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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.

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.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.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.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.

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.

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.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.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%).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.

Introduction 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 sulphur hexafluoride (SF

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.

IntroductionCystic fibrosis (CF) is characterized by increased ventilation inhomogeneity (VI), as measured by multiple breath washout (MBW), from infancy. Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulphur hexafluoride (SF6) MBW outcomes, to data collected using updated commercial SF6MBW equipment and to produce device specific equations if necessary.MethodSF6MBW was performed in 327 healthy children aged 0.1-18.4 years (151 [46%] girls), 191 (58.4%) < 3 years. Z-scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression 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.ResultsHistorical 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 gender, and log10(height), gender and posture.Conclusion1/LCI (e.i., FRC/CEV[%]) reflecting ventilation distribution efficiency (VDE) in the lungs was a superior index of ventilation inhomogeneity compared to LCI and log10(LCI) due to its linear relationship to VD/VT.

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.

Introduction: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6MBW commonly viewed as the reference method. The use of N2MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N2signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2MBW,corrected—such as tidal volume reduction during N2 washout with pure O2. Method: This was a longitudinal multicenter cohort study. SF6MBW and N2MBW 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 SF6MBW. 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 N2MBWcorrected, compared to SF6MBW (−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 N2MBW did not affect differences. The corrected N2MBW can now be used with confidence in young children with CF, although not interchangeably with SF6.

Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SFThis was a longitudinal multicenter cohort study. SFMean functional residual capacity, FRCOnly minor residual differences between FRC

Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/10 0 0 pwCF. Incidence was higher in lung-transplanted patients (n = 23) versus non transplanted patients (n = 107) (8.43 versus 2.36 cases/10 0 0). Incidence was higher in pwCF versus the age-matched general population in the age groups < 15, 15-24, and 25-49 years (p < 0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p = 0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Recent studies indicate limited utility of nitrogen multiple-breath washout (N

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.

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.

Background Monitoring changes in the epidemiology of cystic fibrosis (CF) pathogens is essential for clinical research, quality improvement, and clinical management. Methods We analyzed data reported to the European Cystic Fibrosis Society Patient Registry (ECFSPR) from 2011 to 2016 to determine the overall and the age-specific annual prevalence and incidence of selected CF pathogens and their trends during these years. The ECFSPR collects data on three chronic infections: Pseudomonas aeruginosa (PsA), Burkholderia cepacia complex Species (BCC) and Staphylococcus aureus (SA), as well as on the occurrence of non-tuberculous mycobacteria (NTM) and Stenotrophomonas maltophilia (SM). The same analyses were performed for different country groups, according to their gross national income (GNI). Results The pathogens with the highest prevalence were SA and PsA, with prevalence, in 2016, equal to 38.3% and 29.8% respectively, followed by SM (8.1%). The pathogens with the lowest prevalence were NTM (3.3%) and BCC (3.1%). The overall prevalence and incidence significantly decreased for PsA; they also decreased for BCC, while they increased significantly for SA. The overall prevalence of NTM and SM increased significantly. The most considerable prevalence changes were observed for PsA, which decreased across all income country groups and all age strata (with the exception of 0–1 years) The prevalence and incidence of pathogens differed significantly according to GNI. Conclusions The epidemiology of CF pathogens in Europe has changed; epidemiologic data differ significantly among countries with different socio-economic status. The causes of these observations are multifactorial and include improvements in clinical care and infection control.

Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678

Streszczenie Istotny wzrost oczekiwan wzgledem zycia kolejnych grup osob z mukowiscydozą ( cystic fibrosis ; CF) wynika ze skuteczniejszego leczenia choroby. Obecnie juz powszechnie wiadomo, ze wyniki leczenia znajdujących sie pod opieką specjalistycznych centrow mukowiscydozy są lepsze w porownaniu z wynikami pacjentow nieobjetych taką opieką. Kluczem do skuteczności specjalistycznych centrow mukowiscydozy jest wielodyscyplinarny zespol ( multidisciplinary team ; MDT), w sklad ktorego powinni wchodzic konsultanci, specjalista pielegniarstwa, mikrobiolog, fizjoterapeuta, dietetyk, farmaceuta, psycholog kliniczny, pracownik socjalny, genetyk kliniczny i związani z nimi pracownicy sluzby zdrowia – wszyscy doświadczeni w opiece nad pacjentami z CF. Od czlonkow MDT oczekuje sie rowniez biezącej wiedzy dotyczącej nowych odkryc z zakresu CF, ciąglego rozwoju osobistego, uczestnictwa w konferencjach, audytach i badaniach. Specjalistyczne centra CF powinny wraz z innymi krajowymi i miedzynarodowymi ośrodkami tworzyc jedną siec oraz wpisywac swoje dane do rejestrow, co zwieksza mozliwośc zrozumienia choroby. Niniejszy artykul ma na celu określenie ram specjalistycznego centrum CF, w tym organizacji centrum, oraz indywidualnych rol czlonkow MDT, jak rowniez naświetlenie wartości organizacji CF i rejestrow choroby.

