across tea consumption categories (p-trend=0.012) and the lowest OR of association (OR=0.35, 95% CI=0.17– 0.69) with consuming ≥ 3 cups/day after co-variate adjustment.Conclusion: Different kinds of tea showed similar non-significant trends of associations but appeared to be strongest for green tea. Tea consumption in this Asian population was associated with lowered COPD prevalence and incidence.Keywords: phytochemical, polyphenols, theophylline, epidemiological, longitudinal

Kate M Johnson,1 Abdollah Safari,1,2 Wan C Tan,3 Jean Bourbeau,4 J Mark FitzGerald,2 Mohsen Sadatsafavi1,2,5 On behalf of the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study and the Canadian Respiratory Research Network 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 2Institute for Heart and Lung Health, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada; 3Centre for Heart Lung Innovation (the James Hogg Research Centre), St Paul’s Hospital, Vancouver, BC, Canada; 4Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre, Montreal, QC, Canada; 5Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Institute, Vancouver, BC, Canada Background: The burden of symptoms varies markedly between patients with COPD and is only weakly correlated with lung function impairment. While heterogeneity in lung function decline and exacerbations have been previously studied, the extent of heterogeneity in symptoms and the factors associated with this heterogeneity are not well understood.Methods: A sample of the general Canadian population ≥40 years with persistent airflow limitation was followed for up to 3 years. Participants reported whether they experienced chronic coughing, phlegm, wheezing, or dyspnea during visits at 18-month intervals. We used mixed-effect logistic regression models (separately for each symptom) to assess overall heterogeneity in the occurrence of symptoms between individuals, and the proportion of variation in symptom burden explained by lung function vs all other clinical characteristics of participants.Results: Four hundred forty-nine participants (53% male, mean age 67 years) contributed 968 visits in total, and 89% of patients reported at least one symptom during follow-up. There was substantial heterogeneity in the individual-specific probabilities for the occurrence of symptoms. This heterogeneity was highest for wheeze and dyspnea (IQR of probabilities: 0.13–0.78 and 0.19–0.81, respectively). FEV1 explained 28% of the variation between individuals in the occurrence of dyspnea, 8% for phlegm, 3% for cough, and 2% for wheeze. All clinical characteristics of participants (including FEV1) explained between 26% of heterogeneity in the occurrence of cough to 49% for dyspnea.Conclusion: There is marked heterogeneity in the burden of respiratory symptoms between COPD patients. The ability of lung function and other commonly measured clinical characteristics to explain this heterogeneity differs between symptoms. Keywords: population, respiratory symptoms, chronic obstructive pulmonary disease, variability, cough, phlegm, wheeze, dyspnea

Valérie Coats,1 Jean-Pierre Després,1 Natalie Alméras,1 Mickaël Martin,1 Don D Sin,2 Rémi Rabasa-Lhoret,3 Éric Larose,1 Wan C Tan,2 Jean Bourbeau,4 François Maltais1On behalf of the CanCOLD Collaborative Research Group and the Canadian Respiratory Research Network 1Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Université, Laval, QC, Canada; 2University of British Columbia, Vancouver, BC, Canada; 3Institut de Recherches Cliniques de Montréal, Département de Nutrition et Service d’Endocrinologie, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; 4Respiratory Epidemiology and Clinical Research Unit, Research Institute of the McGill University Health Centre, Montreal, QC, CanadaRationale: Obesity/overweight is the most prevalent body composition abnormality in COPD. However, little is known about the impact of fat distribution on cardiometabolic health in COPD.Objective: To study the associations between ectopic adiposity, cardiometabolic health, and COPD.Methods: A total of 263 subjects (166 males; age=65±9 years) were randomly selected from the general population. Subjects were classified as non-COPD controls and COPD, according to the Global initiative for chronic Obstructive Lung Disease (GOLD) classification, and the presence of cardiometabolic comorbidities was recorded. Ectopic fat accumulation was documented from computed tomography measurements of visceral adipose tissue cross-sectional areas and muscle mean attenuation, assessed at L4–L5. Blood glucose, lipid, and adipokine profiles were also evaluated.Results: After correcting for age, sex, and tobacco exposure, visceral adipose tissue cross-sectional area was higher in GOLD 2+ compared to GOLD 1 individuals. Consistent with this, mean muscle tissue attenuation was lower in GOLD 2+ vs GOLD 1 and non-COPD controls (P

Rationale: Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns.Methods: 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction.Results: In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV(1)); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV(1i)); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV(1p)). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVC(i)); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVC(p)). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV(1)/FVC <0.7 and FEV(1)% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV(1)-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds.Conclusions: The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing. [ABSTRACT FROM AUTHOR]

Background: People with known risk factors for chronic obstructive pulmonary disease (COPD) are important targets for screening and early intervention. We sought to measure the prevalence of COPD among such individuals visiting a primary care practitioner for any reason. We also evaluated the accuracy of prior diagnosis or nondiagnosis of COPD and identified associated clinical characteristics.Methods: We recruited patients from three primary care sites who were 40 years or older and had a smoking history of at least 20 pack-years. Participants were asked about respiratory symptoms and underwent postbronchodilator spirometry. COPD was defined as a ratio of forced expiratory volume in the first second of expiration to forced vital capacity (FEV(1)/FVC) of less than 0.7 and an FEV(1) of less than 80% predicted.Results: Of the 1459 patients who met the study criteria, 1003 (68.7%) completed spirometry testing. Of these, 208 were found to have COPD, for a prevalence of 20.7% (95% confidence interval 18.3%-23.4%). Of the 205 participants with COPD who completed the interview about respiratory symptoms before spirometry, only 67 (32.7%) were aware of their diagnosis before the study. Compared with patients in whom COPD had been correctly diagnosed before the study, those in whom COPD had been over-diagnosed or undiagnosed were similar in terms of age, sex, current smoking status and number of visits to a primary care practitioner because of a respiratory problem.Interpretation: Among adult patients visiting a primary care practitioner, as many as one in five with known risk factors met spirometric criteria for COPD. Underdiagnosis of COPD was frequent, which suggests a need for greater screening of at-risk individuals. Knowledge of the prevalence of COPD will help plan strategies for disease management. [ABSTRACT FROM AUTHOR]

