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

2022 ◽  
Vol 12 ◽  
Author(s):  
Fanny Gabrysz-Forget ◽  
Anne-Catherine Maynard-Paquette ◽  
Aileen Kharat ◽  
François Tremblay ◽  
Maité Silviet-Carricart ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Handgrip Strength ◽  
Clinical Care ◽  
Linear Regression Analysis ◽  
Mean Difference ◽  
Contractile Reserve ◽  
Observer Reliability ◽  
Pulmonary Manifestations

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.

scholarly journals Cardiovascular drugs and COVID-19 clinical outcomes: a living systematic review and meta-analysis

2021 ◽  
Author(s):  
Innocent Asiimwe ◽  
Sudeep Pushpakon ◽  
Richard Turner ◽  
Ruwanthi Kolamunnage-Dona ◽  
Andrea Jorgensen ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Disease Severity ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Meta Analysis ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Cardiovascular Drugs ◽  
Mean Difference ◽  
Converting Enzyme Inhibitors ◽  
All Cause Mortality

Aims: To continually evaluate the role of cardiovascular drugs in COVID-19 clinical outcomes. Methods: Eligible publications were identified from >500 databases on 1-Nov-2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer. Results: Of 52,735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with positive COVID-19 status (OR 1.14, 95% CI 1.00–1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 1.34–2.32), disease severity (OR 1.41, 1.27–1.56) and all-cause mortality (OR 1.22, 1.12–1.33) but not hospitalization length (mean difference -0.27, -1.36; 0.82 days). After adjustment, ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.92, 0.71–1.19), hospitalization (OR 0.93, 0.70–1.24), disease severity (OR 1.05, 0.81–1.38), or all-cause mortality (OR 0.85, 0.71–1.01). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.93, 0.79–1.09), hospitalization (OR 0.84, 0.58–1.22), hospitalization length (mean difference -0.14, -1.65; 1.36 days), disease severity (OR 0.92, 0.76–1.11) while it decreased the odds of dying (OR 0.76, 0.65–0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias. Conclusion: Cardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.

scholarly journals Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity

2021 ◽  
Vol 18 (16) ◽  
pp. 8431
Author(s):  
Xuejie Wang ◽  
Carmen Villa ◽  
Yadira Dobarganes ◽  
Casilda Olveira ◽  
Rosa Girón ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Nutritional Status ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Mild Disease ◽  
Wide Range ◽  
Eosinophil Counts

Whether high blood eosinophil counts may define a better phenotype in bronchiectasis patients, as shown in chronic obstructive pulmonary disease (COPD), remains to be investigated. Differential phenotypic characteristics according to eosinophil counts were assessed using a biostatistical approach in a large cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 906 patients who met the inclusion criteria were clustered into two groups on the basis of their eosinophil levels. The potential differences according to the bronchiectasis severity index (BSI) score between two groups (Mann–Whitney U test and eosinophil count threshold: 100 cells/µL) showed the most balanced cluster sizes: above-threshold and below-threshold groups. Patients above the threshold exhibited significantly better clinical outcomes, lung function, and nutritional status, while showing lower systemic inflammation levels. The proportion of patients with mild disease was higher in the above-threshold group, while the below-threshold patients were more severe. Two distinct clinical phenotypes of stable patients with non-cystic fibrosis (CF) bronchiectasis of a wide range of disease severity were established on the basis of blood eosinophil counts using a biostatistical approach. Patients classified within the above-threshold cluster were those exhibiting a mild disease, significantly better clinical outcomes, lung function, and nutritional status while showing lower systemic inflammatory levels. These results will contribute to better characterizing bronchiectasis patients into phenotypic profiles with their clinical implications.

scholarly journals 564 Comparison of clinical outcomes in pregnant women with and without COVID-19 based on disease severity

2021 ◽  
Vol 224 (2) ◽  
pp. S357
Author(s):  
Stacey Gold ◽  
Haleema Saeed ◽  
Neggin Mokhtari ◽  
Rebecca L. Chornock ◽  
Melissa Fries ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Clinical Outcomes ◽  
Disease Severity

scholarly journals A short-term evaluation of a prototype disposable Oscillating Positive Expiratory Pressure (OPEP) device in a cohort of children with cystic fibrosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kevin J. O’Sullivan ◽  
Valerie Power ◽  
Barry Linnane ◽  
Deirdre McGrath ◽  
Magdalena Mulligan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Clinical Investigation ◽  
Mean Difference ◽  
Short Term ◽  
Intervention Participant ◽  
Post Intervention ◽  
Convenience Sample ◽  
Disposable Device ◽  
Positive Expiratory Pressure

