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Olivier Taton,1 Vincent Heinen,2 Benjamin Bondue,1 Dirk-Jan Slebos,3,4 Pallav L Shah,5– 7 Kris Carron,8 Olivia Moens,9 Dimitri Leduc1 1Department of Pneumology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; 2Department of Pneumology, Centre Hospitalier Universitaire de Liège, Liège, Belgium; 3Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 4The Netherlands and GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 5Royal Brompton Hospital, London, UK; 6National Heart & Lung Institute, Imperial College, London, UK; 7Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 8Department of Pneumology, AZ Delta, Menen, Belgium; 9Department of Radiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, BelgiumCorrespondence: Olivier Taton, Department of Pneumology, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik, 808, Brussels, 1070, Belgium, Tel +3225553943, Email Olivier.taton@erasme.ulb.ac.beAbstract: Endoscopic lung volume reduction using unidirectional endobronchial valves is a new technique in the treatment of patients with severe emphysema. However, the movements of the thoracic structures after endobronchial valves insertion are still unpredictable We report the unusual outcome of six patients after valves insertion in the left upper lobe. They all developed a complete atelectasis of the target lobe, a pneumothorax and sequential genuine bullae in the treated left lung of unknown etiology. The chest CT scan prior to the valves insertion was unremarkable. Three patients developed an air–liquid level in the bullae the day before a bacterial infection of their left lower lobe. The three other patients had an uneventful spontaneous resolution of their bullae at long-term follow-up. Therefore, a conservative attitude should be followed in this particular setting.Keywords: endoscopic lung volume reduction, pneumothorax, chest CT scanner, chest tube drainage

Background & Aims Among hospitalized patients with COVID‐19, up to 12% may require intensive care management (ICU). The aim of this prospective cohort study is to assess nutritional status and outcome in patients with COVID‐19 following ICU discharge. Methods All patients with COVID‐19 requiring a minimum of 14 days stay in the ICU with mechanical ventilation were included. Nutritional status was assessed at inclusion (ICU discharge) and follow‐up (after 15, 30 and 60 days). All patients had standardized medical nutrition therapy with defined targets regarding energy (30 kcal/kg/d) and protein intake (1,5g/kg/d). Results Fifteen patients were included (67% Males); median age was 60 (33 ‐75) years old. Body Mass index at ICU admission was 25,7 (IQR, 24 – 31) kg/m². After a median ICU stays of 33 (IQR, 26 – 39) days, malnutrition was present in all patients (11,3% median weight loss and/or low muscle mass based on hand grip strength measurement). Because of post‐intubation dysphagia in 60% of patients, enteral nutrition was administered (57% naso‐gastric tube; 43% percutaneous endoscopic gastrostomy). After 2‐month, a significant improvement in muscle strength was observed (median handgrip strength: 64,7%(IQR, 51 – 73) of the predicted values for age vs 19% (IQR, 4,8 – 28,4) at ICU discharge (p < 0,0005)), as well as weight gain of 4,3 kg (IQR, 2,7 – 6,7) (p< 0,0002). Conclusions Critically ill patients with COVID‐19 requiring ICU admission and mechanical ventilation have malnutrition and low muscle mass at ICU discharge. Nutritional parameters improve during rehabilitation with standardized medical nutrition therapy. This article is protected by copyright. All rights reserved

