Association of serum antibodies against the Mycobacterium avium complex and hemoptysis: a cross-sectional study.

BACKGROUND: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. METHODS: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. To investigate the linear trends in the relationship between MAC-Ab levels and hemoptysis, the subjects were classified into three groups using the tertile distribution of the MAC-Ab. RESULTS: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2 and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15-7.44)). Likewise, when categorizing the subjects into three groups, the risk of hemoptysis increased with increasing MAC-Ab levels (P = 0.03 for trend). CONCLUSIONS: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. There were also positive trends in the association between the MAC-Ab titer and the likelihood of hemoptysis. Measuring the MAC-Ab may contribute not only to early detection of the risk of hemoptysis but also to early intervention with anti-NTM therapy and, as a result, to the prevention of hemoptysis in MAC patients.

Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Disease.

BACKGROUND: Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known. METHODS: A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity. RESULTS: Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%, P=0.005). Antilaminin-521 autoantibodies were predominantly of IgG1 and IgG4 subclasses and significantly associated with lung hemorrhage (P=0.005), hemoptysis (P=0.008), and smoking (P=0.01), although not with proteinuria or serum creatinine at diagnosis. CONCLUSIONS: Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes.

Haemoptysis following shallow breath-hold diving in a cannabis user.

We report the first case of a healthy 24-year-old male with a 6-year history of regular cannabis use, who presented with haemoptysis after a shallow 3 m breath-hold dive. Blood investigations showed mild neutrophilia. CT thorax revealed focal ground-glass changes in the superior segment of the lower lobe. With a suspicion of pneumonia, oral antibiotics were initiated to poor effect. Through bronchoscopic visualisation and lavage, a diagnosis of diffuse alveolar haemorrhage was established. The clinical course was benign with resolution of symptoms and changes on CT thorax within 6 weeks of stopping marijuana use. Since all other causes of haemoptysis were excluded, pathophysiology was attributed to cannabis-induced lung parenchymal damage, exacerbated by a shallow breath-hold dive. To ensure appropriate management, a clinician should therefore have a high index of suspicion for drug use and other factors known to cause chronic lung damage in whom other causes of diffuse alveolar haemorrhage are excluded.

Concurrent pulmonary sequestration and pulmonary hydatid cyst in a child: A case report.

Pulmonary sequestration (PS) happens when an area of the lung receives its arterial blood supply from systemic circulation, resulting in a non-functional lesion (Intralobar or extralobar). Hydatid cyst results from infection of the tapeworm Echinococcus. We report a case of hydatid cyst existed concurrently with intralobar PS. A 12-year-old girl presented with recurrent hemoptysis of 2 years duration. Serology for Echinococcus granulosus was positive. CT chest suggested intralobar PS in the right middle lobe, which was surgically removed. In conclusion, recurrent localized pulmonary infections should raise the suspicion of intralobar PS which may rarely coexist with hydatid cyst.

Hemoptysis in a Patient with Elevated Immunoglobulin E.

Recurrent pneumonia with cavitation leading to pneumatoceles, secondary fungal infections, and hemoptysis are major causes of mortality and morbidity in patients with hyper-IgE syndrome. Prevention and aggressive treatment of pneumonia in these patients are essential to prevent further lung damage, but treatment may be delayed because the classic signs/symptoms of infection such as fever, chills, or rigors may be lacking. Early imaging to identify infection is essential for diagnosis and treatment. The mainstay of therapy is continuous, full-dose daily trimethoprim-sulfamethoxazole and commonly fungal coverage. Because hyper-IgE syndrome is a progressive disease, patients' condition may worsen despite compliance with prophylactic therapy.

Inherited antithrombin deficiency and anabolic steroids: a risky combination.

A 20-year-old male with asymptomatic inherited type 1 antithrombin deficiency and a family history of thrombosis started injecting himself with testosterone 250 mg intramuscularly twice weekly for 5 weeks. He presented to the hospital with progressive dyspnea on exertion, chest pain and hemoptysis. Workup revealed bilateral submassive pulmonary embolism and proximal right lower extremity deep vein thrombosis. He was treated with intravenous (IV) unfractionated heparin and underwent catheter-directed thrombolysis with alteplase to the main pulmonary arteries. Postprocedure, he remained on IV alteplase infusion for 24 h and unfractionated heparin in the intensive care unit. Concomitantly he received plasma-derived antithrombin concentrate. He was transitioned to subcutaneous enoxaparin twice daily and discharged from the hospital on oral rivaroxaban 15 mg twice a day. This case highlights the heightened thrombogenic effect of anabolic steroids in the setting of underlying thrombophilia especially in younger subjects.

