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Ten-year mortality rates for lung cancer and coronary heart disease have been related to cigarette smoking habits in 17 475 male civil servants aged 40-64 and in sample of 8089 male British residents aged 35-69. Both diseases were more frequent in smokers. Lung cancer rates were higher overall for 'non-inhalers', particularly in heavy smokers. Tar yield correlated with the risk of lung cancer in non-inhalers but less so in inhalers. Conversely, coronary deaths were more common among inhalers, and the effect of tar/nicotine yield (such as it was) was confined to inhalers. It appears that there are subtle interactions between the amount smoked, the tar/nicotine yield of the cigarette, and the style of smoking. Thus the effects of a change in cigarette characteristics are hard to predict, and they may be different for respiratory and cardiovascular disease. [ABSTRACT FROM AUTHOR]

From March 1988 to March 1990, 11 children with cystic fibrosis (age 5-15 years) underwent combined heart-lung transplantation at our institutes. Maintenance immunosuppression consisted of cyclosporin and azathioprine with corticosteroids and antithymocyte globulin used perioperatively and during rejection episodes. Six patients (55%) survive from 1.5-23 months all of whom have improved life quality. Actuarial survival to 1 year was 55%. At six months after transplant, mean forced expiratory volume at one second was 73.5% of predicted normal, compared with 25% before transplant. There was one perioperative death, three later deaths associated with obliterative bronchiolitis at two, eight, and nine months, and one from mediastinitis at four months. Of the 15 children accepted for transplantation but not receiving grafts, 10 have died (eight within four months of being placed onto the transplant list). Early postoperative problems included acute reversible rejection (n = 10), meconium ileus equivalent (n = 3), and pancreatitis (n = 1). There was a high incidence of later pulmonary rejection with a mean of 5.7 episodes per patient in the first six months. Pulmonary infection occurred relatively infrequently, with Pseudomonas aeruginosa being the most common pathogen. Persistent diabetes mellitus requiring insulin occurred in four and systemic hypertension developed in one. [ABSTRACT FROM AUTHOR]

Forty five patients with cystic fibrosis (age 5-15 years) were assessed for heart-lung transplantation between September 1987 and March 1990. The two main conditions for acceptance were (i) life expectancy less than 2 years and (ii) a severely impaired quality of life. Patients were accepted onto an active waiting list (n = 26), a provisional waiting list (n = 15), or not accepted (n = 4). Selection was made on clinical grounds with objective measurements used as an aid in assessment. As expected, the mean values for objective measures were significantly different between patients on the active waiting list compared with the provisional waiting list/not accepted group for resting heart rate (118/minute v 101/minute), percentage of ideal weight (83.2% v 93.1%), forced expiratory volume at one second as percent of predicted normal (27.3% v 47.6%), Shwachman-Kulczycki score (33.6 v 52.5), Chrispin-Norman x ray score (25.8 v 22.1), 12 minute walk (540 m v 854 m), and minimal oxygen saturation (81.5% v 92%). Psychological evaluation demonstrated a 55% incidence of individual and a 50% incidence of family morbidity. Of the 26 patients accepted onto the active waiting list, 11 have been transplanted (mean waiting time 3.3 months), 10 have died within a mean of 3.7 months of acceptance, and five remain on the active list (mean 5.6 months). [ABSTRACT FROM AUTHOR]

