Prevalence and impact of rhinitis in asthma. SACRA, a cross-sectional nation-wide study in Japan.

BACKGROUND: Asthma and rhinitis are common co-morbidities everywhere in the world but nation-wide studies assessing rhinitis in asthmatics using questionnaires based on guidelines are not available. OBJECTIVE: To assess the prevalence, classification, and severity of rhinitis using the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria in Japanese patients with diagnosed and treated asthma. METHODS: The study was performed from March to August 2009. Patients in physicians' waiting rooms, or physicians themselves, filled out questionnaires on rhinitis and asthma based on ARIA and Global Initiative for Asthma (GINA) diagnostic guides. The patients answered questions on the severity of the diseases and a Visual Analog Scale. Their physicians made the diagnosis of rhinitis. RESULTS: In this study, 1910 physicians enrolled 29,518 asthmatics; 15,051 (51.0%) questionnaires were administered by physician, and 26,680 (90.4%) patients were evaluable. Self- and physician-administered questionnaires gave similar results. Rhinitis was diagnosed in 68.5% of patients with self-administered questionnaires and 66.2% with physician-administered questionnaires. In this study, 994 (7.6%) patients with self-administered and 561 (5.2%) patients with physician-administered questionnaires indicated rhinitis symptoms on the questionnaires without a physician's diagnosis of rhinitis. Most patients with the physician's diagnosis of rhinitis had moderate/severe rhinitis. Asthma control was significantly impaired in patients with a physician's diagnosis of rhinitis for all GINA clinical criteria except exacerbations. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician's diagnosis of rhinitis (25.4% and 29.7%) by comparison with those without rhinitis (18.0% and 22.8%). CONCLUSION: Rhinitis is common in asthma and impairs asthma control.

Validation of a single-channel airflow monitor for screening of sleep-disordered breathing.

A simple screening method for sleep-disordered breathing (SDB) is desirable for primary care practices. In the present study, a simple monitor, which utilises a new type of flow sensor and a novel algorithm, was prospectively validated. Home recording for 2 nights with the monitor only, followed by in-laboratory recording with the monitor together with polysomnography, were carried out in consecutive patients (n = 100) suspected of SDB. A subjective sleep log was also recorded. The signal was analysed using power spectral analysis, which yielded the flow respiratory disturbance index (flow-RDI). There was no recording failure at home. The reproducibility of the flow-RDI between the 2 nights at home was high (intraclass correlation coefficient = 0.92). The sensitivity and specificity of the in-laboratory flow-RDI to diagnose SDB were 0.96 and 0.82, 0.91 and 0.82, and 0.89 and 0.96, for apnoea/hypopnoea index (AHI) > or =5, > or =15 and > or =30 events x h(-1), respectively. The diagnostic ability in low-severity subgroups (female, normal weight, AHI <15 events x h(-1)) was almost comparable to that in the entire group. Excluding subjective waking time on the sleep log from the recording time had no significant effect on the flow-RDI. The single-channel monitor is considered feasible for ambulatory sleep disordered breathing monitoring because of its easy applicability, high reproducibility and relatively high agreement with polysomnography results.

Pharyngoconjunctival fever caused by adenovirus type 11.

Among a group of hospitalized children in Fukuoka, southern Japan, an epidemic of pharyngoconjunctival fever-like disease caused by adenovirus type 11 was observed in the autumn of 1988. Of the 47 children studied 38 were seronegative in neutralizing antibody for adenovirus type 11 before the epidemic, and seroconversion occurred in 16 (42%) including 5 subclinical cases. Of the 11 symptomatic patients the incidences of conjunctivitis, pharyngitis and fever were 91, 64 and 46%, respectively. Four patients (36%) had all three symptoms. Fifteen patients (94%) were boys. The sex predominance and high incidence of conjunctivitis suggested that infection may have been transmitted in the large bathroom where boys took baths together.

Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.

Twenty asthmatic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients, 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.

Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes guinea pig tracheal smooth muscle by producing epithelium-dependent relaxing factors.

