Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage.

BACKGROUND AND HYPOTHESIS: Pulmonary haemorrhage with hypoxia caused by ANCA-associated vasculitis (AAV) has a high early mortality. Avacopan, an oral C5a receptor antagonist, is an approved treatment for AAV, but patients with pulmonary haemorrhage requiring invasive pulmonary ventilation support were excluded from the ADVOCATE trial. METHODS: A retrospective, observational, multicentre case series of AAV patients with hypoxic pulmonary haemorrhage, requiring oxygen support or mechanical ventilation, who received avacopan. RESULTS: Eight patients (62.5% female), median age 64 years (range 17-80), seven with kidney involvement, median glomerular filtration rate (GFR) 11 (range 5-99) ml/min per 1.73m2, were followed for a median of 6 months from presentation. Seven were newly diagnosed (87.5%), five were MPO-ANCA and three PR3-ANCA positive. All had hypoxia, four requiring mechanical ventilation (three invasive and one non-invasive). Intensive care unit (ICU) stay for the four patients lasted a median of 9 days (range 6-60). Four received rituximab and cyclophosphamide combination, three rituximab and one cyclophosphamide. Four underwent plasma exchange and one received two months of daily extracorporeal membrane oxygenation (ECMO) therapy. Following the initiation of avacopan after a median of 10 days (range 2-40), pulmonary haemorrhage resolved in all patients, even two who had one month of refractory pulmonary haemorrhage prior to avacopan. Additionally, after one month, the median prednisolone dose was 5 mg/day (range 0-50), with three patients successfully discontinuing steroid use. Two patients suffered serious infections, two discontinued avacopan, one permanently due to a rash and one temporarily after three months due to neutropenia. All patients survived and no re-hospitalization occurred. CONCLUSION: We report the use of avacopan as a component of the treatment for pulmonary haemorrhage with hypoxia in AAV. Despite the life-threatening presentations all patients recovered, but attribution of the positive outcomes to avacopan is limited by the concomitant therapies and retrospective observational design.

Life-threatening pulmonary haemorrhage treated with coil embolisation followed by lobectomy in a patient with KCNT1 mutation.

KCNT1 mutations are associated with childhood epilepsy, developmental delay, and vascular malformations. We report a child with a likely pathogenic KCNT1 mutation (c.1885A>C, p.Lys629Glu) with recurrent pulmonary haemorrhage due to aortopulmonary collaterals successfully managed with coil embolisation followed by right upper lobectomy.

Analysing predictors of surgical site infections in patients undergoing emergency surgery for traumatic pulmonary haemorrhage.

Identifying predictors for surgical site infections (SSIs) after emergency surgical treatment for traumatic pulmonary haemorrhage (TPH) is crucial for improving patient outcomes. This study aims to ascertain these predictors. In this comprehensive retrospective study, conducted from January 2020 to December 2023 at our institution, 75 patients were analysed, including a case group of 25 patients with SSIs and a control group of 50 without SSIs post-TPH surgery. Inclusion criteria focused on patients aged 18 and above undergoing thoracotomy or minimally invasive thoracic surgery for TPH. Exclusion criteria included compromised immune systems, chronic pulmonary diseases, prior thoracic surgery or active infections at admission. We assessed several predictors: anaemia; operation time over 2 h; hospital stay over 5 days; intraoperative blood loss exceeding 500 mL; body mass index (BMI) ≥25 kg/m2; age ≥ 50 years; use of surgical drains; the presence of open wounds; diabetes mellitus and non-prophylactic antibiotic use. Statistical analysis involved univariate and multivariate logistic regression, using SPSS Version 27.0. Univariate analysis revealed significant associations between SSIs and surgical drain placement, diabetes mellitus, open wounds and non-prophylactic antibiotic use (p < 0.01). Multivariate analysis confirmed these factors as significant predictors of SSIs, with notable odds ratios. Other variables like anaemia, extended hospital stay, excessive intraoperative blood loss, older age and higher BMI did not significantly predict SSIs. Significant predictors for SSIs following TPH surgery include surgical drain placement, diabetes mellitus, open wounds and non-prophylactic antibiotic use. Identifying and managing these risks is crucial in clinical practice to reduce SSIs incidence and improve patient outcomes.

Diffuse alveolar haemorrhage in systemic lupus erythematosus: A multicentre retrospective study in Singapore.

