Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients : a 4-year longitudinal study.

BACKGROUND: It is not certain whether inhaled corticosteroid (ICS) therapy reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. OBJECTIVE: To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on BMD in asthmatic patients. DESIGN: A 4-year longitudinal study. METHOD: Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/- 0.1 years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. RESULTS: The average period of BDP treatment was 7.7 +/- 2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 microg (range, 100 to 1,730 microg), and the frequency of SC-OCS was 1.9 +/- 2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, > 1,000 microg/d; n = 9) were not significantly different from those of patients receiving lower doses (ie, 2.5 courses per year; n = 9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie,

Long-term follow-up of patients with a history of near fatal episodes; can inhaled corticosteroids reduce the risk of death from asthma?

We retrospectively studied the use of inhaled corticosteroids in patients who experienced near fatal episodes (NFE) to determine whether such therapy reduces the risk of death. Forty-eight patients who had near fatal episodes of asthma between January 1981 and December 1989 were divided into two groups. Group A comprised 19 patients who received beclomethasone dipropionate (BDP) daily (mean dose of BDP:687 micrograms/day: 200-2,000) following NFE, and Group B, 28 patients who did not take BDP or who took less than 6 mg BDP/month. During the follow-up period (Group A:82.9 months, Group B:66.2 months), no patients in Group A died, but eight deaths occurred in Group B (mean period between near fatal episode and death was 31.5 months: 12-66). These results suggest that the regular use of inhaled corticosteroids, even at low doses, may reduce the risk of death in patients who experience NFE.

Duration of systemic corticosteroids in the treatment of asthma exacerbation; a randomized study.

OBJECTIVE: To determine an appropriate duration for a short course of oral steroids in cases of asthma exacerbations. SETTING: A 1,000 bed city hospital in Kobe, Japan. PATIENTS: Patients with asthma exacerbations who needed hospital admission. METHODS: Following an initial treatment with a 3-day course of intravenous methylprednisolone, patients were allocated to either a 1-week (1 W) or a 2-week (2 W) course of oral prednisolone (PSL, 0.5 mg/kg). OUTCOME MEASURES: Peak expiratory flow rate (PEF) and rate of unscheduled hospital visits and readmission. RESULTS: Twenty patients were enrolled (10 in 1 W, 10 in 2 W). Mean PEF just before starting oral PSL in 1 W and 2 W were 51 and 58% of each patient's best value. PEF was significantly improved and to a similar degree over the course of time in both 1 W and 2 W. The frequency of unexpected hospital visits during a 3-month period after discharge was similar (2 in 1 W and 2 in 2 W). No readmission occurred during the same period. CONCLUSIONS: Because both the 1-week and the 2-week course of oral PSL were equally effective in the treatment of asthma exacerbations, 1 week may be appropriate as the maximum duration of a short rescue course of oral steroids.

Influence of high dose inhaled steroids on hypothalamo-pituitary-adrenal axis function in Japanese patients with asthma: a comparison over the course of time.

Although the influence of high dose inhaled steroids on hypothalamo-pituitary-adrenal (HPA) function in patients with asthma has been extensively studied worldwide, there has been limited information on Japanese asthmatics, especially in terms of a prospective analysis of HPA function in the course of time. We analyzed the changes in HPA function using 2 serial short tetracosactrin tests (STT) separated by an interval of one year in 11 Japanese asthmatics who were treated with high dose inhaled steroids alone [beclomethasone dipropionate (BDP); mean dose 982 micrograms/day] during the period between 2 STTs. Mean values of plasma cortisol before administration of ACTH, maximum cortisol and the rise in cortisol in response to ACTH in the 2 STTs were 7.8, 20.5 and 12.7 micrograms/dl for the 1st test, and 8.9, 23.6 and 14.7 micrograms/dl for the 2nd test, respectively. Overall, there was no significant change in the course of time in each of these 3 values. Although the results of the 1st STT proved to be abnormal in 3 patients who had been receiving systemic steroids before their 1st STT, they improved uniformly in their 2nd STT. In the remaining 8 patients, who had never received systemic steroids, 4 patients showed improvements while the other 4 showed deterioration in HPA function in their serial STTs over the course of time. The dose of BDP was 800 micrograms/day in the former 4 patients, while it was 1,200 micrograms/day in the latter 4. Furthermore, only one patient, in whom BDP had been increased from 800 micrograms/day to 1,200 micrograms/day between the 2 tests, developed an abnormal response in the 2nd STT. On the other hand, one patient whose BDP dose was increased from 800 micrograms/day to 1,600 micrograms/day showed an improvement in HPA function in the 2nd test. These results indicate that the threshold dose of BDP which may cause HPA suppression in Japanese asthmatics lies between 800-1,200 micrograms/day, although there is a large inter-individual variation in terms of such doses.