A non-phorbol ester-type tumor promoter, thapsigargin has been reported to deplete Ca(2+) stores in endothelial cells by inhibiting Ca(2+)-ATPase, which in turn increases intracellular Ca(2+) by mobilization of extracellular Ca(2+), leading to activation of constitutive nitric oxide synthase (cNOS) and resultant generation of nitric oxide (NO). In the present study, to evaluate the role of Ca(2+) in the release of epithelium-dependent relaxing factor (EpDRF), we determined the effect of thapsigargin (10(-6) M) on the contraction evoked by exogenous Ca(2+) or acetylcholine (10(-5) M) in epithelium-denuded or epithelium-intact smooth muscle from guinea pig trachea. The following results were obtained: (1) In epithelium-denuded smooth muscle, the contraction evoked by exogenous Ca(2+) in Ca(2+)-free solution or by acetylcholine (10(-5) M) in Ca(2+)-containing solution did not change within 20 min after thapsigargin application, but the contraction evoked by exogenous Ca(2+) increased markedly after 120 min, indicating that thapsigargin had no effect on smooth muscle itself within 20 min of application. The following experiments were performed within 20 min of thapsigargin application. (2) In epithelium-intact smooth muscle, thapsigargin significantly suppressed the contraction evoked by acetylcholine, suggesting that thapsigargin stimulate the epithelium to produce EpDRF. N(G)-nitro-L-arginine methylester (L-NAME) partly, but significantly, attenuated this inhibitory effect of thapsigargin. (3) In epithelium-denuded smooth muscle, atropine (10(-6) M) and L-NAME (10(-5) M) did not change the contraction evoked by exogenous Ca(2+) after application of thapsigargin, suggesting that thapsigargin did not stimulate acetylcholine and NO release from nerve terminals. These results suggest that thapsigargin (10(-6) M) may stimulate EpDRF, including NO and other factor(s) by Ca(2+)-dependent mechanisms.

Effects of epinastine hydrochloride on cholinergic neuro-effector transmission in canine tracheal smooth muscle.

We determined the effects of epinastine hydrochloride, an anti-asthmatic drug, on cholinergic neuro-effector transmission in canine trachea. Isometric tension of tracheal strips was measured in the presence of indomethacin and propranolol. Epinastine (10(-6) M) significantly suppressed the contraction evoked by electrical field stimulation, but had no effect on the acetylcholine-evoked contraction. An L-type Ca2+ channel blocker, nicardipine, did not suppress the electrical field stimulation-induced smooth muscle contraction and did not alter the inhibitory effect of epinastine. An N-type Ca2+ channel blocker, omega-conotoxin, suppressed the electrical field stimulation-induced contraction in a dose-dependent manner, and in a subthreshold/intermediate concentration abolished the inhibitory effect of epinastine. These findings indicate that epinastine exerts prejunctional inhibitory effects on airway smooth muscle of dogs, presumably by inhibiting acetylcholine release from vagal nerve terminals, and suggest that this effect is mediated by N-type Ca2+ channels.

Neutrophil elastase inhibitor, ONO-5046 suppresses ozone-induced airway mucus hypersecretion in guinea pigs.

To investigate the role of neutrophil elastase in ozone-induced airway hypersecretion, we measured goblet cell secretion by using a semiquantitative morphometric technique in guinea pigs. The magnitude of mucus discharge was estimated from the mucus score, which is inversely related to the degree of mucus discharge in histological sections of trachea stained for mucus glycoprotein with periodic acid Schiff/Alcian blue. Mucus hypersecretion of goblet cells was induced by ozone exposure and persisted for up to 5 h after exposure. Pretreatment with N-[2-¿4-(2,2-dimethyl-propionyloxy) phenyl-sulfonylamino¿ benzoyl] aminoacetic acid (ONO-5046), a specific neutrophil elastase inhibitor (200 mg/kg, intraperitoneally), significantly inhibited goblet cell hypersecretion both just after and 5 h after ozone-exposure, but the latter inhibition was not complete. In bronchoalveolar lavage fluid, ozone exposure significantly increased the number of neutrophils just after and 5 h after exposure, while ONO-5046 significantly inhibited the increase in neutrophils only 5 h after ozone-exposure. These results indicate that neutrophil elastase may play an important role in the ozone-induced tracheal goblet cell hypersecretion and influx of neutrophils.

Acute interstitial pneumonia induced by ONO-1078 (pranlukast), a leukotriene receptor antagonist.

A 62-year-old woman treated with pranlukast for 2 months developed interstitial pneumonitis with a high fever. A lymphocyte stimulation test was reactive to pranlukast. Her clinical symptoms improved with discontinuation of pranlukast and administration of systemic corticosteroid. To our knowledge, this is the first reported case of drug-induced lung disease involving a leukotriene. The steps that can be taken to promptly reach a diagnosis and to successfully treat this life-threatening condition are described.

Suppression of tuberculin reactivity during natural rubella. Observations with 54 patients.

Fifty-four patients with previously positive tuberculin reactions were followed for tuberculin sensitivity, between the incubation period of natural rubella and the 40th day after the onset of rash. In many instances, tuberculin sensitivity was partially or completely depressed beginning in the incubation period and extending for up to 4 weeks after rash onset. Two of 3 cases of subclinical rubella infection also showed this phenomenon. The highest incidence of negative reactions was 83% in the first 3 days after rash onset. A few subjects had a larger skin reaction to tuberculin than the baseline reading during the 2 to 5 weeks after rash onset.

