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Background: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent.Methods: We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). This trial is registered with ClinicalTrials.gov number NCT00419068.Findings: 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90-2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (p(interaction)=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36-48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (p(interaction)=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6-88·2; p<0·0001).Interpretation: Administration of four doses of 2·5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism.Funding: British Lung Foundation. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of tuberculosis (TB) has increased over the last two decades. Many patients with TB preferentially access healthcare via the emergency department (ED) prediagnosis, presenting an early opportunity for diagnosis., Methods: We looked at the number of patients who presented to ED in the 3 months prior to TB notification, and their outcomes., Results: 42% of all notifications had accessed ED prior to notification. The majority were hospitalised, with a proportion of these patients previously attending ED only to be discharged. 37% of patients were discharged from ED with many having TB symptoms, and only a minority referred onto TB clinic., Conclusions: The ED is often the first contact that urban TB patients have with healthcare. Healthcare professionals should ensure this diagnosis is not missed in high incidence areas as it has significant clinical and infection control consequences., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived and validated in tuberculosis patients of different ethnic origin.

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Setting: Newham Chest Clinic, London, UK., Objective: To determine the safety and efficacy of the administration of bolus-dose vitamin D(2) in elevating serum 25-hydroxyvitamin D (25[OH]D) concentrations in tuberculosis (TB) patients., Design: A multi-ethnic cohort of TB patients was randomised to receive a single oral dose of 2.5 mg vitamin D(2) (n = 11) or placebo (n = 14). Serum 25(OH)D and corrected calcium concentrations were determined at baseline and 1 week and 8 weeks post-dose, and compared to those of a multi-ethnic cohort of 56 healthy adults receiving an identical dose of vitamin D(2)., Results: Hypovitaminosis D (serum 25[OH]D < 75 nmol/l) was present in all patients at baseline. A single oral dose of 2.5 mg vitamin D2 corrected hypovitaminosis D in all patients in the intervention arm of the study at 1 week post-dose, and induced a 109.5 nmol/l mean increase in their serum 25(OH)D concentration. Hypovitaminosis D recurred in 10/11 patients at 8 weeks post-dose. No patient receiving vitamin D(2) experienced hypercalcaemia. Patients receiving 2.5 mg vitamin D(2) experienced a greater mean increase in serum 25(OH)D at 1 week post-dose than healthy adults receiving 2.5 mg vitamin D(2)., Conclusion: A single oral dose of 2.5 mg vitamin D(2) corrects hypovitaminosis D at 1 week but not at 8 weeks post-dose in TB patients.

Rationale: Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed., Objectives: To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status., Methods: A double-blind randomized controlled trial was conducted in 192 healthy adult TB contacts in London, United Kingdom. Participants were randomized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks., Measurements and Main Results: The primary outcome measure was assessed with a functional whole blood assay (BCG-lux assay), which measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the readout is expressed as a luminescence ratio (luminescence postinfection/baseline luminescence). IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay. Vitamin D supplementation significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro compared with placebo (mean luminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95% confidence interval for difference, 0.01-0.25; p=0.03) but did not affect antigen-stimulated IFN-gamma secretion., Conclusions: A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection. Clinical trial registered with www.clinicaltrials.gov (NCT 00157066).

Neutrophils contain antimicrobial peptides with antituberculous activity, but their contribution to immune resistance to tuberculosis (TB) infection has not been previously investigated to our knowledge. We determined differential white cell counts in peripheral blood of 189 adults who had come into contact with patients diagnosed with active TB in London, United Kingdom, and evaluated them for evidence of TB infection and capacity to restrict mycobacterial growth in whole-blood assays. Risk of TB infection was inversely and independently associated with peripheral blood neutrophil count in contacts of patients diagnosed with pulmonary TB. The ability of whole blood to restrict growth of Mycobacterium bovis bacille Calmette Guérin and Mycobacterium tuberculosis was impaired 7.3- and 3.1-fold, respectively, by neutrophil depletion. In microbiological media, human neutrophil peptides (HNPs) 1-3 killed M. tuberculosis. The neutrophil peptides cathelicidin LL-37 and lipocalin 2 restricted growth of the organism, the latter in an iron-dependent manner. Black African participants had lower neutrophil counts and lower circulating concentrations of HNP1-3 and lipocalin 2 than south Asian and white participants. Neutrophils contribute substantially to innate resistance to TB infection, an activity associated with their antimicrobial peptides. Elucidation of the regulation of neutrophil antimicrobial peptides could facilitate prevention and treatment of TB.

