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.

Clinical characteristics of HNF1B-related disorders in a Japanese population.

BACKGROUND: Hepatocyte nuclear factor 1ß (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. METHODS: We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. RESULTS: Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m2; p = 0.0091). CONCLUSION: We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.

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.

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.

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.

Effects of COVID-19 pandemic-associated reduction in respiratory infections on infantile asthma development.

Background: It is speculated that the coronavirus disease 2019 (COVID-19) pandemic-associated reduction in the prevalence of respiratory tract infections has influenced the incidence of asthma in young children. Objectives: We investigated an association between the reduction in viral infections and the reduction in asthma in young children. Methods: The subjects were infants born in the early stages of the COVID-19 pandemic in Japan, which began in February 2020. A questionnaire survey related to asthma and allergy was conducted at 18 months and 3 years of age. These results were compared to those of age-matched infants during the nonpandemic period. Results: There were no epidemics of viral infectious diseases until the target child was 18 months old. At 18 months, the incidence of asthma/asthmatic bronchitis diagnosed by physicians in pandemic children was significantly lower than that in nonpandemic children. In 3-year-olds, no marked difference was observed between nonpandemic infants and pandemic children, except for an increase in respiratory syncytial virus infection in pandemic children. In a comparative study of the same children at ages 18 months and 3 years, an increased prevalence of asthma/asthmatic bronchitis was observed in pandemic children. Furthermore, the incidence of asthma after respiratory syncytial virus infection in pandemic infants was significantly lower than that in nonpandemic children. Conclusion: The COVID-19 pandemic-associated reduction in respiratory tract infections may have reduced the incidence of asthma in early childhood, and respiratory syncytial virus infection after 18 months of age had little effect on the onset of asthma. These results indicate the importance of preventing respiratory tract infections in early infancy.

Lung sound analysis for predicting recurrent wheezing in preschool children.

Background: In young healthy children, assessing airflow limitation may be difficult because of narrowing of the airways, which is a pathology of asthma, and responsiveness to bronchodilators. Objective: We investigated whether lung sound analysis could predict the development of recurrent wheezing (RW), which is one of the signs of asthma. Methods: In healthy children aged 3 to 24 months, we recorded and analyzed lung sounds before and after inhalation of bronchodilators and conducted a questionnaire survey. The children were followed up and assessed for the development of RW at age 3 years. Results: Of the 62 patients analyzed, 19 (30.6%) developed RW. The parameters ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (RPF50) and ratio of power and frequency at 75% of the highest frequency of the dB power spectrum (RPF75), calculated by lung sound analysis, were lower in the RW group, with odds ratios of 0.77 (95% CI = 0.61-0.98) and 0.81 (95% CI = 0.66-0.99), respectively. The rate of change of lung sound analysis parameters after bronchodilator inhalation did not differ among the participants as a group; however, in the subgroup of children with a history of atopic dermatitis, the fourth area under the curve (B4) divided by the total area under the curve of 100 Hz to the highest frequency of the dB power spectrum (AT) and difference between the values of the ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (ΔRPF50) were elevated in the RW group (P = .015 and P = .041, respectively). In the subgroup of children with total a IgE level greater than 20 kUA/L, the sensitivities and specificities for predicting the development of RW were 85.7% (95% CI = 48.7-99.3) and 68.8% (95% CI = 44.4-85.8), respectively, when the cutoff value of ΔRPF50 was set at 10.5%. Conclusion: The method of lung sound analysis allows noninvasive assessment of the airway, including airway hypersensitivity, in young children and may predict the risk of development of RW.

Characteristics of Breath Sounds During Methacholine-induced Bronchoconstriction in Children with Asthma.

OBJECTIVE: The utility of an analysis of breath sounds as a non-invasive lung function test in children and adults has been studied. Analyzing specific breath sounds during methacholine inhalation challenge is useful for evaluating airway constriction in asthmatic patients. PATIENTS AND METHODS: The study population included 57 children with atopic asthma (male: female = 38: 19; median age, 10 years [range, 5-16 years]). The breath sound spectrum was measured before a methacholine inhalation test, just after the methacholine inhalation challenge and after ß2 agonist inhalation. The values of breath sound parameters were analyzed and the direct changes of the sound spectrum during methacholine inhalation challenge were evaluated. RESULTS: The values of breath sound parameters, RPF75 and RPF50, were significantly decreased after methacholine inhalation (P < 0.001, p < 0.001, respectively), indicationg bronchoconstriction, and increased after ß2 agonist inhalation (P < 0.001, p < 0.001, respectively), indicating bronchodilation. The high-pitch area of the sound spectrum curve around 1,500 Hz was significantly increased after methacholine inhalation (P < 0.001). The values returned to the baseline level after ß2 agonist inhalation. CONCLUSIONS: Bronchoconstriction by methacholine inhalation induced a reversible high-pitch sound. The assessment of changes in the high-pitch area of the breath sound spectrum may be useful for the detection of airway narrowing in asthmatic patients.

