PubMed Health⌕ Search

Biomedical subjects

A B Breslin

Publications and source records attributed to A B Breslin.

At least 19 recordsLinked to original sources
PubMed1994

Pathogenesis of chronic persistent cough associated with gastroesophageal reflux.

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

New developments in anti-asthma drugs.

OBJECTIVE: To review the current approach to the management of bronchial asthma with particular reference to drug therapy. DATA SOURCES: All significant English language journals were searched for current studies, particularly controlled clinical trials, in the management of asthma. STUDY SELECTION: Sixty articles were reviewed. They were selected on the basis of the known reputation of the author or the unit from which the study emanated, the place that the study has assumed in academic respiratory circles, and whether the study contributed something new to our understanding of drug therapy in asthma. Review articles from eminent scientific bodies were also analysed. CONCLUSIONS: Asthma is an inflammatory disease and therapy must be directed towards this as well as to bronchoconstriction. Inhaled corticosteroids are the mainstay of treatment and inhaled beta-agonists are best used on an as needed basis. Regular objective assessments of patients' progress are essential, as are written, individualised action plans. The adjunctive use of other drugs is discussed and new therapies which may prove useful in the future are reviewed.

Administration, Inhalation↗
PubMed1992

Effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in the well elderly and in patients with chronic bronchitis.

BACKGROUND: Inhalation of the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) produces bronchoconstriction in normal subjects. FMLP thus has a putative role as a mediator of bronchoconstriction associated with bacterial bronchial infection. METHODS: The effects of FMLP inhalation were examined in ten subjects with a history of chronic bronchitis and ten age matched control subjects. Each subject inhaled FMLP doses from 0.025 to 0.8 mumol to determine the provocative dose of FMLP causing a 20% fall in FEV1(PD20FMLP). FEV1 was recorded every five minutes after the final FMLP inhalation until it had returned to 95% of baseline FEV1 or 60 minutes had elapsed. The time to return to 95% baseline FEV1 was recorded or extrapolated from the recovery curve as an index of rapidity of recovery. Total and differential white cell counts were performed on each subject at baseline and five and 15 minutes after the final FMLP inhalation. RESULTS: The geometric mean PD20 FMLP in the patients with chronic bronchitis was 0.06 mumol (95% confidence interval 0.015-0.26), which was significantly lower than that in the control subjects (0.21 mumol (0.02-1.9)). PD20 FMLP in the patients with chronic bronchitis but not age matched controls (p = 0.35) was lower than that found previously in young normal subjects (0.35 mumol (0.07-1.8). The return to 95% baseline FEV1 occurred after 86(10) minutes in subjects with chronic bronchitis and in 81(23) minutes in their age matched controls, in both cases being much slower than that seen in young subjects (29(9) minutes). CONCLUSION: Patients with chronic bronchitis may be especially susceptible to formyl peptides elaborated by bacteria during bacterial bronchial infection.

Administration, Inhalation↗
PubMed1992

Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man.

BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection.

Administration, Inhalation↗
PubMed1992

Chronic persistent cough and clearance of esophageal acid.

Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.

Chronic Disease↗
PubMed1991

Chronic persistent cough and gastro-oesophageal reflux.

