Yukio Nagasaka

Assessment of Serum CYFRA 21-1 in Lung Cancer

Cytokeratins are the intermediate filaments of the cytoskeletal protein located in normal epithelia, tumor, and cultured cells. Recently, a fragment of cytokeratin subunit 19, referred to as CYFRA 21‐1, detected in the serum of patients with nonsmall cell lung cancer, has been reported as a new tumor marker. This article reports the results of a study of serum fragment CYFRA 21‐1, measured by immunoradiometric assay, as a marker of lung cancer.

High-pitched breath sounds indicate airflow limitation in asymptomatic asthmatic children

Background and objective:  Asthmatic children may have airway dysfunction even when asymptomatic, indicating that their long‐term treatment is less than optimal. Although airway dysfunction can be identified on lung function testing, performing these tests can be difficult in infants. We studied whether breath sounds reflect subtle airway dysfunction in asthmatic children.

Correlation among the Indices of High-Resolution Computed Tomography, Pulmonary Function Tests, Pulmonary Perfusion Scans and Exercise Tolerance in Cases of Chronic Pulmonary Emphysema

Background: Mismatched distribution of pulmonary blood flow is a common characteristic in emphysematous patients. But few reports have mentioned the relationships between the morphological changes in the lungs as assessed by high-resolution computed tomography (HRCT), pulmonary blood flow (PBF) scan and the indices of exercise tolerance. We investigated these relationships. Objective: Pulmonary function tests (PFT), HRCT, single photon emission computed tomography (99mSPECT) and treadmill exercise tests were performed on emphysematous patients, and the correlations between these examinations were studied. Methods: We evaluated 20 patients (M 18, F 2, age 66 ± 8.0 years). CT evaluation was performed according to the grade of emphysematous change. 99mSPECT was performed to evaluate mismatched PBF by the score method. The better flow of the middle lobe was selected to be the standard lobe for the basic PBF. That score was set to 1 when the blood flow was below 60 or above 140%. PBF between 60 and 140% was scored as 0. Results: FEV1 (r = 0.648, p = 0.002) and VC (r = 0.767, p = 0.001) correlated significantly with v̇O2 peak . FEV1 (r = 0.667, p = 0.0018) correlated significantly with anaerobic threshold (AT). CT grade did not correlate with PBF mismatch score (r = 0.266, p = 0.3376). %v̇O2 peak did not correlate with CT grade (r = –0.467, p = 0.0689) or with mismatch PBF score (r = –0.327, p = 0.2377). Conclusions: HRCT and 99mSPECT were advantageous for detecting the progression of disease and emphysematous changes. However, the severity of anatomical emphysematous changes did not necessarily correlate with the indices of exercise tolerance and pulmonary function tests.

Lung Sounds in Bronchial Asthma

Modern understanding of lung sounds started with a historical article by Forgacs. Since then, many studies have clarified the changes of lung sounds due to airway narrowing as well as the mechanism of genesis for these sounds. Studies using bronchoprovocation have shown that an increase of the frequency and/or intensity of lung sounds was a common finding of airway narrowing and correlated well with lung function. Bronchoprovocation studies have also disclosed that wheezing may not be as sensitive as changes in basic lung sounds in acute airway narrowing. A forced expiratory wheeze (FEW) may be an early sign of airway obstruction in patients with bronchial asthma. Studies of FEW showed that airway wall oscillation and vortex shedding in central airways are the most likely mechanisms of the generation of expiratory wheezes. Studies on the genesis of wheezes have disclosed that inspiratory and expiratory wheezes may have the same mechanism of generation as a flutter/flow limitation mechanism, either localized or generalized. In lung sound analysis, the narrower the airways are, the higher the frequency of breathing sounds is, and, if a patient has higher than normal breathing sounds, i.e., bronchial sounds, he or she may have airway narrowing or airway inflammation. It is sometimes difficult to detect subtle changes in lung sounds; therefore, we anticipate that automated analysis of lung sounds will be used to overcome these difficulties in the near future.