[A case of adult respiratory distress syndrome likely due to measles and Mycoplasma pneumoniae].

We described a case of adult respiratory distress syndrome (ARDS) likely due to measles and Mycoplasma pneumoniae. A 24-year-old, previously healthy man was referred to our hospital because of respiratory arrest. He was unconscious and cyanotic. He had erythematous and polymorphic eruptions of his extremities and trunk, but his face was spared. His chest roentgenogram showed consolidation with air bronchograms affecting the whole bilateral lungs. After mechanical ventilation with positive end-expiratory pressure and administration of intravenous hydrocortisone and protease inhibitor "urinastatin" and so on, the patient recovered from his critical condition. No attributable organisms were isolated from the specimens investigated in his acute phase. Serological examinations of the specific IgM antibody to measles during the course indicated a recent measles infection. Mycoplasma pneumoniae indirect hemagglutination test rose from a titre of less than 1/40 to 1/60. ARDS is a rare complication of measles or Mycoplasma pneumoniae infection. Moreover he received measles vaccine before 1970 in Japan, so this case was suspected to be atypical measles.

[Legionella longbeachae pneumonia in a gardener].

A 52-year-old male gardener, who traveled to Guam Island several days ago, was admitted to our hospital with fever, cough and dyspnea. His chest X-ray showed bilateral infiltration and he was severely hypoxic and hypotensive on admission. He died of multiple organ failure in spite of intensive treatment with mechanical ventilation antibiotics including erythromycin. Legionella longbeachae serotype 1 was isolated from his sputum and was regarded as the etiologic agent. Legionella longbeachae was not isolated from the same type of leaf mold that he used as potting soil. This is the first case of Legionella longbeachae pneumonia from whom the organism was isolated in Japan.

[A strain of Pseudomonas vesicularis isolated from shower hose which supports the multiplication of Legionella].

In Japan, a fatal case due to Legionella micdadei was first recognized in our laboratory in 1986. On the epidemiological study just after the case, no Legionella was detected from the environmental samples of the patient's residence, such as shower water, tank water and so on. In the course of prospective investigations, no Legionella was isolated, but many organisms were grown on BCYE alpha and MWY agar plates. In the retrospective study, one of these organisms was found to support satellite growth of Legionella on BCYEagar without L-cysteine. This was the isolate from the shower hose and identified as Pseudomonas vesicularis with the biochemical and DNA-DNA hybridization test. And P. vesicularis type strain ATCC11426 also supported satellite growth of Legionella. Especially in the water supply system, the existence of P. vesicularis seemed to be effective on the growth of Legionella. It must be taken into consideration that efforts made to isolate the nutrient produced organisms as well as Legionella are needed.

[Evaluations of MTD and Amplicor Mycobacterium for direct detection of Mycobacteria from clinical specimens].

MTD (GEN-PROBE AMPLIFIED MYCOBACTERIUM TUBERCULOSIS DIRECT TEST) for Mycobacterium tuberculosis, and Amplicor Mycobacterium for Mycobacteria (AMP-M. tb for M. tuberculosis, AMP-M. av for M. avium and AMP-M. in for M. intracellulare) were used for the detection of relevant Mycobacterium. Their sensitivity and specificity were evaluated. Total 244 clinical specimens including 164 sputa were examined by the above two tests. The results were compared with those obtained by the conventional methods. Of 244 samples, number of the M. tuberculosis positive samples by microscopy, cultural test, MTD and AMP-M. tb were 32, 33, 38 and 35, respectively. Among 33 culture positive samples, 25 were MTD positive and 26 were AMP-M. tb positive. Therefore, sensitivity of MTD and AMP-M. tb were 75.8% and 78.8%, and their specificity were 93.8% and 95.7%, respectively. When only sputa were used for the tests as the clinical specimens, both sensitivity of MTD and AMP-M. tb were increased to 94.4%. For MAC, positive samples of M. avium complex by culture, M. avium by AMP-M. av and M. intracellulare by AMP-M. in were 13, 16, and 8, respectively. Sensitivity and specificity of AMP-M. av/M. in were 100% and 95.2%, respectively. Clinical findings of the patients whose MTD tests were positive but negative by culture were reexamined. Three of 9 specimens were also positive in AMP-M. tb. From the records of the isolations of tubercle bacilli or other important pathogens from the other kind of clinical specimens, smear tests and patients' response to tuberculosis chemotherapy, four of 9 specimens were confirmed as true positive, three were suspected as positive, and two other specimens were false positive which might be caused by contamination. From these observations, it could be concluded that MTD and AMP-M. tb are more sensitive than conventional culture method, and MTD is more sensitive than AMP-M. tb but needs more careful treatment to avoid the contamination.

