Respiratory comorbidities and treatments in Duchenne muscular dystrophy: impact on life expectancy and causes of death.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death. METHODS: All male patients living in Sweden with DMD, born and deceased 1970-2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features. RESULTS: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients. CONCLUSIONS: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia.

Characterization of CFTR mutations in people with cystic fibrosis and severe liver disease who are not eligible for CFTR modulators.

Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. The severe CFLD variant with cirrhosis or portal hypertension has a poor prognosis and life expectancy. CFTR modulator therapies are now available for people with CF and eligibility for such treatment is based on their CFTR genotype. We evaluated the genetic eligibility for elexacaftor, tezacaftor, ivacaftor (ETI), and ivacaftor (IVA) monotherapy in a previously reported CF cohort of 1591 people with CF of whom 171 with severe CFLD. Based on their CFTR mutations, 13% (N=184/1420) of subjects without CFLD and 11% (N=19/171) of those with severe CFLD are not eligible for either ETI or IVA therapy. The non-eligible patients without CFLD or with severe CFLD can currently not take advantage of the potential benefits of these new treatments. Although this study cannot provide any data regarding the effect of ETI or IVA on the progression of severe CFLD, the consequences for ineligibility of patients with extreme liver phenotype may be even more significant because of their poorer disease risk profile.

Turning lung clearance index on its head. Reference data for SF6 multiple-breath washout derived ventilation distribution efficiency.

Cystic fibrosis (CF) lung disease is characterized by increased ventilation inhomogeneity (VI), as measured by multiple-breath washout (MBW). Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulfur hexafluoride (SF6) MBW outcomes, to data collected using updated commercial SF6MBW equipment, and to produce device-specific equations if necessary. SF6MBW was performed in 327 healthy children aged 0.1-18.4 yr [151 (46%) girls], 191 (58.4%) <3 yr. z-Scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression was performed to produce device-specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF (n = 138 test occasions), and 49 adults with lung disease. Historical SF6MBW reference equations were unsuitable for EXHALYZER D data. In contrast to LCI and log10(LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log10(FRC). Significant predictors for VDE and log10(FRC), respectively, were log10(age) and sex, and log10(height), sex, and posture. VDE is potentially a better index of VI than LCI, particularly in more advanced CF lung disease and also for longitudinal monitoring. Further confirmatory clinical studies, particularly longitudinal imaging studies of structural or ventilatory changes, are warranted.NEW & NOTEWORTHY Lung clearance index (LCI) is the most used outcome from the multiple-breath washout test. As known for decades, the LCI is not linearly related to dead space ventilation, giving difficulties interpreting changes over time and in clinical trials. We present a new and improved outcome based on LCI, the ventilation distribution efficiency (VDE), which solves this problem by being linearly related to dead space ventilation. A pediatric age range reference equation for VDE is presented.

Prevalence, trends and outcomes of long-term inhaled antibiotic treatment in people with cystic fibrosis without chronic Pseudomonas aeruginosa infection - A European cystic fibrosis patient registry data analysis.

BACKGROUND: Long-term treatment with inhaled antibiotics is recommended for people with cystic fibrosis (pwCF) chronically infected with Pseudomonas aeruginosa (PA). However, pwCF without chronic PA infection are also commonly treated with inhaled antibiotics. Using data from the European Cystic Fibrosis Patient Registry (ECFSPR) we aimed to determine the prevalence and factors associated with inhaled antibiotic treatment in pwCF without chronic PA infection, and long-term outcomes with inhaled antibiotics use. METHODS: The ECFSPR was searched for pwCF 6 years of age and older who were not chronically infected with PA at baseline. Factors associated with inhaled antibiotic use were first assessed through a logistic regression. From this model a propensity score was computed for each individual, providing the likelihood of being treated with inhaled antibiotics. Long-term outcomes with and without inhaled antibiotics were assessed separately for propensity scores tertiles. RESULTS: 7210 pwCF without chronic PA infection at baseline were included, with 2722 (37.75%) receiving long-term treatment with inhaled antibiotics. Treatment with inhaled antibiotics was more prevalent with severe genotype, diabetes, pancreatic insufficiency, and past infection with chronic PA (OR 3.8, 95% CI, 2.88-5.04). Treatment with inhaled antibiotics was not associated with a reduced risk for acquisition of PA or other resistant pathogens, or with improved lung function decline, mortality, or transplantation. CONCLUSIONS: Many pwCF without chronic PA infection are receiving long-term treatment with inhaled antibiotics despite lack of support from clinical trials or practice guidelines. We did not observe improve outcomes with inhaled antibiotics. Our findings suggest controlled studies evaluating specific inhaled antibiotic regimens targeting specific pathogens or indications be performed to determine their effect.

