A case of anti-myeloperoxidase antibodies-associated idiopathic crescentic glomerulonephritis with pulmonary hemorrhage]

We report a case of idiopathic crescentic glomerulonephritis with pulmonary hemorrhage associated with anti-myeloperoxidase antibodies (anti-MPO ab). A 74 year-old female was admitted to our hospital because of rapidly progressive glomerulonephritic syndrome and dyspnea with bloody sputum. On admission anti-MPO ab, one of anti-neutrophil cytoplasmic antibodies, were detected but anti-GBM antibodies and immune complexes were not detected. Renal biopsy showed crescentic glomerulonephritis and lung biopsy showed massive alveolar hemorrhage. Both tissue had pauci-immune deposit by immunofluorescence microscopy. Hemodialysis and steroid administration were started. Pulmonary hemorrhage was improved remarkably, but renal failure progressed rapidly to end stage kidney, then hemodialysis was continued. Although subsequent 3 years uneventful maintenance hemodialysis had been performed, she admitted to our hospital again because of progressive dyspnea with hemoptysis after upper respiratory tract infection. On admission anti-MPO ab were detected again and steroid administration was started. Pulmonary hemorrhage was improved with decreased anti-MPO ab titer. While tapering the dosis of steroid, anti-MPO ab again increased and pulmonary hemorrhage recurred. Although pulse methylprednisolone therapy and plasma exchange were performed, respiratory failure progressed rapidly and she died of sepsis. Postmortem examination showed no evidence of systemic vasculitis. In this case, titer of anti-MPO ab was associated with not only idiopathic crescentic glomerulonephritis but also with pulmonary hemorrhage. We tried to detect enzymatically active MPO in serum. Titer of serum MPO was also associated with disease activity and anti-MPO ab. It is suggested that both anti-MPO ab and serum MPO are closely related to the pathogenesis of idiopathic crescentic glomerulonephritis and pulmonary hemorrhage.     

Idiopathic Goodpasture's syndrome. Fatal pulmonary haemorrhage and crescentic glomerulonephritis in the absence of immune-reactant deposition

A 58-year-old woman was hospitalized with acute renal failure and unilateral pulmonary consolidation. Ten days later she developed massive pulmonary haemorrhage with diffuse pulmonary consolidation. Renal biopsy revealed 100% crescentic nephritis without immunofluorescence (IF) or electron microscopic evidence of immune reactant deposition. Circulating anti-glomerular basement membrane (antiGBM) antibody was not detectable by radioimmunoassay. Despite aggressive therapy pulmonary haemorrhage eventually proved fatal. IF of lung tissue revealed no immune-reactant deposition. This report represents a case of idiopathic Goodpasture's syndrome, both from an aetiological and an immunopathological viewpoint. It emphasizes that Goodpasture's syndrome (i.e. pulmonary haemorrhage and glomerulonephritis) occurs in a variety of situations which are not mediated by antiGBM antibody deposition and that alveolar haemorrhage should be considered in the differential diagnosis of all radiological pulmonary infiltrates, including unilateral opacities, when abnormalities of renal function coexist.     

Wegener granulomatosis – an atypical case

 An unusual sequence of the clinical manifestations of microvascular disease is described in a 15 year-old girl. She initially presented with acute renal failure caused by a crescentic glomerulonephritis associated with positive tests for MPO-ANCA. Eighteen months later she had pulmonary hemorrhage and respiratory failure. An open lung biopsy showed granulomas that were diagnostic for Wegener granulomatosis. We discuss the diagnostic dilemmas faced in attempts to distinguish infective causes of pulmonary granulomas, such as tuberculosis or fungi, from granulomas associated with vasculitis, in a patient previously treated with immunosuppressive therapy. Received: 4 August 1999 / Revised: 28 October 1999 / Accepted: 3 January 2000     

Unusual Evolution in Wegener's Granulomatosis: Recovery of Pulmonary Involvement While Renal Disease Progressed to End-Stage

