Case 327: Exogenous Lipoid Pneumonia.

HISTORY: A 58-year-old male patient with an active smoking status was admitted twice to the intensive care unit (ICU) of a tertiary referral thoracic center for severe hypercapnic acute respiratory failure and persistent bilateral chest radiograph opacities that were unchanged over the course of the two ICU admissions within a 3-month period. The patient had obesity (body mass index, 36), stage 3 vascular chronic renal insufficiency, and hebephrenic schizophrenia treated with haloperidol, carbamazepine, and cyamemazine. He reported chronic dyspnea on exertion, which worsened for 6 months. At the second ICU admission, the patient was afebrile, with a blood pressure of 160/72 mm Hg and pulse oximetry of 93% on 6 L/min oxygen therapy through a nonrebreathing mask. Physical examination showed signs of respiratory failure with wheezing and active abdominal expiration, and bilateral pulmonary crackles without chest pain, hemoptysis, clubbing, or signs of cardiac failure. The patient had no peripheral lymphadenopathy and no enlarged spleen. Blood gases (on 6 L/min oxygen) showed respiratory acidosis (pH, 7.15 [normal range, 7.38-7.42]; PaO2 level, 67 mm Hg [normal range, 80-100 mm Hg]; PaCO2 level, 102 mm Hg [normal range, 38-42 mm Hg]; bicarbonate [HCO3-], 29 mmol/L [normal range, 22-27 mmol/L]). Noninvasive ventilation was initiated. Imaging performed during the second ICU hospitalization included CT and MRI of the chest without contrast enhancement, and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT.

Case 327.

HISTORY: A 58-year-old man who was an active smoker was admitted twice to the intensive care unit (ICU) of a tertiary referral thoracic center for severe hypercapnic acute respiratory failure and persistent bilateral chest radiograph opacities that were unchanged over the course of the two ICU admissions within a 3-month period (Fig 1). He had obesity (body mass index, 36 kg/m2), stage 3 vascular chronic renal insufficiency, and hebephrenic schizophrenia treated with haloperidol, carbamazepine, and cyamemazine. He reported chronic dyspnea on exertion, which worsened for 6 months. At the second ICU admission, he was afebrile, with a blood pressure of 160/72 mm Hg and pulse oximetry of 93% on 6 L/min oxygen therapy through a nonrebreathing mask. Physical examination showed signs of respiratory failure with wheezing and active abdominal expiration, bilateral pulmonary crackles without chest pain, hemoptysis, clubbing, or signs of cardiac failure. He had no peripheral lymphadenopathy and no enlarged spleen. Blood gases (on 6 L/min oxygen) showed respiratory acidosis (pH, 7.15 [normal range, 7.38-7.42]; Pao2 level, 67 mm Hg [normal range, 80-100 mm Hg]; Paco2 level, 102 mm Hg [normal range, 38-42 mm Hg]; Hco3- level, 29 mmol/L [normal range, 22-27 mmol/L]). Noninvasive ventilation was initiated. Imaging performed during the second ICU hospitalization included noncontrast chest CT (Fig 2), MRI of the chest without contrast enhancement (Fig 3), and fluorine 18 fluorodeoxyglucose PET/CT (Fig 4).

Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with EPHB4 pathogenic variants.

BACKGROUND: EPHB4 loss of function is associated with type 2 capillary malformation-arteriovenous malformation syndrome, an autosomal dominant vascular disorder. The phenotype partially overlaps with hereditary haemorrhagic telangiectasia (HHT) due to epistaxis, telangiectases and cerebral arteriovenous malformations, but a similar liver involvement has never been described. METHODS: Members of the French HHT network reported their cases of EPHB4 mutation identified after an initial suspicion of HHT. Clinical, radiological and genetic characteristics were analysed. RESULTS: Among 21 patients with EPHB4, 15 had a liver imaging, including 7 with HHT-like abnormalities (2 female patients and 5 male patients, ages 43-69 years). Atypical epistaxis and telangiectases were noted in two cases each. They were significantly older than the eight patients with normal imaging (median: 51 vs 20 years, p<0.0006).The main hepatic artery was dilated in all the cases (diameter: 8-11 mm). Six patients had hepatic telangiectases. All kind of shunts were described (arteriosystemic: five patients, arterioportal: two patients, portosystemic: three patients). The overall liver appearance was considered as typical of HHT in six cases.Six EPHB4 variants were classified as pathogenic and one as likely pathogenic, with no specific hot spot. CONCLUSION: EPHB4 loss-of-function variants can be associated with HHT-like hepatic abnormalities and should be tested for atypical HHT presentations.

