The analysis of lung sounds in infants and children with a history of wheezing/asthma using an automatic procedure.

BACKGROUND: Lung sound analysis parameters have been reported to be useful biomarkers for evaluating airway condition. We developed an automatic lung sound analysis software program for infants and children based on lung sound spectral curves of frequency and power by leveraging machine learning (ML) technology. METHODS: To put this software program into clinical practice, in Study 1, the reliability and reproducibility of the software program using data from younger children were examined. In Study 2, the relationship between lung sound parameters and respiratory flow (L/s) was evaluated using data from older children. In Study 3, we conducted a survey using the ATS-DLD questionnaire to evaluate the clinical usefulness. The survey focused on the history of wheezing and allergies, among healthy 3-year-old infants, and then measured lung sounds. The clinical usefulness was evaluated by comparing the questionnaire results with the results of the new lung sound parameters. RESULTS: In Studies 1 and 2, the parameters of the new software program demonstrated excellent reproducibility and reliability, and were not affected by airflow (L/s). In Study 3, infants with a history of wheezing showed lower FAP0 and RPF75p (p < 0.001 and p = 0.025, respectively) and higher PAP0 (p = 0.001) than healthy infants. Furthermore, infants with asthma/asthma-like bronchitis showed lower FAP0 (p = 0.002) and higher PAP0 (p = 0.001) than healthy infants. CONCLUSIONS: Lung sound parameters obtained using the ML algorithm were able to accurately assess the respiratory condition of infants. These parameters are useful for the early detection and intervention of childhood asthma.

Clinical application of a lung sound analysis in infants with respiratory syncytial virus acute bronchiolitis.

BACKGROUND: Objective investigation of the characteristics of acute bronchiolitis in infants is important for its diagnosis and treatment. METHODS: Lung sound data of 50 patients diagnosed with respiratory syncytial virus (RSV) acute bronchiolitis (m:f = 29:21, median of age 7 months), 20 patients with RSV acute respiratory tract infections without acute bronchiolitis (m:f = 10:10, 5 months) and 38 age-matched control infants (m:f = 23:15, 8 months) were analyzed using a conventional method and compared. Furthermore, the relationships between lung sound parameters and clinical symptoms (clinical score, length of hospital stay and SpO2 level) in the bronchiolitis and the non-bronchiolitis patients were examined. RESULTS: Results of lung sound analysis showed that the inspiratory sound power of patients with RSV respiratory tract infections was low and the expiratory sound power was high compared with those of the controls. When the patients with RSV respiratory tract infections were divided into the bronchiolitis and non-bronchiolitis groups, the expiratory/inspiratory ratio of the bronchiolitis patients was greater than that of the non-bronchiolitis patients. There was no difference in the clinical symptoms, clinical score and length of hospital stay between the bronchiolitis and non-bronchiolitis patients, except for the SpO2 level on admission. CONCLUSION: Lung sound analysis confirmed that patients with RSV acute bronchiolitis present with marked airway narrowing. Considering these results as a characteristic of acute bronchiolitis, it would be meaningful to reflect it in the improvement of diagnosis, treatment and subsequent management.

Effect of wheeze and lung function on lung sound parameters in children with asthma.

BACKGROUND: In children with asthma, there are many cases in which wheeze is confirmed by auscultation with a normal lung function, or in which the lung function is decreased without wheeze. Using an objective lung sound analysis, we examined the effect of wheeze and the lung function on lung sound parameters in children with asthma. METHODS: A total of 114 children with asthma (males to females = 80: 34, median age 10 years old) were analyzed for their lung sound parameters using conventional methods, and wheeze and the lung function were checked. The effects of wheeze and the lung function on lung sound parameters were examined. RESULTS: The patients with wheeze or decreased forced expiratory flow and volume in 1 s (FEV1) (% pred) showed a significantly higher sound power of respiration and expiration-to-inspiration sound power ratio (E/I) than those without wheeze and a normal FEV1 (% pred). There was no marked difference in the sound power of respiration or E/I between the patients without wheeze and a decreased FEV1 (% pred) and the patients with wheeze and a normal FEV1 (% pred). CONCLUSIONS: Our data suggest that bronchial constriction in the asthmatic children with wheeze similarly exists in the asthmatic children with a decreased lung function. A lung sound analysis is likely to enable an accurate understanding of airway conditions.

