Objective To study the difference of clinical manifestations,treatment and prognosis between idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disorder, secondary pulmonary fibrosis(SPF). Methods The elderly patients≥ 60 yrs old, diagnosed as IPF or SPF in PUMC Hospital between 1990 and 2002 were reviewed and analyzed. Results Cough and dyspnea appeared to be the most common complaints in both groups. The most common signs were Velcro rales and clubbing fingers. The symptoms and signs were more common in IPF group. The mean course was shorter in SPF group (8.5 months vs 24.0 months). Mortality rate was high in both groups (26.3% and 30.0%) and showed no significant difference. The common causes of SPF were Sjogren syndrome, polymyositis, rheumatoid arthritis and progressive systemic sclerosis (9/40, 8/40, 7/40, 7/40, respectively). The most common radiograghic findings were bibasilar reticular patterns and showed more severe in IPF than in SPE〔41(71.9%) vs 14(35.0%)〕,P

AIM:To explore whether the balance between endothelin(ET) and nitric oxide(NO) plays an important role in airway hyperresponsiveness of asthmatic rats. METHODS:The tension of isolated perfused rat tracheal rings was measured after ET-1 stimulation and incubation of JKC 302 and L-NAME. RESULTS:ET-1 constricted isolated rat tracheal ring, produced slowly developing and long-lasting contraction. The ET-1-induced contraction response of asthmatic rat tracheal ring was higher than that of normal control group (P＜0.01). JKC 302, a selective ETA receptor antagonist, partly blocked ET-1-induced contraction in asthmatic rat trachea ring. L-NAME significantly augmented the constriction caused by ET-1. CONCLUSION:The effects of ET on bronchomotor tone may be modified by NO as this is a bronchomotor, and the imbalance between ET and NO may play an important role in asthma pathogenesis.

Objectives To evaluate the value of detecting p53 gene point mutations in sputum samples and its validity and reliability as a surveillance index in the early diagnosis of lung cancer in suspicious patients.Methods Sputum samples were collected from 54 cases identified as lung cancer and 114 cases identified as pulmonary benign disease. The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was performed for the detection of point mutations at exons 5-8 of the p53 gene, and sputum smears were also used for each sample. Conclusion Detection of p53 gene alterations in sputum samples by PCR-SSCP-silver stain can be used as a follow-up surveillance index for the early diagnosis of lung cancer in suspicious patients.

Objectives To identify the effects of tuberculin purified protein derivative (PPD) sensitization on attenuating pulmonary T helper 2 (Th2) reaction and eosinophil infiltration in ovalbumin sensitized mice, and to search for the possibility of its clinical use in the management of asthma in a new way.Methods　Sixty C57BL/6 mice were sensitized with PPD and then with ovalbumin and aluminum hydroxide, and randomized into 4 groups: ovalbumin (OVA), pre-PPD, post-PPD and control groups. Aerosol PPD were administered 3 h before or after ovalbumin challenge in the pre-PPD and post-PPD groups respectively, and control group received aerosol PPD only. IL-4, IL-5 expression was detected by immunocytochemistry in situ hybridization. Lung slides were stained with eosin and hemotoxylin, and pathological changes were observed.Results　Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice. 87.5%-89.7% and 89.0%-89.2% of the CD4+ T lymphocytes were IL-4 mRNA+ and IL-5 mRNA+ respectively. 88.7%-91.2% of IL-4 mRNA+ cells and 89.8%-90.6% of IL-5 mRNA+ cells were CD4+ T lymphocytes in OVA group. Aerosol administration of PPD markedly suppressed IL-4 and IL-5 expression, and lung eosinophil infiltration. It was more effective in pre-PPD group. 76.6%-78.0% of IL-4 mRNA+ and 73.8%-79.7% of IL-5 mRNA+ cells were CD4+ and 78.1%-84.9% and 78.4%-85.3% of the CD4+ cells were IL-4 mRNA+ or IL-5 mRNA+ respectively in pre-PPD group, both were markedly lower than that of OVA group. CD4+ percentage of IL-4 mRNA+ and IL-5 mRNA+ cells were 80.7%-82.0% and 78.0%-83.9% in post-PPD group, which were markedly lower than that of OVA group.Conclusions　Sensitization with PPD by intraperitoneal injection and then challenged by PPD inhalation markedly suppressed IL-4, IL-5 expression and eosinophil infiltration, and attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. This induces Th1 type reaction and inhibits Th2 cell differentiation. It may be beneficial for glucocorticoids dependent or resistant patients.

OBJECTIVETo evaluate the efficacy and safety of oseltamivir phosphate as treatment for naturally acquired influenza infection.

METHODSThis study was conducted as a double-blind, randomized, placebo-controlled, multicenter trial during the influenza epidemic season from January to April 2001 at 7 centers in China. A total of 478 adults without other medical history, aged 18 to 65 years, were enrolled into the study. All subjects demonstrated febrile respiratory illness of no more than 36 hours' duration with a temperature of 37.8 degrees C or more plus at least two of the following symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscles aches and pain, fatigue, headache or chills/sweats. Individuals were randomized into either the oseltamivir phosphate or placebo group with identical-looking capsules. Either oral oseltamivir phosphate, 75 mg twice daily, or placebo was administered to the subjects for 5 days.