The Effect of TYB-2285 on Dual Phase Bronchoconstriction and Airway Hypersensitivity in Guinea-pigs Actively Sensitized with Ovalbumin

Abstract— The effect of a new anti‐asthmatic drug, TYB‐2285 (3,5‐bis(acetoxyacetylamino)‐4‐chloro‐benzonitrile), was investigated in ovalbumin‐sensitized guinea‐pigs. When guinea‐pigs were pretreated with TYB‐2285 (300 mg kg−l, p.o., single dose or consecutively for 7 days), the immediate asthmatic response was inhibited as demonstrated by diminished cyanosis, but not the bronchoconstriction. TYB‐2285, given singly or consecutively, inhibited the appearance of late asthmatic response and the infiltration of inflammatory cells, such as eosinophils, into the airway. Additionally, airway hyper‐responsiveness was also reversed by the single administration of TYB‐2285. Luminol‐dependent chemiluminescence of airway‐infiltrated cells stimulated with A23187 was inhibited by TYB‐2285 in a dose‐dependent manner. The present study suggests that TYB‐2285 inhibits late asthmatic response and airway hyper‐responsiveness by inhibiting the accumulation of eosinophils and other inflammatory cells into the airway, and also by inhibiting the production of oxygen radicals from airway‐infiltrated cells.

Changes in the highest frequency of breath sounds without wheezing during methacholine inhalation challenge in children.

A breath sound analyser was used to detect bronchoconstriction without wheezing during methacholine inhalation challenge in children. The highest frequency of inspiratory breath sounds increased significantly during bronchoconstriction and decreased after inhalation of a bronchodilator. The highest frequency of inspiratory breaths sounds was correlated with bronchial reactivity.

A New Modality Using Breath Sound Analysis to Evaluate the Control Level of Asthma

BACKGROUND Reliable symptom assessment is essential in asthma management. We developed new technology for analyzing breath sounds and assessed its clinical usefulness for monitoring asthmatic children. METHODS Eighty asthmatic children and 59 non-asthmatic children underwent breath sound analysis in an asymptomatic state. Their asthma control was assessed by the Asthma Control TestTM or Childhood ACTTM scores and divided into two groups, namely, well-controlled (perfect) (n = 19) and not well-controlled (not perfect) (n = 61). Breath sounds were recorded using two sensors, located on the right anterior chest and trachea. We calculated the acoustic transfer characteristics between the two points, which indicated the relationship between frequencies and attenuation during breath sound propagation. Two indices of sound parameters, the chest wall sound index (CWI) and the tracheal sound index (TRI), were calculated from the transfer characteristics and tracheal sounds. We also developed a new parameter, the breath sound index (BSI), on a 2-dimensional diagram of CWI and TRI and tried to determine whether BSI may clarify asthma control better than CWI or TRI alone. RESULTS There was a significant difference in TRI and BSI between asthmatic and non-asthmatic children (p = 0.007, p < 0.001). There was a significant difference in CWI and TRI between the well-controlled and not-wellcontrolled groups (p < 0.001). BSI discriminated between the two groups accurately (p < 0.001). The sensitivity and specificity of BSI for asthma control were 83.6% and 84.2%, respectively. CONCLUSIONS Asthma control could be evaluated using a new index calculated from breath sound analysis.BACKGROUND Reliable symptom assessment is essential in asthma management. We developed new technology for analyzing breath sounds and assessed its clinical usefulness for monitoring asthmatic children. METHODS Eighty asthmatic children and 59 non-asthmatic children underwent breath sound analysis in an asymptomatic state. Their asthma control was assessed by the Asthma Control TestTM or Childhood ACTTM scores and divided into two groups, namely, well-controlled (perfect) (n = 19) and not well-controlled (not perfect) (n = 61). Breath sounds were recorded using two sensors, located on the right anterior chest and trachea. We calculated the acoustic transfer characteristics between the two points, which indicated the relationship between frequencies and attenuation during breath sound propagation. Two indices of sound parameters, the chest wall sound index (CWI) and the tracheal sound index (TRI), were calculated from the transfer characteristics and tracheal sounds. We also developed a new parameter, the breath sound index (BSI), on a 2-dimensional diagram of CWI and TRI and tried to determine whether BSI may clarify asthma control better than CWI or TRI alone. RESULTS There was a significant difference in TRI and BSI between asthmatic and non-asthmatic children (p = 0.007, p < 0.001). There was a significant difference in CWI and TRI between the well-controlled and not-well-controlled groups (p < 0.001). BSI discriminated between the two groups accurately (p < 0.001). The sensitivity and specificity of BSI for asthma control were 83.6% and 84.2%, respectively. CONCLUSIONS Asthma control could be evaluated using a new index calculated from breath sound analysis.

