tbuckley/cabot-search huggingface dataset:
Occurrence of a late response to exercise in asthmatic children: multiple regression approach using time-matched baseline and histamine control days
Authors: WB Hofstra, PJ Sterk, HJ Neijens, JM Kouwenberg, PG Mulder, EJ Duiverman
Journal: European Respiratory Journal (1996)

At the present time, there is still controversy concerning the presence of a late asthmatic response (LAR) to exercise challenge in asthma. We have, therefore, investigated the occurrence of a LAR after exercise in asthmatic children visiting an out-patient clinic, using time-matched baseline and histamine control days, and a statistical analysis according to recently published recommendations. After a screening exercise day, 17 children (aged 7-14 yrs) randomly performed, on three subsequent study days, either: a second standardized exercise challenge; or a histamine challenge whilst matching the bronchoconstriction after exercise; or measurement of baseline lung function without any challenge. Measurements of forced expiratory volume in one second (FEV1) were made repeatedly during 8 h. Analysis was performed using multiple regression analysis for each patient, with FEV1 as the dependent, and test day (exercise or control) and clock time as independent variables during the period 2-8 h after exercise. A significant interaction (p &lt; 0.05) between test day and clock time was considered to be indicative of a LAR. Fifteen children completed the study. All children showed an early asthmatic reaction to exercise (range 14-62% fall in FEV1). In two children, a significant interaction (p &lt; 0.05) was found between test day and clock time. However, the difference in FEV1 between exercise and control days for each clock time did not exceed the 99.6% confidence limits of normal diurnal variation in any of the children. We conclude that, in children with mild-to-moderate asthma, a LAR to exercise does not occur. This suggests that exercise is only a symptomatic trigger of asthma. Whether exercise is capable of inducing inflammation needs to be further investigated.
Assessment of the relative systemic potency of inhaled fluticasone and budesonide
Authors: M Boorsma, N Andersson, P Larsson, A Ullman
Journal: European Respiratory Journal (1996)

Studies using dry powder devices have suggested that fluticasone propionate (FP) has a greater systemic effect than budesonide (BUD). The aim of the present study was to investigate and compare the relative systemic potency of FP and BUD from their respective pressurized metered-dose inhalers (pMDIs). A placebo-controlled, open, randomized, cross-over study was conducted in 21 healthy male volunteers. Placebo, BUD (200, 400 and 1,000 micrograms b.i.d.) and FP (200, 375 and 1,000 micrograms b.i.d.) were inhaled for 4 days, with a wash-out period of at least 3 days between treatments. Blood samples for cortisol analysis were drawn during the last 24 h of each treatment period. Cortisol levels, measured as 24 h pooled plasma cortisol, were statistically significantly lower (p = 0.0001) for all dose levels during FP pMDI treatment (21, 39 and 84% suppression from placebo) than during BUD pMDI treatment (1, 3 and 27% suppression from placebo). The relative systemic potency FP:BUD was 3.7:1 (95% confidence interval (95% CI) 2.9-4.8)). The relative systemic potency based on the single 08:00 h samples was 5.2:1 (95% CI 3.0-9.3). In conclusion, in healthy male volunteers using pressurized metered-dose inhalers, fluticasone propionate was shown to have a stronger systemic effect than budesonide.
MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial
Authors: M Luisetti, C Sturani, D Sella, E Madonini, V Galavotti, G Bruno, V Peona, U Kucich, G Dagnino, J Rosenbloom, B Starcher, C Grassi
Journal: European Respiratory Journal (1996)

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.
Exogenous lipid pneumonia: a retrospective multicentre study of 44 cases in France
Authors: A Gondouin, P Manzoni, E Ranfaing, J Brun, J Cadranel, D Sadoun, JF Cordier, A Depierre, JC Dalphin
Journal: European Respiratory Journal (1996)

