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Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic, global sequencing efforts have led in the field of inborn errors of immunity, and inspired particularly by previous research on life-threatening influenza, they have revealed that known and novel inborn errors affecting type I interferon immunity underlie critical COVID-19 in up to 5% of cases. In addition, neutralizing autoantibodies against type I interferons have been identified in up to 20% of patients with critical COVID-19 who are older than 80 years and 20% of fatal cases, with a higher prevalence in men and individuals older than 70 years. Also, inborn errors impairing regulation of type I interferon responses and RNA degradation have been found as causes of multisystem inflammatory syndrome in children, a life-threatening hyperinflammatory condition complicating otherwise mild initial SARS-CoV-2 infection in children and young adults. Better understanding of these immunologic mechanisms can aid in designing treatments for severe COVID-19, multisystem inflammatory syndrome in children, long COVID, and neuro-COVID.

Since the arrival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, its characterization as a novel human pathogen, and the resulting coronavirus disease 2019 (COVID-19) pandemic, over 6.5 million people have died worldwide—a stark and sobering reminder of the fundamental and nonredundant roles of the innate and adaptive immune systems in host defense against emerging pathogens. Inborn errors of immunity (IEI) are caused by germline variants, typically in single genes. IEI are characterized by defects in development and/or function of cells involved in immunity and host defense, rendering individuals highly susceptible to severe, recurrent, and sometimes fatal infections, as well as immune dysregulatory conditions such as autoinflammation, autoimmunity, and allergy. The study of IEI has revealed key insights into the molecular and cellular requirements for immune-mediated protection against infectious diseases. Indeed, this has been exemplified by assessing the impact of SARS-CoV-2 infection in individuals with previously diagnosed IEI, as well as analyzing rare cases of severe COVID-19 in otherwise healthy individuals. This approach has defined fundamental aspects of mechanisms of disease pathogenesis, immunopathology in the context of infection with a novel pathogen, and therapeutic options to mitigate severe disease. This review summarizes these findings and illustrates how the study of these rare experiments of nature can inform key features of human immunology, which can then be leveraged to improve therapies for treating emerging and established infectious diseases.

INTRODUCTION : Les pneumopathies d’hypersensibilité (PHS) font partie des pneumopathies interstitielles diffuses les plus courantes. Elles sont caractérisées par une réaction inflammatoire et/ou fibrosante pulmonaire vis-à-vis d’antigènes inhalés. ÉTAT DES CONNAISSANCES : Leur hétérogénéité de présentation et l’absence de recommandations internationales rend leur prise en charge complexe. En outre, le traitement actuel, qui repose principalement sur l’éviction de l’antigène causal et les médicaments immunosuppresseurs, est moins efficace dans les formes fibrosantes de PHS. Cet article établit une synthèse des dernières données et des nouvelles recommandations de l’American Thoracic Society (ATS) sur le diagnostic des PHS. CONCLUSIONS : Les nouvelles recommandations de l’ATS établissent une approche diagnostique plus précise et plus rigoureuse des PHS. La discussion multidisciplinaire joue un rôle pivot tant dans le diagnostic que dans le traitement de la maladie. Le nintedanib a récemment fait preuve de son efficacité dans les PHS fibrosantes. PERSPECTIVES : Il demeure des incertitudes sur la stratégie thérapeutique à adopter dans les PHS fibrosantes, ce qui souligne le besoin de réaliser des études à grande échelle. [New developments in the management of hypersensitivity pneumonitis] INTRODUCTION: Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases, characterized by an inflammatory and/or fibrotic reaction to inhaled antigens. BACKGROUND: The heterogeneity of presentation and the lack of international guidelines makes management complex. In addition, the current treatment, based on antigen eviction and immunosuppressive drugs, is less effective in the fibrotic forms of HP. This article summarizes the latest data on HP and the new recommendations of the American Thoracic Society (ATS) on the diagnosis of HP. CONCLUSION: The new ATS recommendations establish a more precise and rigorous diagnostic approach to HP. Multidisciplinary discussion plays a pivotal role both in the diagnosis and the treatment of the disease. Nintedanib has recently been shown to be effective in fibrotic HP. PERSPECTIVES: Questions remain unanswered about the optimal therapeutic strategy in fibrotic HP, which underlines the need to carry out large-scale studies.

