Lung Sound Analysis Is Useful for Monitoring Therapy in Patients With Bronchial Asthma.

BACKGROUND AND OBJECTIVE: Lung sound analysis (LSA) has been reported to be useful for predicting airway obstruction and inflammation in patients with bronchial asthma. Objectives: We examined whether the exhalation-to-inhalation sound pressure ratio in the middle frequency range (200-400 Hz) (E/I MF) is useful for monitoring therapy in patients with asthma. METHODS: The study population comprised 84 patients with mild to moderate asthma whose LSA data were available before and after 1 year of daily treatment with (budesonide 800 µg). We analyzed whether the E/I MF before and after treatment was associated with the fractional exhaled nitric oxide (FeNO) level, sputum eosinophil percentage, respiratory function, and airway hyperresponsiveness. RESULTS: Prior to treatment with budesonide, the E/I MF was significantly correlated with respiratory function, airway hyperresponsiveness, FeNO, and sputum eosinophil percentage. The cutoff values for the E/I MF to detect the abnormalities of respiratory function, FeNO, and sputum eosinophil percentage were 0.367, 0.358, and 0.363, respectively. With respect to the reference value, the E/I MF improved significantly in patients whose respiratory function and FeNO benefited from therapy with budesonide compared with patients whose respiratory function did not benefit from budesonide (odds ratios of 6.39 and 4.78, respectively). According to the multivariate analysis, patients whose E/I MF did not improve had a longer history of smoking (P=.038), poorer posttreatment respiratory function (P=.028), and higher posttreatment FeNO (P=.0095). CONCLUSIONS: Similar to respiratory function and FeNO, E/I MF based on LSA is a useful indicator for monitoring the efficacy of therapy in asthmatic patients.

Lung sound analysis is useful for monitoring therapy in patients with bronchial asthma

Background: Lung sound analysis (LSA) has been reported to be useful for predicting airway obstruction and inflammation in patients with bronchial asthma. Objectives: We examined whether the exhalation-to-inhalation sound pressure ratio in the middle frequency range (200-400 Hz) (E/I MF) is useful for monitoring therapy in patients with asthma. Methods: The study population comprised 84 patients with mild to moderate asthma whose LSA data were available before and after 1 year of daily treatment with (budesonide 800 μg). We analyzed whether the E/I MF before and after treatment was associated with the fractional exhaled nitric oxide (FeNO) level, sputum eosinophil percentage, respiratory function, and airway hyperresponsiveness. Results: Prior to treatment with budesonide, the E/I MF was significantly correlated with respiratory function, airway hyperresponsiveness, FeNO, and sputum eosinophil percentage. The cutoff values for the E/I MF to detect the abnormalities of respiratory function, FeNO, and sputum eosinophil percentage were 0.367, 0.358, and 0.363, respectively. With respect to the reference value, the E/I MF improved significantly in patients whose respiratory function and FeNO benefited from therapy with budesonide compared with patients whose respiratory function did not benefit from budesonide (odds ratios of 6.39 and 4.78, respectively). According to the multivariate analysis, patients whose E/I MF did not improve had a longer history of smoking (P=.038), poorer posttreatment respiratory function (P=.028), and higher posttreatment FeNO (P=.0095). Conclusion: Similar to respiratory function and FeNO, E/I MF based on LSA is a useful indicator for monitoring the efficacy of therapy in asthmatic patients (AU)