A nationwide retrospective study of exogenous lipid pneumonia (ELP) was carried out to update the data on this disease, with emphasis on thoracic computed tomography (CT) scan and bronchoalveolar lavage (BAL) findings. The inclusion criteria were: 1) presence of abnormal imaging features compatible with the diagnosis of ELP; 2) presence of intrapulmonary lipids; and 3) exogenous origin of the lipid pneumonia. Forty four cases were included (20 males and 24 females; mean age 62 +/- 11 yrs), of which four were occupational (chronic inhalation of cutting mist or oily vapour in an industrial environment). Thirty of the 40 nonoccupational cases were related to aspiration of liquid paraffin used for the treatment of constipation. A condition possibly favouring oil aspiration or inhalation was present in 34 patients (77%), most commonly gastro-oesophageal reflux (n = 20) and neurological or psychiatric illness (n = 14). Fever (39%), weight loss (34%), cough (64%), dyspnoea (50%) and crepitations (45%) were the most frequent symptoms. BAL was performed in 39 cases: 23% had a lymphocytic alveolitis; 14% neutrophilic alveolitis; and 31% a mixed alveolitis (lymphocytic and neutrophilic). Alveolar consolidations (57%), ground glass opacities (39%), and alveolar nodules (23%) were the most common radiological abnormalities. The changes were bilateral (79%), predominant in the posterior and lower zones of the lobes concerned (74%), hypodense (71%), and spared the subpleural zones (52%). In 13 cases, hypodensity was retrospectively established on CT scan by the presence of a "positive angiogram". This sign may be of diagnostic value when the density measurement is either not possible or not reliable. In conclusion, this study provides an update of the clinical, biological and radiological profile of exogenous lipid pneumonia and, in particular, confirms the diagnostic benefit of computed tomography scan, which revealed bilateral and hypodense changes in a large majority of cases.
Guinea-pig tracheal responsiveness in vitro following general anaesthesia with halothane
Authors: FJ Mercier, A Denjean
Journal: European Respiratory Journal (1996)

Halothane and isoflurane induce potent bronchodilation during general anaesthesia and have been used successfully during status asthmaticus. The aim of this study was to determine whether airway hyporesponsiveness was prolonged after halothane administration. Sixteen guinea-pigs were submitted for 2 h to either 1.5% halothane in oxygen or 100% oxygen, and were killed 24 h later to elicit isometric tracheal contractions in organ baths with various agonists. Cumulative concentration-response curves to histamine or to KCl and contractions evoked with acetylcholine 1 mM (4.7 +/- 0.8 vs 4.6 +/- 0.5 g) or carbachol 10 microM in calcium-free buffer (4.3 +/- 0.6 vs 4.4 +/- 0.6 g) exhibited no difference between groups. Moreover, when 4% halothane or 4.6% isoflurane were directly bubbled through the organ baths, a significant decrease (13 +/- 1% and 37 +/- 2%) of maximal contractions evoked with acetylcholine and KCI, respectively, was obtained but these relaxant effects did not persist 30 min after cessation of anaesthetic. These results indicate that, even though halothane induces transient airway hyporesponsiveness in vitro, previous halothane anaesthesia in guinea-pigs does not alter subsequent tracheal responsiveness assessed in vitro. Our findings may explain the transient renewal of bronchospasm reported during intermittent periods off halothane in status asthmaticus.
Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor
Authors: LJ Dupont, CJ Meade, MG Demedts, GM Verleden
Journal: European Respiratory Journal (1996)

Electrical field stimulation (EFS) of guinea-pig airways, in vitro, evokes an excitatory nonadrenergic noncholinergic (eNANC) contraction mediated by release of tachykinins from sensory nerve endings. Epinastine (WAL 801CL) is an antihistaminic drug with binding affinity at certain other receptors, including alpha-adrenergic receptors and various serotonin (5-HT) receptor subtypes. It is used in asthma treatment; however, its mechanism of action remains to be fully defined. We have investigated whether epinastine could modulate the eNANC contraction in guinea-pig airways in vitro, and have tried to elucidate its receptor mechanism. Epinastine (0.1-100 microM) produced a concentration-dependent inhibition of the noncholinergic contraction, with a maximum inhibition of 91 +/- 7% at 100 microM. Pretreatment of the tissues with combined 5-HT1/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect. Chlorpheniramine (10 microM), another histamine H1 receptor antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction. Epinastine (100 microM) did not displace the dose-response curve to exogenously applied substance P (0.01-10 microM). These results suggest that epinastine, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.
Primary diffuse alveolar septal amyloidosis with multiple cysts and calcification
Authors: S Ohdama, S Akagawa, O Matsubara, Y Yoshizawa
Journal: European Respiratory Journal (1996)

We report an extremely rare case of primary diffuse alveolar septal amyloidosis associated with multiple cysts and calcification. Development of multiple cysts may have resulted from fragile alveolar walls, as a consequence of amyloid deposition both on alveolar walls and around capillaries.
Lower airway responses to rhinovirus 39 in healthy allergic and nonallergic subjects
Authors: DP Skoner, WJ Doyle, J Seroky, MA Van Deusen, P Fireman
Journal: European Respiratory Journal (1996)

Acute asthma is considered to be a complication of respiratory viral infections. This investigation assessed the effects of rhinovirus 39 (RV-39) infection both on the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 50) and without AR (non-AR; n = 46) were intranasally inoculated with RV-39, and monitored for 8 days in an enclosed environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected postinoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on days 2-3. Cough was a relatively minor symptom and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No allergy status effects were observed. Under these experimental conditions, rhinovirus 39 infection did not produce detectable alterations in lower airway function in healthy subjects with and without allergic rhinitis.
Evaluation of a new interrupter device for measuring bronchial responsiveness and the response to bronchodilator in 3 year old children
Authors: SB Phagoo, NM Wilson, M Silverman
Journal: European Respiratory Journal (1996)

