Evaluation of symptoms and risks in stable chronic obstructive pulmonary disease patients with radiographic bronchiectasis.

OBJECTIVE: To investigate the presence of previously undiagnosed radiographic bronchiectasis in stable chronic obstructive pulmonary disease (COPD) patients using high resolution computed tomography (HRCT) and to evaluate the effect of radiographic bronchiectasis on the symptoms and risks in stable COPD patients. METHODS: From May 2012 to April 2014, there were 347 patients enrolled in COPD database. Data describing the general conditions, the frequency of acute exacerbations the year before, COPD assessment test, modified medical research council (mMRC) score, spirometric classification, and HRCT were collected. COPD patients were classified into two groups: COPD with bronchiectasis and COPD without bronchiectasis. The clinical characteristics of both groups were compared. RESULTS: Bronchiectasis was presented in 18.4% (n = 64). The proportion of smokers, smoking index, and forced expiratory volume in 1 second predicted value were 62.5%, 27.3 ± 13.2, 48.2 ± 26.4, respectively, in the bronchiectasis group, which were lower than those of the group without bronchiectasis (82.0%, 32.6 ± 17.6, and 57.9 ± 18.8) (P < 0.05). Complications, COPD assessment test (CAT) and the rate of CAT ≥ 10 in the bronchiectasis group were 2.8 ± 1.7,13.6 ± 7.4 and 26.6%, respectively, which were higher than those of the group without bronchiectasis (2.3 ± 1.5,11.3 ± 6.0, and 11.7%) (P < 0.05). The proportion of type D (high-risk more-symptoms) in the bronchiectasis group was 50.0%; it was significantly higher than that of 35.7% in the group without bronchiectasis (P < 0.05). CONCLUSIONS: COPD with bronchiectasis is associated with more complications, symptoms, and risks. More attention should be paid to the treatment of COPD with bronchiectasis to reduce the frequency of exacerbation and improve the health status.

[Chinese literature review of etiology distribution of adult patients with fever of unknown origin from 1979 to 2012].

OBJECTIVE: To review the etiology of 10 201 adult patients with fever of unknown origin (FUO) in China from 1979 to 2012, and to compare the reasons between the South and the North of China, and to illustrate the change in different periods. METHODS: Literatures containing key word "fever of unknown origin" were selected in China National Knowledge Infrastructure (CNKI) database from 1979 to 2012. Articles were excluded if patient population were less than 100. Diagnostic criteria of FUO were confirmed by the standard of Petersdorf and Beeson in 1961. Totally 43 literatures including 10 201 patients were enrolled in this study. The period of the literatures were divided into the early, middle and later period, and the regions were partitioned into the South and the North. RESULTS: A total of 42 articles (including 9787 patients) provided the gender information with 5063 men and 4724 women. The etiologies of 10 201 FUO patients included infectious diseases (53.5%), rheumatic diseases (20.1%) and tumor (12.0%). The positive diagnostic rate was 91.8%. Tuberculosis (23.8%) was the most common reason in infectious diseases. Adult Still's disease (7.0%) was the most common cause of FUO among rheumatic diseases. Lymphoma (3.4%) was the most common tumor in FUO patients. Besides, drug-induced fever (1.7%) should also be considered. In the recent 30 years, the proportion of FUO caused by infectious diseases had decreased, rheumatic diseases and other reason had increased (P < 0.05). The proportion of tumor in middle period was significantly higher than that in the early and later period (P < 0.05). The negative diagnostic rate had increased (all P < 0.05). The proportion of infectious diseases in North China was significantly lower than that in the South (P < 0.05). The proportion of other reason was significantly higher in the North (P < 0.05). CONCLUSION: In the recent 30 years, the most common cause of FUO was still infectious diseases, especially tuberculosis.

Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.

BACKGROUND: The persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery. METHODS: Thirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression. RESULTS: When compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035. CONCLUSIONS: CIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.

[Evaluation of chronic obstructive pulmonary disease screening in a high risk population].

