Cryo-EM structure of the ß3-adrenergic receptor reveals the molecular basis of subtype selectivity.

The ß3-adrenergic receptor (ß3AR) is predominantly expressed in adipose tissue and urinary bladder and has emerged as an attractive drug target for the treatment of type 2 diabetes, obesity, and overactive bladder (OAB). Here, we report the cryogenic electron microscopy structure of the ß3AR-Gs signaling complex with the selective agonist mirabegron, a first-in-class drug for OAB. Comparison of this structure with the previously reported ß1AR and ß2AR structures reveals a receptor activation mechanism upon mirabegron binding to the orthosteric site. Notably, the narrower exosite in ß3AR creates a perpendicular pocket for mirabegron. Mutational analyses suggest that a combination of both the exosite shape and the amino-acid-residue substitutions defines the drug selectivity of the ßAR agonists. Our findings provide a molecular basis for ßAR subtype selectivity, allowing the design of more-selective agents with fewer adverse effects.

Association between the Combination of Speed-Eating and Eating until Full and Overweight/Obesity in Part-Time High School Students.

INTRODUCTION: This cross-sectional study aimed to examine the association between overweight/obesity and the combined behavior of speed-eating and eating until full among part-time high school students. METHODS: In 2015, 2,507 male and female part-time high school students from Hyogo Prefecture, Japan, who completed a self-reported questionnaire on lifestyle, were included in the analysis. Overweight/obesity was defined as a body mass index of 25 kg/m2 or more. Responses regarding speed-eating and eating until full were obtained by self-reporting. Logistic regression analysis was used to estimate the odds ratio (OR) for overweight/obesity. RESULTS: Among the participants, 340 (13.6%) were overweight/obese and 468 (18.7%) reported both speed-eating and eating until full. Compared to neither speed-eating nor eating until full group, after adjustment for sex, age, work pattern, physical activity level, sleep duration, frequency of picky eating, frequency of snack intake, fast food intake frequency, frequency of adding salty condiments, frequency of eating less food to save money, and survey schools, the OR (95% CI) for overweight/obesity in speed-eating and not eating until full, eating until full and not speed-eating, and speed-eating and eating until full was 2.11 (1.38-3.22), 1.54 (1.12-2.10), and 2.94 (2.08-4.16), respectively. CONCLUSIONS: The combination of speed-eating and eating until full was associated with overweight/obesity among part-time high school students independent of other lifestyle factors.

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.

Differences in needs for community collaboration for heart failure between medical and nursing care staff.

The increased numbers of older and frail patients with heart failure (HF) means there is an urgent need to establish regional collaborative systems for medical and nursing care. However, expectations related to collaborative HF care among medical and care staff remain unclear. We conducted a questionnaire survey with staff in hospitals, clinics, and nursing care facilities (NCFs) who had experienced collaboration through the common HF collaborative pathway in the western region of Tottori Prefecture, Japan, from July 2019 to July 2020. We received 150 responses from hospitals and 41 responses from clinics and NCFs. Following introduction of the collaborative pathway, 57% of respondents from hospitals, 35% from clinics, and 71% from NCFs rated collaboration as improved. Staff from hospitals and clinics were most satisfied with improved education interventions following implementation of the collaborative pathway, and NCF staff were most satisfied with improved information sharing. Staff from hospitals and NCFs placed the highest importance on improving information sharing through collaboration, and clinic staff placed the highest importance on improving efficiency. The needs for collaborative HF care differ between hospitals, clinics, and NCFs. A collaboration program should be designed to meet the different needs of diverse staff in the community.

Simple Score to Predict Treatment Response to Low-Dose Tolvaptan in Patients with Heart Failure.