Introducción: El análisis de los sonidos pulmonares ha demostrado ser una prueba de utilidad para objetivar la presencia de obstrucción e inflamación en las vías respiratorias de pacientes con asma bronquial. Objetivos: Hemos evaluado si el cociente sonido inspiración-espiración por presión en el rango de frecuencias medias, de 200 a 400 Hz, (E/I MF) tenía utilidad en la evaluación de la respuesta al tratamiento en pacientes con asma bronquial. Métodos: El estudio incluyó 84 pacientes con asma leve o moderada que tuvieran registros de LSA antes y tras un año de tratamiento con 800 μg de budesonida inhalada. Analizamos si los cambios en E/I MF tras el tratamiento se correlacionaban con los cambios en los niveles de óxido nítrico en aire exhalado (FeNO), el porcentaje de eosinófilos en muestras de esputo inducido, la función pulmonar y la hiperreactividad bronquial. Resultados: Antes de iniciar el tratamiento con budesonida inhalada, el cociente E/I MF se correlacionaba significativamente con la función pulmonar, la hiperreactividad bronquial, los niveles de FeNO y el porcentaje de eosinófilos en las muestras de esputo. Los puntos de corte del cociente E/I MF para detectar valores anómalos en la función pulmonar, los niveles de FeNO, y el porcentaje de eosinófilos en esputo eran 0,367, 0,358 y 0,363 respectivamente. El cociente E/I MF mejoraba significativamente en el grupo de pacientes en los que la budesonida inhalada inducía cambios significativos en la función pulmonar o en los niveles, con respecto a los valores de referencia apropiados comparados con los de los grupos de pacientes que no presentaban mejoría en estos parámetros (odds ratios de 6,39 y 4,78, respectivamente). En un análisis multivariante los pacientes que no presentaban mejoras significativas en el cociente E/I MF presentaban una historia de tabaquismo activo significativamente más larga (p=,038), unos niveles de función pulmonar tras tratamiento significativamente más bajos (p=,028), y paralelamente unos niveles de FeNO, tras tratamiento, más elevados (p=,0095). Conclusiones: Al igual que la función pulmonar y los niveles de FeNO, el cociente E/I MF obtenido mediante el LSA es un indicador útil para evaluar la eficacia del tratamiento en pacientes con asma bronquial (AU)

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.

[Pollen surveys in Sapporo for 6 years during 1992 to 1997].

We carried out pollen surveys for 6 years from 1992 to 1997. The method of pollen survey studied was based on the standardization board of air born pollen survey and pollen information in Japan. The pollen samples were collected in Nishioka-area of Toyohira-ku, and Kawazoe-area of Minami-ku in Sapporo. As the pollen sample device. IS Rotary pollen trap was used at Nishioka-area during 1992 to 1994 and at Kawazoe-area in 1993, and Durham's pollen trap was used at Kawazoe-area during 1995 to 1997. The yearly pollen counts were highly fluctuated in trees, particularly Yew (Taxus spp.), Alder (Alnus spp.), Birch (Betula spp.), Pine (Pinus spp.), Fir (Abies spp.), than in Grasses (Gramineae) and Weeds (Polygonaceae, Plantago spp., Artemisia spp., Chenopodiaceae). In addition, the starting date of pollination was widely fluctuated year by year in trees. For instance, the pollen of Birch was confirmed on April 13 in 1993, as the first day in Nishioka-area, while it was on April 28 in 1994. It should be considered that the pollen counts and the starting date of pollination were highly dependent on the weather condition of the previous year and the current year.

[The pollen survey and dynamic statistics of patients with allergic rhinitis in Hakodate].

We have investigated the pollen survey (1994-1998) and dynamic statistics of patients with allergic rhinitis (1999-2000) in Hakodate, which is located southern part of Hokkaido. We have noted the pollen dispersion of Cryptomeria japonica, Cupressaceae, white birch, Gramineae and Artemisia. Especially, a lot of dispersion of Cryptomeria japonica has been noted in April. Concerning the dynamic statistics of patients with allergic rhinitis, we have investigated the 192 patients with allergic rhinitis in Hakodate municipal hospital. There has been a lot of pollinosis in March, April, May and September. Frequency of positive reaction to the specific IgE have been 38.0% of house dust, 16.9% of Artemisia, 13.2% of Gramineae, 10.3% of white birch, 9.0% of Cryptomeria japonica and 6.9% of cat in 379 subjects. In conclusion, we have noted that Cryptomeria japonica and white birch in addition to Gramineae and Artemisia are becoming more important antigen in patients with pollinosis in Hakodate, south part of Hokkaido.

[Long-term study of airborne allergic pollen count, C. Japonica and cupressaceae in Japan].

We have investigated the distribution of airborne pollen at the different eleven points in Japan from 1987 to 1998 using gravity sampler. To clarify the characteristics causative pollen for Japanese cedar pollinosis, we examined annual change of pollen counts, dispersing period and geographical difference of C. japonica and Cupressaceae pollen. C. japonica pollen occupied much more in Central Japan and Cupressaceae in the west of Japan than the other area. In Hamamatsu City, both of pollen counts were most of all and we found a tendency that the more pollen counts the longer dispersing period. As they reported that at the starting day of pollen in this method some patients had already suffered from allergic symptoms, we considered pollen grains were dispersing in spite of being continuously captured. In these twelve years we found that patients with Japanese pollinosis are exposured by causative agents during about 100 days every spring. But we could not observe the trend of increasing pollen counts and earlier starting day because of global warming. Further more we found that the pollen counts of C. japonica in autumn was increasing since 1994. As one of the factors of increasing patients with pollinosis, we thought that total exposure period of causative pollen every year were longer than that of 1980s.

