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Background: Dose dependent anti-inflammatory effects of inhaled corticosteroids in asthma are difficult to demonstrate in clinical practice. The anti-inflammatory effect of low dose inhaled budesonide on non-invasive exhaled markers of inflammation and oxidative stress were assessed in patients with mild asthma. Methods: 28 patients entered a double blind, placebo controlled, parallel group study and were randomly given either 100 or 400 µg budesonide or placebo once daily, inhaled from a dry powder inhaler (Turbohaler), for 3 weeks followed by 1 week without treatment. Exhaled nitric oxide (NO), exhaled carbon monoxide (CO), nitrite/nitrate, S-nitrosothiols, and 8-isoprostanes in exhaled breath condensate were measured four times during weeks 1 and 4, and once a week during weeks 2 and 3. Results: A dose-dependent speed of onset and cessation of action of budesonide was seen on exhaled NO and asthma symptoms. Treatment with 400 µg/day reduced exhaled NO faster (–2.06 (0.37) ppb/day) than 100 µg/day (–0.51 (0.35) ppb/day; p

Fecal coliforms are indicator bacteria that are used for determining water quality. Poultry growers may be implicated when fecal coliforms are found in surface waters following runoff events from broiler litter-amended pastures and hayfields. This study determined the numbers of fecal coliforms in fresh and stacked broiler litter. In 1998, 10 of 20 fresh and all 19 stacked broiler litter samples from eight different Georgia counties contained less-than-detectable numbers of fecal coliforms ( 10,000,000 fecal coliforms per g of dry weight litter) were added to five different broiler litter samples, numbers of fecal coliforms declined to below detectable levels within 8 days. When water was added to two of the five stacked litter samples, survival of fecal coliforms did not increase, but survival did increase when the temperature was lowered from 28 to 18 °C. The data suggest that poultry growers should consider stacking broiler litter for a reasonable period of time (> 8 days) to eliminate fecal coliforms in runoff from landspread broiler litter.

AIM: To compare the results of DNA amplification by the polymerase chain reaction (PCR) with immunofluorescence staining for detecting Pneumocystis carinii in bronchoalveolar lavage specimens taken from symptomatic HIV seropositive patients with suspected P carinii pneumonia (PCP). METHODS: Bronchoalveolar lavage specimens were obtained from 28 symptomatic HIV seropositive patients. Specimens were examined for P carinii using immunofluorescence, and by DNA amplification with PCR to obtain results on gel electrophoresis (gel) and a more sensitive Southern hybridisation (blot) technique. Specimens positive by immunofluorescence and gel electrophoresis were serially diluted to a 10(-6) concentration and each dilution strength tested for P carinii using PCR to compare quantitatively immunofluorescence with PCR. RESULTS: Of the 28 specimens analysed, 18 were negative for P carinii by both immunofluorescence and PCR, two were positive only by the blot technique of PCR, four were equivocally positive and four unequivocally positive by immunofluorescence. Three of the four equivocally positive patients tested by immunofluorescence were negative for P carinii by PCR, although one was positive by PCR (blot) technique. This patient had clinically confirmed PCP. Of the four unequivocally positive patients tested by immunofluorescence, three were gel and blot positive by PCR and had PCP clinically, but one was negative by both gel and blot techniques, although the patient certainly had PCP on clinical grounds. This patient had received nine days of treatment with high dose co-trimoxazole before bronchoalveolar lavage specimens were obtained. The three specimens positive by gel and blot techniques remained gel positive down to dilutions of between 10(-4) and 10(-6). CONCLUSIONS: PCR results may become negative soon after starting treatment for PCP. Specimens should therefore be taken before, or soon after, starting treatment. PCR seems to be between 10(4) and 10(6) times more sensitive than immunofluorescence.

BACKGROUND--Pneumocystis carinii pneumonia was thought to occur from reactivation of latent infection, but recent studies with the polymerase chain reaction have failed to detect P carinii in normal subjects. If pneumocystis pneumonia is therefore caused by new infection the source and mode of transmission of P carinii remains unknown. METHODS--Natural exposure to P carinii was detected by measuring antibodies by indirect immunofluorescence in 24 health care workers working continuously with patients with AIDS and 24 control health care workers exclusively treating elderly patients. RESULTS--P carinii antibody titres were significantly higher in the health care workers exposed to AIDS than in the control group (median titre 1:32 v 1:16 respectively). Three control subjects had no antibodies compared with none of the subjects exposed to AIDS, and 10 of the 12 highest titres came from the exposed group. CONCLUSIONS--Raised P carinii antibody titres in health care workers caring for patients with AIDS suggest that patients infected with HIV may be a potentially infectious source of P carinii for susceptible subjects.

Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml.

Tracheobronchomegaly is a rare cause of recurrent chest infections often with persistent, unproductive cough. A case is described which presented as a severe life threatening pneumonia in which the bronchoscopic, radiographic, and computed tomographic findings are given.

Pyogenic non-tuberculous vertebral osteomyelitis presented with pleuritic chest pain and basal shadowing on the chest radiograph.

The severity, duration, and reversibility of pentamidine induced bronchial narrowing was studied with and without pretreatment with nebulised terbutaline 10 mg in an open study of 40 patients seropositive for the human immunodeficiency virus (HIV). All subjects received pentamidine 300 mg in 5 ml water via an Acorn System 22 jet nebuliser. The forced expiratory volume in one second (FEV1) fell in all 20 patients given pentamidine alone, the mean maximum fall being 20.6%. In the 20 patients given pentamidine preceded by nebulised terbutaline the mean maximum fall in FEV1 was 4%; three subjects had a fall in FEV1 of more than 10%.

Inhaled radioisotopes were employed to study the role of tracheobronchial clearance in sputum induction, a technique used to diagnose Pneumocystis carinii pneumonia in patients with acquired immune deficiency syndrome (AIDS). Seven normal nonsmoking male subjects inhaled a nebulized aerosol of technetium-labelled human serum albumen, which was cleared from the lung solely by tracheobronchial clearance. The aerosol's particle size distribution ensured both alveolar and proximal airway deposition, the site of P. carinii organisms and tracheobronchial clearance mechanisms, respectively. Pulmonary emission counts were measured for 12 continuous 5-min periods before, and immediately after, sputum induction with nebulized 3% saline. A further 10-min scan was performed at 24 h to determine the alveolar fraction of deposited aerosol. Tracheobronchial clearance rates (log10[activity]/time) were calculated after log linear regression, for the time periods before, during and after sputum induction, having corrected for isotope decay and alveolar deposition. Results were analysed by the Wilcoxon rank sum test. Tracheobronchial clearance rates increased significantly in all subjects during sputum induction, with a mean 65.5% reduction in pulmonary activity over this period. Mean clearance gradients for the three time periods before, during and after sputum induction were -1.2 x 10(-3) min-1, -15.0 x 10(-3) min-1 and 0.4 x 10(-3) min-1, respectively (P < 0.025), which probably underlies the principal mechanism for success of the technique.

The flexible fibreoptic bronchoscope was first made commercially available in 1970 (Anderson and Faber, 1978) and it has since had a major impact on the diagnosis and management ofpulmonary disease. Within 3 years of its introduction, 25,000 bronchofibrescopic examinations had been performed in the United States in 191 centres (Sackner, 1975). At the Brompton Hospital an average of 855 fibreoptic bronchoscopies have been performed annually since 1975. An earlier analysis of 1,223 of these showed that in most (81%), a histological diagnosis was made and no further diagnostic procedure was required (Mitchell et al., 1980). Following suitable preparation and pre-medication the fibrescope is normally passed through the nose under local anaesthesia; if the nasal passages cannot be negotiated it is passed through the mouth (Knight, 1981). Diagnostic indications for fibreoptic bronchoscopy include: (1) Possible endobronchial lesions. (2) Peripheral lung lesions. (3) Collection of samples for microbiological examination. (4) Diffuse lung disease of unknown aetiology.

A double-blind, randomised, placebo-controlled, crossover trial of prednisolone (40 mg daily for 14 days) was carried out in 43 patients with chronic airflow limitation (mean age 60 years, mean FEV 1 1·02 litres, FEV 1 /FVC ratio 43·7%). Several subjective and objective variables for response were measured. Significant improvements occurred with prednisolone in most variables measured, but improvements also occurred with placebo in some variables. The improvements with prednisolone in general wellbeing, 12 min walk distance, peak expiratory flow, FEV 1 , and relaxed vital capacity were significantly greater than those with placebo. Clinical assessment and assessment of atopic status did not reveal any feature of major predictive value for steroid responsiveness. A proportion of patients with chronic airflow limitation do improve on oral corticosteroids and the continued use of such trials in clinical practice is justified, though a placebo period should be included, and several variables for response should be measured.