Background The aim of this position statement was to inform the choice of physical activity tools for use within CF research and clinical settings. Methods A systematic review of physical activity tools to explore evidence for reliability, validity, and responsiveness. Narrative answers to "four key questions" on motion sensors, questionnaires and diaries were drafted by the core writing team and then discussed at the Exercise Working Group in ECFS Lisbon 2013. Results and summary Our current position is that activity monitors such as SenseWear or ActiGraph offer informed choices to facilitate a comprehensive assessment of physical activity, and should as a minimum report on dimensions of physical activity including energy expenditure, step count and time spent in different intensities and sedentary time. The DigiWalker pedometer offers an informed choice of a comparatively inexpensive method of obtaining some measurement of physical activity. The HAES represents an informed choice of questionnaire to assess physical activity. There is insufficient data to recommend the use of one diary over another. Future research should focus on providing additional evidence of clinimetric properties of these and new physical activity assessment tools, as well as further exploring the added value of physical activity assessment in CF.

Background Genotyping of Pseudomonas aeruginosa ( P.a ) is used for surveillance at our CF clinic. Methods P.a from 1999 to 2012 were analysed, using pulsed-field gel electrophoresis (PFGE) and multiple-locus variable number of tandem repeats analysis (MLVA). Results Among 232 isolates from 104 patients, we identified 78 unique strains, of which 56 were isolated from individual patients. The B-clone was isolated from 13 patients and the camp transmission clone J-strains from 8 patients at the start of the study. There was no indication of transmission within the clinic. PFGE and MLVA clone identification was in 91% agreement. For patients who provided more than 2 P.a isolates, similar strains were identified over time for 45/49 chronically- and for 6/16 intermittently-colonized patients despite, periods of no detectable P.a after eradication therapy. Conclusions Analyses revealed high genotypic diversity, acceptable outcome of eradication therapy and no indication of cross-infection at the CF centre.

© 2015 Wolters Kluwer Health, Inc. Preferential flowand transport throughmacropores affect plant water use efficiency and enhance leaching of agrochemicals and the transport of colloids, thereby increasing the risk for contamination of groundwater resources. The effects of soil compaction, expressed in terms of bulk density (BD), and organic carbon (OC) content on preferential flow and transport were investigated using 150 undisturbed soil cores sampled from 15 15-mgrids on two field sites. Both fields had loamy textures, but one site had significantly higher OC content. Leaching experiments were conducted in each core by applying a constant irrigation rate of 10mmh-1 with a pulse application of tritium tracer. Five percent tritium mass arrival times and apparent dispersivities were derived from each of the tracer breakthrough curves and correlated with texture, OC content, and BD to assess the spatial distribution of preferential flow and transport across the investigated fields. Soils fromboth fields showed strong positive correlations between BD and preferential flow. Interestingly, the relationships between BD and tracer transport characteristics were markedly different for the two fields, although the relationship between BD and macroporosity was nearly identical. The difference was likely caused by the higher contents of fines and OC at one of the fields leading to stronger aggregation, smaller matrix permeability, and a more pronounced pipe-like pore system with wellaligned macropores.

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.

Introduction: Cystic fibrosis (CF) lung disease is characterized by uneven ventilation distribution, which can be measured by the N 2 multiple breath washout (MBW) and the vital capacity single breath washout (VC SBW) test. A MBW test is more time consuming than a VC SBW test. Aims: To determine the prevalence of abnormal MBW and SBW test results in teenagers and adults with CF. Methods: Spirometry and triplicates of N 2 MBW and N 2 VC SBW were performed in 31 subjects (9 females) with CF, aged 13-45 yrs (median 23 yrs) using the Exhalyzer D washout device. Washout results were related to 400 healthy control subjects for N 2 MBW and 224 for N 2 VC SBW. Results: FEV 1 was abnormal in 7/31 (23%) subjects, VC SBW phase III slope (S III ) was abnormal in 20/31 (65%), LCI 29/31 (94%), S cond 30/31 (97%), S acin 24/31 (77%) and fast-to-slow regions specific ventilation ratio in 30/31 (97%). Among the 11 subjects with normal VC SBW S III , 10 (91%) showed abnormal MBW results. Consclusions: Abnormal N 2 VC SBW S III was seen in the majority of teenagers and adult CF subjects with normal FEV 1 , suggesting additional value of this method, but normal S III does not exclude pathological MBW outcomes.

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) FEV 1 % 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 FEV 1 % 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 FEV 1 % 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.

Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis–derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28–18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r2 = 0.70, P < 0.001) vs. Sacin (r2 = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis.

