Distinctive patterns of pulmonary function change according to baseline lung volume and diffusing capacity.

SETTING: Multicentre retrospective study in South Korea.OBJECTIVE: To longitudinally evaluate changes in lung volume and diffusing capacity for carbon monoxide (DLCO) with forced expiratory volume in 1 sec (FEV1).DESIGN: A total of 155 patients with chronic obstructive pulmonary disease (COPD), whose pulmonary function parameters were measured annually for 5 years, were selected from a prospective cohort in South Korea. A random coefficients model was used to estimate mean annual FEV1, lung volume parameter and DLCO change rates.RESULTS: Patients were classified into four groups based on baseline DLCO and residual volume/total lung capacity (RV/TLC) measurements. The annual FEV1 decline rate was greater in patients with low DLCO than in those with normal DLCO, with the greatest decline occurring in patients with low DLCO and normal RV/TLC. RV and RV/TLC declined in patients with high RV/TLC, whereas these increased in patients with normal RV/TLC. DLCO decreased longitudinally in all four groups, with the greatest decline occurring in patients with normal DLCO and normal RV/TLC.CONCLUSIONS: Different subgroups of patients with COPD exhibited distinctive pulmonary function change patterns. Baseline DLCO and RV/TLC may be used as physiological markers to predict long-term changes in pulmonary function.

Association of plasma fibrinogen concentrations and blood eosinophil counts with clinical phenotypes of COPD.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the plasma fibrinogen level is associated with a decline in lung function and exacerbation of COPD. High blood eosinophil count is also associated with exacerbation of COPD in some studies but not others.OBJECTIVE: To investigate the associations between clinical phenotypes and plasma fibrinogen levels and blood eosinophil counts in patients with COPD.METHODS: Outpatients with COPD, in whom plasma fibrinogen level and blood eosinophil count were measured at least once simultaneously, were analysed retrospectively. Patients were classified into four groups, based on plasma fibrinogen level (threshold, 350 mg/dl) and blood eosinophil percentage (threshold, 2%). Clinical characteristics, comorbidities, laboratory data, COPD severity and exacerbations were compared in the four groups.RESULTS: Of 370 patients with COPD, the group with both high fibrinogen levels and eosinophil counts had more severe airflow limitation, more comorbidities and higher COPD severity indexes than the groups with low plasma fibrinogen. The annual rates of severe (0.29/year) and total (0.42/year) exacerbations were significantly higher in patients with both high fibrinogen and eosinophils than in the other three groups.CONCLUSION: Plasma fibrinogen levels and blood eosinophil counts may predict the clinical phenotype and frequency of exacerbations of COPD.

Identification of chronic obstructive pulmonary disease subgroups in 13 Asian cities.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment. OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup. METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis. RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score. CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

Sterile Neutrino Search at the NEOS Experiment.

An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.

Factors affecting the trajectory of health-related quality of life in COPD patients.

BACKGROUND: Health-related quality of life (HR-QoL) is an important issue in patients with chronic obstructive pulmonary disease (COPD), as in other chronic illness groups. However, there is limited information on longitudinal changes in HR-QoL over time with the illness trajectory model. OBJECTIVE: To identify different patterns of HR-QoL changes in longitudinal data, and reveal potential predictors affecting these trajectories. METHODS: Subjects with COPD (n = 249) were drawn from the Korean Obstructive Lung Disease cohort, which was conducted from 2005 to 2012. Longitudinal data were drawn from the St George's Respiratory Questionnaire and clinical measures. Growth mixture modelling was used to estimate distinct patterns, and binary and ordinal logistic regression were used to determine factors affecting different trajectory HR-QoL patterns using STATA 12.0. RESULTS: Five distinct HR-QoL patterns were identified. Results show that the level of baseline HR-QoL was significantly associated with age, the BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index at baseline, sleep disturbance, experience of exacerbation in previous year and level of depression. Distinct patterns in HR-QoL that improved vs. worsened were significantly associated with BODE index, number of respiratory symptoms and depression level. CONCLUSIONS: These findings suggest that comprehensive assessment and individualised management programmes are needed to improve HR-QoL in COPD patients.