Allergic Sensitization Is Crucial for the Suppressive Role of Streptococcus pneumoniae in the Acute Exacerbation of Asthma.

INTRODUCTION: Allergic sensitization is an important factor in the development, severity, and exacerbation of asthma, which is attributed to type 2 (T2) inflammation. Evidence suggests that respiratory bacterial pathogens (e.g., Streptococcus pneumoniae) exert suppressive effects on airway T2 inflammation. To clarify the role of allergic inflammation in bacterial colonization in asthma based on allergic sensitization, we investigated pharyngeal bacterial colonization, biomarkers (e.g., serum eosinophil cationic protein (ECP) and cytokines/chemokines), and symptoms in the acute exacerbation of childhood asthma. METHODS: Pharyngeal samples were collected from 53 children (mean/median age 2.7/2.5 years). Serum levels of total and allergen-specific IgE against aeroallergens, ECP, and 17 cytokines/chemokines were measured. RESULTS: Allergic sensitization was recognized in 62.2% patients. S. pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and other bacteria were detected in 47.1%, 11.3%, 11.3%, and 30.1% of all patients, respectively. Patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.7 ± 3.6 vs. 7.1 ± 3.5 days, p = 0.024). In patients with allergic sensitization, patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.0 ± 3.6 vs. 7.7 ± 4.0 days, p = 0.003). Serum total IgE was significantly lower in patients with S. pneumoniae than in those without (81.9 [7.8-894] vs. 287 [4.4-1,840] IU/mL, p = 0.014). Serum ECP was significantly higher (33.1 [2-109] vs. 7.8 [3-35] ng/mL, p = 0.042), and IFN-γ was significantly lower (5.6 [4-10] vs. 16.4 [7-28] pg/mL, p = 0.032) in patients with allergic sensitization than those without. DISCUSSION/CONCLUSION: Our results suggested that the suppressive effects of S. pneumoniae colonization were observed only in patients with allergic sensitization, wherein serum total IgE, ECP, and IFN-γ may have an important role on acute exacerbation of asthma.

Antibiotic Treatments Prolong the Wheezing Period in Acute Exacerbation of Childhood Bronchial Asthma.

INTRODUCTION: Although current guidelines recommend against routine antibiotic prescription for acute exacerbation of bronchial asthma, children with acute exacerbation of asthma receive antibiotic treatment more frequently. In addition, those antibiotics are often prescribed only for exacerbation of asthma without concurrent bacterial infection. OBJECTIVE: To clarify the association between antibiotic treatment and bacterial colonization in acute exacerbation of asthma, we investigated whether or not antibiotics affect the clinical condition, laboratory findings, and pharyngeal bacterial colonization in those patients. METHODS: Potential bacterial pathogens were investigated in pharyngeal samples of 111 children with acute exacerbation of asthma (mean/median age: 2.8/2.6 years old, respectively). We collected clinical data, such as the duration of wheezing and antibiotic use, and measured the peripheral white blood cell counts, C-reactive protein, and serum levels of total and allergen-specific IgE. RESULTS: Antibiotics were used in 50.5% patients with acute asthma exacerbation and included cephalosporin, penicillin, macrolide, and others. Episodes of wheezing were significantly longer in patients with antibiotic treatment than in those without it (6.7 ± 3.6 days vs. 6.0 ± 3.1, p = 0.044). Similarly, episodes of wheezing were significantly longer in moderate exacerbation patients with antibiotics than in those without them. Furthermore, in patients with Streptococcus pneumoniae, antibiotic treatment was associated with an extended duration of wheezing in cases of acute moderate exacerbation (7.0 ± 2.4 days vs. 4.8 ± 4.1, p = 0.043). CONCLUSIONS: These results suggest that antibiotic treatment in acute exacerbation of asthma might lead to longer asthmatic symptoms, specifically in patients with pharyngeal S. pneumoniae colonization.

The Suppressive Role of Streptococcus pneumoniae Colonization in Acute Exacerbations of Childhood Bronchial Asthma.

