Asthma and COVID-19 Associations: Focus on IgE-Related Immune Pathology.

Management of patients with asthma during the coronavirus disease 2019 (COVID-19) pandemic is a concern, especially since asthma predisposes patients to respiratory problems. Interestingly, asthma characterized by type 2 inflammation, also known as T-helper type 2-high endotype, displays a cellular and molecular profile that may confer protective effects against COVID-19. The results of experimental and clinical studies have established the actions of immunoglobulin E (IgE) in inducing airway hyperreactivity and weakening an interferon-mediated antiviral response following respiratory viral infection. Robust evidence supports the beneficial effect of the anti-IgE biologic treatment omalizumab on reducing respiratory virus-induced asthma exacerbations and reducing the frequency, duration, and severity of respiratory viral illness in patients with asthma. Indeed, accumulating reports of patients with severe asthma treated with omalizumab during the pandemic have reassuringly shown that continuing omalizumab treatment during COVID-19 is safe, and in fact may help prevent the severe course of COVID-19. Accordingly, guidance issued by the Global Initiative for Asthma recommends that all patients with asthma continue taking their prescribed asthma medications, including biologic therapy, during the COVID-19 pandemic. The impact of biologic treatments on patients with asthma and COVID-19 will be better understood as more evidence emerges.

Early achievement and maintenance of stable asthma control using initially higher-dose inhaled corticosteroids as part of combination therapy: an open-label pilot study.

BACKGROUND: Uncontrolled asthma is characterized by considerable variability. Well controlled asthma is associated with less unplanned use of health care resources and fewer acute exacerbations. In this study, we attempted to increase inhaled corticosteroid (ICS) doses initially in suboptimally controlled asthmatics, hypothesizing that early achievement of asthma control using this strategy would be associated positively with a higher level of stability. METHODS: This was a randomized, open-label, prospective study including patients with uncontrolled asthma who were randomized to receive higher-dose (HD) ICS in combination with a long-acting beta-agonist (LABA) for one month and then shifted to doses suggested in the practice guidelines (GD) or to receive GD therapy alone. Lung function, ie, forced expiratory volume in one second (FEV(1)), peak expiratory flow, Asthma Control Test scores, and frequency of acute exacerbations, was followed up for one year. RESULTS: Seventy-six patients were treated with the HD strategy and 80 with the GD strategy. The increase in FEV(1) from baseline was greater in the HD group than in the GD group, especially during the first month of treatment (304 ± 49 mL versus 148 ± 39 mL, respectively, P = 0.01). Numbers of patients with completely or well controlled asthma were higher in the HD group than in the GD group (92.1% versus 81.1%, respectively, P = 0.03). Further, there was a significant difference between the groups with regard to frequency of acute exacerbations (9.2% in the HD group versus 21.3% in the GD group, P = 0.02); this effect was more pronounced for patients in the HD group with partially controlled or uncontrolled asthma. CONCLUSION: Patients receiving HD therapy achieved asthma control more rapidly and maintained greater stability than those receiving GD therapy. This represents a novel strategy for gaining disease control in patients with uncontrolled asthma.

Risk factors for high mesothelial cell counts in HIV-negative patients with tuberculous pleural effusion.

