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Transplantation and Cellular Therapy Jan 2023Although transplant-associated thrombotic microangiopathy (TA-TMA) commonly complicates pediatric hematopoietic cellular therapy (HCT), pulmonary manifestations and...
Although transplant-associated thrombotic microangiopathy (TA-TMA) commonly complicates pediatric hematopoietic cellular therapy (HCT), pulmonary manifestations and histology of TA-TMA (pTA-TMA) are rarely reported, with scant data available on timing, risk factors, pathogenesis, and outcomes. Pulmonary hypertension (PH) and diffuse alveolar hemorrhage (DAH) are recognized manifestations of pTA-TMA. The objective of this study was to characterize the pathologic findings, outcomes, and coincident diagnoses preceding biopsy-proven pTA-TMA. In Institutional Review Board- approved retrospective studies, available lung tissue was reviewed at 2 institutions between January 2016 and August 2021 to include those with pulmonary vascular pathology. Histologic features of pTA-TMA were present in 10 children with prior respiratory decline after an allogeneic HCT (allo-HCT; n = 9) or autologous HCT (n = 1). Pathologic lesions included muscular medialization, microthrombi, and red cell fragments, in addition to perivasculitis and intimal arteritis. Parenchymal findings included diffuse alveolar damage, organizing pneumonia, and plasmocytic infiltrates. Six children were clinically diagnosed with TA-TMA, and all were treated with eculizumab, at a median of 2.5 days after clinical diagnosis (range, 0 to 11 days). Four were identified postmortem. Coincident pulmonary infection was confirmed in 8 of the 10 patients. Five allo-HCT recipients (56%) experienced graft-versus-host disease (GVHD; 4 acute, 1 chronic) prior to the onset of respiratory symptoms. Two patients (20%) had clinically recognized DAH, although 9 (90%) had evidence of DAH on histology. Although all 10 patients underwent echocardiography at the time of symptom onset and 9 had serial echocardiograms, only 2 patients had PH detected. Treatments varied and included sildenafil (n = 3), steroids (n = 1), and eculizumab (n = 6). One patient was alive at the time of this report; the remaining 9 died, at a median of 52 days after onset of respiratory symptoms (range 4 to 440 days) and a median of 126 days post-HCT (range, 13 to 947 days). pTA-TMA is a heterogeneous histologic disease characterized by arteriolar inflammation, microthrombi, and often DAH. pTA-TMA presented with respiratory decline with systemic TA-TMA in all patients. Clinicians should maintain a high degree of suspicion for DAH in patients with TA-TMA and pulmonary symptoms. Coincident rates of GVHD and pulmonary infections were high, whereas the rate of PH identified by echocardiography was 20%. Outcomes were poor despite early use of eculizumab and other therapies. Our data merit consideration of pTA-TMA in patients with acute respiratory decline in the setting of systemic TA-TMA, GVHD, and infection. Investigation of additional therapies for pTA-TMA is needed as well. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Topics: Child; Humans; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Thrombotic Microangiopathies; Thrombosis; Hemorrhage; Lung Diseases; Graft vs Host Disease; Hypertension, Pulmonary; Pneumonia; Lung
PubMed: 36202334
DOI: 10.1016/j.jtct.2022.09.026 -
Zhonghua Jie He He Hu Xi Za Zhi =... May 2022We reported a case of vascular Ehlers-Danlos syndrome presenting with recurrent pulmonary hemorrhage. A 22-year-old man was admitted for intermittent hemoptysis and...
We reported a case of vascular Ehlers-Danlos syndrome presenting with recurrent pulmonary hemorrhage. A 22-year-old man was admitted for intermittent hemoptysis and chest pain during the past 18 months. Computed tomography of chest showed bilateral nodules and cavities with halo sign. Inflammatory markers, including erythrocyte sedimentation rate, C reactive protein and interleukin 6, were within normal range. The microbiological and pathological examination of bronchoalveolar lavage fluid and CT-guided percutaneous lung biopsy failed to draw a diagnosis. The pulmonary lesions waxed and waned despite empirical antibacterial, antifungal, antimycobacterial, and anti-parasite treatment. Video-assisted thoracoscopic lung biopsy showed pulmonary hemorrhage, hematoma, ossification, and fibrous nodules, suggesting vascular Ehlers-Danlos syndrome. The molecular testing revealed a heterozygous missense variant in the COL3A1 gene which confirmed the diagnosis of vascular Ehlers-Danlos syndrome. The patient had no skin hyperextensibility or joint hypermobility. During 3-year follow-up, there were no evidence of other vascular or organ involvement except he had intermittent minor hemoptysis. Through this clinical pathological discussion, we aimed to remind pulmonologist to consider the possible diagnosis of vascular Ehlers-Danlos syndrome in young patients with recurrent hemoptysis and waxing and waning pulmonary nodules, cavities, or cysts on CT scan who has neither obvious systematic inflammation nor effective reaction on empirical antimicrobial therapy. Molecular testing should be carried out as soon as possible in a suspected patient to avoid unnecessary invasive examinations.