OBJECTIVE: To investigate the results of spirometry testing used in the screening of COPD from at risk populations. METHODS: A survey of the population aged over 40 years with any of chronic cough and sputum, dyspnea, heavy tobacco smoke was performed, using a questionnaire on clinical characteristics of COPD. Spirometry and chest X ray examination were performed. Different screening methods were compared for sensitivity and specificity for COPD diagnosis. RESULTS: Of 241 surveyed persons, 156 were diagnosed as having COPD, among whom 126 cases were firstly diagnosed. Among all surveyed persons, 87 (36. 1%) cases had mild and moderate COPD, while 69 (28. 6%) had severe and very severe disease. The sensitivity and specificity for diagnosis of COPD of shortness of breath were 61.5% and 61.2% respectively. Combination of respiratory symptoms and risk factors improved the screening power. More than 40 years of age combined with any of heavy smoking, chronic cough and sputum, or shortness of breath, improved the sensitivity to more than 90 percent. CONCLUSIONS: Spirometry test screening of the at risk population can effectively improve early diagnosis of COPD.

[Epidemiologic study on the relationship between smoking and sleep apnea/hypopnea syndrome].

OBJECTIVE: To investigate how smoking was affecting the prevalence of sleep apnea/ hypopnea syndrome (SAHS) among adults aged over 30 years in Chengde city of Hebei province. METHODS: 1168 subjects, over 30 years of age were derived from a random sample from a community-based population in Shuangqiao district of Chengde city. All subjects responded to a questionnaire at their own houses regarding their habits of snoring and smoking. 1168 subjects (95.2%) answered the questions satisfactorily. RESULTS: (1) Among the smoking groups, the prevalence of snoring was 69.09%, higher than that in the nonsmoking groups 45.07% (P = 0.000). (2) In males, the smoking group had a higher prevalence (69.72%) of snoring than in the nonsmoking group (60.80%, P = 0.033). (3) Females in the smoking group had a higher prevalence of snoring (61.80%) than in the nonsmoking group (39.70%, P = 0.011). (4) The prevalence of snoring in males (60.80%) was significantly higher than that in females (39.70%, P = 0.000). (5) The prevalence (69.72%) of snoring in smoking males was similar to that in smoking females (61.80%, P = 0.336). (6) Data from logistic regression analysis indicated that smoking was one of the factors affecting snoring. (7) According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated. According to the AHI > or = 5 and the ESS > or = 9 cutoff-points, the prevalence rates of SAHS in smoking groups were both significantly higher than that in nonsmoking groups (P < 0.001). CONCLUSION: Smoking and snoring among adults aged over 30 years had correlation in our city.

[The effect of chronic intermittent hypoxia caused by obstructive sleep apnea hypopnea syndrome on blood pressure].

