Role of PGE(2) in protease-activated receptor-1, -2 and -4 mediated relaxation in the mouse isolated trachea.

1. The potential mediator role of the prostanoid PGE(2) in airway smooth muscle relaxations induced by peptidic and proteolytic activators of PAR-1, PAR-2, PAR-3 and PAR-4 was investigated in carbachol-precontracted mouse isolated tracheal segments. 2. The tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced smooth muscle relaxation that was abolished by the non-selective cyclo-oxygenase (COX) inhibitor, indomethacin. The relative order for mean peak relaxation was SLIGRL-NH(2)>GYPGKF-NH(2) approximately amp; SFFLRN-NH(2)>SFNGGP-NH(2). 3. SFFLRN-NH(2), SLIGRL-NH(2) and GYPGKF-NH(2), but not SFNGGP-NH(2), induced significant PGE(2) release that was abolished by indomethacin. Like that for relaxation, the relative order for mean PGE(2) release was SLIGRL-NH(2)>GYPGKF-NH(2)>SFFLRN-NH(2)>SFNGGP-NH(2). 4. In dose-response studies, SLIGRL-NH(2) induced concentration-dependent increases in PGE(2) release (EC(50)=20.4 microM) and smooth muscle relaxation (EC(50)=15.8 microM). 5. The selective COX-2 inhibitor, nimesulide, but not the COX-1 inhibitor valeryl salicylate, significantly attenuated SLIGRL-NH(2)-induced smooth muscle relaxation and PGE(2) release. 6. Exogenously applied PGE(2) induced potent smooth muscle relaxation (EC(50)=60.3 nM) that was inhibited by the mixed DP/EP(1)/EP(2) prostanoid receptor antagonist, AH6809. SLIGRL-NH(2)-induced relaxation was also significantly inhibited by AH6809. 7. In summary, the results of this study strongly suggest that PAR-mediated relaxation in murine tracheal smooth muscle is dependent on the generation of the spasmolytic prostanoid, PGE(2). PAR-stimulated PGE(2) release appears to be generated preferentially by COX-2 rather than COX-1, and induces relaxation via activation of the EP(2) receptor.

Modulation of airway smooth muscle tone by protease activated receptor-1,-2,-3 and -4 in trachea isolated from influenza A virus-infected mice.

Relaxant and contractile effects of the tethered ligand domain sequences of murine PAR-1, PAR-2, PAR-3 and PAR-4, and of the proteases thrombin and trypsin were examined in mouse isolated tracheal preparations. The epithelium- and cyclo-oxygenase-dependence of these effects and the potential modulatory effects of respiratory tract viral infection were also investigated. In carbachol-contracted preparations, trypsin, thrombin, and the tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced transient, relaxant responses that were abolished by the cyclo-oxygenase inhibitor indomethacin. Repeated administration of SFFLRN-NH(2), SLIGRL-NH(2) or GYPGKF-NH(2) (30 microM) was associated with markedly diminished relaxation responses (homologous desensitization), although there was no evidence of cross-desensitization between these peptides. The tethered ligand domain sequences for PAR-1 and PAR-4 induced a rapid, transient contractile response that preceded the relaxant response. Contractions were not inhibited by indomethacin and were not induced by either thrombin or trypsin. Influenza A virus infection did not significantly affect the responses induced by either the proteases or peptides. Furthermore, epithelial disruption caused by mechanical rubbing had no significant effect on responses to these PAR activators in preparations from either virus- or sham-infected mice. In summary, the proteases trypsin and thrombin, and peptide activators of PAR-1, PAR-2 and PAR-4 induced relaxant responses of mouse isolated tracheal smooth muscle preparations, which were mediated by a prostanoid, probably PGE(2). Interestingly, PAR-mediated relaxations were not significantly diminished following acute damage to the epithelium caused by mechanical rubbing and/or the respiratory tract viral pathogen, influenza A. British Journal of Pharmacology (2000) 129, 63 - 70.

Oxygen, arterial blood gases and ventilation are unchanged during dialysis in patients receiving pressure support ventilation.

