Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

CAR and CSTR Cardiac Computed Tomography (CT) Practice Guidelines: Part 2-Non-Coronary Imaging.

The cardiac computed tomography (CT) practice guidelines provide an updated review of the technological improvements since the publication of the first Canadian Association of Radiologists (CAR) cardiac CT practice guidelines in 2009. An overview of the current evidence supporting the use of cardiac CT in the most common clinical scenarios, standards of practice to optimize patient preparation and safety as well as image quality are described. Coronary CT angiography (CCTA) is the focus of Part I. In Part II, an overview of cardiac CT for non-coronary indications that include valvular and pericardial imaging, tumour and mass evaluation, pulmonary vein imaging, and imaging of congenital heart disease for diagnosis and treatment monitoring are discussed. The guidelines are intended to be relevant for community hospitals and large academic centres with established cardiac CT imaging programs.

CAR and CSTR Cardiac Computed Tomography (CT) Practice Guidelines: Part 1 Coronary CT Angiography (CCTA).

Imaging the heart is one of the most technically challenging applications of Computed Tomography (CT) due to the presence of cardiac motion limiting optimal visualization of small structures such as the coronary arteries. Electrocardiographic gating during CT data acquisition facilitates motion free imaging of the coronary arteries. Since publishing the first version of the Canadian Association of Radiologists (CAR) cardiac CT guidelines, many technological advances in CT hardware and software have emerged necessitating an update. The goal of these cardiac CT practice guidelines is to present an overview of the current evidence supporting the use of cardiac CT in various clinical scenarios and to outline standards of practice for patient safety and quality of care when establishing a cardiac CT program in Canada.

Accuracy, Reproducibility and User Experience With Standardized Instructions for Measurement of Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease.

PURPOSE: Total kidney volume (TKV) measurement is integral in clinical management of autosomal dominant polycystic kidney disease (ADPKD) but the gold standard of measurement via stereology/manual planimetry is time-consuming and not readily available to clinicians. This study assessed whether standardized measurement instructions based on an ellipsoid equation enhanced TKV assessment on computed tomographic (CT) images of the kidneys as determined by accuracy, reproducibility, efficiency and/or user acceptability. METHODS: Participating radiologists were randomized to perform TKV measurements with or without standardized instructions. All participants measured the same 3 non-contrast, low-dose CT scans. Accuracy was assessed as variation from TKV measurements obtained by planimetry. Intraclass correlation coefficients and time to complete the measurements were assessed. Surveys assessed prior experience with TKV measurement and user acceptability of the instructions. RESULTS: 49 radiologists participated. There was no difference in accuracy or measurement time between instructed and non-instructed participants. There was a trend towards greater reproducibility with standardized instructions (ICC .8 vs .6). 92% of respondents indicated the instructions were easy to use, 86% agreed the instructions would enhance their comfort with TKV measurement and 75% agreed they would recommend these instructions to colleagues. CONCLUSIONS: Instructed and non-instructed participants demonstrated similar accuracy and time required for TKV measurement, but instructed participants had a trend towards greater reproducibility. There was high acceptability including enhanced user confidence with the instructions. Standardized instructions may be of value for radiologists seeking to improve their confidence in providing clinicians with TKV measurements necessary to appropriately manage this patient population.

Knowledge and Perceptions of Competency-Based Medical Education in Diagnostic Radiology Post-Graduate Medical Education: Identifying Priorities and Developing a Framework for Professional Development Activities.

Introduction: We evaluated knowledge and perceptions of an established Competency-Based Medical Education (CBME) model developed by the Royal College of Physicians and Surgeons of Canada, Competence by Design (CBD), and identified evidence-informed priorities for professional development activities (PDAs). Materials and Methods: Teaching faculty and residents at a single, large diagnostic radiology post-graduate medical education (PGME) program were eligible to participate in this cross-sectional, survey-based study. Knowledge of CBD was evaluated through multiple choice questions (MCQs), which assessed participants' understanding of major principles and terms associated with CBD. Participants' perceptions of the anticipated impact of CBD on resident education and patient care were evaluated and priorities for PDAs were identified, which informed a framework for CBD PDAs. Results: Fifty faculty and residents participated. The faculty and resident response rates were 11.6% (n = 29/249) and 55.3% (n = 21/38), respectively. The mean ± standard deviation overall score on MCQs was 39.0% ± 20.4%. The majority of participants perceived the impact of CBD on resident education to be equivocal and to not impact patient care. Knowledge of CBD was not statistically significantly associated with participants' perceptions of the impact of CBD on either resident education or patient care (P > .05). Delivery of high-quality feedback was the greatest priority identified for PDAs. Discussion: Our results and proposed CBD PDAs framework may help to guide diagnostic radiology PGME programs in designing evidence-informed PDAs, which may meaningfully contribute to the successful implementation of CBD in diagnostic radiology PGME. As diagnostic radiology PGME programs throughout the world increasingly implement CBME models, evidence-informed PDAs will become of increasing importance.