OBJECTIVE: To explore the effect of chronic intermittent hypoxia caused by obstructive sleep apnea hypopnea syndrome (OSAHS) and chronic continuous hypoxia caused by chronic obstructive pulmonary disease (COPD) on blood pressure and levels of nitric oxide (NO)/endothelin (ET). METHODS: A total of 85 cases were selected, including OSAHS patients over 18 years old visited this hospital from June to August 2006, stable COPD patients and healthy volunteers. According to the results of clinical questionnaire, pulmonary function test and polysomography (PSG), they were divided into 4 groups: non-smoking OSAHS patients (n = 26), smoking OSAHS patients (n = 22), patients with stable COPD (n = 17) and healthy control subjects (n = 20). Blood pressure measurement was performed before and after the PSG examination while the subjects were resting. The levels of ET and NO in blood samples and exhaled breath condensates (EBC) were measured by radioimmunoassay and nitrate reductase, respectively. Measurement data were analyzed by ANOVA, numeration data were analyzed by chi-square test, data of normal distribution were analyzed by Pearson correlation analysis, and non-normal data were analyzed by Spearman correlation analysis. Multiple linear regression analysis was also performed. RESULTS: Regardless of the smoking status, the difference of morning-evening diastolic blood pressure (DBP) in the morning of patients with OSAHS [non-smoking OSAHS: (88 +/- 10) mm Hg, 1 mm Hg = 0.133 kPa; smoking OSAHS: (95 +/- 17) mm Hg] was higher than that of patients with COPD [(76 +/- 7) mm Hg] and healthy subjects [(70 +/- 6) mm Hg]. The difference of morning-evening NO level in EBC of patients with OSAHS [non-smoking OSAHS: (-4.5 +/- 7.9) micromol/L; smoking OSAHS: (-3.4 +/- 5.5) micromol/L] was lower than that of patients with COPD [(1.4 +/- 6.1) micromol/L] and healthy subjects [(3.1 +/- 4.0) micromol/L]. The ratio of NO to ET in serum of the smoking OSAHS group (1.0 +/- 0.5) was lower than that of the COPD group (1.4 +/- 0.7). After adjustment for sex, age, BMI, waist circumference, history of smoking and alcohol, level of hypertension, and category of antihypertensive drugs, the morning-evening difference of NO level in EBC was negatively associated with the morning-evening difference of DBP (r = -0.301, P = 0.021), and was positively associated with apnea hypopnea index (AHI) (r = 0.116, P < 0.05). The morning-evening difference of DBP was associated with AHI (r = -0.303, P = 0.011), amplitude of oxygen desaturation with pulse oxygen saturation (SpO(2)) less than 90% (OLA90%, r = -0.281, P = 0.018), and gradient of oxygen desaturation with SpO(2) less than 90% (OLG90%, r = 0.286, P = 0.035). Multiple linear regression analysis showed that, if AHI increased by 1/h, the morning-evening difference of DBP would increase 0.41 mm Hg; if the morning-evening difference of NO level in EBC increased by 1 micromol/L, the morning-evening difference of DBP would decrease 0.27 mm Hg; and if AHI increased by 1/h, the morning-evening difference of NO level in EBC would increase 0.40 micromol/L. CONCLUSION: The DBP of OSAHS patients in the morning is significantly higher than that in the evening. The morning-evening difference of NO level in EBC reflects indirectly the consumption of NO in the body, and is associated with the degree of OSAHS and the morning-evening difference of DBP.

Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis.

Akt, a downstream mediator of phosphatidylinositol 3-kinase (PI3K), is a signal transduction protein that plays a central role in tumorigenesis. The tumor suppressor gene PTEN negatively regulates the PI3K/Akt signaling pathway. However, the roles of Akt and PTEN function in patients with non-small cell lung cancer (NSCLC) is not well established. To clarify roles of expression of phosphorylated Akt (p-Akt) and loss of PTEN expression in biological behavior and prognosis of NSCLC. Immunohistochemical staining was used to determine the expression of p-Akt and PTEN in 20 cases of normal lung tissues and 102 cases patients with NSCLC. All patients with NSCLC were followed from 3 to 60 months. The positive incidence of p-Akt expression and loss incidence of PTEN expression in NSCLC were 41.2% (42/102) and 46.1% (47/102), while negative of p-Akt expression (0%, 0/20) and positive of PTEN expression (100%, 20/20) in normal lung tissues. Overexpression of p-Akt and loss of PTEN expression were correlated to poor differentiation, lymph node involvement, distant metastasis and late stages. A significant negative correlation was observed between expression of p-Akt and PTEN (r = -0.425, P < 0.001). Patients with p-Akt positive expression (42/102) and loss of PTEN expression (47/102) showed significantly worse 5 years survival rate and median survival time than relevant those with p-Akt negative expression (14.29% versus 33.33%, 14 months versus 32 months, Log-rank test X(2) = 14.24, P < 0.001) and PTEN positive expression (10.64% versus 38.18%, 15 months versus 40 months, Log-rank test X(2) = 21.06, P < 0.001). A univariate analysis revealed that smoking, tumor size, lymph node involvement, distant metastasis, stage, p-Akt and loss of PTEN expression were significant correlative factors with prognosis. The result of multivariate Cox analysis showed that smoking, stage and loss of PTEN expression were independent prognosticators. p-Akt is overexpressed and accompanied by the loss of PTEN in clinical specimens of NSCLC. Both p-Akt and PTEN are concerned with invasion and metastasis of NSCLC. Loss of PTEN expression is an independent poor prognostic factor for patients with NSCLC.

