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.

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.

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.

How to Approach a Hip PARTI With Confidence: Ultrasound-Guided Parallel Transverse in-Plane Technique for Intra-articular Hip Interventions.

The "parallel transverse in-plane" technique for ultrasound-guided intra-articular hip interventions ensures needle visualization for the entire procedure, with the needle clearly shown entering the joint. With the widely described longitudinal in-plane approach, needle visualization can be poor, necessitating reliance on tissue distortion, which can reduce user confidence and safety. The parallel transverse in-plane approach is invaluable in those with anterior thigh skin breakdown and where anterior access is contraindicated. The approach also allows a broad width of the synovium to be traversed and is therefore well suited to synovial biopsy. This short Technical Innovation highlights this alternative approach to hip joint intervention.

Dynamic ultrasound-guided trochanteric bursal injection.

Injection of steroid and anesthetic into the greater trochanteric bursa is commonly performed for trochanteric bursitis, gluteus medius/minimus tendinopathy, or as a part of a barbotage procedure for gluteus medius or minimus calcific tendonosis. Trochanteric bursal injection is widely performed both with and without image guidance, and is typically viewed as low-difficulty; however optimum needle tip position can be challenging. We discuss a simple dynamic technique to aid the practitioner in optimal needle placement.

Impact of sublingual nitroglycerin dosage on FFRCT assessment and coronary luminal volume-to-myocardial mass ratio.

OBJECTIVES: Fractional flow reserve computed tomography (FFRCT) depends upon nitroglycerin (NTG) inducing maximal hyperemia. However, the impact of NTG dosages on FFRCT analysis including coronary volume-to-mass ratio (V/M) is unknown. METHODS: Eighty patients with repeat coronary CT angiograms (CCTAs) with different sublingual spray NTG doses (0.4 mg and 0.8 mg) were retrospectively analyzed with 45 patients excluded. Patient and scan demographics, post-stenosis and nadir FFRCT values, coronary volume, and coronary volume-to-mass ratio (V/M) were compared at initial CCTA (0.4 mg NTG) and follow-up CCTA (0.8 mg NTG). Differences were compared by Wilcoxon signed-rank test. RESULTS: Thirty-five patients were included (time between CCTAs, 3.9 ± 1.6 years). Segment involvement score was 2.4 ± 3.3 and 2.8 ± 3.4 at initial and repeat CCTA (0.4 and 0.8 mg NTG), respectively (p = 0.004). There was similar image quality (4.1 ± 0.7 vs 4.1 ± 0.8; p = 0.51). Nadir FFRCT values did not differ in the left (0.4 mg, 0.80 ± 0.08 vs 0.8 mg, 0.80 ± 0.03; p = 0.66), right (0.4 mg, 0.90 ± 0.04 vs 0.8 mg, 0.90 ± 0.06; p = 0.25), or circumflex coronaries (0.4 mg, 0.87 ± 0.06 vs 0.8 mg, 0.88 ± 0.06; p = 0.34). Post-stenosis FFRCT values did not differ (p = 0.65). Coronary volume increased with 0.8 mg of NTG (2639 ± 753 mm3 vs 2844.8 ± 827 mm3; p = 0.009) but V/M ratio did not (p = 0.20). CONCLUSIONS: Use of 0.8 mg versus 0.4 mg of NTG in routine clinical CCTAs significantly increased coronary volume determined from FFRCT analysis but did not alter FFRCT or V/M. Further evaluation of repeat CCTAs in a more contemporaneous fashion using varied nitrate doses and disease severity is needed. KEY POINTS: • Fractional flow reserve from computed tomography (FFRCT) is a noninvasive method for evaluating the coronary arteries and relies on nitroglycerin (NTG) to induce coronary vasodilation, but the impact of different NTG dosages is unknown. • Retrospective analysis evaluated use of different NTG doses on FFRCT. • Increased NTG dose increased coronary luminal volume on FFRCTanalysis, but did not change FFRCTvalues.

Anatomic Considerations for Injection of the Lateral Atlanto-Axial Joint.

OBJECTIVE: We aimed to define the potential complications of intra-articular steroid injections into the lateral C1-2 articulations and safety margins to the relevant structures. METHODS: A total of 488 contrast-enhanced computed tomography angiogram (CTA) "arch to vertex" studies were retrospectively reviewed for theoretical intersection of the vertebral artery or thecal sac and distance of the named structures from the anticipated/theoretical trajectory of injection into the lateral C1-C2 joint. RESULTS: Patients were 60.4±15.8 years old and 55.5% male. In total, seven vertebral arteries and 11 thecal sac theoretical intersections were found. In cases without a direct intersection, the distance from the trajectory (range) was 0.71±0.18 (0.22-1.44) cm to the vertebral artery and 0.6±0.22 (0.14-1.8) cm to the thecal sac. CONCLUSIONS: Although injection of steroid into the lateral C1-C2 articulation for pain management has historically been reported to carry risk of severe complications due to close proximity and location variability of surrounding structures, our study quantifies the potential risk of such injections. Further, our analysis suggests that preprocedural imaging should be considered.