OBJECTIVE: Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We describe the clinical characteristics, treatment and survival outcomes of SLE patients with DAH in Singapore. METHODS: We conducted a retrospective review of the medical records of SLE patients with DAH hospitalised in 3 tertiary hospitals between January 2007 and October 2017. Patient demographics, clinical characteristics, laboratory, radiologic and bronchoscopic findings, as well as the treatments, were compared between survivors and non-survivors. Survival rates were analysed between the various treatment groups. RESULTS: A total of 35 patients with DAH were included in this study. Majority of them were female (71.4%) and of Chinese ethnicity (62.9%). Median age was 40.0 years (IQR: 25-54), with a median disease duration of 8.9 months (IQR: 0.13-102.4). Haemoptysis was the most common clinical presentation, and majority had concomitant cytopaenia and lupus nephritis. All patients received high dose glucocorticoids; 27 (77.1%), 16 (45.7%) and 23 (65.7%) received cyclophosphamide (CYP), rituximab (RTX), and plasmapheresis (PLEX), respectively. Twenty-two patients required mechanical ventilation with a median duration of 12 days. Overall mortality rate was 40%, with a median survival time of 162 days. Twenty-six patients (74.3%) achieved remission, with an overall median time to remission of 12 days (IQR: 6-46) after diagnosis of DAH. Patients on triple therapy (CYP, RTX and PLEX) had a median survival of 162 days as compared to 14 days in patients on PLEX alone (p = .0026). CONCLUSIONS: The overall mortality of DAH in SLE patients remained high. There were no significant differences in patient demographics or clinical characteristics between the survivors and non-survivors. However, better survival appears to be associated with treatment with cyclophosphamide.

Evaluation of newborns with Down syndrome with weight less than 1500 g in the neonatal intensive care unit: A Japanese multicentre study.

AIM: This study aimed to clarify the characteristics and their mortality-related factors in very low birthweight infants with Down syndrome (DS) in Japan. METHODS: This retrospective case-control study enrolled newborns with DS weighing <1500 g admitted to neonatal intensive care unit (NICU) of the perinatal centre registered with the Neonatal Research Network of Japan (NRNJ) database from 2008 to 2019. The clinical characteristics and their mortality-related factors were compared among the Dead group (newborns with DS who died in the NICU), the Survival group (newborns with DS who were alive from the NICU) and the Control group (newborns without congenital or chromosomal condition). RESULTS: A total of 53 656 newborns weighing <1500 g were registered in the NRNJ database for 12 years. Of these, 310 (0.6%) were diagnosed with DS: 62 newborns in the Dead group, 248 in the Survival group and 49 786 in the Control group without chromosomal condition. Logistic analysis revealed that there was a significant difference in the mortality-related factors in congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn; the adjusted odds ratios were 8.6, 121 and 9.5, respectively. Newborns with DS weighing <1000 g showed the earliest death in the NICU on the Kaplan-Meier survival curve (P < 0.01). CONCLUSION: The mortality rate for newborns with DS weighing <1500 g was 20% (5% in the Control group). The mortality-related factors were complications of congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn.

Local pulmonary administration of factor VIIa (rFVIIa) in massive pulmonary haemorrhage in post-operative cardiac infant.

Diffuse pulmonary haemorrhage is an ominous condition that has a high paediatric mortality rate. Recombinant activated factor VIIa (rFVIIa) is a powerful haemostatic agent which has been used intravenously in life-threatening haemorrhage in variety of conditions in which conventional medical or surgical therapy are unsuccessful. We report off-label successful use of endotracheal rFVIIa for massive life-threatening respiratory haemorrhage following aspiration and cardiopulmonary resuscitation in a 3-month-old infant who was anticoagulated with enoxaparin following corrective cardiac surgery with other comorbidities. Off-label administration of endotracheal rFVIIa permitted rapid safe control of massive pulmonary haemorrhage and prevented further detrimental decline in respiratory function with satisfactory outcome.

Pulmonary haemorrhage in neonates: Systematic review of management.