Forty-four adult patients with acute severe asthma were studied on admission to a general hospital to determine the mode of presentation and clinical severity of the acute illness. Most patients described poorly controlled wheezing for a mean period of five weeks before a more rapid deterioration, usually over 24 hours, caused them to seek medical attention. The clinical severity of the acute attach was not related to the duration of acute wheezing before admission to hospital. Recovery, studied in 11 of the patients, was slow, and most had reached only 70% of their predicted spirometric values after seven days' treatment in hospital. The rate of recovery was not influenced by the antecedent history of acute wheezing. Very sudden deterioration from a background of good control appears to be uncommon in adults with asthma who present to hospital as emergencies, and it is likely that improvement in the standard of routine management of asthmatics at home would prevent many such admissions.

Fibreoptic bronchoscopy was performed in 43 of 52 consecutive patients with opportunistic pneumonia in the acquired immune deficiency syndrome (AIDS). The 15 patients in whom a likely pathogen was not found by bronchoscopy (including the nine not having the procedure) were treated for Pneumocystis carinii pneumonia (PCP) alone and all responded. In 11 of these a diagnosis of AIDS was confirmed because of an alternative opportunistic infection within 6 months. PCP was confirmed in 38 of the 52 patients and cytomegalovirus (CMV) was isolated from 15 patients. The lower the partial pressure of arterial oxygen (PaO2) on admission the more likely was a pathogen to be found by bronchoscopy. The admission PaO2 while the patient was breathing room air was the single most reliable prognostic indicator. The mean PaO2 for survivors was 9.6 kPa and 6.7 kPa for non-survivors (P less than 0.01 Student's t-test), with 50% mortality for patients with a PaO2 of less than 8 kPa on admission. Temperature and pulse rate were sensitive indicators of response to treatment, obviating the need for frequent arterial gas measurements and chest radiography. Our findings suggest that although fibreoptic bronchoscopy contributed little to the treatment and final outcome of the infection, it identified the causative pathogen in most patients.

Sucrose density gradient ultracentrifugation can be used to detect specific 19S antibodies of the IgM class in the sera of patients recently infected with influenza A virus, provided steps are taken to remove non-specific inhibitors of haemagglutination. The usefulness of the procedure for the diagnosis of influenza requires further evaluation.

The speed and patterns of recovery of airflow obstruction were analysed in 209 patients receiving a standard therapeutic regime for severe acute asthma. Initial rates of recovery were rapid. Three-quarters of the patients had achieved 50% of their total improvement in peak expiratory flow rate (PEFR) within 24 hr. The time taken to reach eventual maximum PEFR was very much longer, 50% of the patients taking one week or more. Diurnal variation of moderate or severe degree was seen in 78% of patients. Length of history of asthma, time of deterioration and other measures of the severity of attack on admission did not differ in faster and slower responders. The rise of PEFR within 4 hr of starting treatment was highly significantly correlated with a higher PEFR at 24 hr and a shorter time to full recovery. Although the mean arterial PCO2 was higher (P less than 0.01) in the slower responding group and they were slightly older (P less than 0.05) and had lower mean FEV1 (P less than 0.02) and FVC (P less than 0.05) these differences were less helpful in predicting which patients responded fastest.

The pharmacokinetics of prednisolone have been studied in asthmatic patients following intravenous injection at three different doses and in normal volunteers at five oral doses. Plasma prednisolone concentrations were measured by radioimmunoassay. With increasing dose there is an increase in the apparent volume of distribution, plasma clearance and half life. The relationship between area under the plasma concentration time curve, maximum concentration and dose is linear but the regression lines do not pass through the origin. These findings following oral and intravenous administration confirm that prednisolone shows non-linear kinetics.

