Lung function over the life course of paediatric and adult patients with cystic fibrosis from a large multi-centre registry

Abstract A key measure of lung function in people with Cystic Fibrosis (CF) is Forced Expiratory Volume in the first second FEV1 percent predicted (FEV1pp). This study aimed to address challenges in identifying predictors of FEV1pp, specifically dealing with non-linearity and the censoring effect of death. Data was obtained from a large multi-centre Australian Cystic Fibrosis Data Registry (ACFDR). A linear mixed model was used to study FEV1pp as the endpoint. There were 3655 patients (52.4% male) included in our study. Restricted cubic splines were used to fit the non-linear relationship between age of visit and FEV1pp. The following predictors were found to be significant in the multivariate model: age of patient at visit, BMI z-score, age interaction with lung transplantation, insulin dependent diabetes, cirrhosis/portal hypertension, pancreatic insufficiency, Pseudomonas aeruginosa infection and baseline variability in FEV1pp. Those with P. aeruginosa infection had a lower mean difference in FEV1pp of 4.7 units, p < 0.001 compared to those who did not have the infection. Joint modelling with mortality outcome did not materially affect our findings. These models will prove useful for to study the impact of CFTR modulator therapies on rate of change of lung function among patients with CF.

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Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study

Thorax ◽

10.1136/thoraxjnl-2019-213179 ◽

2019 ◽

Vol 75 (2) ◽

pp. 123-131 ◽

Cited By ~ 6

Author(s):

Daniela K Schlüter ◽

Kevin W Southern ◽

Carol Dryden ◽

Peter Diggle ◽

David Taylor-Robinson

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Clinical Outcomes ◽

Health Inequalities ◽

Social Inequalities ◽

Forced Expiratory Volume ◽

Rate Of Change ◽

Average Weight ◽

The Uk ◽

The Impact

BackgroundNewborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear.MethodsWe undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV1) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders.ResultsNBS was associated with higher average lung function trajectory (+1.56 FEV1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (−0.02 SD per year; 95% CI −0.03 to −0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life.ConclusionsChildren diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.

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Discrepancy between Lung Function Measurements at Home and in the Hospital in Children with Asthma and CF

Journal of Clinical Medicine ◽

10.3390/jcm9061617 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1617 ◽

Cited By ~ 2

Author(s):

Frederick L.G.R. Gerzon ◽

Quirijn Jöbsis ◽

Michiel A.G.E. Bannier ◽

Bjorn Winkens ◽

Edward Dompeling

Keyword(s):

Lung Function ◽

Mixed Model ◽

Linear Mixed Model ◽

Early Stage ◽

Home Monitoring ◽

Clinical Situation ◽

Forced Expiratory Volume ◽

Mixed Model Analysis ◽

Children With Asthma ◽

At Home

The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We investigated whether lung function measurements at home were comparable to measurements during clinical visits. We analysed prospectively collected data of two one-year observational cohort studies in 117 children (36 with CF and 81 with asthma). All patients performed forced expiratory volume in one second (FEV1) measurements with a monitor at home. Paired FEV1 measurements were included if the measurement on the home monitor was performed on the same day as the FEV1 measurement on the pneumotachometer during a two monthly clinical visit. Bland-Altman plots and linear mixed model analysis were used. The mean difference (home measurement was subtracted from clinical measurement) in FEV1 was 0.18 L in CF (95% confidence interval (CI) 0.08–0.27 L; p < 0.001) and 0.12 L in asthma (95%CI 0.05–0.19 L; p < 0.001). FEV1 measurements at home were significantly lower than clinically obtained FEV1 measurements, which has implications for the application of this technique in the daily clinical situation.

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Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0005 ◽

2017 ◽

Vol 30 (8) ◽

Cited By ~ 13

Author(s):

Nicolas Terliesner ◽

Mandy Vogel ◽

Anna Steighardt ◽

Ruth Gausche ◽

Constance Henn ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Children And Adolescents ◽