[Endoscopic approach to pulmonary diseases: Transbronchial needle aspiration].

Transbronchial needle aspiration (TBNA) is a bronchoscopic technique to obtain cytologic and histologic specimen from deep site of bronchial wall. We investigated the utility and safety of TBNA in 200 patients who had mass lesions in the lung or in the mediastinum. 101 patients had submucosal or peribronchial malignant lesions (central malignancy) and TBNA was the only diagnostic method in 28 patients (28%). 39 patients had peripheral malignant lesions (peripheral malignancy) and TBNA was the only diagnostic method in 12 patients (31%). The other 60 patients had benign lesions and TBNA was diagnostic in only 5 patients (8%); bronchogenic cyst in 2, tuberculous lymph adenitis in 1, parathyroid adenoma in 1 and lung abscess in 1. In central malignancy, the yield of TBNA as exclusive means of diagnosis was higher for mediastinal tumor than for lung cancer. In peripheral malignancy it was higher for metastatic lung tumor than for primary lung tumor. In order to stage patients of lung cancer, we sampled 39 lymph nodes and 21 of them were proved to be positive. TBNA was thought to be of greatest value in the diagnosis of peritracheal mediastinal tumor and peribronchial metastatic lung tumor and in the staging of lung cancer. We used 19-gauge transbronchial histology needle in 8 patients and 2 cases were diagnostic. Low diagnostic yields were probably due to the lack of our experience and it was expected that training on this technique would increase diagnostic utility of the histology needle. No significant complications occurred and all patients tolerated TBNA well.

[A resected case of mediastinal tuberculous lymphadenitis with pericostal tuberculosis].

A case of 22-year-old female with mediastinal tuberculous lymphadenitis and pericostal tuberculosis was reported. Her complaint was right chest pain and subcutaneous mass on the right chest wall. Chest contrast CT showed right paratracheal lymph node swelling with central low density area and surrounding rim enhancement, which has been reported as typical characteristics of mediastinal tuberculous lymphadenitis. Pigeon-egg sized subcutaneous mass with fluctuation was palpable on the right sternal border and the smear of its content showed acid-fast bacilli. In spite of two months therapy with antituberculous drugs, both masses were unchanged in size. The lesions resected surgically, were both encapsulated abscesses containing yellowish pus, and microscopic examination of these specimen disclosed the finding of tuberculosis. Mycobacterium tuberculosis was cultured from contents of both masses. After nine months of anti-tuberculous therapy, no sign of recurrence is observed until now. Both masses were discontinuous and the possibility of lymphangitic spread of organism was speculated as its etiology.

[Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer].

Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1 +/- 2.9 x 10(6)/kg (n = 10) and 3.1 +/- 1.5 x 10(5)/kg (n = 8), respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed.

[A comparison of a 3 day course with a 2 week course of oral prednisolone in patients with chronic asthma].

