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.

Palivizumab prophylaxis in preterm infants and subsequent wheezing/asthma: 10-year follow-up study.

BACKGROUND: Respiratory syncytial virus (RSV) causes not only infantile recurrent wheezing but also the development of asthma. To investigate whether palivizumab, an anti-RSV monoclonal antibody, prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing and/or development of asthma, at 10 years of age. METHODS: We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 6 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice (SCELIA study). Here, we followed these subjects until 10 years of age. Parents of study subjects reported the patients' physician's assessment of recurrent wheezing/asthma, using a report card and a novel mobile phone-based reporting system using the internet. The relationship between RSV infection and asthma development, as well as the relationship between other factors and asthma development, were investigated. RESULTS: Of 154 preterm infants enrolled, 113 received palivizumab during the first year of life. At 10 years, although both recurrent wheezing and development of asthma were not significantly different between the treated and untreated groups, maternal smoking with aeroallergen sensitization of the patients was significantly correlated with physician-diagnosed asthma. CONCLUSIONS: In contrast to the prior study results at 6 years, by 10 years palivizumab prophylaxis had no impact on recurrent wheezing or asthma, but there was a significant correlation between maternal passive smoking with aeroallergen sensitization and development of asthma by 10 years of age.

Hematologic Abnormalities and Diseases Associated with Moderate-to-Marked Basophilia in a Large Cohort of Dogs.

Basophilia is a rare hematologic finding in dogs. This research aimed to describe the hematologic and clinical characteristics of dogs with moderate-to-marked basophilia. CBC reports with blood smear examinations from dogs presented to the North Carolina State University Veterinary Teaching Hospital were retrospectively reviewed for basophilia (>193 cells/µL). We classified basophilia as moderate when counts were ≥500 cells/µL and marked when they reached ≥1000 cells/µL. We compared the hematologic and clinical profiles of dogs with moderate-to-marked basophilia (the basophilia group) to those without basophilia, serving as our control group. In addition, we investigated differences between dogs with marked basophilia versus those with moderate basophilia, as well as between dogs in the basophilia group with and without concurrent eosinophilia. Diseases associated with moderate-to-marked basophilia included eosinophilic lung disease (p < 0.0001), leukemia/myeloproliferative neoplasms (p = 0.004), parasitic infection (p = 0.004), mast cell tumor (p = 0.005), and inflammatory bowel disease (p = 0.02). Overall, dogs with marked basophilia had a lower frequency of inflammatory diseases (51% vs. 70%, p = 0.009) and a higher frequency of neoplastic diseases (48% vs. 26%, p = 0.003) compared to those with moderate basophilia. In the basophilia group, concurrent eosinophilia was only seen in 36% of dogs. Dogs with concurrent eosinophilia were more often diagnosed with inflammatory diseases (77% vs. 58%, p = 0.006), with fewer diagnoses of neoplasia (19% vs. 40%, p = 0.001), compared to dogs without concurrent eosinophilia. The findings of this study offer veterinary clinicians valuable guidance in determining diagnostic priorities for dogs with moderate-to-marked basophilia.

Eosinophilic cavitary effusions in cats: 48 cases (2010-2020).