BACKGROUND/PURPOSE: Higher mesothelial cell counts (HM) greater than 5% of total cell counts in tuberculous pleural effusions (TBPE) have been described in human immunodeficiency virus (HIV)-infected patients, however the nature and risk factors in HIV-negative patients with TBPE are unknown. The purpose of the study was to characterize the clinical manifestation of HM in HIV-negative patients with TBPE and evaluate the risk factors of developing HM-TBPE. METHODS: This retrospective study was undertaken in HIV-negative patients with TBPE from the Far Eastern Memorial Hospital Tuberculosis database. The cytologist and examining specialist differentiated and quantified the cell counts. HM-TBPE was defined when more than 5% of total cell counts in the pleural fluid were mesothelial cells. Multivariate analysis was calculated with stepwise logistic regression for HM-TBPE risk factors. RESULTS: Nineteen patients were diagnosed as HM-TBPE, while 30 were diagnosed with lower mesothelial cell counts TBPE (LM-TBPE). Compared with LM-TBPE patients, those with HM-TBPE had significantly decreased hemoglobin and serum albumin levels (p<0.05). Organ dysfunction such as congestive heart failure, liver cirrhosis and renal failure was significantly more common in patients with HM-TBPE (47.4%) than in patients with LM-TBPE (13.3%; p=0.01). Multivariate analysis revealed that independent risk factors for developing HM-TBPE included hypoalbuminemia (odds ratio =1.6; 95% confidence interval = 1.1-13.8) and the presence of organ dysfunction (odds ratio =4.5; 95% confidence interval = 1.4-17.5). CONCLUSION: Baseline hypoalbuminemia and comorbidities were independent risk factors for development of HM-TBPE in HIV-negative patients. Mesothelial cell counts should not be used alone in the diagnosis of TBPE. An understanding of the organ dysfunction associated with HM-TBPE in HIV-negative patients could avoid delayed diagnosis and treatment of tuberculosis.

Severity staging of chronic obstructive pulmonary disease: differences in pre- and post-bronchodilator spirometry.

PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) uses the post-bronchodilator spirometry for diagnosis and severity staging. We evaluated differences in the severity classification of COPD, based on pre- and post-bronchodilator spirometry. MATERIALS AND METHODS: From 2000 to 2004, 207 COPD patients who underwent spirometry before and after inhalation of 400 microg of fenoterol were analyzed. A responder to the bronchodilator test (BDT) was defined by the American Thoracic Society (ATS) as an increase in forced expiratory volume in one second (FEV(1)) or forced vital capacity > or = 12% and > or = 200 mL, and by the European Respiratory Society (ERS) as an increase in FEV(1) > or = 10% of the predicted value. COPD severity was classified according to the 2008 GOLD guidelines. RESULTS: For the entire study population, the FEV(1) increased by 11.8 +/- 12.5% of baseline after BDT and 41.1% and 27.1% of subjects were classified as responders using the ATS and ERS criteria, respectively. Based on pre-BDT spirometry, 55, 85, 58, and 9 patients were classified as Stage I-IV COPD, respectively. Sixty-seven (32.4%) patients changed severity staging after BDT, including 20.0%, 28.2%, 44.8%, and 66.7% of pre-BDT patients Stages I through IV, respectively. More ATS or ERS BDT-responders had a change in severity staging than non-responders (52.9% vs. 18.9% and 62.5% vs. 21.2%, both p < 0.001). CONCLUSION: Our data suggest that the severity staging of COPD using pre-BDT spirometry might lead to significant differences as compared to staging, based on post-BDT spirometry, as recommended by the current GOLD guidelines.

Budesonide/formoterol combination as a maintenance and rescue therapy: physicians' perspectives.

BACKGROUND: To investigate the rationale of clinicians when treating asthmatics with combined budesonide/formoterol in a single inhaler as a maintenance and rescue therapy (BFMRT). METHODS: A questionnaire was used to investigate, from the perspective of outpatient clinic physicians, why, how, and for whom BFMRT should be prescribed. Participants (N = 274) were employed in medical centers, regional hospitals, district hospitals, and private clinics; the majority of the clinicians were pulmonologists (75.5%). RESULTS: Most participants (84.9%) prescribed BFMRT primarily because of its convenience; 60.4% prescribed 1 puff (budesonide/formoterol, 160/4.5 microg/puff) twice daily and as needed and 38.5% 2 puffs twice daily and as needed; 70.4% did not insist that patients use budesonide/formoterol as a rescue treatment. There was no agreement on the dose (1 or 2 puffs as needed) or interval (5, 10, or 20 min) required for rescue treatment. Almost half (48.2%) of the physicians reported that they would not prescribe BFMRT because of patients' lack of understanding of the treatment. Further analysis showed that physicians practicing in medical centers, those specializing in chest medicine, and those working in higher socioeconomic regions may appreciate the benefits of BFMRT more than non-pulmonologists, those working in settings other than medical centers, and those employed in lower socioeconomic areas. CONCLUSIONS: More effort needs to be expended in the education of physicians responsible for asthma management, non-pulmonologists, those working outside of medical centers, and those practicing in rural areas in new treatment concepts to achieve optimal asthma control throughout the country.