Diffuse cystic lung disease in sickle cell anaemia: a series of 22 cases and a case-control study.

Chronic interstitial lung abnormalities have been described in sickle cell disease (SCD) and attributed to repetitive episode of acute chest syndrome. We report a series of 22 cases of diffuse cystic lung disease in SCD with a case-control study to hunt for mechanism. On pathological analysis of a surgical lung biopsy of the index case, the bronchioles had the appearance of constrictive bronchiolitis. Pulmonary function test results revealed lower forced expiratory flow from 25% to 75% of vital capacity in cases versus controls. These findings suggest a bronchiolar mechanism that was not associated with more acute chest syndrome.

Chronic pulmonary aspergillosis: prevalence, favouring pulmonary diseases and prognosis.

Chronic pulmonary aspergillosis (CPA) is an emerging disease in patients with common chronic pulmonary diseases (CPDs). While its prevalence is linked to tuberculosis (TB) in endemic countries, epidemiological and prognostic data are lacking in low TB incidence countries. The aim of this study was to describe these features in CPA patients hospitalised in France between 2009 and 2018.We estimated the prevalence and mortality of hospitalised CPA patients using the French nationwide administrative hospital database. We also assessed the association with CPD, thoracic interventions and malnutrition.From 2009 to 2018, 17 290 patients were hospitalised in France for CPA, with an increasing prevalence during this period. Most patients were male (63.5%) with a median age of 65 years at CPA diagnosis, living in farming regions and large cities. The proportion of underlying chronic obstructive pulmonary disease (COPD) and emphysema during the previous 5 years was 44% and 22%, respectively, whereas it was only 3% for both TB and non-TB mycobacterial (NTM) infections. The mortality rates during the first hospitalisation, at 1 year and at 5 years were 17%, 32% and 45%, respectively. In multivariate analysis, mortality rates were increased in patients aged >65 years, male patients and patients with malnutrition, diabetes or lung cancer history. The risk of mortality in patients with COPD or emphysema was higher than in those with previous mycobacterial lung infection.In France, CPA is an emerging infection commonly associated with non-mycobacterial CPD. This shift in the distribution profile of underlying CPD will likely worsen CPA mortality.

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required intensive care unit (ICU) admission in patients with autoimmune diseases. METHODS: French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016. RESULTS: One hundred four patients (54% of men) with median age of 56 [32-68] years were included with 79 (76%) systemic vasculitis and 25 (24%) connective tissue disorders. All patients received steroids, and 72 (69%), 12 (11.5%), and 57 (55%) patients had cyclophosphamide, rituximab, and plasma exchanges, respectively. During ICU stay, 52 (50%), 36 (35%), and 55 (53%) patients required mechanical ventilation, vasopressor use, and renal replacement therapy, respectively. Factors associated with mechanical ventilation weaning were age (HR [95%CI] 0.97 [0.96-0.99] per 10 years, p < 0.0001), vasculitis-related DAH (0.52 [0.27-0.98], p = 0.04), and time from dyspnea onset to ICU admission (0.99 [0.99-1] per day, p = 0.03). ICU mortality was 15%. Factors associated with alive status at ICU discharge were chronic cardiac failure (HR [95%CI] 0.37 [0.15-0.94], p = 0.04), antiphospholipid syndrome-related DAH (3.17 [1.89-5.32], p < 0.0001), SAPS II (0.98 [0.97-0.99], p = 0.007), and oxygen flow at ICU admission (0.95 [0.91-0.99] per liter/min, p = 0.04). CONCLUSION: DAH in autoimmune diseases is a life-threatening complication which requires mechanical ventilation in half of the cases admitted to ICU.

Rare respiratory diseases in the ICU: when to suspect them and specific approaches.