Topics: Adult; Ehlers-Danlos Syndrome; Hemoptysis; Hemorrhage; Humans; Lung; Male; Multiple Pulmonary Nodules; Young Adult
PubMed: 35527463
DOI: 10.3760/cma.j.cn112147-20211103-00768 -
Clinical Radiology Sep 2022To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided...
AIM
To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTLB).
MATERIALS AND METHODS
A retrospective study was performed involving patients with undiagnosed pulmonary lesions scheduled for PTLB between January 2020 and March 2021. Patients were assigned to the haemocoagulase group or the non-haemocoagulase group. After CT-guided biopsies were performed with a 17 G coaxial system, patients in the haemocoagulase group received a haemocoagulase injection (0.2-0.5 units) in the biopsy tract as the sheath was withdrawn. Postoperative image studies were performed to evaluate complications, including pneumothorax and pulmonary haemorrhage. Factors, including the patient's position, lesion location, and pathological results, were evaluated to determine their associations with the complications.
RESULTS
A total of 100 patients were included, with 44 men and a mean age of 53 years old. The overall incidences of pneumothorax and pulmonary haemorrhage were 15% and 13%, respectively. The incidences of pneumothorax and pulmonary haemorrhage were statistically significantly lower in the haemocoagulase group (8% and 6%, respectively) than in the non-haemocoagulase group (22% and 20%, respectively; p=0.04 and 0.03, respectively). There was no statistically significant difference in haemoptysis between the haemocoagulase (6%) and non-haemocoagulase (2%) groups (p=0.23). There were also no statistically significant associations of pneumothorax or pulmonary haemorrhage with the patients' positions, lesion location, or pathological results.
CONCLUSION
Biopsy tract haemocoagulase injection reduced the incidences of postoperative pneumothorax and pulmonary haemorrhage after PTLB.
Topics: Batroxobin; Female; Hemorrhage; Humans; Image-Guided Biopsy; Lung; Lung Diseases; Male; Middle Aged; Pneumothorax; Radiography, Interventional; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed
PubMed: 35788268
DOI: 10.1016/j.crad.2022.05.019 -
The European Respiratory Journal Jan 2023Transbronchial lung cryobiopsy is an emerging technique for diagnosing pulmonary rejection. However, no prospective studies of this procedure for critically ill lung... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Transbronchial lung cryobiopsy is an emerging technique for diagnosing pulmonary rejection. However, no prospective studies of this procedure for critically ill lung transplant recipients who require mechanical ventilation in the intensive care unit (ICU) have been performed.
METHODS
From March 2017 to January 2020, we performed a prospective, randomised, comparative study to assess the diagnostic yield, histological quality and safety of transbronchial lung biopsy using biopsy forceps, a 1.9-mm cryoprobe or a 2.4-mm cryoprobe.
RESULTS
89 out of 129 consecutive transbronchial biopsy procedures (forceps group, 28 procedures; 1.9-mm cryoprobe group, 31 procedures; 2.4-mm cryoprobe group, 30 procedures) were randomised. Compared with lung samples from the forceps and 1.9-mm cryoprobe groups, lung samples from the 2.4-mm cryoprobe group allowed the most definitive diagnoses (p<0.01 and p=0.02, respectively), the most diagnoses of acute lung rejection (p<0.01 and p=0.01, respectively) and the most diagnoses of rejection severity (p<0.01 and p<0.01, respectively). These samples were larger (p<0.01 and p=0.04, respectively), had the most adequate alveolar tissue (p<0.01 and p=0.02, respectively), had more vessels per procedure (p<0.01 and p=0.01, respectively) and had no significant crush artefacts. Moderate bleeding was observed in 23% of cases (p=0.01 and p=0.08, respectively). No severe bleeding was observed.