Cytologically proven meningeal carcinomatosis in patients with lung cancer: clinical observation of 34 cases.

BACKGROUND/PURPOSE: Meningeal carcinomatosis (MC) is a rare neurologic complication of lung cancer. Occasionally, it is the initial presentation of lung cancer. The clinical features of MC exclusively in lung cancer patients have not been well identified and characterized. The purpose of this report is to disclose the clinical features, laboratory findings, treatment and survival of patients with MC from lung cancer. METHODS: We reviewed the medical records of 34 lung cancer patients with cytologically diagnosed MC at National Taiwan University Hospital from 1992 to 2002. Clinical symptoms and signs, cerebrospinal fluid parameters and lung cancer staging at the time of presentation were summarized. Previous treatment modalities for lung cancer, various treatments and response of MC, complications and survival times were also analyzed. RESULTS: Cerebrospinal fluid cytology revealed adenocarcinoma in 32 patients, and small cell carcinoma and squamous cell carcinoma in one each. MC occurred in approximately 0.7% of lung cancer patients. Nine patients had MC as the initial presentation of lung cancer. Symptom improvement was found in six patients who had whole brain irradiation for MC and one patient who had a ventriculoperitoneal shunt. Two of the patients with whole brain irradiation survived for longer than 1 year. Survival from cytologic diagnosis of MC ranged from 1 day to 82 weeks (median, 5.1 weeks). There was no difference in survival between patients treated by whole brain irradiation and other treatment modalities. CONCLUSION: The prognosis of MC from lung cancer is poor. A prospective study is needed to establish the effectiveness of combined modality therapy for patients with MC from lung cancer.

Analysis of fine-needle aspiration cytology of the salivary gland.

BACKGROUND/PURPOSE: Fine needle aspiration (FNA) cytology has been widely accepted as a safe method for diagnosis of salivary gland lesions. This study investigated the accuracy of FNA cytology of salivary gland lesions by correlation between histology and cytology. METHODS: One hundred and thirty-one archived salivary gland FNA specimens collected between January 1994 and December 2002 from 131 patients were correlated with histopathology findings. The major reasons for false-negative and false-positive results in cytologic diagnosis were determined. RESULTS: Considering the results of histopathology as the diagnostic standard, the sensitivity of FNA cytology in diagnosing malignancy was 74% (17/23) after excluding two cases which had a cytodiagnosis of suspicion of malignancy. Excluding eight cases that had a cytodiagnosis of suspicion of malignancy, the diagnostic specificity was 99% (97/98). There were six false-negative and one false-positive cases. CONCLUSION: This study demonstrated that FNA cytology of the salivary gland is a useful technique for diagnosis of salivary gland lesions. Inadequate labeling of the aspiration sites and insufficient cellularity were the most important factors that resulted in incorrect cytologic interpretation.

Antibody responses to pneumococcal polysaccharide vaccine in Taiwanese patients with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: A study was undertaken to assess the antibody responses to a 23-valent pneumococcal polysaccharide vaccine and clinical outcome in Taiwanese patients with chronic obstructive pulmonary disease (COPD). METHODS: From January to December 1999, 80 Taiwanese patients with COPD were enrolled. Each patient received a 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23). Specific IgG antibodies to pneumococcal capsular antigens of serotypes 4, 6B, 7F, 9V, 14, 18C, 19F, and 23F were measured before vaccination, and 6 weeks and 52 weeks after vaccination. RESULTS: Detectable prevaccination IgG antibody (> 1 microg/mL) was found in the range of 27.5% of patients for serotype 7F to 96.2% for serotype 14. Antibody concentrations in prevaccination sera were not different between middle-aged (< 65 years old) and elderly patients (> or = 65 years old). The percentage of elderly patients with postvaccination antibody concentration > 2 -fold higher than that prior to vaccination ranged from 84% for serotype 18C to 90% for serotypes 7F, 9V, and 19F. The change in antibody level (fold and absolute increases) postvaccination was not significantly different among the different age groups. CONCLUSION: Taiwanese elderly adults with COPD, even in advanced age, can mount a significant antibody response to pneumococcal polysaccharide vaccine. This study may support the existing recommendation that pneumococcal vaccine be offered to persons > or = 65 years old with COPD.