PURPOSE OF REVIEW: A prompt identification of the cause of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS) is required in order to initiate a targeted treatment. Yet, almost 10% of ARDS patients have no identified ARDS risk factor at ARDS diagnosis. Numerous rare causes of ARF have been reported in this setting. The purpose of this review is to delineate the main rare causes of ARF/ARDS and to provide clinicians with a pragmatic diagnostic work-up. RECENT FINDINGS: Recent epidemiological data have proposed the identification of a subgroup of ARDS patients lacking exposure to common risk factors. These can be categorized as having immune, drug-induced, malignant and idiopathic diseases. A standardized diagnostic work-up including chest imaging, the objective assessment of left heart filling pressures, bronchoalveolar lavage fluid microbiological investigations and cytological analysis, immunological tests and search for pneumotoxic drugs may allow for identifying the cause of ARF in most cases. Open lung biopsy should be considered in other cases. SUMMARY: A prompt identification of the cause of ARF is required to initiate a targeted treatment. Patients with no identified ARDS risk factor should undergo a comprehensive and hierarchized diagnostic work-up.

Pulmonary Arteriovenous Malformations: Safety and Efficacy of Microvascular Plugs.

OBJECTIVE: The purpose of this study is to assess the safety and efficacy of microvascular plugs for the treatment of pulmonary arteriovenous malformations (PAVMs). MATERIALS AND METHODS: From July 2014 to March 2017, 22 consecutive patients with hereditary hemorrhagic telangiectasia underwent treatment of PAVMs using microvascular plugs. The number, location, and type (simple or complex) of PAVM and the diameter of the feeding artery were assessed at angiography. Safety was evaluated by successful detachment and absence of migration of the microvascular plug after deployment. Efficacy was assessed by technical success, defined as immediate stasis in the feeding artery above the microvascular plug at the time of angiography, and by the persistence rate at 1-year follow-up CT. RESULTS: Thirty-nine PAVMs (36 simple and three complex) were treated with 52 microvascular plugs in 22 consecutive patients. Thirty-three PAVMs were undergoing initial treatment and six were undergoing retreatment after previous embolotherapy. All microvascular plugs were successfully detached. No microvascular plug migration was observed. The mean (± SD) feeding artery diameter was 2.3 ± 0.7 mm. Technical success was achieved for 51 of 52 (98%) microvascular plug deployments. Follow-up CT, which was available for 20 of 22 (91%) patients, with a mean delay of 12.6 ± 3.1 months, showed two persistent PAVMs (persistence rate, 6%), one due to recanalization through the microvascular plug and the other due to reperfusion from an untreated adjacent pulmonary feeding artery. CONCLUSION: Microvascular plugs are safe and effective for treatment of PAVMs, with a low persistence rate (6%) 1 year after treatment.

Severe Hemoptysis Associated with Bacterial Pulmonary Infection: Clinical Features, Significance of Parenchymal Necrosis, and Outcome.

PURPOSE: Severe hemoptysis (SH) associated with non-tuberculosis bacterial lower respiratory tract infection (LRTI) is poorly described, and the efficacy of the usual decision-making process is unknown. This study aimed at describing the clinical, radiological patterns, mechanism, and microbiological spectrum of SH related to bacterial LRTI, and assessing whether the severity of hemoptysis and the results of usual therapeutic strategy are influenced by the presence of parenchymal necrosis. METHODS: A single-center analysis of patients with SH related to bacterial LRTI from a prospective registry of consecutive patients with SH admitted to the intensive care unit of a tertiary referral center between November 1996 and May 2013. RESULTS: Of 1504 patients with SH during the study period, 65 (4.3%) had SH related to bacterial LRTI, including non-necrotizing infections (n = 31), necrotizing pneumonia (n = 23), pulmonary abscess (n = 10), and excavated nodule (n = 1). The presence of parenchymal necrosis (n = 34, 52%) was associated with a more abundant bleeding (volume: 200 ml [70-300] vs. 80 ml [30-170]; p = 0.01) and a more frequent need for endovascular procedure (26/34; 76% vs. 9/31; 29%; p < 0.001). Additionally, in case of parenchymal necrosis, the pulmonary artery vasculature was involved in 16 patients (47%), and the failure rate of endovascular treatment was up to 25% despite multiple procedures. CONCLUSIONS: Bacterial LRTI is a rare cause of SH. The presence of parenchymal necrosis is more likely associated with bleeding severity, pulmonary vasculature involvement, and endovascular treatment failure.

