Sodium metabisulphite induced airways disease in the fishing and fish-processing industry.

BACKGROUND: Sodium metabisulphite (SMBS) is recognized as a potential cause of airway irritation and possibly occupational asthma, but awareness of its use in the fishing and fish-processing industry is low. AIMS AND METHODS: To describe three cases of occupational airways disease due to SMBS exposure and to review the literature. RESULTS: Three patients, one trawlerman and two prawn processors, developed work-related airways disease due to exposure to SMBS, one with irritant-induced asthma with a positive-specific bronchial challenge associated with very high sulphur dioxide exposures, one with occupational asthma and one with vocal cord dysfunction and underlying asthma. Of the nine cases recorded in the literature, most were non-atopic and responses to specific bronchial challenge when undertaken showed an immediate response. Exposures to sulphur dioxide in these settings are very high, in excess of 30 ppm. CONCLUSION: SMBS should be regarded as a cause of occupational airways disease and its use in the fish and prawn-processing industry investigated further to better identify risks from exposure and handling of the agent in the workplace.

Metastatic pulmonary ameloblastoma. An unusual case.

We present a patient who had a large metastatic pulmonary ameloblastoma resected 25 years after removal of an apparently benign primary ameloblastoma of the jaw. It highlights three areas: problems with the histopathological diagnosis of pulmonary metastases using fine needle aspiration; a noted radiological improvement after a 5-year course of oral cyclophosphamide, in keeping with occasional patients who have responded to chemotherapy; and the technical difficulties of resection of a large pulmonary metastasis, particularly when it is adherent to the mediastinum.

Non-adrenergic, non-cholinergic function in the human airway.

Alterations in non-adrenergic, non-cholinergic (NANC) function may contribute to nocturnal asthma. We have attempted to clarify the importance of the NANC system in the circadian variation in airway calibre in mild asthmatics and nocturnal asthmatics. NANC function in the human airway was studied at 0400 and 1600 hours in 12 nocturnal asthmatics and 12 mild asthmatics by measuring oscillatory resistance (Ros) following capsaicin inhalation. Measurements were made after combined beta- and atropinic blockade in the mild asthmatics but after atropinic blockade alone in the nocturnal asthmatics, in whom beta-blockade is contraindicated. To determine whether beta-blockade influences NANC bronchodilatation, we also studied 12 normal subjects with and without beta-blockade at 1600 hours only. The mild asthmatics showed differing (P = 0.007) resistance changes 1-3 min after capsaicin at 1600 hours (fall in Ros + 1%, CI -2% to 3%) from that at 0400 hours (-4%, CI -8% to -1%) but the nocturnal asthmatics showed no significant difference in response to capsaicin at the two times (fall in Ros: 1600 hours -9%, CI -15% to -3%; 0400 hours -3%, -7% to 1%). The normal subjects showed greater (P = 0.0001) bronchodilatation 1-3 min after capsaicin following atropine plus propranolol (-7%, -11% to -3%) than after atropine alone (-2%, -6% to 2%), supporting interaction between the beta-sympathetic and NANC systems in the human airway, NANC bronchodilatation being inhibited by beta-sympathetic activity. Our observations confirm circadian variation in NANC function in mild asthmatics and suggest interaction between the beta-adrenergic and the NANC bronchodilating system in the normal human airway.

Features and outcome of Pneumocystis carinii pneumonia according to risk category for HIV infection.

A retrospective study of Pneumocystis carinii pneumonia (PCP) was undertaken to examine differences between the presentation and outcome of PCP in AIDS patients from different risk categories for HIV infection. There were 176 PCP episodes recorded in 126 patients from the following risk categories: 69 intravenous drug misusers (IDMs), 36 homosexually infected men and 21 heterosexually infected patients. Most clinical features did not differ significantly between the 3 groups but hypercapnia was almost exclusively seen in IDMs and, if recorded, was associated with a poorer survival. Pneumothorax was more likely to complicate PCP in IDMs and, although present in all groups, concomitant bacterial respiratory infections were more common in IDMs. Recovery from PCP and the incidence of adverse events during treatment did not differ according to risk category. Subsequent survival time was shorter amongst IDMs, but the uptake of antiretrovirals in this group was significantly lower. We conclude that there are few differences in the presentation of PCP between IDMs and other risk categories for HIV infection and that these do not influence the outcomes of illness. The lower post-PCP survival in IDMs can be accounted for by a reduced uptake of antiretroviral drugs by this group.

