Clinical importance of Bcl-2-like 11 deletion polymorphism in idiopathic pulmonary fibrosis.

BACKGROUND: Reactive oxygen species (ROS) can play a role in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) by contributing to epithelial damage. Bcl-2-like 11 (BIM) is involved in the generation of ROS via forkhead box O3 (FOXO3), and a BIM deletion polymorphism related to apoptosis has been reported to be specific to Asians. Here we examine the clinical features of IPF in patients with BIM deletion polymorphism. METHODS: In this single-center retrospective study, we reviewed the medical records of 63 patients with IPF who were treated at our hospital from January 2006 through April 2018. Patients with and without BIM deletion polymorphism were compared in relation to clinical characteristics, pulmonary function test results, frequency of acute exacerbation (AE)-IPF, and redox status [including oxidized glutathione (GSSG), reduced glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane (8-iso)] at baseline and at 1 and 2 years after treatment. RESULTS: No fatal AE-IPF occurred in patients with BIM deletion polymorphism (0% vs. 36.4% of polymorphism-negative cases; P=0.038). Change in forced vital capacity from baseline (ΔFVC) at 2 years was significantly lower in patients with the BIM deletion polymorphism than in those without the polymorphism (‒0.42±0.50 vs. ‒0.88±0.83 L, respectively; P=0.045). Total blood glutathione (tGSH) was significantly higher in patients with the deletion polymorphism than in those without the polymorphism (988±48.3 vs. 858±25.8 µM, respectively; P=0.042). 8-iso was significantly lower in the former group (246.1±81.6 vs. 400.9±334.1 pg/mL, respectively; P=0.022). CONCLUSIONS: IPF patients with BIM deletion polymorphism had a good redox balance and may thus have a better clinical outcome than patients without this polymorphism.

Serial change in serum biomarkers during treatment of Non-HIV Pneumocystis pneumonia.

BACKGROUND: For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. OBJECTIVE: This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. METHODS: We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (ß-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. RESULTS: There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated ß-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03). CONCLUSION: Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.

New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia.

BACKGROUND: Fatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP. METHODS: A review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model. RESULTS: The anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0-5, 47% for a score of 6-10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%. CONCLUSIONS: The present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.

Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium complex infection.

BACKGROUND: We occasionally treat patients with clinically suspected pulmonary Mycobacterium avium complex (MAC) infection and negative MAC culture on bronchoscopy. OBJECTIVE: This study aimed to investigate the usefulness of bronchoscopy in patients with suspected MAC lung disease with nodular bronchiectasis on chest computed tomography (CT) and to clarify the clinical characteristics of these patients. METHODS: We reviewed the records of 71 patients with clinically suspected pulmonary MAC infection on chest CT who underwent bronchoscopy. The patients were classified on the basis of MAC culture result, and their clinical characteristics were compared. RESULTS: MAC was detected in 33 of the 71 (46.5%) patients (positive group), and 35 (49.3%) were culture-negative for nontuberculous mycobacteria (NTM) (negative group). NTM other than MAC were detected in 3 of 71 (4.2%) patients. MAC was not detected in 14 of 38 (36.8%) patients positive for GPL core IgA antibody. Patients in the positive group had a higher body mass index (20.1 ± 3.4 vs 18.5 ± 2.9 kg/m2; p = 0.047) and positive rate for GPL core IgA antibody (72.7% vs 40%; p = 0.006) and a lower chronic obstructive pulmonary disease assessment test score (6.6 ± 6.6 vs 11.7 ± 8.5; p = 0.016) and rate of positive culture for Pseudomonas aeruginosa or Haemophilus influenzae (12.1% vs 45.7%; p = 0.003), as compared with the negative group. CONCLUSION: Bronchoscopy is useful for diagnosis of MAC in patients who cannot be diagnosed by sputum examination. In addition, patients with pulmonary MAC disease had less severe subjective symptoms and weight loss than did those with a negative MAC culture on bronchoscopy.

PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma.

Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and ß-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis.

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a ß-d-glucan (ßDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and ßDG testing of BALF, respectively. The sensitivity and specificity of the GM test, ßDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and ßDG tests had the highest diagnostic odds ratio. The combination of the GM and ßDG tests on BALF was more useful than any single test for diagnosing CPA.

Characterization and evaluation of a novel immunochromatographic assay for pharyngeal Mycoplasmapneumoniae ribosomal protein L7/L12 antigens.

Point-of-care testing for Mycoplasma pneumoniae infection may be ideal and useful because significant numbers of the cases will be seen as outpatients. Recently, a new immunochromatographic method (ICM) targeting M. pneumoniae ribosomal protein L7/L12 (RP-L7/L12) in pharyngeal swabs became available in Japan, although clinical data and basic information regarding efficacy and characterization of this ICM are limited. The present study examined the fate of M. pneumoniae RP-L7/L12 during in vitro growth and the correlation between M. pneumoniae concentration in clinical specimens and the sensitivity of the ICM test. The usefulness of the ICM was investigated in patients suspected of having M. pneumoniae pneumonia and upper respiratory tract infection (137 children and 39 adults). The limit of detection for the ICM test was 1.1×104 c.f.u. ml-1 of M. pneumoniae. Bacterial production of RP-L7/L12 correlated positively with the viable M. pneumoniae concentration in vitro; antigen was then degraded in culture broth, with an in vitro half-life of approximately 2 days. Five other Mycoplasma spp. and 14 representative respiratory pathogens were ICM assay negative at bacterial concentrations of 106 c.f.u. ml-1. The clinical sensitivity and specificity of the ICM assay were 57.1 % (20/35) and 92.2 % (130/141), respectively, in comparison with bacterial culture. Clinical specimens containing ≥106 c.f.u. ml-1 of M. pneumoniae burden were ICM positive in 13 of 18 cases (72.2 %). The ICM is a poorly sensitive but reasonably specific means for detecting M. pneumoniae infections.

Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study.

BACKGROUND AND OBJECTIVE: Treatment with pirfenidone may slow the decline in vital capacity and increase progression-free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N-acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF. METHODS: Patients with a diagnosis of advanced IPF (Japanese Respiratory Society stage III/IV IPF) and a relative decline in forced vital capacity (FVC) of ≥ 10% within the previous 6 (± 2) months were enrolled. Outcomes were evaluated in a 12-month follow-up pulmonary function test. Treatment was considered ineffective if the decline in FVC was ≥ 10% and effective if the decline was <10%. We compared clinical characteristics, effectiveness and PFS between patients receiving inhaled NAC plus pirfenidone (n = 24) and those receiving pirfenidone alone (control; n = 10). RESULTS: Data from 34 IPF patients (age range, 59-82 years) were analysed. At the 12-month follow-up examination, treatment was deemed effective in 8 of 17 (47%) patients receiving NAC plus pirfenidone and in 2 of 10 (20%) receiving pirfenidone alone. The annual rate of change in FVC was -610 mL in the NAC plus pirfenidone group and -1320 mL in the pirfenidone group (P < 0.01). PFS was longer (304 days) in the NAC plus pirfenidone group than in the pirfenidone group (168 days; P = 0.016). CONCLUSIONS: Combination treatment with inhaled NAC and oral pirfenidone reduced the rate of annual FVC decline and improved PFS in patients with advanced IPF.

Usefulness of nanofluidic digital PCR arrays to quantify T790M mutation in EGFR-mutant lung adenocarcinoma.