BACKGROUND: Eosinophilic effusions are commonly defined as effusions with ≥10% eosinophils. Eosinophilic cavitary effusions are infrequently observed in cats, with few case reports comprising the majority of the recent literature. OBJECTIVE: The objective was to review disease associations of cats with eosinophilic cavitary effusions and to assess if a lower threshold of eosinophils (5%-9%) may warrant consideration of similar etiologies associated with effusions with ≥10% eosinophils. METHODS: Cytology reports were retrospectively reviewed for all feline cavitary effusions submitted for fluid analysis from 2010 to 2020 at a veterinary teaching hospital. Cases were included if the manual leukocyte differential included ≥5% eosinophils and separated into 5%-9% and ≥10% eosinophils groups. Patient records were reviewed for associated medical conditions. RESULTS: A total of 669 effusions were submitted from 579 cats; 50 effusions from 48 cats had a leukocyte differential with ≥5% eosinophils. The eosinophil proportion was ≥10% in 22 cats; the most common underlying cause was neoplasia (10/22, 45%), followed by inflammatory disease (4/22, 18%), cardiac disease (3/22, 14%), suspect neoplasia (3/22, 14%), and undetermined (2/22, 9%). The underlying causes for the 26 cats with 5%-9% eosinophils were similar; neoplasia (8/26, 31%), cardiac disease (6/26, 23%), inflammatory disease (4/26, 15%), suspect neoplasia (3/26, 12%), undetermined (3/26, 12%), and idiopathic chylothorax (2/26, 8%). Cats with eosinophil proportions ≥10% in the fluid exhibited peripheral eosinophilia more frequently (35%) compared to those with 5%-9% eosinophils (5%). CONCLUSIONS: Consistent with the current literature, neoplasia, particularly lymphoma, remains a primary consideration for cats with eosinophilic effusions. Previously unreported associated diseases included cardiovascular and inflammatory disorders. Our findings suggest an eosinophil differential of 5%-9% is seen with similar etiologies considered for classically defined eosinophilic effusions.

Skull Base Fracture or Abuse Suspicion Based on Intraorbital Lymphangioma Secondary to Periorbital Hematoma.

Intraorbital lymphangiomas are among the orbital tumors that can cause sudden eye protrusion in children. In children with periorbital hematoma (panda eye sign), a skull fracture or abuse is likely first considered as the differential diagnosis. A 7-month-old boy presented to the ophthalmologist with complaints of swelling of the right upper eyelid, subconjunctival hemorrhage on the right ear side, and periorbital subcutaneous hemorrhage, which had appeared since the morning of the day before the visit. The eyeball did not protrude. Based on the interview and clinical findings, right eyeball contusion was suspected. The patient was then followed up for observation. Later, during the physical examination, the abovementioned symptoms were noted. Hence, the patient was admitted for a close examination based on the suspicion of skull base fracture and abuse. Contrast-enhanced magnetic resonance imaging (MRI) after admission revealed a multifocal cystic structure within the right intraorbital muscular cone. Thus, he was diagnosed with right intraorbital lymphangioma. Intraorbital lymphangioma may not show ocular protrusion, and this disease should be considered in cases where abuse is suspected, considering the periorbital subcutaneous hemorrhage.

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.

A Boy Presenting with a Fever and Pancytopenia Diagnosed with Systemic Lupus Erythematosus without a Positive Anti-ds-DNA Antibody Result or Hypocomplementemia: A Case Report.

BACKGROUND: Hematological involvement, including anemia, leukopenia, lymphopenia, and thrombocytopenia, is one of the most common manifestations of childhood-onset systemic lupus erythematosus (cSLE). Specifically, relatively severe forms of hematological involvement, such as macrophage activation syndrome (MAS) and thrombotic microangiopathy, occur in the course of the disease. Positivity for anti-double stranded-DNA (ds-DNA) antibody and hypocomplementemia are important as not only criteria of diagnosing cSLE but also in the determination of the disease activity. CASE REPORT: A 13-year-old boy without pre-existing disease was referred to our hospital chiefly complaining of a fever for > 7 days, long-lasting malaise, nausea, and non-malar face rash. His blood examination showed pancytopenia and hyperferritinemia, but positive results for anti-ds-DNA antibody and hypocomplementemia were not recognized. Bone marrow aspiration revealed no evidence of malignant diseases, hemophagocytic lymphohistiocytosis, or MAS. A renal biopsy for the differential diagnosis of proteinuria and hematuria revealed class IIIa +V lupus nephritis, leading to the diagnosis of cSLE. CONCLUSIONS: It is important for cSLE to be considered in patients with pancytopenia, even those without positive anti-ds-DNA antibody findings or hypocomplementemia, and for aggressive approaches to be adopted for the differential diagnosis, including a renal biopsy.

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.

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.

Effect of Post-nasal Drip on Overnight-cough Frequency and Cough Pattern in Children with Asthma.