CONCLUSIONS
Transbronchial lung biopsy using a 2.4-mm cryoprobe allows the safe collection of lung tissue samples from critically ill lung transplant recipients who require mechanical ventilation in the ICU and has good diagnostic performance.
Topics: Humans; Critical Illness; Respiration, Artificial; Bronchoscopy; Lung; Biopsy; Hemorrhage; Allografts
PubMed: 35896217
DOI: 10.1183/13993003.02354-2021 -
Seminars in Arthritis and Rheumatism Dec 2023To describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement,...
OBJECTIVES
To describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement, laboratory, radiological, and pathological findings.
METHODS
This retrospective cross-sectional study includes all patients grouped in the "CAPS Registry". All cases were reviewed, and those with pulmonary thromboembolism (PE) and/or diffuse alveolar hemorrhage (DAH) were selected. Data on pulmonary and extrapulmonary clinical presentation, radiologic patterns, laboratory findings, associated autoimmune diseases, treatments, and outcomes were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test, while T-test for independent variables was used to compare groups regarding continuous variables. IBM-SPSS v.22 was used for data analysis.
RESULTS
PE was reported in 129 (48.6 %) episodes, DAH in 75 (28.3 %) episodes, and overlap (DAH plus PE) in 7 (2.6 %) episodes. Bronchoalveolar lavage (BAL) was performed in 35 (4.9 %) CAPS episodes, and lung pathology samples were obtained in 84 (10.5 %) episodes (including autopsies). A significant relationship was observed between DAH and laboratory features of thrombotic microangiopathy (TMA). A meaningful relationship was also found between triple antiphospholipid antibody positivity and pathological TMA (26.5 %) as well as hypocomplementemia and DAH (24 %).
CONCLUSIONS
Pulmonary involvement may include both TMA and non-thrombotic inflammation, which can be differentiated into three patterns: PE, DAH with systemic TMA with hypocomplementemia or DAH without systemic TMA with/without hypocomplementemia.
Topics: Humans; Antiphospholipid Syndrome; Retrospective Studies; Cross-Sectional Studies; Lung; Lung Diseases; Hemorrhage; Thrombotic Microangiopathies; Registries; Lupus Erythematosus, Systemic
PubMed: 37857048
DOI: 10.1016/j.semarthrit.2023.152265 -
Pediatric and Developmental Pathology :... Aug 2020Perinatal pulmonary hemorrhage (PH) is a condition characterized by blood loss via the respiratory tract with an approximate incidence of 0.1% in all newborns. The...
Perinatal pulmonary hemorrhage (PH) is a condition characterized by blood loss via the respiratory tract with an approximate incidence of 0.1% in all newborns. The histologic characteristics of the lung in PH are not well characterized, and we hypothesized that pulmonary maldevelopment such as pulmonary hypoplasia may contribute to PH. In addition, we sought to find any correlations with placental pathology. Retrospective study of fetal and neonatal autopsies with diagnosis of PH was performed between the years from 2009 to 2015. Autopsy reports, placental pathology reports, and hematoxylin and eosin sections of the lung were reviewed. Of the 17 cases which were identified meeting inclusion criteria, PH ranged from mild (<5% in each lung) to severe (>75% in both lungs). PH involved >50% of both lungs in 6 cases. Pulmonary hypoplasia was designated in 7 of 17 (41.17%) cases with PH. Pulmonary hypoplasia and/or persistence of intra-acinar arterioles was seen in 13 of 17 (76.4%) cases. No specific placental pathology was seen universally in the cases of PH, but either maternal or fetal vascular malperfusion was noted in 14 of 17 (82%) cases. Our data suggest a high prevalence of pulmonary maldevelopment, such as pulmonary hypoplasia and persistence of intra-acinar arterioles, in cases with PH. Although no specific placental pathology is seen in PH, maternal and fetal vascular pathology is common.