Persistent Aspergillus fumigatus infection in cystic fibrosis: impact on lung function and role of treatment of asymptomatic colonization-a registry-based case-control study.

BACKGROUND: Aspergillus fumigatus is the most common filamentous fungus isolated from the airways of people with cystic fibrosis (CF). The aim of this study was to investigate how chronic A. fumigatus colonization affects lung function in people with CF, to identify risk factors for colonization, and to evaluate antifungal treatment of asymptomatic Aspergillus colonization. METHODS: Data from 2014-2018 was collected from the Swedish CF registry and medical records. Baseline data before the start of A. fumigatus colonization was compared with the two succeeding years to evaluate how colonization and treatment affected lung function and other clinical aspects. RESULTS: A total of 437 patients were included, of which 64 (14.6%) became colonized with A. fumigatus during the study period. Inhaled antibiotics was associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6-5.9, p < 0.05). Fungal colonization was not associated with a more rapid lung function decline or increased use of IV-antibiotics compared to the non-colonized group, but patients with A. fumigatus had more hospital days, a higher increase of total IgE, and higher eosinophil counts. In the Aspergillus group, 42 patients were considered to be asymptomatic. Of these, 19 patients received antifungal treatment. Over the follow up period, the treated group had a more pronounced decrease in percent predicted Forced Expiratory Volume in one second (ppFEV1) compared to untreated patients (- 8.7 vs - 1.4 percentage points, p < 0.05). CONCLUSION: Inhaled antibiotics was associated with A. fumigatus colonization, but no association was found between persistent A. fumigatus and subsequent lung function decline. No obvious benefits of treating asymptomatic A. fumigatus colonization were demonstrated.

Chest X-rays are less sensitive than multiple breath washout examinations when it comes to detecting early cystic fibrosis lung disease.

AIM: Annual chest X-ray is recommended as routine surveillance to track cystic fibrosis (CF) lung disease. The aim of this study was to investigate the clinical utility of chest X-rays to track CF lung disease. METHODS: Children at Gothenburg's CF centre who underwent chest X-rays, multiple breath washouts and chest computed tomography examinations between 1996 and 2016 were included in the study. Chest X-rays were interpreted with Northern Score (NS). We compared NS to lung clearance index (LCI) and structural lung damage measured by computed tomography using a logistic regression model. RESULTS: A total of 75 children were included over a median period of 13 years (range: 3.0-18.0 years). The proportion of children with abnormal NS was significantly lower than the proportion of abnormal LCI up to the age of 4 years (p < 0.05). A normal NS and a normal LCI at age 6 years were associated with a median (10-90th percentile) total airway disease of 1.8% (0.4-4.7%) and bronchiectasis of 0.2% (0.0-1.5%). CONCLUSION: Chest X-rays were less sensitive than multiple breath washout examinations to detect early CF lung disease. The combined results from both methods can be used as an indicator to perform chest computed tomography less frequently.

Contemporary N2 and SF6 multiple breath washout in infants and toddlers with cystic fibrosis.

INTRODUCTION: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6 MBW commonly viewed as the reference method. The use of N2 MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N2  signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2 MBW,corrected-such as tidal volume reduction during N2 washout with pure O2 . METHOD: This was a longitudinal multicenter cohort study. SF6 MBW and N2 MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N2,original and N2,corrected for comparison with SF6 MBW. RESULTS: Mean functional residual capacity, FRCN2,corrected was 14.3% lower than FRCN2, original , and 1.0% different from FRCSF6 . Lung clearance index, LCIN2,corrected was 25.2% lower than LCIN2,original , and 7.3% higher than LCISF6 . Mean (SD) tidal volume decreased significantly during N2 MBWcorrected , compared to SF6 MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCIN2,corrected and LCISF6 . The absolute differences in LCI increased significantly with higher LCISF6 (0.63/LCISF6 ) and (0.23/LCISF6 ), respectively, for N2,original and N2,corrected , but the relative differences were stable across disease severity for N2,corrected , but not for N2,original . CONCLUSION: Only minor residual differences between FRCN2,corrected and FRCSF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N2 MBW did not affect differences. The corrected N2 MBW can now be used with confidence in young children with CF, although not interchangeably with SF6 .

Ursodeoxycholic acid and liver disease associated with cystic fibrosis: A multicenter cohort study.

