Catherine M. Owens

Lung Clearance Index and HRCT are complementary markers of lung abnormalities in young children with CF

Rationale High resolution computed tomography (HRCT) is a more sensitive tool for detecting early cystic fibrosis (CF) lung disease than either spirometry or plain radiography, but its relationship to other measures of lung function has not been established in young children. Objectives 1) To assess whether the lung clearance index (LCI) derived from multiple breath inert-gas washout (MBW) is as effective as HRCT in identifying pulmonary abnormalities; and 2) explore the relationships between abnormalities detected by HRCT and by spirometry, plethysmography and MBW (collectively, LFTs) in young children with CF. Methods Children with CF underwent LFTs and volumetric HRCT on the same day. Healthy age-matched controls underwent identical LFTs without HRCT. Scans were anonymised, and scored using the Brody-II CT scoring system, to assess for presence and extent of bronchiectasis, airway wall thickening, mucus plugging, and parenchymal opacities. Results Assessments were undertaken in 60 children with CF (mean (SD) 7.8 (1.3) years) and 54 healthy controls (7.9 (1.2) y). Among children with CF, 84% (47/56) had abnormal LCI, 58% (27/47) abnormal plethysmographic lung volumes (FRCpleth or RV), 35% (21/60) abnormal sRaw and 47% (28/60) abnormal spirometry (FEV1 or FEF25–75); whereas HRCT scans were abnormal in 85% (51/60): median total Brody-II score: 9.5% (range 0–51%). Total CT score correlated more strongly with LCI (Spearman correlation=0.77) than with spirometry (R=−0.43) or any other marker of lung function. Of the nine children with normal LCI, five had abnormalities on HRCT, whereas five children with normal HRCT had raised LCI. Conclusions These results suggest that while LCI and HRCT have similar sensitivity to detect CF lung disease, complimentary information may be gained in individual patients.

The radiological spectrum of invasive aspergillosis in children: a 10-year review

BackgroundInvasive aspergillosis is an uncommon but life-threatening event in the immunocompromised child. Attempts at fungal isolation are often unrewarding and a high index of radiological suspicion is essential in the early diagnosis of infected children.ObjectiveTo document the radiological spectrum of disease in invasive aspergillosis in the paediatric population.Materials and methodsA retrospective review of the imaging performed in 27 consecutive patients (age 7 months to 18 years) with documented invasive Aspergillosis encountered over a 10-year period at a single institution.ResultsRadiographic findings of pulmonary disease (20 patients) included segmental and multilobar consolidation, perihilar infiltrates, multiple small nodules, peripheral nodular masses and pleural effusions. No cavitating lesions were seen on CXR. Small cavitating nodules were present on CT in two of eight children. Chest wall disease was particularly associated with underlying chronic granulomatous disease. Disseminated disease manifested as osteomyelitis (n=5), cerebral (n=3), oesophageal (n=1), hepatic (n=2), renal (n=2) and cutaneous (n=5) involvement. Imaging findings are discussed. Twelve patients (44%) subsequently died from Aspergillus-related complications.ConclusionsInvasive aspergillosis presents with a wide variety of radiographic findings involving multiple organ systems. Respiratory findings are varied but often non-specific, and a high index of suspicion is necessary in immunocompromised patients. In contrast to adult disease, the incidence of cavitation of pulmonary lesions appears low.

Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice

Background: Most Wilms tumours occur in otherwise healthy children, but a small proportion occur in children with genetic syndromes associated with increased risks of Wilms tumour. Surveillance for Wilms tumour has become widespread, despite a lack of clarity about which children are at increased risk of these tumours and limited evidence of the efficacy of screening or guidance as to how screening should be implemented. Methods: The available literature was reviewed. Results: The potential risks and benefits of Wilms tumour surveillance are finely balanced and there is no clear evidence that screening reduces mortality or morbidity. Prospective evidence-based data on the efficacy of Wilms tumour screening would be difficult and costly to generate and are unlikely to become available in the foreseeable future. Conclusions: The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3–4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith–Wiedemann syndrome, Simpson–Golabi–Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.