A 54-year-old male patient was admitted for acute respiratory distress with fever. He was suffering from chronic sinusitis/rhinitis and had persistent otitis for the past 2 months before admission despite several antibiotics courses. He developed a complex pulmonary involvement (embolism and diffuse alveolar hemorrhage) with acute glomerular disease (proteinuria and hematuria but initially no renal failure). Clinical suspicion of Wegener’s granulomatosis was confirmed by the positive high titer of antineutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and despite a negative nasal biopsy. Treatment including cyclophosphamide and methylprednisolone intravenous pulses permitted pulmonary recovery over 4 weeks contrasting with the development of rapidly progressive glomerulonephritis and polyneuropathy of lower limbs. Renal biopsy showed pauci-immune crescentic and necrotizing glomerulonephritis. However, despite additional plasma exchanges, acute kidney injury worsened and the patient ended up in dialysis. Such a dissociated evolution was unexpected in this case since pulmonary and renal involvements reflected the same pathological process (small vessels vasculitis/capillaritis) and the same pathogenic mechanism (antiproteinase 3 autoantibodies).     

Unusual evolution in Wegener's granulomatosis: recovery of pulmonary involvement while renal disease progressed to end-stage

A 54-year-old male patient was admitted for acute respiratory distress with fever. He was suffering from chronic sinusitis/rhinitis and had persistent otitis for the past 2 months before admission despite several antibiotics courses. He developed a complex pulmonary involvement (embolism and diffuse alveolar hemorrhage) with acute glomerular disease (proteinuria and hematuria but initially no renal failure). Clinical suspicion of Wegener's granulomatosis was confirmed by the positive high titer of antineutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and despite a negative nasal biopsy. Treatment including cyclophosphamide and methylprednisolone intravenous pulses permitted pulmonary recovery over 4 weeks contrasting with the development of rapidly progressive glomerulonephritis and polyneuropathy of lower limbs. Renal biopsy showed pauci-immune crescentic and necrotizing glomerulonephritis. However, despite additional plasma exchanges, acute kidney injury worsened and the patient ended up in dialysis. Such a dissociated evolution was unexpected in this case since pulmonary and renal involvements reflected the same pathological process (small vessels vasculitis/capillaritis) and the same pathogenic mechanism (antiproteinase 3 autoantibodies).     

Rhinovirus/enterovirus identification by electron microscopy in lower respiratory tract infection in a patient with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation and donor lymphocyte infusion

Donor lymphocyte infusion (DLI) is a curable treatment option, inducing a graft-versus-tumor effect in patients with relapsed hematological malignancies after allogeneic hematopoietic cell transplantation (allo-HCT). However, not only graft-versus-host disease but also pulmonary complications are problematic adverse events after DLI. Although viral infections can be associated with pulmonary complications after DLI, the mechanism underlying these complications remains unclear. Detecting the causative virus infections after pulmonary complications following DLI is challenging, as invasive examinations, such as bronchoalveolar lavage and lung biopsies, are necessary. Family Picornaviridae, including Human-Rhinovirus (HRV) and Enterovirus (EnV), can induce fatal lower respiratory tract infection (LRTI) in recipients who undergo allo-HCT, which can be underdiagnosed. We encountered a 62-year-old man with relapsed myelodysplastic syndrome 20 days after a second HLA-haplo-identical allo-HCT and 4 DLI procedures who was later found to have HRV and EnV LRTI by postmortem electron microscopy. Despite high-dose immunosuppression, severe hypoxemia did not improve, and he succumbed to respiratory failure. Immunosuppressive therapy for idiopathic pneumonia syndrome after allo-HCT may be effective, but its efficacy for acute respiratory failure after DLI is controversial. Our case indicated that the control of viral replication should be prioritized over that of inflammation in HRV and EnV LRTI after DLI.     