Radial artery aneurysm secondary to dynamic entrapment by extensor pollicis longus tendon: a case of snapping thumb.

Aneurysms of the distal radial artery at the level of the wrist are rare. Most reported cases are posttraumatic, either from iatrogenic arterial puncture for radial arterial access or from a penetrating injury. Other causes include infection and connective tissue disorders. Early diagnosis is important to avoid the potential complications of thrombus formation, distal digital ischemia, and rupture. Evaluation of the radial artery is typically performed using non-invasive modalities like ultrasonography, computed tomographic angiography (CTA), and magnetic resonance angiography (MRA). Invasive angiography can also be performed, particularly if minimally invasive treatment options are being considered. We report a case of a 35-year-old male mechanic who presented with pain at the base of the left thumb dorsally, with reproducible painful snapping on dynamic exam. Ultrasound demonstrated a fusiform aneurysm of the radial artery. At the level of the aneurysm, there was dynamic entrapment of the artery between the extensor pollicis longus (EPL) tendon and the underlying trapezium. The patient's symptoms improved with conservative management and avoidance of the snapping-producing maneuvers. To our knowledge, this is the first published case of snapping at the base of the thumb resulting in repetitive entrapment of the radial artery by the EPL tendon captured on dynamic ultrasound examination.

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.

The bronchial epithelial cell bacterial microbiome and host response in patients infected with human immunodeficiency virus.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is an important comorbidity in patients living with human immunodeficiency virus (HIV). Previous bacterial microbiome studies have shown increased abundance of specific bacterium, like Tropheryma whipplei, and no overall community differences. However, the host response to the lung microbiome is unknown in patients infected with HIV. METHODS: Two bronchial brush samples were obtained from 21 HIV-infected patients. One brush was used for bacterial microbiome analysis using the Illumina MiSeqTM platform, while the other was used to evaluate gene expression patterns of the host using the Affymetrix Human Gene ST 2.0 array. Weighted gene co-expression network analysis was used to determine the relationship between the bacterial microbiome and host gene expression response. RESULTS: The Shannon Diversity was inversely related to only one gene expression module (p = 0.02); whereas evenness correlated with five different modules (p ≤ 0.05). After FDR correction only the Firmicutes phylum was significantly correlated with any modules (FDR < 0.05). These modules were enriched for cilia, transcription regulation, and immune response. Specific operational taxonomic units (OTUs), such as OTU4 (Pasteurellaceae), were able to distinguish HIV patients with and without COPD and severe emphysema. CONCLUSION: These data support the hypothesis that the bacterial microbiome in HIV lungs is associated with specific host immune responses. Whether or not these responses are also seen in non-HIV infected individuals needs to be addressed in future studies.

Best method for right atrial volume assessment by two-dimensional echocardiography: validation with magnetic resonance imaging.

AIM: Echocardiographic methods for estimating right atrial (RA) volume have not been standardized. Our aim was to evaluate two-dimensional (2D) echocardiographic methods of RA volume assessment, using RA volume by magnetic resonance imaging (MRI) as the reference. METHODS AND RESULTS: Right atrial volume was assessed in 51 patients (mean age 63 ± 14 years, 33 female) who underwent comprehensive 2D echocardiography and cardiac MRI for clinically indicated reasons. Echocardiographic RA volume methods included (1) biplane area length, using four-chamber view twice (biplane 4C-4C); (2) biplane area length, using four-chamber and subcostal views (biplane 4C-subcostal); and (3) single plane Simpson's method of disks (Simpson's). Echocardiographic RA volumes as well as linear RA major and minor dimensions were compared to RA volume by MRI using correlation and Bland-Altman methods, and evaluated for inter-observer reproducibility and accuracy in discriminating RA enlargement. All echocardiography volumetric methods performed well compared to MRI, with Pearson's correlation of 0.98 and concordance correlation ≥0.91 for each. For bias and limits of agreement, biplane 4C-4C (bias -4.81 mL/m(2) , limits of agreement ±9.8 mL/m(2) ) and Simpson's (bias -5.15 mL/m(2) , limits of agreement ±10.1 mL/m(2) ) outperformed biplane 4C-subcostal (bias -8.36 mL/m(2) , limits of agreement ±12.5 mL/m(2) ). Accuracy for discriminating RA enlargement was higher for all volumetric methods than for linear measurements. Inter-observer variability was satisfactory across all methods. CONCLUSIONS: Compared to MRI, biplane 4C-4C and single plane Simpson's are highly accurate and reproducible 2D echocardiography methods for estimating RA volume. Linear dimensions are inaccurate and should be abandoned.

MR epidurography: distribution of injectate at caudal epidural injection.