We report our experience of heart-lung transplantation for the treatment of children with terminal respiratory disease. Between May 1987 and October 1988 we performed heart-lung transplantation in five children under the age of 16 (age range 11-15). All the patients were severely disabled by dyspnoea and hypoxia. Two had primary pulmonary hypertension, two cystic fibrosis, and one had Eisenmenger's syndrome. All five children are alive and well five to 17 months after operation and have returned to activities normal for their age. Three of the five patients had episodes of infection after operation. These were staphylococcal pneumonia, herpes simplex pneumonitis and, in one of the patients with cystic fibrosis, persistent purulent sputum. The mean number of episodes of rejection per child was 2.7 per half year. Heart-lung transplantation is a practical treatment for children in these disease groups with terminal respiratory failure. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Amphetamine-like appetite suppressants, particularly fenfluramines, have been implicated in the aetiology of primary pulmonary hypertension. At one specialist centre in France 20% of patients with primary pulmonary hypertension had been exposed to fenfluramine. The prevalence of primary pulmonary hypertension associated with fenfluramines and other appetite suppressants in the United Kingdom is unknown. This study was performed to measure prior exposure to appetite suppressants in patients with primary pulmonary hypertension. SETTING--Heart lung transplantation centres in England. PATIENTS--United Kingdom residents with proven primary pulmonary hypertension referred for consideration of heart lung transplantation. METHODS--Case surveillance study, obtaining data from the hospital and general practitioner's notes and directly from the patients or their relatives. RESULTS--55 patients were identified. Drug histories were available from hospital records in all patients, from the general practitioner's notes in 51, and from the patients or relatives in 44. Of these, 3 female patients had been exposed to appetite suppressants (2 fenfluramine, 1 diethylpropion): 2 have since died. In each case exposure was brief and apparently predated the development of symptoms by several years. CONCLUSIONS--Exposure of patients with severe primary pulmonary hypertension to fenfluramine and other appetite suppressants is uncommon in the United Kingdom unlike in France, where most of the cases associating primary pulmonary hypertension with fenfluramine use have originated. This may reflect more conservative prescribing of these agents in the United Kingdom. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To determine whether epoprostenol (prostacyclin, PGI2) or heart-lung transplantation (HLT), or both improves survival of patients with severe pulmonary hypertension. DESIGN--This was a prospective study where the effects of epoprostenol were compared with conventional treatment. Also, the benefits of epoprostenol and HLT were assessed by comparing survival in this group with that of 120 patients at the Mayo Clinic before HLT and epoprostenol treatment became available. PATIENTS AND INTERVENTIONS--Forty four patients were studied; 25 received continuous epoprostenol over a four year period (mean (SD) cardiac index 1.8 (0.4) 1 min-1 m-2 and mean (SD) pulmonary artery pressure (PAP) 70 (16) mm Hg) and 19 did not (cardiac index 2.1 (0.6) 1 min-1 m-2 and PAP 64 (13) mm Hg). Ten patients underwent HLT: seven had received epoprostenol, and three had not. RESULTS--The therapeutic intervention with epoprostenol, or HLT, or both improved survival compared with the Mayo clinic patients (p = 0.05). Most of the benefit was conferred by epoprostenol, which prolonged survival twofold from a median time of eight to 17 months and doubled the changes of successful HLT. The improved survival with epoprostenol was not related to its immediate capacity to cause pulmonary vasodilation. Those patients who had limited acute pulmonary vasodilation when treated with epoprostenol showed the greatest improvement in survival. CONCLUSIONS--These preliminary results indicate that those pulmonary hypertensive patients with the poorest chance of survival can be helped by epoprostenol and by HLT. [ABSTRACT FROM PUBLISHER]

Ten patients with severe primary pulmonary hypertension and pronounced disability who were unresponsive to oral vasodilators were treated with intravenous epoprostenol (prostacyclin). All had been referred for heart and lung transplantation. Short term administration of epoprostenol (mean dose 5.5 ng/kg/min) increased the mean cardiac index from 1.8 to 2.2 1/min/m2, improved pulmonary artery oxygen saturation from 48% to 57%, and increased calculated tissue oxygen delivery from 10 to 11.8 ml/kg/min. The mean pulmonary vascular resistance fell by 18% while mean systemic artery pressure fell by 32%. Pulmonary artery pressure rose in only two patients. Continued intravenous infusion of epoprostenol for 1-25 months was associated with subjective and clinical improvement. Exercise tolerance improved as measured by an increase in the maximum rate of oxygen consumption during progressive exercise testing. In those six patients who were able to exercise before treatment it rose from a mean of 7 to 15 ml/kg/min. Those who had been unable to exercise before treatment achieved comparable rates of oxygen consumption after treatment. Two patients died on treatment, three have undergone heart-lung transplantation, and in five the treatment is continuing. Complications included episodes of septicaemia and ascites. In this uncontrolled study of patients with severe pulmonary hypertension epoprostenol seemed to offer a means of optimally dosing the patients with a vasodilator to reduce pulmonary vascular resistance and thus increasing cardiac output and oxygen tissue delivery. There was no evidence to suggest that this treatment influenced the progress of the disease. [ABSTRACT FROM PUBLISHER]