High dose inhaled atrial natriuretic peptide is a bronchodilator in asthmatic subjects.

Atrial natriuretic peptide (ANP) has been shown to be an effective bronchodilator when given intravenously, but its efficacy by inhalation has not been assessed. In the first part of the current study, six asthmatic subjects, mean (SEM) forced expiratory volume in one second (FEV1) 2.09 (0.30) l, received 0.1 and 1 mg atrial natriuretic peptide by inhalation, and in the second study five subjects, FEV1 1.92 (0.40) l, received 5 mg ANP by inhalation. ANP was given in a placebo-controlled, double blind, randomized manner, with measurement of FEV1 over the following 60 min. Nebulized salbutamol was given at 60 min as a measure of the maximal bronchodilator response attainable by conventional therapy. No significant bronchodilator effect was seen following the 0.1 or 1 mg inhalation, although the latter produced a minimal transient elevation in peripheral atrial natriuretic peptide plasma levels. A bronchodilator effect was seen with the 5 mg dose, which produced delta FEV1 0.42 (0.09) l compared to 0.93 (0.13) l subsequently produced by salbutamol. This effect peaked at 5 min and was no different from placebo from 10 min onwards. We conclude that atrial natriuretic peptide may produce significant bronchodilation when given by inhalation in high doses, and speculate that substances which generate cyclic guanosine monophosphate (cGMP) in airway smooth muscle warrant further investigation as potential bronchodilatory agents.

Activity of the renin-angiotensin system in acute severe asthma and the effect of angiotensin II on lung function.

BACKGROUND: The activity of the renin-angiotensin system in asthma has not been studied previously and the effect of angiotensin II (AII) on bronchomotor tone in vivo is unknown. METHODS: Plasma levels of renin and AII levels were measured in 20 patients with acute severe asthma, nine with mild asthma, 10 with severe chronic asthma, and 16 normal volunteers. The effect of AII, given as an intravenous infusion, on bronchomotor tone was also investigated in eight mild asthmatic patients. RESULTS: In acute severe asthma plasma levels of renin [median (interquartile range)] were elevated on days 1, 2, and 5 after admission [48.7 (24-79), 44.2 (15-75), and 45.5 (21-70) microU/ml, respectively]. Plasma AII levels were significantly elevated at day 5 [56 (12-109) pg/ml]. In the second study a bronchoconstrictor response to intravenous AII was seen with a mean (SE) maximal fall in FEV1 of 0.34 (0.13) litres or 12.4 (3.3)% from baseline following the high dose infusion of AII (8 ng/kg/min) with a corresponding plasma AII concentration of 121.3 pg/ml. CONCLUSIONS: The renin-angiotensin system is activated in acute asthma and AII causes bronchoconstriction in vivo in man. These observations suggest that in some patients AII may contribute to bronchoconstriction during acute severe asthma.

Bronchodilator, cardiovascular, and cyclic guanylyl monophosphate response to high-dose infused atrial natriuretic peptide in asthma.