Pancreatic Insufficiency ◽

Growth Failure ◽

Forced Expiratory Volume ◽

Exocrine Pancreatic Insufficiency ◽

Retrospective Case ◽

Poor Growth ◽

Impaired Lung Function

AbstractBackground:Impaired glucose metabolism and cystic fibrosis (CF)-related diabetes (CFRD) are associated with insufficient weight gain and impaired lung function in children and adolescents with CF. We have asked whether imminent CFRD may be a cause of poor growth in children and adolescents.Methods:A retrospective case control study including 32 patients with CF with or without diabetes was conducted. Sixteen pairs, matched according to age, gender and exocrine pancreatic insufficiency, were analysed. Standard deviation scores (SDS) of height, growth, weight, body mass index (BMI), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and forced expiratory flow at 75% of expired FVC (FEF75) were recorded during a mean observation period of 13 years per patient.Results:SDS of height and weight were reduced in CF patients with diabetes compared to those without, not only at the point of diagnosis (both p<0.05) but years before the evidence of diabetes. Afterwards there was a significant decline in height (p<0.001) and weight (p<0.01) SDS in CFRD patients and an increasing difference between the height and weight of CF patients with or without diabetes. In contrast, no significant reduction of BMI-SDS was observed in CFRD patients. All analysed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to the diagnosis of diabetes.Conclusions:Deteriorating growth, reduced weight and impaired lung function are related to the development of CFRD and are obvious several years before the actual diagnosis of diabetes.

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Chronisch pulmonale Erkrankungen bei Kindern: Chancen von E-Health zur Verbesserung der Therapiesteuerung nutzen

Karger Kompass Pneumologie ◽

10.1159/000510893 ◽

2020 ◽

Vol 8 (5) ◽

pp. 264-265

Author(s):

Maximilian Jorczyk

Keyword(s):

Lung Function ◽

Mixed Model ◽

Linear Mixed Model ◽

Early Stage ◽

Home Monitoring ◽

Clinical Situation ◽

Forced Expiratory Volume ◽

Mixed Model Analysis ◽

One Year ◽

At Home

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Lung function and disease severity in cystic fibrosis patients heterozygous for p.Arg117His

ERJ Open Research ◽

10.1183/23120541.00056-2016 ◽

2017 ◽

Vol 3 (1) ◽

pp. 00056-2016 ◽

Cited By ~ 5

Author(s):

Michal Shteinberg ◽

Damian G. Downey ◽

Diane Beattie ◽

John McCaughan ◽

Alastair Reid ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Disease Severity ◽

Pancreatic Insufficiency ◽

Forced Expiratory Volume ◽

Class I ◽

Lung Function Decline ◽

Diagnostic Features ◽

Sweat Chloride ◽

In Trans

Expression of p.Arg117His cystic fibrosis (CF) transmembrane conductance regulator is influenced by a polythymidine (poly-T) tract and a thymidine–guanine (TG) repeat on intron 9, which vary in length and affect exon 10 skipping.We compared clinical characteristics and the rate of progression of lung disease of CF patients carrying the p.Arg117His mutation with different intron 9 varying sequences (poly-T) and mutation classes in trans.Data were collected from patients in Northern Ireland, UK, including diagnostic features, sweat chloride, nutritional status, sputum microbiology, CF-related complications and lung function. Poly-T and TG repeats were determined by PCR. Forced expiratory volume in 1 s (FEV1) decline was determined from linear regression of FEV1 measurements of patients over time.We identified 62 patients with p.Arg117His, 55 with a class I/II mutation in trans and six with p.Arg117His/p.Gly551Asp. 42 patients had 5T and 13 had 7T. All patients had 12 TG repeats. Patients with p.Arg117His-5T had greater lung function decline, sweat chloride concentrations, pancreatic insufficiency and prevalence of Pseudomonas aeruginosa infection compared with patients with p.Arg117His-7T.Lung function decline and disease severity in p.Arg117His is determined by the poly-T tract length and identity of the mutation in trans. Patients with p.Arg117His-5T and a second class I/II mutation have a severity similar to p.Phe508del homozygous patients, although lung function decline is delayed to an older age. There may be linkage disequilibrium between p.Arg117His and 12 TG repeats.

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New Insights in Microbial Species Predicting Lung Function Decline in CF: Lessons from the MucoFong Project

Journal of Clinical Medicine ◽

10.3390/jcm10163725 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3725

Author(s):

Florence Francis ◽

Raphael Enaud ◽

Perrine Soret ◽

Florian Lussac-Sorton ◽

Marta Avalos-Fernandez ◽

...