Hydralazine-Induced ANCA-Positive Pauci-immune Glomerulonephritis: A Case Report and Literature Review

We report a case of hydralazine-induced alveolar hemorrhage and anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis, with serum anti-histone antibodies present, features not previously described in the literature with this drug. A 50-year-old Caucasian female had hypertension treated with hydralazine 75mg TID for three years, and a lung nodule followed up periodically with chest-computed tomographies. She was admitted to the hospital for hemoptysis and newly discovered diffuse pulmonary ground-glass opacities. Transbronchial lung biopsy showed alveolar hemorrhage. Serum creatinine was 3.5 mg/dL and urinalysis showed 2+blood, 30-50RBC/hpf and red blood cell casts. ANCA against myeloperoxidase were present. Anti-double-stranded DNA, ANA, and anti-histone antibodies were positive. Serum complements were normal. Renal biopsy revealed focal crescentic necrotizing glomerulonephritis with negative immunofluorescence, consistent with pauci-immune ANCA-positive vasculitis. Serum creatinine returned to baseline three days after hydralazine was discontinued, and the hemoptysis resolved after treatment with cyclophosphamide and prednisone was started. We concluded that this case represents a hydralazine-induced small vessel vasculitis rather than an idiopathic one. The possibility of hydralazine-induced vasculitis should be considered when patients treated with hydralazine develop a pulmonary-renal syndrome. Anti-histone antibodies may be present in the absence of full classification criteria of drug-induced lupus.     

Pulmonary Contusion: An Update on Recent Advances in Clinical Management

Pulmonary contusion is a common finding after blunt chest trauma. The physiologic consequences of alveolar hemorrhage and pulmonary parenchymal destruction typically manifest themselves within hours of injury and usually resolve within approximately 7 days. Clinical symptoms, including respiratory distress with hypoxemia and hypercarbia, peak at about 72 h after injury. The timely diagnosis of pulmonary contusion requires a high degree of clinical suspicion when a patient presents with trauma caused by an appropriate mechanism of injury. The clinical diagnosis of acute parenchymal lung injury is usually confirmed by thoracic computed tomography, which is both highly sensitive in identifying pulmonary contusion and highly predictive of the need for subsequent mechanical ventilation. Management of pulmonary contusion is primarily supportive. Associated complications such as pneumonia, acute respiratory distress syndrome, and long-term pulmonary disability, however, are frequent sequelae of these injuries.     

Cytopathology of pulmonary alveolar proteinosis complicating lung transplantation.

Pulmonary alveolar proteinosis is a disorder of unknown origin that occurs rarely after lung transplantation. We identified a patient with pulmonary alveolar proteinosis 66 days after undergoing single lung transplantation for idiopathic pulmonary fibrosis. We based the diagnosis on the presence of amorphous clumps or globules of acellular and finely granular material in bronchoalveolar lavage fluid (BALF). This material persisted for an 18.5-month period and was present in 9 of 14 lavage specimens. However, despite its presence in the native lung at autopsy, the material was seen in only 1 of 14 transbronchial lung biopsy specimens. Although uncommon, pulmonary alveolar proteinosis can be diagnosed readily in BALF by its distinctive cytopathologic features and should be considered in the differential diagnosis of pulmonary disease in lung transplant recipients.     

Crescentic Glomerulonephritis Associated with Non-Tuberculous Mycobacteria Infection

A 72-year-old woman with a previous diagnosis of non-tuberculous mycobacteria (NTM) pulmonary disease was admitted because of hemoptysis and acute renal failure. A chest x-ray showed interstitial infiltration over bilateral lung fields. A kidney biopsy showed immune complex-mediated crescentic glomerulonephritis and diffuse endocapillary hypercellularity with exudative neutrophils. Reactive NTM infection of the lungs was suspected when mycobacterial cultures of the sputum repeatedly yielded Mycobacterium avium. A lung biopsy revealed chronic inflammation without evidence of alveolar capillaritis. NTM pulmonary disease was further confirmed by tissue culture of the lung biopsy specimens. Anti-tuberculous drugs in combination with clarithromycin were given for the treatment of NTM infection. Because of the risk of aggravating underlying infectious disease, immunosuppressive therapy for crescentic glomerulonephritis was not carried out. Pulmonary symptoms promptly responded to treatment. Furthermore, renal function steadily improved after the initiation of anti-NTM therapy. To our knowledge, this is the first report of crescentic glomerulonephritis associated with NTM infection.     