BACKGROUND: The efficacy and safety of ursodeoxycholic acid (UDCA) for the treatment of liver disease associated with cystic fibrosis (CF) are under discussion, and clinical practice varies among centers. The study aimed at evaluating if the incidence of severe liver disease differs between CF centers routinely prescribing or not prescribing UDCA. METHODS: We carried out a retrospective multicenter cohort study including 1591 CF patients (1192 patients from UDCA-prescribing centers and 399 from non-prescribing centers) born between 1990 and 2007 and followed from birth up to 31 December 2016. We computed the crude cumulative incidence (CCI) of portal hypertension (PH) at the age of 20 years in the two groups and estimated the subdistribution hazard ratio (HR) through a Fine and Gray model. RESULTS: Over the observation period, 114 patients developed PH: 90 (7.6%) patients followed-up in UDCA prescribing centers and 24 (6.0%) in non-prescribing centers. The CCI of PH at 20 years was 10.1% (95% CI: 7.9-12.3) in UDCA-prescribing and 7.7% (95% CI: 4.6-10.7) in non-prescribing centers. The HR among patients followed in prescribing centers indicated no significant difference in the rate of PH either in the unadjusted model (HR: 1.21, 95% CI: 0.69-2.11) or in the model adjusted for pancreatic insufficiency (HR: 1.28, 95% CI: 0.77-2.12). CONCLUSIONS: CF patients followed-up in UDCA prescribing centers did not show a lower incidence of PH as compared to those followed in centers not prescribing UDCA. These results question the utility of UDCA in reducing the occurrence of severe liver disease in CF.

Improved agreement between N2 and SF6 multiple-breath washout in healthy infants and toddlers with improved EXHALYZER D sensor performance.

Recent studies indicate limited utility of nitrogen multiple-breath washout (N2MBW) in infancy and advocate for using sulfur hexafluoride (SF6) MBW in this age-group. Modern N2MBW systems, such as EXHALYZER D (ECO MEDICS AG, Duernten, Switzerland), use O2 and CO2 sensors to calculate N2 concentrations (in principle, N2% = 100 - CO2% - O2%). High O2 and CO2 concentrations have now been shown to significantly suppress signal output from the other sensor, raising apparent N2 concentrations. We examined whether improved EXHALYZER D N2 signal, accomplished after thorough examination of this CO2 and O2 interaction on gas sensors and its correction, leads to better agreement between N2MBW and SF6MBW in healthy infants and toddlers. Within the same session, 52 healthy children aged 1-36 mo [mean = 1.30 (SD = 0.72) yr] completed SF6MBW and N2MBW recordings (EXHALYZER D, SPIROWARE version 3.2.1) during supine quiet sleep. SF6 and N2 SPIROWARE files were reanalyzed offline with in-house software using identical algorithms as in SPIROWARE with or without application of the new correction factors for N2MBW provided by ECO MEDICS AG. Applying the improved N2 signal significantly reduced mean [95% confidence interval (CI)] differences between N2MBW and SF6MBW recorded functional residual capacity (FRC) and lung clearance index (LCI): for FRC, from 26.1 (21.0, 31.2) mL, P < 0.0001, to 1.18 (-2.3, 4.5) mL, P = 0.5, and for LCI, from 1.86 (1.68, 2.02), P < 0.001, to 0.44 (0.33, 0.55), P < 0.001. Correction of N2 signal for CO2 and O2 interactions on gas sensors resulted in markedly closer agreement between N2MBW and SF6MBW outcomes in healthy infants and toddlers.NEW & NOTEWORTHY Modern nitrogen multiple-breath washout (N2MBW) systems such as EXHALYZER D use O2 and CO2 sensors to calculate N2 concentrations. New corrections for interactions between high O2 and CO2 concentrations on the gas sensors now provide accurate N2 signals. The correct N2 signal led to much improved agreement between N2MBW and sulfur hexafluoride (SF6) MBW functional residual capacity (FRC) and lung clearance index (LCI) in 52 sleeping healthy infants and toddlers, suggesting a role for N2MBW in this age-group.

Th17 associated cytokines in sputum samples from patients with cystic fibrosis.

Cystic fibrosis (CF) is a genetic disease leading to chronic bacterial airway infection and inflammation. T helper 17 (Th17) cells are identified by their production of interleukin (IL)-17A, which recruit neutrophils to the site of airway infection. IL-23 is an important inducer of IL-17 and IL-22 production. The aim of this study was to study the role of Th17 cells in CF airway infection by measuring the levels of Th17 associated cytokines in sputum from CF patients with or without airway infection and by comparison with non-CF-controls. In a cross-sectional screening study, cytokine levels were measured with a Th17 multiplex cytokine ELISA. Significantly lower levels of IL-17A and IL-23 were found in sputa from infected CF patients. The lowest levels of IL-17A were found in patients chronically infected with P. aeruginosa, which also had the lowest IL-17/IL-22 ratio, while children had a higher ratio. Children also had higher IL-23 levels than adults. IL-1ß and IL-10 were significantly lower in CF sputum compared to controls. Thus, in our study CF patients with chronic infections had a lower production of Th17 associated cytokines in sputum compared with non-infected CF patients and infected patient without CF.