Keyword(s):

Lung Function ◽

Mixed Model ◽

Linear Mixed Model ◽

Forced Expiratory Volume ◽

Achromobacter Xylosoxidans ◽

Published Data ◽

Lung Function Decline ◽

Mixed Model Analysis ◽

Microbial Risk ◽

Fungal Colonisation

Several predictive models have been proposed to understand the microbial risk factors associated with cystic fibrosis (CF) progression. Very few have integrated fungal airways colonisation, which is increasingly recognized as a key player regarding CF progression. To assess the association between the percent predicted forced expiratory volume in 1 s (ppFEV1) change and the fungi or bacteria identified in the sputum, 299 CF patients from the “MucoFong” project were included and followed-up with over two years. The relationship between the microorganisms identified in the sputum and ppFEV1 course of patients was longitudinally analysed. An adjusted linear mixed model analysis was performed to evaluate the effect of a transient or chronic bacterial and/or fungal colonisation at inclusion on the ppFEV1 change over a two-year period. Pseudomonas aeruginosa, Achromobacter xylosoxidans, Stenotrophomonas maltophilia, and Candida albicans were associated with a significant ppFEV1 decrease. No significant association was found with other fungal colonisations. In addition, the ppFEV1 outcome in our model was 11.26% lower in patients presenting with a transient colonisation with non-pneumoniae Streptococcus species compared to other patients. These results confirm recently published data and provide new insights into bacterial and fungal colonisation as key factors for the assessment of lung function decline in CF patients.

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Short term effect and effect on rate of lung function decline after surgery for neuromuscular or syndromic scoliosis

10.22541/au.163276567.73176151/v1 ◽

2021 ◽

Author(s):

Esther Veldhoen ◽

Anneloes de Vries ◽

Tom Schlosser ◽

Moyo Kruyt ◽

Ruben van Eijk ◽

...

Keyword(s):

Lung Function ◽

Neuromuscular Diseases ◽

Lung Function Test ◽

Forced Expiratory Volume ◽

Rate Of Change ◽

Scoliosis Surgery ◽

Lung Function Decline ◽

Linear Mixed Effects ◽

The Impact ◽

Restrictive Lung Function

Introduction Understanding the impact of scoliosis surgery on lung function is important for counseling patients about risks and benefits of surgery. We prospectively compared the trends in lung function test (LFT) results prior to and after scoliosis surgery in children with neuromuscular diseases, or dysmorphic syndromes. We hypothesized a stabilization. Methods We prospectively included children with neuromuscular or syndromic scoliosis able to perform LFTs. We studied (Forced) Vital Capacity ((F)VC), the ratio of Forced Expiratory Volume in 1 second (FEV1) and FVC, and Peak Expiratory Flow (PEF). Preoperative LFT results were compared with results 3-4 months after surgery. The mean monthly change in LFT results up to 2 years after surgery was compared with the preoperative natural history using linear mixed effects models. Results We included 43 patients. No significant change was observed in absolute values of (F)VC, FEV1/FVC and PEF prior to and after surgery. Median standardized VC, FVC and PEF decreased significantly after surgery from 59 to 58%, 60 to 51% and 61 to 53% respectively. The monthly rate of change in FVC was -0.13 % (95% CI -0.42 to 0.17) prior to surgery and -0.20% (95% CI -0.42 to 0.03) after surgery, mean difference -0.07 (95% CI -0.46 to 0.31; p=0.36). Conclusion No stabilization of lung function 3-4 months after scoliosis surgery was observed in children with neuromuscular and syndromic scoliosis with restrictive lung function disease. The effect of surgery on the rate of lung function decline remains inconclusive.

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Factors associated with professional identity formation within psychiatry residency training: A longitudinal study

Perspectives on Medical Education ◽

10.1007/s40037-021-00673-w ◽

2021 ◽

Author(s):

Qian Hui Chew ◽

Yvonne Steinert ◽

Kang Sim

Keyword(s):

Professional Identity ◽

Identity Formation ◽

Psychiatry Residency ◽

Mixed Model ◽

Linear Mixed Model ◽

Developmental Stages ◽

Rate Of Change ◽

Psychiatry Residents ◽

Factors Associated ◽

Over Time

Abstract Introduction Conceptual frameworks for professional identity (PI) formation highlight the importance of developmental stages and socialization as the learner progresses from legitimate peripheral to full participation. Based on extant literature and clinical impressions, the authors aimed to explore factors associated with PI formation in psychiatry residents over time, and hypothesized that time in training, seniority status, and duration of exposure to psychiatry prior to residency would be associated with PI formation. Methods Eighty out of 96 psychiatry residents (response rate, 83.3%) from the National Psychiatry Residency Program in Singapore participated and rated their PI development using the Professional Self Identity Questionnaire (PSIQ) across four timepoints from January 2016–December 2019. The residents were classified as junior (first 3 years) or senior residents (years 4–5). Linear mixed model analyses were conducted, with time in training, seniority status (junior versus senior residents), duration of psychiatry postings prior to residency, and their interaction as associated factors with PI over time. Results Time in training, seniority, and duration of psychiatry postings before residency (all p < 0.01) were significantly associated with higher PSIQ scores at baseline. Over time, although all residents had increases in PSIQ scores, this rate of change did not differ significantly between junior and senior residents. Discussion Exposure to psychiatry postings before residency, time in learning, and seniority are factors which influence PI development in residents. This has implications for psychiatry residency selection and training, adequate clinical exposure during training rotations, and continual support for new and senior residents to foster PI formation over time.