Sputum bacteriology in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease in Taiwan with an emphasis on Klebsiella pneumoniae and Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVE: Bacterial infection is one of the major causes of acute exacerbation of COPD (AECOPD). This study was undertaken to investigate the microbiology of AECOPD. METHODS: Medical records from 494 episodes of AECOPD in patients admitted to the National Taiwan University Hospital from January 2000 to June 2004 were reviewed. Severity of COPD was classified according to the 2003 Global Initiative for Chronic Obstructive Lung Disease guideline. RESULTS: Potential pathogenic microorganisms were isolated from patients in 328 (66.4%) episodes of AECOPD. The predominant bacteria were Klebsiella pneumoniae (19.6%), Pseudomonas aeruginosa (16.8%) and Haemophilus influenzae (7.5%), followed by Acinetobacter baumannii (6.9%), Enterobacter species (6.1%) and Staphylococcus aureus (6.1%). The incidence of Streptococcus pneumoniae was 2.4%. Spirometry results obtained within 1 year of the exacerbation were available in 186 cases. K. pneumoniae was more frequently isolated in stage I COPD (39.1%) than stage II (16.6%), III (13.8%) and IV (9.4%). No glucose non-fermentative Gram-negative bacilli were isolated in stage I patients. Multivariate logistic regression analysis revealed that P. aeruginosa (odds ratio (OR) 3.19; 95% confidence interval (CI): 1.21-8.38), intubation (OR 14.81; 95% CI: 5.08-43.12) and age (OR 1.1; 95% CI: 1.03-1.17) were independent risk factors for mortality. CONCLUSIONS: Klebsiella pneumoniae and P. aeruginosa are the most common sputum pathogens in hospitalized patients with AECOPD in Taiwan, with the former being more commonly isolated from mild COPD and the latter associated with poor clinical outcome. These results should be considered when deciding which antibiotics should initially be used to treat patients with AECOPD.

Utility of thyroid transcription factor-1 expression in the differential diagnosis of metastatic adenocarcinoma of serous effusion specimens prepared using the cell transfer technique.

BACKGROUND/PURPOSE: Pulmonary adenocarcinoma is a common malignancy of the pleural cavity. The cell transfer technique can be used to create multiple slides from a single smear. The goal of this study was to investigate the pulmonary origin of metastatic adenocarcinoma by evaluating the immunocytochemical reactivity to thyroid transcription factor-1 (TTF-1) of slides of serous effusion specimens prepared by the cell transfer technique. METHODS: In 2001, a total of 76 archived serous effusion specimens containing adenocarcinoma from patients were used in this study. The primary site of metastatic adenocarcinoma was determined by a review of the medical records. The cell transfer technique was used to create multiple slides from a single Papanicolaou-stained smear. If more than 10% of the target cells reacted with perceptible intensity, nuclear staining was considered to indicate a positive TTF-1 result. RESULTS: Positive rates of TTF-1 for body fluids collected from patients with lung, stomach, ovarian, breast, colorectal and liver carcinomas were 41/50, 0/11, 0/6, 0/5, 0/2 and 0/1, respectively. Lung adenocarcinoma showed TTF-1 positivity in 82% of specimens, and all other adenocarcinomas had negative TTF-1 staining results. CONCLUSION: This study demonstrated that TTF-1 immunostaining in serous effusion specimens prepared using the cell transfer technique is a sensitive and highly specific marker for metastatic lung adenocarcinoma.