Background: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which can improve gas exchange in acute lung injury. However, it is uncertain that this effect on arterial oxygenation can be generalised to all lung diseases.Methods: The effects of inhaled NO on gas exchange were studied in nine patients with chronic obstructive pulmonary disease (COPD), 11 patients with severe pulmonary hypertension, and 14 healthy volunteers. A randomized sequence of 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask.Results: Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension (TcPO2) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to 7.0 (0.5) kPa in patients with COPD. There was no change in TcPO2 in patients with severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon dioxide tension (TcPCO2), arterial oxygen saturation (SaO2) measured by pulse oximeter, or cardiac output determined by the transthoracic impedance method.Conclusions: Inhaled NO does not improve TcPO2 nor increase cardiac output in normal subjects and patients with COPD, suggesting that inhaled NO worsens gas exchange. This could represent inhaled NO overriding hypoxic pulmonary vasoconstriction in COPD. The finding that TcPO2 also fell when normal subjects inhaled NO suggests that a similar mechanism normally contributes to optimal gas exchange. Whilst inhaled NO can improve oxygenation, this effect should not be considered to be a general response but is dependent on the type of lung disease. [ABSTRACT FROM AUTHOR]

The main clinical problems that follow heart-lung transplantation are opportunist infections of the lungs and pulmonary rejection. Of 23 patients undergoing heart-lung transplantation, eight had opportunist infections and 12 had at least one episode of pulmonary rejection. Cardiac rejection occurred in only one patient, who did not need treatment. Of the 12 patients who had pulmonary rejection, nine recovered fully after augmented immunosuppression with high dose corticosteroids, although one patient required additional low dose corticosteroids for eight months before making a full recovery. Fatal opportunist lung infection followed treatment for rejection in two patients. One patient developed obliterative bronchiolitis. Of the eight patients with opportunist infections, five had primary cytomegalovirus pneumonitis, acquired from the donor. All three patients treated with acyclovir died, whereas the two treated with hyperimmune globulin and dihydroxy proxymethylguanine recovered fully. Two patients developed Pneumocystis carinii pneumonia, which was treated successfully in one patient with intravenous sulphadimidine and trimethoprim. The other patient died after a further episode of rejection and aspergillus bronchitis. One patient developed a tuberculous empyema. The calculated actuarial survival at one year was 78% and at two years 67.2%. Although it is still in its innovative stage heart-lung transplantation appears to have complications and results similar to those of transplantation of other organs. [ABSTRACT FROM AUTHOR]

Peak plasma concentrations of lignocaine were recorded in 41 patients receiving topically applied lignocaine for fiberoptic bronchoscopy. Adequate anaesthesia was achieved in all patients with an average dose per unit weight of 9.3 +/- 0.5 mg/kg (SEM) giving a mean peak plasma concentration of 2.9 +/- 0.5 mg/l-1 (SEM) (+/- SEM 0.5). The plasma concentration exceeded toxic levels of 5.0 mg/l-1 in only two patients, and no complications were observed. Peak concentrations were influenced only by dose per unit weight administered and not by factors considered likely to influence mucosal absorption from the bronchial tree, such as sputum production, airflow obstruction, or cigarette smoking. A major proportion of the total dose of lignocaine was required to anaesthetise the nose, pharynx, and larynx, only a small proportion being needed for the bronchial tree. Lignocaine gel (2% w/v) was preferred by patients, and in a study of 10 volunteers, produced lower plasma concentrations when used as a topical anaesthetic than did lignocaine aerosol (10% w/v) or lignocaine solution (4% w/v). [ABSTRACT FROM AUTHOR]