[The combination of amoxicillin-clavulanic acid and ofloxacin in the treatment of multidrug-resistant Mycobacterium tuberculosis].

A 67-year-old [correction of 53] man with multidrug resistant tuberculosis (MDR-TB) had been persistently positive for acid-fast bacilli (AFB) both on sputum smear and also on culture with the Ogawa egg medium for 30 years since 1951. The case had been treated previously with isoniazid, rifampin, streptomycin, ethambutol, kanamycin, ethionamide, paraaminosalicylate and cycloserine; however, M. tuberculosis strains isolated from this patient acquired a high resistance to all of these agents. Then, a new regimen of chemotherapy, INH combined with ofloxacin (OFLX) and amoxicillin-clavulanic acid (AMPC/ CVA), was applied to the case. He was successfully treated with this regimen, and a marked decrease in the amount of AFB on smear as well as on culture was observed during the course of chemotherapy. No adverse effects were seen meanwhile. These data suggest that it is worth while to try a regimen containing AMPC/CVA and OFLX in the treatment of MDR-TB.

[A study on the prevalence of bronchial asthma in school children in western districts of Japan--comparison between the studies in 1982 and in 1992 with the same methods and same districts. The Study Group of the Prevalence of Bronchial Asthma, the West Japan Study Group of Bronchial Asthma].

UNLABELLED: The prevalence of bronchial asthma in school children was examined both in 1982 (55,388 children) and in 1992 (45,674 children) in 11 western districts of Japan. Both studies were conducted with the same Japanese version of a modified ATS-DLD children's questionnaire in the same districts. RESULTS: 1) The study in 1992 established a prevalence rate of 5.6% in males and 3.5% in females with an overall average of 4.6%, which was 1.4 times higher than that of 10 years ago. The higher prevalence was observed in every grade of school children and in all districts. 2) The study in 1992 showed no differences based on the grades of the school children were in. The prevalence rate in males was 1.6 times higher than that in females with fewer regional differences than in the 1982 study. 3) Higher prevalence rates were found in those who had histories of respiratory diseases during their infancy, family histories of allergic disease or who lived in urban areas. The prevalence rate was 13.3% in children living in urban areas with family histories of bronchial asthma. 4) The prevalence rate of wheezing was 5.2%, which was 1.3 times higher than that of 10 years ago. The rate had increased in every district, but it decreased as the children moved into higher grades.

[Relationship between PEF and SpO2 on acute asthma attack in children].

We evaluated the relationship between PEF and SpO2 on 126 acute asthma attacks of 52 asthmatic children (25 males, 27 females, age 6-17 yrs-old) whose PEF and SpO2 being measured either before or after inhalation of beta-agonist at out-patient clinic. In the whole age group over 6 yrs-old, values of %PEF were proportional to individual SpO2 (n = 76, R = 0.472, p < 0.001). However, the relationship between %PEF and SpO2 in the present study was different from that of the guideline proposed by WHO (Global Initiative for asthma, GINA), showing that the value of SpO2 corresponding to %PEF was higher in the present study than in GINA. Regarding the difference in age group, significant relationship between %PEF and SpO2 was observed in both lower (6-9 yrs-old) and middle age group (10-12 yrs-old) but not in older age group (over 12 yrs-old). Also, there was a significant relationship between %PEF and SpO2 in cases whose pulmonary function during stable condition showed no-obstructive change (FEV1.0% > 80%), but not in cases with obstructive change. On the other hand, averaged values of %PEF, SpO2, heart rate (HR), respiratory rate (RR) before inhalation of beta-agonist at out-patient clinic in cases with or without admission were 32.3% vs 50.0%, 93.0%, vs 95.0%, 115 bpm vs 100 bpm, and 27/min vs 25/min respectively, those difference being statistically significant. Although measurement of SpO2 is thought to be a useful index for assessing severity of childhood asthma exacerbation, clinician should recognize that value of SpO2 could be greater than 91% even though % predicted PEF is less than 60%. Especially in older age group, obstructive change during stable condition may disturb the relation of SpO2 to %PEF. In such cases, not only SpO2 but also PEF, which is objective index of airway obstruction, should be taken into account for assessing severity of exacerbation.

[Air pollution (NO2, suspended particulate material) and the number of acute hospitalization of patients with asthmatic attack].

