scholarly journals How do growth and nutrition explain social inequalities in lung function in children with cystic fibrosis? A longitudinal mediation analysis using interventional disparity effects with time-varying mediators and intermediate confounders.

2022 ◽  
Author(s):  
Daniela K Schlueter ◽  
Ruth Keogh ◽  
Rhian Daniel ◽  
Schadrac Agbla ◽  
David Taylor-Robinson
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Mediation Analysis ◽  
Social Inequalities ◽  
Early Growth ◽  
Forced Expiratory Volume ◽  
Time Varying ◽  
Disadvantaged Children ◽  
The Uk ◽  
Weight Trajectories

Background Deprivation is associated with poorer growth, worse lung function and shorter life expectancy in children with cystic fibrosis (CF). While early growth is associated with lung function when first measured at around age 6, it is unclear whether improving early growth in the most disadvantaged children would reduce inequalities in lung function. Methods We used data from children born 2000-2010 and followed up to 2016 in the UK CF Registry. To estimate the association between deprivation and lung function at around age six, and the causal contribution of early weight trajectories, we extended the mediation analysis approach based on interventional disparity effects to the setting of a longitudinally measured mediator. We adjusted for baseline confounding by sex, birthyear and genotype and accounted for time-varying intermediate confounding by lung infection. Results 853 children were included in the study, including 165 and 172 children from the least and most deprived population quintiles, respectively. The average difference in lung function between the least and most deprived quintile of children, was 4.51 percent of predicted forced expiratory volume in one second (95% CI: 1.08-7.93). We estimated this would be reduced to 3.97 percentage points (95% CI: 0.57-7.38) if early weight trajectories in the most deprived children were shifted to the distribution observed in the least disadvantaged children. Conclusion Socio-economic conditions are strongly associated with lung function for children with CF which we estimated would only be marginally reduced if early weight trajectories could be improved for the most disadvantaged children.

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

Thorax ◽  
2019 ◽  
Vol 75 (2) ◽  
pp. 123-131 ◽  
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.

scholarly journals Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-216849
Author(s):  
Daniela K Schlüter ◽  
Josh S Ostrenga ◽  
Siobhán B Carr ◽  
Aliza K Fink ◽  
Albert Faro ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Hypertonic Saline ◽  
Early Growth ◽  
National Registry ◽  
Cross Sectional ◽  
Growth And Nutrition ◽  
Inhaled Antibiotics ◽  
The Usa ◽  
The Uk

RationaleA previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results.ObjectivesTo compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences.MethodsWe used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections (Pseudomonas aeruginosa, Staphylococcus aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics).ResultsWe included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK.ConclusionsChildren with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.

scholarly journals Integrating latent classes in the Bayesian shared parameter joint model of longitudinal and survival outcomes

2020 ◽  
Vol 29 (11) ◽  
pp. 3294-3307
Author(s):  
Eleni-Rosalina Andrinopoulou ◽  
Kazem Nasserinejad ◽  
Rhonda Szczesniak ◽  
Dimitris Rizopoulos
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Latent Class ◽  
Joint Model ◽  
Forced Expiratory Volume ◽  
Optimal Number ◽  
Latent Classes ◽  
Joint Models ◽  
Number Of Classes ◽  
Strength Of Association

Cystic fibrosis is a chronic lung disease requiring frequent lung-function monitoring to track acute respiratory events (pulmonary exacerbations). The association between lung-function trajectory and time-to-first exacerbation can be characterized using joint longitudinal-survival modeling. Joint models specified through the shared parameter framework quantify the strength of association between such outcomes but do not incorporate latent sub-populations reflective of heterogeneous disease progression. Conversely, latent class joint models explicitly postulate the existence of sub-populations but do not directly quantify the strength of association. Furthermore, choosing the optimal number of classes using established metrics like deviance information criterion is computationally intensive in complex models. To overcome these limitations, we integrate latent classes in the shared parameter joint model through a fully Bayesian approach. To choose the optimal number of classes, we construct a mixture model assuming more latent classes than present in the data, thereby asymptotically “emptying” superfluous latent classes, provided the Dirichlet prior on class proportions is sufficiently uninformative. Model properties are evaluated in simulation studies. Application to data from the US Cystic Fibrosis Registry supports the existence of three sub-populations corresponding to lung-function trajectories with high initial forced expiratory volume in 1 s ( FEV1), rapid FEV1 decline, and low but steady FEV1 progression. The association between FEV1 and hazard of exacerbation was negative in each class, but magnitude varied.

scholarly journals 1014 Relationship Between Lung Function and Obstructive Sleep Apnea in Cystic Fibrosis

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A385-A385
Author(s):  
A Shakkottai ◽  
S Z Nasr ◽  
F Hassan ◽  
L M O’Brien ◽  
R D Chervin
Keyword(s):  
Cystic Fibrosis ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Lung Function ◽  
Forced Expiratory Volume ◽  
Apnea Hypopnea Index ◽  
Lung Function Decline ◽  
Obstructive Sleep ◽  
Larger Sample ◽  
Training Grant