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.

The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the group's work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF. © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V.

BackgroundThe quality of chest Computed Tomography (CT) images in children is dependent upon a sufficient breath hold during CT scanning. This study evaluates the influence of spirometric breath hold monitoring with biofeedback software on inspiratory and expiratory chest CT lung density measures, and on trapped air (TA) scoring in children with cystic fibrosis (CF). This is important because TA is an important component of early and progressive CF lung disease.MethodsA cross sectional comparison study was completed for chest CT imaging in two cohorts of CF children with comparable disease severity, using spirometric breath hold monitoring and biofeedback software (Copenhagen (COP)) or unmonitored breath hold manoeuvres (Gothenburg (GOT)). Inspiratory–expiratory lung density differences were calculated, and TA was scored to assess the difference between the two cohorts.ResultsEighty-four chest CTs were evaluated. Mean (95%CI) change in inspiratory–expiratory lung density differences was 436 Hounsfield Units (HU) (408 to 464) in the COP cohort with spirometric breath hold monitoring versus 229 HU (188 to 269) in the GOT cohort with unmonitored breath hold manoeuvres (p

It is known that solute transport through soil is heterogeneous at all spatial scales. However, little data are available to allow quantification of these heterogeneities at the field scale or larger. In this study, we investigated the spatial patterns of soil properties, hydrologic state variables, and tracer breakthrough curves (BTCs) at the field scale for the inert solute transport under a steady-state irrigation rate which produced near-saturated conditions. Sixty-five undisturbed soil columns approximately 20 cm in height and diameter were sampled from the loamy topsoil of an agricultural field site in Silstrup (Denmark) at a sampling distance of approximately 15 m (with a few exceptions), covering an area of approximately 1 ha (60 m x 165 m). For 64 of the 65 investigated soil columns, we observed BTC shapes indicating a strong preferential transport. The strength of preferential transport was positively correlated with the bulk density and the degree of water saturation. The latter suggests that preferential macropore transport was the dominating transport process. Increased bulk densities were presumably related with a decrease in near-saturated hydraulic conductivities and as a consequence to larger water saturation and the activation of larger macropores. Our study provides further evidence that it should be possible to estimate solute transport properties from soil properties such as soil texture or bulk density. We also demonstrated that estimation approaches established for the column scale have to be upscaled when applied to the field scale or larger. Citation: Koestel, J. K., T. Norgaard, N. M. Luong, A. L. Vendelboe, P. Moldrup, N. J. Jarvis, M. Lamande, B. V. Iversen, and L. Wollesen de Jonge (2013), Links between soil properties and steady-state solute transport through cultivated topsoil at the field scale, Water Resour. Res., 49, doi: 10.1002/wrcr.20079.

Background: Chronic graft-versus-host disease (GvHD) in the lungs is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) affecting the peripheral airways as obliterative bronchiolitis. Multiple Breath Washout (MBW) is a sensitive method for assessing the function of the small peripheral airways. The aim of this study was to examine whether MBW can facilitate an earlier diagnosis of lung GvHD. Methods: 110 children (mean age: 9,6 years) underwent allogeneic HSCT in Queen Silvias Children Hospital between 2006 and 2014. LCI (Lung Clearing Index) was determined in 62 children using MBW with sulphur hexafluoride (SF6) as tracer gas before and one year after HSCT. All children ≥ 6 years also performed spirometry. Results: Overall there was no significant difference in mean LCI before (7.09(0,8 SD)) and after HSCT (7.47(1,41 SD)) (p: 0.056). In 11/62 children LCI increased ≥ 1 unit one year after HSCT . 4 of these children were diagnosed with lung GvHD (3 within one year from HSCT and one after 3 years) based on clinical symptoms and lungfunction tests. LCI in children who developed lung GvHD was 6.60 (0.16 SD) before and 9,93 (2,79 SD) one year after HSCT. The other seven children with increased LCI ≥ 1 unit at one year have had repeated airway infections causing increased LCI. No child with an incease in LCI Conclusion: MBW can be used to identify children with lung GvHD after allogeneic HSCT. For earlier detection of lung GvHD, MBW should probably be done earlier than one year post HSCT. Prospective studies are required to confirm this.