There were many reports about the relationship between the air pollution and the incidence of asthma. In Japan some of the concentrations of air pollutants, for example, SO2, CO, have been reduced in these ten-twenty years. However the concentrations of suspended particulate material (SPM) and NO2 have not been reduced, and the incidence of bronchial asthma have been increasing gradually. The relationship between the concentrations of NO2, SPM and the number of patients admitted to our hospital because of asthmatic attack was studied. The concentration of each air pollutant was measured at the air quality monitoring stations in Minami-ku and Jonan-ku Fukuoka, Japan. Between Jan, 1988 and Dec. 1991, 3661 patients with asthmatic attacks were admitted to our hospital. The relationship between the monthly averaged one-hour mean value for a day, and monthly max. of one-hour mean. value for a day, and one-day max. value for a month of NO2 and SPM and the numbers of asthmatic attack patients admitted was evaluated. There was a statistically significant relationship between concentrations of NO2 and SPM levels and the numbers of asthmatic patients admitted aged 6 or less. However, there was no such a relationship when the patients were aged between 7 and 20. These results suggested that the airways of asthmatic patients in the age of 6 or less might be more sensitive to NO2 and SPM than that of those patients in the age of 7 to 20.

[A simple personal computer-based system for lung sound analysis].

Although lung sounds provide important information about the respiratory system, the analysis of lung sounds has not been widely used in clinical practice because of the complicated procedure involved. However, personal computer technology has made impressive strides in recent years. Today, practically all personal computer models on the market are equipped with the capacity for audio signal input and output. We developed a new computer system for lung sounds acquisition and analysis. The system hardware comprises only a personal computer and a microphone, and the software was developed for a widely used operating system (Windows 95). Our system can record, save, and replay lung sounds and analyze their time and frequency domains. To verify the accuracy of sound acquisition, we examined the frequency characteristics of the system as installed and utilized on 4 different machines. The characteristics were essentially flat throughout the 200-2,000 Hz spectrum within which almost all lung sounds were contained. We feel our system can serve as a simple and useful tool for lung sound analysis.

[Evaluation of sleep fragmentation by EEG spectrography in patients with obstructive sleep apnea syndrome].

Sleep fragmentation is considered to have a central role in the pathophysiology of sleep-disordered breathing. However, the evaluation of sleep fragmentation can be very troublesome work. We sought to evaluate sleep fragmentation in 10 patients with obstructive sleep apnea syndrome by utilizing fast-fourier transforms to render their sleep encephalograms as spectrograms (horizontal axis: time, vertical axis: frequency, color: power). Detailed 5-minute spectrograms revealed relatively uniform patterns of change in EEG spectra during and after apnea episodes. In non-REM sleep, delta activity during apnea was followed by alpha and beta activity during resumed breathing. In REM sleep, flat and low-power spectral patterns during apnea were followed by relatively weak alpha and beta activity during resumed breathing. In compressed, 1-hour views of the spectrograms, repeated apnea events appeared as vertical striped patterns of spectral change. These patterns were thought to be representative of sleep fragmentation. The spectrographic display of EEGs may be a very simple and easy method for the evaluation of sleep-fragmentation in sleep disordered breathing.

[The impact of obesity on oxygen desaturation in patients with sleep apnea/hypopnea syndrome].

We performed a cross-sectional investigation on the impact of obesity on clinical manifestations in patients with obstructive sleep apnea/hypopnea syndrome (SAHS). The subjects were 87 patients who underwent overnight polysomnography with an apnea/hypopnea index (AHI) of 15/h or more. We divided these patients into non-obese (N) and obese (O) groups based on the median value of the body mass index (BMI), 27 kg/m2. Subjective symptoms, sleep quality and AHI were similar in both groups, but every parameter related to oxygen desaturation was worse in group O than in group N. There was no difference in the mean duration of apnea events between the two groups. The rate of fall in oxygen saturation during apnea events was highly correlated to the BMI (r = 0.72; p < 0.00001). Accordingly, we concluded that profound desaturation in group O is due to a rapid fall in oxygen saturation during apnea events compared with group N. Anthropometric measurements revealed that the rate of fall in oxygen saturation was more related to abdominal circumference (AC) than the neck circumference (NC), which is contrasted with the finding that AHI was more related to NC than AC. This fact suggests that abdominal obesity may deteriorate oxygenation during apnea events and may therefore aggravate the risk of cardiovascular disease in patients with SAHS.

[Subcutaneous sarcoidosis of the extremities].