Telomeres are non-coding DNA sequences that protect chromosome ends and shorten with age. Short telomere length (TL) is associated with chronic diseases and immunosenescence. The main risk factor for mortality of coronavirus disease 2019 (COVID-19) is older age, but outcome is very heterogeneous among individuals of the same age group. Therefore, we hypothesized that TL influences COVID-19-related outcomes. In a prospective study, we measured TL by Flow-FISH in 70 hospitalized COVID-19 patients and compared TL distribution with our reference cohort of 491 healthy volunteers. We also correlated TL with baseline clinical and biological parameters. We stained autopsy lung tissue from six non-survivor COVID-19 patients to detect senescence-associated β-galactosidase activity, a marker of cellular aging. We found a significantly higher proportion of patients with short telomeres (

Vaccination against COVID-19 constitutes a huge hope and a major challenge. For the first time in modern history, a global vaccination campaign has started worldwide in a short period of time and with products that were recently developed. Consequently, legitimate concerns regarding the safety and tolerability of COVID-19 vaccines arise. In line with international allergy societies, the Belgian Society for Allergy and Clinical Immunology (BelSACI) provides this statement to guide health care providers (general practitioners, specialists including allergists) and stakeholders. In this statement, we first review current evidence on allergic reactions to vaccines and the potential risk factors that have been identified. Second, we provide a risk stratification method that may be used as a worksheet during the vaccination campaign. Finally, we discuss the management of suspected or confirmed allergic reactions following vaccination.

Genetic predisposition to pulmonary fibrosis has been confirmed by the discovery of several gene mutations that cause pulmonary fibrosis. Although genetic sequencing of familial pulmonary fibrosis (FPF) cases is embedded in routine clinical practice in several countries, many centres have yet to incorporate genetic sequencing within interstitial lung disease (ILD) services and proper international consensus has not yet been established. An international and multidisciplinary expert Task Force (pulmonologists, geneticists, paediatrician, pathologist, genetic counsellor, patient representative and librarian) reviewed the literature between 1945 and 2022, and reached consensus for all of the following questions: 1) Which patients may benefit from genetic sequencing and clinical counselling? 2) What is known of the natural history of FPF? 3) Which genes are usually tested? 4) What is the evidence for telomere length measurement? 5) What is the role of common genetic variants (polymorphisms) in the diagnostic workup? 6) What are the optimal treatment options for FPF? 7) Which family members are eligible for genetic sequencing? 8) Which clinical screening and follow-up parameters may be considered in family members? Through a robust review of the literature, the Task Force offers a statement on genetic sequencing, clinical management and screening of patients with FPF and their relatives. This proposal may serve as a basis for a prospective evaluation and future international recommendations.

BACKGROUND: The impact of the COVID-19 pandemic on functional exercise capacity seemed quickly clinically evident. The objective of this study was to assess the functional exercise capacity of patients with severe COVID-19 and to evaluate the effect of a telerehabilitation program in the specific context of the COVID-19 pandemic. METHOD: Patients hospitalized for severe or critical COVID-19 were recruited. The functional exercise capacity (1-min sit-to-stand test (STST)) was prospectively quantified at discharge. A telerehabilitation program was then proposed. A control group was composed with the patients refusing the program. RESULTS: At discharge, none of the 48 recruited patients had a STST higher than the 50th percentile and 77% of them were below the 2.5th percentile. SpO2 was 92.6 ± 3.0% after STST and 15 patients had oxygen desaturation. After 3-months of follow-up, the number of repetitions during STST significantly increased either in telerehabilitation (n = 14) (p < 0.001) or in control groups (n = 13) (p = 0.002) but only one patient had a result higher than the 50th percentile (in Telerehabilitation group) and 37% of them were still under the 2.5th percentile for this result. The improvement was significantly and clinically greater after the telerehabilitation program (p = 0.005). No adverse events were reported by the patients during the program. CONCLUSIONS: Patients hospitalized for COVID-19 have a low functional exercise capacity at discharge and the recovery after three months is poor. The feasibility and the effect of a simple telerehabilitation program were verified, this program being able to substantially improve the functional recovery after three months.