Bacteraemic pneumonia caused by Neisseria lactamica with reduced susceptibility to penicillin and ciprofloxacin in an adult with liver cirrhosis.

This report presents a case of bacteraemic pneumonia caused by Neisseria lactamica in an adult patient with liver cirrhosis who was successfully treated with ceftriaxone. The isolate was confirmed as N. lactamica by analysis of a partial sequence of the 16S rRNA gene; it had reduced susceptibilities to penicillin (MIC 0.75 microg ml(-1)) and ciprofloxacin (MIC > or =0.5 mg l(-1)).

Predictive value of rapid shallow breathing index measured at initiation and termination of a 2-hour spontaneous breathing trial for weaning outcome in ICU patients.

BACKGROUND/PURPOSE: The rapid shallow breathing index (RSBI) is a weaning parameter usually measured at the start of a spontaneous breathing trial (SBT). This study investigated the value of RSBI measured at the beginning and termination of SBT as a predictor of weaning outcome. METHODS: RSBI was measured during the initial 1 minute (RSBI1) and at termination (RSBI2) of an SBT in 172 patients recovering from acute respiratory failure. RESULTS: Weaning was successful in 106 patients and failed in 66 patients. Among the 66 patients with weaning failure, 12 required reintubation within 48 hours (extubation failure), and the remaining 54 patients could not be extubated after SBT (trial failure). There were no differences between RSBI1 in the three groups (69.4 +/- 27.5, 81.7 +/- 24.4 and 75.5 +/- 26.5, respectively), but RSBI2 was significantly higher in patients with extubation failure (95.9 +/- 20.6) and trial failure (98.0 +/- 50.0) than in patients with weaning success (64.6 +/- 26.3) (both p < 0.001). Logistic regression revealed that RSBI2 was superior to RSBI1 and various physiologic indices in predicting weaning outcome. For the 118 extubated patients, the mean area under the receiver operating characteristic curve for RSBI2 and RSBI1 was 0.83 and 0.63, respectively. Using a threshold value of 105, the sensitivity, specificity, accuracy and likelihood ratio for weaning outcome were 0.91, 0.25, 0.85 and 1.38 for RSBI2 and 0.89, 0.16, 0.60 and 1.06 for RSBI1, respectively. CONCLUSION: This study found that RSBI measured at the completion of SBT was superior to that measured at the start in predicting weaning outcome in critically ill patients.

Elevation of telomerase activity positively correlates to poor prognosis of patients with non-small cell lung cancer.

Increased telomerase activity has been found in various types of human malignancies, including lung cancer. However, the correlation between the level of telomerase activity and the clinical characteristics of lung cancer patients remains unclear. The levels of telomerase activity in lung cancer specimens and adjacent non-neoplastic tissues obtained from 68 patients who underwent surgery were measured by using a non-radioactive quantitative method. Clinical and pathologic parameters were evaluated with respect to the level of telomerase activity. Prominent telomerase activity was detected in 58 (85.3%) lung cancer tissues and 21 (30.9%) adjacent non-neoplastic tissues. There was a trend of increase in relative telomerase activity in regard to the advanced pathological stage, and lymph node metastasis. Using Cox regression analysis, we found that every 100 unit of increase in relative telomerase activity was associated with an increase in the hazard ratio of death by 13% after controlling for other variables such as age, gender, and stage (Hazard ratio=1.13; 95% CI: 1.03-1.23, P=0.006). For patients with stage I disease, an increase of every 100unit of relative telomerase activity was associated with an even higher increase of 33% in the hazard ratio of death (Hazard ratio=1.33; 95% CI: 1.07-1.65, P=0.011) and a 16% increase in the hazard of disease recurrence (Hazard ratio=1.16, 95% CI: 1.01-1.33, P=0.032). The level of telomerase activity is positively correlated with the risk of recurrence and mortality of lung cancer. The level of telomerase activity would predict the prognosis of lung cancer patients.