Ten patients with ulcerative colitis, all of whom were non-smokers, presented with a productive cough. In six, the chest radiography was normal and cough was the only symptom; three of these patients had a minor obstructive ventilatory defect on testing. Four patients complained of exertional dyspnoea and had both an abnormal chest radiograph with bilateral pulmonary shadows and a mixed obstructive and restrictive ventilatory defect. Bronchial epithelial biopsies from four patients (two with and two without pulmonary shadows) revealed basal reserve cell hyperplasia, basement membrane thickening, and submucosal inflammation, changes more usually associated with cigarette smoking. Inhaled beclomethasone diproprionate relieved cough in seven patients. The occurrence of airway epithelial disease in association with ulcerative colitis raises the possibility of a systemic mechanism affecting both bronchial and colonic epithelium. It does not seem likely that sulphasalazine was the cause of the pulmonary syndrome in these subjects. [ABSTRACT FROM AUTHOR]

The acute airway response to smoking varying numbers (one to four) of identical cigarettes in rapid succession and smoking single cigarettes of differing tar/nicotine yields was assessed repeatedly in 13 healthy smokers. The airway response was variable, indicating airway narrowing consistently in only three subjects. There appeared no difference between forced spirometry and measurement of airway resistance in detecting the airway response. No relationship was observed between the airway response and amount of smoke inhaled into the lungs as measured either by changes in venous blood nicotine or percentage carboxyhaemoglobin. When five smokers inhaled smoke directly from a cigarette acute airway narrowing was consistently observed. A normal smoking pattern consisting of an initial drag of smoke into the mouth, followed after a pause by inhalation of smoke diluted with air, did not consistently cause airway narrowing although similar amounts of smoke as the direct drag were inhaled as assessed by changes in venous blood nicotine. The manner of smoke inhalation affects the relative concentrations of the different constituents of smoke reaching the lungs and also appears to be the main determinant of the acute airway response to smoking, which was unrelated to the number of cigarettes smoked or the tar content of the smoke. This suggests that patterns of smoke inhalation may influence the pathogenesis of bronchial disease associated with smoking. [ABSTRACT FROM AUTHOR]

The use of a single pair of magnetometer coils placed centrally on the trunk to record tidal volumes and breath times has been evaluated in five normal subjects in five positions. Breath times were accurate in all positions tested but tidal volumes were only reliable with the subjects lying and the backrest raised to 45° or in the supine position only for volumes up to 1000 ml. Using this system, recordings have been made in seven patients with barbiturate overdose, five with salicylate overdose, and five undergoing anaesthesia with thiopentone. The single pair of coils was satisfactory for measuring changes in the pattern of breathing in these patients. In barbiturate overdose in five patients there was initially an increase in respiratory frequency with a decrease in tidal volume. As these patients recovered the tidal volume increased and the respiratory rate slowed. In two patients who had a raised PaCO there was initially reduction of both tidal volume and respiratory rate, both increasing as the patients recovered. Monitoring respiratory rate appears to be a useful guide in barbiturate overdose; a slowing of the rate without recovery of consciousness warrants further investigation to assess the need for ventilatory support. The single pair of coils were also satisfactory for measuring the increased tidal volume in salicylate overdose. As after other respiratory stimuli in man, increased ventilation occurred predominantly through changes in tidal volume and expiratory time while inspiratory time changed very little. [ABSTRACT FROM PUBLISHER]