Background. Bronchoalveolar lavage (BAL) is currently not recommended in noncritically ill patients for the diagnosis of SARS-CoV-2 infection. Indeed, the diagnosis is based on the RT-PCR test on a nasopharyngeal swab (NPS) and abnormal findings on the chest CT scan. However, the sensitivity of the NPS and the specificity of the chest CT scan are low. Results of BAL in case of negative NPS testing are underreported, especially in the subgroup of immunocompromised patients. Objectives. The added value of BAL in the management of unstable, but noncritically ill patients, suspected of having SARS-CoV-2 infection despite one previous negative NPS and the side effects of the procedure for the patients and the health-care providers, were assessed during the epidemic peak of the COVID-19 outbreak in Belgium. Methods. This multicentric study included all consecutive noncritically ill patients hospitalized with a clinical and radiological suspicion of SARS-CoV-2 infection but with a negative NPS. BAL was performed according to a predefined decisional algorithm based on their state of immunocompetence, the chest CT scan features, and their respiratory status. Results. Among the 55 patients included in the study, 14 patients were diagnosed with a SARS-CoV-2 infection. Interestingly, there was a relationship between the cycle threshold of the RT-PCR and the interval of time between the symptom onset and the BAL procedure (Pearson's correlation coefficient=0.8, p=0.0004). Therapeutic management was changed in 33 patients because another infectious agent was identified in 23 patients or because an alternative diagnosis was made in 10 patients. In immunocompromised patients, the impact of BAL was even more marked (change in therapy for 13/17 patients). No significant adverse event was noted for patients or health-care staff. All health-care workers remained negative for SARS-CoV-2 NPS and serology at the end of the study. Conclusions. In this real-life study, BAL can be performed safely in selected noncritically ill patients suspected of SARS-CoV-2 infection, providing significant clinical benefits that outweigh the risks., SCOPUS: ar.j, info:eu-repo/semantics/published

The different waves of the COVID-19 pandemic caused dramatic issues regarding the organization of care. In this context innovative solutions have to be developed in a timely manner to adapt to the organization of the care. The establishment of middle care (MC) units is a bright example of such an adaptation. A multidisciplinary MC team, including expert and non-expert respiratory health care personnel, was developed and trained to work in a COVID-19 MC unit. Important educational resources were set up to ensure rapid and effective training of the MC team, limiting the admission or delaying transfers to ICU and ensuring optimal management of palliative care. We conducted a retrospective analysis of patient data in the MC unit during the second COVID-19 wave in Belgium. The aim of this study was to demonstrate the feasibility of quickly developing an effective respiratory MC unit mixing respiratory expert and non-expert members from outside ICUs. The establishment of an MC unit during a pandemic is feasible and needed. MC units possibly relieve the pressure exerted on ICUs. A highly trained multidisciplinary team is key to ensuring the success of an MC unit during such kind of a pandemic. The authors would like to thank all the doctors, nurses, physiotherapists, psychologists and social workers who participated in the care of patients in this middle care unit. Olivier Van Hove and Alexis Gillet received grants from “Fonds Erasme pour la recherche médicale” to support their research.

Supplemental Digital Content is available in the text., OBJECTIVES: Venovenous extracorporeal membrane oxygenation has been largely used in patients with refractory acute respiratory distress syndrome due to coronavirus disease 2019. Few data on long-term pulmonary function among venovenous extracorporeal membrane oxygenation survivors are available. DESIGN: Retrospective, observational cohort. SETTING: Two mixed medical-surgical tertiary (30 beds) and secondary (22 beds) ICUs. PATIENTS: All critically ill adult coronavirus disease 2019 survivors treated with venovenous extracorporeal membrane oxygenation between March 10, and April 30, 2020. MEASUREMENTS AND MAIN RESULTS: The last available lung function and 6-minute walking tests, performed after a median of 178 days (ranges, 72–232 d) from ICU admission, were analyzed. Among the 32 coronavirus disease 2019 patients treated by venovenous extracorporeal membrane oxygenation during the study period, 11 (34%; median age 56 yr; median duration of mechanical ventilation and extracorporeal membrane oxygenation therapy of 26 and 15 d, respectively) were successfully weaned and discharged home. Spirometry was performed in nine patients; the volumetric lung function was preserved, that is, median forced vital capacity was 83% of predicted value (51–99% of predicted value), and median forced expiratory volume in 1 second was 82% of predicted value (60–99% of predicted value). Also, the median residual volume and the lung capacity were 100% of predicted value (50–140% of predicted value) and 90% of predicted value (50–100% of predicted value); only the diffusion capacity of the lung for carbon monoxide and 6-minute walking test were decreased (58% of predicted value [37–95% of predicted value] and 468 meters (365–625 meters), corresponding to [63–90% of predicted value], respectively). CONCLUSIONS: Among survivors from severe coronavirus disease 2019 pneumonia treated with venovenous extracorporeal membrane oxygenation, preserved long-term volumetric lung function with decreased diffusion capacity of lung carbon monoxide was observed.