Matrix remodeling is a salient feature of idiopathic pulmonary fibrosis (IPF). Targeting cells driving matrix production and remodeling could be a promising avenue for IPF treatment. Analysis of public transcriptomic database identified paired-related homeobox protein-1 (PRRX1) as an upregulated mesenchymal transcription factor (TF) in IPF. We confirmed that PRRX1 isoforms were upregulated in IPF lung tissue and strongly expressed by lung fibroblasts. In vitro, PRRX1 expression was up-regulated by cues associated with proliferative and anti-fibrotic properties in lung fibroblasts, while IPF fibroblast-derived matrix increased PRRX1 TFs expression in a PDGFR dependent manner in control ones. Meanwhile, signals promoting myofibroblastic differentiation decreased PRRX1 TF. We demonstrated that PRRX1 inhibition decreased fibroblast proliferation by downregulating the expression of S phase cyclins. PRRX1 inhibition also impacted TGF-{beta} driven myofibroblastic differentiation by inhibiting SMAD2/3 phosphorylation through phosphatase PPM1A upregulation and TGFBR2 downregulation, leading to a TGF-{beta} response global decrease. Finally, targeted inhibition of Prrx1 TFs attenuated fibrotic remodeling both in vivo with intra-tracheal antisense oligonucleotides in the bleomycin mice model of lung fibrosis and ex vivo using mouse and Human precision-cut lung slices stimulated with fibrosis cytokine cocktail. Altogether, our results identified PRRX1 as a mesenchymal transcription factor driving myofibroblastic phenotype and lung fibrogenesis. Brief SummaryInhibition of a single fibroblast-associated transcription factor, namely paired-related homeobox protein 1, is sufficient to dampen lung fibrogenesis.

International audience; Introduction Patients with short telomere-related interstitial lung disease (ILD) have worse outcomes after lung transplantation. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD lung transplant population. Methods We conducted a multi-institutional (Brigham and Women's Hospital, Groupe de Transplantation de la SPLF) retrospective cohort study of 63 recipients between 2009 and 2019 with ILD and short telomeres, compared to 4359 recipients from the Scientific Registry of Transplant Recipients with ILD and no known telomeropathy. Results In the short telomere cohort, six recipients (9.5%) developed dehiscence and nine recipients (14.3%) developed stenosis, compared to 60 (1.4%) and 149 (3.4%) in the control, respectively. After adjusting for age, sex, and bilaterality, the presence of short telomeres was associated with higher odds of dehiscence (odds ratio (OR) = 8.24, 95% confidence interval (CI) = 3.34 20.29, p < .001) and stenosis (OR = 4.63, 95% CI 2.21 9.69, p < .001). Conclusion The association between the presence of short telomeres and post-transplant dehiscence and stenosis suggest that airway complications may be a contributor to increased morbidity and mortality in patients with telomere-related ILD.

Epstein-Barr virus-associated smooth pulmonary tumor is a rare condition that mostly affects immunosuppressed patients. This case describes a young boy with a history of kidney transplantation who presented recurrent pneumonia. Multiple endobronchial soft tissue tumors affecting both right and left bronchial tree were found and partially removed by bronchoscopy. Immunohistologic analysis demonstrated Epstein-Barr virus-associated smooth pulmonary tumor. Immunosuppressive therapy was changed from tacrolimus to sirolimus. A few months later, new right upper lobe and inferior left lobe tumors were found. Recurrent left lower lobe pneumonia prompted lobectomy. In the present case, complete resection and change of immunosuppressive treatment were effective.

Introduction L’immunoglobuline A est l’immunoglobuline la plus abondante dans les muqueuses respiratoires. Elle est transportee a travers l’epithelium grâce au polymeric immunoglobulin receptor (pIgR) et secretee, liee a la partie extracellulaire de ce recepteur (secretory component, SC), sous la forme d’IgA secretoire (S-IgA). Vu les donnees recentes associant le taux serique d’IgA a la mortalite dans la fibrose pulmonaire idiopathique (FPI), nous formulons l’hypothese d’un role deletere du systeme IgA-pIgR dans le developpement de la fibrose pulmonaire. Methodes Nous avons etudie : – l’expression de pIgR, CK5 et proSPC dans du tissu pulmonaire de patients FPI et de temoins ; – les effets de l’IgA sur des fibroblastes en culture primaire pour l’expression d’α-SMA ; – un modele experimental de fibrose pulmonaire persistante chez des souris C57/bl6 sauvages (WT), pIgR-/− et IgA-/− de 12 semaines induit par instillations intratracheales de 6 doses successives de 0,015 UI de bleomycine. Le degre de fibrose etait quantifie apres 95 jours par la mesure d’OH-proline (μg/lobe), le LBA recupere pour comptage cellulaire et dosage de (S-)IgA, et le tissu pulmonaire marque par le Sirius Red (SR) et pour le pIgR et les marqueurs proSPC etCK5. Resultats Une expression distale aberrante du pIgR est observee au sein des kystes en rayon de miel, a proximite de cellules CK5+, ainsi qu’une augmentation de la production de SC chez les patients atteints de FPI. La fibrose experimentale est caracterisee par des taux majores d’IgA et de S-IgA dans le LBA ainsi que par une expression parenchymateuse distale du pIgR proche de cellules CK5+. En comparaison avec les souris sauvages, les souris pIgR-/− sont protegees de la fibrose, contrairement aux souris IgA-/-, comme atteste par l’OH-proline et le SR. Nos experiences preliminaires montrent que la S-IgA (et pas l’IgA non-secretoire) induit l’expression de α-SMA dans des fibroblastes pulmonaires primaires. Conclusions La fibrose pulmonaire est associee a une expression aberrante du pIgR exprime dans le parenchyme malade tant chez l’homme (FPI) que dans un modele murin. La protection des souris pIgR-/− suggere un role deletere du pIgR, potentiellement via l’activation des fibroblastes par la S-IgA.