The incidence of tuberculosis (TB) has increased throughout London, especially in inner city boroughs. Ethnicity, poverty, and the success of TB control measures all affect the distribution of cases between boroughs. This study was conducted to see which factors affect the distribution of cases between electoral wards within an inner London borough. The Borough of Newham in the East End of London is made up of 24 electoral wards and has one of the highest notification rates in the United Kingdom. Our analysis showed that the percentage of the population who were non-white made a strong contribution to the variance in TB rates between wards (p < 0.0001), but the age distribution of the population and Jarman scores for poverty did not, the latter because the entire borough is deprived. Measures to control TB should be targeted at those areas where members of the community are most at risk.

We assessed bone mineral density (BMD) in 20 asthmatics who had been taking inhaled budesonide (BUD) (median daily dose 800 micrograms) for over a year, 13 of whom had taken previous courses of systemic steroids. Their results were compared with those of 20 patients receiving inhaled high-dose beclomethasone dipropionate (BDP) (median daily dose 1,000 micrograms), all of whom had received previous courses of systemic corticosteroids, and with those of 17 mild asthmatics who had never taken either inhaled or systemic steroids. Mean (standard deviation) (SD)) BMD in the patients taking BUD was 139.5 (28.6) mg/ml. This was significantly lower (p < 0.05) than in the control patients who had never taken inhaled or systemic steroids (160.4 (27.4) mg/ml). Mean BMD in the patients taking BUD did not differ significantly from that observed in patients taking BDP (127.5 (22.6) mg/ml). Although the reduction in BMD in the asthma patients taking regular high-dose BUD could have been due to previous courses of corticosteroid, the magnitude of bone loss is similar to that seen in patients taking high-dose inhaled BDP and intermittent corticosteroids.

1. The rates of change in mean peak expiratory flow and in diurnal variation in peak flow were compared in 14 patients recovering from acute severe asthma. 2. Peak expiratory flow was measured on hospital admission, and at 6-hourly intervals for the next 3 weeks. 3. Diurnal variation in peak flow was assessed by measuring the following: amplitude (the highest minus the lowest peak expiratory flow during any given 24 h period), amplitude % mean (the highest minus the lowest peak expiratory flow during any given 24 h period divided by the mean peak expiratory flow over that period) and residual amplitude (the maximum variation about the mean peak expiratory flow during any given 24 h period). 4. Plots of diurnal variation in peak flow and peak expiratory flow against time were constructed for each patient. To enable comparison of changes in peak expiratory flow and diurnal variation in peak flow the data were transformed. 5. The rate of change for mean peak expiratory flow and for the three measures of diurnal variation in peak flow was assessed by fitting an exponential function to each set of data, and calculating the slope of the exponential curve halfway through the period of observation (10.5 days). 6. Median (range) slope for peak expiratory flow was 0.055 (0-2.57). The comparable value for amplitude was -3.15 (-1.27 to -4.22) (absolute median values compared, P = 0.0029), for amplitude % mean was -1.87 (-0.18 to -5.95) (P = 0.012) and for residual amplitude was -1.43 (-0.62 to -3.09) (P = 0.033).(ABSTRACT TRUNCATED AT 250 WORDS)

Four patients with chronic airflow obstruction developed spontaneous sternal fractures. All had received repeated courses of high dose corticosteroids and three were receiving long term treatment with low dose corticosteroids. It is important to consider sternal fracture in the differential diagnosis when patients with chronic airflow obstruction present with chest pain.