RESULTSA total of 451 individuals were analyzed for efficacy as the intent-to-treat population (ITT) (216 oseltamivir and 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test, who were then defined as the intent-to-treat infected population (ITTI) (134 oseltamivir and 139 placebo). Four hundred and fifty nine individuals were included in the safety analysis. In the ITTI population, the cumulative alleviation proportion of oseltamivir group was significantly higher than that of the placebo group (P = 0.0466)). The median duration of illness was 91.6 h [95% confidence interval (CI) = 80.2 - 101.3 h] in the oseltamivir group and 95 h (95% CI = 84.5 - 105.3 h) in the placebo group. The median area under the curve of decreased total score was significantly higher in the oseltamivir group than in the placebo group, 1382.9 and 1236.7 score-hours, respectively (P = 0.0196). For the ITT population, similar results were observed. Adverse events (AE) were similarly reported in both the oseltamivir group and the placebo group. The main adverse events following test drug were gastrointestinal symptoms, neurological symptoms and rashes.

CONCLUSIONOseltamivir was effective and well tolerated as treatment of early naturally acquired influenza.

Acetamides ; adverse effects ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Influenza, Human ; drug therapy ; Male ; Middle Aged ; Neuraminidase ; antagonists & inhibitors ; Oseltamivir

Objective. Angiotensin-converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion-deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness.Methods. A case-control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho-provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P＜0.05; odd ratio 4.98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P＜0.05; odd ratio 3.8). Accordingly, the mean values of FEV1% and FEV1/FVC were higher in asthmatics carrying non-DD alleles than patients with DD genotype (73.78% vs 56.56%, P＜0.05; 79.19% vs 69.29%, P＜0.05, respectively).Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.

Objective To elucidate the mechanism of anti-inflammatory effect of dexamethasone and methotrexate on pulmonary Th2 reaction and eosinophil infiltration in ovalbumin sensitized mice, and search for the possibility of aerosol administration of other anti-inflammatory drugs in the management of asthma except for glucocorticoids.Methods Sixty C57b1/6 mice were sensitized and challenged with ovalbumin, aerosol dexamethasone and methotrexate were administered after challenge. Mice lung were fixed in paraformaldehyde and IL-4, IL-5 expression was detected by immunocytochemistry-in situ hybridization. Lung slides were also stained with eosin and hematoxylin, and pathological changes were observed.Results Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice. 85.2%-88.2% and 81.4%-91.8% of the CD4+ T lymphocytes were IL-4 mRNA+ or IL-5 mRNA+ respectively, and few CD8+ T lymphocytes were IL-4 or IL-5 positive (<2%). 78.8%-80.8% of IL-4 mRNA+ cells and 78.0%-86.8%of IL-5 mRNA+ cells were CD4+ T lymphocytes. Aerosol administration of dexamethasone and methotrexate after challenge inhibited IL-4 and IL-5 expression, and lung eosinophil infiltration were attenuated. And dexamethasone was more effective. These two drugs had no effect on the ratio of IL-4 or IL-5 expression of CD4+ T lymphocytes, and the percentages of CD4+ T lymphocytes of the IL-4 mRNA+ or IL-5 mRNA+ cells were not affected. The anti-inflammatory effect was non-specific. In addition, aerosol administration of dexamethasone enhanced IL-4 expression and methotrexate promoted eosinophil infiltration 12 h after challenge.Conclusion Aerosol administration of dexamethasone and methotrexate attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. Aerosol administration of drug exerts its effect at the site of inflammation, which is more effective with less side effects. But at the beginning, aerosol administration might promote inflammation. In this way, oral or intravenous injection of glucocorticoids should be given to moderate to severe asthmatic patients, and aerosol gulcocorticoids should be adminstered after the disease was under control. Methotrexate was less effective than dexamethasone but more irritative, and should not be given by inhalation, Intravenous injection of methotrexate should be administrated to asthmatic patients who respond poorly to glucocorticoids as an auxiliary therapeutic measure.

OBJECTIVEDiffuse panbronchiolitis, a distinct clinical entity of unknown etiology, has been reported originally and primarily in Japanese and rarely in non-Japanese populations. Macrolide therapy is effective for this once dismal disease. Diffuse panbronchiolitis complicated with thymoma is uncommon; only 2 cases have been reported to date. The aims of this study were to describe the clinical profiles, assess the response to macrolide therapy, and to discuss the possible pathogenesis of diffuse panbronchiolitis in this setting.

METHODSThe clinical profiles, macrolide therapy response of diffuse panbronchiolitis complicated with encapsulated thymoma in 2 histologically confirmed cases were described and discussed with the 2 cases reported in the literature: one complicated with encapsulated thymoma, another with invasive thymoma.

RESULTSOf the 2 cases, both had negative PPD skin testing and abnormal serum levels of various immunoglobulins, 1 had positive anti-nuclear antibody, but none had elevated cold hemagglutinin titers, and both had an excellent response to macrolide therapy. Of the 2 cases reported in the literature, both had negative PPD or tuberculin skin testing, 1 had severe hypogammaglobulinemia, 1 had elevated IgA, 1 had positive anti-DNA, 1 had elevated cold hemagglutinin titers, but both died of respiratory failure in spite of macrolide therapy in 1 case.

CONCLUSIONSPrognosis for diffuse panbronchiolitis complicated with thymoma may depend on the nature of the thymoma and on the disease course. Macrolide therapy is also effective if administered early in the disease course and if the thymoma is cured. Immunological factors may play an important role in the pathogenesis of diffuse panbronchiolitis in this setting.

Adult ; Bronchiolitis ; complications ; drug therapy ; mortality ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Thymoma ; complications ; Thymus Neoplasms ; complications