Publications of Anne-Noëlle Frix
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See detailYKL-40 as a new promising prognostic marker of severity in COVID infection.
Schoneveld, Lauranne ULiege; LADANG, Aurélie ULiege; HENKET, Monique ULiege et al

in Critical care (London, England) (2021), 25(1), 66

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See detailA review in radiomics: Making personalized medicine a reality via routine imaging.
Guiot, Julien ULiege; Vaidyanathan, Akshayaa; DEPREZ, Louis ULiege et al

in Medicinal Research Reviews (2021)

Radiomics is the quantitative analysis of standard-of-care medical imaging; the information obtained can be applied within clinical decision support systems to create diagnostic, prognostic, and/or ... [more ▼]

Radiomics is the quantitative analysis of standard-of-care medical imaging; the information obtained can be applied within clinical decision support systems to create diagnostic, prognostic, and/or predictive models. Radiomics analysis can be performed by extracting hand-crafted radiomics features or via deep learning algorithms. Radiomics has evolved tremendously in the last decade, becoming a bridge between imaging and precision medicine. Radiomics exploits sophisticated image analysis tools coupled with statistical elaboration to extract the wealth of information hidden inside medical images, such as computed tomography (CT), magnetic resonance (MR), and/or Positron emission tomography (PET) scans, routinely performed in the everyday clinical practice. Many efforts have been devoted in recent years to the standardization and validation of radiomics approaches, to demonstrate their usefulness and robustness beyond any reasonable doubts. However, the booming of publications and commercial applications of radiomics approaches warrant caution and proper understanding of all the factors involved to avoid "scientific pollution" and overly enthusiastic claims by researchers and clinicians alike. For these reasons the present review aims to be a guidebook of sorts, describing the process of radiomics, its pitfalls, challenges, and opportunities, along with its ability to improve clinical decision-making, from oncology and respiratory medicine to pharmacological and genotyping studies. [less ▲]

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See detailAsthma and COPD Are Not Risk Factors for ICU Stay and Death in Case of SARS-CoV2 Infection
CALMES, Doriane ULiege; Graff, Sophie ULiege; MAES, Nathalie ULiege et al

in Journal of Allergy and Clinical Immunology: In Practice (2021), 9(1), 160-169

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if ... [more ▼]

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19). METHODS: We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic. RESULTS: Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death. CONCLUSION: Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection. [less ▲]

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See detailCan predicting COVID-19 mortality in a European cohort using only demographic and comorbidity data surpass age-based prediction: An externally validated study.
Chatterjee, Avishek; Wu, Guangyao; Primakov, Sergey et al

in PLoS ONE (2021), 16(4), 0249920

OBJECTIVE: To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a ... [more ▼]

OBJECTIVE: To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a precursor to implementing smart lockdowns and vaccine distribution strategies. METHODS: The training cohort comprised 2337 COVID-19 inpatients from nine hospitals in The Netherlands. The clinical outcome was death within 21 days of being discharged. The features were derived from electronic health records collected during admission. Three feature selection methods were used: LASSO, univariate using a novel metric, and pairwise (age being half of each pair). 478 patients from Belgium were used to test the model. All modeling attempts were compared against an age-only model. RESULTS: In the training cohort, the mortality group's median age was 77 years (interquartile range = 70-83), higher than the non-mortality group (median = 65, IQR = 55-75). The incidence of former/active smokers, male gender, hypertension, diabetes, dementia, cancer, chronic obstructive pulmonary disease, chronic cardiac disease, chronic neurological disease, and chronic kidney disease was higher in the mortality group. All stated differences were statistically significant after Bonferroni correction. LASSO selected eight features, novel univariate chose five, and pairwise chose none. No model was able to surpass an age-only model in the external validation set, where age had an AUC of 0.85 and a balanced accuracy of 0.77. CONCLUSION: When applied to an external validation set, we found that an age-only mortality model outperformed all modeling attempts (curated on www.covid19risk.ai) using three feature selection methods on 22 demographic and comorbid features. [less ▲]

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See detailCould KL-6 levels in COVID-19 help to predict lung disease?
Frix, Anne-Noëlle ULiege; Schoneveld, Lauranne ULiege; LADANG, Aurélie ULiege et al

in Respiratory Research (2020), 21(309),

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of ... [more ▼]

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. MATERIALS AND METHODS: Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. DISCUSSION AND CONCLUSION: Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary. [less ▲]

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See detailCOVID-19 et asthme.
Louis, Renaud ULiege; CALMES, Doriane ULiege; Frix, Anne-Noëlle ULiege et al

in Revue medicale de Liege (2020), 75(S1), 130-132

Given the prominent role of respiratory viruses in asthma exacerbations it has been feared that the SARS-CoV-2 pandemic may result in massive irruption of asthmatic patients in the hospital emergency ... [more ▼]

