Genetic defects in cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene cause CF. Infants with CFTR mutations show a peribronchial neutrophil infiltration prior to the establishment of infection in their lung. The inflammatory response progressively increases in children that include both upper and lower airways. Infectious and inflammatory response leads to an increase in mucus viscosity and mucus plugging of small and medium-size bronchioles. Eventually, neutrophils chronically infiltrate the airways with biofilm or chronic bacterial infection. Perpetual infection and airway inflammation destroy the lungs, which leads to increased morbidity and eventual mortality in most of the patients with CF. Studies have now established that neutrophil cytotoxins, extracellular DNA, and neutrophil extracellular traps (NETs) are associated with increased mucus clogging and lung injury in CF. In addition to opportunistic pathogens, various aspects of the CF airway milieux (e.g., airway pH, salt concentration, and neutrophil phenotypes) influence the NETotic capacity of neutrophils. CF airway milieu may promote the survival of neutrophils and eventual pro-inflammatory aberrant NETosis, rather than the anti-inflammatory apoptotic death in these cells. Degrading NETs helps to manage CF airway disease; since DNAse treatment release cytotoxins from the NETs, further improvements are needed to degrade NETs with maximal positive effects. Neutrophil-T cell interactions may be important in regulating viral infection-mediated pulmonary exacerbations in patients with bacterial infections. Therefore, clarifying the role of neutrophils and NETs in CF lung disease and identifying therapies that preserve the positive effects of neutrophils, while reducing the detrimental effects of NETs and cytotoxic components, are essential in achieving innovative therapeutic advances.

/pdf/progression-of-cystic-fibrosis-lung-disease-from-childhood-50136kprr5.pdf

Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) Formation, and NET Degradation.

Purpose The purpose of this study was to characterize the technical capabilities and feasibility of a large field-of-view clinical spectral photon-counting computed tomography (SPCCT) prototype for high-resolution (HR) lung imaging. Materials and methods Measurement of modulation transfer function (MTF) and acquisition of a line pairs phantom were performed. An anthropomorphic lung nodule phantom was scanned with standard (120 kVp, 62 mAs), low (120 kVp, 11 mAs), and ultra-low (80 kVp, 3 mAs) radiation doses. A human volunteer underwent standard (120 kVp, 63 mAs) and low (120 kVp, 11 mAs) dose scans after approval by the ethics committee. HR images were reconstructed with 1024 matrix, 300 mm field of view and 0.25 mm slice thickness using a filtered-back projection (FBP) and two levels of iterative reconstruction (iDose 5 and 9). The conspicuity and sharpness of various lung structures (distal airways, vessels, fissures and proximal bronchial wall), image noise, and overall image quality were independently analyzed by three radiologists and compared to a previous HR lung CT examination of the same volunteer performed with a conventional CT equipped with energy integrating detectors (120 kVp, 10 mAs, FBP). Results Ten percent MTF was measured at 22.3 lp/cm with a cut-off at 31 lp/cm. Up to 28 lp/cm were depicted. While mixed and solid nodules were easily depicted on standard and low-dose phantom images, higher iDose levels and slice thicknesses (1 mm) were needed to visualize ground-glass components on ultra-low-dose images. Standard dose SPCCT images of in vivo lung structures were of greater conspicuity and sharpness, with greater overall image quality, and similar image noise (despite a flux reduction of 23%) to conventional CT images. Low-dose SPCCT images were of greater or similar conspicuity and sharpness, similar overall image quality, and lower but acceptable image noise (despite a flux reduction of 89%). Conclusions A large field-of-view SPCCT prototype demonstrates HR technical capabilities and high image quality for high resolution lung CT in human.

Feasibility of lung imaging with a large field-of-view spectral photon-counting CT system.

The objective of this study was to investigate the feasibility of defining diagnostic reference levels (DRLs) on a European basis for specific clinical indications (CIs), within the context of the European Clinical DRLs (EUCLID) European Commission project. A prospective, multicenter, industry-independent European study was performed to provide data on 10 CIs (stroke, chronic sinusitis, cervical spine trauma, pulmonary embolism, coronary calcium scoring, coronary angiography, lung cancer, hepatocellular carcinoma, colic/abdominal pain, and appendicitis) via an online survey that included information on patient clinical, technical, and dosimetric parameters. Data from at least 20 patients per CI were requested from each hospital. To establish DRLs, a methodology in line with the International Commission on Radiological Protection (ICRP) Report 135 good practice recommendations was followed. Data were collected from 19 hospitals in 14 European countries on 4299 adult patients and 10 CIs to determine DRLs. DRLs differ considerably between sites for the same CI. Differences were attributed mainly to technical protocol and variable number of phases/scan lengths. Stroke and hepatocellular carcinoma were the CIs with the highest DRLs. Coronary calcium scoring had the lowest DRL value. Comparison with published literature was limited, as there was scarce information on DRLs based on CI. This is the first study reporting on feasibility of establishing CT DRLs based on CI using European data. Resulting values will serve as a baseline for comparison with local radiological practice, national authorities when DRLs are set/updated, or as a guideline for local DRL establishment. • First study reporting on the feasibility of establishing CT diagnostic reference levels based on clinical indication using data collected across Europe. • Only one-fourth of the hospitals had CT machines less than 5 years old. • Large dose variations were observed among hospitals and CT protocols were quite different between hospitals.