Prognosis and Predictors of Rebleeding After Bronchial Artery Embolization in Patients with Active or Inactive Pulmonary Tuberculosis.

INTRODUCTION: The aim of this study was to characterize the prognosis and identify factors that contribute to rebleeding after bronchial artery embolization (BAE) in patients with active or inactive pulmonary tuberculosis (PTB). METHODS: Following a retrospective review, 190 patients had hemoptysis requiring BAE due to PTB in one hospital between 2006 and 2013. RESULTS: The median age at the time of diagnosis of PTB was 37 years and 54 years at the time of first episode of hemoptysis. Among 47 patients (24.7 %) who experienced rebleeding after BAE during the median follow-up period of 13.9 months [interquartile range (IQR) 2.3-36.0 months], bleeding recurred in 12 patients (6.3 %) within 1 month and in 15 patients (7.9 %) after 1 year. The median non-recurrence time was 8.6 months (IQR 1.2-27.6 months). Independent predictors of rebleeding after BAE were tuberculous-destroyed lung [hazard ratio (HR) 3.0; 95 % confidence interval (CI) 1.5-6.2; p = 0.003], the use of anticoagulant agents and/or antiplatelet agents (HR 2.6; 95 % CI 1.1-5.8; p = 0.022), underlying chronic liver disease (HR 2.7; 95 % CI 1.1-4-6.9; p = 0.033), elevated pre-BAE C-reactive protein (CRP) (mg/dL) (HR 2.4; 95 % CI 1.0-5.5; p = 0.048), and the existence of fungal ball (HR 2.1; 95 % CI 1.0-4.3; p = 0.050). CONCLUSIONS: The risk of rebleeding after BAE in active or inactive PTB was high, particularly in patients with tuberculous-destroyed lung, chronic liver disease, the use of anticoagulant agents and/or antiplatelet agents, elevated pre-BAE CRP, and the existence of fungal ball.

Clinical features of children with pulmonary microscopic polyangiitis: report of 9 cases.

Kidneys and lungs are the most common organs involved in microscopic polyangiitis (MPA). A retrospective analysis of pediatric MPA patients with pulmonary lesions over the past 10 years was performed to investigate clinical features of MPA in children with pulmonary lesions. There were 9 patients enrolled in our study, including 2 boys and 7 girls, with a median age of 6.6 years at the time of disease onset and a median disease course of 2 months. All of the patients exhibited tachypnea, and 7 exhibited cough and hemoptysis. The most common presentation on pulmonary imaging was ground glass or patchy shadows, which were observed in 6 cases. Seven patients manifested with hematuria and proteinuria, with renal histopathology of fibrinoid necrosis/exudation of the glomerular capillaries. All of the patients presented with normocytic normochromic anemia. Of the 9 patients, 7 were positive for perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and/or myeloperoxidase (MPO), and 2 were positive for p-ANCA/MPO and cytoplasmic ANCA/proteinase 3. Eight patients had normal complement 3 (C3) levels, and one had an elevated C3 level. Five of the 9 patients were positive for antinuclear antibody ANA, and 4 were positive for double strand DNA (ds-DNA) antibody (3 were positive for both). The 7 patients who exhibited renal involvement received steroid plus cyclophosphamide (CTX) treatment. Of these patients, 4 achieved various degrees of remission, 2 were at the beginning of induction therapy, and one was lost to follow-up. Two patients with isolated pulmonary involvement received steroid plus leflunomide treatment and achieved complete remission. Diffuse alveolar hemorrhage was the most frequent presentation of lung involvement in children with MPA, and tachypnea, cough, hemoptysis and anemia were the common clinical symptoms. The majority of these patients exhibited hematuria, proteinuria and renal insufficiency. The efficacy of steroid plus CTX or leflunomide was evident in these patients.

A 27-year-old woman presenting with refractory hypoxaemic respiratory failure, haemoptysis and thyrotoxicosis: a rare manifestation of propylthiouracil therapy.