Pediatric Parapneumonic Effusion/Pleural Empyema in Japan: A Nationwide Survey.

BACKGROUND: Pediatric parapneumonic effusion/ pleural empyema (PPE/PE) is a severe infectious condition, and its management should be guided by local epidemiology and the patient's medical history. This survey aimed to determine the clinical and bacteriologic features of PPE/PE in Japan. METHODS: A nationwide retrospective questionnaire survey was conducted, targeting 159 pediatric specialist training medical facilities for inpatients ≤18 years of age who were admitted for PPE/PE between January 2007 and December 2016. RESULTS: Valid responses were obtained from 122 facilities, and 96 patients were identified from 38 facilities. The median age (interquartile range) was 2.7 (0.8-7.8) years. Overall, 60 (63 %) patients were men and 49 (51%) had comorbidities. The causative bacteria were identified in 59% of patients by culture except in one case identified using PCR. Streptococcus pyogenes (16%), Staphylococcus aureus (14%) and Streptococcus pneumoniae (13%) were the major pathogens. Carbapenems were administered to 34% of patients without comorbidities. Chest tube drainage was performed in 71%, intrapleural fibrinolytic therapy in 9.4%, surgery in 25% and mechanical ventilation in 29% of the patients. Five patients (5.2%) had complications and one (1.1%) had sequelae, but all patients (100%) survived. CONCLUSIONS: This is first report of a nationwide survey pertaining to pediatric PPE/PE in Japan. We found that the etiology showed a different trend from that reported in other countries. It is worrisome that molecular methods were rarely used for pathogenic diagnosis and carbapenems were overused. Thus, it is imperative to establish clinical guidelines for PPE/PE in Japan.

Lung sound analysis in infants with risk factors for asthma development.

BACKGROUND AND OBJECTIVES: Using a lung sound analysis, the prognosis of asthma was investigated in infants with risk factors for asthma development by a long-term observation. METHODS: A total of 268 infants were included (median age: 8 months old). The lung sound parameters (the ratio of the third and fourth area to the total area under the curve [A3/AT and B4/AT], and the ratio of power and frequency at 50% and 75% of the highest frequency [RPF50 and RPF75]) were evaluated at the first visit. At 3 years old, using a questionnaire, we examined the relationship between the lung sound parameters and risk factors of asthma development. RESULTS: Among the 268 infants, 175 infants were in good health and 93 had a history of acute respiratory infection (ARI) within 7 days at the first visit. Among the 3- to 12-month-old infants with an ARI, the A3/AT, B4/AT values in those with a history of asthma/asthmatic bronchitis, atopic dermatitis, and atopy were smaller than in the infants without such histories. Among the 13- to 24-month-old infants with an ARI, the A3/AT and B4/AT values in those with a wheezing history were larger than in the infants without such a history. CONCLUSIONS: The characteristics of the lung sounds in infants with risk factors for asthma development were demonstrated over long-term follow-up. Lung sound analyses may be useful for assessing the airway condition of infants.

Changes in the Breath Sound Spectrum with Bronchodilator Inhalation in Asthmatic Children with Long-term Management.

OBJECTIVE: Using a commercially available breath sound analyzer, the airway reversibility in asthmatic children during healthy periods was investigated. METHODS: Fifty samples of 34 children with asthma (median age, 11 years; range, 6-16 years) who visited our hospital and whose lung function was normal were included. The breath sound parameters, the frequency limiting 99% of the power spectrum (F99) and spectrum curve indices, the total area under the curve of the dBm data (A3/AT and B4/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 before and after ß2 agonist inhalation. RESULTS: The values of spectrum curve indices were significantly increased after ß2 agonist inhalation. The changes in these parameters were more marked than the changes in the FOT parameters. The changes in A3/AT and B4/AT were significantly related to two FOT parameters: R5-R20 and X5. CONCLUSIONS: Our study suggested that significant changes in breath sound parameters were present in asthmatic children during the period of good control. A breath sound analysis may be useful for assessing the airway condition of asthmatic children during long-term management.

New Technique to Analyze the Breath Sound Spectrum in Children with Asthma.

OBJECTIVE: Breath sound parameters have been reported as useful biomarkers for evaluating the airway condition. METHODS: The reliability of breath sound analysis using an improved method was investigated. Eighty-three asthmatic children were included in the present study. After adjusting the 0 level based on the background noises of the breath sound spectrum, the total area under the curve of the dBm (AT), the roll-off from 600-1200 Hz (Slope), the ratio of the third and fourth area to the AT (A3/AT and B4/AT), and the ratio of power and frequency at 50% and 75% of the highest frequency (RPF75 and RPF50), were evaluated before and after ß2 agonist inhalation. Spirography and the forced oscillation technique were also used to evaluate all subjects. RESULTS: Using the new method, A3/AT, B4/AT, RPF75 and RPF50, were significantly increased after ß2 agonist inhalation. The increase in A3/AT and B4/AT were significantly correlated with the increase in FEV1 and FEE25-75, and the increase in RPF75 was reversibly correlated with that in R5-R20. CONCLUSIONS: The spectrum curve indices using the adjusted 0 level can indicate bronchial dilation with ß2 agonist inhalation. These parameters may be useful for the assessment of bronchial reversibility in asthmatic children.