AIM: The present pilot study assessed the usefulness of nanofluidic digital polymerase chain reaction (PCR) arrays in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma after tyrosine kinase inhibitor (TKI) resistance. PATIENTS AND METHODS: We enrolled 12 patients with primary lung adenocarcinoma with sensitive EGFR mutation-confirmed T790M status by re-biopsy after TKI resistance. Nanofluidic digital PCR arrays were used to quantify T790M in genomic DNA from the pre-treatment primary site and in serum cell-free DNA (cfDNA). RESULTS: On digital PCR, quantified T790M at the pre-treatment primary site was higher in re-biopsy-positive T790M patients (n=4) than in re-biopsy-negative patients (n=8) (0.78%±0.36% vs. 0.07%±0.09%, p<0.01). T790M at the pre-treatment primary site correlated with progression-free survival (PFS) after gefitinib therapy (r=0.67, p=0.016). CONCLUSION: Use of digital PCR to quantify T790M at the primary site of EGFR-mutant lung adenocarcinoma predicted T790M emergence in re-biopsies after TKI resistance and PFS after gefitinib therapy.

Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone.

BACKGROUND AND OBJECTIVE: The results of studies examining the outcome and the factors predicting prognosis in combined pulmonary fibrosis and emphysema (CPFE) have so far been contradictory. Our objective was to determine prognosis and the prognostic factors for CPFE. METHODS: Of 108 consecutive idiopathic pulmonary fibrosis (IPF) patients admitted to our hospital, 46 were diagnosed as having CPFE and 62 patients diagnosed as having IPF alone. We retrospectively compared the clinical features between these two groups. RESULTS: Annual increase in estimated systolic pulmonary arterial pressure (esPAP) was significantly greater in CPFE patients, and survival time was significantly lower. Moreover, the prognosis was unfavourable regardless of the presence of lung cancer. The multivariate Cox proportional hazard regression model showed that predictive factors were an increase in the modified Medical Research Council dyspnoea score and esPAP ≥ 30.4 mm Hg. We classified patients into the following four groups: CPFE with high esPAP (esPAP ≥ 30.4 mm Hg), CPFE with normal esPAP (esPAP < 30.4 mm Hg), IPF alone with high esPAP and IPF alone with normal esPAP. Survival in the CPFE with high esPAP group was significantly worse than that in the other three subgroups. Furthermore, CPFE with the paraseptal type of emphysema and high esPAP had the worst prognosis. CONCLUSIONS: This study demonstrated that the prognosis of CPFE is significantly worse than that of IPF alone. In particular, CPFE with paraseptal emphysema associated with high esPAP has an extremely poor prognosis.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

BACKGROUND: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non-small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. METHODS: We studied 70 patients with EGFR mutation-positive non-small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. RESULTS: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864-8.547; p < 0.001). CONCLUSIONS: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

An anomalous unilateral single pulmonary vein associated with a bone morphogenetic protein receptor II gene mutation.

Anomalous unilateral single pulmonary vein (AUSPV), a rare congenital anomaly, is associated with an aberrant course but normal drainage, and resembles arteriovenous malformation (AVM). We treated a 26-year-old man with AUSPV in the right lung and an anomalous segmental pulmonary vein in the left lung. CT revealed a tortuous vascular shadow with an enhancement pattern identical to that of the pulmonary vein, suggesting AUSPV. This was confirmed by pulmonary angiography. Although pulmonary AVMs were not detected on angiography, microvascular AVMs could not be excluded because delayed bubbles appeared on contrast echocardiography. A genetic examination revealed a missense mutation of BMPR2.

Everolimus-induced pneumonitis after drug-eluting stent implantation: a case report.

Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

Acquired hemophilia A associated with IgG4-related lung disease in a patient with autoimmune pancreatitis.