Introduction Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0.06% (16/27,294) of all EGFR mutations and is an oncogenic driver. Several partial responses to afatinib have been described. Case description We report the first case, to the best of our knowledge, of the complete response to afatinib of a 57-year-old patient with stage IV lung adenocarcinoma with a delE709_T710insD mutation in the EGFR gene detected by next-generation sequencing. Oral afatinib was prescribed and despite treatment interruptions and dosage tapering due to cutaneous adverse events, a complete response was achieved 12 months after treatment initiation and is currently maintained at 17 months. Conclusion When EGFR mutation is suspected, complete DNA sequencing of exons 18 to 21 should be carried out and we suggest that afatinib should be the first-line treatment for exon 18 delE709_T710insD-mutated advanced lung adenocarcinomas. Learning points Rare EGFR gene mutations are not detected by standard diagnostic kits.DNA sequencing is required to diagnose rare mutations of the EGFR gene.delE709_T710insD-mutated stage IV lung adenocarcinomas respond to afatinib.

The surgical lung biopsy (SLB) is the recommended sampling technique when the pathological analysis of the lung is required in the work-up of an interstitial lung disease (ILD) but trans-bronchial lung cryobiopsy (TBLC) is increasingly recognized as an alternative approach. As TBLCs have lower mortality and morbidity risks than SLB, this study aimed to investigate the safety of TBLCs in patients at higher risk of complications and for whom SLB was not considered as an alternative., info:eu-repo/semantics/published

Our aims were to explore the feasibility, safety, and efficacy of peroperative transbronchial lung cryobiopsy (TBLC) guided by electromagnetic navigation bronchoscopy (ENB) and ENB-guided methylene blue marking of presumably non-palpable pulmonary nodules, and to assess its impact on video-assisted thoracoscopic surgery (VATS) and postoperative lung function.This approach was applied to 16 consecutive patients (Group A, mean age 64 years) who were compared retrospectively to a historical group of 49 patients (Group B, mean age 62 years) with similar nodules resected without guidance. The usefulness of dye marking was graded. The success rates of both ENB-guided TBLC and nodule localization through dye marking were computed. The type of resection, volume of resected parenchyma, duration of procedures, and postoperative lung function were compared between groups. Unpaired t-test, chi-square test, unpaired Wilcoxon test, and exact Fisher test were used when appropriate.Malignancy was pathologically proven in all patients. TBLC revealed malignancy in 9 patients in Group A. The success rate of ENB-guided dye marking was 94%. Lobectomy was less frequently performed in Group A than in Group B (p = 0.022). Forced expiratory volume in 1 s and total lung capacity were significantly less reduced in Group A than in Group B (p = 0.006 and p = 0.019, respectively). Combined procedure was longer than surgery alone (p0.001), but its surgical part was shorter than VATS without guidance (p 0.001).Peroperative ENB-guided TBLC with methylene blue marking of non-palpable lung nodules is feasible. A sparing lung parenchyma procedure could be achieved thanks to the ENB-guided dye marking before VATS.