Preparedness of Residents and Medical Students for the Transition to Competence by Design in Diagnostic Radiology Post-Graduate Medical Education.

Introduction: This needs assessment evaluated residents' and medical students' knowledge of Competence by Design (CBD), perceived benefits of and challenges or barriers to the transition to CBD for residents, and perceived overall preparedness for the transition to CBD in diagnostic radiology. Materials and Methods: All diagnostic radiology residents and medical students in Canada were eligible to participate in this national cross-sectional, questionnaire-based needs assessment. Knowledge of CBD was evaluated through participants' self-reported rating of their knowledge of CBD on a 5-point Likert scale. Perceived benefits of and challenges or barriers to the transition to CBD for residents were rank ordered. Participants' overall self-reported preparedness for the transition to CBD was assessed on a 5-point Likert scale. Data were summarized by descriptive statistics and bivariate analyses were conducted as appropriate. Results: Ninety-four residents (n = 77) and medical students (n = 17) participated in this needs assessment. Participants' mean ± standard deviation self-reported rating of their overall knowledge of CBD was 2.86 ± .94. Provision of meaningful feedback to learners and learners' ability to identify their own educational needs were among the highest ranked perceived benefits of the transition to CBD, while demands on time and increased frequency of evaluation were among the highest ranked perceived challenges or barriers to the transition to CBD. Few participants reported being either "prepared" (4.7%) or "somewhat prepared" (14.0%) for the transition to CBD. Conclusion: Preparedness for the transition to CBD in diagnostic radiology may be improved. Targeted interventions to augment the preparedness of residents and medical students should be considered.

Oncologic Outcomes Associated With MRI-detected Extramural Venous Invasion (mrEMVI) in Rectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: The role of MRI-detected EMVI (mrEMVI) as a reliable prognostic factor in rectal cancer has been emphasized in recent years but this finding remains underreported by many institutions. OBJECTIVE: This review aimed to demonstrate the importance of pre- and post-treatment MRI-detected EMVI as independent prognostic factors of adverse oncologic outcomes in patients undergoing neoadjuvant therapy followed by total mesorectal excision. METHODS: This review was designed using the PRISMA guidelines. The following electronic databases were searched from January 2002 to January 2020: CENTRAL, Ovid MEDLINE, PubMed, and Ovid Embase. Main outcomes included DFS and overall survival (OS). Other outcomes of interest comprised positive resection margin and synchronous metastases. RESULTS: Seventeen studies involving a total of 3821 patients were included for data synthesis. For preneoadjuvant treatment mrEMVI, pooled hazard ratio (HR) estimate for DFS was 2.30 (95% confidence intervals (CI) 1.54-3.44) for higher recurrence in mrEMVI-positive patients. mrEMVI-positive patients were found to have a lower OS with a pooled HR of 1.68 (95%CI 1.27-2.22). Pooled risk ratio for synchronous metastasis was 4.11 (95%CI 2.80-6.02) for mrEMVI-positivity. For postneoadjuvant treatment EMVI (ymrEMVI), positive status showed a lower DFS with a pooled HR of 2.04 (95%CI 1.55-2.69). Risk ratio of having a positive resection margin status was 2.95 (95%CI 1.75-4.98) for ymrEMVI-positive patients. CONCLUSIONS: This review showed that oncologic outcomes are significantly worse for both pre- and post-neoadjuvant treatment mrEMVI-positive patients. MRI-detected EMVI should be consistently reported in rectal cancer staging and may provide guidance for the targeted use of additional systemic therapy.

Small Airway Reduction and Fibrosis Is an Early Pathologic Feature of Idiopathic Pulmonary Fibrosis.