INTRODUCTION: Little is known about the association between bacterial infections and exacerbations of bronchial asthma. OBJECTIVE: To elucidate the effect of bacterial infections on bronchial asthma, we examined pharyngeal bacterial colonization, duration of wheezing, and serum levels of cytokines and chemokines during acute exacerbations of asthma in children. METHODS: Potential bacterial pathogens were investigated in pharyngeal samples and viruses obtained from nasal secretions of 111 children who were outpatients and/or in patients with acute exacerbations of asthma (mean/median age: 2.8/2.6, respectively). We also measured serum levels of 27 different cytokines/chemokines. RESULTS: Pharyngeal bacterial cultures were positive in 110 of 111 children. The 3 major bacterial pathogens were Streptococcus pneumoniae (29.7%), Moraxella catarrhalis (11.7%), and Haemophilus influenzae (10.8%). M. catarrhalis was detected more frequently in patients with pneumonia. Furthermore, patients with S. pneumoniae colonization had significantly shorter wheezing episodes than those without it. In contrast, the duration of wheezing did not differ significantly among cases with other bacteria such as M. catarrhalis and H. influenzae. Furthermore, the length of wheezing episode in patients with S. pneumoniae colonization showed significant inverse correlation with peripheral white blood cell count, neutrophil count, and C-reactive protein, while there was no significant correlation between duration of wheezing and these 3 parameters among patients with M. catarrhalis or H. influenza. Among the 27 cytokines/chemokines, only serum tumor necrosis factor (TNF)-α was significantly lower in patients with S. pneumoniae colonization than in those without it. CONCLUSIONS: These results suggested that pharyngeal S. pneumoniae colonization plays a suppressive role on the pathophysiology during acute exacerbations of asthma.

[EFFECT OF INSPIRATORY FLOW ON BREATH SOUND ANALYSIS IN CHILDREN WITH ASTHMA].

BACKGROUND: In order to determine the optimal breathing method for childhood lung sound analyses, it is important to study the effect of airflow on the parameters of lung sounds. METHODS: Sixty-one well-controlled children with atopic asthma (median; 12 years) participated. After confirming that there was no wheezing or respiratory symptoms, the lung sound spectrums of the inspiratory flow before and after inhalation of a ß2 stimulant were analyzed. At the same time, their lung function was measured by a spirogram and the forced oscillation technique. RESULTS: Before ß2 agonist inhalation, the area under the entire curve (AT) and 99% frequency (F99) in the lung sound of inspiratory flow around 2.0L/s due to slightly strong breathing were significantly higher than the lung sound of inspiratory flow around 1.0L/s due to rest breathing. However, no marked differences were observed in the lung sound parameters based on the lung sound spectrum. The improvement in the lung sound parameters after ß2 agonist inhalation was clearer at an inspiratory flow around 1.0L/s than that around 2.0L/s. CONCLUSION: The present study showed that changes after ß2 agonist inhalation and the correlation with the lung function parameters were clear during resting breathing. This method may be used for the long-term montoring of children with asthma.

Objective evaluation of wheezing in normal infants.

BACKGROUND: To evaluate the frequency of wheezing in infants, the presence of wheezing was examined in normal infants using a breath sound analyzer, METHODS: A total of 443 infants (age range, 3-24 months) were included in the present study. The existence of audible wheezing and faint wheezing/inaudible wheezing-like noises (FW) was confirmed on chest auscultation and a sound spectrogram. The breath sound parameters of the sound spectrum, frequency limiting 99% of power spectrum (F99 ), roll-off from 600 to 1,200 Hz (slope) and spectrum curve indices, total area under the curve of dB data (A3 /AT and B4 /AT ), and ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF50 and RPF75 ) were calculated. Using an original Japanese questionnaire, we examined the characteristics of the airway condition of all infants. RESULTS: Finally, a total of 398 infants were analyzed in the present study, and 283 were in good health while 115 had acute respiratory infection (ARI) in the last 7 days. No infants had audible wheezing on auscultation. Three infants without ARI (1.1%) and 10 infants with ARI (8.7%) had FW. In the evaluation of breath sound parameters, there were no marked differences between the infants with and without FW. CONCLUSIONS: Using a breath sound analyzer, wheezing and FW were recognized in only a few infants in good health. Infants recognized to have audible wheezing in daily practice may be at risk of developing recurrent wheezing/asthma.

A breath sound analysis in children with cough variant asthma.