Topics: Abnormalities, Multiple; Autopsy; Female; Hemorrhage; Humans; Infant, Newborn; Lung; Lung Diseases; Male; Placenta; Placenta Diseases; Pregnancy; Prevalence; Retrospective Studies
PubMed: 32075513
DOI: 10.1177/1093526619900728 -
Clinical Rheumatology Feb 2022This narrative review provides an overview of diffuse alveolar hemorrhage (DAH) associated with rheumatologic and autoimmune diseases and their differentiation from... (Review)
Review
This narrative review provides an overview of diffuse alveolar hemorrhage (DAH) associated with rheumatologic and autoimmune diseases and their differentiation from idiopathic pulmonary hemosiderosis (IPH). Relevant immunologic diseases associated with DAH are discussed, and a diagnostic flowchart is proposed to establish a "definitive" diagnosis of IPH within the spectrum of DAH. IPH is a rare cause of recurrent DAH both in children and adults. In adults, a definitive diagnosis of IPH requires a lung biopsy and histopathologic examination demonstrating intraalveolar hemorrhage, hemosiderin-laden macrophages, and a variable degree of fibrosis in the absence of both capillaritis and cellular inflammation. The presence of small vessel vasculitis points towards immunologic, well-differentiated, or sometimes undifferentiated rheumatologic diseases. However, it is essential to recognize that many rheumatologic diseases may in the initial phase present with DAH without any evidence of capillaritis, thus mimicking IPH. Although not definitely established, it is likely that immunologic processes are involved in IPH, and we, therefore, suggest the consideration of a more suitable term for the disease, e.g., "Immune-mediated Pulmonary Hemosiderosis" to acknowledge the aberrancy in the immune parameters and a positive response to immunosuppressive therapy.
Topics: Adult; Arthritis, Rheumatoid; Autoimmune Diseases; Child; Hemorrhage; Hemosiderosis; Humans; Lung; Lung Diseases; Hemosiderosis, Pulmonary
PubMed: 34491458
DOI: 10.1007/s10067-021-05895-1 -
The American Journal of Emergency... Nov 2021A healthy young man presented to the emergency department with mild hemoptysis associated with cannabis abuse. He was on no medications and cocaine abuse was ruled out...
A healthy young man presented to the emergency department with mild hemoptysis associated with cannabis abuse. He was on no medications and cocaine abuse was ruled out by both history and negative toxicology screens. There were neither signs of an infection, nor of a systemic or cardiac disease. Imaging studies were consistent with diffuse alveolar hemorrhage, a reported, albeit rare adverse drug reaction of tetrahydrocannabinol (Naranjo score 6). The patient improved spontaneously within a few days, hemoptysis stopped and repeat imaging was entirely normal. With the increase in cannabis abuse and enhanced cannabis potency worldwide clinicians may increasingly encounter even unusual cannabis-associated adverse drug reactions, including associated diffuse alveolar hemorrhage.
Topics: Hemoptysis; Humans; Male; Marijuana Abuse; Pulmonary Alveoli; Smokers; Young Adult
PubMed: 34001429
DOI: 10.1016/j.ajem.2021.05.003 -
Tidsskrift For Den Norske Laegeforening... May 2022
Topics: Hemorrhage; Humans; Lung
PubMed: 35635406
DOI: 10.4045/tidsskr.22.0008 -
Seminars in Immunopathology May 2023Acute ischaemic and haemorrhagic stroke account for significant disability and morbidity burdens worldwide. The myeloid arm of the peripheral innate immune system is... (Review)
Review
Acute ischaemic and haemorrhagic stroke account for significant disability and morbidity burdens worldwide. The myeloid arm of the peripheral innate immune system is critical in the immunological response to acute ischaemic and haemorrhagic stroke. Neutrophils, monocytes, and dendritic cells (DC) contribute to the evolution of pathogenic local and systemic inflammation, whilst maintaining a critical role in ongoing immunity protecting against secondary infections. This review aims to summarise the key alterations to myeloid immunity in acute ischaemic stroke, intracerebral haemorrhage (ICH), and subarachnoid haemorrhage (SAH). By integrating clinical and preclinical research, we discover how myeloid immunity is affected across multiple organ systems including the brain, blood, bone marrow, spleen, and lung, and evaluate how these perturbations associate with real-world outcomes including infection. These findings are placed in the context of the rapidly developing field of human immunology, which offers a wealth of opportunity for further research.
Topics: Humans; Stroke; Brain Ischemia; Hemorrhagic Stroke; Subarachnoid Hemorrhage
PubMed: 36346451
DOI: 10.1007/s00281-022-00968-y