AIM: Pulmonary haemorrhage (PH) is an acute catastrophic event with low incidence yet high mortality among neonates. We aimed to systematically review the management of PH. METHODS: A search was carried out of the PubMed, EMBASE and Cochrane databases according to the PRISMA guidelines. Data were extracted on study design and size, patient demographics, primary and adjunctive treatment methods, and treatment outcomes. RESULTS: Sixteen studies with 385 newborn infants were included and were significantly heterogeneous regarding treatment methods. Primary treatments included surfactant, high-frequency oscillatory ventilation (HFOV), epinephrine, coagulopathy management, intermittent positive pressure ventilation, cocaine and tolazoline. Adjunctive treatment methods included blood products, HFOV, increased positive end-expiratory pressure, vitamin K, surfactant, adrenaline, vasopressors and inotropes. All five studies using surfactant as primary treatment were effective in improving oxygenation index measures and preventing recurrence of PH, and three studies found no association between surfactant and death or long-term disability. Ventilatory support, epinephrine, management of coagulopathy and tolazoline were all found to be effective primary treatments for PH. CONCLUSION: There are several effective methods of managing PH in neonates. Further understanding of the aetiology of PH and ongoing research will allow future prevention and improvements in management of PH.

Pulmonary manifestations and outcomes in paediatric ANCA-associated vasculitis: a single-centre experience.

OBJECTIVES: ANCA-associated vasculitis (AAV) usually involves the renal and respiratory systems, but the paediatric literature on pulmonary manifestations and outcomes is limited. We aimed to describe pulmonary manifestations and outcomes after therapy in a cohort of paediatric AAV (pAAV) patients. METHODS: A retrospective chart review of all patients <19 years presenting to our institution with AAV between 1/2008 and 2/2018 was conducted. Patient demographics, clinical presentation, diagnostic testing, therapy and pulmonary outcomes over the first 3 years after presentation were evaluated. RESULTS: A total of 38 patients were included; all had ANCA positivity by immunofluorescence. A total of 23 had microscopic polyangiitis (MPA), 13 had granulomatosis with polyangiitis and 2 had eosinophilic granulomatosis with polyangiitis. A total of 30 (79%) had pulmonary manifestations, with cough (73%) and pulmonary haemorrhage (67%) being the most common. Abnormalities were noted in 82% of chest CT scans reviewed, with nodules and ground-glass opacities being the most common. At 6, 12 and 36 months follow-up, respectively, 61.8%, 39.4% and 29% of patients continued to show pulmonary manifestations. Five MPA patients with re-haemorrhage are described in detail. CONCLUSION: MPA was more common than granulomatosis with polyangiitis, with pulmonary involvement being common in both. MPA patients had more severe pulmonary manifestations. Chest CT revealed abnormal findings in a majority of cases. A subgroup of young MPA patients experienced repeat pulmonary haemorrhage. Treatment modality and response were comparable in different subtypes of AAV, except for this young MPA group. Additional prospective studies are needed to better understand the different phenotypes of pAAV.

A Before-and-After Study of Evidence-Based Recommendations for On-Call Bronchoscopy.

BACKGROUND: Bronchoscopy is widely used and regarded as standard of care in most intensive care units (ICUs). Data concerning recommendations for on-call bronchoscopy are lacking. OBJECTIVES: Evaluation of recommendations, complications, and outcome of on-call bronchoscopies. METHOD: A retrospective single-centre analysis was conducted in a large university hospital. All on-call bronchoscopies performed outside normal working hours in the year before (period 1) and after (period 2) establishing a catalogue of recommendations for indications of on-call bronchoscopy on November 1, 2016, were included. RESULTS: Overall, 924 bronchoscopies in 538 patients were analysed. A relative reduction of 83.6% from 794 bronchoscopies in 432 patients (1.84 per patient) during period 1 to 130 in 107 patients (1.21 per patient) during period 2 was observed. Most bronchoscopies (812/924, 87.9%) were performed in ICUs, and 416 patients (77.3%) were intubated. Bronchoscopies for excessive secretions decreased significantly during period 2. Fifty-three of 130 bronchoscopies (40.8%) fulfilled the specified recommendations during period 2, in comparison with 16.8% in period 1 (p < 0.001). Complications were recorded in 58 of 924 procedures (6.3%) and were more frequent in period 2, especially moderate bleeding. In-hospital mortality of patients undergoing on-call bronchoscopy did not differ between periods and was 28.7 and 30.2% in periods 1 and 2, respectively. CONCLUSION: The introduction of recommendations for on-call bronchoscopy led to a significant decline of on-call bronchoscopies without negatively affecting outcome. More evidence is needed in on-call bronchoscopy, especially for ICU patients with intrinsic higher complication rates.