Chronic cough persisting for two months or more that remains unexplained after extensive investigations is a common clinical problem. The purpose of this study was to determine whether such cough is associated with otherwise asymptomatic gastro-oesophageal reflux. Thirteen patients with chronic persistent cough that was unexplained after a standard diagnostic assessment were identified. All were non-smokers. The mean (SE) duration of cough was 17.8 (8.0) months. Ten had never had reflux symptoms and three had had mild symptoms only after the onset of the cough. All the patients completed standardised cough diary cards for eight weeks and underwent 24 hour ambulatory oesophageal pH monitoring. A reflux episode was defined as a fall in oesophageal pH to below 4.0. Nine control subjects were matched for age, lung function, and body mass index. The patients experienced significantly more episodes of reflux per 24 hours than the controls (115.8 (SE 31.7) versus 4.7 (1.4) and longer reflux episodes (15.5 (5.8) versus 1.7 (0.5) minutes), and the oesophageal pH was below 4.0 considerably longer (84.5 (20.2) versus 3.8 (1.3) minutes). Cough occurred simultaneously with 13% (2.2%) of reflux episodes and within five minutes in another 35% (5.8%) of episodes, whereas gastro-oesophageal reflux occurred simultaneously with 78% (5.5%) of cough episodes and within five minutes in another 12% (2.3%) of episodes. It is concluded that chronic persistent cough that remains unexplained after a standard diagnostic assessment is associated with otherwise asymptomatic gastro-oesophageal reflux. It is suggested that a self perpetuating mechanism may exist whereby acid reflux causes cough via a local neuronal oesophageal-tracheo-bronchial reflex, and the cough in turn amplifies reflux via increased transdiaphragmatic pressure or by inducing transient lower oesophageal sphincter relaxation. Further study of this mechanism and the role of specific antireflux treatment in chronic persistent cough is warranted.

Adolescent↗
PubMed1991

Effect of neutral endopeptidase inhibition of f-Met-Leu-Phe-induced bronchoconstriction in the rabbit.

Inhalation of f-Met-Leu-Phe (FMLP) produces dose-dependent increases in pulmonary resistance (RL) in rabbits. We hypothesized that inhibition of neutral endopeptidase (NEP), which has high affinity for FMLP, would augment the response to FMLP inhalation. We found the increase in RL above baseline in response to FMLP to be reduced from 56 +/- 18 to 8 +/- 10% (P less than 0.01) by phosphoramidon (1 mg/kg) and to 15 +/- 6% (P less than 0.02) by thiorphan (3 mg/kg). The geometric mean dose of FMLP producing a 20% rise in RL (PC20RL FMLP) was increased by phosphoramidon from 1.1 to 4.5 mg/ml (P less than 0.05). Enkephalins, which are also NEP substrates, modulate cholinergic neurotransmission in the airway. Inhibition of the FMLP response by phosphoramidon was reversed by coadministration of naloxone (0.1 mg/kg); after atropine (2 mg/kg) the change in RL in response to FMLP was reduced to 7 +/- 4% (P less than 0.01), whereas morphine (0.15 mg/kg) increased PC20RL FMLP to 5.1 mg/ml (P less than 0.05). FMLP-induced bronchoconstriction in the rabbit is vagally mediated, and reduced responses after NEP inhibition may reflect modulation of cholinergic bronchoconstriction by enkephalins. Changes in airway NEP activity may influence the activity of a wide range of its substrates, of which some are bronchoconstrictors and others bronchodilators.

Airway Resistance↗
PubMed1991

Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits.

On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation.

Administration, Inhalation↗
PubMed1990

Sarcoidosis presenting as recurrent alcohol-induced pancreatitis.

A previously well 27-year-old Caucasian woman presented with five episodes of alcohol-induced abdominal pain over two years culminating in severe acute pancreatitis. Chest x-ray showed bilateral hilar lymphadenopathy and nodular pulmonary infiltrates. In hospital she developed a unilateral facial nerve palsy and other features of sarcoidosis, which was confirmed by biopsy of a pretracheal lymph node. No previous case is reported of sarcoidosis presenting with recurrent pancreatitis apparently induced on each occasion by moderate alcohol consumption and in the absence of other risk factors. Pancreatic involvement as part of sarcoidosis is uncommon but is treatable if recognized and has a good prognosis.

Adult↗
PubMed1989

The effect of anticholinergic and beta-agonist pretreatment on bronchoconstriction induced by N-formyl-methionyl-leucyl-phenylalanine.