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

The current gold-standard treatment for COVID-19-related hypoxemic respiratory failure is invasive mechanical ventilation. However, do not intubate orders (DNI), prevent the use of this treatment in some cases. The aim of this study was to evaluate if non-invasive ventilatory supports can provide a good therapeutic alternative to invasive ventilation in patients with severe COVID-19 infection and a DNI. Data were collected from four centres in three European countries. Patients with severe COVID-19 infection were included. We emulated a hypothetical target trial in which outcomes were compared in patients with a DNI order treated exclusively by non-invasive respiratory support with patients who could be intubated if necessary. We set up a propensity score and an inverse probability of treatment weighting to remove confounding by indication. Four-hundred patients were included: 270 were eligible for intubation and 130 had a DNI order. The adjusted risk ratio for death among patients eligible for intubation was 0.81 (95% CI 0.46 to 1.42). The median length of stay in acute care for survivors was similar between groups (18 (10–31) vs. (19 (13–23.5); p = 0.76). The use of non-invasive respiratory support is a good compromise for patients with severe COVID-19 and a do not intubate order., info:eu-repo/semantics/published

Rationale: Among hospitalized patients with COVID 19 pneumonia, up to 32% may require admission in intensive care units (ICU) The aim of this prospective cohort study is to assess nutritional parameters in patients with COVID 19 following ICU Methods: All patients with COVID 19 requiring ICU stay (minimum 14 days) with mechanical ventilation were included after ICU discharge Recorded parameters at the time of post-ICU rehabilitation unit (PIRU) admission included demographics, body mass index (BMI), weight loss (%), Hand Grip Test (kg), nutrition therapy modalities, and albumin dosage (gr/l) Quantitative parameters were expressed in median and range Results: Until May 5th2020, 11 patients were included (age 58(33-75) years old, and 5 men (45%)) BMI at ICU admission was 25 7 (22 2-33 3) kg/m2 Duration regarding ICU stay and ventilation were respectively 29 (25-39) and 22 (13-28) days Three patients (27%) required extracorporeal membrane oxygenation and tracheostomy was performed in 5 (45%) During ICU stay, enteral nutrition was administered to all patients through a naso-gastric tube;a percutaneous endoscopic gastrostomy was placed in the ICU in two patients One patient required complementary parenteral nutrition At the time of admission in the PIRU, BMI was 22 9 (19 1-32 9) kg/m2 and nutrition dosage was calculated at a median of 2553kcal/day (≥28 kcal/kg/day) and 128 gr protein/day (≥1 3 gr/kg/day) Weight loss since ICU admission was estimated at 8 3% (4 3%>14%) Post-extubation dysphagia requiring texture adaptation was present in 5 patients (45%) Albumin levels were 30 (26-36) gr/L Hand-grip was 12 (8-26) kg and 0 (0-20) kg for respectively men and women, reflecting significant sarcopenia Conclusion: Critical illpatients with COVID 19 pneumonia are malnourished and have severe sarcopenia following ICU stay despite adequate nutrition management Optimal nutrition therapy remains crucial during the rehabilitation period Disclosure of Interest: None declared

Background. An increasing number of pulmonary nodules of unknown nature are detected as a result of screening by CT in high lung cancer risk patients. Objectives. The purposes of this study were to assess the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) combined with transbronchial lung cryobiopsy (TBLC) and to compare it with standard transbronchial biopsy (TBB) in pulmonary nodules of less than 2 cm in diameter. Methods. We prospectively included 32 patients (18 men and 14 women, mean age 68 ± 9 years) with nodules of less than 2 cm in diameter and no metastasis at 18FDG PET-CT. The nodule position was determined by ENB, radial endobronchial ultrasonography miniprobe, and fluoroscopy. Eight samples were obtained, six by TBB and two by TBLC. Results. Nodule diameter averaged 16 ± 3 mm. Twenty-five nodules were malignant and 18 were surgically resected. Surgery was avoided in four patients as the biopsies revealed a benign disease. The samples obtained by TBLC were five times larger than those by TBB. The diagnostic yields of TBLC and TBB were 69% and 38%, respectively (p=0.017). Adverse events consisted in 15 mild or moderate bleedings and one pneumothorax. Conclusions. In the setting of peripheral pulmonary lesions of less than 20 mm in diameter, ENB-combined TBLC is feasible and safe, provides larger samples, and has higher diagnostic yield than TBB., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction. Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like Aspergillus galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the Aspergillus galactomannan assay is not frequent. Case presentation. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution. Conclusion. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.

