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Background: Both ventilation (V) and perfusion (Q) of the lungs are altered in asthma, but their relationships with allergen-induced airway responses and gas exchange are not well described., Methods: The effects of aerosolized allergen provocation of V/Q abnormalities in nonsmoking, male atopic asthmatics (six dual responders and two isolated early responders) were compared with measurements of airflow limitation (forced expiratory volume in 1 s [FEV(1)]), gas exchange (arterial oxygen saturation, arterial oxygen partial pressure and alveolar-arterial oxygen gradient) and airway reactivity (provocative concentration of histamine causing a decrease of 20% in FEV(1)). V and Q lung scans at 30 min and 6 h following allergen challenge and changes in all variables were compared with prechallenge data. Digital image data were registered to baseline scans, and quantitative comparisons of changes made were supported by qualitative assessments of the images., Results: All subjects showed evidence of impaired gas exchange, as reflected by lowered arterial oxygen tension and widened alveolar arterial oxygen gradients. Baseline V/Q scans were abnormal, and there were allergen-induced changes in V and Q at 30 min, with scans at 6 h showing additional changes in Q, particularly in dual responders. Allergen-induced gas trapping was evident at 30 min and was sustained at 6 h., Conclusions: Regional patterns of V and Q derived from lung scintigraphy showed a wider range of disturbances than were indicated by the magnitude of airflow limitation and arterial hypoxemia following allergen provocation, and they remained abnormal despite normalization of FEV(1). Imaging of regional abnormalities of gas exchange may be relevant in the evaluation of patients with asthma.

A number of risk factors for the development and severity of asthma in childhood are known. Particularly, there is information on allergens, excessive use of beta2- agonists, and indoor environmental pollutants. Similar information on elderly patients is lacking. We examined the risk factors for current asthma and for the severity of asthma in 95 elderly subjects (>65 years old) compared to 274 elderly subjects with obstructive spirometry who did not have asthma as defined by the following criteria: symptoms of episodic wheeze, cough, or chest tightness and forced expiratory volume in 1 sec/vital capacity (FEV1/VC) <70% with >15% or 200 mL reversibility in FEV1 to 200 microg salbutamol given from a metered-dose inhaler. The severity of airflow limitation was graded on the basis of the FEV1/VC ratio as mild (60%-70%), moderate (40%-60%), and severe (<40%). Asthma history was collected using the Medical Research Council respiratory questionnaire and a follow-up postal questionnaire. Data were analyzed using multiple logistic regression and the overall goodness-of-fit of the model was checked using the Hosmer-Lemeshow (HL) statistic. History of allergy (to one or more of the following allergens: cat, house dust, or grass or tree pollen) (odds ratio [OR] 25; 95% confidence interval [CI] 13-51; p = 0.0001) and history of childhood wheeze (OR 8; 95% CI 4-9; p = 0.004) were strong predictors of current asthma. Duration of wheezing, smoking history, indoor heating, history of working in coal mines, and sex were not predictors (HL 6.75, degrees of freedom [df] = 8, p = 0.56). Use of >4 puffs of salbutamol/ day (OR 5.3; 95% CI 2-14; p = 0.005), more than 10 years of asthma symptoms (OR 4.2; 95% CI 4.1-36.2; p = 0.0001), and >500 mL reversibility in FEV1 (OR 4.2; 95% CI 1.2-14.3; p = 0.05) were independent predictors of moderate to severe asthma. History of atopy was the strongest predictor of asthma in the elderly population studied. Indoor heating, presence of pets at home, sex, smoking history, and history of working in coal mines were not predictors of asthma. The severity of asthma as assessed by measurement of airflow limitation was related to the frequency of use of beta2-agonists, duration of symptoms of asthma, and increased reversibility of FEV1 to beta2-agonist.

Pulmonary hypertension often has a lethal outcome in systemic sclerosis and the treatment is challenging. Epoprostenol is a potent pulmonary vasodilator and its efficacy has been demonstrated when delivered by the intravenous and aerosolized routes. We report the haemodynamic and functional benefits of epoprostenol administered by inhalation to a spontaneously breathing patient with partially reversible pulmonary hypertension due to systemic sclerosis. Aerosolized epoprostenol, equivalent to the maximum tolerated intravenous dose (31.2 micrograms), produced a 58% fall in pulmonary vascular resistance, increased the cardiac output by 42% and improved functional performance by one MET (3.5 ml kg-1 min-1 of oxygen uptake) without any significant side-effects. Selective distribution of epoprostenol by the inhaled route may offer a new strategy for treatment of pulmonary hypertension.