[Effects of uvulopalatopharyngoplasty surgery on subsequent continuous positive airway pressure in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To determine the effect of uvulopalatopharyngoplasty (UPPP) therapy on post-surgery continuous positive airway pressure (CPAP) treatment during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and to evaluate the use of Bi-level positive airway pressure (BiPAP) in whom CPAP therapy failed. METHODS: Thirty-four OSAHS patients after UPPP surgery were tested more than 3 months after the procedure. Among them 25 patients were treated with classical UPPP (cUPPP), in which all of the uvula and part of the soft palate were removed. Nine underwent modified UPPP (mUPPP), keeping part of the uvula. The control group consisted of 34 age, body mass index (BMI) and apnea hypopnea index (AHI) matched, newly diagnosed OSAHS patients without prior treatment. Four patients receiving both pre- and post-surgery tests were included in both groups. A manual titration of CPAP to determine the optimal CPAP pressure (oCPAP) and the highest CPAP pressure (hCPAP) the patient can tolerate was performed during both NREM and REM sleep in all 68 patients. RESULTS: 72% of the UPPP patients had less than 50% decrease in AHI, and 82% of the 34 patients still had AHI > 15 during post-operation PSG test. Hence, most of them needed further therapy. All of the untreated OSAHS patients could tolerate 17-20 cm H2O of CPAP during NREM and REM sleep. None had severe mouth air leak before an oCPAP was reached. In contrast, five in the surgery group failed to respond to CPAP treatment during both NREM and REM sleep, and one more during REM sleep. All of the nine patients who had a mUPPP could tolerate CPAP. One of the four tested both before and after surgery failed to respond to CPAP treatment after surgery during REM sleep and one during both NREM and REM sleep. However, the six patients failed to respond to CPAP treatment tolerated BiPAP therapy well. CONCLUSIONS: In a considerable number of patients with OSAHS, UPPP may compromise the applicability of nasal CPAP as a subsequent therapy, and BiPAP might be a treatment option for patients who could not tolerate CPAP treatment.

[A prospective study of clinical characteristics of fever after flexible fiberoptic bronchoscopy].

OBJECTIVE: To assess the incidence and clinical characteristics of fever after fiberoptic bronchoscopy (FOB). METHODS: Between May 2004 and April 2005, the clinical characteristics of fever in immunocompetent and hospitalized patients undergoing FOB were prospectively studied. RESULTS: One hundred and seventy-two hospitalized patients underwent FOB in this period, and 37 cases (22%) developed fever following FOB; in 32 (19%) the fever subsided within 24 h with a mean fever onset time of (3.5 +/- 1.7) h and mean fever duration of (10.8 +/- 6.7) h. There were significant increases in total leukocyte and neutrophil counts in the peripheral blood at 6 h after FOB compared to levels prior to FOB (all P < 0.01), but the numbers of leukocytes and neutrophils in patients with fever were significantly higher than those in patients without fever (all P < 0.01). CONCLUSIONS: Fever after FOB occurs relatively frequently but transiently in immunocompetent adults. No special treatment is needed.

[Study on matrix metalloproteinase 1, 9, 12 polymorphisms and susceptibility to chronic obstructive pulmonary disease among Han nationality in northern China].

OBJECTIVE: To study the association between the functional polymorphism of matrix metalloproteinases (MMPs) and the development of chronic obstructive pulmonary disease (COPD). METHODS: 147 COPD patients and 120 healthy smoking controls were selected. Spirometry and chest X-rays had been taken. Questionnaires including sex, age, smoking history, occupational exposure were completed. MMP-9 (-1562 C/T), MMP-1(-1607 1G/2G), MMP-12 (-82 A/G), MMP-12(-357 Asn/ Ser) alleles were determined using PCR-RFLP method. Independent samples T test analysis was carried out to compare patients' age, smoking index, FEV1 /FVC, FEV1 % pred with that of healthy controlled group. The frequencies of genotypes and alleles between groups were analyzed by chi-square tests and multilogistic regression. RESULTS: MMP12 Asn/Asn, CT/AsnAsn were risk factors for smoking-induced COPD. The ORs were 2.361 (95% CI: 1.369-4.017) and 2.433(95% CI: 1.159-5.342) respectively while CC/1G1G/ SerSer seemed to be a protective factor for smoking-induced COPD, with OR as 0.457 and 95% CI as 0.231-0.911. CONCLUSION: Asn/Asn, CT/AsnAsn might be susceptible genotypes while CC/GG/SerSer might serve as protective genotype.