Rationale: To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically. Objectives: Perform three-dimensional assessment of the IPF lung microstructure using stereology and multiresolution computed tomography (CT) imaging. Methods: Explanted lungs from patients with IPF (n = 8) and donor control subjects (n = 8) were inflated with air and frozen. CT scans were used to assess large airways. Unbiased, systematic uniform random samples (n = 8/lung) were scanned with microCT for stereological assessment of small airways (count number, and measure airway wall and lumen area) and parenchymal fibrosis (volume fraction of tissue, alveolar surface area, and septal wall thickness). Measurements and Main Results: The total number of airways on clinical CT was greater in IPF lungs than control lungs (P < 0.01), owing to an increase in the wall (P < 0.05) and lumen area (P < 0.05) resulting in more visible airways with a lumen larger than 2 mm. In IPF tissue samples without microscopic fibrosis, assessed by the volume fraction of tissue using microCT, there was a reduction in the number of the terminal (P < 0.01) and transitional (P < 0.001) bronchioles, and an increase in terminal bronchiole wall area (P < 0.001) compared with control lungs. In IPF tissue samples with microscopic parenchymal fibrosis, terminal bronchioles had increased airway wall thickness (P < 0.05) and dilated airway lumens (P < 0.001) leading to honeycomb cyst formations. Conclusions: This study has important implications for the current thinking on how the lung tissue is remodeled in IPF and highlights small airways as a potential target to modify IPF outcomes.

A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations.

The long-term respiratory morbidity of COVID-19 remains unclear. We describe the clinical, radiological and pulmonary function abnormalities that persist in previously hospitalised patients assessed 12 weeks after COVID-19 symptom onset, and identify clinical predictors of respiratory outcomes. At least one pulmonary function variable was abnormal in 58% of patients and 88% had abnormal imaging on chest CT. There was strong association between days on oxygen supplementation during the acute phase of COVID-19 and both DLCO-% (diffusion capacity of the lung for carbon monoxide) predicted and total CT score. These findings highlight the need to develop treatment strategies and the importance of long-term respiratory follow-up after hospitalisation for COVID-19.

Spatial Dependence of CT Emphysema in Chronic Obstructive Pulmonary Disease Quantified by Using Join-Count Statistics.

Background Existing CT emphysema measurements quantify the extent or clustering of emphysema voxels in chronic obstructive pulmonary disease (COPD); however, these measurements do not quantify how those voxels are clustered. Purpose To develop a CT measurement to quantify the "compactness" of emphysema voxels, called the normalized join count (NJC), and to determine whether the NJC measurement differentiates COPD disease severity and correlates with lung function and visual emphysema scores. Materials and Methods In this secondary analysis of a prospective study, lung function and CT images were obtained from the Canadian Cohort Obstructive Lung Disease study visit 1 from 2009 to 2013. Participants were categorized as never-smokers, at risk, mild COPD, or moderate-severe COPD. Diffusion capacity for carbon monoxide/alveolar volume was measured. CT emphysema was scored visually by radiologists. CT measurements included the percentage low-attenuation area with attenuation less than -950 HU (%LAA-950insp), low-attenuation cluster (LAC), and lowest 15th percentile point of the CT lung density histogram. NJC was developed to measure compactness of CT emphysema voxels. An analysis of variance determined differences between groups. Multivariable ridge regression determined association between CT measurements with lung function and radiologist scores. Results A total of 1294 participants (750 men; mean age, 67 years ± 10) were analyzed (277 never-smokers, 306 at risk, 427 mild COPD, and 284 moderate-severe COPD). NJC, %LAA-950insp, and LAC measurements were higher in moderate-severe COPD than in never-smokers and at-risk participants (P < .05 for all comparisons), but only NJC was different between mild and ;moderate-severe COPD (mean, 1.98% ± 3.61 vs 1.44% ± 2.14; P < .05). In multivariable regression analysis, among all CT measurements NJC had the greatest relative contribution to diffusion capacity for carbon monoxide/alveolar volume (P = .002) and visual emphysema score (P < .001). Conclusion The relationship of normalized join count with severity of chronic obstructive pulmonary disease may indicate that the assessment of this disease is dependent on the number of low attenuating voxels or the size of clusters and the spatial arrangement of such voxels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

Pathological Comparisons of Paraseptal and Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease.

Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE.Objectives: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD).Methods: Air-inflated frozen lung specimens (n = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n = 8) and peripheral (n = 8) regions of each lung, scanned with micro-computed tomography (microCT), and processed for histology. The core locations were registered to the MDCT, and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Furthermore, microCT-based volume fractions of CLE and PSE allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant.Measurements and Main Results: The percentages of PSE measured on MDCT and microCT were positively associated (P = 0.015). The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with mild emphysema and PSE-dominant regions (all P < 0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all P > 0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (P = 0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared with CLE regions.Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD.

