Prognosis-Based Early Intervention Strategies to Resolve Exacerbation and Progressive Lung Function Decline in Cystic Fibrosis

Vij, Neeraj

doi:10.3390/jpm11020096

Cited by 3 publications

(3 citation statements)

References 83 publications

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Section: Transferencia En La Práctica De Dra Luisa Fernanda Martínez-...unclassified

“…El daño pulmonar y las exacerbaciones causan un deterioro de la función pulmonar, lo cual es una causa importante de mortalidad [1]. Es importante monitorizar y detectar cambios a nivel pulmonar para dar tratamientos óptimos y mejorar la expectativa de vida, es ahí donde herramientas como el índice de aclaramiento pulmonar (lung clearance index, LCI) nos permite evaluar la falta de homogeneidad de la ventilación y documentar cambios de forma temprana en la enfermedad [2,3]. A nivel pancreático existe una pérdida de la función de las enzimas pancreáticas causando malabsorción de grasas y de vitaminas liposolubles, por lo tanto, las personas con FQ presentan deficiencia de vitamina D. La vitamina D tiene un papel importante en la función del sistema inmune, regulando la respuesta inflamatoria y disminuyendo la colonización bacteriana en la vía respiratoria.…”

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Fibrosis quística: Mantener niveles óptimos de vitamina D para preservar la función pulmonar y mejorar la calidad de vida

Martínez-Valdeavellano¹

2022

Kompass Neumol

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Background: Life expectancy has increased in cystic fibrosis (CF) patients; however, the rate of mortality is still high, and in a majority of cases, the cause of death is due to respiratory deterioration. Vitamin D plays an important role in immunity and infection prophylaxis, as its deficiency is associated with frequent infections. In CF patients, a deficit of liposoluble vitamins is common, despite daily supplementation. The aim of this study is to evaluate the relation between vitamin D status and lung function expressed by lung clearance index (LCI) in patients with CF. We also assessed the relation of factors such as nutritional status, genotype, and associated comorbidities such as Pseudomonas infection, cystic fibrosis-related diabetes (CFRD), and cystic fibrosis liver disease (CFLD) with vitamin D and LCI. Methods: A cross-sectional study was conducted at the National Cystic Fibrosis Center by analyzing patients with CF who presented in our center between November 2017 and November 2019. We enrolled in the study patients diagnosed with CF, who were followed up in our CF center and who were able to perform lung function tests. Patients in exacerbation were excluded. Results: A strong negative correlation was found between vitamin D and LCI (r = -0.69, p = 0.000). A lower vitamin D storage was found in patients with CFLD and CFRD. Higher LCI values were found among patients with chronic Pseudomonas infection, with BMI under the 25th percentile, or with associated CFLD. Conclusion: In CF patients, vitamin D plays an important role, and its deficit correlates with an impaired LCI. Vitamin D deficit is a risk factor in patients with associated comorbidities such as CFLD and CFRD. Chronic infection with Pseudomonas, the presence of impaired nutritional status, and CFLD are associated with a prolonged LCI.

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Section: Transferencia En La Práctica De Dra Luisa Fernanda Martínez-...unclassified

Section: Contexto Del Estudiounclassified

Fibrosis quística: Mantener niveles óptimos de vitamina D para preservar la función pulmonar y mejorar la calidad de vida

Martínez-Valdeavellano¹

2022

Kompass Neumol

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“…Cases featuring normal or equivocal sweat chloride concentrations, CFTR variants with unknown phenotypic signification and equivocal CFTR function make room for the development of new CF biomarkers. Moreover, in the context of personalized medicine, prognostic biomarkers and companion diagnostic biomarkers are valuable for the earliest and most appropriate therapeutic intervention [ 8 ]. In addition, in the context of therapeutic development, biomarkers of clinical response and phenotypic rescue (e.g., CFTR/F508del CFTR physical or functional protein interactors) are critical to the emergence and advance of new therapies [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Sweat Proteomics in Cystic Fibrosis: Discovering Companion Biomarkers for Precision Medicine and Therapeutic Development