OBJECTIVE: In children, post-nasal drip (PND)-induced cough is speculated. However, the relationship between PND and cough is still unclear. METHODS: During acute exacerbation of asthma, the number of overnight coughs and the cough pattern were compared in the children with atopic asthma with PND (n = 8) and the children with atopic asthma without PND (n = 27). All subjects had allergic rhinitis according to our original cough monitor. RESULTS: The total number of overnight coughs was significantly higher in the subjects with PND than in the subjects without PND (P < 0.05). In contrast, the overnight cough pattern of the subjects with PDN was found to be the same as in the subjects without PND, showing an increase in the number of coughs at the sleep onset and in the early morning. CONCLUSION: Our results suggest that PND may increase the number of nighttime coughs in children with atopic asthma and allergic rhinitis. In contrast, the overnight cough pattern was the same in the two groups, suggesting that this specific cough pattern is due to allergic inflammation of the upper and lower airways.

Breath sound analyses of infants with respiratory syncytial virus acute bronchiolitis.

INTRODUCTION: The reliability of a breath sound analysis using an objective method in infants has been reported. OBJECTIVE: Breath sounds of infants with respiratory syncytial virus (RSV) acute bronchiolitis were analyzed via a breath sound spectrogram to evaluate their characteristics and examine their relationship with the severity. SUBJECTS AND METHODS: We evaluated the inspiratory and expiratory breath sound parameters of 33 infants diagnosed with RSV acute bronchiolitis. The sound powers of inspiration and expiration were evaluated at the acute phase and recovery phase of infection. Furthermore, the relationship between the breath sound parameters and the clinical severity of acute bronchiolitis was examined. RESULTS: Analyses of the breath sound spectrogram showed that the power of expiration as well as the expiration-to-inspiration sound ratio in the mid-frequency (E/I MF) was increased in the acute phase and decreased during the recovery phase. The E/I MF was inversely correlated with the SpO2 and positively correlated with the severity score. CONCLUSION: In infants with RSV acute bronchiolitis, the sound power of respiration was large at the acute phase, significantly decreasing in the recovery phase. In 61% of participants, nonuniform, granular bands were shown in the low-pitched region of the expiratory spectrogram.

A new method for objectively evaluating nocturnal cough in adults.

BACKGROUND: For the management of cough diseases in adults, an objective method of evaluating nocturnal cough is required. METHODS: In Study 1, a cough monitoring system was evaluated using 25 adult volunteers. In Study 2, the cough monitoring system was validated using 20 samples from 10 adult patients with cough diseases obtained overnight. In hospitalized patients, our original cough monitoring system with a microphone and accelerometer was used. At the same time, coughs were recorded using a video camera with digital sound recording. The number of coughs in each 8-h video-audio recording was counted manually by three trained observers. All cough data were printed out, and the basal number of cough events, using both the printed-out data and video-audio recordings, were then calculated by three observers. RESULTS: In Study 1, the cough monitoring system demonstrated good agreement with the number of coughs counted by examiners (sensitivity 99.2%, specificity 98.9%). In Study 2, there was significant agreement in the counts of natural coughs between our system and the video-audio method (p < 0.0001) and between our system and the basal cough events (p < 0.0001). CONCLUSIONS: Our method demonstrated excellent agreement with the video-audio recording method in adults and is considered extremely useful for the objective monitoring of overnight cough in adult patients with cough diseases.

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.

A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation.

Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model. Circulating tumor cell clusters that successfully extravasated the vasculature as multicellular units were isolated under intravital imaging (n = 6). These extravasation-positive tumor cell clusters sublines were then molecularly profiled by RNA-Seq. Using a systems-level analysis, we pinpointed the downregulation of KRAS signaling, immune pathways, and extracellular matrix (ECM) organization as enriched in extravasated cells (p < 0.05). Within the extracellular matrix remodeling pathway, we identified versican (VCAN) as consistently upregulated and central to the ECM gene regulatory network (p < 0.05). Versican expression is prognostic for a poorer metastasis-free and overall survival in patients with osteosarcoma. Together, our results provide a novel experimental framework to study discrete steps in the metastatic process. Using this system, we identify the versican/ECM network dysregulation as a potential contributor to osteosarcoma circulating tumor cell metastasis.

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.