The assessment of short and long term changes in lung function in CF using 129Xe MRI.

INTRODUCTION: 129Xe ventilation MRI is sensitive to detect early CF lung disease and response to treatment. 129Xe-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change. METHODS: 29 children and adults with CF and a range of disease severity were assessed twice, a median [IQR] of 16.0 [14.4,19.5] months apart. Patients performed 129Xe-MRI, lung clearance index (LCI), body plethysmography and spirometry at both visits. Eleven patients repeated 129Xe-MRI in the same session to assess the within-visit repeatability. The ventilation defect percentage (VDP) was the primary metric calculated from 129Xe-MRI. RESULTS: At baseline, mean (sd) age=23.0 (11.1) years and FEV1 z-score=-2.2 (2.0). Median [IQR] VDP=9.5 [3.4,31.6]%, LCI=9.0 [7.7,13.7]. Within-visit and inter-visit repeatability of VDP was high. At 16 months there was no single trend of 129Xe-MRI disease progression. Visible 129Xe-MRI ventilation changes were common, which reflected changes in VDP. Based on the within-visit repeatability, a significant short-term change in VDP is >±1.6%. For longer-term follow up, changes in VDP of up to ±7.7% can be expected, or ±4.1% for patients with normal FEV1. No patient had a significant change in FEV1, however 59% had change in VDP >±1.6%. In patients with normal FEV1, there were significant changes in ventilation and in VDP. CONCLUSIONS: 129Xe-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome measure of lung function and endpoint for clinical trials.

Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout.

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIV T). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection-diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIV T strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=-0.79 and r=-0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIV T, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities.

Integrating teaching into everyday clinical practice.

The teaching and training of doctors-in-training in paediatrics has become increasingly challenging in recent times. All too often there is a perception that training must come second to service provision. In this article, the case of a child with community-acquired pneumonia is considered and used to illustrate how a culture of teaching can be embedded in everyday clinical practice.

Congenital absence of the vas deferens and unilateral renal agenesis: implications for patient and family.

BACKGROUND AND AIMS: At routine groin surgery in male paediatric patients occasionally the vas deferens may be absent. This finding usually leads to investigations to establish the status of the contralateral vas deferens and the status of the kidneys. It is not uncommon to find either an ipsilateral renal agenesis or congenital bilateral absence of the vas deferens. The latter finding prompts a test for cystic fibrosis. We report three patients who upon investigation were found to have the rare combination of congenital bilateral absence of the vas deferens and unilateral renal agenesis, and discuss the possible embryological basis, the clinical management and the long-term implications of these findings. PATIENTS AND METHODS: We present three patients who were incidentally found to have absence of the vas deferens whilst undergoing elective groin surgery and following further tests were diagnosed with congenital bilateral absence of the vas deferens and unilateral renal agenesis. The case notes were reviewed, together with the results of radiological investigations, cystic fibrosis screening and the status of the contralateral vas deferens. RESULTS: All three patients were found to have congenital bilateral absence of the vas deferens, unilateral renal agenesis and were not found to have cystic fibrosis. CONCLUSIONS: The combination of congenital bilateral absence of the vas deferens and unilateral renal agenesis, without cystic fibrosis, is rare and not reported previously in the paediatric literature. These findings require appropriate counselling of the parents and child, with regards to the long-term implications of infertility and renal function.

Lung MRI with hyperpolarised gases: current & future clinical perspectives.

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique - hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe - a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

The effect of acute maximal exercise on the regional distribution of ventilation using ventilation MRI in CF.

BACKGROUND: The importance of exercise in the management of people with CF is well recognised, yet the effect of exercise on lung function is not well understood. FEV1 is insensitive to the detection of small changes in lung function. Ventilation MRI and LCI are both more sensitive to mild lung disease than FEV1 and may be better suited to assess the effects of exercise. Here we assessed the short-term effects of maximal exercise on the distribution of ventilation using ventilation MRI and LCI. METHODS: Patients with CF and a range of lung disease were assessed. Baseline LCI and ventilation MRI was followed by a maximal cardio-pulmonary exercise test (CPET). Repeated ventilation MRI was performed within 30 minutes of exercise termination, followed by LCI and finally by FEV1. RESULTS: 13 patients were recruited and completed all assessments. Mean (SD) age was 25 (10) years and mean (SD) FEV1 z-score was -1.8 (1.7). Mean LCI at baseline was 8.2, mean ventilation defect percentage on MRI (VDP) was 7.3%. All patients performed maximal CPET. Post-exercise, there was a visible change in lung ventilation in 85% of patients, including two patients with increased ventilation heterogeneity post-CPET who had normal FEV1. VDP and LCI were significantly reduced post-exercise (p < 0.05) and 45% of patients had a significant change in VDP. CONCLUSIONS: Acute maximal exercise directly affects the distribution of ventilation on ventilation MRI in patients with CF. This suggests that exercise is beneficial in CF and that ventilation MRI is suitable to assess airway clearance efficacy.

Investigating the feasibility of text message reminders to improve adherence to nebulized medication in children and adolescents with cystic fibrosis.

BACKGROUND: Children with cystic fibrosis (CF) often have suboptimal adherence rates to nebulized medication. Adherence barriers cited include forgetting to take the nebulizers, due to busy home and social lives. Text message reminders have been shown to be effective at improving adherence rates in other chronic diseases such as asthma and diabetes. OBJECTIVE: The objective of this study was to assess the feasibility and efficacy of sending text reminders for a prolonged period of time to children with CF. MATERIALS AND METHODS: Children with CF aged 5-16 years taking at least one medication via a nebulizer with an electronic adherence monitor were consented for the study. Text message reminders were sent to participants and/or parents via the hospital's automated text service, up to twice a day, for 6 months. The adherence rates for the 6-month text period were compared to the previous 6 months before the study. Rates were calculated for weekdays, weekends, and school holidays. RESULTS: Seventeen participants were recruited to the study, with a mean age of 12 years and a mean forced expiratory volume in 1 second (FEV1) of 81% predicted. Fifteen children completed the 6-month text period, and I-neb data were accurately analyzed for 13 participants. The mean adherence rate in the 6 months receiving texts was 80%, compared to 81% in the prior 6 months. Overall adherence rates on weekdays, weekends, and school holidays were equivalent during the 2 time periods. A subgroup of patients with moderate baseline adherence showed increased adherence during the text period, particularly at weekends. CONCLUSION: It is feasible to send text message reminders to children with CF, and they are amenable to this approach. Although text reminders do not increase rates in patients with existing optimal adherence, they may be of value in patients with more moderate baseline rates.

Tension pneumatocoele in a child with an empyema.

A previously well 13-month-old child presented to our institution with a pneumonia which developed into a tension pneumatocoele. Management was conservative and the patient fully recovered. Streptococcus pneumoniae type 7F was isolated and is not covered by the current heptavalent vaccine.