This study was undertaken to observe whether dialysis-induced alveolar hypoventilation and arterial hypoxaemia occur during bicarbonate haemodialysis in patients receiving partial mechanical support with pressure support ventilation. Nineteen patients admitted to the medical intensive care unit requiring mechanical ventilation and haemodialysis were enrolled. Arterial blood gas, white blood cell (WBC) count, minute ventilation, respiratory rate, breathing pattern and blood pressure were measured according to the following time schedule: pre-dialysis (time 0), and at 15, 30, 60, 120, 180, 240 min thereafter. Results showed that, with the use of cuprammonium dialyser, the WBC count dropped immediately and reached the nadir 15 min after haemodialysis. Thereafter, it recovered and overshot the pre-dialysis values until the end of dialysis. The bicarbonate dialysate indeed resulted in rapid and significant metabolic alkalosis. However, no decrease of PaO2 occurred throughout haemodialysis. The tidal volume, minute ventilation and breathing pattern remained stable during haemodialysis. We conclude that neither dialysis-induced alveolar hypoventilation nor arterial hypoxaemia developed during bicarbonate dialysis in patients mechanically ventilated with the pressure support ventilation.

Telomerase activity in pleural effusions: diagnostic significance.

PURPOSE: To determine the diagnostic value of pleural fluid telomerase activity in distinguishing a malignant from a nonmalignant pleurol effusion in a cohort of patients undergoing thoracentesis. PATIENTS AND METHODS: Using a polymerase chain reaction (PCR)-based assay, telomerase activity was examined in the pleural fluid cells obtained from 144 consecutive, unselected patients. According to the final diagnosis achieved, these patients were classified into three groups: group I consisted of 70 malignant pleural effusions diagnosed by either fluid cytology or pleural biopsy, group II consisted of 52 nonmalignant pleural effusions, and another 22 samples were categorized to be suspicious malignant pleural effusions (group III) due to inconclusive results in effusion cytology and percutaneous pleural biopsy, but were strongly suspicious in clinical settings. RESULTS: The presence of telomerase activity was observed in 64 of 70 samples in group I (91.4%), three of 52 samples in group II (5.8%), and 20 of 22 samples in group III. All three nonmalignant, telomerase-positive pleural effusion samples in group II were obtained from patients with tuberculosis. As a diagnostic criterion for malignant pleural effusion in group I and group II patients, positive telomerase activity had a sensitivity of 91.4%, a specificity of 94.2%, and a positive and negative predictive value of 0.96 and 0.89, respectively. CONCLUSION: Our results indicate that the detection of telomerase activity may be a useful adjunct to cytopathologic methods in the diagnosis of malignant pleural effusions.

Respiratory drive and pulmonary mechanics during haemodialysis with ultrafiltration in ventilated patients.

The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.

Elastance of the pleural space: a predictor for the outcome of pleurodesis in patients with malignant pleural effusion.

BACKGROUND: In patients who have malignant pleural effusion, it is difficult to diagnose trapped lung before thoracoscopy, thoracostomy, and drainage of the effusion. Predicting the outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung is also difficult. OBJECTIVE: To investigate the factors that may be useful in diagnosing trapped lung and predicting the outcome of pleurodesis. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: 65 patients with symptomatic malignant pleural effusion. INTERVENTION: A chest tube was inserted for drainage of the effusion, and pleurodesis was done using bleomycin as the sclerosant. MEASUREMENTS: The pH and glucose levels of the effusion and the elastance of the pleural space (defined as the decline in pleural fluid pressure in cm H2O after removal of 500 mL of effusion) were measured. The outcome of pleurodesis was evaluated 1 month after the chest tube was removed. RESULTS: Patients with an elastance of 19 cm H2O or more had a higher incidence of trapped lung (11 of 14 patients) than did those with an elastance less than 19 cm H2O (3 of 51 patients) (P < 0.001). None of the 14 patients with an elastance of 19 cm H2O or more and none of the 14 patients with a trapped lung had successful pleurodesis. Forty-two of 43 patients with an elastance less than 19 cm H2O who did not have a trapped lung had successful pleurodesis. Elastance seemed to be the best predictor for trapped lung and outcome of pleurodesis, although outcome was also correlated with pH and glucose levels of the effusion. Low-dose bleomycin (30 mg) is as effective as the usual dose of bleomycin (60 mg) for pleurodesis. CONCLUSION: In patients with symptomatic malignant pleural effusion, measurement of the elastance of the pleural space is a simple and effective method for the diagnosis of trapped lung and prediction of the outcome of chemical pleurodesis with bleomycin.