RATIONALE: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. OBJECTIVES: To determine whether severe asthma exacerbations are associated with a persistent decline in lung function. METHODS: The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5-66 yr) with persistent asthma for less than 2 years, to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. MEASUREMENTS AND MAIN RESULTS: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable, 190 in the placebo group and 115 in the budesonide group. In the placebo group, the change in post-bronchodilator FEV(1) % predicted from baseline to the end of the study, in patients who did or did not experience a severe exacerbation was -6.44% and -2.43%, respectively (P < 0.001). A significant difference was seen in both children and in adults, but not in adolescents. In the budesonide group, the change in the post-bronchodilator FEV(1) % predicted in patients who did or did not experience a severe exacerbation was -2.48% and -1.72%, respectively (P = 0.57). The difference in magnitude of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). CONCLUSIONS: Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses of inhaled corticosteroid is associated with an attenuation of the decline. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objectives of this systematic review were to assess the survival rate of implants placed in sites with transalveolar sinus floor elevation. MATERIAL AND METHODS: An electronic search was conducted to identify prospective and retrospective cohort studies on transalveolar sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates/ year proportions. RESULTS: The search provided 849 titles. Full-text analysis was performed for 176 articles, resulting in 19 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37-4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4-96.0%) for implants placed in transalveolarly augmented sinuses, after 3 years in function. Furthermore, subject-based analysis revealed an estimated annual failure of 3.71% (95% CI: 1.21-11.38%), translating to 10.5% (95% CI: 3.6-28.9%) of the subjects experiencing implant loss over 3 years. CONCLUSION: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable to those in non-augmented sites. This technique is predictable with a low incidence of complications during and post-operatively. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objectives of this systematic review were to assess the survival rate of grafts and implants placed with sinus floor elevation. MATERIAL AND METHODS: An electronic search was conducted to identify studies on sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. RESULTS: The search provided 839 titles. Full-text analysis was performed for 175 articles resulting in 48 studies that met the inclusion criteria, reporting on 12,020 implants. Meta-analysis indicated an estimated annual failure rate of 3.48% [95% confidence interval (CI): 2.48%-4.88%] translating into a 3-year implant survival of 90.1% (95% CI: 86.4%-92.8%). However, when failure rates was analyzed on the subject level, the estimated annual failure was 6.04% (95% CI: 3.87%-9.43%) translating into 16.6% (95% CI: 10.9%-24.6%) of the subjects experiencing implant loss over 3 years. CONCLUSION: The insertion of dental implants in combination with maxillary sinus floor elevation is a predictable treatment method showing high implant survival rates and low incidences of surgical complications. The best results (98.3% implant survival after 3 years) were obtained using rough surface implants with membrane coverage of the lateral window. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the clinical and microbiological effects of full-mouth debridement with (FMD) and without the use of antiseptics [full-mouth scaling and root planing (FMSRP)] in comparison with conventional staged debridement (CSD) in patients with chronic periodontitis after at least 6 months. MATERIAL AND METHODS: The search in MEDLINE (PubMed), covering a period of 1975 to October 2007, and hand searching yielded 207 titles. Forty-two abstracts and 17 full-text articles were screened for inclusion. RESULTS: Twelve articles allowed a direct comparison of FMD with CSD, FMSRP with CSD and FMD with FMSRP. Probing pocket depth reductions were significantly greater (0.2 mm) with FMD and FMSRP compared with CSD. Moreover, a modest reduction in BOP (9%) favoured FMD. Likewise, clinical attachment levels were improved by 0.2-0.4 mm in favour of FMD and FMSRP, respectively. In all comparisons, single-rooted teeth and deep pockets benefitted slightly from FMD and FMSRP. Limited differences in the changes of the subgingival microbiota were noted between the treatment modalities. CONCLUSIONS: Despite the significant differences of modest magnitude, FMD or FMSRP do not provide clinically relevant advantages over CSD. Hence, all three treatment modalities may be recommended for debridement in the initial treatment of patients with chronic periodontitis. [ABSTRACT FROM AUTHOR]

Rationale: COPD is associated with reduced life expectancy.Objectives: To determine the association between small airway pathology and long-term survival after lung volume reduction in chronic obstructive pulmonary disease (COPD) and the effect of corticosteroids on this pathology.Methods: Patients with severe (GOLD-3) and very severe (GOLD-4) COPD (n = 101) were studied after lung volume reduction surgery. Respiratory symptoms, quality of life, pulmonary function, exercise tolerance, chest radiology, and corticosteroid treatment status were assessed preoperatively. The severity of luminal occlusion, wall thickening, and the presence of small airways containing lymphoid follicles were determined in resected lung tissue. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the relationship between survival and small airway pathology. The effect of corticosteroids on this pathology was assessed by comparing treated and untreated groups.Measurements and Main Results: The quartile of subjects with the greatest luminal occlusion, adjusted for covariates, died earlier than subjects who had the least occlusion (hazard ratio, 3.28; 95% confidence interval, 1.55-6.92; P = 0.002). There was a trend toward a reduction in the number of airways containing lymphoid follicles (P = 0.051) in those receiving corticosteroids, with a statistically significant difference between the control and oral +/- inhaled corticosteroid-treated groups (P = 0.019). However, corticosteroid treatment had no effect on airway wall thickening or luminal occlusion.Conclusions: Occlusion of the small airways by inflammatory exudates containing mucus is associated with early death in patients with severe emphysema treated by lung volume reduction surgery. Corticosteroid treatment dampens the host immune response in these airways by reducing lymphoid follicles without changing wall thickening and luminal occlusion. [ABSTRACT FROM AUTHOR]

Background: Although inhaled glucocorticosteroids are recommended for persistent asthma, their long-term effect on recent onset, mild, persistent asthma has yet to be established.Methods: We did a randomised, double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids. Patients aged 5-66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications. The daily budesonide dose was 400 microg, or 200 microg for children younger than 11 years. The primary outcome was time to first severe asthma-related event, and analysis was by intention to treat.Findings: 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation; hazard ratio 0.56 (95% CI 0.45-0.71, p<0.0001). Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo. Compared with placebo, budesonide increased postbronchodilator forced expiratory volume in 1 s (FEV1) from baseline by 1.48% (p<0.0001) after 1 year and by 0.88% (p=0.0005) after 3 years (expressed as percent of the predicted value). The corresponding increase in prebronchodilator FEV1 was 2.24% after 1 year and 1.71% after 3 years (p<0.0001 at both timepoints). The effect of treatment on all outcome variables was independent of the baseline lung function (prebronchodilator or postbronchodilator) or baseline medication. In children younger than 11 years, 3-year growth was reduced in the budesonide group by 1.34 cm. The reduction was greatest in the first year of treatment (0.58 cm) than years 2 and 3 (0.43 cm and 0.33 cm, respectively).Interpretation: Long-term, once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex-related differences in the lungs. However, normal sex-related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography-derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never-smokers. We analyzed full-inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross-sectional area >10, 5-10, and <5 mm 2 into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p  < 0.001). Females also had lower vessel volume >10 mm 2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5-10 mm 2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm 2 (68 ± 18 vs. 82 ± 19 mL) (all p  < 0.001). Normalized to total vessel volume, vessel volume >10 mm 2 (11 ± 4 vs. 16 ± 4%, p  < 0.001) and 5-10 mm 2 (30 ± 6 vs. 34 ± 5%, p  = 0.001) remained lower in females but vessel volume <5 mm 2 relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p  < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males., (© 2024 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

Diagnostic imaging, particularly MRI, plays a key role in the evaluation of many spine pathologies. Recent progress in artificial intelligence and its subset, machine learning, has led to many applications within spine MRI, which we sought to examine in this review. A literature search of the major databases (PubMed, MEDLINE, Web of Science, ClinicalTrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search yielded 1226 results, of which 50 studies were selected for inclusion. Key data from these studies were extracted. Studies were categorized thematically into the following: Image Acquisition and Processing, Segmentation, Diagnosis and Treatment Planning, and Patient Selection and Prognostication. Gaps in the literature and the proposed areas of future research are discussed. Current research demonstrates the ability of artificial intelligence to improve various aspects of this field, from image acquisition to analysis and clinical care. We also acknowledge the limitations of current technology. Future work will require collaborative efforts in order to fully exploit new technologies while addressing the practical challenges of generalizability and implementation. In particular, the use of foundation models and large-language models in spine MRI is a promising area, warranting further research. Studies assessing model performance in real-world clinical settings will also help uncover unintended consequences and maximize the benefits for patient care.