Immunoglobulin G4 (IgG4)-related lung diseases can occur in patients with autoimmune pancreatitis (AIP). However, the causal relationship between AIP and acquired hemophilia A (AH) is unknown. We herein report the first case of AH associated with IgG4-related lung disease that developed in a patient with AIP. A 65-year-old asymptomatic man with a history of AIP and sclerosing cholangitis diagnosed at the age of 57 was admitted to our hospital due to an abnormal reticulonodular shadow on chest X-ray. An examination of lung biopsy specimens revealed IgG4-positive plasma cell infiltration in the interstitium. The serum IgG4 level was elevated. One year later, the patient developed a progressive severe hematoma in the left femoral muscle. On admission, laboratory examinations revealed severe anemia with a markedly prolonged activated partial prothrombin time, a decreased level of factor VIII (FVIII) activity, and the existence of anti-FVIII antibodies. These findings were consistent with a diagnosis of AH. No relapse has been observed over the past 25 months, during which time, corticosteroid therapy has been continuously administered.

Pathological response and prognosis of stage III non-small cell lung cancer patients treated with induction chemoradiation.

AIM: The aim of this study was to clarify the relationship between pathological effects and the prognosis of patients with stage III non-small cell lung cancer (NSCLC) treated with induction chemoradiation. METHODS: Patients who were untreated and potentially resectable with stage III NSCLC were enrolled. They received carboplatin and docetaxel with concurrent radiotherapy (5 × 2 Gy/week with a total dose of 40 Gy) followed by surgery. We assessed the relationship between the pathological effect (Ef) (Ef 1: slight pathological response, Ef 2: moderate pathological response, Ef 3: complete pathological response) and prognosis. RESULTS: In all, 30 patients with stage III NSCLC (24 men and 6 women, mean age 60.7 years, 17 with adenocarcinomas and 13 with squamous cell carcinomas, 21 with clinical stage IIIA and nine with stage IIIB) participated in the trial and underwent induction chemoradiation. A total of 27 patients (90%) with complete response, partial response and stable disease had surgical resection. The pathological effect was Ef 1 and Ef 2 in 10 patients each, and Ef 3 in seven patients. Median survival was 10.9 months in patients with Ef 1 and 49.6 months in patients with Ef 2. Six out of seven Ef 3 patients are alive at the time of writing with a mean survival of 77.1 months (14-104 months). There was a significant difference in overall survival based on pathological effect rating (P = 0.0036). CONCLUSION: The Ef rating was well correlated with prognosis after induction chemoradiation.

Clinical significance of circulating tumor cells and free DNA in non-small cell lung cancer.

AIM: This pilot study assessed correlations between circulating tumor cells (CTCs) and circulating free DNA (cfDNA) of metastatic non-small cell lung cancer (NSCLC) after acquisition of resistance to epidermal growth factor receptor tyrosine kinase inhibitors. PATIENTS AND METHODS: CTCs were counted using the CellSearch system (Veridex). cfDNA was analyzed for EGFR mutation status by the Cycleave real-time PCR assay. RESULTS: Twenty-four patients participated in this study. CTCs were detected in 8 of 24 cases (33.3%), at a mean of 2.6 CTCs per 7.5 ml blood (range: 1-24). EGFR mutations in cfDNA were detected in 6 out of 24 cases (25%). The EGFR mutation detection rates in cfDNA were significantly higher in patients with ≥ 2 CTCs per 7.5 ml (100%) than in those with <2 CTCs per 7.5 ml (10%) (p=0.0001). CONCLUSION: The presence of CTCs was correlated with the positivity of EGFR mutation in cfDNA.

Role of fluoro-2-deoxyglucose positron emission tomography for the detection of gastrointestinal tract lesions in patients with lung cancer.