Five patients are reported who developed evidence of acute lung damage after proved ingestion of paraquat. In two the lung changes resolved; in one an aspiration pneumonia occurred, which was successfully treated, while two developed fatal pulmonary oedema. These pulmonary complications after paraquat intoxication appear more common than the progressive pulmonary fibrosis previously described. It is suggested that acute pulmonary oedema is a response to large doses, usually of Gramoxone, that subclinical lung changes result from small doses, usually of Weedol, and that pulmonary fibrosis occurs after intermediate doses. Preliminary data on plasma paraquat concentrations suggest that these are of value in prognosis. [ABSTRACT FROM PUBLISHER]

A man aged 57 years who had lived most of his life in London, suffered from asthma which had begun during army service in Burma 37 years previously. Latterly he was treated with increasing doses of corticosteroids but his symptoms continued to worsen and he died of asthma. Necropsy revealed a heavy opportunistic infection of the bronchi and lungs by the nematode Strongyloides stercoralis which he had presumably acquired while on service abroad. The case illustrates the need, even in non-endemic areas, to suspect opportunistic pulmonary strongyloidiasis when a patient's asthma worsens despite treatment with increasing doses of corticosteroids. Although it is a potentially lethal iatrogenic opportunistic infection, it is amenable to treatment with anthelminthic agents if recognized in time. [ABSTRACT FROM PUBLISHER]

Fourteen cigarette brands manufactured in Nigeria in 1981 were analysed to determine the tar, nicotine, and carbon monoxide yields. Five of the brands belonged to the high and middle to high tar category (greater than 22 mg/cigarette) and nine to the middle tar (17-22 mg/cigarette) category. None of the cigarettes was in the low to middle and low tar (less than 17 mg/cigarette) category. The nicotine and carbon monoxide yields were similar to those of European cigarettes. Tobacco companies need to manufacture low tar cigarettes in the Third World as is the practice in the economically developed parts of the world. [ABSTRACT FROM PUBLISHER]

Background: The first successful single lung transplantation was carried out in 1983 for pulmonary fibrosis. Because of the inherent advantages of single lung transplantation, a transplantation programme has been started for patients with end stage lung disease due to emphysema.Methods: Between October 1990 and August 1993 25 patients with severe emphysema (15 men, mean age 51 years) received a single lung transplant at our institution. All patients were severely disabled with a mean (SD) 12 minute walking distance of 281 (165) metres. There were five deaths in the series, four in the first 20 days and one on day 503. Two patients suffered graft compression by air trapping in the native lung. Bronchial narrowing requiring insertion of endobronchial stenting occurred in four patients.Results: Mean (SD) FEV1 improved from a preoperative value of 17.8(13%) predicted to a six month value of 53.6(13)%, and FEV1/FVC from 23.8(12)% to 68.6(15)%. After the transplant 12 patients are in New York Heart Association (NYHA) class I and the rest of the survivors are in NYHA II. Actuarial survival was 82% at one year and 74% at three years.Conclusions: Single lung transplantation is an effective treatment for end stage lung disease due to emphysema and carries an acceptable mortality and morbidity. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide is released from pulmonary endothelial cells and contributes to the low pulmonary vascular resistance. The resistance pulmonary arteries are in close anatomical proximity to membranous airways, so it is likely that some pulmonary endothelial nitric oxide will enter the airspace to allow its measurement in the exhaled breath.Methods: Exhaled air was collected from a single full exhalation and during tidal breathing. This was analysed for concentrations of nitric oxide, nitrogen dioxide, and carbon dioxide to give alveolar (FA) and mixed expired (FE) concentrations. Eight normal subjects were studied and laboratory air was similarly analysed using, respectively, chemiluminescent and infrared analysers.Results: There was no relation between FA concentrations and the laboratory air concentrations. From the single breath, the ratio of (Fano/Faco2) x (Feco2/Feno) had a mean value of 0.92 (95% confidence interval 0.7 to 1.14). As this does not differ from unity, nitric oxide is likely to be derived from the same regions of the lungs as carbon dioxide. During tidal breathing the Feno ranged from 8.3 to 20.3 parts per billion.Conclusions: It is possible to measure endogenous pulmonary nitric oxide production in the exhaled air in man. [ABSTRACT FROM AUTHOR]