In spinal oncology, integrating deep learning with computed tomography (CT) imaging has shown promise in enhancing diagnostic accuracy, treatment planning, and patient outcomes. This systematic review synthesizes evidence on artificial intelligence (AI) applications in CT imaging for spinal tumors. A PRISMA-guided search identified 33 studies: 12 (36.4%) focused on detecting spinal malignancies, 11 (33.3%) on classification, 6 (18.2%) on prognostication, 3 (9.1%) on treatment planning, and 1 (3.0%) on both detection and classification. Of the classification studies, 7 (21.2%) used machine learning to distinguish between benign and malignant lesions, 3 (9.1%) evaluated tumor stage or grade, and 2 (6.1%) employed radiomics for biomarker classification. Prognostic studies included three (9.1%) that predicted complications such as pathological fractures and three (9.1%) that predicted treatment outcomes. AI's potential for improving workflow efficiency, aiding decision-making, and reducing complications is discussed, along with its limitations in generalizability, interpretability, and clinical integration. Future directions for AI in spinal oncology are also explored. In conclusion, while AI technologies in CT imaging are promising, further research is necessary to validate their clinical effectiveness and optimize their integration into routine practice.

Rationale and Objectives: The structural lung features that characterize individuals with preserved ratio impaired spirometry (PRISm) that remain stable overtime are unknown. The objective of this study was to use machine learning models with computed tomography (CT) imaging to classify stable PRISm from stable controls and stable COPD and identify discriminative features., Materials and Methods: A total of 596 participants that did not transition between control, PRISm and COPD groups at baseline and 3-year follow-up were evaluated: n = 274 with normal lung function (stable control), n = 22 stable PRISm, and n = 300 stable COPD. Investigated features included: quantitative CT (QCT) features (n = 34), such as total lung volume (%TLC CT ) and percentage of ground glass and reticulation (%GG+Reticulation texture ), as well as Radiomic (n = 102) features, including varied intensity zone distribution grainy texture (GLDZM ZDV ). Logistic regression machine learning models were trained using various feature combinations (Base, Base+QCT, Base+Radiomic, Base+QCT+Radiomic). Model performances were evaluated using area under receiver operator curve (AUC) and comparisons between models were made using DeLong test; feature importance was ranked using Shapley Additive Explanations values., Results: Machine learning models for all feature combinations achieved AUCs between 0.63-0.84 for stable PRISm vs. stable control, and 0.65-0.92 for stable PRISm vs. stable COPD classification. Models incorporating imaging features outperformed those trained solely on base features (p < 0.05). Compared to stable control and COPD, those with stable PRISm exhibited decreased %TLC CT and increased %GG+Reticulation texture and GLDZM ZDV ., Conclusion: These findings suggest that reduced lung volumes, and elevated high-density and ground glass/reticulation patterns on CT imaging are associated with stable PRISm., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wan C. Tan MD reports financial support was provided by Canadian Institute of Heath Research(CIHR), Astra Zeneca Canada Ltd., Boehringer Ingelheim Canada Ltd., GlaxoSmithKline Canada Ltd., Merck Canada Inc., Novartis Pharmaceuticals Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. Jean Bourbeau MD reports financial support was provided by Canadian Institute of Heath Research (CIHR), Réseau en santé respiratoire du FRQS, McGill University, McGill University Health Centre, AstraZeneca Canada Ltd., Boehringer Ingelheim Canada Ltd., GlaxoSmithKline Canada Ltd., Grifols Canada Ltd., Novartis Pharmaceuticals Canada Inc., Sanofi, Trudell Canada Ltd., COVIS Pharma Canada Ltd. Miranda Kirby PhD reports financial support was provided by Natural Sciences and Engineering Research Council (NSERC) Discovery Grant, The Early Researchers Award Program, The Canada Research Chair Program (Tier II). Miranda Kirby PhD reports a relationship with VIDA Diagnostics Inc that includes consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Recent advances in texture-based computed tomography (CT) radiomics have demonstrated its potential for classifying COPD., Methods: Participants from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study were evaluated. A total of 108 features were included: eight quantitative CT (qCT), 95 texture-based radiomic and five demographic features. Machine-learning models included demographics along with texture-based radiomics and/or qCT. Combinations of five feature selection and five classification methods were evaluated; a training dataset was used for feature selection and to train the models, and a testing dataset was used for model evaluation. Models for classifying COPD status and severity were evaluated using the area under the receiver operating characteristic curve (AUC) with DeLong's test for comparison. SHapely Additive exPlanations (SHAP) analysis was used to investigate the features selected., Results: A total of 1204 participants were evaluated (n=602 no COPD; n=602 COPD). There were no differences between the groups for sex (p=0.77) or body mass index (p=0.21). For classifying COPD status, the combination of demographics, texture-based radiomics and qCT performed better (AUC=0.87) than the combination of demographics and texture-based radiomics (AUC=0.81, p<0.05) or qCT alone (AUC=0.84, p<0.05). Similarly, for classifying COPD severity, the combination of demographics, texture-based radiomics and qCT performed better (AUC=0.81) than demographics and texture-based radiomics (AUC=0.72, p<0.05) or qCT alone (AUC=0.79, p<0.05). Texture-based radiomics and qCT features were among the top five features selected (15th percentile of the CT density histogram, CT total airway count, pack-years, CT grey-level distance zone matrix zone distance entropy, CT low-attenuation clusters) for classifying COPD status., Conclusion: Texture-based radiomics and conventional qCT features in combination improve machine‑learning models for classification of COPD status and severity., Competing Interests: Conflict of interest: We would like to note that there is no overlap with our study and other previously published CanCOLD studies. Further, there are no conflicts of interest or industry support in relation to this project for any of the authors. M. Kirby is a consultant for VIDA Diagnostics Inc. (Coralville, IA, USA)., (Copyright ©The authors 2024.)