[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.

[Clinicopathological study of cases with Mycobacterium szulgai infection].

Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis, Mycobacterium avium complex, or Mycobacterium kansasii. There are, however, other slow-growing mycobacteria which can cause pulmonary infection. Mycobacterium szulgai, first reported in 1972, is a scotochromogenic species which can affect human lungs, although human-to-human spread of infection is thought to be unlikely. We have recently treated three cases of middle-aged to elderly persons (45-87 year-old), two of them had underlying diseases (one with intrapulmonary and the other with extrapulmonary). All patients had constitutional symptoms (cough, sputum, dyspnea), and chest roentgenograms demonstrated either cavitation with scattered nodules or peripheral infiltrates predominantly in upper lobes, resembling pulmonary tuberculosis. In two cases, M. szulgai was identified by using DNA-DNA hybridization method. The in vitro susceptibility of M. szulgai to antimycobacterial drugs was better than that of M. avium complex, and it was resistant only to paraaminosalicylate, cycloserine, and partially to isoniazid. Pulmonary disease of three patients were successfully treated with a combination of multiple antimycobacterial agents including rifampin, ethambutol, isoniazid, or streptomycin.

[Long-term effects of bicycle-ergometry training on exercise endurance and dyspnea in patients with chronic pulmonary emphysema].

Exercise reconditioning has long been considered an essential component of the pulmonary rehabilitation regime. To investigate the long-term effects of exercise training on exercise endurance and dyspnea in patients with chronic pulmonary emphysema (CPE), we developed a supervised exercise program using bicycle ergometers. Nineteen patients (mean age: 67) with moderate to severe airflow limitation (average FEV1/FVC, 39.8%) were enrolled in a predominantly outpatient rehabilitation program. After their lactate thresholds were measured by an incremental symptom-limited maximum test, patients engaged in exercise training 15 to 30 minutes per day in an arbitrary frequency and at a work rate at or below their lactate threshold (average: 20.1 w). No significant improvements were observed in resting pulmonary function, blood gas, nutrition, or systemic muscle volume. After long-term exercise training (average period: 33 months; average frequency: 6.5 times per month, individually), the patients demonstrated significantly improved exercise endurance and relief of their dyspnea during exercise. These findings provide a physiologic rationale for long-term exercise training by patients with CPE.

[Sarcoidosis presenting as a diffuse micronodular shadow on a chest radiograph].

A 36-year-old man was admitted to our hospital with chest-radiographic findings of diffuse ground-glass shadows in both lungs. A chest CT scan revealed disseminated micronodules with mediastinal lymphadenopathy. Histological examination of a transbronchial lung-biopsy specimen showed non-caseous epithelioid cell granulomata. Marked lymphocytosis and an abnormally high CD 4/CD 8 ratio was found in bronchoalveolar lavage fluid. These findings suggested a diagnosis of sarcoidosis despite the atypical radiographic findings.

[Cough variant asthma among patients with chronic persistent cough and its clinical outcome].

Thirty-nine patients with chronic persistent cough continuing more than eight weeks were examined regarding to their airway responsiveness to methacholine challenge using the Astograph (TCK-6100H, Chest Corp. Japan). Of these, twenty-three individuals (59%) had airway hyperresponsiveness, leading to diagnose as having cough variant asthma (CVA). Patients with CVA had a higher percentage of eosinophils in peripheral blood and a lower forced expiratory volume in one second than those in non-CVA group. Furthermore, four patients (17%) developed the classic signs and symptoms of asthma, whereas 7 cases (30%) resolved their cough without further treatment and 12 cases (52%) continued to have CVA. These data suggested that a significant proportion of patients with chronic persistent cough had CVA and some of them may develop to classic wheezing asthma.

[Respiratory failure based on pulmonary tuberculosis sequelae and its management].