The interrupter technique for measuring airway resistance is non-invasive and convenient, and therefore ideally suited for the assessment of induced changes in airway calibre in preschool children. The aim of this study was to evaluate a commercially available interrupter device (based on Microlab 4000), which calculates the interrupter resistance (Rint) from pressure and flow following a brief interruption of expiration during quiet breathing. The repeatability of Rint was assessed, and its response to methacholine challenge and the bronchodilator salbutamol were compared with an indirect technique, the fall in transcutaneous oxygen tension (Ptc,O2), using the sensitivity index (SI, i.e. the change after challenge expressed in multiples of the baseline standard deviation) in 12 wheezy children (aged 3 yrs +/- 2 months). The mean (SD) baseline value of Rint was 0.91 (0.20) kPa.L-1.s. Short-term repeatability and baseline variability were satisfactory for Rint (intraclass correlation coefficient = 0.6; mean intrasubject coefficient of variation = 13%). Although 10 of the 12 subjects obtained a significant response using Rint at maximal bronchoconstriction (i.e. SI &gt; 2), overall, Rint was five times less sensitive than Ptc,O2 (geometric mean SI: Rint 3 vs Ptc,O2 16; p &lt; 0.0001). Reversal of obstruction with administration of a bronchodilator was clearly demonstrated in almost all subjects: Rint after challenge (mean +/- SD) 1.25 (0.22) kPa.L-1.s; after salbutamol 0.78 (0.19) kPa.L-1.s; p &lt; 0.001. In conclusion, the convenient interrupter resistance method appears more promising for detecting bronchodilator responses than induced bronchoconstriction in wheezy preschool children; however, measurement of transcutaneous oxygen tension provides a reliable indirect means of detecting induced airway obstruction in this age-group.
Twenty two year survival after incomplete resection of advanced adenoid cystic bronchogenic carcinoma
Authors: N Schoenfeld, W Rahn, R Loddenkemper
Journal: European Respiratory Journal (1996)

In 1972, a 42 year old patient underwent thoracotomy for adenoid cystic carcinoma of the left main-stem bronchus. Pneumonectomy was performed, but the resection was not complete as the tumour had invaded the aortic and tracheal wall. The patient did not receive postoperative radiotherapy. In 1993, the patient was readmitted with severe respiratory insufficiency due to complete endobronchial tumour obstruction of the intermediate bronchus and extensive tumour growth in the mediastinum. Endobronchial laser treatment followed by stent implantation led to immediate symptomatic relief. The tumour then responded well to combined endobronchial and percutaneous radiotherapy. The patient died 7 months after readmission from ileus due to pancreatitis. We conclude that patients with advanced adenoid cystic carcinoma may profit from palliative surgery with respect not only to symptoms but also to duration of life.
The biology of bacterial colonization and invasion of the respiratory mucosa
Authors: R Wilson, RB Dowling, AD Jackson
Journal: European Respiratory Journal (1996)

Despite being regularly exposed to particulate matter during breathing, which contains bacteria from the commensal flora in the nasopharynx and from the environment, the healthy lung is kept sterile by efficient defence mechanisms. Bacterial infections of the respiratory mucosa represent a dynamic interaction, to which both host and bacterial factors contribute. The abnormal host defences associated with chronic respiratory infections (e.g. cystic fibrosis and other forms of bronchiectasis) serve to emphasize their permissive role. The bacteria that cause bronchial infections possess a wide array of potential virulence factors that contribute to their pathogenicity. Many of these factors influence the mucociliary system, an important first-line defence mechanism. The multiplication, spread and persistence of bacteria within the bronchial lumen, and consequent damage to the epithelium, stimulates a chronic inflammatory response, which also impairs mucociliary clearance and damages lung tissue. A greater understanding of host-bacterial interactions during mucosal infections should in the future lead to the development of new therapies and treatment strategies.
Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma
Authors: S Shimura, Y Andoh, M Haraguchi, K Shirato
Journal: European Respiratory Journal (1996)