BACKGROUND: Cough variant asthma (CVA) is characterized by a chronic cough and bronchial hyperresponsiveness without confirmation of wheezing. Using a breath sound analyzer, we evaluate the characteristics of breath sound in children with CVA. METHODS: Nine children with CVA (median age, 7.0 years) participated. The existence of breath sounds was confirmed by sound spectrogram. Breath sound parameters, the frequency limiting 50% and 99% of the power spectrum (F50 and F99), the roll-off from 600 to 1200 Hz (Slope) and spectrum curve indices, the ratio of the third and fourth area to the total area of the power spectrum (P3/PT and P4/PT) and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50) were calculated before and after ß2 agonist inhalation. A spirogram and/or forced oscillation technique were performed in all subjects. RESULTS: On a sound spectrogram, wheezing was confirmed in seven of nine patients. All wheezing on the image was polyphonic, and they almost disappeared after ß2 agonist inhalation. An analysis of the breath sound spectrum showed that PT, P3/PT, P4/PT, RPF50 and RPF75 were significantly increased after ß2 agonist inhalation. CONCLUSIONS: Children with CVA showed a high rate of inaudible wheezing that disappeared after ß2 agonist inhalation. Changes in the spectrum curve indices also indicated the bronchial reversibility. These results may suggest the characteristics of CVA in children.

Characteristics of breath sound in infants with risk factors for asthma development.

BACKGROUND: Breath sound parameters have been suggested as biomarkers of the airway narrowing in children. Using a commercially available breath sound analyzer, the characteristics of the airway condition were investigated in infants with the risk factors for asthma development. METHODS: A total of 443 infants (mean age, 9.9 months; range, 3-24 months) were included in the present study. The breath sound parameters of the frequency limiting 99% of the power spectrum (F99), the roll-off from 600 to 1200 Hz (Slope) and spectrum curve indices, the total area under the curve of the dBm data (A3/AT) and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50), were evaluated. Using an ATS-DLD based original Japanese questionnaire, we examined the characteristics of airway condition of infants. RESULTS: Finally, 283 infants in good health were included in the present study. The RPF75, RPF50, Slope and F99 in infants with positive results of allergy and atopic dermatitis were significantly increased more than those in the infants with negative result. CONCLUSIONS: Our data highlight the characteristics of breath sounds in infants with risk factors for asthma. The breath sound analysis may be useful for assessing the airways of infants for asthma development.

Genomic profiling of canine mast cell tumors identifies DNA copy number aberrations associated with KIT mutations and high histological grade.

Mast cell tumor (MCT) is the most common skin malignancy of domestic dogs and presents with a widely variable clinical behavior. Although activating KIT mutations are present in approximately 20% of canine MCTs, molecular etiology is largely unknown for the majority of this cancer. Characterization of genomic alterations in canine MCTs may identify genomic regions and/or genes responsible for their development and progression, facilitating the discovery of new therapeutic targets and improved clinical management of this heterogeneous cancer. We performed genome-wide DNA copy number analysis of 109 primary MCTs derived from three popular canine breeds (the Boxer, Labrador Retriever, and Pug) as well as nontarget breeds using oligonucleotide array comparative genomic hybridization (oaCGH). We demonstrated a stepwise accumulation of numerical DNA copy number aberrations (CNAs) as tumor grade increases. DNA sequencing analysis revealed that KIT mutations were found less frequently in the Pug tumors and were strongly associated with high histological grade. Tumors with KIT mutations showed genome-wide aberrant copy number profiles, with frequent CNAs involving genes in the p53 and RB pathways, whereas CNAs were very limited in tumors with wild-type KIT. We evaluated the presence of four CNAs to predict aggressive tumor phenotypes. This approach predicted aggressive tumors with a sensitivity of 78-94% and specificity of 88-93%, when using oaCGH and droplet digital PCR platforms. Further investigation of genome regions identified in this study may lead to the development of a molecular tool for classification and prognosis, as well as identification of therapeutic target molecules.

Changes in the breath sound spectrum during methacholine inhalation in children with asthma.