Neonatal bronchopulmonary dysplasia predicts abnormal pulmonary HRCT scans in long-term survivors of extreme preterm birth

Background: There is an increasing understanding that extreme preterm birth carries a risk of long-term pulmonary sequelae. A study was undertaken to investigate if, and in what way, neonatal factors were associated with subsequent abnormalities on pulmonary high-resolution CT (HRCT) scanning and if pulmonary function was related to these abnormalities. Methods: HRCT scanning and pulmonary function tests were performed less than 2 weeks apart in 74/86 eligible subjects (86%) born at a gestational age of ⩽28 weeks or with a birth weight of ⩽1000 g within a defined area in Western Norway in 1982–5 (n = 42) or 1991–2 (n = 32). Mean age at examination was 18 and 10 years, respectively. HRCT scans were interpreted by a paediatric radiologist blinded to the clinical data using a structured system allowing scores from 0 to 50. Results: Lung parenchymal abnormalities were found in 64 subjects (86%), the median (interquartile range) score being 3.0 (1.75–5.0) points. Prolonged neonatal requirement for oxygen treatment predicted poor outcome, and an increase of 100 days increased the average HRCT score by 3.8 points (p<0.001). There was also a positive association of the severity of pulmonary function abnormalities with the extent of HRCT abnormalities, exemplified by the relation between forced expiratory volume in 1 s and total HRCT score (β = −0.090; p<0.001). Conclusions: In area-based cohorts of long-term survivors of extremely preterm birth, prolonged neonatal requirements for oxygen treatment predicted subsequent structural abnormalities on HRCT scans and in pulmonary function, and these two outcome measures were interrelated.

The paediatric wrist revisited: redefining MR findings in healthy children

Objectives During a multicentre study on juvenile idiopathic arthritis, wide variations were observed in bone shape, signal intensity and volume of joint fluid as shown by MRI which in part appeared to be unrelated to disease activity. A study was undertaken to examine these features in a cohort of healthy children. Methods 88 children of mean age 9.8 years (range 5–15) underwent MRI imaging (T1-weighted Spin Echo and Spectral Selection Attenuated Inversion Recovery (SPAIR)) of the left wrist. The number of bony depressions, distribution and amount of joint fluid and the presence of bone marrow changes were assessed. Results Bony depressions were present in all children, increasing with age from a mean of 4.0 in children aged 4–6 years to 9.2 in those aged 12–15 years (p<0.001)). 45 of 84 children (53.6%) had a high signal on SPAIR with a corresponding low signal on T1 in at least one bone. No associations were seen between bone marrow change (present or not) and sex (p=0.827) or sports club membership (p=0.616). All children had visible joint fluid in at least one of the joints assessed. No associations were seen between the presence of joint fluid and age group, except for the radius/scaphoid and capitate-scaphoid joints and a recess lateral to the hamate. Conclusions It is important to be aware of the high prevalence of bony depressions, signal changes suggestive of bone marrow oedema and the volume of joint fluid seen in normal children. Such findings must be interpreted with care in children with suspected disease such as juvenile arthritis.

Pleuroparenchymal fibroelastosis in patients with pulmonary disease secondary to bone marrow transplantation

This study presents four patients who underwent bone marrow transplantation and subsequently developed pleuroparenchymal fibroelastosis, hitherto reported as an idiopathic condition. All presented clinically with pneumothorax and subpleural fibrosis on high-resolution computed tomography. In addition to the expected obliterative bronchiolitis, histopathology showed coexistent subpleural changes, and the relationship of pathology in multiple anatomic compartments in post bone marrow transplantation pulmonary disease is discussed.

Post mortem magnetic resonance imaging in the fetus, infant and child: a comparative study with conventional autopsy (MaRIAS Protocol).