Given the prominent role of respiratory viruses in asthma exacerbations it has been feared that the SARS-CoV-2 pandemic may result in massive irruption of asthmatic patients in the hospital emergency departments. It seems, however, that asthma is not a particular risk factor for SARS-COV-2 infection nor for death resulting from severe infection. Inhaled corticosteroids (ICS) were found to reduce expression of ACE2 receptor in sputum cells, thereby maybe reducing the risk of lung infection. Only the more severe asthmatic patients treated with oral corticoids or high dose ICS were found to be at risk of death, presumably because of associated comorbidities. Biologicals directed towards IgE or interleukin-5 do not seem to confer an increased risk of severe infection. [less ▲]

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See detailEffectiveness of omalizumab on patient reported outcomes, lung function, and inflammatory markers in severe allergic asthma
Frix, Anne-Noëlle ULiege; Schleich, Florence ULiege; PAULUS, Virginie ULiege et al

in Biochemical Pharmacology (2020), 179

Background: Omalizumab arose as a therapeutic option in patients suffering from moderate to severe refractory allergic asthma. It acts as a humanized monoclonal antibody neutralizing circulating IgE ... [more ▼]

Background: Omalizumab arose as a therapeutic option in patients suffering from moderate to severe refractory allergic asthma. It acts as a humanized monoclonal antibody neutralizing circulating IgE antibodies. Randomized clinical trials and real life clinical studies have already confirmed benefits, cost-effectiveness and applicability of the medication. Method: Our study retrospectively reports on the clinical outcomes and airway inflammation in 157 severe allergic asthmatics who were initiated with omalizumab between 2007 and 2019. Results: After 4 months of therapy, 76% of the patients were judged to have benefited from omalizumab and were admitted to prolonged treatment. During follow-up, we observed an improvement in asthma control, quality of life and spirometric performance. There was also a sustained reduction in exacerbation rate over the years. As for T2 biomarkers, FeNO significantly decreased and, in a subgroup of patients who had repeated sputum inductions, there was also significant reduction in sputum eosinophils but no change in blood eosinophil count. Lastly, we found a correlation between high FeNO levels at baseline and reduction in ACQ scores at 1 year. Conclusion: We conclude that omalizumab shows effectiveness in severe allergic asthma in a real life setting, by reducing exacerbation rate, improving patient perspective outcomes and airway calibre, together with reducing type-2 airway inflammation. © 2020 Elsevier Inc. [less ▲]

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See detailUne décennie d’avancées dans l’asthme : l’apport des biothérapies.
Schleich, Florence ULiege; Frix, Anne-Noëlle ULiege; Paulus, Virginie ULiege et al

in Revue medicale de Liege (2020), 75(5-6), 350-355

Asthma is a chronic heterogeneous airway disease. There are different asthma inflammatory phenotypes with various responses to treatment and different disease severities. When asthma requires chronic ... [more ▼]

Asthma is a chronic heterogeneous airway disease. There are different asthma inflammatory phenotypes with various responses to treatment and different disease severities. When asthma requires chronic systemic corticosteroids or hospitalizations despite maximal inhaled therapies in asthmatic patients in whom comorbidities have been managed and who are considered as compliant, the pulmonologist may propose biological treatment to reduce exacerbations and the dose of systemic corticosteroids. During the last ten years, the number of biologics for the management of type-2 severe asthma has increased. Anti-IgE monoclonal antibodies (omalizumab) are available for more than ten years and recommended in severe allergic asthma. New biologics are now available to block IL-5 (mepolizumab, reslizumab) or its receptor (benralizumab). These treatments allow a reduction of exacerbations and of the dose of systemic corticosteroids, an improvement in asthma control, in asthma quality of life and for some of them, an increase in lung function. New biologics will soon be available in Belgium for the management of severe asthma. In addition to the improvement of asthma control in severe asthma, biological treatments have improved the understanding of the mechanisms leading to severe asthma. [less ▲]

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See detailSingle-center experience of patients with interstitial lung diseases during the early days of te COVID-19 pandemic.
GUIOT, Julien ULiege; HENKET, Monique ULiege; Frix, Anne-Noëlle ULiege et al

in Respiratory Investigation (2020), 58(6), 437-9

Introduction: Patients with interstitial lung diseases (ILD) can be suspected to be at risk of experiencing a rapid flare-up due to COVID-19. However, no specific data are currently available for these ... [more ▼]