Successful treatment of pulmonary haemorrhage and acute respiratory distress syndrome caused by fulminant Stenotrophomonas maltophilia respiratory infection in a patient with acute lymphoblastic leukaemia - case report.

BACKGROUND: Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment. CASE PRESENTATION: We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days. CONCLUSIONS: Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.

Massive paediatric pulmonary haemorrhage in Dieulafoy's disease: Roles of CT angiography, embolisation and bronchoscopy.

Acute, major pulmonary haemorrhage in children, is rare, may be life-threatening and at times presents atypically. Dieulafoy's disease of the bronchus presenting with recurrent or massive hemoptysis was first described in adults. Prior to reviewing the literature, we report an illustrative case of bronchial Dieulafoy's disease (BDD) in a child presenting unusually with massive apparent hematemesis. The source of bleeding is a bronchial artery that fails to taper as it terminates within the bronchial submucosa. A high index of suspicion is required to identify such lesions via radiological imaging and the role of bronchial artery embolisation is highlighted with video images of angiography included.

A life-threatening complication due to pulmonary haemorrhage following hump-nosed viper bite.

BACKGROUND: Hump-nosed viper bite, the commonest venomous snake bite in Sri Lanka, is associated with significant morbidity. Specific anti-venom is not available for hump-nosed viper envenomation which is usually managed with supportive treatment. Pulmonary haemorrhage is an unusual manifestation of hump-nosed viper bite. Here we present a case of hump-nosed viper envenomation which complicated by pulmonary haemorrhage and was successfully treated with systemic steroids. To the best of our knowledge, it has not been reported in the literature before. CASE PRESENTATION: A previously healthy 55-year-old man presented to the local hospital 18 h after a hump-nosed viper bite. He developed bilateral severe pulmonary haemorrhages, evidenced by rapid desaturation which needed intubation and mechanical ventilation, bleeding from the endotracheal tube and bilateral alveolar shadows in a chest x-ray. He had no other bleeding manifestations. Because of the life-threatening situation, he was treated with methylprednisolone pulse therapy. There was a rapid improvement of hypoxia with a resolution of x-ray changes. He was successfully weaned off from the ventilation after 24 h. CONCLUSION: This case highlights the importance of suspecting pulmonary haemorrhage in a patient who develops desaturation and alveolar shadow following hump-nosed viper bite even in the absence of other bleeding manifestation. Early and timely treatment with systemic steroid can be lifesaving in such patients.

Severe pulmonary haemorrhage syndrome in leptospirosis in a returning traveller.

Clinical presentation of leptospirosis ranges from asymptomatic infection to fulminant, life-threatening disease. Pulmonary involvement in terms of severe pulmonary haemorrhage syndrome (SPHS) has recently become a more frequently reported facet of leptospirosis and correlates with high mortality rates. It has not yet been described in returning German travellers. We present a case of a healthy young man developing massive pulmonary haemorrhage and severe ARDS requiring mechanical ventilation and high-dose catecholamines after travelling to Indonesia. Leptospirosis was verified by blood PCR as well as serology and treated with high-dose, intravenous penicillin. Outcome was favourable, the patient recovered completely. Leptospirosis and SPHS should be taken into account as an emerging infectious disease in patients with fever and lung involvement.

[Use of extracorporeal membrane oxygenation for pulmonary haemorrhage after pulmonary endarterectomy]. / Primenenie ékstrakorporal'noi membrannoi oksigenatsii pri legochnom krovotechenii posle legochnoi éndarteréktomii.

Pulmonary haemorrhage is one of the most severe complications of pulmonary endarterectomy. To the most effective methods of combating this potentially fatal complication belongs extracorporeal membrane oxygenation (ECMO). In this article we describe a clinical case report regarding intraoperative use of central veno-arterial ECMO for pulmonary haemorrhage following thromboendarterectomy from the pulmonary arteries. According to the data of some authors, long-term ECMO support (for more than 4 days) may lead to such severe consequences as rethrombosis of pulmonary arteries and impairment of cerebral circulation. In our case we managed to avoid such complications, taking into consideration that the duration of ECMO amounted to 21 days. Resulting from the carried out comprehensive therapeutic measures by the time of discharge from hospital, a significant decrease in pulmonary artery pressure was achieved, with events of residual pulmonary hypertension.