The recommended starting dose of Tolvaptan for heart failure (HF) is 7.5 mg/day in Japan; the recommended dose is 3.75 mg/day for older patients to avoid excessive diuresis and hypernatremia. However, low-dose Tolvaptan may delay the release of congestion in some patients. We aimed to develop a score to predict treatment responders to 3.75 mg tolvaptan.We retrospectively analyzed 106 patients with HF who initially received 3.75 mg/day of Tolvaptan in the derivation cohort (April 2013-December 2017) and 63 patients receiving 3.75 mg/day of Tolvaptan in the validation cohort (January 2018-April 2021). Treatment responders to 3.75 mg tolvaptan did not require dose escalation of Tolvaptan for congestion relief. In multivariate analysis, blood urea nitrogen (BUN) < 39 mg/dL and hematocrit > 35% were selected as variables to predict treatment responders. These were assigned 1 point each, and patients were stratified into groups with 2 points (n = 32), 1 point (n = 39), and 0 points (n = 35). The frequency of treatment responders was 82.9% in the 2-point group, 61.5% in the 1-point group, and 34.4% in the 0-point group (P < 0.05). The predictive ability of the score was acceptable with an area under the receiving operator characteristic curve (AUC) 0.726 (P < 0.05); its performance was maintained in the validation cohort (AUC 0.733, P < 0.05).A simple score using BUN and hematocrit could identify treatment responders to 3.75 mg tolvaptan, which may help determine the appropriate starting dose of Tolvaptan, balancing efficiency with safety for older patients with HF.

Sleep Disorder and Heart Failure with Preserved Ejection Fraction.

It is generally considered that obstructive sleep apnea is a potential cause of heart failure (HF), and insomnia and central sleep apnea are results of HF. However, the number of reports describing the bidirectional relationship between sleep disorder and HF has increased. Sleep disorder may contribute to left ventricular diastolic dysfunction via left atrial overload, left ventricular remodeling, pulmonary hypertension, and atrial fibrillation, which lead to HF with preserved left ventricular ejection fraction. Overnight rostral fluid shift and lung congestion may lead to airflow obstruction in the upper pharynx and stimulate pulmonary irritant receptors, which induce hyperventilation and sleep disorder.

Induction of adaptive immune responses against antigens incorporated within the capsid of simian virus 40.

Simian virus 40 (SV40) is a monkey polyomavirus. The capsid structure is icosahedral and comprises VP1 units that measure 45 nm in diameter. Five SV40 VP1 molecules form one pentamer subunit, and a single icosahedral subunit comprises 72 pentamers; a single SV40 VP1 capsid comprises 360 SV40 VP1 molecules. In a previous study, we showed that an influenza A virus matrix protein 1 (M1) CTL epitope inserted within SV40 virus-like particles (VLPs) induced cytotoxic T lymphocytes (CTLs) without the need for an adjuvant. Here, to address whether SV40 VLPs induce adaptive immune responses against VLP-incorporated antigens, we prepared SV40 VLPs containing M1 or chicken ovalbumin (OVA). This was done by fusing M1 or OVA with the carboxyl terminus of SV40 VP2 and co-expressing them with SV40 VP1 in insect cells using a baculovirus vector. Intraperitoneal (i.p.) or intranasal administration of SV40 VLPs incorporating M1 induced the production of CTLs specific for the M1 epitope without the requirement for adjuvant. The production of antibodies against SV40 VLPs was also induced by i.p. administration of SV40 VLPs in the absence of adjuvant. Finally, the administration of SV40 VLPs incorporating OVA induced anti-OVA antibodies in the absence of adjuvant; in addition, the level of antibody production was comparable with that after i.p. administration of OVA plus alum adjuvant. These results suggest that the SV40 capsid incorporating foreign antigens can be used as a vaccine platform to induce adaptive immune responses without the need for adjuvant.

Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein.

Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications.

Low signal intensities of MRI T1 mapping predict refractory diplopia in Graves' ophthalmopathy.