Pathologic separation of idiopathic pulmonary fibrosis from fibrotic hypersensitivity pneumonitis.

Accurate separation of idiopathic pulmonary fibrosis from fibrotic (chronic) hypersensitivity pneumonitis is crucial to patient management, but is frequently a difficult problem. Our objective was to identify pathologic variables that help make this separation. Clinical, radiological, and pathologic data were re-reviewed for 23 patients with a fibrotic interstitial lung disease and biopsy suggesting idiopathic pulmonary fibrosis or fibrotic hypersensitivity pneumonitis. Clinical features, high-resolution computed tomography, and surgical lung biopsies were each examined independently using a prespecified approach. This was followed by a multidisciplinary discussion in which the likelihood of an idiopathic pulmonary fibrosis diagnosis was assigned by the clinician alone based only on clinical data, by the clinician and radiologist based on integrated clinical and radiologic data, and by the clinician, radiologist, and pathologist based on all three domains. A higher multidisciplinary discussion-based confidence of idiopathic pulmonary fibrosis was associated with older age at diagnosis, male sex, higher forced vital capacity, and absence of ground glass changes. Pathologic variables associated with a higher multidisciplinary discussion-based confidence of idiopathic pulmonary fibrosis included increased number of fibroblast foci/cm2 and increased subpleural fibrosis. Pathologic variables associated with a higher multidisciplinary discussion-based confidence of hypersensitivity pneumonitis included an increased fraction of bronchioles with peribronchiolar metaplasia, increased foci of peribronchiolar metaplasia/cm2, and presence of giant cells/granulomas. These results provide guidance in separating idiopathic pulmonary fibrosis from hypersensitivity pneumonitis; however, a third of cases could not be confidently classified even when using these pathologic features combined with clinical and radiologic information in a multidisciplinary discussion.

Gender Disparity Among Leaders of Canadian Academic Radiology Departments.

OBJECTIVE. Underrepresentation of women in the top hierarchy of academic medicine exists despite women comprising more than half of the medical school graduates and residency positions. The purpose of this study is to analyze and quantify the relationship of gender, research productivity, and career advancement in Canadian academic radiology departments. MATERIALS AND METHODS. Seventeen academic radiology departments with affiliated residency programs in Canada were searched for publicly available data on faculty to generate a database for gender and academic profiles of the radiologists. Bibliometric data were collected using Scopus archives. The associations of gender, academic ranks, and leadership positions were assessed, and a p value of ≤ 0.05 was defined as significant. Significant variables were analyzed using a multivariate linear regression model. RESULTS. Of 1266 faculty members, gender information and academic rank were available for 932 faculty members: 597 (64.05%) were men and 335 (35.95%) were women (χ2 = 21.82; p < 0.0001). Of a total of 563 assistant professors, 331 (58.79%) were men and 232 (41.21%) were women; of 258 associate professors, 177 (68.60%) were men and 81 (31.40%) were women; and of 111 professors, 89 (80.18%) were men and 22 (19.82%) were women. The gender gap widens at higher academic ranks, displaying a threefold drop in the ratio of women holding the rank of full professor (6.57%) compared with 14.91% male professors; 29.55% of women radiologists have first-in-command leadership positions compared with 70.45% of men. A comparable or higher h-index is noted for women Canadian radiologists after adjusting for number of citations, number of publications, and years of active research. CONCLUSION. Canadian academic radiology departments have fewer women radiologists in senior faculty and leadership positions. Our study results show that Canadian female radiologists at the professor level have more publications than their male counterparts.

Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes.

BACKGROUND: The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. OBJECTIVE: To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. METHODS: We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with <5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. RESULTS: Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (p = 0.0242). Visual analysis showed a higher prevalence of emphysema (p = 0.0001) and higher emphysema score (p < 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. CONCLUSIONS: Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.

CT of Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: Accuracy, Reproducibility, and Radiation Dose.