Bronchospasm during anesthesia in a patient with Pena-Shokeir syndrome

A 3-month-old boy with Pena-Shokeir syndrome underwent tracheotomy under general anesthesia. Patients with this syndrome may present anesthetic problems involving difficulties in tracheal intubation, possibilities of malignant hyperthermia, as well as perioperative respiratory complications related to hypoplasia of the lung. General anesthesia was induced and maintained with sevoflurane (2-3%) and nitrous oxide (0-50%) in oxygen (50-100%). The patient developed bronchospasm during tracheotomy. Atropine and epinephrine were administered intravenously and 5% sevoflurane was inhaled. The bronchospasm was improved gradually and surgery was successfully finished. Pena-Shokeir syndrome is an uncommon disease first reported by Pena & Shokeir in 1974 and characterized by congenital multiple arthrogryposis, characteristic facies, camptodactyly and pulmonary hypoplasia. In the perioperative management for a patient with Pena-Shokeir syndrome, special attention should be paid to abnormalities in the upper and lower respiratory systems, especially bronchospasm.     

Crescentic glomerulonephritis associated with non-tuberculous mycobacteria infection

A 72-year-old woman with a previous diagnosis of non-tuberculous mycobacteria (NTM) pulmonary disease was admitted because of hemoptysis and acute renal failure. A chest x-ray showed interstitial infiltration over bilateral lung fields. A kidney biopsy showed immune complex-mediated crescentic glomerulonephritis and diffuse endocapillary hypercellularity with exudative neutrophils. Reactive NTM infection of the lungs was suspected when mycobacterial cultures of the sputum repeatedly yielded Mycobacterium avium. A lung biopsy revealed chronic inflammation without evidence of alveolar capillaritis. NTM pulmonary disease was further confirmed by tissue culture of the lung biopsy specimens. Anti-tuberculous drugs in combination with clarithromycin were given for the treatment of NTM infection. Because of the risk of aggravating underlying infectious disease, immunosuppressive therapy for crescentic glomerulonephritis was not carried out. Pulmonary symptoms promptly responded to treatment. Furthermore, renal function steadily improved after the initiation of anti-NTM therapy. To our knowledge, this is the first report of crescentic glomerulonephritis associated with NTM infection.     

体外膜肺氧合在肺移植前支持过渡中的应用

目的 探讨体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)在肺移植前支持过渡中应用的可行性和疗效.方法 终末期肺病患者5例,原发病为特发性肺间质纤维化3例,结核性毁损肺1例,淹溺致吸入性肺炎合并急性呼吸窘迫综合征(ARDS)1例.药物治疗和呼吸机无法纠正呼吸衰竭,紧急行E...     

Pulmonary hemorrhage in children with glomerulonephritis

Pulmonary hemorrhage may occur in patients with immune-mediated glomerulonephritis. This association can be seen in a variety of disorders including systemic lupus erythematosus, vasculitis, Wegener's granulomatosis, anaphylactoid purpura and Goodpasture's syndrome. Immune mechanisms, such as immune complexes and/or autoantibodies, play a role in the pathogenesis of pulmonary and glomerular injury. Acute pulmonary hemorrhage can lead to respiratory failure and has a high mortality. Therapy with immunosuppressive agents such as pulse methylprednisolone and cyclophosphamide will control the hemorrhage and improve pulmonary function in most cases.     

Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection

OBJECTIVE: Pulmonary fibrosis is associated with an increased risk of lung cancer and outcome of surgical resection in this setting is unknown. METHODS: We studied 22 patients (24 operations) with pulmonary fibrosis and non-small cell lung cancer treated between 1991 and 2000 (study group) and compared outcome with 951 other patients (964 operations) treated for non-small cell lung cancer over the same period (control patients). RESULTS: The two groups did not differ significantly in age (68 vs 65 years), smoking history (86% vs 95% smokers), forced expiratory volume in 1 second (2.5 L/min vs 2.3 L/min) or forced vital capacity (3.2 L vs 3.7 L), but patients with pulmonary fibrosis were more likely to be male (72% vs 58%, P <.05). The operative mortality was higher in patients with pulmonary fibrosis than in control patients (17% vs 3.1%, P <.01) and there was a higher procedure-specific mortality in pulmonary fibrosis for pneumonectomy (33% vs 5.1%, P <.01) and lobectomy (12% vs 2.6%, P <.01). Patients with pulmonary fibrosis had a higher incidence of postoperative lung injury, (21% vs 3.7%, P <.01) and a longer mean hospital stay (17 vs 9 days, P <.05). In patients with pulmonary fibrosis, the actuarial 3-year survival was 54%. There were 11 deaths in the study group, 4 postoperatively (all acute respiratory distress syndrome) and 7 late deaths (metastatic disease, n = 2; progressive pulmonary fibrosis, n = 5). Median follow-up (to death or last review) was 13 months (range, 0-120 months). Five patients developed postoperative acute respiratory distress syndrome and in 4 of these patients this proved to be fatal. Postoperative acute respiratory distress syndrome was associated with lower preoperative total lung carbon monoxide diffusion capacity (median, 58% vs 70%, P =.03) and lower preoperative carbon monoxide diffusion capacity corrected for alveolar volume (median, 48% vs 58%, P =.05) and a higher preoperative composite physiological index (median, 44 vs 33, P =.008). None of the preoperative lung function parameters or operative finding were predictors of late death. CONCLUSION: Patients with pulmonary fibrosis undergoing pulmonary resection for non-small cell lung cancer have increased postoperative morbidity and mortality, but an important subgroup has a good long-term outcome. Postoperative acute respiratory distress syndrome is associated with low preoperative gas transfer and a high composite physiological index. Resection of non-small cell lung cancer is appropriate in pulmonary fibrosis, provided that the level of functional impairment is carefully factored into patient selection.     

The influence of intraoperative oxygen inhalation on patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a high risk factor for acute exacerbation of interstitial pneumonia (IP) after pulmonary resection. Other risk factors for inducing IP exacerbation are thought to be intraoperative inhalation of high concentration of oxygen, high pressure mechanical ventilation, major thoracic surgery, massive blood transfusion and preoperative chemotherapy and irradiation. The prophylactic strategy for this phenomenon has not been established, although mechanical ventilation by low pressure and low oxygen concentration, minimum invasive surgery and prophylactic administration of steroid, ulinastatin and sivelestat sodium hydride are performed. Acute exacerbation of IP is the same concept with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). This pulmonary injury is closely associated with reactive oxygen species (ROS). In particular, high concentration of oxygen induces excessive production of ROS. ROS stimulates alveolar macrophages and neutrophils to release inflammatory cytokines, such as TNF-alpha, IL-8, IFN-gamma, IL-6 and IL-1beta. These cytokines injure pulmonary endothelium and alveolus, and atelectasis, pulmonary hemorrhage, lung edema, hyalinization and alveolar thickness occur, and this is a manifestation of ALL Therefore, although there is no evidence, high pressure ventilation and inhalation of high oxygen concentration during anesthesia should be avoided.     

Ventilator-induced lung injury and sepsis: two sides of the same coin?