Clinical Features of Patients with Diffuse Alveolar Hemorrhage due to Negative-Pressure Pulmonary Edema.

PURPOSE: Diffuse alveolar hemorrhage (DAH) with negative-pressure pulmonary edema (NPPE) is an uncommon yet life-threatening condition. We aimed at describing the circumstances, clinical, radiological, and bronchoscopic features, as well as the outcome of patients with NPPE-related DAH. METHODS: We performed a retrospective, observational cohort study, using data prospectively collected over 35 years in an intensive care unit (ICU). RESULTS: Of the 149 patients admitted for DAH, we identified 18 NPPE episodes in 15 patients, one admitted four times for recurrent NPPE-related DAH. The patients were primarily young, male, and athletic. The NPPE setting was postoperative (n = 12/18, 67%) or following generalized tonic-clonic seizures (n = 6/18, 33%). Hemoptysis was almost constant (n = 17/18, 94%), yet rarely massive (>200 cc, n = 1/18, 6%), with anemia observed in 10 (56%) episodes. The DAH triad (hemoptysis, anemia, and pulmonary infiltrates) was observed in 50% of episodes (n = 9/18), and acute respiratory failure in 94% (n = 17/18). Chest computed tomography revealed diffuse bilateral ground glass opacities (n = 10/10, 100%), while bronchoscopy detected bilateral hemorrhage (n = 12/12, 100%) and macroscopically bloody bronchoalveolar lavage, with siderophage absence in most (n = 7/8, 88%), indicating acute DAH. While one episode proved fatal, the other 17 recovered rapidly, with a mean ICU stay lasting 4.6 (2-15) days. Typically, the evolution was rapidly favorable under supportive care. CONCLUSION: NPPE-related DAH is a rare life-threatening condition occurring primarily after tonic-clonic generalized seizure or generalized anesthesia. Clinical circumstances are a key to its diagnosis. Early diagnosis and recognition likely allow for successful management of this potentially serious complication, whereas ictal-DAH appears ominous in epileptic patients.

Severe haemoptysis in patients with nonsmall cell lung carcinoma.

Severe haemoptysis due to nonsmall cell lung cancer (NSCLC) is considered a grim condition, and there is still scarce data on its characteristics and outcome, despite new imaging and treatment modalities. This retrospective study sought to describe the clinical characteristics, pathophysiology and outcome of NSCLC-related haemoptysis. We included 125 consecutive patients with severe haemoptysis (>100 mL) at admission, 65 (52%) exhibiting squamous cell carcinoma. Tumour cavitation/necrosis was reported in 26 (21%) patients. 52 patients had received anticancer treatment, but none had received anti-angiogenic agents. Severe haemoptysis was related mainly to the bronchial artery (82%), and major pulmonary artery involvement was rare (6.4%). Interventional radiology was performed in 102 patients. Bleeding cessation was achieved in 108 (87%) out of 125 patients. The overall in-hospital and 1-year survival rates were 69% and 30%, respectively. Performance status (PS) ≥ 2 (OR 3.6, 95% CI 1.3-9.6), advanced stage (OR 8.6, 95% CI 2-37) and mechanical ventilation (OR 13, 95% CI 4.5-36) were independent predictors of in-hospital mortality. Performance status ≥ 2 (hazard ratio (HR) 2.4, 95% CI 1.5-3.7), advanced stage (HR 4, 95% CI 2.1-7.7), cancer progression (HR 2, 95% CI 1.01-2.7) and cavitation/necrosis (HR 1.7, 95% CI 1.21-3.2) were independently associated with 1-year mortality. Management of severe haemoptysis related to NSCLC should be improved, given our observed survival rates after hospital discharge.

Low titers of serum antibodies inhibiting hemagglutination predict fatal fulminant influenza A(H1N1) 2009 infection.