BACKGROUND AND OBJECTIVE: An effort-independent breath sound analysis is expected to be a safe and simple method for clinical assessment of changes in airway function. The effects of bronchoconstriction and bronchodilation on novel breath sound parameters in asthmatic children were investigated. METHODS: The study population included 49 children with atopic asthma (male = 33; mean age: 10.2 years). We evaluated breath sound parameters of the highest frequency of the power spectrum (HFp), frequency limiting 50% and 99% of the power spectrum (F50 and F99 ) and roll-off from 600 Hz to the HFp (Slope). We also assessed new parameters obtained using the ratios of sound spectrum parameters (spectrum curve indices), such as the ratio of the third and fourth power area to the total power area (P3 /PT and P4 /PT ), the ratio of the third and fourth areas to the total area under the curve (A3 /AT and B4 /AT ) and the ratio of power and frequency at 75% of HFp and 50% of HFp (RPF75 and RPF50 ). This was measured before and after methacholine inhalation challenge and after ß2 agonist inhalation. RESULTS: The parameters, F50 and F99 , showed no changes after methacholine inhalation. Conversely, the A3 /AT (12.5-10.0%, P < 0.001), B4 /AT (7.6-5.5%, P < 0.001), RPF75 (6.7-4.0 dBm/Hz, P < 0.001) and RPF50 (5.8-4.3 dBm/Hz, P < 0.001) were significantly decreased. These values returned to the original level after ß2 agonist inhalation. CONCLUSION: Spectrum curve indices indicate bronchoconstriction and bronchodilation. These parameters may play a role in the assessment of airway narrowing in asthmatic children.

Hybrid Lead Halide Layered Perovskites with Silsesquioxane Interlayers.

Hybrid organic-lead halide perovskites exhibit remarkable properties as semiconductors and light absorbers. Here, we report the formation of silsesquioxane-lead halide hybrid layered perovskites. We prepared silsesquioxane with a cubic cage-like structure and fabricated hybrid silsesquioxane-lead halide layered perovskites in a self-assembled manner. It is demonstrated that the silsesquioxane maintain their cage-like structure between lead halide perovskite layers. The silsesquioxane-lead halide perovskites also show excitonic absorption and emission in the visible light region similar to typical lead halide layered perovskites.

Palivizumab Prophylaxis in Preterm Infants and Subsequent Recurrent Wheezing. Six-Year Follow-up Study.

RATIONALE: Respiratory syncytial virus (RSV) induces not only infantile recurrent wheezing but also potentially atopic asthma. OBJECTIVES: To test the effect of RSV infection on development of subsequent atopic asthma, we evaluated whether palivizumab, an anti-RSV monoclonal antibody, by preventing severe RSV disease in the first year of life, could impact subsequent recurrent wheezing and atopic asthma at 6 years of age. METHODS: During the 2007 to 2008 RSV season, the decision to administer palivizumab was made based on standard medical practice and an observational prospective multicenter (n = 52) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed from 0 to 3 years (preceding Committee on Recurrent Wheezing study). The 52 investigators at hospitals then followed these subjects until 6 years of age, reported here (Effects of Preventive Treatment for Respiratory Syncytial [RS] Virus Infection During Infancy on Later Atopic Asthma in Preterm Infants; Scientific Committee for Elucidation of Infantile Asthma). Parents of study subjects reported the infants' physicians' assessment of recurrent wheezing, using a report card and a novel mobile phone-based reporting system using the Internet. The primary endpoint was the incidence of atopic asthma. MEASUREMENTS AND MAIN RESULTS: Of 444 preterm infants enrolled, 349 received palivizumab during the first year of life. At 6 years, atopic asthma was not different in the groups: 15.3 and 18.2% of infants in the treated and untreated groups, respectively (P = 0.57). On the other hand, physician-diagnosed recurrent wheezing was observed in 15.3 and 31.6% in the treated and untreated groups, respectively (P = 0.003). CONCLUSIONS: Palivizumab prophylaxis administered to preterm infants did not suppress the onset of atopic asthma but resulted in a significantly lower incidence of recurrent wheezing during the first 6 years. Clinical trial registered with www.clinicaltrials.gov (NCT 01545245).

Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.

BACKGROUND: Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease. METHODS AND RESULTS: Five-wk-old C57/BL6J male mice were intraperitoneally injected with Lactobacillus casei cell wall extract to induce coronary inflammation and divided into four groups: placebo, intravenous immunoglobulin (IVIG), losartan, and IVIG+losartan. After 2 wk, mice were harvested. The coronary perivasculitis was significantly attenuated by losartan but not by IVIG alone, and further dramatic attenuation by IVIG+losartan was observed. The frequency of Lactobacillus casei cell wall extract-induced myocarditis (80%) was markedly lowered by losartan (22%) and IVIG+losartan (0%). Furthermore, interleukin (IL)-6 mRNA was markedly attenuated by IVIG+losartan. Serum levels of IL-6, TNF-α, MCP-1, and IL-10 after Lactobacillus casei cell wall extract injection were slightly decreased by IVIG or losartan. Moreover, IL-1ß, IL-10, and MCP-1 levels were significantly decreased by IVIG+losartan. CONCLUSION: The addition of losartan to IVIG strongly attenuated the severity of coronary perivasculitis and the incidence of myocarditis, along with suppressing systemic/local cytokines as well as the activated macrophage infiltration. Therefore, losartan may be a potentially useful additive drug for the acute phase of Kawasaki disease to minimize coronary artery lesions.