Unequivocal evidence from both experimental and clinical research has shown that mechanical ventilation can damage the lungs and initiate an inflammatory response, possibly contributing to extrapulmonary organ dysfunction. This type of injury, referred to as ventilator-induced lung injury (VILI), resembles the syndromes of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). VILI can trigger a complex array of inflammatory mediators, resulting in a local and systemic inflammatory response. Substances produced in the lungs can be translocated into the systemic circulation as a result of injury to the pulmonary epithelium and to the capillary endothelium. This type of injury forms the basis for the use of low tidal volumes (5-7 mL/kg of predicted body weight) during mechanical ventilation of patients with ALI/ARDS. The recognition of VILI has prompted a number of investigators to suggest that ALI/ARDS may be, in part, a product of our efforts to mechanically ventilate patients rather than the progression of the underlying disease. On the other hand, current scientific evidence supports a link between VILI and the development of extrapulmonary organ dysfunction, similar to how most severe cases of sepsis are clinically manifested. In addition, functional genomics approaches using a gene array methodology to measure lung gene expression have identified differential patterns of gene expression in animal models of VILI, similar to those gene pathways activated during experimental and clinical sepsis. In this line of thought, we hypothesize that injurious mechanical ventilation could be responsible for the perpetuation and worsening of sepsis in some patients and for the development of a sepsis-like syndrome in others.     

Leptospiral nephropathy

Renal involvement is common in leptospirosis. Clinical manifestations vary from urinary sediment changes to acute renal failure. Renal failure is observed in 44% to 67% of patients. Hypokalemia frequently occurs. Severe hypotension is an important warning sign for the later development of renal and pulmonary complications. Prognosis of the disease is generally good except for its association with pulmonary complications, especially pulmonary hemorrhage and acute respiratory distress syndrome. Interstitial nephritis is the basic renal lesion. Vasculitis is observed in the acute phase of the disease. Tubular necrosis and interstitial nephritis are responsible for renal failure. Glomerular changes usually are not remarkable. Hemodynamic alterations, immune response, and direct nephrotoxicity are responsible for the development of renal lesions. As in many infectious diseases, decreased renal blood flow and glomerular filtration rate play a basic role. Bacterial invasion and toxicity of outer membrane with generation of cytokines, chemokines, and cellular infiltration are important in cellular injury.     

Delayed presentation: negative pressure pulmonary hemorrhage

Negative pressure pulmonary hemorrhage (NPPH) is a rare, life-threatening complication that develops after an acute upper airway obstruction. A 26 year old, healthy African-American man with no underlying lung disease developed negative pressure pulmonary edema and subsequently NPPH during recovery from general anesthesia for elective spine surgery. Diagnostic bronchoscopy confirmed an alveolar source of the bleeding. Clinical improvement was quick with supportive care in the medical intensive care unit.     

Alveolar recruitment in pulmonary and extrapulmonary acute respiratory distress syndrome: comparison using pressure-volume curve or static compliance

BACKGROUND: Alveolar recruitment in response to positive end-expiratory pressure (PEEP) may differ between pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS), and alveolar recruitment values may differ when measured by pressure-volume curve compared with static compliance. METHODS: The authors compared PEEP-induced alveolar recruitment in 71 consecutive patients identified in a database. Patients were classified as having pulmonary, extrapulmonary, or mixed/uncertain ARDS. Pressure-volume curves with and without PEEP were available for all patients, and pressure-volume curves with two PEEP levels were available for 44 patients. Static compliance was calculated as tidal volume divided by pressure change for tidal volumes of 400 and 700 ml. Recruited volume was measured at an elastic pressure of 15 cm H2O. RESULTS: Volume recruited by PEEP (10 +/- 3 cm H2O) was 223 +/- 111 ml in the pulmonary ARDS group (29 patients), 206 +/- 164 ml in the extrapulmonary group (16 patients), and 242 +/- 176 ml in the mixed/uncertain group (26 patients) (P = 0.75). At high PEEP (14 +/- 2 cmH2O, 44 patients), recruited volumes were also similar (P = 0.60). With static compliance, recruitment was markedly underestimated and was dependent on tidal volume (226 +/- 148 ml using pressure-volume curve, 95 +/- 185 ml for a tidal volume of 400 ml, and 23 +/- 169 ml for 700 ml; P < 0.001). CONCLUSION: In a large sample of patients, classification of ARDS was uncertain in more than one third of patients, and alveolar recruitment was similar in pulmonary and extrapulmonary ARDS. PEEP levels should not be determined based on cause of ARDS.