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Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery

Neurosurgical Review ◽

10.1007/s10143-021-01577-3 ◽

2021 ◽

Author(s):

Judith Rösler ◽

Stefan Georgiev ◽

Anna L. Roethe ◽

Denny Chakkalakal ◽

Güliz Acker ◽

...

Keyword(s):

User Satisfaction ◽

Mixed Model ◽

Linear Mixed Model ◽

Intraoperative Complications ◽

Rank Test ◽

User Group ◽

Clinical Implementation ◽

Physical Strain ◽

Conventional Microscope ◽

The Impact

AbstractExoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand–eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.

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The influence of xylanase on the fermentability, digestibility, and physiochemical properties of insoluble corn-based fiber along the gastrointestinal tract of growing pigs

Journal of Animal Science ◽

10.1093/jas/skab159 ◽

2021 ◽

Author(s):

Amy L Petry ◽

Nichole F Huntley ◽

Michael R Bedford ◽

John F Patience

Keyword(s):

Mixed Model ◽

Linear Mixed Model ◽

Nutrient Digestibility ◽

Growing Pigs ◽

Neutral Detergent Fiber ◽

Adaptation Period ◽

High Fiber ◽

Gross Energy ◽

Digesta Viscosity ◽

The Impact

Abstract In theory, supplementing xylanase in corn-based swine diets should improve nutrient and energy digestibility and fiber fermentability, but its efficacy is inconsistent. The experimental objective was to investigate the impact of xylanase on energy and nutrient digestibility, digesta viscosity, and fermentation when pigs are fed a diet high in insoluble fiber (>20% neutral detergent fiber; NDF) and given a 46-d dietary adaptation period. Three replicates of 20 growing gilts were blocked by initial body weight, individually housed, and assigned to 1 of 4 dietary treatments: a low-fiber control (LF) with 7.5% NDF, a 30% corn bran high-fiber control (HF; 21.9% NDF), HF+100 mg xylanase/kg [HF+XY, (Econase XT 25P; AB Vista, Marlborough, UK)] providing 16,000 birch xylan units/kg; and HF+50 mg arabinoxylan-oligosaccharide (AXOS) product/kg [HF+AX, (XOS 35A; Shandong Longlive Biotechnology, Shandong, China)] providing AXOS with 3-7 degrees of polymerization. Gilts were allowed ad libitum access to fed for 36-d. On d 36, pigs were housed in metabolism crates for a 10-d period, limit fed, and feces were collected. On d 46, pigs were euthanized and ileal, cecal, and colonic digesta were collected. Data were analyzed as a linear mixed model with block and replication as random effects, and treatment as a fixed effect. Compared with LF, HF reduced the apparent ileal digestibility (AID), apparent cecal digestibility (ACED), apparent colonic digestibility (ACOD), and apparent total tract digestibility (ATTD) of dry matter (DM), gross energy (GE), crude protein (CP), acid detergent fiber (ADF), NDF, and hemicellulose (P<0.01). Relative to HF, HF+XY improved the AID of GE, CP, and NDF (P<0.05), and improved the ACED, ACOD, and ATTD of DM, GE, CP, NDF, ADF, and hemicellulose (P<0.05). Among treatments, pigs fed HF had increased hindgut DM disappearance (P=0.031). Relative to HF, HF+XY improved cecal disappearance of DM (162 vs. 98g; P=0.008) and NDF (44 vs. 13g; P<0.01). Pigs fed xylanase had a greater proportion of acetate in cecal digesta and butyrate in colonic digesta among treatments (P<0.05). Compared with LF, HF increased ileal, cecal, and colonic viscosity, but HF+XY decreased ileal viscosity compared with HF (P<0.001). In conclusion, increased insoluble corn-based fiber decreases digestibility, reduces cecal fermentation, and increases digesta viscosity, but supplementing xylanase partially mitigated that effect.

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