Background Total kidney volume (TKV) assessment is valuable in autosomal dominant polycystic kidney disease (ADPKD) but the reference standard method of MRI planimetry requires access to MRI and time-consuming interpretation. Purpose To determine whether accurate TKV measurements comparable to the resource-intensive reference standard of MRI planimetry can be obtained by using alternate methods including dose-reducing CT protocols and time-saving measurement equations. Materials and Methods In this prospective study conducted September 2016 to June 2017, adult participants with ADPKD underwent one MRI and two CT examinations. Low-dose (LD) and ultra-low-dose (ULD) CT examinations were performed with radiation doses 1.4 and 2.6 times lower, respectively, than the authors' institution's standard abdomen and pelvis CT. ULD CT examinations were reconstructed via model-based iterative reconstruction. Three TKV measurement equations were applied to all image sets, and MRI manual planimetry was the reference standard. Spearman correlation with the reference standard, simple linear regression, and root mean square error (RMSE) calculation analyzed accuracy of these methods; intraclass correlation coefficient examined reproducibility. Results Thirty participants (mean age, 41 years; age range, 24-67 years) had a mean TKV of 1368.9 mL ± 1146.13 (standard deviation). The ULD and LD CT protocols had median dose-length product of 58.8 and 115.5 mGy ∙ cm, respectively (P = .01), and CT dose index of 1.2 and 3.9 mGy, respectively (P < .001). All imaging modalities and measurement equations had excellent correlation with the reference standard (r2 > 0.98). RMSE ranged from 80.5 to 157.3 mL (5.9%-11.5% of mean TKV). Intraclass correlation coefficients were greater than 0.98 for all methods. Mean measurement times for the ellipsoid method ranged from 4.6 to 5.2 minutes compared with a mean of 27.7 minutes (range, 14-60 minutes) for manual planimetry. Conclusion Accurate and reproducible total kidney volume measurements comparable to the reference standard of MRI planimetry can be obtained by using a dose-minimizing ultra-low-dose CT protocol and volume measurement based on discrete linear measurements. © RSNA, 2019 Online supplemental material is available for this article.

Total Airway Count on Computed Tomography and the Risk of Chronic Obstructive Pulmonary Disease Progression. Findings from a Population-based Study.

RATIONALE: Studies of excised lungs show that significant airway attrition in the "quiet" zone occurs early in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine if the total number of airways quantified in vivo using computed tomography (CT) reflects early airway-related disease changes and is associated with lung function decline independent of emphysema in COPD. METHODS: Participants in the multicenter, population-based, longitudinal CanCOLD (Canadian Chronic Obstructive Lung Disease) study underwent inspiratory/expiratory CT at visit 1; spirometry was performed at four visits over 6 years. Emphysema was quantified as the CT inspiratory low-attenuation areas below -950 Hounsfield units. CT total airway count (TAC) was measured as well as airway inner diameter and wall area using anatomically equivalent airways. MEASUREMENTS AND MAIN RESULTS: Participants included never-smokers (n = 286), smokers with normal spirometry at risk for COPD (n = 298), Global Initiative for Chronic Obstructive Lung Disease (GOLD) I COPD (n = 361), and GOLD II COPD (n = 239). TAC was significantly reduced by 19% in both GOLD I and GOLD II compared with never-smokers (P < 0.0001) and by 17% in both GOLD I and GOLD II compared with at-risk participants (P < 0.0001) after adjusting for low-attenuation areas below -950 Hounsfield units. Further analysis revealed parent airways with missing daughter branches had reduced inner diameters (P < 0.0001) and thinner walls (P < 0.0001) compared with those without missing daughter branches. Among all CT measures, TAC had the greatest influence on FEV1 (P < 0.0001), FEV1/FVC (P < 0.0001), and bronchodilator responsiveness (P < 0.0001). TAC was independently associated with lung function decline (FEV1, P = 0.02; FEV1/FVC, P = 0.01). CONCLUSIONS: TAC may reflect the airway-related disease changes that accumulate in the "quiet" zone in early/mild COPD, indicating that TAC acquired with commercially available software across various CT platforms may be a biomarker to predict accelerated COPD progression.

Oesophageal diameter is associated with severity but not progression of systemic sclerosis-associated interstitial lung disease.

BACKGROUND AND OBJECTIVE: It is unknown whether oesophageal disease is associated with systemic sclerosis-associated interstitial lung disease (SSc-ILD) severity, progression or mortality. METHODS: High-resolution computed tomography (HRCT) scans from 145 SSc-ILD patients were scored for fibrosis score, oesophageal diameter and presence of hiatal hernia. Fibrosis asymmetry was calculated as: (most affected side - least affected side)/(most affected side + least affected side). Mixed effects models were used for repeated measures analyses. RESULTS: Mean fibrosis score was 8.6%, and most patients had mild-to-moderate physiological impairment. Every 1 cm increase in oesophageal diameter was associated with 1.8% higher fibrosis score and 5.5% lower forced vital capacity (FVC; P ≤ 0.001 for unadjusted and adjusted analyses). Patients with hiatal hernia had 3.9% higher fibrosis score, with persistent differences on adjusted analysis (P = 0.001). Oesophageal diameter predicted worsening fibrosis score over the subsequent year (P = 0.02), but not when adjusting for baseline fibrosis score (P = 0.16). Oesophageal diameter was independently associated with mortality (P = 0.001). Oesophageal diameter was not associated with asymmetric disease or radiological features of gross aspiration. CONCLUSION: Oesophageal diameter and hiatal hernia are independently associated with SSc-ILD severity and mortality, but not with ILD progression or asymmetric disease. Oesophageal disease is unlikely to be a significant driver of ILD progression in SSc.