Background In cystic fibrosis, the respiratory epithelium is the target tissue of both the genetic abnormality of the disease and of external aggressions, notably by pathogens (Pseudomonas aeruginosa). A detailed characterisation of the cystic fibrosis bronchial epithelium is however lacking, as most previous studies focused on the nasal epithelium or on cell lines. This study aimed to characterise the abnormal phenotype and epithelial-to-mesenchymal transition in cystic fibrosis bronchial epithelium and to evaluate in cell cultures whether abnormalities persist ex vivo. Methods Explant lung tissues (n = 44) were assessed for bronchial epithelial cell phenotyping by immunostaining. Human bronchial epithelial cells were derived from basal cells isolated from cystic fibrosis patients or control donors and cultured in air-liquid interface for 2, 4 or 6 weeks. Results Enhanced mucin 5AC and decreased β-tubulin expression were observed in cystic fibrosis airways reflecting a decreased ciliated/goblet cell ratio, associated with increased number of vimentin-positive cells, indicating epithelial-to-mesenchymal transition process. These features were recapitulated in vitro, in cystic fibrosis-derived reconstituted epithelium. However, they were not induced by CFTR inhibition or Pseudomonas infection, and most abnormalities tended to disappear in long-term culture (6 weeks) except for increased fibronectin release, an epithelial-to-mesenchymal transition marker. Conclusions This study provides new insights into airway epithelial changes in cystic fibrosis, which are imprinted through an acquired mechanism that we could not relate to CFTR function.

Current understanding of fibrosis remains incomplete despite the increasing burden of related diseases. Preclinical models are used to dissect the pathogenesis and dynamics of fibrosis, and to evaluate anti-fibrotic therapies. These studies require objective and accurate measurements of fibrosis. Existing histological quantification methods are operator-dependent, organ-specific, and/or need advanced equipment. Therefore, we developed a robust, minimally operator-dependent, and tissue-transposable digital method for fibrosis quantification. The proposed method involves a novel algorithm for more specific and more sensitive detection of collagen fibers stained by picrosirius red (PSR), a computer-assisted segmentation of histological structures, and a new automated morphological classification of fibers according to their compactness. The new algorithm proved more accurate than classical filtering using principal color component (red-green-blue, RGB) for PSR detection. We applied this new method on established mouse models of liver, lung, and kidney fibrosis and demonstrated its validity by evidencing topological collagen accumulation in relevant histological compartments. Our data also showed an overall accumulation of compact fibers concomitant with worsening fibrosis and evidenced topological changes in fiber compactness proper to each model. In conclusion, we describe here a robust digital method for fibrosis analysis allowing accurate quantification, pattern recognition, and multi-organ comparisons useful to understand fibrosis dynamics.

Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts. These changes in lung architecture require the activation of developmental pathways that are important regulators of cell transformation, growth and migration. Among others, aberrant expression of profibrotic Wnt-β-catenin, transforming growth factor-β and Sonic hedgehog pathways in IPF fibroblasts has been assessed. In the present review, we will discuss the transcriptional integration of these different pathways during IPF as compared with lung early ontogeny. We will challenge the hypothesis that aberrant transcriptional integration of these pathways might be under the control of a chaotic dynamic, meaning that a small change in baseline conditions could be sufficient to trigger fibrosis rather than repair in a chronically injured lung. Finally, we will discuss some potential opportunities for treatment, either by suppressing deleterious mechanisms or by enhancing the expression of pathways involved in lung repair. Whether developmental mechanisms are involved in repair processes induced by stem cell therapy will also be discussed.