OBJECTIVE: In Graves' ophthalmopathy (GO), fibrosis in extraocular muscles (EOMs) may be related to intravenous glucocorticoid (ivGC)-resistant diplopia. Signal intensity (SI) of magnetic resonance imaging (MRI) T1 mapping can quantify properties of EOM components, including fibrosis. We investigated EOM features of GO patients with diplopia using T1 mapping SI and the predictive value of T1 mapping SI in the response of diplopia to ivGCs. DESIGN: We performed a cross-sectional study that included 13 active GO patients, 34 inactive GO patients with history of diplopia, including 20 with a history of diplopia disappearance, 14 GO patients with refractory diplopia and 35 control subjects. In nine active GO patients, the relationship between T1 mapping SI at pretreatment and at diplopia outcome after ivGC treatment was prospectively investigated. METHODS: T1 mapping SI of left and right inferior rectus and medial rectus muscles was measured in all participants. RESULTS: T1 mapping SI in inactive GO patients with refractory diplopia was significantly lower than that of other groups in all evaluated EOMs. Diagnostic accuracy for refractory diplopia by T1 mapping SI in GO patients with a history of diplopia disappearance was excellent (AUC 0.89) compared with other assessments. Furthermore, among nine active GO patients, pretreatment T1 mapping SI in four patients with ivGC-resistant diplopia tended to be low compared with the other five patients with improved diplopia. CONCLUSIONS: Low intensity T1 mapping in EOMs is likely to be associated with refractory diplopia and may be useful in predicting the response of diplopia to ivGCs.

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.

Neurological Prognostic Value of Adjusted Ca2+ Concentration in Adult Patients with Out-of-Hospital Cardiac Arrest.

Many patients are transferred to hospital due to out-of-hospital cardiac arrest (OHCA), and, unfortunately, most suffer from cerebral damage. Currently, it is difficult to predict the recovery of neurological function after return of spontaneous circulation (ROSC) in the acute phase. Increased intracellular Ca2+ induces cell death in the acute phase. Accordingly, we predicted that serum adjusted Ca2+ will decrease following Ca2+ influx into cells. Consequently, serum adjusted Ca2+ in the acute phase may be able to predict recovery of neurological function in patients with ROSC from OHCA. This is a retrospective and observational study from 2 centers. A total of 190 consecutive patients with ROSC from OHCA were recruited, with 33 patients meeting the inclusion criteria. The relationship between serum adjusted Ca2+ within 48 hours after ROSC and neurological function at discharge (as evaluated by the Glasgow-Pittsburgh cerebral performance category) was examined. Serum adjusted Ca2+ was measured every 4 hours within a 48-hour period after ROSC. There were no significant differences in hemodynamical state and laboratory data between the 2 groups. However, lowest serum adjusted Ca2+ within 48 hours after ROSC was significantly lower in the poor neurological outcome group (0.96 ± 0.06 versus 1.02 ± 0.06 mmol/L, P = 0.011). Thus, lowest serum adjusted Ca2+ within 48 hours after ROSC may be a predictive factor for recovery of neurological function at discharge in patients with ROSC from OHCA.

Purification and functional characterization of tomato mosaic virus 130K protein expressed in silkworm pupae using a baculovirus vector.

Tomato mosaic virus (ToMV; genus, Tobamovirus) is a member of the alpha-like virus superfamily of positive-strand RNA viruses, which includes many plant and animal viruses of agronomical and clinical importance. The genomes of alpha-like viruses encode replication-associated proteins that contain methyltransferase, helicase and/or polymerase domains. The three-dimensional structure of the helicase domain fragment of ToMV has been determined, but the structures of the other domains of alpha-like virus replication proteins are not available. In this study, we expressed full-length ToMV replication-associated protein 130 K, which contains the methyltransferase and helicase domains, using the baculovirus-silkworm expression system and purified the recombinant protein to near homogeneity. Purified 130 K, which was stable in phosphate buffer containing magnesium ions and ATP, formed a dimer in solution and hydrolyzed nucleoside 5'-triphosphates.

Pre-ablation levels of brain natriuretic peptide are independently associated with the recurrence of atrial fibrillation after radiofrequency catheter ablation in patients with nonvalvular atrial fibrillation.