Asthma and COPD overlap syndrome is associated with increased risk of hospitalisation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with poor prognosis and a high health care burden. The incidence of asthma and COPD overlap syndrome is increasing, and contributes to a high financial burden and poor prognosis. OBJECTIVE: To investigate clinical features of the overlap syndrome among Asian patients and to analyse its impact on hospitalisation due to respiratory problems or death compared to COPD alone. DESIGN: We performed a retrospective cohort analysis of 2933 COPD patients presenting at the Asan Medical Center from 1 January 2000 to 31 December 2009. Kaplan-Meier and Cox proportional hazard models were used to analyse the significance of clinical parameters, including age, sex, smoking history, body mass index (BMI), severity of airflow limitation, airway obstruction reversibility and overlap syndrome with hospitalisation due to respiratory problems or death. RESULTS: Overlap syndrome patients were older, included smaller proportions of males and of smokers and had lower forced expiratory volume in 1 s (FEV1) (% predicted). Shorter hospitalisation-free and survival periods were noted among overlap syndrome patients. Overlap syndrome was significantly associated with risk of hospitalisation due to respiratory problems after adjusting for age, smoking history, BMI, FEV1 (% predicted) and changes in FEV1 (P < 0.001). CONCLUSION: Asthma and COPD overlap syndrome is associated with a higher risk of hospitalisation due to respiratory problems than COPD alone.

Vertebral compression fractures may increase mortality in male patients with chronic obstructive pulmonary disease.

BACKGROUND: Vertebral compression fracture (VCF) is frequent in chronic obstructive pulmonary disease (COPD) patients. However, little is known about whether VCF affects mortality in COPD patients. OBJECTIVE: To investigate whether VCFs might increase death in COPD patients. METHODS: In this retrospective cohort study, we enrolled 254 COPD patients with a recent history of hospitalisation due to respiratory problems. Patients were assessed for VCF using quantitative morphometric analyses of lateral chest radiographs; 211 patients received follow-up examinations for 2 years. RESULTS: Of the 211 COPD patients analysed, 60 (28.4%) had VCF at enrolment. During the follow-up period, 33/60 (55.0%) patients with and 46/151 patients (30.5%) without VCF died (P = 0.003, log-rank test). Cox proportional hazard analysis revealed that VCF is an independent risk factor for death after adjusting for age, sex, body mass index, smoking, dyspnoea scale, forced expiratory volume in 1 sec (FEV1) and comorbidities (hazard ratio for VCF = 1.79, 95%CI 1.11-2.89, P = 0.02). CONCLUSION: VCF might be an independent risk factor for death in male COPD patients.

Synthetic lethal screening reveals FGFR as one of the combinatorial targets to overcome resistance to Met-targeted therapy.

Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin ß3 is another potential target for combination treatment with SAIT301. Suppression of integrin ß3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin ß3 are resistant to crizotinib treatment, suggesting that FGFR and integrin ß3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.

Emphysematous phenotype is an independent predictor for frequent exacerbation of COPD.

SETTING: Frequent exacerbation is an important phenotype in chronic obstructive pulmonary disease (COPD), while emphysema is associated with many comorbidities and lung function decline. OBJECTIVE: To investigate unique features of frequent exacerbators and test the hypothesis that emphysematous phenotype is associated with frequent exacerbations of COPD. METHODS: A total of 380 COPD patients were recruited from 16 hospitals in Korea from June 2005 to April 2012 for analysis. We searched for independent predictors of frequent exacerbators in comparison with non-exacerbators. RESULTS: As the severity of emphysema increased, forced expiratory volume in 1 s (FEV1), and FEV1/FVC (forced volume capacity) worsened; hyperinflationary features characterised by higher total lung capacity (TLC) were observed (P < 0.05). Frequent exacerbators had lower body mass index (BMI), higher St George's Respiratory Questionnaire (SGRQ) scores, higher residual volume (RV)/TLC, more severe airflow limitation (lower FEV1 and FEV1/FVC), lower carbon monoxide diffusion capacity, lower serum protein levels and a higher emphysema index than non-exacerbators (P < 0.05). In multivariate analysis, frequent exacerbators were independently associated with a higher emphysema index, lower serum protein levels and higher RV/TLC (P < 0.05). CONCLUSION: Our data show that the severity of emphysema, severe static hyperinflation and serum lower protein levels are independent predictors of frequent exacerbations in COPD patients.