CD44 splicing pattern is associated with disease progression in pulmonary adenocarcinoma.

BACKGROUND AND PURPOSE: Certain alternatively spliced exons of CD44 gene have been associated with specific functions. However, these functions may have come from inclusion of a central array of alternatively spliced exons, rather than a single one. The goals of this study were to analyze all of the variant exons included by alternative splicing, the entire population of CD44 mRNA transcripts, and the prognostic implications of CD44 mRNA and protein isoforms expressed by non-small cell lung cancer (NSCLC). METHODS: Using a polymerase chain reaction protocol with short reaction times, we amplified, sequenced and quantified CD44 mRNA transcripts from 52 samples of NSCLC to determine the splicing patterns of alternatively included exons and the proportion of each CD44 mRNA transcript. The expression of CD44 standard form and variant isoforms CD44v3 and CD44v6 were also analyzed by immunohistochemistry (IHC). RESULTS: Normal lung and NSCLC expressed CD44 mRNA transcripts containing variant exons v10, v8-10, v6-10, v3-10 and v2-10. In squamous cell carcinoma, the expression rates of these mRNA transcripts were equal to or higher than those of the normal lung, and the splicing pattern was not associated with disease progression. In adenocarcinoma, the expression rates of CD44v6-10, v3-10 and v2-10 mRNA were lower than in normal lung. The down-regulation of CD44v6-10, CD44v3-10 mRNA and CD44v6 protein paralleled the progression of adenocarcinoma. Recurrence of adenocarcinoma was associated with negative expression of CD44v6-10 or CD44v3-10 mRNA, and with low-level expression of CD44v6 or CD44v3 by IHC. Negative expression of CD44v6-10 mRNA and reduced expression of CD44 v6 protein were associated with a shorter disease-free and overall survival in the univariate but not the multivariate analysis. CONCLUSION: Our data suggest that CD44 splicing pattern is associated with disease progression in adenocarcinoma.

Distribution according to histologic type and outcome by gender and age group in Taiwanese patients with lung carcinoma.

BACKGROUND: The results from previous studies suggested that the clinical characteristics and outcomes of patients with lung carcinoma vary between gender and age groups. The objective of the current study was to assess the trend in the evolution of the histologic types in Taiwan and to compare the outcomes of patients with lung carcinoma between different gender and age groups. METHODS: Patients with primary lung carcinoma were identified through the cancer registry system. Clinical records were reviewed and analyzed for age, gender, disease stage, histology, treatment modalities, and survival. A multivariate analysis using a Cox proportional hazards model was applied for gender, age (by decade), histologic type, disease stage, and treatment modality. RESULTS: Between 1991-1999, 2714 patients with histologically or cytologically proven lung carcinoma were included. Adenocarcinoma was the major cell type of lung carcinoma (52.5%), with a significant trend toward an increase in adenocarcinoma during the study period. A significantly high percentage of adenocarcinoma was demonstrated in female patients (73.5%), who also had better survival compared with male patients (P = 0.002), especially in the group age 50-69 years. Patients age < 40 years also had a poor prognosis, which was worse compared with the prognosis for patients age 40-59 years. patients who had adenocarcinoma had a better survival rate compared with patients who had other histologic types (relative risk, 0.78; 95% confidence interval, 0.69-0.87). CONCLUSIONS: Adenocarcinoma was predominant in female patients and emerged as a greater problem than other histologic types in Taiwan, potentially raising the importance of studies regarding the benefit of population diversity in new antitumor therapies, such as gefitinib. Female patients with lung carcinoma had a better prognosis than male patients in the group age 50-69 years, warranting further studies on potential prognostic factors associated with middle age, such as hormone status.

The role of bronchoscopic assessment in esophageal cancer - clinical and survival analysis in 153 patients.