Objectives: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure., Materials and Methods: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS)., Results: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis., Conclusions: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Saw reports grants from Astra Zeneca, consulting fees from Pfizer, Bayer, Astra Zeneca and Daiichi Sankyo, honoraria from Astra Zeneca, MSD, Bristol-Myers Squibb, Daiichi Sankyo, Roche and Takeda, meeting support from MSD and Astra Zeneca from Pfizer, advisory board participation from Astra Zeneca, Daiichi Sankyo and Pfizer, outside the submitted work. Dr Lai reports grants from Astra Zeneca, Roche and Amgen and meeting support from Astra Zeneca, outside the submitted work. Dr Chan reports meeting support from Roche, Astra Zeneca and Ipsen, outside the submitted work. Dr W.C. Tan reports grants from Singhealth, honoraria from Merck & Co, MSD and Astra Zeneca, meeting support from Ipsen Pharmaceuticals and Merck & Co, outside the submitted work. Dr A. Tan reports consulting fees from Amgen, Bayer and Pfizer, honoraria from Amgen, Guardant Health, Takeda, Juniper Biologics and Astra Zeneca, outside the submitted work. Dr W.L. Tan reports grants from Astra Zeneca, honoraria from Novartis and Merck, meeting support from Astra Zeneca, MSD, Boehringer Ingelheim and Ipsen, outside the submitted work. Dr Kanesvaran reports honoraria from Astellas, MSD and Ipsen, leadership roles in ESMO and SIOG, outside the submitted work. Dr Lim reports grants from Taiho Pharmaceuticals, consulting fees from Daiichi Sankyo, Amgen, Janssen and Alentis Therapeutics, honoraria from MSD and Takeda, meeting support from Astra Zeneca and Alentis Therapeutics, outside the submitted work. Dr. Tan reports grants from ACM Biolabs, Amgen, Astra Zeneca, Bayer and Pfizer, consulting fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, DKSH, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche and Takeda, honoraria from Amgen, Bayer, Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda, Beigene, Regeneron, Zymeworks, meeting support from Bayer, Merck, Pfizer, Regeneron and Zymeworks, outside the submitted work. Dr Mok reportsgrantsfrom AstraZeneca, Bristol Myers Squibb, G1 Therapeutics, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery, consulting fees from Abbvie Inc, ACEA Pharma, Adagene, Alentis Therapeutics AG, Alpha Biopharma Co., Ltd, Amgen, Amoy Diagnostics Co,AnHeart Therapeutics Inc,AVEO Pharmaceuticals, Inc,Bayer Healthcare Pharmaceuticals Ltd,BeiGene,BerGenBio ASA,Berry Oncology,Boehringer Ingelheim,Blueprint Medicines Corporation,Bristol Myers Squibb,Bowtie Life Insurance Company Limited,Bridge Biotherapeutics Inc,Covidien LP,C4 Therapeutics Inc,Cirina Ltd,CStone Pharmaceuticals,Curio Science,D3 Bio Ltd,Da Volterra,Daiichi Sankyo,Eisai,Elevation Oncology,F. Hoffmann-La Roche Ltd./ Genentech,Fishawack Facilitate Ltd,G1 Therapeutics Inc,geneDecode Co., Ltd,Gilead Sciences, Inc,GLG’s Healthcare,Gritstone Oncology, Inc,Guardant Health,Hengrui Therapeutics Inc,HiberCell, Inc.,HutchMed,Ignyta Inc.,Illumina Inc.,IncyteCorporation,Inivata,IQVIA,Janssen,Lakeshore Biotech Ltd,Lilly,Lunit USA, Inc,Loxo-Oncology,Lucence Health Inc,Medscape LLC/ WebMD,Medtronic,Merck Serono,MSD,Mirati Therapeutics Inc,MiRXES,MoreHealth,Novartis,Novocure GmbH,Omega Therapeutics Inc,OrigiMed,OSE Immunotherapeutics,PeerVoice,Pfizer,PrIME Oncology,Prenetics Global Limited,Puma Biotechnology Inc,Qiming Development (HK) Ltd,Regen Medtech Holdings Limited,Regeneron Pharmaceuticals Inc.,Roche Pharmaceuticals/ Diagnostics/ Foundation One,Sanofi-Aventis,SFJ Pharmaceutical Ltd,Simcere of America Inc,Synergy Research,Summit Therapeutics Sub, Inc,Takeda Pharmaceuticals HK Ltd,Tigermed,Vertex Pharmaceuticals,Virtus Medical Group,XENCOR, Inc,Yuhan Corporation,honorariafromACEA Pharma,Alpha Biopharma Co.Ltd,Amgen,Amoy Diagnostics Co. Ltd,AstraZeneca (before 1/1/19),BeiGene,BI,BMS,Daiichi Sankyo,Daz Group,Fishawack Facilitate Ltd.,InMed Medical Communication,Janssen Pharmaceutica NV,Jiahui Holdings Co. Limited,LiangYiHui Healthcare,Lilly,Lucence Health Inc.,MD Health Brazil,Medscape LLC,Merck Pharmaceuticals HK Ltd.,Merck Sharp & Dohme,MiRXES,Novartis,OrigiMed Co. Ltd.,P. Permanyer SL,PeerVoice, Physicians’ Education Resource,Pfizer,PrIME Oncology,Research to Practice,Roche Pharmaceuticals/ Diagnostics/ Foundation One,Sanofi-Aventis,Shanghai BeBirds Translation & Consulting Co. Ltd,Taiho Pharmaceutical Co. Ltd,Takeda Oncology,Touch Independent Medical Education Ltd,meeting support fromNovartis,Roche,Pfizer, AstraZeneca,Daiichi Sankyo,BI,MiRXES,BMS,MSD,Abbvie,Zai Lab,Liangyihui,advisory boardforAbbVie Inc.,ACEA Pharma,Amgen,AstraZeneca,Alentis Therapeutics AG,BerGenBio ASA,Berry Oncology,Blueprint Medicines Corporation,Boehringer Ingelheim,Bowtie Life Insurance Co Ltd,Bristol Myers Squibb,C4 Therapeutics Inc,Covidien LP,CStone Pharmaceuticals,Curio Science,D3 Bio Ltd.,Daiichi Sankyo Inc.,Eisai,Fishawack Facilitate Ltd.,G1 Therapeutics Inc.,Gilead Sciences Inc.,Gritstone Oncology Inc,Guardant Health,geneDecode Co. Ltd. (uncompensated),Hengrui Therapeutics Inc.,HutchMed,Ignyta Inc.,Incyte Corporation,Imagene AI Ltd.,Inivata,IQVIA,Janssen,Lakeshore Biotech,Lily,Loxo-Oncology Inc.,Lunit Inc,Merck Serono,Merck Sharp & Dohme,Mirati Therapeutics Inc.,MiRXES Group,Novartis,OrigiMed,Pfizer,Prenetics Global Limited,Puma Biotechnology Inc.,Roche/Genentech,Regeneron Pharmaceuticals Inc,Sanofi-Aventis R&D,SFJ Pharmaceutical,Simcere of America Inc.,Simcere Zaiming, Inc.,Takeda,Vertex Pharmaceuticals,Virtus Medical Group,XENCOR, Inc,Yuhan Corporation,being member in the Board of DirectorsforAstraZeneca PLC,HutchMed,Aurora,Insighta,holding stock / stock optionofAstraZeneca,Aurora Tele-Oncology Ltd.,Biolidics Ltd.,HutchMed,Prenetics Global Limited,D3 Bio,Lunit,Bowtie Life Insurance, Lakeshore Biotech Ltd,Loxo-oncology,Virtus Medical Group,Yinson Capital Pte. Ltd.,Phanes Therapeutics, Inc.,Insighta,Alentis Therapeutics AG, outside the submitted work. Dr Li reports grants from Gilead, MSD and Astra Zeneca, honoraria from Astra Zeneca, Novartis, Amgen, Pfizer. Takeda, ACE Oncology, Merck, Guardant Health, Gilead, Janssen and MSD, meeting support from Astra Zeneca, Pfizer, Daiichi Sankyo, MSD, Amgen, advisory board for Astra Zeneca, Pfizer, AnHeart Therapeutics, Amgen, Takeda, Yuhan and Blossomhill therapeutics, outside the submitted work. No other conflicts of interest were declared.]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Exertional breathlessness is a cardinal symptom of cardiorespiratory disease., Research Question: How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiologic responses in people with chronic airflow limitation (CAL)?, Study Design and Methods: An analysis was done of people aged ≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output, rate of oxygen uptake, and minute ventilation at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy people; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated., Results: We included 330 participants (44% women): mean ± SD age, 64 ± 10 years (range, 40-89 years); FEV 1 /FVC, 57.3% ± 8.2%; FEV 1 , 75.6% ± 17.9% predicted. Abnormally low exercise capacity (peak rate of oxygen uptake < lower limit of normal) was present in 26%. Relative to peak power output, rate of oxygen uptake, and minute ventilation, abnormally high breathlessness was present in 26%, 25%, and 18% of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiologic abnormalities during CPET., Interpretation: Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. B. and W. C. T. report receiving institutional funding for the CanCOLD study from AstraZeneca Canada Ltd., Boehringer Ingelheim Canada Ltd., GlaxoSmithKline Canada Ltd., Merck, Novartis Pharma Canada Inc., as well as Nycomed Canada Inc. (W. C. T.), Pfizer Canada Ltd. (W. C. T.), Trudell (J. B.), and Grifolds (J. B.). None declared (P. Z. L., M. E., H. L., D. J.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Pre-existing emphysema is recognized as an indicator of future worsening in patients with chronic obstructive pulmonary disease (COPD) when observed through CT imaging. However, it remains uncertain whether additional factors, such as the spatial compactness of CT emphysema, might also serve as predictors of disease progression. Purpose To evaluate the relationship between the compactness of CT emphysema voxels and emphysema progression. Materials and Methods This secondary analysis uses data from the prospective Canadian Cohort Obstructive Lung Disease (CanCOLD) study, examining CT images obtained in participants with and without COPD at baseline and a 3-year follow-up time point (November 2009 to November 2018). Measurements of forced expiratory volume in first second of expiration (FEV 1 ) and diffusing capacity of lung for carbon monoxide (DLco) were collected. The normalized join-count (NJC) measurement from baseline CT images and lung density (LD) changes were analyzed. Emphysema progression was defined as an annualized LD change of less than half an SD below the mean of the participants without COPD with no smoking history. Multivariable linear and logistic regression models were used to assess the association between baseline CT NJC measurements and the annualized change in LD, FEV 1 , DLco, and emphysema progression versus nonprogression. Results A total of 524 participants (mean age, 66 years ± 10 [SD]; 293 male) (FEV 1 percent predicted, 88% ± 19; FEV 1 /FVC, 67% ± 9; DLco percent predicted, 105% ± 25) were analyzed, 187 (36%) of whom had COPD. CT NJC was associated with the annualized change in LD ( P < .001), FEV 1 ( P = .02), and DLco ( P = .01). Additionally, CT NJC predicted emphysema progression versus nonprogression (odds ratio, 2.24; 95% CI: 1.37, 3.50; P < .001). Conclusion The spatial distribution, or "compactness," of CT emphysema voxels predicted emphysema progression in individuals with and without COPD. ClinicalTrials.gov Identifier: NCT00920348 © RSNA, 2024 Supplemental material is available for this article.