Bronchoalveolar lavage was used to sample inflammatory cells from the lungs of 51 patients with cryptogenic fibrosing alveolitis (CFA) (24 smokers, 12 ex-smokers, and 15 non-smokers). The smokers with CFA have been compared with 15 smoking control subjects in whom there was no radiographic abnormality or clinical evidence of chronic bronchitis. Significantly lower volumes of lavage fluid were recovered from the smokers with CFA (p < 0.001) and the fluid contained lower percentages of macrophages (p < 0.01), reflecting increased percentages of eosinophils (p < 0.001) and neutrophils (p < 0.01). Similar changes were seen in the ex-smokers and non-smokers. There was also an increase in the percentages of lymphocytes when the whole group of CFA patients was compared with the control subjects (p less than or equal to 0.05). No significant differences were found when patients with "lone" CFA were compared with those having associated systemic disease. The only feature distinguishing smokers from non-smokers with CFA was the presence of pigmented cytoplasmic inclusions in the macrophages from the smokers (p < 0.001). However, there were lower numbers of pigmented macrophages in the smoking CFA patients by comparison with the control subjects suggesting either a change in phagocytic capacity or turnover rate in this disease. Profiles of differential cell counts in individual patients showed that increases of eosinophils over 3% or neutrophils over 4% or both with lymphocyte counts of less than 11% related to a poor clinical response to corticosteroids, but lymphocyte percentages greater than 11% related to improvement (p < 0.05).

Transbronchial lung biopsy was performed via the fibreoptic bronchoscope in 433 patients. In 183 patients, whose chest radiographs showed bilateral diffuse shadows a histologic diagnosis was established by transbronchial biopsy in 61%, including sarcoidosis (58), fibrosing alveolitis (18) and carcinoma (14). Histologically normal lung or inadequate pulmonary tissue for diagnosis was obtained from 71 patients in this group. In 225 patients with solitary chest radiography opacity, a diagnosis of bronchial carcinoma was finally made in 130, of whom 82 (63%) had a histological diagnosis established by transbronchial biopsy. In 84 patients finally shown to have sarcoidosis, 65 (77%) had positive histology by transbronchial biopsy whereas only 19 (40%) of 48 patients with fibrosing alveolitis yielded histology compatible with the diagnosis. Pneumothorax developed in three patients after the procedure but only one required intercostal drainage. Haemorrhage of 50-100 ml occurred in seven patients and bleeding ceased spontaneously in all cases. There were no fatalities.

Fifty-five patients requiring oral surgery and orthopaedic care were studied prospectively and compared to a control group. Six patients received no antibiotics and one developed an orthopaedic operative site infection due to a mouth organism. Seventeen patients had concurrent surgery and perioperative antibiotic usage and no infections occurred. Twenty-six patients required multiple operations and courses of antibiotic treatment and five developed infections. Enterobacter infections were common and emerge because they are resistant to first-generation cephalosporins. Treatment by a perioperative first-generation cephalosporin is recommended, followed by throat cultures and treatment by antibiotics specific for cultured organisms for patients requiring subsequent operations.

Seven patients with bronchial asthma requiring continuous medication were subjected to eight weeks of nocturnal exposure to negatively ionized air, and their progress was followed using objective tests of lung function and clinical assessment. During exposure, four patients showed significant increases in morning PEFR, which in two of these patients was not sustained when exposure ceased. In two patients the observed increase in PEFR was accompanied by subjective improvement. From the results of all our assessments we conclude that, although this treatment may lead to an improvement in some patients with asthma, further objective studies are required to determine the value of negatively ionized air in the routine management of asthma.

A series is reported of five patients with acute respiratory failure complicating neuromuscular diseases, three of whom required assisted ventilation. Initially the arterial carbon dioxide tension fell to levels below the normal range in all the patients and this change reflects alveolar hyperventilation which is probably produced by a combination of fear, small airway collapse, and reflex tachypnoea. It is only late in the development of respiratory weakness that alveolar ventilation falls and carbon dioxide tension rises to normal and then elevated levels. Several factors contribute to the reduction in arterial oxygen tension, including airway collapse and infection, and it is important to try to prevent these by correct posture, vibration, and passive deep breathing. We think that objective measurements of respiratory function are essential in the management of these patients and that the most valuable are serial measurements of vital capacity and carbon dioxide tension and the least helpful is the arterial oxygen tension. Assisted ventilation will probably be required if the vital capacity falls below 30% of that predicted for the patient or if the carbon dioxide tension rises from low to normal levels as vital capacity is falling.