Bacterial tracheitis: a case report.

An 18-month-old girl was brought to the emergency room of Chang Gung Children's Hospital with inspiratory stridor, suprasternal retractions and imminent respiratory failure. Despite orotracheal intubation, persistent poor air-entry was noted. Flexible bronchoscopy via the endotracheal tube showed a copious amount of mucopurulent secretions in the tracheobronchial tree without any foreign bodies. With vigorous suctioning and antibiotic treatment, she had a rapid recovery. Tracheal aspirates showed a growth of Haemophilus influenzae. Cefamandole was used with good response. In conclusion, although bacterial tracheitis is an uncommon obstructive upper airway disease in children, using a bronchoscope to diagnose and to guide specific therapy can decrease the morbidity and mortality.

Evaluation of chronic atelectasis in children using chest computed tomography and bronchoscopy.

A heterogeneous group of 11 children with atelectasis persisting longer than one month were investigated for the causes using chest computed tomography and fiberoptic bronchoscope. Four young infants had right upper lobe (RUL) posterior segmental atelectasis simulating RUL lobar collapse in plain chest films; all had only two visible segmental bronchi by bronchoscopic examination. Intraluminal obstruction in the central airway was not a common cause of pediatric chronic atelectasis in this small series of patients. Only one obstructive atelectasis caused by dilated pulmonary arteries was detected in this study. Two patients with pre-existing neuromuscular diseases showed multiple atelectasis. The atelectatic lobes do not spontaneously re-inflate following flexible bronchoscopy. Investigations involving a larger number of cases are needed to substantiate the etiologies and to guide specific therapy for those children with chronic atelectasis.

Home mechanical ventilation: investigation of 34 cases in Taiwan.

To evaluate the characteristics of and acceptance by persons in Taiwan who currently use positive-pressure mechanical ventilation at home (HMV), a survey was conducted in August 1992 through home care and equipment providers to investigate these patients. The 34 cases enrolled, including 18 males and 16 females, were classified into four groups: (1) lung disease group (LD) (n = 7) including chronic obstructive pulmonary disease and bronchiectasis; (2) neuromuscular group (NM) (n = 14) including diverse neuromuscular diseases; (3) spinal disease group (SP) (n = 7) including spinal cord injuries or tumors and (4) unresponsive stroke group (US) (n = 6). The average age of the SP group was much younger than those of the other three groups. The duration of home ventilation was from 1 to 36 months, with a mean duration of 10.6 +/- 8.7 months. Fifteen cases had received HMV for more than one year. Twenty six (76.5%) of the patients were completely dependent. All of the US patients had to be ventilated all day long in contrast to 71.4% of LD completely dependent. The cost of the US group was higher than that of the other three groups. Two of the LD, five of NM and one US patient had been re-admitted because of pneumonia, tracheostomy wound infection, granulation formation or weaning problems before the study. A follow-up survey was done four months, then one year later. The survival rate was 16.7% for LD group, 50% for NM and US group. Of the SP group, all patients were surviving at the end of this study. Most of the present HMV users were satisfied with their setting. It was concluded that HMV is an acceptable alternative way of therapy for long-term ventilation patients in Taiwan. SP and NM patients are better candidates for HMV. The overall one year survival rate is promising, while SP patients had the best prognosis. Patients who had already used HMV for more than 11 months, regardless of the disease, have a better chance to live another year.

Congenital tracheal stenosis: report of six cases.

We experienced six cases of congenital tracheal stenosis during a 3 years' period from October 1991 to September 1994 in Chang Gung Children's Hospital, Taiwan. The presenting symptoms of congenital tracheal stenosis varied from acute obstructive upper respiratory episodes in young childhood, stridor and wheezing since birth, recurrent bronchiolitis, difficult to intubate with endotracheal tube. Although bronchoscopy was diagnostic, but further imaging studies without anesthesia were equivocal. In spite of pericardial patch-tracheoplasties, the two cases undergoing surgery expired. During follow-ups, the remaining four patients suffered from persisting noisy respiration by conservative management.