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP , DSP , and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chen, Wong, Tan, Tay, Tan, Chan, Ho, Cheng, Teoh, Chiu, Wang, Saad, Kanesvaran, Li, Ng, Tuan and Yuen.)

Rationale: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. Objectives: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. Methods: We completed a cross-sectional analysis of the CanCOLD (Canadian Cohort Obstructive Lung Disease) population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV 1  < 80% predicted and FEV 1 /FVC ⩾ 0.7), 264 control participants, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing. Measurements and Main Results: Individuals with PRISm had lower total lung, vital, and inspiratory capacities than healthy controls (all P  < 0.05) and minimal small airway, pulmonary gas exchange, and radiographic parenchymal lung abnormalities. Compared with healthy controls, individuals with PRISm had higher dyspnea/[Formula: see text]o 2 ratio at peak exercise (4.0 ± 2.2 vs. 2.9 ± 1.9 Borg units/L/min; P  < 0.001) and lower [Formula: see text]o 2peak (74 ± 22% predicted vs. 96 ± 25% predicted; P  < 0.001). At standardized submaximal work rates, individuals with PRISm had greater Vt/inspiratory capacity (Vt%IC; P  < 0.001), reflecting inspiratory mechanical constraint. In contrast to participants with PRISm, those with COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas exchange abnormalities. Despite these physiological differences among the three groups, the relationship between increasing dyspnea and Vt%IC during cardiopulmonary exercise testing was similar. Resting IC significantly correlated with [Formula: see text]o 2peak ( r  = 0.65; P  < 0.001) in the entire sample, even after adjusting for airflow limitation, gas trapping, and diffusing capacity. Conclusions: In individuals with PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates. Clinical trial registered with www.clinicaltrials.gov (NCT00920348).

Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume. Percent-predicted airway lumen diameters were calculated using sex-specific reference equations accounting for age, height, and lung volume. The association of airway tree caliber heterogeneity, quantified as the standard deviation (SD) of percent-predicted airway lumen diameters, with baseline forced expired volume in 1-second (FEV 1 ), FEV 1 /forced vital capacity (FEV 1 /FVC) and COPD, as well as longitudinal spirometry, were assessed using regression models adjusted for age, sex, height, race-ethnicity, and mean airway tree caliber. Among 2,505 MESA Lung participants (means ± SD age: 69 ± 9 yr; 53% female, mean airway tree caliber: 99 ± 10% predicted, airway tree caliber heterogeneity: 14 ± 5%; median follow-up: 6.1 yr), participants in the highest quartile of airway tree caliber heterogeneity exhibited lower FEV 1 (adjusted mean difference: -125 mL, 95%CI: -171,-79), lower FEV 1 /FVC (adjusted mean difference: -0.01, 95%CI: -0.02,-0.01), and higher odds of COPD (adjusted odds ratio: 1.42, 95%CI: 1.01-2.02) when compared with the lowest quartile, whereas longitudinal changes in FEV 1 and FEV 1 /FVC did not differ significantly. Observations in CanCOLD and SPIROMICS were consistent. Among older adults, airway tree caliber heterogeneity was associated with airflow obstruction and COPD at baseline but was not associated with longitudinal changes in spirometry. NEW & NOTEWORTHY In this study, by leveraging two community-based samples and a case-control study of heavy smokers, we show that among older adults, airway tree caliber heterogeneity quantified by CT is associated with airflow obstruction and COPD independent of age, sex, height, race-ethnicity, and dysanapsis. These observations suggest that airway tree caliber heterogeneity is a structural trait associated with low baseline lung function and normal decline trajectory that is relevant to COPD.