Bronchial asthma is now increasingly recognized in the elderly and is associated with significant morbidity and mortality. The aims of this study were two-fold: first, to assess the prevalence and, second, to evaluate diagnostic awareness, therapeutic management and patient perception of bronchial asthma among elderly patients in the community. From the age-sex register of an urban general practice in NE England, 2004 patients aged > 65 years were eligible for inclusion. Response to an initial screening questionnaire on respiratory symptomatology was 68% (n = 1362). Of these, 869 patients had respiratory symptoms: 390 voluntarily agreed to be evaluated further including assessment of airway physiology. In this group 369/390 had obstructive spirometry and, of these, 95 patients fulfilled clinical and physiological criteria of bronchial asthma. Prevalence of asthma within this age cohort was minimally and rather crudely assigned at 4.5% (95/2004). Among the 95 patients so-defined patients with asthma [age 70 +/- 8 years (mean +/- SD), FEV1 = 0.96 +/- 0.41, 33 male, 75 life-long non-smokers], subjective awareness, perception and attribution of pulmonary symptoms were poor. Further, despite tangible evidence of reversible and significant airflow limitation, only 21 were receiving inhaled glucocorticoid therapy (median daily dose 400 micrograms). Asthma in the elderly remains poorly perceived, poorly recognized and suboptimally treated. These findings are particularly apposite in the light of current epidemiological trends in asthma mortality and morbidity in elderly age cohorts.

Chest tube insertion is generally considered a safe procedure. We describe a patient who developed winging of the scapula following chest tube insertion. This complication has not been documented before.

Objectives: To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors., Methods: Twenty lifelong non-smoking RA patients (mean age 59 years (range 44-72; 18 females) were studied. Detailed medical and drug histories were taken. Protease inhibitor phenotype (Pi) and HLA-DR4 status were assessed. Schirmer's tear tests were performed to detect keratoconjunctivitis sicca (KCS). Spirometry, flow volume loops, and gas transfer factor measurement were recorded. The degree of bronchial reactivity (PC20 FEV1) was measured by a methacholine inhalation test. Chest and hand radiographs and HRCT of the lung were performed in all patients., Results: Thirteen patients were HLA-DR4 positive. Eighteen had the Pi MM and two the Pi MS phenotype. Eight patients had evidence of KCS on Schirmer's tear testing. Ten patients achieved PC20 FEV1 in the methacholine inhalation test. All the patients had normal chest radiographs and all showed evidence of erosive arthropathy on hand radiographs. Five patients (25%) showed basal bronchiectasis and one mild interstitial lung disease on HRCT. All five patients with bronchiectasis had the Pi MM phenotype, four had HLA-DR4, four had KCS and three achieved PC20 FEV1; these values were not significantly different (p > 0.05) from those in patients without bronchiectasis., Conclusion: Using the highly sensitive technique of HRCT, we found evidence to suggest that the incidence of bronchiectasis in lifelong non-smoking RA patients may be much higher than previously reported.

One-hundred rheumatoid arthritis (RA) patients were assessed for the association of HLA-DR4, protease inhibitor (Pi) phenotype and keratoconjunctivitis sicca (KCS) with a variety of clinical features, airflow obstruction and bronchial reactivity. Spirometry, lung volume and gas transfer factor measurements were performed to detect airflow obstruction. Bronchial reactivity to inhaled methacholine was assessed by measuring the provocative dose of methacholine causing a 20% fall in FEV1 from the baseline (PD20). Sixty-two patients were HLA-DR4 positive, 87 had Pi MM and 13 MS phenotypes and 37 had positive Schirmer's tear tests. Patients with KCS had a significantly increased history of wheeze (11/37 vs 7/63, P = 0.03, relative risk (RR) 1.8 [95% CI 1.04, 3.1]), those with HLA-DR4 had a significantly decreased atopy on skin-prick testing [3/62 vs 7/38, were significantly higher in the Pi MS group compared to Pi MM group. There was no significant association of HLA-DR4, Pi phenotype and KCS with bronchial reactivity. We conclude that there is no overall significant association of HLA-DR4, Pi phenotype and KCS with airflow obstruction and bronchial reactivity in RA.