Pediatric flexible bronchoscopy: a three-year experience.

One hundred and forty-one flexible fiberoptic bronchoscopies were performed in 124 pediatric patients in Chang Gung Children's Hospital between October 1991 and September 1994. Eleven of these patients were younger than 1 month old; 52 patients were younger than 1 year old; 94 patients were younger than 6 years old. The bronchoscope used was Olympus BF 3C20; with a 3.5 mm outer diameter, it also has a build-in 1.2 mm working channel. Most of the procedures were done in the pediatric intensive care unit. Oral chloral hydrate and parenteral benadryl were given as pre-sedation medication 30 minutes before the procedures; for most cases intravenous midazolam and meperidine hydrochloride were given immediately before the examination. The most common diagnoses were laryngomalacia, airway foreign bodies, subglottic stenosis or tracheal stenosis. Six episodes of transient hypoxemia and one brief episode of apnea were encountered. It was concluded that flexible fiberoptic bronchoscopy, very useful and safe in pediatric patients, has been underused in Taiwan.

Pulmonary echinococcosis--a case report.

Pulmonary echinococcosis is a rare disease in Taiwan and has never been reported in Taiwan's literatures. Here we report an overseas Chinese from Calcutta, India, presenting with recurrent hemoptysis and chest pain and with two big lung masses on chest roentgenogram. Rupture and spike fever ensured after fine needle aspiration of the cysts. Successful surgical intervention was obtained and echinococcal infection was documented pathologically.

Multiple brushings with immediate Riu's stain via flexible fibreoptic bronchoscopy without fluoroscopic guidance in the diagnosis of peripheral pulmonary tumours.

BACKGROUND: Accurate diagnosis of peripheral pulmonary lesions usually relies on fluoroscopic guided procedures. As fluoroscopy is not routinely available in many respiratory units, an approach not using fluoroscopy but with a high diagnostic yield is highly desirable. METHODS: Immediate cytological examination of multiple brushings using Riu's stain, a modified Wright's stain, was performed in 38 patients with peripheral pulmonary lesions not visible at bronchoscopy. The results were compared with the final diagnoses determined by histological examination or subsequent Papanicolaou staining of cytological specimens and clinical course. RESULTS: Of the 38 patients 29 were subsequently confirmed to have a malignant tumour. Our method provided a diagnosis of malignancy in 86% of these lesions. The accuracy (91%) and sensitivity (88%) were higher for lesions > 3 cm in diameter than for those of diameter < or = 3 cm (87% and 83%). There were no false positive results. The 29 lesions correctly diagnosed as malignant by Riu's stain required significantly fewer brushings (mean (SD) 3 (2)) than the nine benign lesions (5 (4)). CONCLUSIONS: This technique provides a high diagnostic yield, avoids the need for fluoroscopy, and is probably safer than percutaneous biopsy.

Non-asphyxiating tracheobronchial foreign bodies in adults.

The presentations of 47 adult patients with a non-asphyxiating tracheobronchial foreign body were reviewed. The duration of residence of the foreign body was 1 week or less in nine ("acute group"); 1 month or more in 29 ("chronic group"), uncertain in four ("uncertain group"); and the foreign body was a broncholith in five patients ("broncholith group"). In the chronic and uncertain groups, no precipitating factor was found and bone was the most common foreign body. In the chronic group, a choking history was obtained before bronchoscopy in only 15 patient. Clinical manifestations and roentgenograms were nonspecific in most cases, except in the acute group. In the chronic group, the mean duration of residence of the foreign body was 25.8 months. The diagnosis was delayed due to absence of a choking history and invisibility of the foreign body on chest films in 12, due to patient's ignorance in 14, due to physician's ignorance in 1, and due to previous unsuccessful retrieval attempts in 2 patients. The main indication for bronchoscopy in the acute group was a choking history or a visible foreign body on the chest film. In the chronic group, a choking history or conditions leading to "suspicion of an endobronchial lesion" were the main indications. The foreign body was removed with a fibreoptic bronchoscope in over 90% of patients. It is concluded that the most important diagnostic factor is a high clinical index of suspicion and that flexible fibreoptic bronchoscopy provides a valuable therapeutic option in selected conditions.