Health care use and economic burden of patients with diagnosed chronic obstructive pulmonary disease in Korea.

BACKGROUND: The prevalence and economic burden of chronic obstructive pulmonary disease (COPD) are increasing worldwide. However, little information is available concerning COPD-associated health care use and costs in Korea. OBJECTIVE: To analyse 1) health care use, medical costs and medication use in 2009, and 2) changes in costs and medication use over 5 years (2006-2010). DESIGN: Using the database of the Korean Health Insurance Review and Assessment Service, COPD patients were identified by searching on both ICD-10 codes and COPD medication. RESULTS A total of 192,496 COPD patients were identified in 2009. Total medical costs per person were US$2803 ± 3865; the average annual number of days of out-patient care and days of hospitalisation were respectively 40 ± 36 and 11 ± 33. Methylxanthine and systemic beta-agonists were the most frequently used drugs. However, the number of prescriptions for long-acting muscarinic antagonist increased rapidly. The total cost of COPD-related medications increased by 33.1% over 5 years. CONCLUSION: The present study provides new insight into health care use and the economic burden of COPD in Korea. Changing patterns of COPD-related medication use could help inform COPD management policies.

Unique features of non-obstructive emphysema and pure airway obstruction.

SETTING: Emphysema without airway obstruction or airway obstruction without emphysema are often detected clinically, although they are commonly co-existent. We therefore tested the hypothesis that non-obstructive emphysema and pure airway obstruction have unique features. METHODS: A case-control observation study was undertaken retrospectively in a patient cohort at a single centre. Among 2662 subjects who underwent chest computed tomography and pulmonary function tests, we enrolled 90 patients with non-obstructive emphysema, 119 with pure airway obstruction, 81 with obstructive emphysema and 2031 subjects as normal controls. The features of the four groups were analysed and compared. RESULTS: Higher serum homocysteine (13.4 ± 7.4 vs. 11.6 ± 4.6 mol/l), higher rate of osteoporosis (15.8% vs. 4.5%), higher leukocyte count, higher male ratio, lower serum albumin and lower body mass index were observed in subjects with non-obstructive emphysema than in controls (P < 0.05). In multiple logistic regression analysis of groups without airway obstruction, osteoporosis, hyperhomocysteinaemia, hypoalbuminaemia and higher leukocyte count were independent factors associated with non-obstructive emphysema (P < 0.05). CONCLUSION: Hyperhomocysteinaemia, hypoalbuminaemia, osteoporosis and higher leukocyte count were independent predictors of non-obstructive emphysema.

Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody.

The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met downregulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Castias B-lineage lymphoma (Cbl) E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met overexpressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met-targeting antibody demonstrated intrinsic agonistic activity while being capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met-targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to downregulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies.

The relationship between sagittal spinopelvic parameters and the degree of lumbar intervertebral disc degeneration in young adult patients with low-grade spondylolytic spondylolisthesis.

We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration. There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration.

Netrin-1 protects hypoxia-induced mitochondrial apoptosis through HSP27 expression via DCC- and integrin α6ß4-dependent Akt, GSK-3ß, and HSF-1 in mesenchymal stem cells.