Objectives: To investigate the prevalence of airways obstruction and bronchial reactivity to inhaled methacholine in rheumatoid arthritis patients and unselected controls. The control population consisted of patients attending the rheumatology department for minor degenerative joint problems., Methods: One hundred patients with rheumatoid arthritis (RA) [72 (72%) women, 28 (28%) men; mean (SD) age 58 (10) years] and fifty controls [30 (60%) women, 20 (40%) men; mean (SD) age 56 (9) years] were studied. Detailed medical, smoking and drug histories were taken; skin prick tests were performed to assess atopy and chest and hand radiographs were performed. Spirometry, flow volume loops and gas transfer factor measurement were performed to detect airflow obstruction and methacholine inhalation tests were carried out to assess bronchial reactivity., Results: There was no significant difference between rheumatoid arthritis patients and the controls in age, sex, smoking status and atopy on skin prick testing (p < 0.05). A significantly higher number of patients with RA had a history of wheeze compared with the controls (18% v 4%, p < 0.05). FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower in the rheumatoid arthritis group (p < 0.05). A significantly higher number of patients with RA compared with controls showed bronchial reactivity to inhaled methacholine [55 (55%) v 8 (16%), p < 0.05]. FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower among the patients with RA achieving PD20 FEV1 to inhaled methacholine (p < 0.05)., Conclusion: In unselected rheumatoid arthritis patients both airflow obstruction and bronchial reactivity are significantly increased compared with controls.

A 46-year-old endoscopy nurse developed symptoms suggestive of occupational asthma after seven years of exposure to glutaraldehyde. An initial inhalation challenge test at the endoscopy suite caused a very dramatic immediate fall in FEV1 from 3.6 to 1.5 litres. To further evaluate the case and establish a threshold for the response, a technique was devised to allow a series of double-blind inhalation challenges with activated glutaraldehyde vapour at exposure levels of 0.01-0.32 ppm. The results suggested marked dual asthmatic reactions following challenges with 0.032 ppm glutaraldehyde; however, similar 'reactions' were observed on control days. These were associated with an increase in airway responsiveness to methacholine, with the PD20FEV1 falling from > 6400 micrograms to 135 micrograms. The interpretation of these results was potentially confounded by an intercurrent respiratory tract infection and by technically poor FEV1 recordings, so the challenge series was repeated three weeks later. The second series of double-blind inhalation challenges with carefully controlled exposures to glutaraldehyde (up to 0.32 ppm for 10 min) gave rise to no obvious asthmatic reactions, in marked contrast to the results of the unblinded workplace challenge. There was a slight increase in airway responsiveness, with the PD20FEV1 falling from > 6400 micrograms to 1850 micrograms. These results illustrate the potential for misdiagnosis of occupational asthma when unblinded challenge tests are used and show that, even with sophisticated investigatory techniques, a clear-cut diagnostic result may be elusive.

Haemophilus influenzae is a common cause of epiglottitis and meningitis in children and exacerbation of chronic bronchitis in adults. However, the ability of this organism to cause serious infections in adults is less well recognized. We report a case of a 34-year-old previously healthy female who presented with epiglottitis and later developed bilateral empyema; both blood and pleural fluid grew Haemophilus influenzae.

Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.

A double-blind within-patient investigation was performed to determine whether the interposition of an extension tube (10 cm length X 3.2 cm diameter) between a metered dose inhaler and the mouth alters the bronchodilator efficacy of terbutaline sulphate. On two consecutive study days 14 adult patients with stable reversible airways obstruction inhaled a cumulative dose of 500 micrograms of terbutaline which was delivered from a metered dose inhaler with or without the extension tube attached and received placebo in a similar manner. The drug was inhaled in doses of 125, 125, and 250 micrograms at 20 minutes intervals. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), thoracic gas volume (TGV), and specific airways conductance (sGaw). These were done immediately before and at five and 15 minute intervals after each dose, and were repeated 90, 120, 180, 240, and 300 minutes after the first inhalation of terbutaline. Administration of terbutaline with and without an extension tube achieved significant bronchodilation at all dose levels in all respiratory variables (p < 0.001). There was no statistically significant difference in FEV1, FVC, PEFR, and sGaw values at any time or dose level with either method of administration. The use of the extension tube did not impair the efficacy or duration of action of inhaled terbutaline.

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids.

The effects of some general anaesthetics, for example thiopentone, Althesin (alphaxalone + alphadolone) and ketamine, on cerebral vascular smooth muscle are those which would be expected from their metabolic actions. With other anaesthetics, mainly those administered by inhalation, and especially the volatile agents, cerebral blood flow increases in excess of the metabolic activity, which is usually depressed to varying degrees. During general anaesthesia with any of these agents, responses to changes in arterial Pco2 or blood pressure are maintained. Furthermore, when seizure activity occurs during enflurane administration, there is a flow response to the associated metabolic stimulation. The time course of the flow response to the metabolically depressant drug Althesin has been measured in baboons and shown to be very rapid. Wtih this drug cerebrovascular resistance begins to increase within 2 s of its arrival in the brain. This rapid flow change occurs also after sympathetic denervation. Extracellular fluid pH of the cortex does not alter until after the initiation of the vascular smooth muscle response.