Pulmonary manifestations of hyperthyroidism not only include pulmonary hypertension and hydrostatic pulmonary oedema, but also treatment/drug-associated pulmonary diseases have to be considered as an exclusion diagnosis. A 27-year-old woman with hypoxaemic respiratory failure under an arterial-venous extra-corporeal membrane oxygenator (AV-ECMO) was admitted to the intensive care unit (ICU). The patient had progressive dyspnoea with haemoptysis, palpitations and failure to thrive. The patient had Graves' disease treated previously with propylthiouracil (PTU). Diffuse alveolar haemorrhage is a non-specific syndrome characterised by evidence of diffuse alveolar damage, exclusion of infectious aetiology and progressively bloodier bronchoalveolar lavage (and/or 20% hemosiderin laden macrophages on cytological examination). PTU associated perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) vasculitis appears to be more common in younger female patients presenting with leukocytoclastic vasculitis, myalgias and arthralgias. The latter compared to non-drug associated ANCA vasculitis which are more common in older males with visceral involvement. PTU-induced ANCA vasculitis prognosis appears to be better compared to primary ANCA syndromes.

[A very rare cause of haemoptysis - coexistence of primary oncocytic adenoma of trachea with bronchial carcinoma]. / Eine äußerst seltene Ursache von Hämoptysen. Koexistenz eines primären onkozytären Adenoms der Trachea und eines Adenokarzinoms des linken Oberlappens.

HISTORY AND ADMISSION FINDINGS: A 70-year-old man with a past history of COPD stage GOLD D with home oxygen therapy and tracheotomy due to long-term ventilation (898 hours) 6 years ago was admitted for investigation of haemoptysis during oral anticoagulation. He suffered from peripheral arterial disease (PAD) with bypass and repeated thrombectomy due to recurrent bypass caps, despite effective warfarin therapy. He had all cardiovascular risk factors. INVESTIGATIONS: The suspicion of a bronchial carcinoma was confirmed by CT. Bronchoscopically a 2 cm lesion in the left upper lobe was biopsied. Additionally, bronchoscopy revealed an approximately erythematous, bloody discolored lesion (diameter 7 mm) at a tracheotomy scar. DIAGNOSIS, TREATMENT AND COURSE: The biopsies revealed an adenocarcinoma in the left upper lobe and an oncocytic adenoma of the trachea - an extremely rare adenoma. The staging result was cT1b cN0 cM0 G2 IASLC Ia. Because of his severe multiple diseases the patient was in an inoperable condition. An interdisciplinary tumor conference recommended an individualized approach with a definitive radiotherapy of the adenocarcinoma. Endoscopic control of the macroscopically completely removed oncocytic adenoma of the trachea shall be performed one year later. CONCLUSIONS: Oncocytoma is an extremely rare adenoma (of the trachea), which in this case, has caused haemoptysis in addition to lung cancer during anticoagulation. For tumor genesis a reactive or hyperplasic response after tracheotomy 6 years ago is considered. Resection is the treatment of choice because of the potential for infiltrative growth. But the decision to treat always depends on individual benefit.

Prolonged venovenous extracorporeal membrane oxygenation without anticoagulation: a case of Goodpasture syndrome-related pulmonary haemorrhage.

We present a 16-year-old male with severe acute respiratory and renal failure as a result of Goodpasture syndrome, requiring venovenous extracorporeal membrane oxygenation (VV-ECMO) for pulmonary haemorrhage. The patient received no systemic anticoagulation for 25 of 26 ECMO days (20 days consecutively) and suffered no coagulation-related adverse events. The patient had a subtherapeutic anticoagulation profile according to recommended ECMO guidelines during most of this time. The patient made a full recovery without respiratory compromise, ECMO circuit failure, thrombotic events or the need for ongoing haemodialysis.

Serum vascular endothelial growth factor and angiopoietin-2 are associated with the severity of systemic inflammation rather than the presence of hemoptysis in patients with inflammatory lung disease.

PURPOSE: Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases. MATERIALS AND METHODS: We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009. RESULTS: The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO2) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels. CONCLUSION: Our study suggests that serum VEGF and Ang-2 levels are associated with PaO2 and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.

Neuron-specific enolase and lung cancer.

