Masahiro Shirai

Alterations in Smoking Habits Are Associated With Acute Eosinophilic Pneumonia

BACKGROUND Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, and pulmonary eosinophilia. The etiology of AEP remains unknown, but several studies have proposed a relationship between cigarette smoking and AEP. However, most studies showing this possibility are single-case reports, and cigarette smoke has not been fully validated as a causative agent of AEP in a large series of patients. The present study was conducted to clarify the etiologic role of cigarette smoking in AEP, with special reference to alterations in smoking habits. METHODS We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test. RESULTS Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 +/- 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 +/- 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested. CONCLUSION These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.

Intravenous Immunoglobulin Therapy for Refractory Interstitial Lung Disease Associated with Polymyositis/Dermatomyositis

Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.

Mycobacterium avium complex disease: prognostic implication of high-resolution computed tomography findings

To evaluate the prognostic implications of computed tomography (CT) findings in assessing responses to treatment in Mycobacterium avium complex (MAC) pulmonary disease without underlying lung disease, high-resolution (HR)CT findings were correlated based on the results of sputum conversion after anti-MAC therapy. A total of 59 patients underwent HRCT before treatment and the therapeutic efficacy was evaluated by the results of sputum conversion. Atelectasis, cavities and pleural thickening on HRCT were significantly more frequent and extensive among patients in the sputum nonconverted group than among those in the converted group. Furthermore, bronchiectasis was also significantly more extensive among patients in the nonconverted group, even though there was no significant difference in frequency between these two groups. These results suggest that high-resolution computed tomography findings are good predictors of response to treatment in Mycobacterium avium complex pulmonary disease.

Efficacy of Clarithromycin and Ethambutol for Mycobacterium avium Complex Pulmonary Disease. A Preliminary Study

RATIONALE Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen. OBJECTIVES To compare a three-drug regimen (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung disease. METHODS In a preliminary open-label study, we randomly assigned newly diagnosed, but as-yet untreated, patients with disease caused by Mycobacterium avium complex without HIV infection to either the three-drug or the two-drug regimen for 12 months. The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment. Patient data were analyzed using the intention-to-treat method. MEASUREMENTS AND MAIN RESULTS Of 119 eligible patients, 59 were assigned to the three-drug regimen and 60 to the two-drug regimen. The rate of sputum culture conversion was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence interval, -32.1 to 3.4]). The incidence of adverse events leading to the discontinuation of treatment was 37.2 and 26.6% for the three-drug and the two-drug regimens, respectively. CONCLUSIONS This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin, ethambutol, and rifampicin for Mycobacterium avium complex lung disease. Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000002819).

Drug Lymphocyte Stimulation Test in the Diagnosis of Adverse Reactions to Antituberculosis Drugs

BACKGROUND Tuberculosis (TB) is a worldwide infectious disease. Recently, standard therapy has become very effective for treating patients with TB; however, as a result of this powerful regimen, serious side effects have become an important problem. The aim of this prospective study was to evaluate the usefulness of the drug lymphocyte stimulation test (DLST) to determine anti-TB drugs causing side effects. METHOD Four hundred thirty-six patients with TB were admitted to our hospital for treatment between January 2002 and August 2007. DLST was performed in patients who had certain adverse drug reactions during TB treatment. The causative drug was identified by the drug provocation test (DPT). The tested drugs were mainly isoniazid (INH), rifampin (RIF), ethambutol (EMB) and pyrazinamide (PZA). RESULTS Of 436 patients, 69 patients (15.8%) had certain adverse drug reactions to anti-TB drugs. Of the 261 agents that underwent the DLST and DPT, 28 agents (10.7%) in 20 patients (28.9%) were positive by DLST, and 67 agents (25.7%) in 46 patients (66.6%) were identified as causative drugs by DPT. The sensitivity of DLST was only 14.9% for all drugs (INH, 14.3%; RIF, 13.6%; EMB, 14.3%; PZA, 0%). CONCLUSIONS DLST offers little contribution to the detection of causative agents in patients with adverse anti-TB drug reactions.

Usefulness of serum procalcitonin levels in pulmonary tuberculosis

There are very few data on serum procalcitonin (PCT) levels in pulmonary tuberculosis (PTB) patients who are negative for HIV. We assessed serum PCT in consecutive patients diagnosed with pulmonary tuberculosis or community-acquired pneumonia (CAP) on admission to discriminate between PTB and CAP, and examined the value of prognostic factors in PTB. 102 PTB patients, 62 CAP patients, and 34 healthy volunteers were enrolled. Serum PCT in PTB patients was significantly lower than in CAP patients (mean±sd 0.21±0.49 versus 4.10±8.68 ng·mL−1; p<0.0001). By receiver-operating characteristic curve analysis, serum PCT was an appropriate discrimination marker for PTB and CAP (area under the curve 0.866). PTB patients with ≥0.5 ng·mL−1 (normal cut-off) had significantly shorter survival than those with <0.5 ng·mL−1 (p<0.0001). Serum PCT is not habitually elevated in HIV-negative PTB patients and is a useful biomarker for discriminating between PTB and CAP; however, when serum PCT is outside the normal range, it is a poor prognostic marker.

Clinicopathological features of chronic hypersensitivity pneumonitis

Objective: Only limited information exists concerning the clinical and pathological features of chronic hypersensitivity pneumonitis (HP) in Japan and elsewhere. We present data on clinicopathological features of chronic HP obtained through a Japanese nationwide survey.

The influence of ovarian hormones on the granulomatous inflammatory process in the rat lung

This study was initiated to clarify the relationship between ovarian hormones and the granulomatous inflammatory process in the lung. To assess whether ovarian dysfunction influences the granulomatous inflammatory process, we compared immunological alterations in ovariectomized rats and in sham-operated rats. After a heat-killed, bacilli Calmette-Guérin (BCG)-elicited granulomatous reaction, the lung-body weight ratios, the number of lymphocytes and activated T-cells, and the interferon-gamma levels in the bronchoalveolar lavage fluid from the ovariectomized rats were significantly higher than those of the sham-operated rats. Moreover, exogenous ovarian steroids supplemented in vivo suppressed not only the granulomatous inflammatory process in the lungs, but also the parameters measured in the bronchoalveolar fluid. These results indicate that ovarian dysfunction may adversely affect the formation of granulomas in the lung.

Successful treatment of hepatic sarcoidosis with hormone replacement in a postmenopausal woman

A possible supplementary effect of sex hormone replacement therapy (HRT) for the postmenopausal woman with sarcoidosis is described. A 53‐year‐old woman presented with a 12‐year history of sarcoidosis in the eyes, in the submandibular lymph nodes and in the lungs. In the course of follow up without any medication, her liver function tests were abnormal, and she was diagnosed as having hepatic sarcoidosis. Daily administration of 0.625 mg conjugated oestrogen and 2.5 mg medroxyprogesterone improved her liver function. The results suggest that HRT may help to prevent the progression of sarcoidosis in postmenopausal patients.

Clinical significance of potential pathogenic microorganisms of sputum in patients with pulmonary tuberculosis

Background: Bacterial culture of sputum is frequently positive in patients with pulmonary tuberculosis (TB). However, it remains to be clarified whether detection of potential pathogenic microorganisms (PPM) in sputum represents bacterial infection or only colonization of the respiratory tract. In the present study, we investigated the clinical significance of PPM in patients with pulmonary TB.