Unilateral bronchial occlusion, a complication of many lung diseases, causes dyspnea but the mechanism of this symptom is uncertain. In this study, electromyographic (EMG) activity in the parasternal and external intercostal muscles in the third intercostal space and inspiratory motion of the third rib on both sides of the thorax were assessed during occlusion of a main bronchus for a single breath in anesthetized dogs. Occlusion produced a 65% increase in external intercostal EMG activity in both hemithoraces without altering parasternal EMG activity. Concomitantly, the inspiratory cranial rib motion showed a 50% decrease on both sides of the thorax. These changes were unaffected by bilateral vagotomy. However, when an external, caudally oriented force was applied to the third rib on the right or left side so that its inspiratory cranial displacement was abolished, activity in the adjacent external intercostals showed a twofold increase, but rib motion and external activity in the contralateral hemithorax remained unchanged. It is concluded that during occlusion of a main bronchus, the increase in external intercostal activity is induced by the decrease in inspiratory cranial rib displacement in both hemithoraces, and that this decrease is determined by the increase in pleural pressure swings on both sides of the mediastinum. This mechanism, combined with the decrease in PaO2, induces similar alterations when unilateral bronchial occlusion is maintained for a series of consecutive breaths., SCOPUS: ar.j, info:eu-repo/semantics/published

In this prospective study, cardiac output was measured in 38 intensive care unit patients before and after a fluid challenge, using both pulse contour analysis (Nexfin(®); BMEYE, Amsterdam, the Netherlands) and transthoracic echocardiography. The ability of the Nexfin device to detect significant changes in the velocity-time integral was evaluated. The pulse wave could not be detected by the Nexfin device in five patients (13%), leaving 33 patients for analysis. The Nexfin device adequately tracked changes in the velocity-time integral in 20 (61%) patients. Using a cut-off of a 10% increase in cardiac output estimated by the Nexfin or by echocardiography, the sensitivity of the Nexfin device to detect a response to fluid challenge was 47%, with specificity 81% and accuracy 64%. The percentage error between the Nexfin and echocardiography was 448%; lower limit of agreement -48% (95% CI -62 to -36%) and upper limit of agreement, 32% (95% CI 20-45%). We conclude that the Nexfin device does not adequately track changes in cardiac output in critically ill patients.

Invasive fungal infections are a major cause of mortality among solid organ transplant recipients. Scopulariopsis species and their teleomorph Microascus are molds found in soil and decaying organic matter. We report here the case of a woman who underwent bilateral lung transplantation for severe emphysema. On day 25 after transplantation, endobronchial green-black lesions were detected during routine endoscopy. Endobronchial swabs, biopsies, and bronchoalveolar lavage samples were positive for Microascus cirrosus. This fungal infection developed despite voriconazole given for previous persistent invasive aspergillosis. Treatment consisted of a combination of antifungal medication (voriconazole, terbinafine, amphotericin B, and caspofungin) and endoscopic resection of necrosed bronchial mucosa. A favorable clinical outcome was achieved after 7 weeks of treatment. Seven cases of Scopulariopsis/Microascus infection have been previously described in solid organ transplant recipients. Only two survived after treatment with an antifungal combination therapy including echinocandins, posaconazole, and terbinafine. In immunocompromised patients, infection by Microascus species is a rare but life-threatening event because of innate resistance to most common antifungal drugs. Our patient was successfully cured by combined therapy including intravenous voriconazole and caspofungin, oral terbinafine, and inhaled voriconazole and amphotericin B administered for 7 weeks in association with iterative endoscopic debridement to reduce fungal inoculum.