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Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.

BackgroundInterstitial lung diseases (ILD) are a heterogeneous group of infiltrating lung pathologies, requiring diagnosis and assessment, among which chest CT is of utmost importance. Nevertheless, the imaging modalities for the follow-up do not have formal guidelines and remain at the discretion of the clinician.MethodsOur study restrospectively evaluated the indication of chest CT in a cohort of 129 ILD patients. The aim was to determine whether the realization of the imaging control had a true impact on clinical course and follow-up. We accept 3 different situations for justifying the indication of the CTs as clinical deterioration, decrease in pulmonary function tests (at least 10% drop in a parameter) and monitoring for oncological purposes. The other indications, mainly classical follow-up, were classified as “non justified”. We selected patients from our ambulatory care polyclinic at Liège University Hospital.ResultsWe followed up a total cohort of 129 ILD patients. The mean number of CT scan per patient per year was 1.7±0.4 determining an irradiation in CT Dose Index (mGy)/year of 34.9±64.9 and an irradiation dose x length product in (mGy*cm)/year of 1095±1971. Around 40% of the routinely prescribed monitoring CT scans had no impact on the management of ILD and direct patient care, raising the question of inappropriate irradiation Conclusion Our study identifies overuse of chest CT scanner in the follow-up of ILD outside those performed for clinical exacerbation or oncological investigation. In the particular case of ILD exacerbation, CT-scan valuability stay high underlying the benefit of this validated strategy.

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown.MethodsTwo independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts.ResultsExosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, pDiscussionOur results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts.

Background Patients suffering from combined obstructive and interstitial lung disease (O-ILD) represent a pathological entity which still has to be well clinically described. The aim of this descriptive and explorative study was to describe the phenotype and functional characteristics of a cohort of patients suffering from functional obstruction in a population of ILD patients in order to raise the need of dedicated prospective observational studies and the evaluation of the impact of anti-fibrotic therapies. Methods The current authors conducted a retrospective study including 557 ILD patients, with either obstructive (O-ILD, n = 82) or non-obstructive (non O-ILD, n = 475) pattern. Patients included were mainly males (54%) with a mean age of 62 years. Results Patients with O-ILD exhibited a characteristic functional profile with reduced percent predicted forced expired volume in 1 s (FEV1) [65% (53–77) vs 83% (71–96), p Conclusions The authors individualized a specific functional-based pattern of ILD patients with obstructive lung disease, who are at risk of increased mortality and rapid DLCO decline over time. As classically those patients are excluded from clinical trials, a dedicated prospective study would be of interest in order to define more precisely treatment response of those patients.

SSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc-interstitial lung disease progression has a wide spectrum. Since the treatment is based on aggressive immunosuppression it should not be given to stable or non-progressing disease. The correct identification of disease with high risk of progression remains a challenge for early therapeutic intervention, and biomarkers remain urgently needed. In fact, eight categories of biomarkers have been identified and classified according to the different biological pathways involved. The purpose of this article is to describe the main biomarkers thought to be of interest with clinical value in the diagnosis and prognosis of SSc-interstitial lung disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.Methods: We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n=102), among which SSc-no ILD (n=63) and SSc-ILD (n=39), compared to healthy subjects (HS) (n=39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years.Results: Serum level of IGFBP-2 was significantly increased in SSc patients compared to HS, and negatively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) (r=-0.29, p 105 ng/ml was associated with a poor outcome (KCO Conclusions: We showed for the first time that serum levels of IGFBP-2 might be a prognostic factor of the development of SSc-ILD. Indeed, initial level of IGFBP-2 above 105 ng/ml was associated with a poor patient’s outcome (KCO

Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p

Background Asthmatics and COPD patients have more severe outcomes with viral infections than people without obstructive disease. Objective To evaluate if obstructive diseases are risk factors for ICU stay and death due to COVID19. Methods We collected data from the electronic medical record from 596 adult patients hospitalized in University hospital of Liege between 18th of March and 17th of April 2020 for SARS-CoV2 infection. We classified patients in three groups according to the underlying respiratory disease, present prior to COVID19 pandemics. Results Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7% respectively. The proportions of asthmatics, COPD and patients without obstructive airway disease hospitalized in ICU were 17.5%, 19.6% and 14% respectively. One third of COPD patients died during hospitalization while 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, ICS treatment and OCS treatment were not independent risk factors for ICU admission or death. Male gender (OR:1.9; 95%CI: 1.1 to 3.2) and obesity (OR:8.5; 95%CI: 5.1 to 14.1) were predictors of ICU admission while male gender (OR1.9; 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., Highlights What is already known about this topic? Asthmatics and COPD patients are at risk of more severe outcomes with common cold virus infections. Prior studies have suggested that allergic diseases, asthma and COPD may not be risk factors for SARS-CoV-2 infection. What does this article add to our knowledge? The strength of this study is the characterization of obstructive disease according to lung function testing. In our study, asthma, COPD, treatment with ICS or OCS were not risk factors for admission to the ICU or mortality. How does this study impact current management guidelines? Our results confirm the recommendations that patients with obstructive airway disease should not decrease the dose of ICS during SARS-CoV2 infection. Asthma and COPD treatments should be pursued and adapted to ensure optimal control of the lung disease throughout the pandemic, potentially reducing the risk of severe COVID19 disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.Methods: We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n=102), among which SSc-no ILD (n=63) and SSc-ILD (n=39), compared to healthy subjects (HS) (n=39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts. Results: Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r=0.6, pConclusions: We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.

BackgroundSystemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared.MethodsIn a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%).ResultsThe IS of SSc patients had a lower weight than HV (pConclusionOur study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-□ and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.

Background: IPF is a progressive fibrosing interstitial lung disease of unknown etiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in IPF. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown. Methods: Two independent cohorts were enrolled at the ambulatory care polyclinic of Liege University. Exosomes from sputum were obtained from 16 IPF patients and 14 healthy subjects (HS) (cohort 1), and the ones from plasma derived from 9 IPF patients and 9 HS (cohort 2). Exosomal miR expression was performed by quantitative RT-PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts. Results: Exosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of IPF patients. Correlation analysis revealed that the expression of sputum exosomal miR-142-3p was positively associated with sputum macrophages of IPF patients (r = 0.585; p=0.028), suggesting the macrophage origin of this miR. Overexpression of miR-142-3p in A549 alveolar epithelial cells and MRC5 lung fibroblasts revealed that this miR downregulates the expression of Transforming Growth Factor β Receptor 1 (TGFβ-R1) and pro-fibrotic genes. Furthermore, exosomes isolated from THP-1 macrophages also present anti-fibrotic properties due in part to the transfer of miR-142-3p to alveolar epithelial cells and lung fibroblasts. Conclusion: Our results suggest that macrophage-derived exosomes may exert protective effect against pulmonary fibrosis progression via the delivery of anti-fibrotic miR-142-3p.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with potential rapid evolving interstitial lung disease (SSc-ILD), driving the mortality of these patients. Therefore, a specific biomarker associated with the evolution of that disease is highly needed to identify patients with an increased risk of death. Aim of the Study: Identify specific biomarkers of SSc-ILD to predict the evolution of the disease. Methods: In this prospective longitudinal study, we compared serum levels of biomarkers assumed to be associated with lung fibrosis (TGF-β, IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, IL-8, MMP-7, MMP-9, YKL-40 and TNF-α) among three groups: SSc-ILD (n=39), SSc without ILD (n=63) and healthy subjects (HS)(n=39). We also prospectively analyzed variations of biomarkers and correlated them to pulmonary function tests (n=28). Then, we realized an in vitro analysis to study the potential anti-fibrotic effect of IGFBP-2 (n=3). Results: IGFBP-2, IL-8 and MMP-9 are increased in SSc patients compared to HS (p Conclusion: IGFBP-1 has a potential interest to identify early SSc-ILD whereas IGFBP-2 would rather predict the risk of a rapid evolution of lung fibrosis. Moreover, in vitro studies confirmed the anti-fibrotic effect of IGFBP-2 underlying its potential interest in further mechanical studies and therapeutic aspects.

Introduction: Anti-synthetase syndrome (ASS) is a rare auto-immune disorder combining autoantibodies and specifics clinical manifestations. One of the particularities of the ASS is the pleiomorphic radiological presentation seen at the initial work-up. Evaluating treatment response can also be challenging and requires a specific clinical, functional, biological and radiological monitoring. Aim: To identify specific radiological and clinical features of ASS. Methods: We retrospectively studied all patients suffering from ASS in CHU of Liege until now. The diagnosis of ASS was made according to ERS’s criteria. We analyzed clinical features, pulmonary function test (PFT), computed tomography (CT), and longitudinal evolution with regard to their treatments. Results: In the whole cohort of 31 patients, we identified 19 anti-JO1, 5 anti-PL12 & 7 anti-PL-7. The sex-ratio is slightly in favor of male. Interestingly PL-12 syndrome was present in younger patients than those with others antibodies (mean age 39,8 vs 53,1 (JO1) & 73,3 (PL7) (p Conclusion: In our single center retrospective study, we found different profile of auto-antibodies according to age and radiological apparence.

Immunoglobulin G4-related disease is a rare autoimmune systemic disease with the capability of involving every organ. The disease is microscopically defined by a diffuse tissular inflammation with an infiltration of IgG4 positive plasma cells in the affected organs. IgG4 disease has an increasing incidence in the last few years with a growing interest in its pathophysiology still misunderstood to date. Despite the growing recognition of this pathology, the literature still does not allow to propose a simple diagnostic algorithm. In this article, we present a case of a 56-year-old man with a history of unknown etiology acute pancreatitis and a unilateral pleural effusion.

Introduction Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with an increased incidence since the last few years. Here, we report our eight-year clinical experience in CHU of Liège, Belgium. Methods We have studied retrospectively patients recruited from our ambulatory care polyclinic at CHU of Liège from 1 January 2009 to 1 January 2017. We have excluded all patients treated with a specific anti-fibrotic therapy due to incomplete follow-up. The diagnosis of IPF was made according to the ATS/ERS international recommendations (2015). Results Out of the 114 patients initially selected, 82 cases were found to be suitable for the analysis. The average age was 71.1 ± 9.35 years with a male predominance. The median survival was 43.7 months (23.6-71.7) with a majority (45%) of patients in the group II of the GAP index. The median rate of annual decline in diffusion capacity of CO (DLCO) was 11%, whereas the sub analysis for group III (according to GAP index) showed a decrease annual rate of 30%. Conclusion Our results are in keeping with the literature. One of our major finding is that patients in GAP III exhibit an annual rate of mortality of 42% and a median annual decline in DLCO of 30%. This observation highlights the fact that this specific subgroup of patients presents a high risk of morbi-mortality.