Cough is less common and less severe in systemic sclerosis-associated interstitial lung disease compared to other fibrotic interstitial lung diseases.

BACKGROUND AND OBJECTIVE: The objectives of this study were to determine the prevalence and characteristics of cough in idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP) and systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: Cough severity was measured in consecutive patients with IPF (n = 77), HP (n = 32) and SSc-ILD (n = 67) using a 10-cm visual analogue scale (VAS). Dyspnoea and quality of life were measured using established questionnaires. Cough severity was compared across ILD subtypes and predictors of cough severity were determined using multivariate analysis. RESULTS: Cough was more common in IPF and chronic HP compared to SSc-ILD (87% and 83% vs 68%, P = 0.02). The median (interquartile range) VAS score was 39 (17-65) in the IPF cohort, 29 (11-48) in HP and 18 (0-33) in SSc-ILD (P < 0.0001). Cough was more often productive in chronic HP and IPF (63% and 43% vs 21%, P < 0.001). Cough severity was independently predicted only by ILD diagnosis and higher dyspnoea score. Cough severity was not associated with other common causes of cough. Cough was a significant predictor of quality of life in IPF and SSc-ILD with adjustment for age, sex, dyspnoea and ILD severity; however, cough was not associated with quality of life in chronic HP. CONCLUSION: Cough is more frequent, more severe and more often productive in IPF and chronic HP compared to SSc-ILD, despite similar ILD severity in these cohorts. Cough severity is strongly and independently associated with dyspnoea and pulmonary function, and is a significant contributor to reduced quality of life in both IPF and SSc-ILD.

A Novel Method of Estimating Small Airway Disease Using Inspiratory-to-Expiratory Computed Tomography.

BACKGROUND: Disease accumulates in the small airways without being detected by conventional measurements. OBJECTIVES: To quantify small airway disease using a novel computed tomography (CT) inspiratory-to-expiratory approach called the disease probability measure (DPM) and to investigate the association with pulmonary function measurements. METHODS: Participants from the population-based CanCOLD study were evaluated using full-inspiration/full-expiration CT and pulmonary function measurements. Full-inspiration and full-expiration CT images were registered, and each voxel was classified as emphysema, gas trapping (GasTrap) related to functional small airway disease, or normal using two classification approaches: parametric response map (PRM) and DPM (VIDA Diagnostics, Inc., Coralville, IA, USA). RESULTS: The participants included never-smokers (n = 135), at risk (n = 97), Global Initiative for Chronic Obstructive Lung Disease I (GOLD I) (n = 140), and GOLD II chronic obstructive pulmonary disease (n = 96). PRMGasTrap and DPMGasTrap measurements were significantly elevated in GOLD II compared to never-smokers (p < 0.01) and at risk (p < 0.01), and for GOLD I compared to at risk (p < 0.05). Gas trapping measurements were significantly elevated in GOLD II compared to GOLD I (p < 0.0001) using the DPM classification only. Overall, DPM classified significantly more voxels as gas trapping than PRM (p < 0.0001); a spatial comparison revealed that the expiratory CT Hounsfield units (HU) for voxels classified as DPMGasTrap but PRMNormal (PRMNormal- DPMGasTrap = -785 ± 72 HU) were significantly reduced compared to voxels classified normal by both approaches (PRMNormal-DPMNormal = -722 ± 89 HU; p < 0.0001). DPM and PRMGasTrap measurements showed similar, significantly associations with forced expiratory volume in 1 s (FEV1) (p < 0.01), FEV1/forced vital capacity (p < 0.0001), residual volume/total lung capacity (p < 0.0001), bronchodilator response (p < 0.0001), and dyspnea (p < 0.05). CONCLUSION: CT inspiratory-to-expiratory gas trapping measurements are significantly associated with pulmonary function and symptoms. There are quantitative and spatial differences between PRM and DPM classification that need pathological investigation.