[A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension].

OBJECTIVE: To explore the possible mechanisms underlying cough induced by angiotensin-converting enzyme inhibitors (ACEI) in patients with hypertension. METHODS: 127 patients with hypertension were enrolled to receive ACEI (97 cases prescribed cilazapril and 30 cases prescribed benazepril hydrochloride) for 8 weeks. Patients who had coughed in the period were assigned to the cough group (48 cases) and patients who hadn't coughed were assigned to the non-cough group (79 cases). The serum ACE activity before and after administration of the drugs and the polymorphism of ACE gene (including homozygous-alleles II, DD, and heterozygous ID) were analyzed. Binary logistic regression was used as a statistical method to determine the factors associated with cough. RESULTS: The frequencies of the I alleles and II genotype of ACE gene in the cough group (0.70% and 56.3%) were significantly higher than those in the non-cough group (0.42% and 23.3%, P < 0.05). The mean serum ACE activity before and after administration of the ACEI in the cough group [(26 +/- 6) U/L, (4 +/- 4) U/L] was significantly lower than that in the non-cough group [(33 +/- 8) U/L, (8 +/- 8) U/L, all P < 0.01]. The difference in the range of decrease of serum ACE activity after ACEI between the cough group [(22 +/- 7) U/L] and the non-cough group [(25 +/- 9) U/L] was not significant (P = 0.077). Serum ACE activity before ACEI was highest in the homozygous-alleles DD group [(36 +/- 8) U/L], secondly in the heterozygous ID group [(29 +/- 6) U/L] and the lowest in homozygous-alleles II group [(26 +/- 7) U/L], differences being significant among three groups (P < 0.01). ACEI-related cough showed no relationship with sex, smoking habit and the ACEI used. CONCLUSIONS: The serum ACE activity was associated with polymorphism of ACE gene. Cough induced by ACEI was related to I allele and II genotype. There was a relationship between the serum ACE activity before administration of ACEI and cough induced by ACEI.

[Study on apoptosis of lung tissue cells in patients with severe brain injury complicated with aspiration-induced lung injury].

OBJECTIVE: To investigate the role of apoptosis of pulmonary cells in aspiration induced lung injury in patients with severe brain injury with or without aspiration-induced lung injury. METHODS: The Glasgow scale (GCS) of 11 dead patients with severe closed brain injury was 3-8. There 11 cases were divided into aspiration-induced lung injury (AILI) and non-aspiration-induced lung injury (NAILI) groups. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were measured, and the ratio of apoptosis in lung tissue cells was also determined. RESULTS: The plasma levels of TNF-alpha and IL-8 in NAILI and AILI groups were (2.17+/-0.41)nug/L vs. (3.14+/-0.28)nug/L and (0.42+/-0.05)nug/L vs. (0.91+/-0.08) nug/L (P<0.05) respectively. Lung tissue cell apoptosis ratio was significantly higher in AILI group than NAILI group (P<0.01). CONCLUSION: TNF-alpha and IL-8 may induce apoptosis in lung tissues through different signaling pathway. During the early phase of aspiration-induced lung injury complicating severe closed brain injury, apoptosis in cells of lung tissue may play a role in the pathogenes.

[Comparison of tolerance to sequential continuous positive airway pressure therapy between patients after classical and after modified uvulopalatopharyngoplasty].