Twice daily sustained release theophylline gave satisfactory steady serum theophylline concentrations in asthmatic children aged 7 to 14 years. The children showed improvement in symptoms, less frequent waking at night, reduced use of beta agonist inhalers, and improved early morning peak flows while being treated with this preparation. There was no improvement in peak flow at other times, but the patients recorded increased use of beta agonists during the placebo period. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor concerning assisted discharge for patients with exacerbations of chronic obstructive pulmonary disease.

Background: Exhaled nitric oxide levels are low in patients with cystic fibrosis (CF), despite the chronic inflammation present in the airways. This study aimed to determine whether levels of exhaled nitric oxide were reduced prior to the onset of respiratory symptoms in infants with CF.Methods: The levels of exhaled nitric oxide were measured using a chemiluminescence analyser in five infants with CF and 11 healthy control subjects, both groups having a mean age of 48.6 days.Results: Mean levels of exhaled nitric oxide were significantly lower in infants with CF than in the control group (4.9 ppb v 12.1 ppb; p=0.01).Conclusions: This finding may be the key to understanding the inflammatory processes in early cystic fibrosis and may lead to novel treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Unexplained or primary pulmonary hypertension results in an obliteration and obstruction of resistance pulmonary arteries. In these patients gas exchange is impaired and the measurement of gas transfer for carbon monoxide is usually reduced. This has been thought to represent a reduction in pulmonary alveolar capillary blood volume (Vc). A single breath test, measuring simultaneously the uptake of both nitric oxide (NO) and carbon monoxide (CO), provides a simple and practical measurement of membrane diffusion (Dm) and Vc.Methods: A standard single breath test for the measurement of gas transfer for carbon monoxide (TLCO) was adapted to include NO (40 ppm) in the inhaled gas mixture and a breath-hold time at total lung capacity of 7.5 seconds was used. Twelve patients with primary pulmonary hypertension and 10 similar normal volunteers were studied while seated at rest.Results: The patients had reduced values for TLCO and TLNO. The mean (SD) value of Dm in the patients was 36.7 (32.1) mmol/min.kPa compared with 52.8 (23.9) mmol/min.kPa in the normal subjects. Vc in the patients was 0.03 (0.03) 1 and 0.06 (0.01) 1 in the normal subjects.Conclusions: The simultaneous measurement of NO and CO uptake is possible in healthy volunteers and patients with primary hypertension. In these patients capillary blood volume is reduced compared with normal subjects. [ABSTRACT FROM AUTHOR]

589-595. The abdomen and ribcage volume contribution to the tidal volume have been determined using magnetometers in three groups of subjects—normal males, patients with hemidiaphragmatic palsy, and patients with bilateral diaphragmatic palsy. In all three groups the main moving parts appear to be the anterior surfaces of the abdomen and ribcage even in the presence of bilateral diaphragmatic palsy. In the group of patients with bilateral diaphragmatic paralysis the anterior abdominal wall moved inward paradoxically on inspiration. This `negative' movement increased with larger tidal breaths and was best seen in recumbent patients. The normal subjects and those with hemidiaphragmatic palsy showed an outward movement of the anterior abdominal wall on inspiration which increased with larger tidal breaths. It is believed that the paradoxical movement of the abdomen in bilateral diaphragmatic palsy is a valuable clinical sign of this condition. The contribution of the abdominal volume displacement to the tidal volume in the normal subjects and the hemidiaphragmatic palsy patients varied considerably between subjects and with different postures, but no difference could be discerned between the two groups. This supports the suggestion that the diaphragm is concerned more with maintaining a pressure difference between the abdomen and ribcage than displacing abdominal volume. [ABSTRACT FROM PUBLISHER]