According to the complexity of pathological change of pulmonary tuberculosis sequelae (TB seq), on which respiratory failure based shows the higher incidence of marked degree of hypoxemia and hypercapnia than that based on chronic pulmonary emphysema (CPE). In TB seq, pulmonary artery mean pressure is higher, nocturnal oxyhemoglobin desaturation is much lower than in CPE. Also hypoxemia on exercise is lower, and oxygen inhalation for this hypoxemia is more effective than in CPE. The most effective therapy is continuous oxygen therapy. Home oxygen therapy has improved the prognosis and quality of life (QOL) of patients with respiratory failure based on TB seq. Artificial positive pressure ventilation (TIPPV) with intubation or tracheotomy is carried out for patients with severe hypercapnia and respiratory acidosis. Recently, early application of nasal mask ventilation (NPPV) on patients with TB seq has prohibited acute exacerbation of chronic respiratory failure. And also for patients with severe hypercapnia, NPPV with BIPAP method is effective for their QOL. Comprehensive respiratory rehabilitation is also successfully applied for their management.

[Clinical efficacy of sulbactam/ampicillin in comparison with cefotiam in the treatment of elderly patients with pneumonia].

Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the elderly at 13 National Hospitals of Kyushu island. 37 patients received SBT/ABPC 3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d. for 7 to 14 days. 1. 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety. No statistical differences were noted in the patients' backgrounds of either group. 2. The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2% (17/23 cases). This was found to be statistically significant (Fisher's exact test: p < 0.05). 3. 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM) showed bacterial elimination. 4. No side effects were observed in the study. 5. Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and 3.2% (1/31 cases) for CTM. The major adverse events were mild elevation of GOT, GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM. No statistical differences were noted in both groups. These results are consistent with SBT/ABPC as a highly effective antibiotic in the treatment of elderly patients with pneumonia.

[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.

[Three cases of tuberculous mediastinal lymphadenitis].

Mediastinal lymph node involvement is uncommon in intrathoracic tuberculosis. We report three cases of this disease, each of which had a different clinical course. Chest CT scans showed preferential involvement of right paratracheal nodes, central areas of relatively low density with peripheral rim enhancement after injection of contrast medium. Specimens obtained by mediastinoscopy and fiberoptic bronchoscopy revealed acid-fast bacilli in all cases. In view of its relative frequency, tuberculous mediastinal lymphadenitis in adults must be distinguished from other causes of mediastinal masses.

[Diffuse tracheobronchial amyloidosis with airflow limitation and repeated pneumonias].

A 67-year-old man was first admitted to our hospital complaining of a productive cough, and repeated episodes of pneumonia in different sites. Physical examination revealed expiratory wheezing and airflow limitation wlas documented with lung function tests. A chest X-ray film showed patchy pneumonic infiltrates. Chest computed tomography revealed a marked thickening of the tracheal and bronchial wall with linear calcification. Fiberoptic bronchoscopy revealed a diffuse infiltrative process in the tracheobronchial tree, which uniformly reduced the bronchial lumen. Bronchial biopsy specimens showed amyloid deposits with focal calcification, which was confirmed by Congo red and Dylon staining. Extensive examinations including rectal biopsy were negatie for systemic amyloidosis. We suggest that diffuse tracheobronchial amyloidosis should be included in the differential diagnosis of repeated pulmonary infections with airflow obstruction.

[Exertional hypoxemia evaluated by pulse oximetry in patients with interstitial lung diseases].

The pattern of change in arterial oxyhemoglobin saturation (SpO2) measured by pulse oximetry (PO) during exercise, including daily activities, was studied in 23 patients with interstitial lung disease (ILD), 19 of whom had idiopathic pulmonary fibrosis, 3 collagen vascular disease, and 1 BOOP. Hypoxemia, as detected by PO appeared without dyspnea at the beginning of exertion or at a mild workload. Exercise usually induced significant changes in the same fashion first in heart rate, then in SpO2, and then in dyspnea, but stair climbing had a different pattern. Workload at the lactate threshold (LT) and symptom-limited maximal exercise (SL) in a bicyclergometer incremental exercise test correlated well with distance walked in a 10-minute walking test (10-eMD) (p < 0.01). Similarly, the degree in desaturation in each exercise test was closely correlated (p < 0.01). Exertional hypoxemia was more prominent in patients with ILD than in those with chronic pulmonary emphysema. Nevertheless, dyspne changed less per change in SpO2 in ILD patients. We conclude that prolonged monitoring of SpO2 by PO will disclose the presence of exertional desaturation in ILD patients.

[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.