Evaluation of a five-year predicted survival model for cystic fibrosis in later time periods

Liou, Theodore G.; Kartsonaki, Christiana; Keogh, Ruth H.; Adler, Frederick R.

doi:10.1038/s41598-020-63590-8

Cited by 16 publications

(26 citation statements)

References 62 publications

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“…These results also complement recent findings of Rittayamai et al (2020) reporting a significantly lower DCR in COPD patients with increased disease severity and frequent exacerbations. Although there is little doubt that FEV 1 will remain the standard in evaluating overall disease burden in CF for the foreseeable future (Kerem et al, 2014;Szczesniak et al, 2017;Keogh et al, 2019;Liou et al, 2020), our results support the validity of DCR as a potentially new marker of disease severity that could complement FEV 1 in the longitudinal monitoring of CF patients and their response to therapeutic interventions. In addition, our results raise the possibility that improving DCR with tailored therapeutic interventions such as inspiratory muscle training (IMT) could positively impact dyspnea levels and clinical outcomes, although this remains to be demonstrated in prospective clinical trials.…”

Section: Discussionsupporting

confidence: 61%

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis

et al. 2022

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Introduction: In patients with cystic fibrosis (CF), the monitoring of respiratory muscle activity using electromyography can provide information on the demand-to-capacity ratio of the respiratory system and act as a clinical marker of disease activity, but this technique is not adapted to routine clinical care. Ultrasonography of the diaphragm could provide an alternative, simpler and more widely available alternative allowing the real-time assessment of the diaphragm contractile reserve (DCR), but its relationship with recognized markers of disease severity and clinical outcomes are currently unknown.Methods: Stable patients with CF were prospectively recruited. Diaphragm ultrasound was performed and compared to forced expiratory volume in 1 s (FEV1), residual volume (RV), handgrip strength, fat-free mass index (FFMI), serum vitamin levels, dyspnea levels and rate of acute exacerbation (AE). Diaphragm activity was reported as DCR (the ratio of tidal-to-maximal thickening fractions, representing the remaining diaphragm contractility available after tidal inspiration) and TFmax (representing maximal diaphragm contractile strength). Inter-observer reliability of the measurement of DCR was evaluated using intra-class correlation analysis.Results: 110 patients were included [61 males, median (interquartile range), age 31 (27–38) years, FEV1 66 (46–82)% predicted]. DCR was significantly correlated to FEV1 (rho = 0.46, p < 0.001), RV (rho = −0.46, p < 0.001), FFMI (rho = 0.41, p < 0.001), and handgrip strength (rho = 0.22, p = 0.02), but TFmax was not. In a multiple linear regression analysis, both RV and FFMI were independent predictors of DCR. DCR, but not TFmax, was statistically lower in patients with > 2 exacerbations/year (56 ± 25 vs. 71 ± 17%, p = 0.001) and significantly lower with higher dyspnea levels. A ROC analysis showed that DCR performed better than FEV1 (mean difference in AUROC 0.09, p = 0.04), RV (mean difference in AUROC 0.11, p = 0.03), and TFmax at identifying patients with an mMRC score > 2. Inter-observer reliability of DCR was high (ICC = 0.89, 95% CI 0.84–0.92, p < 0.001).Conclusion: In patients with CF, DCR is a reliable and non-invasive marker of disease severity that is related to respiratory and extra-pulmonary manifestations of the disease and to clinical outcomes. Future studies investigating the use of DCR as a longitudinal marker of disease progression, response to interventions or target for therapy would further validate its translation into clinical practice.

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Section: Discussionsupporting

confidence: 61%

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis

et al. 2022

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“…Several predictive models have been proposed to identify risk factors associated with severe lung function decline, morbidity, or mortality in CF [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. These models underscored the importance of several clinical factors, including microbial airway colonisations, when assessing morbidity and mortality in CF.…”

Section: Introductionmentioning

confidence: 99%

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

Francis

Enaud²,

Soret³

et al. 2021

JCM

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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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“…We fitted a regression model for each biomarker with 5-year prognostic risk score variables (4,5) dependent, using the appropriate regression method as appropriate: linear regressions for age, FEV 1 % and weight-for-age z-score; quasi-Poisson regression for pulmonary exacerbation count in the year prior to enrollment; logistic regressions for pancreatic sufficiency, diabetes and status of infections with MSSA and Burkholderia cepacia complex. Because of their clinical importance (3,21), we evaluated relationships between MRSA and Pseudomonas aeruginosa status with potential biomarkers using logistic regression.…”

Section: Discussionmentioning

confidence: 99%

Associations of Sputum Biomarkers with Clinical Outcomes in People with Cystic Fibrosis

Liou

Argel

Asfour

et al. 2022

Preprint

Self Cite

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BackgroundAirway inflammation promotes bronchiectasis and lung injury in cystic fibrosis (CF). Amplification of inflammation underlies pulmonary exacerbations of disease. We asked whether sputum inflammatory biomarkers provide explanatory information on pulmonary exacerbations.Patients and MethodsWe collected sputum from randomly chosen stable adolescents and adults and prospectively observed time to next exacerbation, our primary outcome. We evaluated relationships between potential biomarkers of inflammation, clinical characteristics and outcomes and assessed clinical variables as potential confounders or mediators of explanatory models. We assessed associations between the markers and time to next exacerbation using proportional hazard models adjusting for confounders.ResultsWe enrolled 114 patients, collected data on clinical variables [December 8, 2014 to January 16, 2016; 46% male, mean age 28 years (SD 12), mean percent predicted forced expiratory volume in 1 s (FEV1%) 70 (SD 22)] and measured 24 inflammatory markers. Half of the inflammatory markers were plausibly associated with time to next exacerbation. Age and sex were confounders while we found that FEV1% was a mediator.Three potential biomarkers of RAGE axis inflammation were associated with time to next exacerbation while six potential neutrophil-associated biomarkers indicate associations between protease activity or reactive oxygen species with time to next exacerbation.ConclusionPulmonary exacerbation biomarkers are part of the RAGE proinflammatory axis or reflect neutrophil activity, specifically implicating protease and oxidative stress injury. Further investigations or development of novel anti-inflammatory agents should consider RAGE axis, protease and oxidant stress antagonists.Tweetable abstractSputum from 114 randomly chosen people with CF show RAGE axis inflammation, protease and oxidative stress injury are associated with time to next pulmonary exacerbation and may be targets for bench or factorial design interventional studies. (242 characters)

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Evaluation of a five-year predicted survival model for cystic fibrosis in later time periods

Cited by 16 publications

References 62 publications

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis

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

Associations of Sputum Biomarkers with Clinical Outcomes in People with Cystic Fibrosis

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