Abstract Introduction The frequency of obstructive sleep apnea (OSA) may be high among patients with cystic fibrosis (CF), a life-shortening, genetic respiratory disease that affects approximately 30,000 Americans. Yet, the potential relationship between OSA and lung function has not been thoroughly explored. Methods Single-center retrospective review of polysomnography (PSG) results from 2009-2017 in referred patients with CF and available pulmonary function data (PFTs) obtained at time of PSG and at 3, 6, 9, and 12-months prior. Results Mean ages were 11.1±3.9 (sd) and 37.1±14.1 years, among 18 children and 16 adults, respectively. Mean body mass index (BMI) was normal in both groups (62.5±26.6% in children; 25.1±6.4 kg/m2 in adults). Twenty-six subjects (76%) had OSA (apnea-hypopnea index >1 in children, ≥5 in adults). Mean forced expiratory volume in 1 second percent predicted (FEV1 PPD) was higher among subjects with vs. without OSA at PSG and at each time-point in the year prior, independent of age and BMI at PSG (longitudinal mixed effects model, β=19.0, SE=8.1, p=0.028). While FEV1 PPD remained unchanged in the non-OSA group, FEV1 PPD at PSG was lower, in comparison to the year prior in subjects with OSA, with the greatest difference observed at 9-months prior to PSG (2-sample t-test, difference of -6.6% vs 0.6% in OSA vs. non-OSA groups respectively, p=0.078). Conclusion The PFTs, as daytime markers of CF lung disease severity, do not seem to reliably predict risk for OSA. In our sample, CF patients with vs. without OSA had better PFTs at baseline but they also showed a greater tendency for decline in PFTs over the year prior to OSA diagnosis. Larger sample size and longer duration of assessment may help, going forward, to assess any potential adverse impact of OSA on lung function decline. Support NIH Training Grant (T32NS007222, F32HL145915)

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

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arul Earnest ◽  
Farhad Salimi ◽  
Claire E. Wainwright ◽  
Scott C. Bell ◽  
Rasa Ruseckaite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Pancreatic Insufficiency ◽  
Forced Expiratory Volume ◽  
Rate Of Change ◽  
Data Registry ◽  
Mortality Outcome ◽  
The Impact

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.

scholarly journals Burkholderia dolosa phenotypic variation during the decline in lung function of a cystic fibrosis patient during 5.5 years of chronic colonization

2014 ◽  
Vol 63 (4) ◽  
pp. 594-601 ◽  
Author(s):  
Ana Sílvia Moreira ◽  
Carla P. Coutinho ◽  
Pilar Azevedo ◽  
Luís Lito ◽  
José Melo-Cristino ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Fungal Pathogens ◽  
Forced Expiratory Volume ◽  
Burkholderia Cenocepacia ◽  
Epidemiological Surveillance ◽  
Lung Function Decline ◽  
Swarming Motility ◽  
Systematic Assessment ◽  
Chronic Colonization

Although rarely isolated from cystic fibrosis (CF) patients, Burkholderia dolosa is associated with accelerated lung function decline. During 18 years of epidemiological surveillance in the major Portuguese CF centre in Lisbon, only one patient was infected with B. dolosa. Pulmonary deterioration, associated with the evolution of forced expiratory volume in 1 s, occurred during 5.5 years of colonization with this B. dolosa clone (with the new sequence type ST-668). Transient co-colonization with Burkholderia cenocepacia and other bacterial and fungal pathogens occurred, but B. dolosa prevailed until the patient’s death. The systematic assessment of relevant phenotypes for the sequential clonal isolates examined in this retrospective study (14 of B. dolosa and four of B. cenocepacia) showed that they were variants, although in general no isolation time-dependent pattern of alteration was identified. However, the first B. dolosa isolate retrieved was more susceptible to gentamicin, imipenem and tobramycin, and exhibited a higher swarming motility compared with most of the isolates obtained during the later stages of disease progression and antimicrobial therapy.

scholarly journals Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient

2017 ◽  
Vol 50 (5) ◽  
pp. 1700326 ◽  
Author(s):  
Gwyneth Davies ◽  
Janet Stocks ◽  
Lena P. Thia ◽  
Ah-Fong Hoo ◽  
Andrew Bush ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Early Life ◽  
Treatment Protocol ◽  
Forced Expiratory Volume ◽  
Z Score ◽  
Average Group ◽  
Significant Difference ◽  
Residual Capacity ◽  
High Risk Infants

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45–1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify “high-risk” infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.

