[Show abstract][Hide abstract] ABSTRACT: There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.
[Show abstract][Hide abstract] ABSTRACT: The Quanjer et al. Global Lung Function Initiative (GLI)-2012 multi-ethnic all-age reference equations for spirometry are endorsed by all major respiratory societies and are the new gold standard. Before the GLI equations are implemented for use in CF patients, the impact of changing equations from those currently used needs to be better understood.
Annual review data submitted to the UK CF Trust Registry between 2007 and 2011 were used to calculate %predicted FEV1, FVC and FEV1/FVC using three widely used reference equations (Wang-Hankinson and Knudson) and the new GLI-2012 equations.
Overall, Knudson and Wang equations overestimated %predicted values in paediatric patients, such that a greater proportion of patients had lung function values in the normal range. Within individual patients, the impact of switching equations varied greatly depending on the patients' age, and which equations were used.
A unified approach to interpreting spirometric lung function measurements would help facilitate more appropriate comparison both within and between centres and countries. Interpretation of longitudinal measurements using a continuous reference equation across all-ages, like the GLI, may further improve our understanding of CF lung disease.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 12/2013; · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants.
To assess changes in pulmonary function during the first year of life in CF NBS infants.
Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV0.5) were measured at 3 months and 1 year of age.
Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV0.5 improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p<0.01) in CF infants between 3 months and 1 year, and by 1 year, FEV0.5 was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRCpleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV0.5 at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year.
This is the first study reporting improvements in FEV0.5 over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.
[Show abstract][Hide abstract] ABSTRACT: Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.
[Show abstract][Hide abstract] ABSTRACT: Cystic Fibrosis (CF) lung disease starts early in life and progresses even in the absence of clinical symptoms. Therefore, sensitive outcome measures to quantify and track these early abnormalities in infants and young children are needed; both for clinical care and interventional trials. Currently, the efficacy of most therapeutic interventions in CF has not been tested in children under the age of 6 years and drug development programs have focused on assessing safety rather than efficacy in this age group. This article summarizes the current status for outcome measures that can be utilized in clinical trials in infants and children with CF. Two methodologies are specifically highlighted in this review; chest computed tomography to assess structural damage of the lung and multiple breath washout as a technique to quantify ventilation inhomogeneity. While not all questions regarding the utility of these outcome measures in infants and young children have been resolved, significant advances have been made and it now appears feasible to design and conduct adequately powered efficacy studies in this age group. This could be a crucial step to further improve outcomes in CF patients as initiating effective treatment early is considered essential to prevent permanent lung damage.
European Respiratory Journal 03/2013; · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: At our hospital the current model of care for children with moderate-severe CF is focused on intensive inpatient intervention, regular outpatient clinic review and specialist outreach care as required. An alternative model providing more regular physiotherapy and dietetic outreach support, in addition to these specialist services, may be more effective. METHODS: 16 children (4 male; 12 female; mean age 10.9±2.93; range 4-15years) who required >40days of IV antibiotics in the 12-months pre-intervention were enrolled. Physiotherapy included weekly-supervised exercise sessions, alongside regular review of home physiotherapy regimens. Dietetic management included 1-2 monthly monitoring of growth, appetite, intake and absorption, and nutrition education sessions. RESULTS: There was a 23% reduction in inpatient IV antibiotic requirement and 20% reduction in home IV antibiotic requirement during the intervention year. Cost-benefit analyses showed savings of £113,570. VO(2Peak) increased by 4.9ml·kg·min(-1) (95%CI 1.01 to 8.71; p=0.02), and 10m-MSWT distance and increment achieved increased by 229m (95%CI 109 to 350; p<0.001) and 2 levels (95%CI 1 to 3; p<0.002) respectively. No significant differences in physiological and patient reported outcomes were demonstrated, although there was a possible trend towards improvement in outcomes when compared to the pre-intervention year. CONCLUSION: This pilot programme demonstrated a reduction in IV and admission requirements with a cost benefit in a small group of children with moderate-severe CF. A fully powered clinical trial is now warranted.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 02/2013; · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inert gas washout tests, performed using the single or multiple breath washout technique (SBW and MBW, respectively), were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests such as spirometry as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence-based where possible but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.