‘Closing volume’, defined as that lung volume at which the dependent lung zones ceases expiration, was measured in 41 healthy non-smokers aged seventeen to sixty-nine years using xenon-133. Subjects were studied erect before and after inhalation of a β-adrenergic bronchodilator aerosol and in 31 subjects the studies were repeated in the supine position. Results in individual subjects showed good reproducibility. The regression with age and standard deviation of the measurements were similar to previous reports and no change was observed after inhalation of bronchodilator. The relationship of Phase 4 to vital capacity was unaltered by change in posture. It is suggested that the use of standard deviation (i.e. ± 2 SD) to define the limits of a normal range may be unduly optimistic. Tolerance limits to include 95% of healthy subjects calculated from studies of this size would provide unacceptably wide ranges for epidemiological purposes if the technique were introduced as a screening test for early disease of small airways. It is suggested that further developmental studies are required.

Sarcoidosis was ultimately diagnosed in a consecutive series of 79 patients, of whom 24 presented with unusual features. Histological support for this diagnosis was obtained in 37 out of 42 patients who underwent transbronchial biopsy; epithelioid and giant-cell granulomas were also found on biopsy of the bronchial mucosa in 17 out of 22 patients. Kveim tests were completed in 44 patients: results were positive in 19, equivocal in 11, and negative in 14. In 16 patients histological support was obtained on biopsy of various other tissues. The clinical presentation of the disease and the degree of histological support provided by the various procedures used in reaching a diagnosis of sarcoidosis varied considerably. Transbronchial biopsy of the lung is a useful advance in diagnosing sarcoidosis and provided a higher diagnostic yield than any other method.

Leukotrienes (LTs) C4 and B4 are potent proinflammatory mediators with a wide variety of biologic activities, including smooth muscle contraction, mucus hypersecretion, and leukocyte activation, which may be of particular relevance to the pathology of asthma and other respiratory diseases. We measured the concentrations of LTC4 and LTB4 in bronchoalveolar lavage fluid from 16 atopic subjects with asthma (eight symptomatic and eight asymptomatic) and from 14 control subjects without asthma (six with hay fever and eight nonatopic). The amounts detected in symptomatic subjects with asthma were significantly higher than in control subjects (LTB4, 0.58 +/- 0.06 versus 0.36 +/- 0.05 pmol/ml, p less than 0.05; LTC4, 0.36 +/- 0.1 versus 0.12 +/- 0.02 pmol/ml, p less than 0.01). LTC4 and LTB4 were also measured in 17 patients: nine with interstitial lung disease of varying etiology (cryptogenic fibrosing alveolitis [CFA] or idiopathic pulmonary fibrosis), three with sarcoidosis, one with extrinsic allergic alveolitis, one with sulphonamide-induced pneumonia, and one patient with eosinophilic granuloma. The concentrations of LTB4 (but not LTC4) were significantly greater in patients with CFA compared with normal control subjects (0.69 +/- 0.3 versus 0.36 +/- 0.05 pmol/ml, p less than 0.01). There was a significant correlation (p less than 0.05) between the percentage of neutrophils and the concentration of LTB4 in the bronchoalveolar lavage fluid) of the group with interstitial lung disease as a whole. This study provides evidence for a role for LTs in the airways of subjects with day-to-day asthma and suggests that LTB4 may also be involved in the recruitment of granulocytes into the lung in patients with CFA.

Twenty-six patients admitted to hospital for treatment of severe exacerbations of asthma unresponsive to bronchodilators were assigned to high-, medium-, or low-dose corticosteroid treatment regimens. The rates of recovery were assessed by changes in pulse rate, peak expiratory flow rate, and spirometric measurements and were not related to the dose of corticosteroids given. Very high systemic doses of corticosteroids do not offer significant advantages in treating severe exacerbations of asthma.

Sixteen patients with intrinsic non-atopic asthma with persistent wheezing who had never been treated with corticosteroids showed normal adrenocortical responses to prolonged stimulation with Tetracosactin Depot. In a subgroup of six patients the hypothalamo-pituitary-adrenal (HPA) response to a standard insulin stress test was normal. It is concluded that impaired responsiveness of the HPA axis is unlikely to be a common factor in initiating or maintaining airways obstruction in patients with intrinsic asthma.

