Gracijela Bozovic

Description and validation of a scoring system for tomosynthesis in pulmonary cystic fibrosis

AbstractObjectivesTo design and validate a scoring system for tomosynthesis (digital tomography) in pulmonary cystic fibrosis.MethodsA scoring system dedicated to tomosynthesis in pulmonary cystic fibrosis was designed. Three radiologists independently scored 88 pairs of radiographs and tomosynthesis examinations of the chest in 60 patients with cystic fibrosis and 7 oncology patients. Radiographs were scored according to the Brasfield scoring system and tomosynthesis examinations were scored using the new scoring system.ResultsObserver agreements for the tomosynthesis score were almost perfect for the total score with square-weighted kappa >0.90, and generally substantial to almost perfect for subscores. Correlation between the tomosynthesis score and the Brasfield score was good for the three observers (Kendall’s rank correlation tau 0.68, 0.77 and 0.78). Tomosynthesis was generally scored higher as a percentage of the maximum score. Observer agreements for the total score for Brasfield score were almost perfect (square-weighted kappa 0.80, 0.81 and 0.85).ConclusionsThe tomosynthesis scoring system seems robust and correlates well with the Brasfield score. Compared with radiography, tomosynthesis is more sensitive to cystic fibrosis changes, especially bronchiectasis and mucus plugging, and the new tomosynthesis scoring system offers the possibility of more detailed and accurate scoring of disease severity.Key Points• Tomosynthesis is more sensitive than conventional radiography for pulmonary cystic fibrosis changes. • The radiation dose from chest tomosynthesis is low compared with computed tomography.• Tomosynthesis may become useful in the regular follow-up of patients with cystic fibrosis.

Increased serum COMP predicts mortality in SSc: results from a longitudinal study of interstitial lung disease

OBJECTIVES COMP is a regulator of assembly and maintenance of the fibrillar collagen I and II networks. Serum COMP reflects skin fibrosis in SSc. The purpose of this study was to examine whether serum COMP reflects fibrotic lung involvement in SSc patients and to study if serum COMP predicts mortality. METHODS Three overlapping cohorts of 244 SSc patients were studied. Two hundred and eighteen patients were included to study survival, 80 patients to study longitudinal changes of pulmonary function tests and 64 to study pulmonary involvement assessed by high-resolution CT (HRCT). Serum COMP was measured by ELISA. Skin involvement was assessed with the modified Rodnan skin score (mRSS). Data about survival were obtained from the central population registry. RESULTS Serum COMP measured within 5 years after the first non-Raynauds manifestation was a predictor of death, and crude mortality increased by 6% for each COMP unit elevation. Serum COMP levels >15 U/l were associated with a 3.13-fold (95% CI 1.73, 5.64; P < 0.001) increased risk of death. During the first year of follow-up serum COMP and vital capacity (VC) changed inversely (r(s) = -0.32; P = 0.005), but there were no correlations between baseline serum COMP and concurrent findings by spirometry or HRCT. CONCLUSION Serum COMP early in disease is a predictor of mortality in SSc patients. Serum COMP changes in parallel with lung fibrosis as measured by VC, but the release from fibrotic skin possibly obscures the influx from the lungs and therefore serum COMP seems to have little utility as a marker of lung fibrosis.

Increased cysteinyl-leukotrienes and 8-isoprostane in exhaled breath condensate from systemic sclerosis patients

