Erratum to: Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts

Erratum to: International Journal of Hematology, 94(1), pp.81-89: 2011DOI 10.1007/s12185-011-0883-yThe original version of this article unfortunately contained some errors in Table 2 in the column headed ‘‘Amino acid changes’’. The corrected table is given here

Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors.

Radiation exposure is a possible predisposing factor for monoclonal gammopathy of undetermined significance (MGUS), but the association has been uncertain. We investigated the relationship between radiation exposure and MGUS prevalence by using data from the M-protein screening for Nagasaki atomic bomb survivors between 1988 and 2004. Radiation exposure was assessed by exposure distance from the hypocenter and exposure radiation dose. We computed prevalence ratios (PRs) and the 95% confidence intervals (CIs) adjusting for exposure age and sex. A total of 1082 cases of MGUS were identified from 52 525 participants. MGUS prevalence was significantly higher in people exposed at distance within 1.5 km than beyond 3.0 km (PR, 1.4; 95% CI, 1.1-1.9) among those exposed at age 20 years or younger, but it was not found among those exposed at age 20 years or older. MGUS prevalence was also significantly higher in people exposed to more than 0.1 Gy than those exposed to less than 0.01 Gy (PR, 1.7; 95% CI, 1.0-2.8) among those exposed at age 20 years or younger. Thus, people exposed at younger age exhibited a significantly high risk of MGUS when exposed to a high radiation dose. There was no clear association between radiation exposure and the malignant progression of MGUS. Further detailed analysis is needed

Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease

To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV + IV group (n = 87) or an IV group (n = 80). The number of patients with CLD experiencing infectious acute exacerbation (P = 0.022), but not pneumonia (P = 0.284), was significantly lower in the PV + IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P = 0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P = 0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P = 0.019), but not during the second year (P = 0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period

Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes

To investigate the long-term usefulness of immunosuppressive therapy (IST) for Japanese patients with lower-risk myelodysplastic syndromes, we retrospectively analyzed 29 MDS patients who were treated with cyclosporine A alone or with anti-thymocyte globulin at a single institute in Japan. A total of 58.6 % of patients showed hematological response to IST. Overall survival of all patients was 74.5 % at 5 years and 48.3 % at 10 years. The major adverse event was the elevation of creatinine level (grade 1 and 2). Eleven patients were still on IST at the time of analysis with, at least, some clinical benefits. Pneumonia was the most frequent cause of death (eight of 12 deaths), followed by bleeding (three of 12); most of the patients who died were non-responders. The presence of paroxysmal nocturnal hemoglobinuria-type cells was significantly associated with both response to IST and long-term survival by univariate analysis. The 10-year overall survival of responders (72.2 %) was significantly superior to that of non-responders (15.6 %, P < 0.0001). These results suggest that IST using cyclosporine A provides long-term benefit for Japanese patients with lower-risk MDS

Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts.

The percentage of myeloperoxidase (MPO)-positive blast cells is a simple and highly significant prognostic factor in AML patients. It has been reported that the high MPO group (MPO-H), in which >50% of blasts are MPO activity positive, is associated with favorable karyotypes, while the low MPO group (≤50% of blasts are MPO activity positive, MPO-L) is associated with adverse karyotypes. The MPO-H group shows better survival even when restricted to patients belonging to the intermediate chromosomal risk group or those with a normal karyotype. It has recently been shown that genotypes defined by the mutational status of NPM1, FLT3, and CEBPA are associated with treatment outcome in patients with cytogenetically normal AML. In this study, we aimed to evaluate the relationship between MPO positivity and gene mutations found in normal karyotypes. Sixty AML patients with normal karyotypes were included in this study. Blast cell MPO positivity was assessed in bone marrow smears stained for MPO. Associated genetic lesions (the NPM1, FLT3-ITD, and CEBPA mutations) were studied using nucleotide sequencing. Thirty-two patients were in the MPO-L group, and 28 patients in the MPO-H group. FLT3-ITD was found in 11 patients (18.3%), NPM1 mutations were found in 19 patients (31.7%), and CEBPA mutations were found in 11 patients (18.3%). In patients with CEBPA mutations, the carrying two simultaneous mutations (CEBPA (double-mut)) was associated with high MPO expression, while the mutant NPM1 without FLT3-ITD genotype was not associated with MPO activity. Both higher MPO expression and the CEBPA (double-mut) genotype appeared to be associated with improved overall survival after intensive chemotherapy. Further studies are required to determine the importance of blast MPO activity as a prognostic factor, especially in CEBPA wild-type patients with a normal karyotype

Lung sound analysis can be an index of the control of bronchial asthma

Background: We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). Methods: 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. Results: E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV1/FVC ratio during the ICS treatment (r = −0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV1/FVC and V50,%pred (p < 0.001), and significantly higher FeNO and sputum eosinophil percentages (p = 0.008 and p < 0.001, respectively). Conclusions: The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients

Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide

Background: We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. Methods: Steroid-naive bronchial asthma patients were classified into four phenotypes, including “Low inflammation” (35 patients), “Eosinophilic type” (58 patients), “Neutrophilic type” (15 patients), and “Mixed type” (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. Results: The median E/I LF value was highest in the “Mixed type” and lowest in the “Low inflammation” group. FeNO differentiated between the “Low inflammation” and “Eosinophilic type” groups, “Low inflammation” and “Neutrophilic type” groups, and “Neutrophilic type” and “Mixed type” (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the “Low inflammation” and “Eosinophilic type” groups (p = 0.006). E/I LF could distinguish the “Mixed type” group from the “Low inflammation” and “Eosinophilic type” groups (p = 0.002). Conclusions: A combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma

Peripheral bronchial obstruction evaluation in patients with asthma by lung sound analysis and impulse oscillometry

Background: Computer-aided lung sound analysis (LSA) has been reported to be useful for evaluating airway inflammation and obstruction in asthma patients. We investigated the relation between LSA and impulse oscillometry with the evaluation of peripheral airway obstruction. Methods: A total of 49 inhaled corticosteroid-naive bronchial asthma patients underwent LSA, spirometry, impulse oscillometry, and airway hyperresponsiveness testing. The data were analyzed to assess correlations between the expiration: inspiration lung sound power ratio (dB) at low frequencies between 100 and 195 Hz (E/I LF) and various parameters. Results: E/I LF and X5 were identified as independent factors that affect V˙50,%predicted. E/I LF showed a positive correlation with R5 (r = 0.34, p = 0.017), R20 (r = 0.34, p = 0.018), reactance area (AX, r = 0.40, p = 0.005), and resonant frequency of reactance (Fres, r = 0.32, p = 0.024). A negative correlation was found between E/I LF and X5 (r = −0.47, p = 0.0006). E/I LF showed a negative correlation with FEV1/FVC(%), FEV1,%predicted, V˙50,%predicted, and V˙25,%predicted (r = −0.41, p = 0.003; r = −0.44, p = 0.002; r = −0.49, p = 0.0004; and r = −0.30, p = 0.024, respectively). E/I LF was negatively correlated with log PC20 (r = −0.30, p = 0.024). Log PC20, X5, and past smoking were identified as independent factors that affected E/I LF level. Conclusions: E/I LF as with X5 can be an indicator of central and peripheral airway obstruction in bronchial asthma patients