Kaposi's sarcoma of the lung patients with the acquired immune deficiency syndrome is often indistinguishable by clinical and radiographic criteria from opportunistic pneumonia. Pulmonary Kaposi's sarcoma and pneumonia may frequently be present in the same patient. Previous observers have commented on the repeated failure to establish a diagnosis of Kaposi's sarcoma of the lung by fibreoptic bronchoscopy. Thirteen fibreoptic bronchoscopies were performed in a series of 11 patients with thoracic manifestations of AIDS and Kaposi's sarcoma was identified in transbronchial or bronchial biopsy specimens in four patients. This diagnostic yield is comparable to that obtained only by open lung biopsy procedures in previous reports. Fibreoptic bronchoscopy may contribute to the correct management of the patient and facilitate an accurate prognosis by differentiating between opportunistic pneumonia and pulmonary Kaposi's sarcoma.

Sucrose density gradient ultracentrifugation followed by haemagglutination inhibition for demonstrating specific influenza IgM was evaluated as a means of confirming recent infection with influenza A viruses. Specific IgM antibodies were found in at least one serum obtained from 83% of patients with proven recent infection with influenza A viruses but in none of the sera from 21 individuals without evidence of infection. Influenza IgM antibodies persisted for up to 112 days after infection. The relative merits of detecting specific IgM and complement fixing antibodies for diagnostic purposes are discussed.

A double blind, randomised, placebo controlled, crossover trial of prednisolone (40 mg/day for 14 days) was carried out in 33 patients with chronic airflow limitation (mean age 62 years, mean FEV1 1.01 litres, mean FEV1/FVC ratio 44%), to assess the value of serial peak expiratory flow (PEF) measurements, taken five times daily in evaluating treatment response by comparison with other objective measurements and with measurements of symptoms. The mean serial PEF after a one week run in period was 189 1 min-1, during the second week of placebo 193 1 min-1, and during the second week on prednisolone 231 1 min-1. The difference in mean PEF values between placebo and prednisolone was significant (p less than 0.01). With regard to the response to steroids of the individual patients, 13 of the 33 had a detectable trend of improvement on visual inspection of serial PEF measurements during prednisolone treatment but only one during placebo administration. Of all the objective measurements made after the run in and after each treatment phase (12 minute walking distance, FEV1, forced vital capacity (FVC), serial PEF), the serial PEF chart provided the best discrimination between placebo and prednisolone treatment. There was no statistically significant association between steroid induced improvement in serial PEF measurements and in breathlessness, partly because of placebo improvements in symptoms in those who had no improvement in serial PEF values. This study indicates the importance of making objective measurements to identify a genuine steroid response rather than relying on symptomatic improvement alone. The best simple measurement to make is serial PEF during steroid trials. This is more sensitive in detecting a steroid response than are the 12 minute walking distance, FEV1, or FVC, and is also less likely than these measurements to show spurious placebo responses.

Prednisolone has been in clinical use since 1955 in a number of conditions, and it is estimated that 5 million people in the United States are currently taking this drug. Through the years prescribing practice has been based on the assumption that the pharmacokinetics of prednisolone were dose in-dependent. Little work has been done to elucidate to what extent kinetics might underly differences in patient reactivity to these drugs. With the advent of methods for measuring plasma prednisolone it becomes possible to evaluate these problems in normal volunteer subjects and patients without recourse to intravenous injection of radioactive substances.

Changes in pulmonary function due to naturally occurring respiratory tract infection were examinated in 26 normal healthy volunteers during a period of 6 months. Forced expiratory maneuvers in each volunteer were recorded at 2-wk intervals throughout the study and daily during illness. Significant impairment of peak expiratory flow rate, forced vital capacity, forced expiratory volume in one second, and maximal mid-expiratory flow rate at 50% of the vital capacity was observed during infection, whereas changes in the maximal expiratory flow rate at 75% of vital capacity were nonsignificant. From these results, we conclude that large airways are certainly affected during uncomplicated respiratory infections in normal healthy persons and from the changes observed in FVC we suggest that more widespread involvement of the small airways may occur.