Forced Expiratory Volume in 1 Second Variability Helps Identify Patients with Cystic Fibrosis at Risk of Greater Loss of Lung Function

2016 ◽  
Vol 169 ◽  
pp. 116-121.e2 ◽  
Author(s):  
Wayne J. Morgan ◽  
Donald R. VanDevanter ◽  
David J. Pasta ◽  
Aimee J. Foreman ◽  
Jeffrey S. Wagener ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
At Risk ◽  
Lung Function ◽  
Forced Expiratory Volume

scholarly journals Pleiotropic associations of heterozygosity for the SERPINA1 Z allele in the UK Biobank

2021 ◽  
pp. 00049-2021
Author(s):  
Katherine A. Fawcett ◽  
Kijoung Song ◽  
Guoqing Qian ◽  
Aliki-Eleni Farmaki ◽  
Richard Packer ◽  
...  
Keyword(s):  
Lung Function ◽  
Disease Risk ◽  
Large Population ◽  
Rare Condition ◽  
Forced Expiratory Volume ◽  
Uk Biobank ◽  
Mineral Density ◽  
Increased Risk ◽  
The Uk ◽  
Reduced Risk

Homozygosity for the SERPINA1 Z allele causes alpha-1 antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on non-respiratory phenotypes, and on lung function in the general population, remain unclear.We conducted a large population-based study to determine Z allele effects on >2400 phenotypes in UK Biobank (N>303 353).Z allele heterozygosity was strongly associated with increased height (β=1.02 cm, p=3.91×10−68), and with other non-respiratory phenotypes including increased risk of gall bladder disease, reduced risk of heart disease and lower blood pressure, reduced risk of osteoarthritis and reduced bone mineral density, increased risk of headache and enlarged prostate, as well as with blood biomarkers of liver function. Heterozygosity was associated with higher height-adjusted forced expiratory volume in 1 s (FEV1) (β=19.36 mL, p=9.21×10−4) and FEV1/forced vital capacity (FEV1/FVC) (β=0.0031, p=1.22×10−5) in non-smokers, whereas in smokers this protective effect was abolished. Furthermore, we show for the first time that sex modifies the association of the Z allele on lung function.We conclude that Z allele heterozygosity and homozygosity exhibit opposing effects on lung function in the UK population, and that these associations are modified by smoking and sex. In exploratory analyses, heterozygosity for the Z allele also showed pleiotropic associations with non-respiratory health-related traits and disease risk.

scholarly journals P051 The bigger you are the harder you fall? Short term effects of LUM/IVA (Orkambi) on lung function in children with cystic fibrosis

2019 ◽  
Vol 104 (7) ◽  
pp. e2.57-e2
Author(s):  
Emma O’ Grady ◽  
Rebecca Finnegan ◽  
Anna Smyth ◽  
Stephanie Ryan ◽  
Michael Williamson
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Pulmonary Function Tests ◽  
Real Life ◽  
Young Patients ◽  
Forced Expiratory Volume ◽  
List Type ◽  
High Resolution Computed Tomography ◽  
Air Trapping ◽  
Female Ratio

AimCystic Fibrosis conductance Transmembrane Regulator (CFTR) protein modulators represent a major breakthrough in the pharmacological management of Cystic Fibrosis (CF). Previous studies report acute changes in lung function after first administration of lumacaftor/ivacaftor (LUM/IVA) without a clear underlying mechanism.1 2 Our aim was to explore links between changes in percent predicted forced expiratory volume in one second (ppFEV1) and a number of potentially influencing factors.MethodsWe conducted a retrospective review of all children with CF who were started on LUM/IVA treatment between September 2016 and August 2017 in our institution. Data was collected from patient charts, electronic laboratory and radiology records. CT Thorax images were reviewed for evidence of air trapping using the Brody score.3 Descriptive and statistical analyses were performed using SPSS. ResultsData was collected from 15 children with CF who were started on LUM/IVA treatment. The mean (±SD) age of starting treatment was 14 years (±1.7 years), with a mean weight of 47.3 kg (±8.9 kg) and male-to-female ratio of 9:6. Ninety-three percent of patients experienced an acute decline in ppFEV1 post initiation of LUM/IVA, with an absolute mean decline of -10.8% (0–20%). There is a statistically significant inverse relationship between absolute change in ppFEV1 (FEV1) and baseline ppFEV1. There is no correlation between FEV1 and weight, gender or air trapping score.ConclusionOur results suggest that a LUM/IVA related decline in lung function is more significant in CF children with higher baseline ppFEV1. This offers reassurance when initiating LUM/IVA as the patients who experience significant declines have a greater respiratory reserve with which to support this reduction. ReferencesRatjen F, Hug C, Marigowda G, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2017;5:557–567.Labaste A, Ohlmann C, Mainguy C, et al. Real-life acute lung function changes after lumacaftor/ivacaftor first administration in paediatric patients with cystic fibrosis. J Cyst Fibros 2017;16:709–712.Brody A, Klein J, Molina P, et al. High- resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests. Journal of Pediatrics 2004;145:32–38.

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