OBJECTIVES SSc is a systemic CTD characterized by fibrosis in skin and internal organs. Interstitial lung disease is a frequent complication with fibrosis in the lung parenchyma. The fibrotic process is believed to be influenced by leukotrienes (LTs) and also by oxidative stress. The aim of this study was to investigate the amount of LTs and 8-isoprostane, a marker of oxidative stress, in exhaled breath condensate (EBC) from SSc patients. METHODS Twenty-two SSc patients with median disease duration of 2.1 years were investigated. Fifteen patients had lcSSc, four patients had dcSSc and three patients only fulfilled criteria for limited SSc. Sixteen healthy controls were enrolled. Cysteinyl-LTs (CysLTs), LTB4 and 8-isoprostane were measured in EBC with EIA and related to the radiologic extent of pulmonary fibrosis. RESULTS Compared with controls, SSc patients displayed higher median (interquartile range) CysLT [6.1 (5.3-6.8) vs 4.9 (3.7-6.3) pg/ml; P=0.040], 8-isoprostane [0.23 (0.20-0.46) vs 0.19 (0.12-0.20) pg/ml; P=0.0020], but similar levels of LTB4 [0.70 (0.50-0.83) vs 0.60 (0.42-0.70) pg/ml]. CysLT correlated to LTB4, while 8-isoprostane did not correlate to any of the LTs. None of the biomarkers measured in EBC correlated to radiologic findings. CONCLUSION Increased levels of CysLT and 8-isoprostane in EBC from patients with SSc reflect the inflammatory pattern involving LTs as well as oxidative stress. These findings may indicate a possible non-invasive assessment of pulmonary involvement in SSc with a potential value for assessment of disease progress and therapy evaluation.

Pharmacological normalization of circulation after acute brain death.

Circulatory instability is a serious problem after brain death in organ donors. The hypotension is often counteracted with infusion of large amounts of crystalloid solutions, which may impair lung function leading to rejection of the lungs as donor organs. The aim was to show that the circulation can be normalized pharmacologically for 24 h in pigs after total removal of the brain and brainstem by decapitation (between C2 and C3).

Circulation stabilizing therapy and pulmonary high-resolution computed tomography in a porcine brain-dead model.

Currently 80% of donor lungs are not accepted for transplantation, often due to fluid overload. Our aim was to investigate if forced fluid infusion may be replaced by a new pharmacological therapy to stabilize circulation after brain death in an animal model, and to assess therapy effects on lung function and morphology trough blood gas parameters and state‐of‐the‐art High‐resolution CT (HRCT).

Airway resistance and reactance are affected in systemic sclerosis

Background Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc. Methods Seventy-eight SSc patients, of which 65 had limited cutaneous SSc (lcSSc) and 13 had diffuse cutaneous SSc (dcSSc), were subjected to high-resolution computed tomography (HRCT) and pulmonary function tests (spirometry, IOS, and single breath CO diffusion capacity test). Twenty-six healthy individuals served as controls. Results Patients with lcSSc had higher levels of peripheral airway resistance, that is, R5–R20 (difference between resistance at 5 Hz and resistance at 20 Hz) showed a median (and interquartile range) of 0.05 (0.02–0.09) in lcSSc, 0.01 (0.00–0.04) in dcSSc and 0.04 (0.01–0.06) in healthy controls. They also had higher levels of reactance: reactance area was 0.26 (0.15–0.56) in lcSSc, 0.20 (0.11–0.29) in dcSSc and 0.18 (0.08–0.30) in healthy controls, and resonant frequency was 10.9 (8.8–14.8) in lcSSc, 9.0 (8.3–11.6) in dcSSc and 9.1 (8.0–13.1) in healthy controls. Airway reactance correlated to fibrotic findings on HRCT, such as ground glass opacities and reticulations. Discussion This implies that IOS parameters to some extent are related to fibrosis in patients with SSc.

Imaging of the Lungs in Organ Donors and its Clinical Relevance: A Retrospective Analysis

Purpose: The aim of the study was to retrospectively evaluate the diagnostic imaging that potential lung donors undergo, the reader variability of image interpretation and its relevance for donation, and the potential information gained from imaging studies not primarily intended for lung evaluation but partially including them. Materials and Methods: Bedside chest radiography and computed tomography (CT), completely or incompletely including the lungs, of 110 brain-dead potential organ donors in a single institution during 2007 to 2014 were reviewed from a donation perspective. Two chest radiologists in consensus analyzed catheters and cardiovascular, parenchymal, and pleural findings. Clinical reports and study review were compared for substantial differences in findings that could have led to a treatment change, triggered additional examinations such as bronchoscopy, or were considered important for donation. Results: Among 136 bedside chest radiographs, no differences between clinical reports and study reviews were found in 37 (27%), minor differences were found in 28 (21%), and substantial differences were found in 71 (52%) examinations (P<0.0001). In 31 of 42 (74%) complete or incomplete CT examinations, 50 of 74 findings with relevance for lung donation were not primarily reported (P<0.0001). Conclusions: The majority of donor patients undergo only chest radiography. A targeted imaging review of abnormalities affecting the decision to use donor lungs may be useful in the preoperative stage. With a targeted list, substantial changes were made from initial clinical interpretations. CT can provide valuable information on donor lung pathology, even if the lungs are only partially imaged.