Netrin (Ntn) has the potential to be successfully applied as an anti-apoptotic agent with a high affinity for tissue, for therapeutic strategies of umbilical cord blood-derived mesenchymal stem cells (UCB-MSC), although the mechanism by which Ntn-1 protects hypoxic injury has yet to be identified. Therefore, the present study examined the effect of Ntn-1 on hypoxia-induced UCB-MSC apoptosis, as well as the potential underlying mechanisms of its protective effect. Hypoxia (72 h) reduced cell viability (MTT reduction, and [(3)H]-thymidine incorporation) and cell number, and induced apoptosis (annexin and/or PI positive), which were reversed by Ntn-1 (10 ng/ml). Moreover, Ntn-1 decreased the increase of hypoxia-induced Bax, cleaved caspase-9, and -3, but blocked the decrease of hypoxia-reduced Bcl-2. Next, in order to examine the Ntn-1-related signaling cascade in the protection of hypoxic injury, we analyzed six Ntn receptors in UCB-MSC. We identified deleted in colorectal cancer (DCC) and integrin (IN) α6ß4, except uncoordinated family member (UNC) 5A-C, and neogenin. Among them, IN α6ß4 only was detected in lipid raft fractions. In addition, Ntn-1 induced the dissociation of DCC and APPL-1 complex, thereby stimulating the formation of APPL-1 and Akt2 complex. Ntn-1 also reversed the hypoxia-induced decrease of Akt and glycogen synthase kinase 3ß (GSK-3ß) phosphorylation, which is involved in heat shock factor-1 (HSF-1) expression. Ntn-1-induced phospho-Akt and -GSK-3ß were inhibited by DCC function-blocking antibody, IN a6b4 function-blocking antibody, and the Akt inhibitor. Hypoxia and/or Ntn-1 stimulated heat shock protein (HSP)27 expression, which was blocked by HSF-1-specific small interfering RNA (siRNA). Furthermore, HSP27-specific siRNA reversed the Ntn-1-induced increase of phospho-Akt. Additionally, HSP27-specific siRNA attenuated the Ntn-1-reduced loss of mitochondrial membrane injury via the inhibition of cytochrome c (cyt c) release and formation of cyt c and HSP27 complex. Moreover, the inhibition of each signaling protein attenuated Ntn-1-induced blockage of apoptosis. In conclusion, Ntn-1-induced HSP27 protected hypoxic injury-related UCB-MSC apoptosis through DCC- and IN α6ß4-dependent Akt, GSK-3ß, and HSF-1 signaling pathways.

Systematic review and meta-analysis of prophylactic antibiotics in COPD and/or chronic bronchitis.

BACKGROUND: Exacerbations contribute substantially to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To assess whether prophylactic antibiotic treatment reduces exacerbations in patients with COPD and/or chronic bronchitis. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, Koreamed and references from relevant publications were searched up to October 2011. Randomised controlled trials comparing the effect of any prophylactic antibiotics with placebo for at least 3 months were included. The co-primary outcomes were the frequency of exacerbations of COPD or chronic bronchitis and adverse treatment events. RESULTS: A total of 19 trials involving 3932 subjects were included in the analysis: 5 recent trials included patients with moderate to severe COPD, whereas 14 older trials included patients with chronic bronchitis. The use of antibiotics significantly reduced the rate of COPD exacerbations (risk ratio [RR] 0.73, 95%CI 0.66-0.82), the number of chronic bronchitis exacerbations (standardised mean difference -0.23, 95%CI -0.35--0.11) and the proportion of patients with exacerbations of chronic bronchitis (RR 0.93, 95%CI 0.87-0.99). CONCLUSION: Prophylactic antibiotic treatment has a significant effect in reducing exacerbations in patients with COPD and/or chronic bronchitis.

Clinical characteristics of patients with tuberculosis-destroyed lung.

SETTING: Multicentre study. OBJECTIVE: To define the clinical characteristics of patients with tuberculosis (TB) destroyed lung due to past TB. DESIGN: We reviewed patients with TB-destroyed lung between May 2005 and June 2011. RESULTS: A total of 595 patients from 21 hospitals were enrolled. The mean age was 65.63 ± 0.47 (mean ± standard error); 60.5% were male. The mean number of lobes involved was 2.59 ± 0.05. Pleural thickening was observed in 54.1% of the patients. Mean forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC, bronchodilator response and number of exacerbations per year were respectively 2.06 ± 0.03 l (61.26% ± 0.79), 1.16 ± 0.02 l (49.05% ± 0.84), 58.03% ± 0.70, 5.70% ± 0.34, and 0.40 ± 0.04. The number of lobes involved was significantly correlated with FVC and FEV(1), and with the number of exacerbations per year. Use of long-acting muscarinic antagonists or long-acting beta-2 agonists plus inhaled corticosteroids resulted in bronchodilatory effects. Multivariable regression analysis showed that age, initial FEV(1) (%) and number of exacerbations during follow-up were independent factors affecting change in FEV(1). CONCLUSION: Decreased lung function with exacerbation, and progressive decline of FEV(1) were observed in patients with TB-destroyed lung.

GenoType® MTBDRplus assay detection of drug-resistant tuberculosis in routine practice in Korea.