CT diagnostic reference levels based on clinical indications: results of a large-scale European survey

Purpose The purpose of this study was to analyze the impact of different options for reduced-dose computed tomography (CT) on image noise and visibility of pulmonary structures in order to define the best choice of parameters when performing ultra-low dose acquisitions of the chest in clinical routine. Materials and methods Using an anthropomorphic chest phantom, CT images were acquired at four defined low dose levels (computed tomography dose index [CTDIvol] = 0.15, 0.20, 0.30 and 0.40 mGy), by changing tube voltage, pitch factor, or rotation time and adapting tube current to reach the predefined CTDIvol-values. Images were reconstructed using two different levels of iteration (adaptive statistical iterative reconstruction [ASIR®]-v70% and ASIR®-v100%). Signal-to-noise ratio (SNR) as well as contrast-to-noise ratio (CNR) was calculated. Visibility of pulmonary structures (bronchi/vessels) were assessed by two readers on a 5-point-Likert scale. Results Best visual image assessments and CNR/SNR were obtained with high tube voltage, while lowest scores were reached with lower pitch factor followed by high tube current. Protocols favoring lower pitch factor resulted in decreased visibility of bronchi/vessels, especially in the periphery. Decreasing radiation dose from 0.40 to 0.30 mGy was not associated with a significant decrease in visual scores (P  Conclusion Favoring high tube voltage is the best option for reduced-dose protocols. A decrease of SNR and CNR does not necessarily go along with reduced visibility of pulmonary structures.

Optimization of acquisition parameters for reduced-dose thoracic CT: A phantom study.

This review summarises the current knowledge about recurrent radiological imaging and associated cumulative doses to patients. The recent conservative estimates are for around 0.9 million patients ...

Radiation protection perspective to recurrent medical imaging: what is known and what more is needed?

Purpose The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT. Materials and methods A total of 52 patients with CF who underwent LT at our institution between January 2001 and December 2006 with at least 3 years of survival were retrospectively included. There were 27 men and 25 women with a mean age of 24.4 ± 9.2 (SD) years (range: 7.6–52.9 years) at the time of LT. Calculation of cumulative effective and organ doses after LT were based on dosimetry information and acquisition parameters of each examination. Cumulative radiation doses were calculated until June 2016, but stopped at the time of de novomalignancy diagnosis, for patients developing the condition. Results Patients received a mean cumulative effective dose of 110.0 ± 51.6 (SD) mSv (range: 13–261.3 mSv) over a mean follow-up of 8.1 ± 3.6 (SD) years (range: 0.5–13.5 years), with more than 100mSv in 5 years in 19/52 patients (37%). Chest CT accounted for 73% of the cumulative effective dose. Mean doses to the lung, breast and thyroid were 152.8 ± 61.1 (SD) mGy (range: 21.2–331.6 mGy), 106.5 ± 43.2 (SD) mGy (range: 11.9–221.4 mGy) and 72.7 ± 31.8 (SD) mGy (range: 9.5–165.0 mGy), respectively. Nine out of 52 patients (17%) developed a total of 10 de novo malignancies, all but one attributable to immunosuppression after a mean post-transplantation follow-up period of 11.1 ± 3.5 (SD) years (range: 3.7–16.3 years). Six-month cumulative effective dose was not greater in patients with de novomalignancies than in those without de novomalignancies (28.9 ± 14.5 (SD) mGy (range: 13.0–53.4) vs 25.6 ± 15.3 (range: 5.0–69.7), respectively, P > 0.05). Conclusion The cumulative effective dose exceeded 100 mSv in 5 years in 37% of LT recipients, the reason why continuous efforts should be made to optimize chest CT acquisitions accounting for 73% of the radiation dose.

Cumulative radiation dose after lung transplantation in patients with cystic fibrosis.

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Cumulative radiation dose after lung transplantation in patients with cystic fibrosis.