Background: Asthmatic patients taking low to moderate doses of inhaled topical corticosteroids have been shown to have lower bone density than those taking bronchodilators only. There is little information on bone density in asthmatic patients taking high dose inhaled corticosteroids., Methods: Bone mass was studied in three age matched groups of asthmatic patients. These comprised: 17 asthmatic patients who had never taken inhaled or systemic corticosteroids (group 1); 20 patients who had taken beclomethasone diproprionate in a dosage of 1000-2000 micrograms daily for at least a year, who had also received courses of systemic corticosteroids in the past (group 2); and 20 patients who were taking both high dose inhaled corticosteroids and regular low dose prednisolone, at a median dose of 7 mg daily (group 3). Vertebral bone density was measured by quantitative computed tomography. Biochemical indices of bone formation and resorption were also measured., Results: Mean bone density in group 2 (127.5(22.6) mg/ml) was similar to that in group 3 (114.5 (36.0) mg/ml). Bone density was significantly lower in both of these groups than in group 1 (160.4 (27.4) mg/ml). There were no significant differences between groups for any of the markers of bone formation and resorption., Conclusions: Asthmatic patients receiving high dose inhaled beclomethasone and intermittent courses of systemic corticosteroids have reduced vertebral bone density. The bone loss is similar in degree to that seen in patients taking high dose inhaled topical corticosteroids and continuous low dose systemic corticosteroids.

Changes in spirometry during consecutive admissions for treatment of pulmonary infective exacerbations were studied in 45 patients (24 males, 21 females) with cystic fibrosis (CF) who had required five or more such admissions. Over the overall study period there was a mean (SD) decline in FEV1 of -112.1 (188.0) ml yr-1 (P less than 0.001) and in FVC of -47.9 (82.4) ml yr-1 (P less than 0.001). FEV1 and FVC increased during each admission with treatment; however, the magnitude of this change became less over consecutive admissions by a mean value of -33.3 ml (45.0) (P less than 0.001) for FEV1, and -26.0 (72.2) ml (P less than 0.05) for FVC. In the majority of patients that died or underwent transplantation, FEV1 at the time of the last admission did not rise above 800 ml despite full treatment.

Asthmatic patients are encouraged to adopt a normal and active life-style. However, following treatment of acute severe asthma, patients may ask for advice about taking exercise. Serial measurements of the cardio-respiratory responses to continuous work load exercise, were made in asthmatic patients convalescing following hospital treatment of an acute exacerbation. Eighteen asymptomatic patients, (seven male) aged 18-48 years, were studied. The first test was performed within 1 week of admission, when the mean (SD) peak expiratory flow rate (PEFR) was 88 (20)% predicted normal and the arterial oxygen tension (PaO2) was 13.1 (1.4) kPa. No significant differences in the mean cardio-respiratory responses, from the last minute of exercise, were found during the 4-week study. There were no significant differences in the four tests, between the resting PEFR, lowest post-exercise PEFR or % change in PEFR. Also, there were no significant differences in the pre-exercise, end of exercise and recovery (10 min after exercise) PaO2, between the four tests. However, taking the four tests as a whole, significant relationships were found between the recovery PaO2 and the lowest post-exercise PEFR, expressed in absolute terms (r = 0.515, P less than 0.001), and as a percentage of predicted normal (r = 0.533, P less than 0.001); and also between the recovery PaO2 and the % change in PEFR after exercise (r = 0.299, P less than 0.05). It is suggested that a formal exercise test should be performed in convalescent asthmatics wishing to participate in active sports. Patients with exercise-induced asthma may then be identified and treated appropriately.

Thirteen cases of group G streptococcal bacteraemia are described. All subjects were hospital in-patients between 1980-1988, and were either middle-aged or elderly. A primary site of infection was identified in 11, of whom nine had soft tissue infection and two had infections derived from the gut/biliary tree. Seven patients had underlying disease, two of whom had malignancy. One patient died of septicaemia. In the majority of patients early institution of treatment led to prompt recovery.

Nocturnal symptoms are common and often disabling in asthmatic subjects. Furthermore, they often persist, in spite of appropriate dosages of inhaled beta 2-agonists and topical steroids. In such a clinical situation, theophylline preparations may have a therapeutic role. This double-blind, placebo-controlled, cross-over trial was designed to evaluate the effectiveness of a twice-daily Bioavail slow-release theophylline capsule in a group of out-patient asthmatics, with a history of nocturnal and/or early morning wheeze or chest tightness. Theophylline was initially prescribed and monitored in an 'open' phase to obtain the drug dosage required to achieve a serum level in the therapeutic range of 10-20 mg/l. In the ten patients who completed the study, serum theophylline levels were stable throughout. During active treatment there was an improvement in morning peak expiratory flow rate (PEFR), and a reduction in measurements of diurnal variation. In addition, the bronchodilator response to an inhaled beta 2-agonist was preserved. Bioavail theophylline has thus been shown to be an effective agent in the management of adults with nocturnal asthma.