End-expiratory lung volume remains stable during N2 MBW in healthy sleeping infants.

We have previously shown that functional residual capacity (FRC) and lung clearance index were significantly greater in sleeping healthy infants when measured by N2 (nitrogen) washout using 100% O2 (oxygen) versus 4% SF6 (sulfur hexafluoride) washout using air. Following 100% O2 exposure, tidal volumes decreased by over 30%, while end-expiratory lung volume (EELV, i.e., FRC) rose markedly based on ultrasonic flow meter assessments. In the present study to investigate the mechanism behind the observed changes, N2 MBW was performed in 10 separate healthy full-term spontaneously sleeping infants, mean (range) 26 (18-31) weeks, with simultaneous EELV monitoring (respiratory inductance plethysmography, RIP) and oxygen uptake (V´O2 ) assessment during prephase air breathing, during N2 washout by exposure to 100% O2 , and subsequently during air breathing. While flow meter signals suggested a rise in ELLV by mean (SD) 26 (9) ml over the washout period, RIP signals demonstrated no EELV change. V'O2 /FRC ratio during air breathing was mean (SD) 0.43 (0.08)/min, approximately seven times higher than that calculated from adult data. We propose that our previously reported flow meter-based overestimation of EELV was in fact a physiological artifact caused by rapid and marked movement of O2 across the alveolar capillary membrane into the blood and tissue during 100% O2 exposure, without concomitant transfer of N2 to the same degree in the opposite direction. This may be driven by the high observed O2 consumption and resulting cardiac output encountered in infancy. Furthermore, the low resting lung volume in infancy may make this error in lung volume determination by N2 washout relatively large.

Risk factors for progression of structural lung disease in school-age children with cystic fibrosis.

BACKGROUND: Computed tomography (CT) is used to monitor progression of structural lung disease (SLD) in children with cystic fibrosis (CF). Our goals were to identify the risk factors for the annual progression of SLD and the impacts of airway pathogens on SLD. METHOD: Seventy-five school-aged children diagnosed with CF underwent 200 CT scans at Gothenburg CF Centre in the period 2003-2015. SLD was evaluated with a quantitative scoring system. Mixed models were used to calculate the yearly progression rates of SLD and FEV1 and to analyse the effects of common airway pathogens in CF. RESULTS: The yearly mean progression (95% CI) rates for total disease (%Dis), bronchiectasis (%Be), and FEV1 were 0.62 (0.38-0.86), 0.43 (0.28-0.58) and -0.16 (-0.18-0.13), respectively. Adjusting for airway pathogens, the yearly mean progression rates for %Dis, %Be and FEV1 were 0.23 (-0.04-0.51), 0.12 (0.00-0.25), and -0.12 (-0.16-0.08), respectively. A single infection with P aeruginosa was associated with significant increase in lung damage, assessed as %Dis (p = 0.044) and%Be (p = 0.0047), but not in FEV1 (p = 0.96). At age of 7 years, there was a good correlation between the extent of SLD and subsequent progression of %Dis (r = 0.63, p = 0.0042) and %Be (r = 0.74, p = 0.0057) while there was no significant correlation between the FEV1 and the rate of decline of FEV1 (r = -0.22, p = 0.12). CONCLUSION: Intermittent respiratory infections with P aeruginosa were associated with significant SLD but no change in FEV1. More SLD at the age of 7 years signals a higher progression rate of SLD subsequently.

Variability of lung clearance index in clinically stable cystic fibrosis lung disease in school age children.