The aim of this study was to elucidate the mechanism of the formation of the widespread mucous-plugging observed in autopsied lungs from patients with bronchial asthma. We performed morphometric analysis of airways of autopsied lungs from eight patients with bronchial asthma (Group BA), and compared it with those of six chronic bronchitics (Group CB) and four control patients (Control). The following parameters were measured in paraffin sections: volume proportion of bronchial glands to bronchial wall (Gland%); goblet cell granules to total epithelial layer (Goblet %); intraluminal mucus expressed as the mucus occupying ratio (MOR); volume ratio of intraluminal mucus continuous with goblet cells to total intraluminal mucus (Vc/Vtol %); and surface ratio of the contact surface of intraluminal mucus continuous with goblet cells to the total luminal surface (Sc/Stot %). Gland%, Goblet %, and MOR or inflammatory cell numbers in the airway walls both from Group BA and CB were larger than those from the Control group. However, no significant differences were observed between Group BA and CB in Gland%, Goblet %, MOR or inflammatory cell numbers, except for the eosinophil number: i.e. 23 +/- 3, 22 +/- 3 and 6 +/- 2% in Gland%; 22 +/- 9, 5 +/- 4 and 2 +/- 2% in Goblet%; 10 +/- 3, 18 +/- 3 and 0.3 +/- 0.5% in MOR; 199 +/- 68, 10 +/- 3 and 2 +/- 2 cells. mm-2 in eosinophil number of the peripheral airways from Groups BA, CB and Control, respectively. In contrast, marked and significant increases were observed both in Vc/Vtot% and Sc/Stot% in Group BA compared to Groups CB and Control both in central and peripheral airways: i.e. Vc/Vtot% in the peripheral airways was 53 +/- 5, 4 +/- 3 and 0.8 +/- 0.8% from Groups BA, CB and Control, respectively (BA vs CB or BA vs Control, p &lt; 0.01 each). These findings suggest that the continuity of goblet cells and intraluminal mucus or lack of full release of mucus, from goblet cells, is peculiar to asthmatic airways, and may contribute to the formation of mucous-plugs.
Combined smoke inhalation and body surface burns injury does not necessarily imply long-term respiratory health consequences
Authors: J Bourbeau, Y Lacasse, MY Rouleau, S Boucher
Journal: European Respiratory Journal (1996)

This study was undertaken to assess the long-term respiratory health consequences of smoke inhalation in patients who are burns survivors. Patients with smoke inhalation resulting from domestic flame or fire were studied. Medical records were the primary source for the selection of the patients. Smoke inhalation was diagnosed on the basis of the visual appearance of the airways on the reported bronchoscopy. Patients who participated in the study were compared on important characteristics with those who did not participate. The participants were then assessed by questionnaire, physical examination, chest radiograph and pulmonary function tests. Twenty three out of 45 patients who had survived smoke inhalation participated in the study. Participants and nonparticipants were comparable with respect to gender, age, time since injury, aetiology of injury, and total body surface burned. Participants had more facial burns, more severe bronchoscopic findings of smoke inhalation and required intubation more frequently. Respiratory symptom assessment and pulmonary function tests were performed 45 +/- 23 months after smoke inhalation. Four patients reported an increase in dyspnoea, one an increase in cough and one an increase in phlegm. All the patients had pulmonary function tests and bronchial responsiveness (provocative concentration of histamine resulting in a 20% fall in forced expiratory volume in one second (PC20) &gt; 16 mg.mL-1) within normal limits. The four patients complaining of increased dyspnoea had results within normal limits for cardiac and respiratory variables on maximal exertion. The present study indicates that, in burn patients, smoke inhalation resulting from a single domestic fire does not necessarily imply long-term respiratory health consequences.
Chronic infusion of nitric oxide in experimental pulmonary hypertension: pulmonary pressure-flow analysis
Authors: V Hampl, M Tristani-Firouzi, DP Nelson, SL Archer
Journal: European Respiratory Journal (1996)

Inhaled-nitric oxide (NO) is a selective pulmonary vasodilator in short-term clinical studies. Use of NO inhalation in chronic pulmonary hypertension is complicated by potential problems with ambulatory NO delivery. We hypothesized that long-term infusion of NO solution into the central venous circulation, which did not suffer from this drawback, might reduce chronic pulmonary hypertension. Saturated NO solution was infused in chronically hypoxic rats by implantable minipumps at a rate which was effective in reducing acute hypoxic vasoconstriction in isolated, Krebs' albumin perfused lungs (2.5 microL.h-1). Pulmonary haemo dynamics and the pressure-flow relationship were studied after 4 weeks of infusion. NO was still present in the minipumps at the end of the infusion period. Despite causing methaemoglobinaemia, NO infusion did not significantly attenuate pulmonary arterial pressure, pulmonary vascular resistance, right ventricular hypertrophy, or the parameters of the pulmonary vascular pressure-flow relationship. Pressure-flow curves, analysed with the nonlinear, distensible vessel model, indicated increased near-zero pressure resistance (Ro) in chronic hypoxia. The tendency of chronic NO infusion to reduce Ro did not reach statistical significance. Long-term infusion of nitric oxide solution is technically feasible but does not effectively reverse chronic pulmonary hypertension. The failure of infused NO to reduce pulmonary hypertension is explained by the fact that the inactivation of NO by haemoglobin is much faster than anticipated.