N-Formyl-methionyl-leucyl-phenylalanine (FMLP), an acylated tripeptide bacterial neutrophil chemotactic factor, has been shown to be a bronchoconstrictor by inhalation in man in vivo. It thus has a putative role in the generation of bronchoconstriction associated with bacterial bronchial infection. We have investigated the effect of pretreatment with the anticholinergic agent, ipratropium bromide (IB), and the beta 2-agonist, fenoterol (F), on FMLP-induced bronchoconstriction. Ten non-asthmatic subjects aged 21-28 yrs performed dose-response curves to nebulized FMLP on 3 study days after pretreatment with saline, F or IB. Amongst the 8 subjects who bronchoconstricted by 20% to FMLP there was a significant increase in the provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20FMLP) after both IB and F. F was significantly better than IB. When comparison was made using absolute fall in FEV1 and including all 10 subjects the same results were found. Partial inhibition of FMLP-induced bronchoconstriction by IB suggests that part of the effect of FMLP is vagally mediated. We suggest that F is acting via modulation of FMLP-induced rises in intracellular free calcium.

Adult↗
PubMed1987

Long term study of the effect of sodium cromoglycate on non-specific bronchial hyperresponsiveness.

A double blind, crossover study was undertaken to determine whether non-specific hyperresponsiveness in subjects with asthma was reduced by long term treatment with sodium cromoglycate and, if so, whether this was related to change in lung function. Forty four adult asthmatic subjects (41 atopic, three non-atopic) entered the one year study at intervals staggered over six months. After a baseline period to ensure that asthma control was stable subjects entered the treatment period, during which they inhaled sodium cromoglycate 20 mg four times daily or matching placebo four times daily for 16 weeks each, in random order. Response was assessed at four weekly intervals by measurement of lung function and histamine inhalation tests, from which the provocative concentration of histamine causing a 20% fall in FEV1 (PC20H) was calculated. The assessment included daily symptom score, morning and evening Airflow-meter readings and treatment; mean values for each treatment period and also for the final four weeks of each period were compared. There were no significant differences between placebo and sodium cromoglycate treatment for PC20H, FEV1, morning or evening flow meter readings, bronchodilator usage, or symptom scores for the group as a whole, for the 16 week period or for the final four weeks of each period. Thirteen subjects showed better morning and evening flow meter readings while taking sodium cromoglycate than while taking placebo and eight better readings with placebo than with sodium cromoglycate (p less than 0.05). Improvement in lung function did not correlate with baseline lung function or baseline PC20H, or with features of atopy. These results suggest that long term sodium cromoglycate treatment does not alter non-specific bronchial responsiveness in adult asthmatic subjects.

Adolescent↗
PubMed1985

Passive cigarette smoking and patients with asthma.

A study of the effect of passive smoking on patients with asthma is presented. Six patients were exposed for one hour to the air in a room in which tobacco smoke was produced mechanically over that period. The effects on symptoms, lung function and airways sensitivity to inhaled histamine were then measured and compared with the same patient's responses during a control day when they inhaled smoke-free air. All six patients developed chest tightness and symptoms similar to an attack of asthma. The findings of respiratory and sensitivity tests suggest: (i) that passive smoking may trigger asthma attacks in subjects who suffer from asthma and (ii) that the airways of such subjects show increased histamine reactivity four hours after the passive smoke exposure.

Adult↗
PubMed1985

The role of alpha and beta adrenoceptors in airway hyperresponsiveness to histamine.

The effect of a specific alpha 1-adrenoceptor antagonist, prazosin, on histamine-induced bronchoconstriction was compared to a beta 2-adrenoceptor agonist, salbutamol, in 16 subjects with nonspecific bronchial hyperresponsiveness whose PC20H ranged from 0.10 to 5.12 mg/ml. PC20H was calculated from a histamine inhalation test performed before and after 0.5 mg of prazosin by dry powder inhalation and 200 mcg of salbutamol by pressurized aerosol. PC20H was also measured in six subjects before and after placebo (20 mg lactose) by dry powder inhalation in a randomized double-blind study with prazosin. Mean (+/- SE) PC20H before and after placebo was 1.77 (0.32) and 1.57 (0.38) mg/ml, respectively, an 0.89-fold change. Mean (+/- SE) PC20H before and after prazosin for the 16 subjects was 1.92 (0.34) and 3.10 (0.72) mg/ml, a 1.51-fold change (p less than 0.001), and PC20H before and after salbutamol was 2.08 (0.33) and 9.54 (2.51) mg/ml, a 4.08-fold change (p less than 0.001). There was a positive correlation between the prazosin and salbutamol responses (r = 0.55, p less than 0.05). A dose response for salbutamol was performed in eight subjects, and PC20H was determined by use of increasing doses of salbutamol until PC20H was more than 16 mg/ml. The dose of salbutamol required varied widely between subjects and did not relate to baseline PC20H. The results suggest a role for alpha-adrenoceptors in addition to beta-adrenoceptors in histamine-induced bronchoconstriction.