Burat

Reynaerts²,

Baiwir³

et al. 2022

Cells

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In clinical routine, the diagnosis of cystic fibrosis (CF) is still challenging regardless of international consensus on diagnosis guidelines and tests. For decades, the classical Gibson and Cooke test measuring sweat chloride concentration has been a keystone, yet, it may provide normal or equivocal results. As of now, despite the combination of sweat testing, CFTR genotyping, and CFTR functional testing, a small fraction (1–2%) of inconclusive diagnoses are reported and justifies the search for new CF biomarkers. More importantly, in the context of precision medicine, with a view to early diagnosis, better prognosis, appropriate clinical follow-up, and new therapeutic development, discovering companion biomarkers of CF severity and phenotypic rescue are of utmost interest. To date, previous sweat proteomic studies have already documented disease-specific variations of sweat proteins (e.g., in schizophrenia and tuberculosis). In the current study, sweat samples from 28 healthy control subjects and 14 patients with CF were analyzed by nanoUHPLC-Q-Orbitrap-based shotgun proteomics, to look for CF-associated changes in sweat protein composition and abundance. A total of 1057 proteins were identified and quantified at an individual level, by a shotgun label-free approach. Notwithstanding similar proteome composition, enrichment, and functional annotations, control and CF samples featured distinct quantitative proteome profiles significantly correlated with CF, accounting for the respective inter-individual variabilities of control and CF sweat. All in all: (i) 402 sweat proteins were differentially abundant between controls and patients with CF, (ii) 68 proteins varied in abundance between F508del homozygous patients and patients with another genotype, (iii) 71 proteins were differentially abundant according to the pancreatic function, and iv) 54 proteins changed in abundance depending on the lung function. The functional annotation of pathophysiological biomarkers highlighted eccrine gland cell perturbations in: (i) protein biosynthesis and trafficking, (ii) CFTR proteostasis and membrane stability, and (iii) cell-cell adherence, membrane integrity, and cytoskeleton crosstalk. Cytoskeleton-related biomarkers were of utmost interest because of the consistency between variations observed here in CF sweat and variations previously documented in other CF tissues. From a clinical stance, nine candidate biomarkers of CF diagnosis (CUTA, ARG1, EZR, AGA, FLNA, MAN1A1, MIA3, LFNG, SIAE) and seven candidate biomarkers of CF severity (ARG1, GPT, MDH2, EML4 (F508del homozygous), MGAT1 (pancreatic insufficiency), IGJ, TOLLIP (lung function impairment)) were deemed suitable for further verification.

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Early Diagnosis and Real-Time Monitoring of Regional Lung Function Changes to Prevent Chronic Obstructive Pulmonary Disease Progression to Severe Emphysema

Jung

Vij

2021

JCM

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First- and second-hand exposure to smoke or air pollutants is the primary cause of chronic obstructive pulmonary disease (COPD) pathogenesis, where genetic and age-related factors predispose the subject to the initiation and progression of obstructive lung disease. Briefly, airway inflammation, specifically bronchitis, initiates the lung disease, leading to difficulty in breathing (dyspnea) and coughing as initial symptoms, followed by air trapping and inhibition of the flow of air into the lungs due to damage to the alveoli (emphysema). In addition, mucus obstruction and impaired lung clearance mechanisms lead to recurring acute exacerbations causing progressive decline in lung function, eventually requiring lung transplant and other lifesaving interventions to prevent mortality. It is noteworthy that COPD is much more common in the population than currently diagnosed, as only 16 million adult Americans were reported to be diagnosed with COPD as of 2018, although an additional 14 million American adults were estimated to be suffering from COPD but undiagnosed by the current standard of care (SOC) diagnostic, namely the spirometry-based pulmonary function test (PFT). Thus, the main issue driving the adverse disease outcome and significant mortality for COPD is lack of timely diagnosis in the early stages of the disease. The current treatment regime for COPD emphysema is most effective when implemented early, on COPD onset, where alleviating symptoms and exacerbations with timely intervention(s) can prevent steep lung function decline(s) and disease progression to severe emphysema. Therefore, the key to efficiently combatting COPD relies on early detection. Thus, it is important to detect early regional pulmonary function and structural changes to monitor modest disease progression for implementing timely interventions and effectively eliminating emphysema progression. Currently, COPD diagnosis involves using techniques such as COPD screening questionnaires, PFT, arterial blood gas analysis, and/or lung imaging, but these modalities are limited in their capability for early diagnosis and real-time disease monitoring of regional lung function changes. Hence, promising emerging techniques, such as X-ray phase contrast, photoacoustic tomography, ultrasound computed tomography, electrical impedance tomography, the forced oscillation technique, and the impulse oscillometry system powered by robust artificial intelligence and machine learning analysis capability are emerging as novel solutions for early detection and real time monitoring of COPD progression for timely intervention. We discuss here the scope, risks, and limitations of current SOC and emerging COPD diagnostics, with perspective on novel diagnostics providing real time regional lung function monitoring, and predicting exacerbation and/or disease onset for prognosis-based timely intervention(s) to limit COPD–emphysema progression.

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Prognosis-Based Early Intervention Strategies to Resolve Exacerbation and Progressive Lung Function Decline in Cystic Fibrosis

Cited by 3 publications

References 83 publications

Fibrosis quística: Mantener niveles óptimos de vitamina D para preservar la función pulmonar y mejorar la calidad de vida

Fibrosis quística: Mantener niveles óptimos de vitamina D para preservar la función pulmonar y mejorar la calidad de vida

Sweat Proteomics in Cystic Fibrosis: Discovering Companion Biomarkers for Precision Medicine and Therapeutic Development

Early Diagnosis and Real-Time Monitoring of Regional Lung Function Changes to Prevent Chronic Obstructive Pulmonary Disease Progression to Severe Emphysema

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