A man aged 27 years presented with an acute myocardial infarction after injecting himself intravenously with amphetamine. Soon after admission ventricular fibrillation developed. This was successfully cardioverted. Coronary arteriography was normal.

The effect of exercise on gas exchange was studied in 17 patients (seven male and 10 female) recovering in hospital from acute severe asthma. On admission the patients (mean age 26 (SD 8) years) had a mean peak expiratory flow (PEF) of 26.8% (5.7%) predicted, a mean arterial oxygen tension (PaO2) of 8.63 (1.26) kPa, and a mean alveolar-arterial oxygen difference (A-aDO2) of 5.98 (1.34) kPa. Once resting symptoms had resolved (after 3.7 (1.6) days) patients performed a constant load exercise test (100 watts for men, 75 watts for women) on a bicycle ergometer for five minutes. PEF was measured before exercise and at five minute intervals for 30 minutes after exercise. Blood gas tensions were measured on capillary blood before, during, and 10 minutes after exercise. Treatment was not interrupted for this study. Mean PEF at rest was 87.6% (21.1%) predicted and showed no significant change after exercise. Mean PaO2 was 13.13 (1.37) kPa before exercise; it showed no significant change during exercise (13.93 (1.34) kPa) or 10 minutes after exercise (13.50 (2.15) kPa). Mean A-aDO2 also showed no change, being 1.82 (1.31) kPa before exercise, 1.79 (1.27) kPa during exercise, and 2.53 (0.93) kPa after exercise. It is concluded that moderate exercise carried out shortly after treatment for acute severe asthma is unlikely to result in worsening gas exchange during or after exercise if resting PEF, PaO2 and A-aDO2 have attained normal or near normal values.

BCG vaccination has been routinely offered to infant Asian children in Birmingham since 1965. We conducted a case-control study to assess the protective effect of this scheme. Altogether 108 Asian children aged under 13 years, born since 1965, received treatment for tuberculosis. For each case four controls were selected; they were matched to the case by month and year of birth, sex, and ethnic origin. Cases and controls were all born in Birmingham. Of the cases, 62 out of 108 (57%) had received BCG, and of the controls, 336 out of 432 (78%) had received BCG. The estimated protective efficacy of vaccination was 64% (95% confidence limits, 43% and 77%). Routine BCG vaccination in infant Asians confers useful protection against the development of tuberculosis in childhood.

The dose-response relationships of a combination of the selective beta adrenergic agonist, fenoterol, and the synthetic anticholinergic drug, ipratropium bromide, were studied. In an open cross-over assessment, 20 patients with evidence of reversible airways obstruction inhaled 2, 4, 6 or 8 puffs from a metered dose inhaler, containing 100 micrograms fenoterol and 40 micrograms ipratropium bromide per puff, administered according to a randomization schedule, on four non-consecutive days. Before, and at intervals up to eight hours after inhalation FEV1, FVC, pulse and blood pressure were measured. Immediate and prolonged bronchodilatation followed each dose. The overall analysis of the FEV1, and FVC showed little difference between 2, 4 and 6 puffs. The highest dose, 8 puffs, was more effective, but associated with an increased incidence of side effects.

The ventricular weights in 43 patients with interstitial pulmonary fibrosis were retrospectively compared with those in 172 patients with emphysema and chronic bronchitis. The mean right ventricular weight of patients with interstitial pulmonary fibrosis and those with emphysema and chronic bronchitis was 85.5 g (SD 23.2) and 88.8 g (34.3), respectively. Thirty five patients (81%) with interstitial pulmonary fibrosis had a right ventricular weight over 65 g compared with 124 (72%) of those with emphysema. Fifty three per cent of both those with interstitial pulmonary fibrosis and those with chronic bronchitis and emphysema had a right ventricular weight greater than 80 g. Differences between the two groups were not significant. These results suggest that the prevalence of right ventricular hypertrophy and pulmonary hypertension in interstitial pulmonary fibrosis is similar to that found in chronic bronchitis and emphysema.