SETTING: Korea is an intermediate-burden country with high rates of tuberculosis (TB) drug resistance. OBJECTIVE: To evaluate the performance of the GenoType® MTBDRplus (MTBDR) assay in diagnosing drug-resistant TB in routine practice in Korea. DESIGN: The MTBDR assay was performed on 428 samples, and the results were retrospectively compared with the results of conventional drug susceptibility testing (DST). The interval between treatment and diagnosis of drug resistance was also compared. RESULTS: The sensitivity, specificity and positive and negative predictive values of the MTBDR assay were respectively 96.6%, 98.9%, 93.4% and 99.5% for the detection of rifampicin (RMP) resistance; 93.8%, 98.3%, 92.7% and 98.6% for isoniazid (INH) resistance; and 91.1%, 99.2%, 99.4% and 98.7% for multidrug-resistant TB (MDR-TB). The median interval between the start of anti-tuberculosis chemotherapy and the reporting of results was 88.9 days for conventional DST and 19.8 days for MTBDR using clinical specimens. CONCLUSION: The specificity of the MTBDR assay in detecting MDR-TB was very high, although the sensitivity in detecting INH resistance and MDR-TB was not optimal (<95%). Although the turnaround time in detecting drug resistance was dramatically reduced with MTBDR compared to conventional DST, more effort is needed to shorten the turnaround time.

Clinical features of subjects with an isolated FEV1 reduction.

BACKGROUND: The clinical significance of an isolated reduction in forced expiratory volume in 1 second (FEV(1); i.e., low FEV(1), but normal forced vital capacity [FVC] and FEV(1)/FVC) has not been established. OBJECTIVE: To examine the clinical features of subjects with an isolated FEV(1) reduction. METHODS: Clinical, spirometry and radiological data were retrospectively collected from 15,192 subjects attending a medical check-up at the Health Promotion Center of the Asan Medical Center, Korea. Predicted spirometry values were calculated from the Korean reference equations, and the lower limit of normal was set at the 5th percentile. Subjects were divided into four groups: isolated FEV(1) reduction, normal (normal FVC, FEV(1) and FEV(1)/FVC), obstructive (low FEV(1)/FVC) and restrictive (low FVC and normal FEV(1)/FVC). The groups were compared in terms of clinical characteristics. RESULTS: Of the 15,192 subjects, 323 (2.1%) had an isolated FEV(1) reduction, 10,591 (69.7%) were normal, 951 obstructive (6.3%) and 3327 (22.0%) restrictive. The isolated FEV(1) reduction group had a higher proportion of subjects with smoking history (63.2% vs. 45.7%), radiology abnormalities (15.5% vs. 4.3%) and history of respiratory disease (8.4% vs. 3.0%) than the normal group (all P < 0.001). CONCLUSION: An isolated FEV(1) reduction suggests abnormal spirometry, and further study is needed to evaluate whether these cases belong to the obstructive or restrictive group.

Experimental lung collapse following deployment of a self-expandable bronchial occluder in a rabbit model.

OBJECTIVES: Closure of a bronchopleural fistula is required to prevent fatal empyema or aspiration pneumonia. The purpose of this study was to determine the feasibility and efficacy of bronchial occlusion with a self-expandable occluder to induce experimental lung collapse in a rabbit model. METHODS: 10 bronchial occluders (wine glass appearance; 8 mm in diameter and 15 mm in length) were implanted in the native left main bronchi of 10 rabbits via an endotracheal route. We analysed the following: (1) diameters and morphological changes of the bronchial occluders during follow-up; (2) percentage volume of the collapsed lung during follow-up; and (3) complications and gross pathology. 1-day and 2-week follow-up CT scans were routinely obtained. Rabbits were sacrificed 4 weeks after the experiment. RESULTS: In all 10 rabbits, the bronchial occluders were successfully implanted and were completely expanded within 2 weeks. Complete collapse of the left lung occurred in three rabbits on day 1 and in an additional two rabbits 2 weeks following implantation. Two other rabbits maintained the percentage volume of the collapsed lung between 51% and 99% during follow-up; the other three rabbits had <50% during follow-up. Pneumothoraces occurred in nine rabbits, but completely resolved at the 2-week follow-up. Right lung herniation across the midline progressed 2 weeks after occluder implantation. CONCLUSION: Placement of self-expandable occluders in a rabbit bronchus model was feasible and showed a potential to induce artificial lung collapse. While pneumothoraces were common, they resolved during follow-up.