The dose-response relationships of the anticholinergic bronchodilator drug ipratropium bromide were studied. Cumulative doses totalling 288 micrograms ipratropium were given by inhalation of a liquid aerosol from a Wright nebuliser to each of 10 patients with stable, moderately severe airflow obstruction. Up to 80% of the maximum achievable bronchodilator response, as assessed by a rise in the patients' mean forced expiratory volume in one second (FEV1), was obtained with a cumulative total dose of 72 micrograms; with additional doses beyond 72 micrograms there was no significant further improvement. In the same patients the effects of administration of cumulative doses of ipratropium to a total of 72 micrograms from a Wright nebuliser were compared with those achieved with a metered-dose inhaler. Bronchodilatation was assessed by measurement of peak expiratory flow rate, FEV1, forced vital capacity, thoracic gas volume and specific airways conductance (sGaw). No significant difference was observed in the response at any dose level between the wet and the dry aerosols. By fitting a curve to the mean values of FEV1 and sGaw an estimate was made of the dose of ipratropium bromide required to produce 99% of the achievable bronchodilator response. For FEV1 this dose was 78 micrograms when ipratropium was inhaled as a nebulised solution from the Wright nebuliser and 82 micrograms when it was inhaled from the metered-dose inhaler; for sGaw the respective values were 54 and 58 micrograms. In these patients with stable airflow obstruction there was no therapeutic advantage in the use of ipratropium bromide as a wet aerosol.

1 In the baboon the blood levels of pentazocine between 1 and 60 min after intravenous injection of 0.5 mg/kg were measured by a gas chromatographic technique. From cerebral arteriovenous differences it was shown that the peak of the brain concentration occurred within 15 min and probably within 10 min of intravenous injection. At the time of peak concentration about 10% of the injected dose was in the brain, while the corresponding value at 60 min was 2%.2 The concentration of pentazocine in the brain was an order of magnitude greater than the concentration in cerebral venous blood both at 5 min and 60 min after injection. No major brain interregional differences were demonstrated. Cerebrospinal fluid from the cisterna magna did not yield values from which the cerebral concentration of pentazocine could be predicted.

Continued expansion of an artificial space-occupying lesion produced further increases in mean supratentorial and infratentorial pressures associated with increases in mean arterial pressure, heart rate, and systemic vascular resistance-the `Cushing' or systemic hypertensive response. These primary changes resulted in an increase in transtentorial pressure gradient and a decrease in arrhythmia index. Immediately before the onset of the systemic hypertensive response, supratentorial perfusion pressure was low, and the period of systemic hypertension did not appear to produce any worthwhile improvement in the perfusion pressure or in the blood flow in the supratentorial compartment. The studies demonstrated also that the systemic hypertensive response was a pre-terminal event and was followed rapidly by circulatory failure.

Hypotension to a mean blood pressure of 33 mmHg for periods of 70 to 187 minutes was induced by increasing the inspired halothane concentration in 11 baboons which were already anaesthetized with 0·5% halothane, nitrous oxide, and oxygen. During hypotension, cerebral blood flow, measured by Xenon clearance and by a carotid electromagnetic flowmeter, decreased by more than half, and sagittal sinus oxygen saturation was 46%. Cerebral oxygen uptake fell from 5·15 to 3·56 ml./100 g/min at this deeper level of halothane anaesthesia. Cerebral hyperaemia developed after hypotension in those animals which regained a mean blood pressure greater than 70 mmHg. Acidbase measurements on CSF from the cisterna magna revealed no metabolic acidosis during or after hypotension. In all four animals with intact autoregulation before hypotension, this was absent or impaired afterwards.

The methods used to screen patients for malignant hyperpyrexia at present are not sufficiently accurate. This paper reports more specific methods of detecting patients liable to develop malignant hyperpyrexia. A motor-point muscle biopsy is performed for histopathological examination and to detect muscle contracture in vitro after exposure to halothane and suxamethonium.

Disadvantages associated with the use of ventricular catheters for the prolonged measurement of intracranial pressure have resulted in the search for an alternative technique. Measurement of pressure from the extradural space is one such possibility, but widespread acceptance of this procedure has been limited by the technical difficulties associated with this measurement and lack of information on the relationship between cerebrospinal fluid and extradural pressures. A study to investigate this relationship and to develop a simple and effective technique for measuring extradural pressure is described.