BACKGROUND AND PURPOSE: The diagnostic value and indications for fiberoptic bronchoscopy in the preoperative assessment of patients with esophageal cancer have not been fully studied. We evaluated the role of fiberoptic bronchoscopic examination in the stage work-up of patients with esophageal cancer and correlated the results with survival time analysis. METHODS: The medical records of 153 patients with an initial diagnosis of esophageal cancer were reviewed. Clinical data, bronchoscopic findings, treatment courses, and survival time of these patients were analyzed. RESULTS: On initial bronchoscopic examinations, distortion/compression of the normal structure and protrusion at the posterior wall of the trachea or bronchus were the most common bronchoscopic findings (35.9%). We stratified patients into 3 subgroups according to bronchoscopic findings of direct invasion, external compression, and negative findings. The symptoms of dyspnea, hoarseness, aspiration and fever were more frequent in patients with direct airway invasion compared with patients with external compression and negative bronchoscopic findings (p < 0.02). Washing and brushing cytology examinations were all negative in patients with external compression of the airway. There was a significant difference of survival time among these 3 groups of patients (direct invasion: 5.6 +/- 0.6 months; external compression: 12.3 +/- 0.9 months; negative findings: 13.3 +/- 1.1 months, p < 0.01). Direct airway invasion and original cancer stage were the most important variables for survival in the multivariate analysis, and the hazard ratio for prognosis was 2.5 (95% confidence interval [CI], 1.1-4.6) and 4.2 (95% CI, 1.5-9.3), respectively. Twelve patients (80%) with tracheoesophageal (TE) fistulae died within 3 months after diagnosis due to aspiration pneumonia and septic shock. CONCLUSIONS: The role of bronchoscopic examination in patients with esophageal cancer for preoperative evaluation resides in its ability to predict airway invasion and its impact on survival. Advanced cancer stage (stage IV) and direct airway invasion (especially TE fistula) were significantly associated with poor prognosis. These results suggest that patients suffering from dyspnea, hoarseness, aspiration and fever, implicating a high probability of airway invasion, are more likely to benefit from bronchoscopic examination and proper management in order to prevent aspiration or complications.

Trends in the mortality of chronic obstructive pulmonary disease in Taiwan, 1981-2002.

BACKGROUND AND PURPOSE: The reported prevalence, morbidity and mortality of chronic obstructive pulmonary disease (COPD) varies in different countries due to actual differences and to differences in classification criteria. This study analyzed the trends in COPD mortality and its rank among leading causes of death in Taiwan. METHODS: Using national mortality and population data, we identified COPD as a cause of death according to codes 490 (bronchitis, not specified as acute or chronic), 491 (chronic bronchitis), 492 (emphysema) as has been officially calculated previously in Taiwan, and by adding code 496 (chronic airway obstruction, not elsewhere classified) of the ninth revision of the International Classification of Diseases (ICD-9). We calculated crude, age-adjusted and age-specific mortality rates and analyzed the rank of COPD as a cause of death for the period from 1981 to 2002. RESULTS: Crude COPD mortality was unchanged from 1981 to 1993 at 8.26 to 8.47 deaths per 100,000 population, and steadily increased thereafter to 17.88 per 100,000 in 2002. After age standardization, mortality decreased from 8.26 to 4.91 per 100,000 population from 1981 to 1993 and then increased to a peak of 7.36 per 100,000 in 1999. This increase was due to greater increase in mortality in men. COPD mortality decreased steadily throughout the study period in those younger than 65 years while in older groups, it decreased during 1981-1991 and then increased. ICD-9 code A323 (including codes 490-493) has been previously used in official mortality data for asthma, chronic bronchitis and emphysema in Taiwan without inclusion of a specific code for chronic airway obstruction. According to our analysis, this method underestimated two-thirds of real overall mortality due to COPD and asthma. By including COPD and asthma, the obstructive airway disease category increased from 11th to sixth as a cause of death in 2002. CONCLUSIONS: In Taiwan, mortality rates for COPD decreased from 1981 to 1993 and increased thereafter, which is largely attributable to increased rates in men. COPD is increasingly important and a leading cause of death in Taiwan.