Abstract Background Oscillating Positive Expiratory Pressure (OPEP) devices are important adjuncts to airway clearance therapy in patients with cystic fibrosis (CF). Current devices are typically reusable and require daily, or often more frequent, cleaning to prevent risk of infection by acting as reservoirs of potentially pathogenic organisms. In response, a daily disposable OPEP device, the UL-OPEP, was developed to mitigate the risk of contamination and eliminate the burdensome need for cleaning devices. Methods A convenience sample of 36 participants, all current OPEP device users, was recruited from a paediatric CF service. For one month, participants replaced their current OPEP device with a novel daily disposable device. Assessment included pre- and post-intervention lung function by spirometry, as well as Lung Clearance Index. Quality of life was assessed using the Cystic Fibrosis Questionnaire – Revised, while user experience was evaluated with a post-study survey. Results 31 participants completed the study: 18 males; median age 10 years, range 4–16 years. Lung function (mean difference ± SD, %FEV1 = 1.69 ± 11.93; %FVC = 0.58 ± 10.04; FEV1: FVC = 0.01 ± 0.09), LCI (mean difference ± SD, 0.08 ± 1.13), six-minute walk test, and CFQ-R were unchanged post-intervention. Participant-reported experiences of the device were predominantly positive. Conclusions The disposable OPEP device maintained patients’ lung function during short term use (≤ 1 month), and was the subject of positive feedback regarding functionality while reducing the risk of airway contamination associated with ineffective cleaning. Registration The study was approved as a Clinical Investigation by the Irish Health Products Regulatory Authority (CRN-2209025-CI0085).

scholarly journals Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis

2021 ◽  
Vol 10 (10) ◽  
pp. 2077
Author(s):  
Yi-Min Huang ◽  
Chiao Lo ◽  
Chiao-Feng Cheng ◽  
Cheng-Hsun Lu ◽  
Song-Chou Hsieh ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Serum Biomarkers ◽  
Healthy Controls ◽  
Granulomatous Mastitis ◽  
C Reactive Protein ◽  
Idiopathic Granulomatous Mastitis ◽  
Reactive Protein

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

scholarly journals DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 441
Author(s):  
Fanny Pineau ◽  
Davide Caimmi ◽  
Sylvie Taviaux ◽  
Maurane Reveil ◽  
Laura Brosseau ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dna Methylation ◽  
Clinical Trials ◽  
Lung Disease ◽  
Disease Severity ◽  
Genome Wide ◽  
A Genome ◽  
Lung Disease Severity ◽  
Epigenetic Biomarker

Cystic fibrosis (CF) is a chronic genetic disease that mainly affects the respiratory and gastrointestinal systems. No curative treatments are available, but the follow-up in specialized centers has greatly improved the patient life expectancy. Robust biomarkers are required to monitor the disease, guide treatments, stratify patients, and provide outcome measures in clinical trials. In the present study, we outline a strategy to select putative DNA methylation biomarkers of lung disease severity in cystic fibrosis patients. In the discovery step, we selected seven potential biomarkers using a genome-wide DNA methylation dataset that we generated in nasal epithelial samples from the MethylCF cohort. In the replication step, we assessed the same biomarkers using sputum cell samples from the MethylBiomark cohort. Of interest, DNA methylation at the cg11702988 site (ATP11A gene) positively correlated with lung function and BMI, and negatively correlated with lung disease severity, P. aeruginosa chronic infection, and the number of exacerbations. These results were replicated in prospective sputum samples collected at four time points within an 18-month period and longitudinally. To conclude, (i) we identified a DNA methylation biomarker that correlates with CF severity, (ii) we provided a method to easily assess this biomarker, and (iii) we carried out the first longitudinal analysis of DNA methylation in CF patients. This new epigenetic biomarker could be used to stratify CF patients in clinical trials.

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