Biomedical subjects
Publications and source records attributed to G Joos.
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Rats are increasingly used to study airway inflammation and bronchial responsiveness. Relative little is known on the contribution of small airways in this animal model. We therefore compared the responsiveness to various inflammatory agents of isolated trachea, main bronchi (using classic organ bath) and isolated bronchioles (using small myograph) from Wistar and Fisher 344 rats. The largest contraction was elicited on all preparations by carbachol. Histamine elicited a (small) contraction only on bronchioles. The contractions elicited by serotonin, bradykinin, and the thromboxane A2-mimetic U-46619 were always relatively larger in bronchioles than in trachea and main bronchi. The sensitivities to carbachol and serotonin were smaller in bronchioles. The tachykinins substance P and neurokinin A elicited no substantial contraction on bronchioles or main bronchi. Trachea of Fisher 344 but not of Wistar rats showed a small contraction. No other differences were found between preparations from Wistar and Fisher 344 rats. It is concluded that rat trachea, main bronchi and small bronchioles show regional and strain-dependent variations in their responsiveness to contractile agents.
Serum samples for the determination of neuron-specific enolase (NSE) levels were collected at diagnosis, after induction of chemotherapy and at relapse in order to assess the value of NSE in the diagnosis and management of small-cell lung cancer (SCLC). At diagnosis, 47 of 64 patients with SCLC (73%) had abnormal NSE values (i.e. NSE > 12.5 micrograms/l). Mean NSE values were significantly higher in patients with extensive disease compared to limited disease. Patients with other malignancies or benign lung diseases presented with elevated NSE levels in approximately 15 and 4% of cases. Sensitivity, specificity and predictive value of positive results of NSE at diagnosis were 74, 83 and 71%, respectively, for a cutoff value of 12.5 micrograms/l. In responders mean NSE dropped significantly from 46.1 micrograms/l before chemotherapy to 17.0 micrograms/l after three cycles of chemotherapy. Nonresponders as a group showed a nonsignificant drop. At relapse mean NSE increased from 6.5 micrograms/l at the time of response to 51.9 micrograms/l at the time of progression, but in 5 of the 18 evaluable patients normal levels persisted. Thus, evolution of NSE in patients receiving chemotherapy correlated well with tumor volume in patients who responded, but often failed to predict a therapeutic outcome in patients with apparently chemoresistant tumor (i.e. some nonresponders showed a decrease in NSE levels). A similar lack of correlation between NSE levels and tumor volume was seen at the time of relapse. We conclude that the determination of NSE levels is of doubtful utility in the diagnosis and follow-up of SCLC patients.
Patient and tumour characteristics of 23 patients presenting with a second primary lung cancer were analysed and compared with 534 patients with radically resected stage 1 non-small cell lung cancer (NSCLC). None of these characteristics is associated with a higher occurrence rate for second primary lung cancer. Prognosis in the latter patients is significantly worse than after resection of a 'solitary' NSCLC: the median survival time (MST) after resection of the first tumour is 50 months; after diagnosis of the second tumour only 14 months. Surgically retreated patients have a prognosis that is similar to that after resection of a 'solitary' NSCLC. No separate independent prognostic factors responsible for this survival difference could be isolated. Squamous histology and central location are associated with a longer recurrence free survival time. We conclude that the occurrence of a second primary lung cancer can not be predicted based on patient or tumour characteristics and that only surgical retreatment offers a chance of long survival in these patients.
OBJECTIVE: To assess the usefulness of rigid bronchoscopy and bronchial washings in detecting primary lung carcinomas. SETTING: Department of Otolaryngology, University Hospital of Ghent, Belgium. DESIGN: Prospective analysis of patient investigations. METHOD: The results of 127 rigid bronchoscopies with bronchial washings in patients with a new, untreated head and neck tumour and a normal chest radiograph were analyzed for their usefulness in detecting simultaneous primary lung carcinomas. All patients were followed for a minimum of 2 years or till death. RESULTS: We found positive bronchial washings in 19 cases (21%). Unilateral positive bronchial washings were found in 8 patients (9%). In only one patient was a simultaneous primary lung tumour found. One patient was found to have a pulmonary metastasis. The remaining 6 patients with positive unilateral cytology (6/8) had normal chest roentgenograms and/or CT scans, and did not develop a lung tumour in the course of follow up. Of the 19 positive bronchial washings, 10 patients had a carcinoma of the larynx and two had a large hypopharyngeal carcinoma. CONCLUSIONS: Contamination of bronchial washings with tumour cells from head and neck neoplasms limited seriously the usefulness of positive bronchial cytology. The sensitivity and specificity of the rigid bronchoscopy with bronchial washing is too low to justify its cost.
T helper 2 (Th2)-like cytokines are thought to play a crucial role in the pathogenesis of airway inflammation in atopic asthma, leading to bronchial hyperresponsiveness. To investigate the role of the principal Th2 cytokine interleukin-4 (IL-4) in asthma, we examined the allergen-induced changes in airway morphology and bronchial responsiveness (BR) in an in vivo mouse model. C57BL/6 mice were actively sensitized to ovalbumin (OVA) and exposed daily to aerosolized OVA or saline (SAL) for 7 days. Twenty-four hours after the last allergen exposure, total and differential counts of bronchoalveolar lavage cells revealed a significant increase of eosinophils and lymphocytes in OVA-exposed immunized mice compared with SAL-exposed animals. In IL-4-deficient (IL-4-/-) mice, treated in the same way, there were substantially fewer eosinophils in bronchoalveolar lavage compared with wild-type mice. Allergen exposure of actively sensitized wild-type mice induced a significant increase of BR to carbachol and to serotonin compared with SAL-exposed mice. In contrast, OVA exposure of immunized IL-4-/- mice did not augment BR to serotonin compared with SAL-challenged IL-4-/- mice. In conclusion, these data indicate that repeated allergen exposure in sensitized mice induces airway inflammation and bronchial hyperresponsiveness, and that IL-4 plays a predominant role in the pathogenesis of both phenomena.