European Respiratory Journal 02/2013; · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge of short and longer-term repeatability of lung function in health and disease is essential to determine bronchodilator reversibility (BDR) thresholds and to recognise if changes in lung function represent disease progression, therapeutic intervention or normal variability.Multiple-breath washout (MBW) indices (lung clearance index [LCI], conductive ventilation inhomogeneity [Scond]) and specific airways resistance (sRaw) were measured in healthy children and stable wheezers. Measurements were performed at baseline and after 20 minutes without intervention to assess repeatability and determine BDR thresholds. BDR was assessed by repeating baseline measurements 20 minutes after inhaled salbutamol.Twenty-eight healthy controls, mean age 6.1 (SD 0.7)y and 62 wheezers 5.4 (0.6)y were tested. Baseline variability in MBW indices and sRaw was not significantly different between wheezers and healthy controls. Significant BDR was only observed in wheezers for Scond (16%); but in both wheezers (37%) and healthy controls (20%) for sRaw. Some wheezers and healthy controls demonstrated increases in MBW indices post-bronchodilator.LCI and sRaw demonstrate low baseline variability in health and disease. Neither MBW indices nor sRaw are ideal for assessing BDR in young children with stable wheeze. These findings will help interpret effect of therapeutic interventions in children with respiratory diseases.
European Respiratory Journal 12/2012; · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The lung clearance index(LCI) is more sensitive than spirometry in detecting abnormal lung function in children with cystic fibrosis. LCI is thought to be independent of age, but recent evidence suggests that the upper limit of normal is higher in infants and preschool children than in older subjects. This study examines whether LCI remains independent of body size throughout childhood.Multiple breath washout data from healthy children and adolescents were collated from three centres using the Mass Spectrometer system and inert gas SF6. Reference equations for LCI and functional residual capacity (FRC) were constructed using the LMS (Lambda, Mu, Sigma) method.Data were available from 497 subjects (2weeks to 19 years old) tested on 659 occasions. LCI was dependent on body size, decreasing in a non-linear pattern as height increases. Changes were particularly marked in the first five years of life. Height, age and sex were all independent predictors of FRC. Minimal between-centre differences allowed unified reference equations to be developed.LCI is not independent of body size. Although a constant upper normal limit would suffice for cross-sectional clinical assessments from six years of age, appropriate reference equations are essential for accurate interpretation of results during early childhood.
European Respiratory Journal 11/2012; · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is unclear whether or not the ciliary function following lung transplantation is normal. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation.We studied the ciliary beat frequency (CBF) and beat pattern using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 Cystic Fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients.Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median [IQR] CBF: 10.5 [9.0-11.4]Hz vs 7.4 [6.4-9.2]Hz; p<0.01) and increased dyskinesia (median [IQR] dyskinesia index: 16.5 [12.9-28.2]% vs 42.2 [32.6-56.4]%; p<0.01). In both CF and NSLD groups, compared to epithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post transplant 7-12 months).Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation.
European Respiratory Journal 04/2012; · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Forty-one Mycobacterium abscessus complex isolates from 17 pediatric cystic fibrosis (CF) patients were typed using a novel variable-number tandem repeat (VNTR) scheme and an automated repetitive-PCR (rep-PCR) system. Both VNTR and rep-PCR typing methods differentiate between members of the M. abscessus complex. The isolates from individual patients are indistinguishable, and the data strongly suggest that individual CF patients are persistently infected with one strain and also suggests that different CF patients can harbor the same strain.
Journal of clinical microbiology 03/2012; 50(5):1758-61. · 4.23 Impact Factor