Introduction: Costs related to IPF management are a major concern. Aims and Objectives: To assess real life costs for the medical management of IPF in Belgium based on PROOF-NEXT registry, a prospective longitudinal and observational study set in Belgium and Luxembourg. Methods: We included all antifibrotic naive patients with at least 3 months follow up since enrollment, between 2014 and 2019. Direct costs were calculated by multiplying each item of resource use, obtained from each individual patient chart, with its corresponding unit cost (2020, €) using the National Institute for Health and Disability Insurance perspective (NIHDI). We used a Kaplan–Meier sample average estimator to weigh expected costs by the probability of survival and to adjust for censored data (shorter follow up). Lung transplant costs are excluded (reason for leaving the registry). Results: We included 179 patients (80.4% male patients, mean age 70.9 years). The average observation time was 18.5 months. 88% of patients received AF therapy, pirfenidone being the first line treatment in 71% of cases, 9.5% received pulmonary rehabilitation. Mean overall cost/patient for the first year was 23,707€, 24,688€ for the second year and 22,797€ for the third year. Costs were driven by AF therapy cost (88.5%) followed by rehabilitation cost (5.6%). Conclusions: Management costs of IPF are mainly driven by AF therapy but are not increasing over time.

Background: Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs. Method: We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed. Results: Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies. Conclusions: TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern., SCOPUS: ar.j, info:eu-repo/semantics/published

Hypersensitivity pneumonitis (HP) is a respiratory disease caused by an inappropriate immune response to environmental antigens affecting the small airways and lung parenchyma. With an incidence of 0.3–1.94 cases per 100 000 per year [1, 2], HP is the third cause of interstitial lung disease (ILD) [3]. Seven to 17% of patients with HP report a positive family history for ILD [4, 5], suggesting predisposing genetic factors., This series reports cases of Cladosporium herbarum-related HP due to an uncommon exposure source, illustrating the genetic background underlying HP, and highlighting the role of environmental home inquiry and serum precipitins in diagnosis and follow-up https://bit.ly/3hzvE4w

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome., Graphical abstract

Nintedanib (Ofev®) and pirfenidone (Esbriet®) are recommended by international guidelines as treatment options for idiopathic pulmonary fibrosis (IPF)., info:eu-repo/semantics/published

Introduction: Idiopathic chronic eosinophilic pneumonia (ICEP) is an orphan lung disease characterized by concomitant systemic and local eosinophilia, along with bilateral lung infiltrates. Symptoms include dyspnea of subacute/chronic onset, cough, and general systemic signs. Although all patients do respond to oral corticosteroids, relapse rate is very high, which highlights the need for alternative therapies in case of relapsing ICEP. Mepolizumab is a fully humanized antibody directed against interleukin 5, a key growth factor of eosinophils. In the present study, we retrospectively studied the effect of off-label use of mepolizumab for relapsing ICEP. Materials and Methods: All data from patients treated with mepolizumab for relapsing ICEP were included in our database and diagnoses were reviewed. We analyzed the effect of treatment on relapse rate, oral corticosteroids (OCS) use, and lung lesions on high-resolution computed tomography (HRCT). Results: We included ten patients in the final analysis, with a median follow-up of 9 months after initiation of mepolizumab. Beside its expected effect on circulating eosinophils, treatment with mepolizumab was associated with a significant reduction of annual rate of exacerbations and a reduced consumption of corticosteroids. We also observed a remission of lung lesions on follow-up HRCT. Conclusions: In this open-label retrospective study, treatment of ICEP with mepolizumab was associated with a reduction of relapses, OCS use, and the disappearance of lung infiltrates., SCOPUS: ar.j, info:eu-repo/semantics/published