Association between pre-ablation levels of biomarkers of cardiac and endothelial dysfunctions, CHADS2, CHA2DS2-VASc, and APPLE scores and the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation has not been fully studied. A total of 254 patients with nonvalvular AF were prospectively followed for AF recurrence after a single ablation procedure. During a two-year follow-up period, AF recurred in 65 (25.6%) patients. Patients with AF recurrence had significantly greater baseline ln brain natriuretic peptide (BNP) than those without AF recurrence (P < 0.01), whereas there were no significant differences in the levels of biomarkers of endothelial dysfunction and points of scoring systems. In the Cox regression analyses, the baseline ln BNP was significantly independently associated with AF recurrence (adjusted HR =1.286, 95% CI =1.000-1.655, P < 0.05). The baseline levels of ln BNP were significantly associated with rhythm at blood collection, age, sex, and left atrial diameter, and left ventricular ejection fraction (P < 0.05).The subgroup analysis showed a significant interaction on the risk of AF recurrence between ln BNP, sex difference, and rhythm at blood collection (P for interaction < 0.05). In conclusion, the results suggest that the pre-ablation levels of ln BNP are useful to evaluate the risk of AF recurrence after ablation therapy; however, there is a need to be careful while using BNP as a biomarker for the risk of AF recurrence by taking account of the effects of rhythm status at blood collection and sex difference.

Different Effects of Pulmonary Vein Isolation on Quality of Life Between Patients with Persistent and Paroxysmal Atrial Fibrillation.

The effect of restoring sinus rhythm by pulmonary vein isolation (PVI) on the quality of life (QOL) of patients with persistent atrial fibrillation (PerAF) has not been adequately investigated. This study was performed to compare the changes in QOL after extended PVI between patients with PerAF and paroxysmal AF (PAF).Patients with PAF (n = 38) and PerAF (n = 22) who underwent their first PVI and developed no AF recurrence 6 months after PVI were enrolled. QOL surveys were performed at baseline and 6 months post-ablation using Short Form-36 surveys.The mental component summary score (MCS) (53.4 ± 10.2 to 56.5 ± 7.1, P = 0.019) and physical component summary score (PCS) (46.1 ± 10.6 to 48.5 ± 8.3, P = 0.015) improved after PVI in the PAF group. The PCS, but not the MCS, improved after PVI in the PerAF group (45.8 ± 7.9 to 51.5 ± 6.2, P < 0.001). Changes in the PCS were greater in the PerAF group than in the PAF group (8.6 ± 6.9 versus 2.8 ± 5.2, P = 0.009). Multivariate regression analysis demonstrated that a low baseline MCS and the type of AF (PAF) were independent predictors of an increased MCS and that a low baseline PCS and the type of AF (PerAF) were independent predictors of an increased PCS.The changes in QOL differed between PAF and PerAF after PVI. Although most patients with PerAF were asymptomatic before PVI, their improvement in physical QOL was greater than that in patients with PAF. Such beneficial effects on physical QOL are likely expected in patients with PerAF with a low PCS before PVI.

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.

Diaphragm Muscle Dysfunction in Patients With Heart Failure.

BACKGROUND: Inspiratory muscle weakness is associated with the development of exercise intolerance in patients with heart failure (HF). Ultrasound assessment of the diaphragm is used to evaluate respiratory muscle function, but its application in patients with HF remains undefined. We examined the relationship of diaphragm function as assessed by ultrasonography with inspiratory muscle strength and exercise tolerance in HF. METHODS AND RESULTS: Seventy-seven patients hospitalized with HF were enrolled. Impaired diaphragm muscle function was defined as a diaphragm thickness at end-inspiration of less than the median value of 4.0 mm, which represents diaphragm muscle loss and reduced contraction. Compared with patients with preserved diaphragm muscle function, those with impaired diaphragm muscle function were older; had significantly lower vital capacity, handgrip strength, and inspiratory muscle strength as assessed by the maximum inspiratory pressure; and had a significantly shorter 6-minute walk distance (6MWD; P < .05). Although low handgrip strength was also associated with a short 6MWD, the relationship between impaired diaphragm muscle function and short 6MWD was independent from age, vital capacity, and handgrip strength. CONCLUSION: Diaphragm dysfunction as assessed by ultrasonography represents inspiratory muscle weakness and predicts exercise intolerance independently from comorbid pulmonary dysfunction and dynapenia in patients with HF.