Sarcoid spleens removed at operation for valid clinical indications provide the best available source for the provision of continued supplies of potentially satisfactory Kveim test material. Chase-Siltzbach type 1 suspensions (ref. 1) are prepared from deep-frozen splenic tissue either in sequential Lots of approximately 35g each or by processing the whole spleen. The former necessitates the validation of sequential Lots of test material whilst the latter assumes that all parts of the spleen will yield an acceptable test suspension and runs the risk that a portion of the spleen may impair a large volume of a suspension which may otherwise have proved satisfactory. In any event, less than one half of all potentially acceptable sarcoid spleens will provide suspensions which yield the expected proportion of positive reactions among patients at different stages of sarcoidosis and a negligible proportion among patients with other diseases. These acceptable suspensions should comprise fine splenic tissue particles which are evenly dispersible in suspension. The concentration of these tissue particles will usually range between 3.0 mg/ml – 6.0 mg/ml as measured by alcohol precipitable dry weight. The potency and selectivity of test suspensions can be assessed only by validation in man. The reactivity of a suspension is determined by comparison of papule size and histology with that of a simultaneous test using a previously validated suspension in patients with sarcoidosis. The selectivity of a suspension for sarcoidosis is ascertained by comparing the results of identical simultaneous tests in patients with diseases other than sarcoidosis. The histology must be read by an experienced observer who is unaware of the origin of the test suspensions or the nature of the subjects tested. Although test suspensions can usually be kept satisfactorily at +4°C at least for several years, they should be monitored periodically to ensure that they have not lost either their reactivity or selectivity for sarcoidosis. When a large volume of acceptable test material has been prepared it is therefore usual to ampoule and store at +4°C; alternatively, it could be freeze dried when it appears to retain its potency for long periods at room temperature (refs. 2,3,4,5,6,7).

An off-line digital computer used to calculate the results of routine lung function tests saved an average of 20% (9.8 min) of the time required per patient when compared with the use of a simple electronic calculator. This saving would permit an increase in the work-load of the laboratory from 1250 to 1500 patients per year if the same tests were used. The cost of suitable computer equipment, however, would exceed that of employing an additional lung function technician.

Cochrane, G. M., Benatar, S. R., Davis, J., Collins, J. V., and Clark, T. J. H. (1974.) Thorax, 29, 172-178. Correlation between tests of small airway function. To compare and correlate tests of small airway function we have measured residual volume, frequency dependence of compliance, `closing volume9, maximal expiratory flow rate at 50% and 25% of vital capacity, maximal expiratory flow rate at 50% of total lung capacity, and forced expired time in 10 health non-smoking male subjects and 10 non-smoking asthmatics who on the day of the study had no symptoms of airway obstruction. There was no evidence to suggest that any one particular test was more sensitive than others in detecting the presence of small airways obstruction. The closest correlation was between maximal expiratory flow rate at both 25% of vital capacity and 50% of total lung capacity and the forced expired time. It is argued that a prolonged forced expired time in the presence of normal dynamic lung volumes may be the most easily applicable screening test for early small airways obstruction.

Dans cette etude de 8 patients il se produit une desaturation arterielle de 20,5% et une diminution du debit expiratoire maximum de 50%

Since the advent of TBB through the fibrescope, the technique has been used increasingly at Brompton Hospital, London, for the diagnosis of interstitial lung disease and we present here our findings using this technique and other techniques in the diagnosis of sarcoidosis. We studied a group of 79 patients seen consecutively at Brompton Hospital between January 1977 — December 1978 in whom a diagnosis of sarcoidosis was made.

1. In forty non-smoking healthy subjects and seventy-two patients with left heart diseases measurements were made of the volume expired in the first second of a forced expiration (FEV1) and the total volume expired in a forced expiration (FVC) before and after inhalation of salbutamol. Before and after salbutamol the healthy subjects and patients also inhaled maximally an inspirate, the first part of which contained 133Xe and, during controlled expiration, the radioactivity of the expirate was measured and plotted against its volume. The resulting curves were divided into phases of different slope by eye, the point at which phase 3 changed to phase 4 being nominated the closing volume. 2. In forty non-smoking healthy subjects inhalation of salbutamol was followed by significant increase in FEV1 but FVC and closing volume did not change. 3. Change in posture from seated erect to supine in thirty of these healthy subjects was accompanied by significant reduction in FEV1 and FVC and as closing volume was not significantly different in the two positions the ratio closing volume/vital capacity was increased with recumbency. 4. In seventy-two patients with left heart diseases without a history of cough or wheeze, FEV1, FVC, closing volume and the ratio closing volume/vital capacity were significantly different from values in the healthy subjects. There was no significant difference between non-smokers and ex-smokers amongst the patients. 5. Significant increase in FEV1, FVC and reduction in closing volume and the ratio closing volume/vital capacity followed inhalation of salbutamol in patients with heart diseases but the values remained significantly different from those recorded in the healthy subjects. 6. In twenty patients with heart diseases, FEV1 and FVC were reduced by change in posture from seated erect to supine but the ratio closing volume/vital capacity and the regression with age of this ratio were not significantly changed by change in position. 7. In patients with heart diseases the ratio closing volume/vital capacity was significantly correlated with severity of breathlessness and length of symptom-history but not with left ventricular end-diastolic or pulmonary vein wedge pressures.