Adolescent↗
PubMed1984

Experience with allergic bronchopulmonary aspergillosis: some unusual features.

The clinical and immunologic features of ten patients with allergic bronchopulmonary aspergillosis (ABPA), observed over periods varying from 12 months to 10 years, are reported. Acute attacks of ABPA were characterized by several, or all of: increased cough and sputum, haemoptysis, pleuritic pain, expectoration of sputum plugs, and increasing airways obstruction. Peripheral blood eosinophilia and acutely elevated serum IgE levels were seen in all patients during acute attacks, sputum eosinophilia and recovery of Aspergillus in sputum was less common. However, blood eosinophilia was not present in all attacks of ABPA and sputum eosinophilia varied similarly from one attack to another. Six patients with previously documented multiple precipitin lines have had no demonstrable precipitins to Aspergillus on several occasions between attacks, three of these patients have also been negative during attacks. Five of the six patients have again developed positive precipitin lines. The total number of episodes in these ten patients was fifty two, three patients have had more than nine acute attacks of ABPA. There is no seasonal variation in this group of patients. Since diagnosis, only three patients have had an attack-free interval longer than 12 months. Two patients are steroid-dependent because of severe asthma, and nine have symptoms of bronchiectasis.

Adult↗
PubMed1984

Upper respiratory tract infections and airway reactivity in normal and asthmatic subjects.

To assess the effect of an upper respiratory tract infection (URTI) on airway reactivity, histamine inhalation tests (HITs) were performed prospectively in 44 nonsmoking asthmatic (14) and nonasthmatic (30) volunteers. Fifteen of the subjects developed an URTI during the following 4 months. Pulmonary function-forced expiratory volume in one second (FEV1), maximal midexpiratory flow rates (MMEFR) and maximal flow at 50% vital capacity (V50), and HITs, were studied at onset and 2, 3, and 4 wk after infection. There were no significant changes in pulmonary function during the total study period. For the 15 subjects, the mean provocative concentration of histamine causing a 20% fall in FEV1, (PC20H) was 8.73 mg/ml prior to onset of URTI, and at 1, 2, 3, and 4 wk after URTI was 7.97, 8.68, 8.13, and 8.61 mg/ml. These were not significantly different for the group as a whole, nor for the subgroups of asthmatics and nonasthmatics. Small changes in PC20H outside the normal range of variability occurred in 5 of 15 subjects. These were short-lived and no predictive factor for change in PC20H was identified in this group. Thus, URTI was not associated with significant changes in PC20H in this group of asthmatic and nonasthmatic subjects.

Adult↗
PubMed1983

Asthmatic reactions to a commonly used aerosol insect killer.

Seven patients with asthma and a history of chest tightness on exposure to aerosol insecticide sprays were studied. Under controlled conditions, objective measures of airways narrowing were taken before and after exposure to an aerosol insect killer (Mortein Pressure Pak). Chest tightness described as asthma was produced in all seven subjects, but only one showed a greater than 20% fall in FEV1, compared to baseline values. A further two subjects showed small changes in the maximum mid-expiratory flow rate. No changes were observed in the subjects' sensitivity to inhaled histamine before, and 24 hours after, exposure to the insecticide. Thus, exposure to a commonly used household insecticide spray produced marked symptoms in all subjects, but objective evidence of airways obstruction was present in only three, and no changes in bronchial reactivity to inhaled histamine occurred in any of the subjects.

Adult↗