BACKGROUND: The purpose of this study was to clarify the clinical characteristics of lung cancer patients with abnormal accumulation of fluoro-2-deoxyglucose (FDG) in the gastrointestinal tract imaged by positron emission tomography (PET). METHODS: Of 1071 consecutive patients with primary lung cancer who underwent PET from October 2005 through to March 2010, 25 patients (2.3%) showed localized abnormal FDG accumulation in the gastrointestinal tract. We retrospectively compared the location of abnormal accumulation in the gastrointestinal tract, the maximum standardized uptake value in 1 hour, and final clinical diagnosis. RESULTS: Of the 25 cases, 12 (48%) were true PET-positive cases (esophageal cancer in one case, gastric cancer in one, colorectal cancer in seven, gastrointestinal stromal tumor in one, and lung cancer metastasis to the stomach and small intestine in one patient each). The 13 cases with false PET-positives were gastric polyp in one, gastritis in four, colon polyp in two, diverticulitis in one, and normal physiological accumulation in five. There was also a significant difference between malignancy and benign intestinal accumulation excluding the stomach (P = 0.002). CONCLUSION: PET was useful for screening the gastrointestinal tract (except the stomach) for malignancy in lung cancer patients.

Bird fancier's lung which developed in a pigeon breeder presenting organizing pneumonia.

Bird fancier's lung (BFL) is one of the most common types of hypersensitivity pneumonitis. We report a rare case of acute-on-chronic bird fancier's lung that developed in a pigeon breeder and presented subpleural curvilinear shadow and ground glass opacity on high-resolution computed tomography (HRCT) of the chest. The results of surgical lung biopsy showed mainly intraalveolar organization and alveolitis in addition to the pattern of usual interstitial pneumonia with centrilobular fibrosis. Examination of bronchoalveolar lavage (BAL) fluid revealed an increase in lymphocytes. The results of immunoglobulin (Ig) G and IgA antibodies against pigeon dropping extracts were positive in sera and BAL fluid. Consequently, the patient was diagnosed as having BFL. Avoidance of pigeons and corticosteroid therapy led to rapid improvement.

Churg-Strauss syndrome presenting with diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis.

A 46-year-old man with a 4-month history of bronchial asthma was admitted to our hospital complaining of progressive dyspnea, weakness of the lower extremities, multiple truncal erythematous purpura and hemoptysis. Neurological examination identified the presence of mononeuritis multiplex. Laboratory data indicated marked anemia, eosinophilia, severe renal failure with nephrotic condition and elevated serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels (1,050 EU). Chest computed tomography showed diffuse ground glass opacity in both lungs. Bronchoalveolar lavage fluid revealed bloody fluid with eosinophilia (81%). Microscopic findings of a transbronchial lung biopsy were consistent with alveolar hemorrhage. A skin biopsy revealed eosinophilic vasculitis consistent with Churg-Strauss syndrome (CSS). A renal biopsy specimen revealed pauci-immune crescentic necrotizing glomerulonephritis. Consequently, he was diagnosed as having CSS presenting with diffuse alveolar hemorrhage (DAH) and rapidly progressive glomerulonephritis (RPGN) with MPO-ANCA-associated systemic vasculitis. His clinical condition markedly improved with the administration of intravenous corticosteroid (CS) and cyclophosphamide (CY). Thus, we report a case of CSS presenting with the rare complication of DAH and RPGN.

Miliary tuberculosis associated with chronic neutrophilic leukemia.

We report a case of miliary tuberculosis associated with chronic neutrophilic leukemia (CNL). A 70-year-old woman was referred to our hospital complaining of a 1-month history of persistent fever and anorexia. Chest and abdominal computed tomography images revealed diffuse small nodular lesions in the bilateral lung fields and extreme splenomegaly. Sputum cultures isolated Mycobacterium tuberculosis. After anti-tuberculous therapy for 1 year, the patient underwent splenectomy for massive splenomegaly and progressive leukocytosis. The presence of the homozygous JAK2 V617F tyrosine kinase mutation was also demonstrated in the peripheral blood. She was finally diagnosed as having miliary tuberculosis associated with CNL based on the histopathological examination of spleen. The patient was treated with a daily dose of 500 mg of hydroxyurea. As a result, 18 months after the splenectomy, her leukocyte count was decreased and her clinical condition was markedly improved; there was no relapse of the CNL.