Bronchoalveolar lavage, open lung biopsy, and cell extraction from the biopsy material have been studied in 21 symptomatic patients with progressive pulmonary fibrosis (18 with cryptogenic fibrosing alveolitis, fulfilling also the criteria for “usual interstitial pneumonia” (UIP), and three with rapidly progressive disease probably related to asbestos exposure). The total and differential cell counts between the three different samples have been compared as well as the influence on them of smoking and their correlation with steroid responsiveness and later progress. There was no correlation between semiquantitative scores of cell types observed within alveolar spaces and in alveolar walls and the differential or total cell counts obtained from extraction or lung lavage samples. There was, however, some correlation between differential counts obtained from lung lavage and extractions (neutrophils p

One hundred and seventy patients with interstitial lung diseases undergoing bronchoalveolar lavage (BAL), were contrasted with 51 patients undergoing fibreoptic bronchoscopy alone to define the factors which predispose to post-lavage side-effects. Transient post-bronchoscopy fall in the peak expired flow (PEF) greater than or equal to 20% occurred in both groups (24% and 23% respectively), and thus was probably related to the bronchoscopy procedure. Post-lavage pyrexia (greater than or equal to 1 degree C) occurred only in the patients undergoing BAL (26%), p less than 0.001. Only 4% with pyrexia required antibiotics, and only 2% with falls in PEF needed bronchodilator therapy. The only significant clinical association was more frequent pyrexia in patients on treatment with prednisolone, particularly in women (p less than 0.01). Pyrexia was also associated with higher lavage fluid introduction volumes (greater than 240 ml). Side effects did not relate to the percentages of lavage fluid recovered, although smokers had lower recoveries and, recoveries tended to be higher in sarcoidosis than cryptogenic fibrosing alveolitis. Serial lavages in 25 patients caused no significant increase in side effects.

The effects of salbutamol inhaled by three different methods were compared in groups of adult patients with severe acute asthma. 2 x 400 micrograms Rotacaps was the optimum dose of dry powder but about 40% of patients failed to respond to it. 5 mg salbutamol nebulized with IPPB resulted in a significant increase in peak expiratory flow rate when given before or after either Rotacaps or salbutamol nebulized without IPPB, whereas neither the dry powder nor the nebulized drug without IPPB resulted in significant change when given after salbutamol nebulized with IPPB. The extra benefit derived with IPPB is only slight and requires a device of appropriate characteristics. Occasional patients fail to respond to salbutamol inhaled by any means, generally those with the most severe airflow limitation.

Etude chez 50 malades soumis a la bronchoscopie. D'apres les reponses des malades et des operateurs, la tolerance est meilleure si le malade peut suivre lui-meme visuellement la bronchoscopie. Cependant la frequence de la toux pendant la scopie n'est pas influencee

A study of 23 patients admitted to hospital with severe acute asthma is reported in which plasma cortisol level on admission was significantly correlated with the degree of acidaemia and pulse rate. Patients who had not previously received treatment with corticosteroids responded satisfactorily to repeated daily injections of tetracosactrin depot, the rate of improvement being comparable to that observed in other patients treated with intravenous hydrocortisone hemisuccinate. A prompt and sustained rise in plasma cortisol was also seen following tetracosactrin. The total daily dose of hydrocortisone required to achieve plasma cortisol levels above 100 mug/100 ml was less when given by continuous intravenous infusion compared with intermittent injections, and a regime of 3 mg/kg body weight every six hours by infusion appeared satisfactory. Most patients reported subjective improvement by about four hours after starting treatment but objective evidence did not appear until about six hours from the start. Measurements of FEV1 and FVC proved to be the most reliable indices of the beginning of improvement although pulse rate was the first index to show maximum improvement. Previous maintenance treatment with corticosteroids in patients with asthma did not appear materially to affect the plasma half-life of intravenous hydrocortisone (4 mgm/kg body weight) when compared with healthy subjects or other patients with asthma who had not previously been treated with corticosteroids.