Objective measurement of frequency and pattern of nocturnal cough in children with asthma exacerbation.

BACKGROUND: Although a number of patients with asthma report experiencing persistent cough during sleep, it has not yet been objectively investigated. OBJECTIVE: To classify cough severity and evaluate a characteristic pattern of cough frequency in children with asthma using an objective cough monitoring system. METHODS: An objective cough monitoring system that specialized in children was used to measure cough frequency and nocturnal cough patterns. Coughs were recorded with microphone and accelerometer and analyzed using a customized software program. The number of nocturnal coughs and the pattern of cough frequency in 30-minute intervals were measured along with the severity of each asthma exacerbation, and the results were compared with children without asthma. RESULTS: The total overnight cough count of 34 children with asthma was higher than that of 15 children without asthma (P < .001). The total overnight cough count in children with severe asthma exacerbation was higher than that in children with moderate asthma exacerbation (P < .05). The cough counts were significantly increased at the time of falling asleep and waking. This pattern was not observed in children without asthma. The total cough counts and cough patterns in children with asthma were not affected by sex, age, cause of asthma exacerbation, or therapy. CONCLUSION: Our data indicate huge cough counts and characteristic nocturnal cough patterns in children with asthma. Objective and precise cough monitoring is useful for the management of childhood asthma.

Hemophagocytic lymphohistiocytosis caused by systemic herpes simplex virus type 1 infection: Successful treatment with dexamethasone palmitate.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition resulting from an uncontrolled and ineffective immune response. Here, we report a case of HLH caused by disseminated herpes simplex virus (HSV)-1 infection. The patient was initially treated with prednisolone and high-dose acyclovir. Although liver enzymes, coagulation abnormalities, and inflammatory markers were remarkably improved, the platelet count remained low. Prednisolone was therefore switched to dexamethasone palmitate. Thereafter, the platelet count normalized. Inflammatory markers normalized 30 days after admission and serum HSV-DNA became undetectable on day 41. The patient was discharged on day 91 and no developmental delay was evident at 7 months of age. These findings suggest that dexamethasone palmitate is effective for neonatal HLH.

Successful acute lymphoblastic leukemia-type therapy in two children with mixed-phenotype acute leukemia.

Mixed-phenotype acute leukemia (MPAL) is a rare type of leukemia expressing both myeloid and lymphoid markers. There is limited information, especially on pediatric cases. Therefore, the optimal therapeutic approach to pediatric MPAL has not been defined. Here, we report two pediatric cases of MPAL. According to the 2008 World Health Organization (WHO) classification and European Group for the Immunological Characterization of Leukemias (EGIL) criteria, patient 1 was diagnosed with overt MPAL positive for the myeloid marker myeloperoxidase (MPO), and B-lymphoid markers. Patient 2 was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) using EGIL criteria. According to the 2008 WHO classification, however, patient 2 was diagnosed with overt MPAL positive for CD3, T-lymphoid markers and MPO. We chose an ALL-type therapy consisting of both lymphoid- and myeloid-directed agents; these patients have maintained complete remission following treatment. Further information on pediatric MPAL is needed to establish an appropriate therapeutic strategy including stem cell transplantation for this rare condition.

Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma.

BACKGROUND: Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. METHODS: We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. RESULTS: Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged <3 years and children aged ≥3 years. Serum concentrations of ECP, IL-5, and IP-10 were significantly elevated in virus-induced acute asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients <3 years than in those ≥3 years. Serum ECP and IL-5 production correlated significantly with age, whereas serum IP-10 showed an inverse correlation with age. CONCLUSIONS: Age-related differences in cytokine profiles and eosinophil activation may be related to virus-induced acute exacerbations of childhood asthma.