Influencing factors of pneumothorax and parenchymal haemorrhage after CT-guided transthoracic needle biopsy: single-institution experience.

PURPOSE: To evaluate the incidences and influencing factors of pneumothorax and parenchymal haemorrhage after computed tomography (CT)-guided transthoracic needle biopsy (TTNB). MATERIAL AND METHODS: A retrospective analysis of 216 patients who underwent CT-guided TTNB was performed. The frequencies and risk factors of pneumothorax and parenchymal haemorrhage were determined. P values less than 0.05 were considered statistically significant. RESULTS: The incidences of pneumothorax and parenchymal haemorrhage were 23.1% and 45.4%, respectively. Twenty-two per cent of patients with pneumothorax needed percutaneous drainage, but all patients with parenchymal haemorrhage had clinical improvement after conservative treatment. No procedure-related mortality was detected. Univariate analysis showed that underlying pulmonary infection, lesion size of less than 1 cm, and lesion depth of more than 2 cm were significant influencing factors of pneumothorax. A significant relationship between the underlying chronic obstructive pulmonary disease (COPD) and the need for drainage catheter insertion was found. Pulmonary haemorrhage was more likely to occur in patients with underlying malignancy, solid pulmonary nodule, lesion size of 3 cm or less, and lesion depth of more than 3 cm. Consolidation was the protective factor for pulmonary haemorrhage. Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV), and accuracy of CT-guided core needle biopsy (CNB) for the diagnosis of malignancy were 95.7%, 100%, 100%, 93.3%, and 97.3%, respectively. The rate of diagnostic failure was 10.2%. CONCLUSIONS: Pulmonary hemorrhage is the most common complication after CT-guided TTNB. Influencing factors for pneumothorax are underlying pulmonary infection, lesion size < 1 cm, and lesion depth > 2 cm. Underlying malignancy, solid pulmonary nodule, lesion size ≤ 3 cm, and lesion depth > 3 cm are associated with pulmonary haemorrhage.

Role of therapeutic plasmapheresis in ANCA-associated vasculitis.

Plasma exchange, or plasmapheresis, is a treatment method that developed over a period of two decades and involves the removal and replacement of a patient's circulating plasma. The aim of treatment is to remove disease-associated molecules and therefore interrupt disease progression. This article summarizes the developmental history of this treatment and then looks in more detail at data on the use of plasma exchange in treating antineutrophil antibody (ANCA)-associated vasculitis. The eight randomized trials and the Cochrane Systematic Review on treating renal vasculitis are summarized to show that plasma exchange may be effective in this disease, specifically in reducing the development of end-stage kidney disease (ESKD) by approximately 40%. The plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS) study is a currently enrolling study aiming to answer some of the outstanding questions relating to the use of this treatment in ANCA-associated vasculitis.

Pulmonary haemorrhage due to an aortopulmonary collateral artery after arterial switch.

A neonate with transposition of the great arteries and intact ventricular septum presented without pulmonary over-circulation, and subsequently developed pulmonary haemorrhage after corrective surgery. Postoperative CT revealed an aortopulmonary collateral artery arising from the descending aorta, and we performed successful embolisation on postoperative day 9. Aggressive imaging modalities such as angiography and/or CT imaging with contrast can detect unexpected extra-pulmonary blood supply and guide further management.

Fatal quinine-induced thrombocytopenia from pulmonary haemorrhage.

Severe drug-induced thrombocytopenia is a well known but rare complication of quinine. This paper presents a discussion on quinine-induced thrombocytopenia based on a patient who developed fatal thrombocytopenia and pulmonary haemorrhage.

Paediatric pulmonary haemorrhage: Independent lung ventilation as effective strategy in management.

Pulmonary haemorrhage is an uncommon symptom in paediatrics with the etiology varying among the series by age, location, and the diagnostic tests employed. Once airway protection and volume resuscitation are ensured, localization of the anatomic site of bleeding, isolation of the involved airway, control of haemorrhage and treatment of the underlying cause of becomes essential. In localized persistent bleeding, airway control may be achieved by lung isolation with double lumen endotracheal tube and synchronous independent lung ventilation.

Pulmonary haemorrhage and haemoptysis associated with bevacizumab-related treatment regimens: a retrospective, pharmacovigilance study using the FAERS database.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified. Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14-90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78-6.02] vs. ROR 4.19 [95% CI, 3.56-4.91], p = 0.0147). Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.