RATIONALE: The biology of fatal pandemic influenza infection remains undefined. OBJECTIVES: To characterize the virologic and immune parameters associated with severity or death in patients who required mechanical ventilation for A(H1N1) 2009 pneumonia of various degrees of severity during the two waves of the 2009-2011 pandemic in Paris, France. METHODS: This multicenter study included 34 unvaccinated patients with very severe or fatal confirmed influenza A(H1N1) infections. It analyzed plasma A(H1N1) 2009 reverse-transcriptase polymerase chain reaction, hemagglutinin 222G viral mutation, and humoral and cellular immune responses to the virus, assessed in hemagglutination inhibition (HI), microneutralization, ELISA, lymphoproliferative, ELISpot IFN-γ, and cytokine and chemokine assays. MEASUREMENTS AND MAIN RESULTS: The patients' median age was 35 years. Influenza A(H1N1) 2009 viremia was detected in 4 of 34 cases, and a 222G hemagglutinin mutation in 7 of 17 cases, all of them with sequential organ failure assessment greater than or equal to 8. HI antibodies were detectable in 19 of 26 survivors and undetectable in all six fatal fulminant cases. ELISA and microneutralization titers were concordant. B-cell immunophenotyping and plasma levels of immunoglobulin classes did not differ between patients who survived and died. After immune complex dissociation, influenza ELISA serology became strongly positive in the bronchoalveolar lavage of the two fatal cases tested. H1N1-specific T-cell responses in lymphoproliferative and IFN-γ assays were detectable in survivors' peripheral blood, and lymphoproliferative assays were negative in the three fatal cases tested. Plasma levels of IL-6 and IL-10 were high in fatal cases and correlated with severity. Finally, a negative HI serology 4 days after the onset of influenza symptoms predicted death from fulminant influenza (P = 0.04). CONCLUSIONS: Early negative A(H1N1) 2009 HI serology can predict death from influenza. This negative serology in fatal cases in young adults reflects the trapping of anti-H1N1 antibodies in immune complexes in the lungs, associated with poor specific helper T-cell response. Clinical trial registered with www.clinicaltrials.gov (NCT 01089400).

Outcomes of adult patients with sickle cell disease admitted to the ICU: a case series*.

OBJECTIVE: Sickle cell disease is associated with a decreased life expectancy, half of the deaths occurring in the ICU. We aimed to describe the characteristics of sickle cell disease patients admitted to ICU and to identify early predictors of a complicated outcome, defined as the need for vital support or death. DESIGN: Retrospective observational cohort study of sickle cell disease patients over a 6-year period. SETTING: ICU of a French teaching hospital and sickle cell disease referral center. PATIENTS: Hundred thirty-eight ICU admissions in 119 sickle cell disease patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU admission was mainly indicated for sickle cell disease-related events, especially acute chest syndrome. Mechanical ventilation, vasoactive drugs, and renal replacement therapy were administered to 25 (18%), 10 (7%), and 10 (7%) episodes, respectively. The complicated outcome group (n = 28; 20%) was characterized by a more aggressive acute disease within the 48 hours preceding ICU admission, with a higher respiratory rate, a more frequent acute kidney injury, and a more sustained drop of hemoglobin (all p < 0.01). All nine deaths (7%) were sickle cell disease related. None of the sickle cell disease baseline characteristics predicted accurately a complicated outcome. In multivariate analysis, hemoglobin less than or equal to 7.8 g/dL (odds ratio, 3.6; 95% CI, 1.1-11.9), respiratory rate more than or equal to 32 cycles/min (odds ratio, 5.6; 95% CI, 1.8-17.2), and acute kidney injury on ICU admission (odds ratio, 11.5; 95% CI, 2.5-52.6) were independently associated with a complicated outcome. CONCLUSIONS: Sickle cell disease patients are at high risk of complications when admitted to the ICU. A sustained drop of hemoglobin, acute respiratory distress, and kidney injury at admission are strong predictors of a complicated outcome.

Immune diffuse alveolar hemorrhage: a retrospective assessment of a diagnostic scale.