Rationale: Although numerous candidate features exist for predicting risk of higher risk of healthcare utilization in patients with chronic obstructive pulmonary disease (COPD), the process for selecting the most discriminative features remains unclear., Objective: The objective of this study was to develop a robust feature selection method to identify the most discriminative candidate features for predicting healthcare utilization in COPD, and compare the model performance with other common feature selection methods., Materials and Methods: In this retrospective study, demographic, lung function measurements and CT images were collected from 454 COPD participants from the Canadian Cohort Obstructive Lung Disease study from 2010-2017. A follow-up visit was completed approximately 1.5 years later and participants reported healthcare utilization. CT analysis was performed for feature extraction. A two-step hybrid feature selection method was proposed that utilized: (1) sparse subspace learning with nonnegative matrix factorization, and, (2) genetic algorithm. Seven commonly used feature selection methods were also implemented that reported the top 10 or 20 features for comparison. Performance was evaluated using accuracy., Results: Of the 454 COPD participants evaluated, 161 (35%) utilized healthcare services at follow-up. The accuracy for predicting subsequent healthcare utilization for the seven commonly used feature selection methods ranged from 72%-76% with the top 10 features, and 77%-80% with the top 20 features. Relative to these methods, hybrid feature selection obtained significantly higher accuracy for predicting subsequent healthcare utilization at 82% ± 3% (p < 0.05). Selected features with the proposed method included: DL CO , FEV 1 , RV, FVC, TAC, LAA 950 , Pi-10, LAA 856 , LAC total hole count, outer area RB1, wall area RB1, wall area and Jacobian., Conclusion: The hybrid feature selection method identified the most discriminative features for classifying individuals with and without future healthcare utilization, and increased the accuracy compared to other state-of-the-art approaches., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Miranda Kirby reports a relationship with Vida Diagnostics Inc. that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: An expanded access program (EAP) is a regulatory mechanism that provides access to an investigational drug, which is not approved for use, in treating life-threatening conditions when all the standard-ofcare treatments are exhausted., Materials and Methods: An online, anonymous, voluntary survey was conducted to assess the level of knowledge and understanding about EAPs among Malaysian oncologists using SurveyMonkey® between April 2020 and June 2020. Oncologists who had enquired about EAP in the past, were invited at random to participate in the survey. Participants who did not provide consent or failed to complete the survey were excluded., Results: A total of 15 oncologists participated in the survey, from both public (46.6%) and private (46.6%) practices. Most respondents (80%) had filed between 1 to 10 EAP applications in the past 12 months. For 73.3% respondents, resources or training were not provided for EAPs from institutions. Around 53% of the respondents reported that their knowledge of EAPs and application processes including country regulations is 'good'. The majority of respondents (73.3%) reported that the educational modules on an overview of EAPs, country regulations and the EAP application process will be beneficial. Most participants received information about the existing EAPs either by reaching out to a pharmaceutical sponsor or through another health care provider and some received information about the existing EAPs through their institutions or patients/caregivers. Most of the respondents recommended that pharmaceutical companies should have readily available information related to the availability and application of EAPs for all pipeline products on their websites., Discussion: EAPs are crucial treatment access pathways to provide investigational drugs to patients who have exhausted their treatment options and are not eligible for participation in clinical trials. Malaysian oncologists have a fair understanding about the EAPs and the application processes., Conclusion: Additional training and awareness are needed for Malaysian oncologists to upscale the utilisation of EAPs.

Background: We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester., Case Presentation: Patient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks' gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith-Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks' gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami-Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks' gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome., Conclusion: These cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team., (© 2024. The Author(s).)

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇ E ) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n  = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p  < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p  < 0.001). During exercise, there was a significant effect of V̇ E , sex, and their interaction on dyspnoea (all p  < 0.05), indicating that dyspnoea increased as a function of V̇ E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r  < 0.34; all p  > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea., Competing Interests: The authors declare there are no competing interests.

Background: Computed tomography (CT)-derived pectoralis muscle area (PMA) measurements are prognostic in people with or at-risk of COPD, but fully automated PMA extraction has yet to be developed. Our objective was to develop and validate a PMA extraction pipeline that can automatically: 1) identify the aortic arch slice; and 2) perform pectoralis segmentation at that slice., Methods: CT images from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study were used for pipeline development. Aorta atlases were used to automatically identify the slice containing the aortic arch by group-based registration. A deep learning model was trained to segment the PMA. The pipeline was evaluated in comparison to manual segmentation. An external dataset was used to evaluate generalisability. Model performance was assessed using the Dice-Sorensen coefficient (DSC) and PMA error., Results: In total 90 participants were used for training (age 67.0±9.9 years; forced expiratory volume in 1 s (FEV 1 ) 93±21% predicted; FEV 1 /forced vital capacity (FVC) 0.69±0.10; 47 men), and 32 for external testing (age 68.6±7.4 years; FEV 1 65±17% predicted; FEV 1 /FVC 0.50±0.09; 16 men). Compared with manual segmentation, the deep learning model achieved a DSC of 0.94±0.02, 0.94±0.01 and 0.90±0.04 on the true aortic arch slice in the train, validation and external test sets, respectively. Automated aortic arch slice detection obtained distance errors of 1.2±1.3 mm and 1.6±1.5 mm on the train and test data, respectively. Fully automated PMA measurements were not different from manual segmentation (p>0.05). PMA measurements were different between people with and without COPD (p=0.01) and correlated with FEV 1 % predicted (p<0.05)., Conclusion: A fully automated CT PMA extraction pipeline was developed and validated for use in research and clinical practice., Competing Interests: Conflicts of interest: D. Genkin reports no conflicts of interest. Conflicts of interest: A.R. Jenkins acknowledges salary support from Le Fonds de Recherche du Québec Santé - Postdoctoral Training fellowship. Conflicts of interest: N. van Noord reports no conflicts of interest. Conflicts of interest: K. Makimoto reports no conflicts of interest. Conflicts of interest: S. Collins reports no conflicts of interest. Conflicts of interest: M.K. Stickland acknowledges salary support from the Canadian Institutes of Health Research, Natural Sciences and Engineering Council of Canada, and University Hospital Foundation. Conflicts of interest: W.C. Tan reports no conflicts of interest. Conflicts of interest: J. Bourbeau acknowledges salary support from the Canadian Institute of Health Research, Réseau en santé respiratoire du FRQS, McGill University Health Centre Foundation, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Grifols, Novartis, Sanofi, Trudell Canada Ltd, Pfizer Canada Ltd and COVIS Pharma Canada Ltd. Conflicts of interest: D. Jensen reports no conflicts of interest. Conflicts of interest: M. Kirby is a paid consultant at VIDA Diagnostics., (Copyright ©The authors 2024.)

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition., Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors., Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job., Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors., Funding: Wellcome Trust., Competing Interests: Fatima Rodrigues declares grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. Wan C. Tan received grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93,326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD. David Mannino is a consultant to GSK, AstraZeneca, Regeneron, Genentech, COPD Foundation, and expert witness on behalf of people suing Tobacco Industry (Schlesinger Law Firm). Sonia Buist is Chair of the Data Safety & Monitoring Board for the RELIANCE Clinical Trial. Frits Franssen declares personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, MSD, Pieris, and Verona Pharma. Robab Breyer-Kohansal declares consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis Pharma, and Sanofi, and participation on advisory boards for AstraZeneca, Menarini, and Sanofi. Thorarinn Gislason received a grant from the Icelandic Research Fund. Kevin Mortimer declares participation on advisory boards for AstraZeneca and GlaxoSmithKline. Sylvia Hartl declares grants from GSK, Chiesi Farma, Menarini Pharma, and AstraZeneca, and participation on advisory boards for Menarini Pharma and GSK. AFSA declares a grant from the COLT Foundation (CF/01/21)., (© 2024 The Author(s).)

Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, the interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0-10 category ratio) response in men and women aged ⩾40 years during CPET, in relation to power output (watts), oxygen uptake, and minute ventilation. Methods: Analysis of ostensibly healthy people aged ⩾40 years undergoing symptom-limited incremental cycle CPET (10 W/min) in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study. Participants had smoking histories <5 pack-years and normal lung function and exercise capacity. The probability of each Borg 0-10 category ratio breathlessness intensity rating by power output, oxygen uptake, and minute ventilation (as an absolute or a relative value [percentage of predicted maximum]) was predicted using ordinal multinomial logistic regression. Model performance was evaluated by fit, calibration, and discrimination (C statistic) and externally validated in an independent sample ( n  = 86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; the mean age was 65 (range, 42-91) years, and the mean body mass index was 26.3 (standard deviation, 3.8) kg/m 2 . Reference equations were developed for women and men separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (C statistic for men = 0.81-0.92, C statistic for women = 0.81-0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings among individuals or groups and to identify and quantify abnormal breathlessness responses (scores greater than the upper limit of normal) during CPET.

Introduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations., Methods: Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine kinase inhibitors (TKIs) were included. pEGFR were measured at baseline and first response assessment using ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time-to-treatment failure (TTF). In exploratory analysis, corresponding change in carcinoembryonic antigen (CEA) levels was evaluated., Results: Between January 1, 2020, and December 31, 2021, 27 patients were recruited. Ex19del comprised 74% (20 of 27) and L858R 26% (seven of 27). Osimertinib was used in 59% (16 of 27), dacomitinib 4% (one of 27), and gefitinib/erlotinib 37% (10 of 27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19 of 27) and 78% (21 of 27), respectively ( p  = 0.16). All patients with detectable pEGFR by ddPCR were detected by NGS.At a median of 8 (range 3-24) weeks post-TKI initiation, clearance of pEGFR was achieved in 68% (13 of 19) and 71% (15 of 21) using ddPCR and NGS, respectively. Concordance between ddPCR and NGS was 79% (kappa = 0.513, p  = 0.013). Clearance of pEGFR was associated with longer median TTF (not reached versus 6 months, p  = 0.03) and median decrease in CEA levels by 70% from baseline.In another cohort of 124 patients, decrease in CEA levels by greater than 70% within 90 days of TKI initiation was associated with doubling of both TTF and overall survival., Conclusions: Plasma NGS trended toward higher sensitivity than ddPCR in detecting pEGFR, although both had similar concordance in detecting pEGFR clearance. Our results support using NGS at diagnosis and interchangeability of NGS and ddPCR for monitoring, whereas CEA could be explored as a surrogate for pEGFR clearance., (© 2023 The Authors.)

Background: Identifying individuals at risk of progressing to COPD may allow for initiation of treatment to potentially slow the progression of the disease or the selection of subgroups for discovery of novel interventions., Research Question: Does the addition of CT imaging features, texture-based radiomic features, and established quantitative CT scan to conventional risk factors improve the performance for predicting progression to COPD in individuals who smoke with machine learning?, Study Design and Methods: Participants at risk (individuals who currently or formerly smoked, without COPD) from the Canadian Cohort Obstructive Lung Disease (CanCOLD) population-based study underwent CT imaging at baseline and spirometry at baseline and follow-up. Various combinations of CT scan features, texture-based CT scan radiomics (n = 95), and established quantitative CT scan (n = 8), as well as demographic (n = 5) and spirometry (n = 3) measurements, with machine learning algorithms were evaluated to predict progression to COPD. Performance metrics included the area under the receiver operating characteristic curve (AUC) to evaluate the models. DeLong test was used to compare the performance of the models., Results: Among the 294 at-risk participants who were evaluated (mean age, 65.6 ± 9.2 years; 42% female; mean pack-years, 17.9 ± 18.7), 52 participants (23.7%) in the training data set and 17 participants (23.0%) in the testing data set progressed to spirometric COPD at follow-up (2.5 ± 0.9 years from baseline). Compared with machine learning models with demographics alone (AUC, 0.649), the addition of CT imaging features to demographics (AUC, 0.730; P < .05) or CT imaging features and spirometry to demographics (AUC, 0.877; P < .05) significantly improved the performance for predicting progression to COPD., Interpretation: Heterogeneous structural changes occur in the lungs of individuals at risk that can be quantified using CT imaging features, and evaluation of these features together with conventional risk factors improves performance for predicting progression to COPD., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. K. is a consultant for VIDA Diagnostics Inc. None declared (K. M., J. C. H., J. B., W. C. T.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The 6-min walk test (6MWT) is widely used to assess exercise capacity across chronic health conditions, but is currently not useful to assess symptoms, as the scores do not account for the 6-min walk distance (6MWD). We aimed to 1) develop normative reference equations for breathlessness and leg discomfort intensity expressed as modified Borg (mBorg)/6MWD ratios; and 2) validate the equations in people with COPD., Methods: Analysis of people aged ≥40 years who performed two 6MWTs (on a 20-m course) in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study: a healthy cohort (n=291; mean±sd age 67.5±9.4 years; 54% male) with normal 6MWD and lung function, and a COPD cohort (n=156; age 66.2±9.0 years; 56% male; forced expiratory volume in 1 s (FEV 1 )/forced vital capacity 56.6±8.2%; FEV 1 74.4±18.6% pred). The mBorg score was calculated as the Borg 0-10 category ratio intensity rating of breathlessness or leg discomfort recorded at the end of the 6MWT +1 (range 1-11), to avoid zeros and yield ratios proportional to the symptom score and 6MWD-1., Results: Using data from the healthy cohort, sex-specific normative reference equations for breathlessness and leg discomfort mBorg/6MWD ratios were developed using multivariable linear regression, accounting for age, and body mass or body mass index. In the COPD cohort, abnormal breathlessness and leg discomfort (mBorg/6MWD>upper limit of normal) showed strong concurrent validity with worse airflow limitation, Medical Research Council breathlessness and COPD Assessment Test scores., Conclusion: Normative references for the mBorg/6MWD ratio are presented to assess breathlessness and leg discomfort responses to the 6MWT in COPD., Competing Interests: Conflict of interest: J. Bourbeau and W.C. Tan report receiving institutional funding for the CanCOLD study from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc. (W.C. Tan), Pfizer Canada Ltd (W.C. Tan), Trudell (J. Bourbeau) and Grifols (J. Bourbeau). No conflicts of interest exist for any of the other authors., (Copyright ©The authors 2023.)