To investigate an appropriate duration of short course of a oral prednisolone (PSL), we compare the results of a 3 day course of PSL (3D) with those of a 2 week course of PSL (2W) in 20 patients with chronic asthma. All subjects had been inhaling beclomethasone dipropionate (BDP, mean daily dose: 1325 micrograms), and had been self-monitoring their peak expiratory flow rate (PEF) for at least 6 months. Mean +/- SE of the best PSL-induced PEF in 2W (2W-best) was not different from that in 3D (397 +/- 29 and 356 +/- 23 L/min, respectively, p = 0.26). Mean weekly morning PEF/2W-best before and 1, 2, 3 and 4 weeks after PSL was 60, 76, 80, 76 and 76% in 2W, and 63, 73, 67, 67 and 65% in 3D, respectively. Both changes over the course of time were significant. The frequency of emergency room visits and/or unscheduled hospital visits was not significantly different between 2W and 3D. However, both the frequency of use of inhaled beta 2 agonists and the symptom score significantly decreased only in 2W. Seven patients (35%) did not need additional oral PSL during the 4-week period after initiating 3D, and among these patients, emergency room visits and/or unscheduled hospital visits were completely controlled. In conclusion, although the effect of 3D was inferior than that of 2W, it was a sufficient duration in 35% of the patients, and thus, may be appropriate as a initial duration of rescue course of oral steroids.

[Impact of discontinuing peak flow monitoring in stable asthma].

We conducted a prospective study to examine the influence of discontinuing peak flow monitoring (PFM) in stable asthmatics who had already been properly educated and were monitoring their own peak expiratory flows (PEF). All subjects had been performing PFM for at least 3 months prior to their entry into the study, and PFM was then stopped for a period of 3 months. Comparisons of endpoints were made between a period of 3 months prior to, and after discontinuing PFM. Forty patients with a mean age of 52 were studied. Only one patient experienced a single emergency room visit either before or after discontinuing PFM. Short courses of oral steroids were administered in 6 patients (15%), both before and after discontinuing PFM. There was no significant change in pulmonary function, beta 2-agonist use and asthma symptoms during a 3-month period before and after discontinuing PFM. These results suggest that simply continuing PFM in stable, educated asthmatics may have little impact on asthma control, although its long term influence should be carefully examined.

[Concurrent chemoradiotherapy followed by surgery for advanced stage III non-small cell lung cancer (NSCLC)].

Forty-two patients with stage IIIA (bronchoscopically T3 and/or bulky N2) and stage IIIB NSCLC were treated with concurrent chemoradiotherapy (CRT). Treatment consisted of CDDP, 20 mg/m2 and etoposide, 40 mg/m2 by continuous infusion (day 1-5) of weeks 1 and 5 simultaneously with chest radiotherapy (RT), 50 Gy, 2 Gy/Fx, 5 Fx/week. Surgery was attempted 3-5 weeks after RT in pts clinically downstaged. Between 10/90 and 12/92, 43 previously untreated pts were enrolled and 42 were eligible. Pts characteristics were: male/female = 37/5; mean age, 61 yrs (range, 31-74 yrs); stage IIIA/IIIB = 10/32; 15 adenocarcinoma, 24 squamous cell, 2 large cell, 1 unclassified; PS 0/1/2 = 11/24/7. Excluding 1 ineligible pts, 42 pts were evaluated for CRT response. The response rate was 81% (1 CR, 33 PR, 5 NC, 1 PD, 2 NE). Clinical downstaging was achieved in 20 pts (48%). Twenty-one pts (50%) received surgery and 19 of them were completely resected. In 7 resection specimens, no tumor was observed. Toxicity of CRT was well tolerable (Grade 4 leukopenia, 15%; Grade 2-3 esophagitis, 15%). We conclude that this intensive combined modality therapy is acceptable and appears to increase the response rate as well as resectability. Prospective randomized studies should be conducted for further evaluation of this treatment modality.

[Outpatient chemotherapy for advanced lung cancer].

We reviewed the records of outpatient chemotherapy for advanced lung cancer in our institution. Thirty-two patients received 122 courses of cisplatin-free chemotherapy as outpatient treatments. Before outpatient treatment, every patient received the first chemotherapy as an inpatient treatment and the dose of cytotoxic drugs was reduced accordingly when side effects were judged to be untolerable. Only 1 patient needed hospitalization because of pneumonia with grade IV neutropenia. The overall response included partial responses (PR) 18%, no change (NC) 55%, progressive disease (PR) 11% and the median survival from the start of outpatient chemotherapy was 384 days. The monthly average cost of medical care per inpatient was more than three times as high as that of outpatients. Cisplatin-free chemotherapy for advanced lung cancer should be given as outpatient treatment not only to maintain the quality of life of patients, but also to restrain the total cost of medical care and to use hospital beds efficiently.