OBJECTIVE: To investigate the effect of uvulopalatopharyngoplasty (UPPP) on postoperation continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: 66 OSAHS patients underwent UPPP were recruited and all were followed up for more than 12 months. Among them 24 patients were treated with classical UPPP, 42 had modified UPPP treatment. The efficacy of surgery was compared between the two groups. The post-operation tolerance to CPAP pressure was tested during sleep CPAP titration in 24 classical UPPP patients and in 15 modified UPPP patients. RESULTS: The validity ratio is 58.3% and 61.9% 12 months after operation. There was no significant difference between classical UPPP and modified UPPP in regard to surgery efficacy, and most of them need further CPAP therapy. During CPAP treatment, compared with untreated OSAHS patients, the highest CPAP pressure classical UPPP group could tolerant decreased significantly, however, classical UPPP group did not. 16.7% of classical UPPP patients had severe mouth air leak before optimal CPAP pressure was titrated, but none of the 15 post modified UPPP failed to sequential CPAP therapy. CONCLUSION: The efficacy was similar between modified UPPP and classical UPPP treatment, post modified UPPP patients had better tolerance to sequential CPAP treatment. It may be better to treat OSAHS patients with modified UPPP instead of classical UPPP.

[Epidemiologic study on sleep apnea-hypopnea syndrome by home investigation in Chengde city].

OBJECTIVE: To investigate the prevalence of sleep apnea-hypopnea syndrome (SAHS) among adults aged over 30 yr in Chengde city of Hebei province. METHODS: 1 168 subjects (over 30 yr) were derived from a random sample of the population among the Shuangqiao district in Chengde city. All subjects were asked at home to answer questions about their snoring, daytime sleepiness, and habits of smoking and drinking. According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated according to AHI and ESS scores. RESULTS: 1 168 subjects (95.42%) answered the questions. The prevalence of snoring was 53.76%. The prevalence of moderate and severe snoring (>or= second degree) was 28.25%. The prevalence of snoring increased with age before the age of 70. The prevalence of snoring in males was significantly higher than that in females. Smoking and drinking groups were associated with a higher prevalence of snoring. The prevalence of snoring was higher in drivers (42.00%) than that in other populations. The estimated prevalence of SAHS according to both the AHI > 5 and the ESS >or= 9 was 4.63%. CONCLUSIONS: The estimated prevalence of SAHS among adults aged over 30 yr in Chengde city was 4.63%. It means that SAHS needs better understanding and more study.

[The effect of murine interferon-gamma transgene expression on bleomycin-induced pulmonary fibrosis in mice].

OBJECTIVE: To investigate the effect of murine interferon-gamma (IFN-gamma) transgene expression on bleomycin-induced pulmonary fibrosis in mice. METHODS: 6 - 8 week aged pathogen-free male ICR mice were treated with bleomycin (3 mg/kg weight in 70 micro l) by intranasal instillation on day 0 in the model group. Adenoviral vector with murine IFN-gamma cDNA (AdCMVmIFN-gamma) 5 x 10(8) plague forming unit (pfu) was administrated via nastril instillation 48 h before bleomycin treatment in the preventive therapeutic group, but 72 h after bleomycin treatment in the therapeutic group. Mice treated with a same volume of normal saline (NS) and a same dosage of sham recombinant adenoviruses (AdCMVNull) served as controls. The animals were weighted on day 0, 7, 14, and sacrificed on day 14. Bronchial alveolar lavage fluid (BALF) and lungs were recovered. The right lung was stained with either hematoxylin-eosin or masson. The left lung was weighted, and its content of hydroxyproline (HYP) was measured by HCl acid hydrosis method. The IFN-gamma concentration in BALF was determined with enzyme-linked immunosorbent assay. RESULTS: The concentrations of IFN-gamma in BALF from the AdCMVmIFN-gamma treated groups were remarkably increased, (21,250 +/- 6,497) pg/ml and (21,000 +/- 5,451) pg/ml in the IFN-gamma transgenetic preventive therapeutic group and the therapeutic group respectively. IFN-gamma was undetectable in BALF from other groups. Mice in the two groups treated with AdCMVmIFN-gamma had statistically significant weight loss (P < 0.05), higher HYP content (P < 0.05), and tended to have more severe alveolitis and pulmonary fibrosis (P = 0.07) as compared with those in other groups. CONCLUSIONS: (1) mIFN-gamma could be overexpressed in airway and alveolar epithelium by locally administrated AdCMVmIFN-gamma. (2) Early mIFN-gamma transgene expression via adenoviral vector in this bleomycin model aggravated alveolitis and fibrosis to some degree.