Inflammation and chronic colonization of Haemophilus influenzae in sputum in COPD patients related to the degree of emphysema and bronchiectasis in high-resolution computed tomography

The presence of bacteria in the lower airways in COPD results in inflammation, further airway structural damage, and might lead to repeated exacerbations. We have previously shown that chronic colonization of Haemophilus influenzae during stable disease is related to increased inflammation, and we now aimed to relate previous findings of bacterial colonization and inflammation to the degree of radiological findings of bronchiectasis and emphysema. Thirty-nine patients with COPD were included in their stable state, and a high-resolution computed tomography of the lung was performed. They were followed-up monthly for up to a maximum of 6 months or until exacerbation, and they answered questionnaires, performed spirometry, and induced sputum at every visit. Thirty-five patients had emphysema with an emphysema degree of median 20% (interquartile range 10–50), and five patients had bronchiectasis, of which only four could expectorate sputum. The degree of emphysema correlated with several inflammatory mediators in sputum, such as interleukin-8 concentration, myeloperoxidase activity, and Leukotriene B4 concentration. Ten patients were chronically colonized with H. influenzae (ie, had a positive culture for H. influenzae at all visits). The four sputum patients with bronchiectasis were chronically colonized with H. influenzae and showed higher degree of H. influenzae growth compared to patients without bronchiectasis. During exacerbation, there was no longer any correlation between emphysema degree and inflammation, but patients with bronchiectasis showed higher sputum purulence score than patients without bronchiectasis. Emphysema and bronchiectasis in COPD patients show different clinical features. The presence of emphysema is more related to inflammation, while bronchiectasis is associated with bacterial colonization. We believe that both emphysema and bronchiectasis are therefore COPD phenotypes of highest impact and need evaluation to prevent further disease progression.

Impact of donor chest radiography on clinical outcome after lung transplantation

Background Organ donation guidelines recommend a “clear” conventional bedside chest radiograph before lung transplantation despite only moderate accuracy for cardiopulmonary abnormalities. Purpose To evaluate the influence of donor image interpretation on lung transplantation outcome in recipients by following early and late complications, one-year survival, and to correlate imaging findings and blood gas analysis with lung transplantation outcome in recipients. Material and Methods In 35 lung donors from a single institution clinical reports and study reviews of imaging findings of the mandatory bedside chest radiographs and blood gas analyses were compared with clinical outcome in 38 recipients. Hospitalization time, peri- and postoperative complications, early complications (primary graft dysfunction, infection), 30-day and one-year survival, and forced expiratory volume in 1 s percentage of predicted normal value (FEV1%) at one-year follow-up were analyzed. Results Findings in clinical reports and study reviews differed substantially, e.g. regarding reported decompensation, edema, infection, and atelectasis. No correlation was shown between imaging findings in clinical report or study review and blood gas analyses in the lung donors compared to postoperative outcome in recipients. Conclusion The interpretation of the mandatory chest radiograph in its present form does not influence one-year outcome in lung transplantation. Larger imaging studies or a change in clinical routine including computed tomography may provide evidence for future guidelines.

Pulmonary blood density quantified by CMR is reduced in newly diagnosed systemic sclerosis, consistent with pulmonary arteriolar proliferation

Results Compared to healthy subjects, SSc patients had lower PBV (460±85 vs 602±125ml, p<0.01), lower PBD (16±5 vs 21±2%, p<0.001; 15/27 (56%) had PBD below normal limits), but no difference in PBVV/stroke volume (40±8 vs 46±10%, p=0.12). PBD correlated with Doppler echocardiography estimated pulmonary artery pressure (r=-0.36, p<0.05) and the diffusion capacity for carbon monoxide (DLCO) in the lungs (r=0.44, p=0.02), but was not affected by pulmonary fibrosis by high-resolution computed tomography (p=0.34). Conclusions