BACKGROUND: Initiating early steroid treatment in patients with immune diffuse alveolar hemorrhage (DAH) is a key aspect of early management. However, steroid initiation is often delayed until the results of immunological markers and/or tissue biopsy have been obtained, which could contribute to poor outcomes. We previously developed a clinical score allowing for the early diagnosis of DAH of immune causes. However, this score has not been validated in an independent cohort of patients. The aim of this study was to assess the validity of this diagnostic score using an independent cohort of patients admitted for DAH of immune and nonimmune causes. METHODS: We conducted a retrospective cohort study of patients admitted between January 2002 and December 2009 for DAH of immune and nonimmune causes. RESULTS: Forty-six patients were included in the study, with 12 patients having immune DAH and 34 patients with nonimmune DAH. Application of our previously validated clinical scale of immune DAH to this independent population of patients yielded an area under the ROC curve of 0.95 [0.90-1.01]. A score ≥4/10 was associated with the best performances of this scale: sensitivity = 1.00 [0.73-1.00], specificity = 0.88 [0.72-0.97], positive predictive value = 0.75 [0.48-0.93], and negative predictive value = 1.00 [0.88-1.00]. CONCLUSION: While immunological tests and tissue biopsy results are pending, deciding whether to initiate an immunosuppressive treatment is challenging. The initiation of early corticosteroid treatment is warranted in patients with immune DAH and could improve outcomes. This study confirms that this score allows for a good discrimination between patients with immune and nonimmune DAH. Because this series has several limitations, including its single-center and retrospective nature, the small number of patients included, and the lack of therapeutic intervention, a prospective evaluation of this score is warranted to ascertain whether it can improve the adequacy of early treatment strategies and thus improve the outcomes of DAH patients.

Cell and cytokine analyses from bronchoalveolar lavage in non-critical COVID-19 pneumonia.

Cell and cytokine analyses from bronchoalveolar lavage (BAL) in non-critically ill patients with COVID-19 pneumonia are poorly described. This study focused on patients hospitalized in the non-intensive care unit for either suspected COVID-19 pneumonia or persistent respiratory symptoms following proven COVID-19 pneumonia. Overall, 54 patients who underwent BAL between April 2020 and February 2021 for suspected or follow-up of proven COVID-19 pneumonia were included. Based on SARS-CoV-2 polymerase chain reaction test results and clinical follow-up, three pulmonary disease groups were defined: non-COVID-19 (n = 20), acute COVID-19 (n = 13), and post-COVID-19 (n = 24) pneumonia patients. Cytological and cytokine analyses were performed on BAL fluid (IL-1ß, IL-6, IL-8, IL-10, TNF-α, IFN-γ, HGF, and TGF-ß), with investigators blinded to the patient groups. Lymphocytic alveolitis with plasmocytes was observed in acute COVID-19 pneumonia, returning to normal post-COVID-19. The highest cytokine levels were observed in COVID-19 patients, with significantly increased IFN-γ, IL-10, and HGF levels compared to non-COVID-19 patients, while significantly decreased IL-6, IL-8, IL-10, IFN-γ, TNF-α, and HGF levels were noted in post-COVID-19 patients. In COVID-19 patients, correlations between IL-10, TNF-α and IFN-γ concentrations were found. Lymphocytic alveolitis with plasmacytosis was found in non-critical COVID-19 pneumonia This alveolitis is associated with the presence of IL-6, IL-8, IL-10, TNF-α, IFN-γ and HGF. Alveolitis and cytokines levels decreased in post-COVID-19 pneumonia.

Prognostic value of serum Krebs von den Lungen-6 (KL-6) levels in COVID-19 pneumonia.

BACKGROUND AND OBJECTIVES: Krebs von den Lungen-6 (KL-6), expressed by damaged type II pneumocytes, is useful in the diagnosis and severity assessment of many diffuse interstitial lung diseases. The objective of our study was to determine the prognostic value of the initial KL-6 plasma level in COVID-19 pneumonia. METHODS: All patients hospitalized for a suspected COVID-19 pneumonia between March and May 2020 in our Chest department of a French university hospital were included. KL-6 serum concentrations were measured within 72 h of diagnostic suspicion by chemiluminescence enzyme immunoassay Survival analysis was performed using a Cox regression and modeled by a Kaplan-Meier curve. RESULTS: Sixty-six COVID-19 patients (average age = 64 ± 14 years, 71.2 % males) with KL-6 serum measurement were included. Median KL-6 serum concentration was 409 ± 312 U/mL. KL-6 was significantly higher in men (p = 0.003), elders (p = 0.0001) and in patients with greater Charlson's score (p = 0.002). Higher KL-6 concentration was significantly associated with in-hospital mortality (HR: 8.66; 95 % CI:1.1-69.2, p = 0.014), radiological extension of lesions on chest CT scan (p = 0.004) and higher WHO severity score (p = 0.042), but not with admission in intensive care unit. In 9 (14 %) non-surviving COVID-19 patients, KL-6 serum concentration increased whereas it remained stable or decreased in survivors. At 3 months follow-up (n = 48), DLCO was negatively correlated with the initial KL-6 value (r = 0.47, p = 0.001), while FVC, FEV1 and MRC score were not. CONCLUSION: Initial KL-6 serum concentration is significantly associated with in-hospital mortality, unfavorable outcome, and persistent impairment of DLCO at 3 months. Initial KL-6 plasma determination appears as a prognostic biomarker in COVID-19 pneumonia.