OBJECTIVE: To (a) evaluate the feasibility of MR epidurography (MRE) and (b) assess the distribution of injectate using two different volumes at caudal epidural steroid injection. MATERIALS AND METHODS: Twenty patients who were referred with symptomatic low back pain for caudal epidural steroid injection were assigned to have either 10 ml (9/20) or 20 ml (11/20) of injectate administered. Gadolinium was included in the injection. The patients proceeded to MRI where sagittal and coronal T1-weighted fat-saturated sequences were acquired and reviewed in the mid-sagittal and right and left parasagittal views at the level of the exit foramina. RESULTS: Gadolinium was observed at or above the L3/4 disc level in all 11 patients who received 20 ml (100 %), compared with only five of nine patients who received 10 ml (56 %). Injectate was seen to the L4 nerve root level in all 11 patients who received 20 ml (100 %) but only four out of nine patients who received 10 ml (44 %), not even reaching the L5 nerve root level in four further of these nine patients (44 %). Overall, there was a trend to visualize gadolinium at higher levels of the epidural space with higher volumes injected. CONCLUSIONS: Firstly, MR epidurography is a safe technique that allows excellent visualization of the distribution of gadolinium in the epidural space following injection via the caudal hiatus. Secondly, a volume of 10 ml is unlikely to treat L5/S1 disease in almost half of patients at caudal epidural steroid injection and at least 20 ml of injectate is likely required for any medication to reach the desired level.

Bronchoalveolar Lavage Fluid Cellular Analysis and Radiologic Patterns in Patients With Fibrotic Interstitial Lung Disease.

BACKGROUND: Bronchoalveolar lavage (BAL) cellular analysis is often recommended during the initial diagnostic evaluation of fibrotic interstitial lung disease (ILD). Despite recommendation for its use, between-center heterogeneity exists and supportive data concerning the clinical utility and correlation of BAL findings with radiologic features or patterns remain sparse. RESEARCH QUESTION: In patients with fibrotic ILD, are BAL findings associated with radiologic features, patterns, and clinical diagnoses? STUDY DESIGN AND METHODS: Patients with fibrotic ILD who underwent BAL for diagnostic evaluation and who were enrolled in the prospective Canadian Registry for Pulmonary Fibrosis were re-reviewed in a standardized multidisciplinary discussion (MDD). BAL was categorized according to guideline-recommended thresholds, and using thresholds of lymphocytosis > 20% and neutrophils > 4.5%. High-resolution CT (HRCT) scans were scored (blinded to clinical data) for specific features and percentage lung involvement. Radiologists classified HRCT scans according to guideline-defined patterns for idiopathic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis (fHP); then, MDD diagnoses were assigned, considering all available data. RESULTS: Bronchoscopy with cellular analysis was performed in 209 of 1,593 patients (13%). Lymphocyte % was weakly negatively correlated with total fibrosis % (r = -0.16, P = .023) but not statistically significantly correlated with ground glass opacity % (r = 0.01, P = .94). A mixed BAL pattern was the most frequent in all radiologic patterns (range, 45%-69%), with a minority classifiable according to BAL guidelines. BAL lymphocytosis appeared with similar frequency across HRCT patterns of fHP (21%) and usual interstitial pneumonia (18%). Only 5% of patients with MDD-based fHP had a guideline-defined isolated lymphocytosis > 15%. INTERPRETATION: BAL cellular analyses did not significantly correlate with radiologic features, guideline patterns, or MDD-based diagnoses. Ground glass opacities are often interpreted to represent pulmonary inflammation, but were not associated with BAL lymphocytosis in this cohort.

Plantar plate tear diagnosis using dual-energy computed tomography collagen material decomposition application.

Computed tomography (CT) scans of the feet are often obtained in the context of trauma or suspected stress fracture mainly for assessment of osseous pathology. However, compared with magnetic resonance imaging (MRI), soft-tissue assessment on CT is typically limited. Plantar plate injury is a common cause of metatarsalgia and, along with other soft-tissue injuries, is typically diagnosed with MRI. We present a case of plantar plate tear detected on dual-energy CT scan using a collagen material decomposition algorithm confirmed on subsequent MRI.

"Superior cleft sign" as a marker of rectus abdominus/adductor longus tear in patients with suspected sportsman's hernia.

OBJECTIVE: We describe a new imaging sign, the "superior cleft sign", identified at both symphysography and MRI, which should be used as a marker of rectus abdominis/adductor longus attachment tearing. MATERIALS AND METHODS: A study population of 25 patients presenting with clinically suspected sportsman's hernia, who had undergone both symphysography and MRI of the groin were included for study. In each case, images were reviewed to determine the presence of a superior cleft, secondary cleft, and or both abnormalities. RESULTS: Images of all patients complaining of groin crease discomfort similar to sportsman's hernia revealed the presence of a superior cleft at the rectus abdominis/adductor longus attachment. This "superior cleft sign" correlated with the side of symptoms in each case, and, in contrast to the previously described secondary cleft along the inferior margin of the inferior pubic ramus, occurred parallel to the inferior margin of the superior pubic ramus. CONCLUSIONS: The presence of the "superior cleft sign" should be sought in addition to the previously described secondary cleft sign in sportspeople presenting with exercise-related groin pain or pubalgia. It should specifically be sought in patients referred with suspected sportsman's hernia.