Differences in Virus Detection and Cytokine Profiles between First Wheeze and Childhood Asthma.

OBJECTIVE: To distinguish between first wheeze and asthma in early childhood, we investigated respiratory viruses and cytokine/chemokine profiles among patients with first wheeze and established asthma. METHODS: We enrolled children with acute exacerbations of wheezing (17 first wheeze and 32 asthma) and 11 controls (no wheezing) aged between 10 months and 6 years. Nasal aspirates were obtained, and virus detection was performed with antigenic assay kits and/or RT-PCR. Serum 27 cytokines/chemokines were assayed by a multi-cytokine detection system. RESULTS: Rhinovirus and respiratory syncytial (RS) virus were dominant in acute exacerbations of asthma. However, many types of viruses were isolated in first wheeze. Serum IL-8 and IL-12 values were significantly higher in first wheeze than in acute asthma or the controls. IL-5 and IP-10 levels in acute asthma and first wheeze cases were higher than in the controls. Both of them were significantly higher in cases of acute asthma than in convalescence stage of asthma cases. Only IP-10 was significantly higher in first wheeze than in convalescence stage of first wheeze cases. CONCLUSIONS: Different profiles in virus detection and production of IL-8 and IL-12 might distinguish between first wheeze and childhood asthma.

A Lung Sound Analysis in Infants with Risk Factors for Asthma During Acute Respiratory Infection.

Background: The parameters of lung sounds have been suggested as biomarkers of airway changes. Using a commercially available lung sound analyzer, we investigated the characteristics of the lung sounds in infants with acute respiratory infection (ARI). Methods: Infants with ARI who were 6 to 18 months of age were included in this study. The lung sound parameters, the ratio of the third area and fourth areas to the total area under the curve of the sound spectrum (A3/AT and B4/AT), and the ratio of power and frequency at 75% and 50% of the highest frequency of the power spectrum (RPF75 and RPF50) were evaluated. With an original Japanese questionnaire based on American Thoracic Society-Division of Lung Disease, the risk factors of asthma development in infants were examined. Results: One hundred ten infants with ARI and 248 infants in good health for comparison were included. All infants were completely analyzed, and then divided into 2 age groups for a stratification analysis (6-12 and 13-18 months). In the overall analysis, among infants with a history of wheezing, recurrent wheezing, allergy, and atopic dermatitis, the values of RPF50 of infants with ARI were significantly lower compared with those without ARI. In the 6- to 12-month-old group, the RPF50 values of atopy-positive infants with ARI were lower compared with those without ARI (P = 0.003). Conclusions: The lung sounds of the infants with asthma-developing risk factors were more affected by ARI than those of infants without risk factors. Analyzing the changes in the lung sounds induced by ARI may be useful for evaluating the characteristics of the airways in infants.

The Evaluation of Changes in the Breath Sound Spectrum with Bronchoconstriction and Bronchodilatation in Asthmatic Children.

OBJECTIVE: Focusing on the relative-middle sound area of the breath sound spectrum, the relationship between airway changes and breath sounds in asthmatic children was investigated. METHODS: In Study 1, 77 children (6-16 years old) were included. The breath sound parameters, the ratio of the second area to the third area of the power spectrum (A2/A3) and the ratio of the third area to the fourth area (B3/B4) were evaluated 3 times, before and just after methacholine inhalation and after ß2 agonist inhalation. Other breath sound parameters, the frequency limiting 99% of the power spectrum (F99), the rolloff from 600-1200 Hz (Slope) and the ratio of the third and fourth area to the total area under the curve (A3/AT and B4/AT), and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50), were also evaluated. In Study 2, 91 children (6-16 years old) were included, with evaluations performed twice: before and after ß2 a gonist inhalation. Spirography a nd forced o scillation technique were also performed. RESULTS: In Study 1, A2/A3 and B3/B4 were significantly increased after methacholine inhalation and decreased after ß2 agonist inhalation (p < 0.001, P < 0.001, respectively). In Study 2, A2/A3 and B3/B4 were significantly decreased after ß2 agonist inhalation. These changes in A3/AT and B4/AT were the inverse of those in other spectrum curve indices. CONCLUSIONS: A2/A3 and B3/B4, indicate the breath sound changes after bronchoconstriction and bronchodilatation. These parameters may be useful for assessing bronchial reversibility in asthmatic children.