Objective: To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports., Materials and Methods: We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease. We applied transformer models, a bidirectional long short-term memory model, a convolutional neural network model, and conventional machine learning methods to this task. Data augmentation using sentence permutation with consistency loss as well as prompt-based fine-tuning were used on the best-performing models. Models were validated on a hold-out test set and an external validation set based on Response Evaluation Criteria in Solid Tumors (RECIST) classifications., Results: The best-performing model was the GatorTron transformer which achieved an accuracy of 0.8916 on the test set and 0.8919 on the RECIST validation set. Data augmentation further improved the accuracy to 0.8976. Prompt-based fine-tuning did not further improve accuracy but was able to reduce the number of training reports to 500 while still achieving good performance., Discussion: These models could be used by researchers to derive progression-free survival in large datasets. It may also serve as a decision support tool by providing clinicians an automated second opinion of disease response., Conclusions: Large clinical language models demonstrate potential to infer cancer disease response from radiology reports at scale. Data augmentation techniques are useful to further improve performance. Prompt-based fine-tuning can significantly reduce the size of the training dataset., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Rationale: The six-minute walk test (6MWT) is a practical and simple field-based test to assess physical capacity. Several reference equations for six-minute walking distance (6MWD, m) exist, but have a number of limitations that decrease their clinical utility. In addition, no reference equations exist for the 6MWT-derived outcome six-minute walk work (6MWORK, kg.m)., Objectives: To establish new reference equations for 6MWD and 6MWORK on a 20 m course using data from the population-based Canadian Cohort Obstructive Lung Disease study., Methods and Measurements: A total of 335 participants without obstructive or restrictive pulmonary function, with normal self-reported health status, normal exercise capacity, and <30 pack years cigarette smoking history were selected to create a representative sample of Canadian adults aged ≥40 years. All participants performed two 6MWTs. Reference equations were derived using multiple regression analyses., Main Results: On average, 6MWD and 6MWORK were 541±98 m and 41.3 ± 11.2 kg.m, respectively. All outcomes were significantly greater in males than females. Sex-specific reference equations were derived from the results of 6MWD and 6MWORK with an explained variance of 24 to 35%., Conclusions: This study established reference equations for 6MWD and 6MWORK on a 20 m course in Caucasian males and females aged ≥40 years with normal pulmonary function, self-reported health status and exercise capacity. These newly derived reference equations add value to the assessment of functional capacity in clinical practice., Competing Interests: Conflicts of interest The CanCOLD study is and/or was funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Novartis, the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies and the UBC centre for Heart Lung innovation Vancouver Jean Bourbeau reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline, Pfizer Canada Ltd and Trudell Canada Ltd, outside the submitted work. Dennis Jensen reports a grant and consulting fees from Boehringer Ingelheim, outside the submitted work. Martijn A. Spruit reports grants or contracts from Netherlands Lung Foundation, Stichting Astmabestrijding, Astra Zeneca, TEVA, Boehringer Ingelheim and Chiesi, outside the present work. Alex van ‘t Hul, Anouk Vaes, Jeannet Delbressine, Bita Haijan, Pei Li and Wan Tan report no conflicts of interest., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Psoriatic arthritis is a chronic, autoimmune inflammatory arthritis that occurs with psoriasis and has profound impact on patients' physical and psychological well-being. This study aims to determine the prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis., Methods: A single-center, cross-sectional study was conducted over a 12-month period at the Dermatology Clinic, Hospital Pulau Pinang, Malaysia involving all consecutive psoriasis patients. CASPAR (ClASsification of Psoriatic ARthritis) criteria were used to diagnose psoriatic arthritis., Results: A total of 360 patients with psoriasis were recruited, of whom 107 (29.7%) had psoriatic arthritis. Psoriatic arthritis patients had equal gender distribution and the mean age of arthritis onset was 40.7 ± 12.8 years. Psoriasis preceded arthritis in 81.3% of patients (n = 87) with a mean latency interval of 10.5 years. Polyarthropathy was the predominant subtype affecting 46.8% (n = 50) of patients, followed by oligoarthropathy (22.4%, n = 24), axial joint disease (5.6%, n = 6), predominant distal interphalangeal joint disease (2.8%, n = 3), and mixed subtype (22.4%, n = 24). Enthesitis and dactylitis occurred in 12.1% (n = 13) and 20.6% (n = 22) of arthritis patients, respectively, and deformity was present in 37.4% (n = 40). Psoriatic arthritis was significantly associated with being an ever smoker (adjusted odds ratio [aOR] 0.41; 95% confidence interval [CI] 0.18-0.91, p = .029), genital psoriasis (aOR 2.25; 95% CI 1.17-4.33, p = .015), and increased erythrocyte sedimentation rate (ESR) (aOR 1.02; 95% CI 1.01-1.04, p = .005) and C-reactive protein [CRP] (aOR 1.04; 95% CI 1.00-1.08, p = .040)., Conclusion: Our study showed a high prevalence of psoriatic arthritis among the psoriasis cohort. Genital involvement, and increased ESR and CRP were associated with psoriatic arthritis among patients with psoriasis., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Individuals with COPD and preserved ratio impaired spirometry (PRISm) findings in clinical settings have an increased risk of cardiovascular disease (CVD)., Research Question: Do individuals with mild to moderate or worse COPD and PRISm findings in community settings have a higher prevalence and incidence of CVD compared with individuals with normal spirometry findings? Can CVD risk scores be improved when impaired spirometry is added?, Study Design and Methods: The analysis was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Prevalence of CVD (ischemic heart disease [IHD] and heart failure [HF]) and their incidence over 6.3 years were compared between groups with impaired and normal spirometry findings using logistic regression and Cox models, respectively, adjusting for covariables. Discrimination of the pooled cohort equations (PCE) and Framingham risk score (FRS) in predicting CVD were assessed with and without impaired spirometry., Results: Participants (n = 1,561) included 726 people with normal spirometry findings and 835 people with impaired spirometry findings (COPD Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 disease, n = 408; GOLD stage ≥ 2, n = 331; PRISm findings, n = 96). Rates of undiagnosed COPD were 84% in GOLD stage 1 and 58% in GOLD stage ≥ 2 groups. Prevalence of CVD (IHD or HF) was significantly higher among individuals with impaired spirometry findings and COPD compared with those with normal spirometry findings, with ORs of 1.66 (95% CI, 1.13-2.43; P = .01∗) (∗ indicates statistical significane with P < .05) and 1.55 (95% CI, 1.04-2.31; P = .033∗), respectively. Prevalence of CVD was significantly higher in participants having PRISm findings and COPD GOLD stage ≥ 2, but not GOLD stage 1. CVD incidence was significantly higher, with hazard ratios of 2.07 (95% CI, 1.10-3.91; P = .024∗) for the impaired spirometry group and 2.09 (95% CI, 1.10-3.98; P = .024∗) for the COPD group compared to individuals with normal spirometry findings. The difference was significantly higher among individuals with COPD GOLD stage ≥ 2, but not GOLD stage 1. The discrimination for predicting CVD was low and limited when impaired spirometry findings were added to either risk score., Interpretation: Individuals with impaired spirometry findings, especially those with moderate or worse COPD and PRISm findings, have increased comorbid CVD compared with their peers with normal spirometry findings, and having COPD increases the risk of CVD developing., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)