In intensely cultivated regions, it is crucial to have knowledge of the leaching potential related to pesticides in agricultural production. This is especially true in countries, like Denmark, that base its drinking water supply on untreated groundwater. Since fluazifop-P-butyl (FPB) is applied to control perennial and annual weed grasses in agricultural fields, the objective of this study was to evaluate leaching of its two degradation products – fluazifop-P (FP; free acid; (R)-2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid) and TFMP (5-(trifluoromethyl)-2(1H)-pyridinone) – through an agricultural field consisting of loamy soil. Drainage and groundwater samples were collected over a five-year period following four spring/summer applications of FPB, and analysed for both FP and TFMP. FP was only detected once in groundwater, whereas TFMP within the first year after the first and fourth application was detected in concentrations exceeding the value of 0.1 µg L-1 in 100% and 24% of the drainage samples and 9% and 14% of the groundwater samples, respectively. Detections of TFMP up to 18 months after application were obtained both in the drainage and groundwater. What differentiated the first and fourth FPB applications from the two others were heavy precipitation events within one week of FPB application, which resulted in rapid transport of TFMP through the discontinuities in the soil and contributed to relatively high TFMP detections in drainage and groundwater. This study indicated that pesticide degradates like TFMP, often being more soluble than the pesticide, have a relatively high leaching potential especially associated with heavy precipitation events shortly after the application. Hence, such pesticide degradates should like in Denmark be considered “relevant” meaning that the EU value for drinking water applies to them, having its leaching potential regulatory assessed based on high quality estimations of their persistence, and be exposed to an assessment of the risk to consumers of drinking contaminated groundwater.

In view of their crucial role in water and solute transport, enhanced monitoring of agricultural subsurface drain tile systems is important for adequate water quality management. However, existing monitoring techniques for flow and contaminant loads from tile drains are expensive and labour intensive. The aim of this study was to develop a cost-effective and simple method for monitoring loads from tile drains. The Flowcap is a modified Sutro weir (MSW) unit that can be attached to the outlet of tile drains. It is capable of registering total flow, contaminant loads and flow-averaged concentrations. The MSW builds on a modern passive sampling technique that responds to hydraulic pressure and measures average concentrations over time (days to months) for various substances. Mounting the samplers in the MSW allowed a flow-proportional part of the drainage to be sampled. Laboratory testing yielded high linear correlation between the accumulated sampler flow, q total, and accumulated drainage flow, Q total (r (2) > 0.96). The slope of these correlations was used to calculate the total drainage discharge from the sampled volume, and therefore contaminant load. A calibration of the MSW under controlled laboratory condition was needed before interpretation of the monitoring results was possible. The MSW does not require a shed, electricity, or maintenance. This enables large-scale monitoring of contaminant loads via tile drains, which can improve contaminant transport models and yield valuable information for the selection and evaluation of mitigation options to improve water quality. Results from this type of monitoring can provide data for the evaluation and optimisation of best management practices in agriculture in order to produce the highest yield without water quality and recipient surface waters being compromised.

Multiple-breath inert gas washout (MBW) is ideally suited for early detection and monitoring of serious lung disease, such as cystic fibrosis, in infants and young children. Validated commercial options for the MBW technique are limited, and suitability of nitrogen (N2)-based MBW is of concern given the detrimental effect of exposure to pure O2 on infant breathing pattern. We propose novel methodology using commercially available N2 MBW equipment to facilitate 4% sulfur hexafluoride (SF6) multiple-breath inert gas wash-in and washout suitable for the infant age range. CO2, O2, and sidestream molar mass sensor signals were used to accurately calculate SF6 concentrations. An improved dynamic method for synchronization of gas and respiratory flow was developed to take into account variations in sidestream sample flow during MBW measurement. In vitro validation of triplicate functional residual capacity (FRC) assessments was undertaken under dry ambient conditions using lung models ranging from 90 to 267 ml, with tidal volumes of 28-79 ml, and respiratory rates 20–60 per minute. The relative mean (SD, 95% confidence interval) error of triplicate FRC determinations by washout was −0.26 (1.84, −3.86 to +3.35)% and by wash-in was 0.57 (2.66, −4.66 to +5.79)%. The standard deviations [mean (SD)] of percentage error among FRC triplicates were 1.40 (1.14) and 1.38 (1.32) for washout and wash-in, respectively. The novel methodology presented achieved FRC accuracy as outlined by current MBW consensus recommendations (95% of measurements within 5% accuracy). Further clinical evaluation is required, but this new technique, using existing commercially available equipment, has exciting potential for research and clinical use.

The aim of this update is to describe the paediatric highlights from the 2011 European Respiratory Society (ERS) Annual Congress in Amsterdam, the Netherlands. Abstracts from all seven groups of the ERS Paediatric Assembly (Paediatric Respiratory Physiology, Paediatric Asthma and Allergy, Cystic Fibrosis, Paediatric Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Paediatric Respiratory Epidemiology, and Paediatric Bronchology) are presented in the context of current literature.

The black-pigmented fungus Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens from CF patients, transplant recipients, and subjects with other respiratory disorders in Sweden. Second, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples ( n = 492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens from 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6 to 25 days of incubation on erythritol-chloramphenicol agar (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples ( P = 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis . In conclusion, E. dermatitidis is a frequent colonizer of the respiratory tract in CF patients in Sweden and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic remains to be elucidated.