BACKGROUND: Data on long term variability of Lung Clearance Index (LCI) in Cystic Fibrosis (CF) is urgently needed to guide test result interpretation. Our aim was to evaluate LCI variability in clinically stable CF lung disease in school age children. METHODS: Paediatric patients, aged 6 to 17years, attending the outpatient CF clinic performed Multiple Breath Nitrogen Washout (Exhalyzer® D) and spirometry every third month over a period of one year. Clinical stability was assessed by the Cystic Fibrosis Clinical Score (CFCS) at each visit. RESULTS: Twentyfive children were recruited: baseline median (range) FEV1% pred. 91 (55-122)%, LCI 9.1 (6.4-18.6), CFCS 15 (12-23). A total of 107 visits were included in the study, of which 93% were defined as clinically stable. In clinically stable visits, within-subject variability of LCI and FEV1% pred. were 10% and 16%, respectively. The upper limit of normal (ULN, 95% percentile) of LCI variability during clinical stability was 17%. CONCLUSIONS: LCI within-subject variability was low and comparable to FEV1% pred. which strengthen the use of LCI to monitor lung disease progression in CF patients. An increase in LCI >17% compared to previous LCI-measurement in clinically stable CF patients may therefore indicate early lung disease progression.

The effect of inert gas choice on multiple breath washout in healthy infants: differences in lung function outcomes and breathing pattern.

The detrimental effects on breathing pattern during multiple breath inert gas washout (MBW) have been described with different inhaled gases [100% oxygen (O2) and sulfur hexafluoride (SF6)] but detailed comparisons are lacking. N2- and SF6-based tests were performed during spontaneous quiet sleep in 10 healthy infants aged 0.7-1.3 yr using identical hardware. Differences in breathing pattern pre and post 100% O2 and 4% SF6 exposure were investigated, and the results obtained were compared [functional residual capacity (FRC) and lung clearance index (LCI)]. During 100% O2 exposure. mean inspiratory flow ("respiratory drive") decreased transiently by mean (SD) 28 (9)% ( P < 0.001), and end-tidal CO2 (carbon dioxide) increased by mean (SD) 0.3 (0.4)% units ( P < 0.05) vs. air breathing prephase. During subsequent N2 washin (i.e., recovery phase), the pattern of change reversed. No significant effect on breathing pattern was observed during SF6 testing. In vitro testing confirmed that technical artifacts did not explain these changes. Mean (SD) FRC and LCI in vivo were significantly higher with N2 vs. SF6 washout: 216 (33) vs. 186 (22) ml ( P < 0.001) and 8.25 (0.85) vs. 7.55 (0.57) turnovers ( P = 0.021). Based on these results, SF6 based MBW is the preferred methodology for tests in this age range. NEW & NOTEWORTHY Inert gas choice for multiple breath inert gas washout (MBW) in infants has important consequences on both breathing pattern during test performance and the functional residual capacity and lung clearance index values obtained. Data suggest the detrimental effect of breathing pattern of 100% O2 and movement of O2 across the alveolar capillary membrane, with direct effects on MBW outcomes. SF6 MBW during infancy avoids this and can be further optimized by addressing the sources of technical artifact identified in this work.

Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme.

Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report.

The lung clearance index (LCI) is a lung function parameter derived from the multiple-breath washout (MBW) test. Although first developed 60 years ago, the technique was not widely used for many years. Recent technological advances in equipment design have produced gains in popularity for this test among cystic fibrosis (CF) researchers and clinicians, particularly for testing preschool-aged children. LCI has been shown to be feasible and sensitive to early CF lung disease in patients of all ages from infancy to adulthood. A workshop was convened in January 2014 by the North American Cystic Fibrosis Foundation to determine the readiness of the LCI for use in multicenter clinical trials as well as clinical care. The workshop concluded that the MBW text is a valuable potential outcome measure for CF clinical trials in preschool-aged patients and in older patients with FEV1 in the normal range. However, gaps in knowledge about the choice of device, gas, and standardization across systems are key issues precluding its use as a clinical trial end point in infants. Based on the current evidence, there are insufficient data to support the use of LCI or MBW parameters in the routine clinical management of patients with CF.

European Cystic Fibrosis Society Standards of Care: Framework for the Cystic Fibrosis Centre.

A significant increase in life expectancy in successive birth cohorts of people with cystic fibrosis (CF) is a result of more effective treatment for the disease. It is also now widely recognized that outcomes for patients cared for in specialist CF Centres are better than for those who are not. Key to the effectiveness of the specialist CF Centre is the multidisciplinary team (MDT), which should include consultants, clinical nurse specialist, microbiologist, physiotherapist, dietitian, pharmacist, clinical psychologist, social worker, clinical geneticist and allied healthcare professionals, all of whom should be experienced in CF care. Members of the MDT are also expected to keep up to date with developments in CF through continued professional development, attendance at conferences, auditing and involvement in research. Specialists CF Centres should also network with other Centres both nationally and internationally, and feed Centre data to registries in order to further the understanding of the disease. This paper provides a framework for the specialist CF Centre, including the organisation of the Centre and the individual roles of MDT members, as well as highlighting the value of CF organisations and disease registries.