A 65-year-old man was referred to our hospital due to abnormal chest roentgenograms showing bilateral hilar enlargement with diffuse micronodular opacities. He presented with uveitis and elevated serum ACE and tested negative for tuberculin response. Transbronchial lung biopsies as well as bronchoalveolar lavage were performed and yielded a diagnosis of sarcoidosis. Several months later, the patient showed multiple subcutaneous nodules around the knee joints and elbow joints with exacerbation of intrapulmonary lesions. A skin biopsy revealed multiple foci of typical non-caseating epithelioid cell granulomata. These pulmonary and subcutaneous lesions rapidly resolved in response to the systemic administration of corticosteroids. Subcutaneous sarcoidosis may be a subacute variant of sarcoidosis associated with systemic involvement.

[Characteristics of bronchial asthma in the elderly].

To characterize asthma in the elderly, we compared asthma in patients aged over 70 without chronic obstructive pulmonary disease with that in patients in their twenties. In the elderly, 65.5% of the patients had developed asthma after they were fifty years old. The mean duration from onset of asthma was 21.4 years. Of cases in the elderly, 42.1% were severe, and 93.0% were chronic type. IgE was significantly lower in the elderly than in those in their twenties. Among the patients in their twenties, the severe cases had early onset and long duration. In the elderly, however, there were no correlations between severity and age at onset or duration. Severe cases in their twenties had more obstructive ventilatory dysfunction in the stable state than the mild cases. In the elderly, however, the mild cases had the same level of obstructive ventilatory dysfunction as the severe cases. The elderly patients who had more than twenty years duration had lower V50 and V25 than those who had a less than twenty-year history. Small airway obstruction was observed in long-standing cases. As asthma in the elderly causes obstructive ventilatory dysfunction in the stable state, elderly patients might easily develop respiratory failure, even during mild attacks.

[Prognosis of intractable asthma].

Forty-nine intractable asthma patients from January 1981 were divided into three groups. Group I consisted of patients still alive after ten years (January 1991) who were receiving decreased doses of steroids or no steroids at all. Group II patients were also alive, but the doses of steroids they were receiving were unchanged. Group III consisted of patients who had died during the ten years. Of the 49 patients, nine were in Group I, 13 in Group II and 17 in Group III. The condition of the other 10 patients was unknown. The mortality rate of the known 39 patients over 10 years was 43.6%, a very high rate. The groups of living patients (I + II) were younger than the patients in the dead group (III) and the latter patients had more obstructive ventilatory dysfunction in the stable state (FEV1.0/FVC%, and %FEV1.0 were 56.1% and 52.8%) in 1980. In the therapy carried out over the 10 years, antiallergic drugs and inhaled steroids were administered in order to decrease oral steroids in both Group I, II and III. In Group I, however, more patients had received immunotherapy (hyposensitization) or gold therapy than in Group II and III. There were more complications due to steroids during the ten years in Group II and III than in Group I. Aging and obstructive ventilatory dysfunction may be factors which worsen the prognosis of intractable asthma, and decreasing of the doses of oral steroids may be important to prevent complications.

[The relationships of mononuclear leukocyte beta-adrenergic receptors to aerobic capacity and exercise-induced asthma in asthmatic children].

beta-adrenaline receptors exist on peripheral mononuclear leukocytes as well as in lung tissue. We assessed the relationships of plasma catecholamine release by exercise to aerobic capacity and to exercise-induced asthma (EIA) in asthmatic children (Study 1). We then measured mononuclear leukocyte beta-adrenergic receptor densities at rest and assessed the relationships of the number of receptors to aerobic capacity, EIA, and bronchial responsiveness to acetylcholine (Study 2). Study 1: Eleven children (9 males, 2 females; 11-16 years old) with bronchial asthma participated in this study. The subjects underwent an incremental aerobic exercise test on a cycle ergometer to determine their aerobic capacity at the lactic threshold (LT) and VO2max. Each subject underwent an EIA test of which the intensity was 175% of LT, and plasma catecholamine concentrations were measured before and after exercise. A significant negative relationship was found between the degree of EIA and % change of plasma adrenaline concentrations to rest level (p < 0.05), and a significant positive relationship was found between VO2 max/wt and % change of plasma adrenaline concentrations (p < 0.05). Study 2: Twelve asthmatic children (10 males, 2 females; 11-16 years old) participated in this study. Aerobic capacity, and degree of EIA were also measured in each subject by the same method as that used in Study. 1. The number of mononuclear leukocyte beta-adrenergic receptors at rest was determined by (-) [125I]-iodocyanopindolol binding in each subject. A significant negative relationship was found between the number of adrenergic receptors and Max. % fall in FEV1.0 (p < 0.01), and a significant positive relationship was found between the number of adrenergic receptors and VO2max/kg (p < 0.001). These results suggested that a reduced adrenaline production and a reduced number of beta-receptors contributed to the pathogenesis of EIA.