OBJECTIVES: Approximately half of the patients undergoing lung biopsy for nonresolving acute respiratory distress syndrome exhibit another histologic pattern than diffuse alveolar damage, with some of the pathologies characterized by a potential response to corticosteroids. This study aimed to assess whether open lung biopsy performed in the ICU for nonresolving acute respiratory distress syndrome was able to identify steroid-sensitive diseases and whether patients with a steroid-sensitive pathology experienced different clinical courses and outcomes. DESIGN: Retrospective analysis. SETTING: One 22-bed mixed ICU within a tertiary medical center. PATIENTS: Patients age greater than or equal to 16 years old who met the Berlin definition for acute respiratory distress syndrome and underwent open lung biopsy from January 2007 to January 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 695 patients diagnosed with acute respiratory distress syndrome were identified, 51 (7%) of whom underwent open lung biopsy. An alternative diagnosis to diffuse alveolar damage was found in 29 patients (57%), and a steroid-sensitive pathology was identified in 19 (37%). In-hospital and 180-day mortality rates were 55% and 61%, respectively. There was a significant difference in hospital mortality and 180-day mortality rates between patients with steroid-sensitive pathology and those with steroid-resistant pathology (37% vs 65%; p < 0.045 and 37% vs 75%; p < 0.007, respectively). We did not identify any variable that could reliably predict a steroid-sensitive histologic pattern before open lung biopsy. CONCLUSIONS: Open lung biopsy was able to identify a steroid-sensitive pathology in a significant proportion of nonresolving acute respiratory distress syndrome patients. These patients had a better outcome, with lower hospital mortality and 180-day mortality.

A patient with cystic fibrosis presented recurrent pneumonia in the upper right lobe. A polypoid lesion was found during bronchoscopy. We report the first case of a successful endoscopic resection of an inflammatory polyp without need for open surgery and without recurrence of the tumor nor lung infection. Key clinical Message This report highlights the usefulness of bronchoscopy in case of recurrent pneumonia with the same localization even in CF patients where the presence of bronchiectasis as promoting factor of infections could delay the diagnosis.

SCOPUS: le.j, info:eu-repo/semantics/published

International audience; Carriers of telomerase related genes (TRG) mutation seem to present a worst prognosis with more common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT and identify pre-LT prognosis factors in a multicenter cohort of lung transplant recipients with TRG mutation.We retrospectively reviewed all identified patients with pathogenic TRG mutation (n=38; TERT, n=22, TERC, n=10, RTEL1, n=6) who received LT in France, Switzerland and Belgium between 2009 and 2018. The median age at LT was 54 years (46-59), 70% were male, and 60% had idiopathic pulmonary fibrosis (IPF). At diagnosis of pulmonary fibrosis, 84% had a hematological disease, including 8 with myelodysplasia, and 45% had a liver disease. After a median follow up of 2.2 years (1,2-3,7), 16 received a single LT, 22 a double LT and 2 a combined liver-LT.The overall post-LT median survival was 3.75 years (1.8-NA). Patients with myelodysplasia before LT had an increased risk of death after LT (HR= 4.12 (1.47-11.53) p=0.007). After LT, all patients showed anemia, 70% thrombocytopenia, and 60% neutropenia. Four patients showed severe liver disease: portal hypertension, cirrhosis. Sixteen patients (42%) experienced acute renal failure and 18 (47%) developed chronic renal insufficiency during follow up. Four developed chronic lung allograft dysfunction.Overall survival after LT supports LT in TRG mutation carriers. Careful evaluation at diagnosis, might limit LT indication for patients with established myelodysplasia.

Introduction: Familial pulmonary fibrosis (FPF) is defined as lung fibrosis affecting at least 2 members of the 1st degree of a family. Monogenic pulmonary fibrosis is usually investigated in this case and/or when an idiopathic interstitial lung disease occurs in a patient younger than 55 years-old, eventually associated with extra-thoracic involvement. We reviewed all FPF cases seen in our university (2 tertiary hospitals) in 2017 and 2018. Methods: All FPF patients and an equal number of sporadic idiopathic pulmonary fibrosis (IPF) diagnosed between January 1st 2017 and December 31st 2018 were included in a database. Baseline characteristics, lung function tests, HRCT and histological patterns, haematological and liver features and one-year survival were studied. We used Mann-Whitney U and Chi-Square tests for statistical analysis. Our local ethics committee approved the study. Results: In 2017 and 2018, 24 patients had suspected FPF and/or monogenic lung fibrosis (3.9% of all patients discussed in multidisciplinary meeting). They were significantly younger (median age at diagnosis 63 ± 11 years) as compared to the 24 sporadic IPF patients (73 ± 9 years), P = 0.002. Fifteen FPF patients (62.5%) agreed to undergo genetic testing. We identified a mutation of the telomerase complex in 6 of them (40%). Extra-pulmonary involvement was significantly associated with FPF (P = 0.02). One-year mortality was significantly higher in FPF (29%) as compared to IPF (4%), P = 0.02. Conclusion: Our study confirms that FPF represents a substantial part of ILD, has a poor prognosis and is associated with extra-pulmonary involvement and younger age. Those patients require early support, multidisciplinary approach and genetic counselling.