The effect of 5 mg nebulised salbutamol on the cardiorespiratory responses to a progressive maximal exercise test was investigated in eight asthmatic (mean forced expiratory volume in one second (FEV1) 3.48 (1.0) litres) and eight non-asthmatic men. Exercise tests were performed on a bicycle ergometer after administration of nebulised salbutamol or matched saline placebo. In the asthmatic subjects salbutamol increased the resting FEV1 by 11%. The mean (SD) percentage fall in FEV1 after exercise did not change significantly (salbutamol 9.4 (12.8); placebo 15.0 (8.0], but because the FEV1 before exercise was increased the lowest FEV1 after exercise was also significantly higher after salbutamol than placebo (3.60 (1.13) v 2.85 (0.80) litres). Despite the improvement in FEV1 before exercise there was no significant difference in maximal workload, oxygen uptake, heart rate, or ventilation during exercise after salbutamol compared with placebo in the asthmatic patients. Tidal volume was higher at maximal exercise after salbutamol but there was no change in perception of breathlessness or exertion in the asthmatic subjects. During submaximal progressive exercise the perceived rate of exertion was reduced in the asthmatic patients and oxygen pulse was reduced in both groups owing to a small and non-significant increase in heart rate. The FEV1 and cardiorespiratory response to the progressive maximal exercise test in the non-asthmatic subjects were otherwise unchanged after salbutamol. The results suggest that 5 mg nebulised salbutamol has little effect on the cardiorespiratory responses to progressive maximal exercise in patients with mild asthma and in non-asthmatic subjects. Salbutamol in this dose may reduce the severity of exercise induced asthma, but no ergogenic effect on maximal exercise performance was shown.

A patient with alcoholic liver cirrhosis, diabetes mellitus and porphyria cutanea tarda (PCT) is described, who subsequently died of hepatocellular carcinoma. The literature relating PCT to the incidence of primary hepatoma is reviewed, and the mechanisms underlying this possible association are discussed.

An outbreak of acute asthma occurred in Birmingham and the surrounding area on July 6 and 7, 1983. In most patients symptoms began at the time of sudden climatic changes associated with a thunderstorm. Air pollution was not a factor. The large and sudden increase in numbers of airborne fungal spores, especially Didymella exitialis and Sporobolomyces, around the time of the outbreak suggests that they may have been partly contributory, although a direct causal effect has not yet been established.

Ten male stable asthmatic subjects and 10 matched control subjects performed a progressive exercise test on a treadmill to 85% of their predicted maximum heart rate. Blood lactate, pyruvate, hydrogen ion, glucose, alanine, glycerol and total ketone body concentrations were measured at frequent intervals during and up to 60 min after exercise. Carbon dioxide production, oxygen consumption, ventilation, respiratory exchange ratio and oxygen saturation were also measured during and up to 10 min after exercise. There were no significant differences between the asthmatic and control subjects in levels of carbon dioxide production, oxygen consumption and ventilation. The respiratory exchange ratio was greater in the asthmatic subjects during recovery from exercise (P less than 0.05). No changes in oxygen saturation were observed during exercise in either group. In both asthmatic and control subjects, lactate, pyruvate, hydrogen ion, alanine and glycerol concentrations showed an increase from baseline levels, reaching maximum levels up to 10 min after exercise and returning to baseline within 1 h after exercise. Total ketone body concentrations decreased during exercise. There were no significant differences between the asthmatic and control subjects in the concentration of any metabolite over the study period. These data indicate that fuel metabolism during and after short-term progressive exercise is similar in stable asthmatic and normal subjects.

A patient presented with a pneumococcal lobar pneumonia and later developed a subphrenic abscess. Peritonitis and intra-abdominal abscess formation should be remembered as a rare cause of delayed recovery from lobar pneumonia.

Large lung bullae are a rare manifestation of pulmonary sarcoidosis. Of three patients with this complication, all had pulmonary infiltrates at presentation and two had bilateral hilar adenopathy. Hypercalcaemia developed during the course of the illness in all three patients. In each case the bullae had developed within four years of the diagnosis of sarcoidosis. In one woman a bulla resolved almost completely after it had become infected.