Pediatric flexible fiberoptic bronchoscopy--a preliminary report.

The introduction of flexible fiberoptic bronchoscopy into clinical use in 1968 had led a veritable explosion in the application of pulmonary endoscopy. In 1978, Wood and his colleagues, using a 3.5 mm Olympus 3C4 pediatric bronchoscope, expanded this technique to pediatric field. Up-to-now, they have more than 2000 bronchoscopies in pediatric patients, however, there has been no report in this field in Taiwan. I, using a new Olympus pediatric flexible fiberoptic bronchoscope 3C20, sedation and topic anesthesia, performed 24 airway examinations in 22 patients in the past 7-month period. The youngest patient was a 1672 gm, 4 day-old baby. The most frequent indication was stridor and most common diagnosis was laryngomalacia. The complications were not common and could have been avoidable if performed by an expert. My conclusion is that pediatric fiberoptic bronchoscopy is possible even in small babies less than 3 kg of weight.

Repository dexamethasone in the treatment of acute bronchial asthma.

Fifty-two patients with acute asthma requiring immediate therapy but not hospitalization were studied in an emergency department following conventional therapy with bronchodilators. After discharge, the patients were treated with a controlled regimen of long-acting theophylline and beta-agonist inhalation as necessary. They were randomly assigned to one of three groups using a double blind model. Group A received intramuscular and oral placebos. Group B received intramuscular dexamethasone injection along with oral placebo treatment. Group C received oral dexamethasone by a tapering schedule associated with placebo intramuscular injection. Follow-up was carried out 7 days after the treatment in the emergency room. There were no significant statistical differences in the relapse rate among the three groups. Those patients who received oral or intramuscular dexamethasone had a decrease in the need for beta-agonist inhalation and fewer respiratory symptoms. However, there was no significant statistical difference between groups B and C. It was concluded that repository steroids could reduce the respiratory symptoms and frequency of beta-agonist usage as effectively as oral steroid treatment. However, the steroids do not improve the relapse rate in patients with only mild symptoms.

Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease.

We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with beta-thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions.

Whole lung tuberculosis. A disease with high mortality which is frequently misdiagnosed.

The mortality rate of WLTB was significantly higher than non-WLTB in 45 of 516 cases of PTB in a 24-month period. There is no known underlying disease predisposing to WLTB. Clinically, the patients were significantly more toxic and had lower serum albumin and hemoglobin levels than non-WLTB patients. They had a lower rate of positive PPD tuberculin skin tests. The chest roentgenograms revealed three patterns: (1) DBS type in 15--all with multiple or diffuse opacities with or without cavitations; (2) DHS type in 20--eight with typical miliary lesions and 12 with atypical miliary patterns; (3) combined focal PTB and DHS type in ten. We found that atypical chest roentgenographic patterns were common in WLTB and frequently led to misdiagnosis. The delayed diagnosis and treatment of this advanced disease resulted in the high mortality. Early, empirical antituberculosis chemotherapy is indicated and life-saving.

Broncholithiasis: a neglected bronchial disease in this country. Illustration of three cases.

A broncholith is a calcified lymph node which partially or completely erodes into the bronchial lumen. Its manifestations are non-specific and may result in life-threatening complications. In Taiwan, pulmonary tuberculosis, one of the most common etiologies of broncholithiasis, is common. To our knowledge, no report on broncholithiasis can be found in literature in this country. We herein present three cases of broncholithiasis experienced in the past 11 years in Chang Gung Memorial Hospital. The presenting manifestations are obstructive pneumonia in two cases, and hemoptysis in the other one. In two of them, the broncholiths were located in the right side. Fiberoptic bronchoscopy was performed, and the stones were visible in all of them. Bronchoscopic removal of stone was successful in two cases, and the other coughed up stones spontaneously after bronchoscopies. In the absence of significant symptoms or complications, only observation is necessary. For the symptomatic borncholiths, we advocate that bronchoscopic removal is worth trying to eliminate the necessity of thoracotomy unless complications are present, which indicate surgical intervention such as massive hemoptysis, fistula formation between tracheobronchial trees and esophagus or vessels, recurrent pulmonary infection or suspicion of malignancy.