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Intrathoracic involvement is common in non-Hodgkin's lymphoma (NHL). We present the case of a young woman with a secondary pulmonary lymphoma (SPL) of the centroblastic subtype, with B-cell characteristics. The chest radiograph at presentation revealed an extremely rare pattern of multiple cavitating pulmonary nodules. The radiographic patterns of intrathoracic NHL are discussed.
26 months after the onset of alcohol-induced pain, a diagnosis of primary pulmonary Hodgkin's (PPHD) disease could be made in a 34-year-old woman. Standard radiology of the thorax remains normal up to 18 months after the onset of symptoms. A short review of the literature concerning PPHD is given.
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Tracheobronchomegaly (TBM) is a rare disorder of uncertain aetiology, characterized by marked dilatation of the trachea and main bronchi, bronchiectasis and recurrent lower respiratory tract infections. Two patients with TBM are presented. In one case, a marked decrease of elastic and smooth muscle tissue was present in the bronchial biopsy specimens, obtained by rigid bronchoscopy. The airways of the second patient were visualized using computed tomography. The dimensions of the airways of our patients are compared with the normal values supplied in the literature.
Asthma is characterized by the presence of airway inflammation and an increased responsiveness to many different stimuli. The hyperresponsiveness to indirect stimuli such as adenosine, bradykinin, neuropeptides, sulphur dioxide suggest that the hyperresponsiveness in asthma results from the complex interaction between inflammatory cells, neurons and smooth muscle cells. Several mechanisms may be involved in the influence of airway inflammation on airway responsiveness: increased mucosa permeability: enhanced exposure of irritant receptors, modulation of airway smooth muscle behavior by inflammatory mediators, mucosal edema, enhanced release of neurotransmitters, increased local reflex activity, decreased breakdown of neurotransmitters, etc. We have investigated the interaction between airway inflammation and responsiveness in two animal models: acute exposure to endotoxin and chronic exposure to aerosolized antigen. Both models demonstrate the complexity of interaction between inflammatory processes and demonstrate positive controlling mechanisms that inhibit the increase in airway responsiveness due to airway inflammation. The lack of such controlling mechanisms may be involved in the development of the asthmatic airway hyperresponsiveness.
Neuropeptides and purines are possible autonomic neurotransmitters. Both tachykinins (neurokinin A, substance P) and adenosine cause acute airway narrowing by synergistic activation of airway mast cells and postganglionic vagal nerve endings.
Purines and neuropeptides may act as neurotransmitters of the local axon reflex in the airways. Nedocromil sodium has been shown to inhibit adenosine- and neurokinin A-induced bronchoconstriction both in the rat and in man. In this study we used the rat model for further investigation of the mechanism of action of nedocromil sodium in the adenosine- and neurokinin A-challenge. The animals were challenged intravenously, and immediately after maximal bronchoconstriction a bronchoalveolar lavage was performed and histamine was assayed in the supernatant of the lavage fluid. Nedocromil sodium significantly inhibited the adenosine- and the neurokinin A-induced increase in histamine concentration in the lavage fluid. Nedocromil sodium had no influence on the airway responsiveness to serotonin or carbachol. We therefore concluded that the inhibitory effect of nedocromil sodium on adenosine- and neurokinin A-induced bronchoconstriction can be explained by its activity on airway mast cells.
In some animal species substance P and neurokinin A (NKA) cause bronchoconstriction by the release of acetylcholine from postganglionic cholinergic nerve endings. The aim of the present study was to investigate the effect of an anticholinergic drug, oxitropium bromide, on bronchoprovocation with NKA in asthmatics. Eleven mild asthmatics (mean % predicted FEV1 85.5) received on 2 separate days, double blind, in a randomised order, 400 mcg oxitropium bromide or placebo, 90 min before challenge with NKA. NKA was inhaled at 3 concentrations (10(-4), 3.10(-4) and 10(-3) M). Specific airways conductance (sGaw) and forced expiratory volume in 1 s (FEV1) were used as parameters of airway calibre. Compared to the placebo-aerosol, oxitropium bromide caused a significant increase in sGaw and FEV1. On the placebo-treatment day, NKA caused a concentration-dependent decrease in sGaw and FEV1. The percentage changes in sGaw and FEV1 on the oxitropium day were not statistically different from those occurring on the placebo day. We conclude that oxitropium bromide caused a significant bronchodilation but offered no significant protection against NKA-induced bronchoconstriction in mild asthmatic subjects.
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The neuropeptides substance P and neurokinin A are present in sensory airway nerves. Their effect on airway calibre was compared in six healthy non-smoking subjects and six asthmatic subjects. On separate days increasing concentrations (from 10(-9) to 10(-6) mol/ml) of each neuropeptide were administered by nebuliser and the airway response measured as change in specific airway conductance (sGaw). Substance P and neurokinin A caused no change in sGaw in the healthy subjects. Inhalation of substance P up to the highest concentration of 10(-6) mol/ml caused no change in sGaw in the asthmatic subjects. Neurokinin A, however, caused bronchoconstriction with a mean fall in sGaw of 48% (SEM 12%) after 5 x 10(-7) mol/ml. The onset of bronchoconstriction was rapid, but sGaw had returned to baseline values within one hour in all but one patient.