Atrial natriuretic peptide (ANP) has bronchodilator and vasodilator properties thought to be mediated through the generation of cyclic guanylyl monophosphate (cGMP). The current study was designed to examine the effects of infused ANP on respiratory (FEV1), cardiovascular (blood pressure and pulse), and metabolic (plasma cGMP) function in asthmatic patients. Eight patients with a mean +/- SD age of 45.6 +/- 8.2 yr and mean FEV1 of 56.4 +/- 15.4% of predicted were studied using a randomized double-blind crossover design. On one study day after baseline measurements (FEV1, blood pressure, pulse, and plasma cGMP), ANP was infused for 20-min periods at 5 pmol/kg/min and at 25 pmol/kg/min; a placebo (saline) inhalation was then administered. On the other day the placebo infusion was followed by inhalation of 5 mg albuterol. Measurements were repeated at the end of each 20-min period. The highest rate of ANP infusion increased the FEV1 by 0.50 +/- 0.09 L compared with 0.09 +/- 0.05 after the placebo infusion (p < 0.001). The increase in FEV1 produced by ANP plus placebo inhalation (0.50 +/- 0.28 L) was similar to that produced by placebo infusion plus albuterol inhalation (0.61 +/- 0.30 L). There was no clinically significant fall in systolic or diastolic blood pressure (torr) at the 25 pmol/kg/min infusion rate. The mean basal cGMP was 602 +/- 242 fmol/ml and increased to 5,883 +/- 1,460 and 21,182 +/- 2,509 with the two rates of ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of atrial natriuretic peptide given by intravenous infusion on bronchoconstriction induced by ultrasonically nebulized distilled water (fog).

Atrial natriuretic peptide (ANP) is secreted by cardiac atria and lung tissue; it has a bronchodilator action in normal subjects and patients with asthma and has been shown to protect against histamine-induced bronchoconstriction in patients with asthma. Bronchoconstriction caused by inhalation of ultrasonically nebulized distilled water (fog), in contrast to histamine-induced bronchoconstriction, has features in common with exercise-induced asthma but can be given more easily in a dose-response fashion. The present study aimed to determine the effect of elevated plasma ANP concentrations on the bronchoconstrictor response to inhalation of fog. Eight patients with atopic asthma were studied, mean baseline FEV1 3.00 1, equivalent to 89% (range 76-103%) predicted. The provocation dose of fog producing a 25% fall in FEV1 (PD25) was determined for each subject. On 4 study days, subjects received an intravenous infusion of placebo or ANP at a rate of 1.25, 3.0, or 10.0 pmol/kg/min in randomized, double-blind manner for 30 min to allow steady-state plasma concentrations to be achieved; the PD25 fog was then administered and FEV1 recorded over 30 min. Mean (SEM) baseline plasma ANP concentration was 19.3 (4.1) pg/ml and increased to 39.4 (6.6), 106.4 (11.1), and 445.9 (105.4) with the three rates of ANP infusion. The highest rate of infusion increased prechallenge FEV1 by 8.7 (2.4)% (p less than 0.01), but the lower rates of infusion had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating plasma concentrations of atrial natriuretic peptide and catecholamines in response to maximal exercise in normal and asthmatic subjects.

BACKGROUND: Intravenous infusion of atrial natriuretic peptide has been shown to cause bronchodilatation in patients with asthma and endogenous atrial natriuretic peptide is known to rise with exercise. Whether an aberration in release of atrial natriuretic peptide is concerned in the pathogenesis of exercise induced bronchoconstriction has not been studied. METHODS: The atrial natriuretic peptide response to exercise was studied in eight men with exercise induced asthma and eight age matched non-asthmatic men. Subjects exercised to exhaustion on a treadmill, using the Bruce protocol. Atrial natriuretic peptide and catecholamines were measured at the end of each stage of exercise and oxygen consumption and heart rate were monitored throughout. RESULTS: Both groups showed a 3.5 fold increase in plasma atrial natriuretic peptide during exercise (mean (SE): normal subjects 25 (4) pmol/l; asthmatic subjects 24 (5) pmol/l), with no difference between the two groups. There was a close correlation between plasma atrial natriuretic peptide concentrations and oxygen uptake, catecholamine release, and heart rate in both groups. The catecholamine response was similar in the asthmatic and normal subjects, both groups showing a four fold rise in plasma adrenaline and a 4-5 fold rise in plasma noradrenaline. CONCLUSION: A defect in the release of circulating atrial natriuretic peptide does not account for exercise induced asthma; the concentrations of the circulating peptide that were achieved may effect a small reduction in airway reactivity. Our data do not support the idea that asthmatic patients have abnormal sympathoadrenal activity.