BackgroundMinimally invasive autopsy by post mortem magnetic resonance (MR) imaging has been suggested as an alternative for conventional autopsy in view of the declining consented autopsy rates. However, large prospective studies rigorously evaluating the accuracy of such an approach are lacking. We intend to compare the accuracy of a minimally invasive autopsy approach using post mortem MR imaging with that of conventional autopsy in fetuses, newborns and children for detection of the major pathological abnormalities and/or determination of the cause of death.Methods/DesignWe recruited 400 consecutive fetuses, newborns and children referred for conventional autopsy to one of the two participating hospitals over a three-year period. We acquired whole body post mortem MR imaging using a 1.5 T MR scanner (Avanto, Siemens Medical Solutions, Enlargen, Germany) prior to autopsy. The total scan time varied between 90 to 120 minutes. Each MR image was reported by a team of four specialist radiologists (paediatric neuroradiology, paediatric cardiology, paediatric chest & abdominal imaging and musculoskeletal imaging), blinded to the autopsy data. Conventional autopsy was performed according to the guidelines set down by the Royal College of Pathologists (UK) by experienced paediatric or perinatal pathologists, blinded to the MR data. The MR and autopsy data were recorded using predefined categorical variables by an independent person.DiscussionUsing conventional post mortem as the gold standard comparator, the MR images will be assessed for accuracy of the anatomical morphology, associated lesions, clinical usefulness of information and determination of the cause of death. The sensitivities, specificities and predictive values of post mortem MR alone and MR imaging along with other minimally invasive post mortem investigations will be presented for the final diagnosis, broad diagnostic categories and for specific diagnosis of each system.Clinical Trial RegistrationNCT01417962NIHR Portfolio Number: 6794

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

IntroductionThe aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM).MethodsSerum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist).ResultsAnti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease.ConclusionsAnti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed.

Imaging of parapneumonic pleural effusions and empyema in children

Pleural empyema in children is increasing in incidence. The British Thoracic Society published guidelines for the management of empyema in children in 2005, including recommendations regarding imaging. In this article we review the pathophysiology, treatment options and imaging findings of complicated parapneumonic effusion and empyema in children. We also review the published evidence that supports the roles imaging is called upon to play in the management of these conditions. Imaging in the form of chest radiography and US is recommended to identify and guide drainage of complicated parapneumonic effusions. CT is recommended in special circumstances only. Imaging techniques have not been shown to accurately stage empyema, predict outcome or guide decisions regarding surgical versus medical management.

Role of routine computed tomography in paediatric pleural empyema

Background: The incidence of empyema in children is increasing worldwide. While there are emerging data for the best treatment options, there is little evidence to support the imaging modalities used to guide treatment, particularly with regard to the role of routine CT scanning. The aims of this study were to develop a radiological scoring system for paediatric empyema and to assess the utility of routine CT scanning in this disease. Methods: Children with empyema were prospectively enrolled over a 3-year period into a randomised clinical trial of video-assisted thoracoscopic surgery versus percutaneous chest drain insertion and urokinase. All children received a preoperative chest radiograph (CXR), pleural ultrasound scan (USS) and chest CT scan. In the urokinase arm the clinician inserted the drain with USS evidence only and did not have access to the CT scan at the time of insertion to reflect clinical practice. A scoring system was developed for each individual radiological modality and used to compare imaging characteristics of the pleural fluid collection and underlying parenchyma and to assess the utility of USS and CT to predict length of stay after the intervention. Results: Of the 60 subjects recruited, 46 had USS images available for review, 36 had a CT scan which met the inclusion criteria and 31 had all three radiological measurements (CT, USS and CXR) available for analysis. There was substantial interobserver agreement for USS grades (κ = 0.709) and moderate agreement for total CT scores (κ = 0.520). There were weak correlations between USS grade and total CT score as well as CT loculation and density scores. Of the 25 CXRs showing simple opacification of the underlying parenchyma only, CT demonstrated simple consolidation (n = 14), necrotising pneumonia (n = 7), cavitary necrosis (n = 3) and pneumatoceles (n = 1). No abnormality was detected on CT scanning which directly altered clinical management. Neither the USS score nor the CT score, nor a combination of the two, were able to predict length of hospital stay. Conclusions: CT scanning detects more parenchymal abnormalities than chest radiography. However, the additional information does not alter management and is unable to predict clinical outcome. This suggests that there is no role for the routine use of CT scanning in children if treated with urokinase and percutaneous chest drain. The omission of routine CT scanning in empyema will reduce the exposure of children to unnecessary radiation and reduce costs. Trial registration number: The trial is fully registered with clinicaltrials.gov (ID: NCT00144950).