OBJECTIVE: Serum and bronchoalveolar lavage fluid (BALF) neuron-specific enolase (NSE) levels in lung cancer have been investigated widely; however, their diagnostic values have not yet been clarified. The authors investigated the diagnostic validity of NSE in BALF and serum in lung cancer. MATERIALS AND METHODS: In this prospective case-control study, NSE levels in BALF (B-NSE) and serum (S-NSE) of 3 groups of subjects were analyzed: control subjects (group 1, n = 15), patients with chronic obstructive pulmonary disease (COPD; group 2, n = 15), and lung cancer (group 3, n = 35). RESULTS: The differences in S-NSE and B-NSE levels between the groups were not significant (P > 0.05). S-NSE and B-NSE levels did not show any difference between smokers and nonsmokers, small cell lung cancer and nonsmall cell lung cancer patients, and stage I-II and stage III-IV patients in group 3 (P > 0.05). B-NSE or B-NSE/urea did not show any significance in comparison with S-NSE in the diagnosis and/or staging of malignancy (P > 0.05). S-NSE and B-NSE were well correlated with each other (r = 0.84, P = 0.000). The sensitivity of the S-NSE was 60% and the specificity was 40%. CONCLUSION: The authors conclude that, although elevation of B-NSE is a well-known parameter in small cell lung cancer, it can also be elevated considerably in nonsmall cell lung cancer and COPD. Because of the significant correlation between S-NSE and B-NSE, it may be sufficient to measure S-NSE activity because it is easier and less invasive. However, NSE has no role in the exact diagnosis of lung cancer; it can only be investigated in a scientific setting.

Desmopressin therapy for massive hemoptysis associated with severe leptospirosis.

Massive hemoptysis in patients with severe leptospirosis is often resistant to conventional therapies and can rapidly become fatal. Desmopressin is a fast-acting blood-saving agent used in various hereditary and acquired clotting disorders. We used desmopressin infusions to treat massive pulmonary hemorrhage in six leptospirosis patients with respiratory failure, shock, and multiple organ dysfunction. Hemoptysis ceased rapidly in every case, and five patients finally recovered. Two additional patients with less severe hemoptysis were also successfully treated.

[Usefulness of carcinoembryonic antigen and other markers in patients with hemoptysis]. / Utilidad del antígeno carcinoembrionario y otros marcadores en los pacientes con hemoptisis.

OBJECTIVE: We have examined the carcinoembryonic antigen (CEA) and other tumor markers (immunoglobulins, CA 19.9, LDH, alpha-fetoprotein and alpha-1-antitrypsin) with the purpose of recognize their utility in patients with hemoptysis and patients older than 45 years with a positive smoking history and hemoptysis. METHODS: We measured, analyzed and compared these markers in 336 patients with a known etiology of hemoptysis divided in group I (malignant etiology) with 101 cases (30.1%) and II (nonmalignant) with 235 cases (69.9%) (p < 0.001). RESULTS AND CONCLUSIONS: The values of CEA, LDH and CA 19.9 were increased in group I, without differences when we compared immunoglobulins (G, A and M), alpha-fetoprotein and alpha-1-antitrypsin in both groups. CEA and LDH were increased significantly according to the disease extent in nonsmall cell lung carcinoma. Smokers had an increased CEA only in group II. Plasma values of CEA higher than 5 ng/mL meant that the likelihood of bronchial carcinoma was high. Our markers proved to be more specific and with a high positive or negative predictive values than sensitives. These results would suggest that they are not of great help for early diagnosis of lung cancer, however an increase of CEA, LDH and CA 19.9 plasma concentrations could suggest with high probability a bronchial carcinoma, improving their diagnostic sensibility when we used them in combination.

Transbronchial biopsy in the presence of profound elevation of the international normalized ratio.

STUDY OBJECTIVE: To identify a level of coagulopathy, reported as the international normalized ratio (INR), that predicts hemorrhage following transbronchial forceps biopsy (TBBx) in an animal model. DESIGN: Crossover blinded study using Yucatan mini-swine (Sus scrofa). SETTING: Tertiary medical center with a dedicated animal research facility. STUDY DESIGN: A two-stage study. In stage 1, flexible fiberoptic bronchoscopy with TBBx was performed to establish the amount of bleeding in animals with normal coagulation systems. Animals then were administered escalating dosages of warfarin to obtain one of several increased INR levels. The endpoint of stage 1 was defined as the INR that resulted in a blood loss of > or = 100 mL in > or = 50% of the study animals. In stage 2, all the animals were to be anticoagulated to the INR level determined in stage 1. Topical and systemic measures would then be administered in an attempt to decrease postprocedure hemorrhage, and the results were recorded. RESULTS: Eighteen animals were enrolled in the study. Despite INR levels > 10, no animals developed a hemorrhagic complication of the transbronchial forceps biopsy (TBBx). Eleven animals had INRs > 7. Four animal deaths were recorded, with three animal deaths attributed to nonpulmonary hemorrhage, each due to a ruptured ovarian cyst. One death was anesthesia related. Stage 2 of the study was not performed due to the extreme INR levels reached in the animals during stage 1 and to the lack of a procedure-related complication. CONCLUSIONS: Our study suggests that INR elevation does not correlate with an increased risk of bleeding following TBBx in this animal model.