Introduction: Patients with interstitial lung diseases (ILD) can be suspected to be at risk of experiencing a rapid flare-up due to COVID-19. However, no specific data are currently available for these patients. <br /> <br />Methods: We retrospectively analyzed a cohort of 401 patients with ILD and determined the proportion of patients hospitalized for proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific symptoms of COVID-19. <br /> <br />Results: We found that 1% of patients (n = 4) were hospitalized (1 in ICU) for COVID-19. In total, 310 of the 401 patients answered the phone call. Only 33 patients (0.08%) experienced specific symptoms of SARS-CoV-2 infection. <br /> <br />Conclusion: Our study did not demonstrate any increased occurrence of severe COVID-19 in ILD patients compared to the global population. Based on our findings, we could not make any conclusion on the incidence rate of SARS-CoV-2 infection in patients with ILDs, or on the overall outcome of immunocompromised patients affected by COVID-19. [less ▲]

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See detailDevelopment and validation of an automated radiomic CT signature for detecting COVID-19
Vaidyantahan, Akshayaa; GUIOT, Julien ULiege; DEPREZ, Louis ULiege et al

in European Respiratory Journal (2020)

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See detailDevelopment and Validation of an Automated Radiomic CT Signature for Detecting COVID-19.
GUIOT, Julien ULiege; Vaidyanathan, Akshayaa; DEPREZ, Louis ULiege et al

in Diagnostics (Basel, Switzerland) (2020), 11(1),

The coronavirus disease 2019 (COVID-19) outbreak has reached pandemic status. Drastic measures of social distancing are enforced in society and healthcare systems are being pushed to and beyond their ... [more ▼]

The coronavirus disease 2019 (COVID-19) outbreak has reached pandemic status. Drastic measures of social distancing are enforced in society and healthcare systems are being pushed to and beyond their limits. To help in the fight against this threat on human health, a fully automated AI framework was developed to extract radiomics features from volumetric chest computed tomography (CT) exams. The detection model was developed on a dataset of 1381 patients (181 COVID-19 patients plus 1200 non COVID control patients). A second, independent dataset of 197 RT-PCR confirmed COVID-19 patients and 500 control patients was used to assess the performance of the model. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC). The model had an AUC of 0.882 (95% CI: 0.851-0.913) in the independent test dataset (641 patients). The optimal decision threshold, considering the cost of false negatives twice as high as the cost of false positives, resulted in an accuracy of 85.18%, a sensitivity of 69.52%, a specificity of 91.63%, a negative predictive value (NPV) of 94.46% and a positive predictive value (PPV) of 59.44%. Benchmarked against RT-PCR confirmed cases of COVID-19, our AI framework can accurately differentiate COVID-19 from routine clinical conditions in a fully automated fashion. Thus, providing rapid accurate diagnosis in patients suspected of COVID-19 infection, facilitating the timely implementation of isolation procedures and early intervention. [less ▲]

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See detailDevelopment of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study.
Wu, Guangyao; Yang, Pei; Xie, Yuanliang et al

in European Respiratory Journal (2020)

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality. OBJECTIVE: To develop and validate machine-learning model ... [more ▼]

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality. OBJECTIVE: To develop and validate machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission. METHOD: 725 patients were used to train and validate the model including a retrospective cohort of 299 hospitalised COVID-19 patients at Wuhan, China, from December 23, 2019, to February 13, 2020, and five cohorts with 426 patients from eight centers in China, Italy, and Belgium, from February 20, 2020, to March 21, 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion-matrix. RESULTS: The median age was 50.0 years and 137 (45.8%) were men in the retrospective cohort. The median age was 62.0 years and 236 (55.4%) were men in five cohorts. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.89, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 57.5% to 88.0%, all of which performed better than the pneumonia severity index. The cut-off values of the low, medium, and high-risk probabilities were 0.21 and 0.80. The online-calculators can be found at www.covid19risk.ai. CONCLUSION: The machine-learning model, nomogram, and online-calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission. [less ▲]

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See detailThermoplastie bronchique dans le traitement de l’asthme sévère. Analyse rétrospective de 10 cas traités au CHU de Liège
Frix, Anne-Noëlle ULiege; HEINEN, Vincent ULiege; SCHLEICH, FLorence ULiege et al

in Revue Médicale de Liège (2019), 74(2), 74-81

Summary: As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) – ie ... [more ▼]

Summary: As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) – ie. bronchoscopic procedure delivering a thermic form of energy through radiofrequency to the bronchi, in order to interfere with the components of the smooth muscle layer – arose as a promising technique. Our study followed the path of 10 patients from CHU Liège (University Hospital), who underwent this procedure in a context of severe asthma. We compared clinical and spirometric and treatment data in patients at 0 – 6 and 12 months post-procedural intervals, in order to determine whether thermoplasty had been improving asthma. Overall, we observed a stabilization and possibly a clinical improvement while reducing the total amount of exacerbation rate, and the burden of maintenance oral corticoids. © 2019 Revue Medicale de Liege. All Rights Reserved. [less ▲]

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