Total cyclooxygenase-2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non-small cell lung cancer patients.

Interaction between cancer cells and adjacent stromal cells is important to promote tumor development. Our aim was to study total COX-2 mRNA expression in both cancer cells and surrounding stromal cells and its association with angiogenic factor VEGF mRNA expression, tumor angiogenesis and prognosis in patients with NSCLC. COX-2 mRNA expression in both cancer cells and stromal tissue was analyzed using real-time quantitative (RTQ) RT-PCR in 60 NSCLC surgical specimens. Immunohistochemistry (IHC) was used to localize COX-2 protein in tumor specimens. Correlations between tumoral total COX-2 mRNA expression and VEGF mRNA expression (measured by RTQ RT-PCR), intratumoral microvessel counts (evaluated by IHC), other clinicopathologic variables, survival and relapse were tested. COX-2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor-associated microvessels). VEGF protein expression was mainly located in cancer cells. There was a significant association between high tumoral total COX-2 mRNA expression and high VEGF mRNA expression (p = 0.01) or high intratumoral MVC (p < 0.001) but not other clinicopathologic variables, including tumor status and lymph node metastasis. Patients with higher tumoral total COX-2 mRNA expression had a statistically shorter survival time (median 15.0 +/- 2.61 months) and relapse time (median 5.0 +/- 1.37 months) than those with lower tumoral total COX-2 mRNA expression (median 40.0 +/- 3.12 and 34.0 +/- 3.11 months; p < 0.0001 and p < 0.0001, respectively, log-rank test). A significant difference in survival and relapse time was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low intratumoral MVC (p = 0.0046 and p = 0.0038, respectively). After stratification by disease stage or histologic subtype, the prognostic significance of high total COX-2 mRNA expression was still apparent in both stage I and stage II-IV and in both squamous cell carcinoma and adenocarcinoma (p < or = 0.01 for all). Multivariate analysis using the Cox regression model with backward elimination showed that tumoral total COX-2 mRNA expression and lymph node status were the 2 most important independent prognostic predictors for survival and disease relapse. We report that total COX-2 mRNA expression in cancer cells and surrounding stromal cells correlates strongly and positively with VEGF mRNA expression, intratumoral MVC and adverse prognosis in NSCLC patients. This implies that COX-2 expression in both cancer cells and stromal cells within the tumor microenvironment may play an important role in upregulating the expression of the angiogenic factor VEGF and tumor angiogenesis in NSCLC and explains, in part, the adverse prognostic effect of COX-2 overexpression in patients with NSCLC.

Negative expiratory pressure in the assessment of bronchodilator response: comparison of spirometry and the interrupter method.

BACKGROUND AND PURPOSE: The negative expiratory pressure (NEP) method offers a simple and rapid assessment of expiratory flow limitation (EFL) during tidal respiration. This study compared the value of NEP in the assessment of the bronchodilator test (BDT) with those of spirometry and the interrupter method. METHODS: Thirty two patients referred to the lung function laboratory for BDT were investigated. All patients underwent spirometry, interrupter airway resistance (Rint) and NEP measurements in the sitting position before and after inhalation of 500 microg of terbutaline. A positive BDT was defined as an increase in the forced expiratory volume in 1 second (FEV1) of > or = 12%. RESULTS: The ratio of FEV1 to forced vital capacity (FVC) was less than 70% in 21 (65.6%) patients, but EFL as demonstrated by NEP (EFL-N) was present in only 10 patients (31.3%). The baseline EFL-N was only weakly correlated with FEV1 (r = -0.36, p = 0.04), but not with Rint or FEV1/FVC. Among the 14 patients with positive BDT results, the change in FEV1 was correlated with the change in Rint (r = -0.69, p < 0.01), but not with the change in EFL-N. CONCLUSIONS: These data suggest that, compared with spirometry and the interrupter method, NEP applied in the sitting position is not sensitive in the assessment of bronchodilator response in patients with obstructive airway disorders.