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL).

BACKGROUND: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents. OBJECTIVES: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT. METHODS: Retrospective multicenter study in French national HHT Registry patients exposed to AT. RESULTS: We included 126 patients with 180 courses of AT. Median follow-up was 24 [11-52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011). CONCLUSION: Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.

Pulmonary artery occlusion with ethylene vinyl alcohol copolymer in patients with hemoptysis: initial experience in 12 cases.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and efficacy of pulmonary artery occlusion with ethylene vinyl alcohol copolymer in patients with hemoptysis. MATERIALS AND METHODS: We reviewed the cases of 12 consecutively registered patients (10 men, two women; age range, 21-83 years; mean, 54.5 years) who were treated for hemoptysis by pulmonary artery occlusion with ethylene vinyl alcohol copolymer. The indications, immediate hemoptysis control, and clinical tolerability were analyzed. RESULTS: The underlying diseases were necrotizing pneumonia in four patients, necrotizing aspergillosis in one patient, complex aspergilloma in two patients, active tuberculosis in two patients, lung cancer in two patients, and Behçet disease in one patient. Ethylene vinyl alcohol copolymer was used alone in nine patients and with steel coils in three patients. The main indications were a small-necked pulmonary artery pseudoaneurysm in five patients, necrotic process in four patients, presence of systemic reperfusion of a pulmonary artery pseudoaneurysm in one patient, absolute necessity for anticoagulation therapy in one patient, and need to complete pulmonary artery aneurysm sac occlusion in one patient. The injection procedure was well tolerated. Hemoptysis of pulmonary arterial origin was controlled in all but one patient, who had progression of the infectious disease and underwent surgery. In two patients, hemoptysis recurred from systemic arteries and was treated with embolization of the systemic arteries in one patient and surgery in the other patient. CONCLUSION: Ethylene vinyl alcohol copolymer embolization for hemoptysis of pulmonary arterial origin is feasible and efficacious. Use of this embolization agent is beneficial in patients with pulmonary artery injuries, especially those with small-necked lesions.

Early prediction of in-hospital mortality of patients with hemoptysis: an approach to defining severe hemoptysis.

BACKGROUND: The severity of hemoptysis is usually assessed on the amount of blood expectorated, although no threshold has been agreed upon. Respiratory or hemodynamic failures are additional severity criteria but occur in few cases. OBJECTIVES: Early identification of the in-hospital mortality determinants might be helpful to best characterize severe hemoptysis. METHODS: This is a retrospective cohort study of consecutive patients with hemoptysis admitted to the ICU of a teaching hospital during a 14-year period. The model for early prediction of in-hospital mortality was developed on a derivation sample (67% of patients) using multiple logistic regression. Calibration and discrimination of the model were tested using the remaining validation sample. A scoring system was developed for clinical use. RESULTS: The in-hospital mortality of the 1,087 patients (age 54 years, 71% male) was 6.5% (95% CI 5-8). Chronic alcoholism, cancer or aspergillosis, pulmonary artery involvement, infiltrates involving two quadrants or more on the admission radiograph, and mechanical ventilation at referral predicted independently mortality. The model showed good concordance between predicted and observed probabilities of death and good discrimination (receiver operating characteristic curve area 0.87; 95% CI 0.82-0.92). The model-based score (chronic alcoholism, pulmonary artery involvement, and radiographic patterns, 1 point each; cancer, aspergillosis, and mechanical ventilation, 2 points each) predicted the probability of death as follows: score 0, 1%; score 1, 2%; score 2, 6%; score 3, 16%; score 4, 34%; score 5, 58%; score 6, 79%, and score 7, 91%. CONCLUSIONS: Our results provide useful information about the short-term prognosis of patients with hemoptysis, which could help design therapeutic approaches and management plans according to the risk of in-hospital mortality.