Treatment evaluation using lung sound analysis in asthmatic children

Non‐invasive assessment of treatment and prediction of attacks in asthmatic children do not yet exist. Lung sound analysis can non‐invasively evaluate airway obstruction. We used a recently developed technology for analysing lung sounds using ic700 (index of the chest wall at 700 Hz, sound intensity at 700 Hz) to evaluate response to inhaled corticosteroid (ICS) in asthmatic children.

EFFECTS OF CYTOKINES ON OXYGEN RADICAL PRODUCTION BY PERIPHERAL BLOOD MONOCYTES AND ALVEOLAR MACROPHAGES IN PATIENTS WITH LUNG CANCER

The effects of cytokines (interleukin-2, tumor necrosis factor-alpha and interferon-gamma) on the ability of peripheral blood monocytes and alveolar macrophages to produce oxygen radicals were examined by the chemiluminescence assay in patients with lung cancer. Oxygen radical production by peripheral blood monocytes before stimulation with cytokines was lower in the lung cancer group than in healthy controls, suggesting reduced immune function in lung cancer patients. However, the activity in the lung cancer group was elevated to the control level when the monocytes were stimulated by any of the three aforementioned cytokines. Oxygen radical production by alveolar macrophages did not differ significantly between nonstimulated monocytes from lung cancer patients and those from healthy controls. In the lung cancer group, stimulation of the macrophages with any of the three cytokines elevated their ability to produce oxygen radicals to the same extent as in the control group. The results suggest that stimulation of macrophages by interleukin-2, tumor necrosis factor-alpha or interferon-gamma can exert an antitumor action in patients with lung cancer.

Lung sound analysis helps localize airway inflammation in patients with bronchial asthma

Purpose Airway inflammation can be detected by lung sound analysis (LSA) at a single point in the posterior lower lung field. We performed LSA at 7 points to examine whether the technique could identify the location of airway inflammation in patients with asthma. Patients and methods Breath sounds were recorded at 7 points on the body surface of 22 asthmatic subjects. Inspiration sound pressure level (ISPL), expiration sound pressure level (ESPL), and the expiration-to-inspiration sound pressure ratio (E/I) were calculated in 6 frequency bands. The data were analyzed for potential correlation with spirometry, airway hyperresponsiveness (PC20), and fractional exhaled nitric oxide (FeNO). Results The E/I data in the frequency range of 100–400 Hz (E/I low frequency [LF], E/I mid frequency [MF]) were better correlated with the spirometry, PC20, and FeNO values than were the ISPL or ESPL data. The left anterior chest and left posterior lower recording positions were associated with the best correlations (forced expiratory volume in 1 second/forced vital capacity: r=−0.55 and r=−0.58; logPC20: r=−0.46 and r=−0.45; and FeNO: r=0.42 and r=0.46, respectively). The majority of asthmatic subjects with FeNO ≥70 ppb exhibited high E/I MF levels in all lung fields (excluding the trachea) and V50%pred <80%, suggesting inflammation throughout the airway. Asthmatic subjects with FeNO <70 ppb showed high or low E/I MF levels depending on the recording position, indicating uneven airway inflammation. Conclusion E/I LF and E/I MF are more useful LSA parameters for evaluating airway inflammation in bronchial asthma; 7-point lung sound recordings could be used to identify sites of local airway inflammation.