Influence of elevated plasma levels of atrial natriuretic factor on bronchial reactivity in asthma.

Recent studies have demonstrated that elevation of plasma atrial natriuretic factor (ANF) levels may produce significant bronchodilation in the constricted asthmatic airway. The current study was designed to examine the effect of both physiologic and pharmacologic plasma levels of ANF on bronchial reactivity to histamine in asthmatic subjects. A total of eight atopic men with well-controlled asthma were studied, mean (SD) FEV1 3.50 (0.73) L, equivalent to 87 (11)% of predicted; bronchial reactivity as measured by histamine PC20 was 0.77 mg/ml (geometric mean). On four separate study days infusions of 1, 3, or 10 pmol/kg/min of ANF or placebo were administered in a double-blind, randomized manner. Once steady-state plasma levels had been achieved, measurement of bronchial reactivity was repeated. Mean (SEM) basal ANF level was 18.5 (3.5) pg/ml and rose to 41 (4.3), 157 (15), and 500 (30) pg/ml with increasing doses of ANF. With placebo infusion geometric mean histamine PC20 was 0.77 mg/ml and rose to 1.15 mg/ml (p less than 0.05), 1.90 mg/ml (p less than 0.001), and 3.38 mg/ml (p less than 0.001), corresponding to a 1.5-, 2.5-, and 4.4-fold protection with respective ANF infusions. There was no significant change in plasma epinephrine. These results show that at both physiologic and pathophysiologic plasma levels ANF may significantly decrease bronchial reactivity to histamine in asthma.

Management of recurrent malignant pleural effusion in the United Kingdom: survey of clinical practice.

Malignant pleural effusions are often symptomatic and tend to recur after simple aspiration. Pleurodesis may prevent recurrence of the effusion; many agents and techniques have been described. A questionnaire was sent to 448 clinicians in the United Kingdom to determine how pleurodesis is performed in practice. There was a 56% overall response, with replies from 101 respiratory physicians, 88 general physicians, 29 thoracic surgeons, and 35 general surgeons. General surgeons saw few cases of malignant pleural effusion and rarely performed pleurodesis. A patient with recurrent malignant pleural effusion would usually be managed with pleurodesis by 76 (76%) respiratory physicians, 26 (30%) general physicians, and 23 (81%) thoracic surgeons; a further 29 (33%) general physicians would refer such patients to another specialist. Most medical pleurodesis were performed by junior staff, whereas consultant thoracic surgeons were more likely to be concerned with the procedure. All the thoracic surgeons used an intercostal tube drain, usually with suction. An intercostal tube drain was used routinely by only 54 (54%) of the respiratory physicians and 28 (32%) general physicians. Thoracic surgeons preferred talc for pleurodesis whereas physicians most commonly used tetracycline. The variety of methods in use supports the need for randomised, controlled studies to determine the most effective technique of pleurodesis.

Effect of atrial natriuretic factor on bronchomotor tone in the normal human airway.

1. Asthmatic patients bronchodilate in response to infused atrial natriuretic factor. We wished to determine whether the airways of normal subjects responded in a similar way. 2. Changes in airway resistance, as determined by specific airway conductance, were measured in eight normal subjects in response to intravenous infusion of atrial natriuretic factor at doses of 0.5, 2 and 10 pmol min-1 kg-1. 3. No significant effect was observed on specific airway conductance at any rate of infusion despite maximum mean (SEM) plasma levels of 597 (62) pg of atrial natriuretic factor/ml in peripheral venous blood. 4. A second study was performed using six of the eight original subjects and employing a pharmacological dose of 50 pmol of atrial natriuretic factor min-1 kg-1. This produced mean plasma levels of 2056 pg/ml and a mean increase of 31% in specific airway conductance. 5. It is concluded that pharmacological, but not pathophysiological, elevations of plasma atrial natriuretic factor may significantly alter bronchomotor tone in normal subjects.

Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance?

Pretreatment serum levels of neurone specific enolase (NSE) were measured in patients with small cell lung cancer (SCLC). Median values were significantly higher in patients with extensive compared with limited stage disease (48 ng ml-1 v. 17 ng ml-1: P less than 0.001). Serial NSE levels paralleled the clinical response to treatment. In 37 patients with limited SCLC, receiving identical chemotherapy, the pretreatment NSE level was of prognostic significance: with an approximate reduction in median survival of 10% for each 5 ng ml-1 incremental rise in NSE (P = 0.004).

Malignant pleural mesothelioma in western Glasgow 1980-6.

This study reviews all histologically proved cases of malignant pleural mesothelioma seen in the western district of Glasgow during 1980-6. Sixty eight cases were identified (three female) with an age range at presentation of 48-85 (mean 68.9) years. Asbestos exposure was identified in 54 (80%) of the patients, most of whom had been shipyard workers. Pain and dyspnoea were the most common presenting symptoms. Pleural effusion was found in 57 (84%) of the patients, in a ratio of 2.6 right:left. The median survival was only 30 weeks from the time of presentation. Prognosis was significantly better for those presenting with dyspnoea than for those with pain (median survival 44 v 22 weeks). Postmortem examination was performed in 40 cases and metastatic disease found in more than three quarters. There was no significant difference between the incidence of the various tumour cell types or any relation between cell type and survival or the incidence of metastatic disease. A substantial increase in cases of malignant pleural mesothelioma has been found in an area of already high incidence. The use of rigorous histological criteria to determine histological cell type has shown that this previously valued variable is of no discriminatory value with regard to disease activity or survival.

The effect of inhaled ouabain on bronchomotor tone and histamine responsiveness in asthmatic patients.

We have studied the effect of inhaled ouabain on resting bronchomotor tone and histamine responsiveness in eight asthmatic patients in an attempt to clarify the role of Na/K ATPase in airway reactivity. Doses ranged from 50 micrograms to 5000 micrograms and were given in a placebo controlled, double blind manner. Baseline FEV1 was recorded prior to inhalation and at intervals up to 30 min thereafter. At 30 min, a histamine provocation test was performed and results expressed as that concentration producing a 20% fall in FEV1. Maximum fall in FEV1 was not significantly different between placebo or any dose of ouabain, ranging from 4.3%-8.2% (p greater than 0.06) nor was histamine reactivity altered significantly (geometric mean range 0.17 mg-0.29 mg [p greater than 0.2]). Unlike animal studies therefore, we have been unable to demonstrate any effect of Na/K ATPase inhibition on airway reactivity in vivo.

Hypertrophic gastritis associated with increased gastric mucosal prostaglandin E2 concentrations in a patient with the carcinoid syndrome.

A case of a 69 year old man in whom hypertrophic gastritis was associated with the carcinoid syndrome is reported. Concentrations of prostaglandin E2 were increased in plasma, gastric juice, gastric mucosa and urine. He had marked hypochlorhydria in response to pentagastrin stimulation (Peak acid output (PAO) pg:0.2 mmol/h). After successful hepatic arterial embolisation of the metastases (as indicated by an 85% decrease in 24 h urinary 5-HIAA) the concentrations of prostaglandin E2 decreased in the plasma, gastric juice and gastric mucosa. The gastric mucosal hypertrophy regressed and secretion of acid in response to pentagastrin returned (PAO pg:9.0 mmol/h). These findings suggest that the carcinoid tumour was producing a substance which stimulated increased local synthesis of prostaglandin E2 in the gastric mucosa, with concomitant gastric mucosal hypertrophy and inhibition of gastric acid secretion.