A re-audit of pulmonary function laboratories in the West Midlands.

In 1991 the West Midlands Pulmonary Function Audit Group examined the consistency between pulmonary function laboratories in the West Midlands. Three healthy subjects visited 22 centres and performed a standard set of pulmonary function tests. Demographic data on nine hypothetical subjects was also supplied for the laboratories to produce predicted values. Equipment was checked for accuracy using standard methods. The 1991 audit revealed significant inter-laboratory variability. Sources of error were identified and after consultation, recommendations were made to improve consistency. In addition, national and regional training workshops were organized for laboratory staff. In 1995 the audit was repeated using the same three subjects. Significant differences continued for all predicted results except for residual volume (RV) and forced vital capacity (FVC) and for all measured results except for functional residual capacity (FRC). However, improvements in the coefficient of variation were seen compared with 1991 for predicted forced expiratory volume (FEV1), total lung capacity (TLC), gas transfer (TLCO), FVC, FRC and RV. Similar improvements were seen in measured results for FEV1 and FVC. Increased variation was seen for predicted corrected transfer factor (KCO) and actual RV. The majority of variables in the 1995 audit had a coefficient of variation of less than 5% between laboratories. Analysis of the predicted results from the hypothetical subjects continued to show unacceptable variation reflecting continuing computer algorithm inconsistency. The improvements seen are encouraging and suggest that a regular audit programme is worthwhile.

An audit of pulmonary function laboratories in the West Midlands.

BACKGROUND: Pulmonary function testing has become an integral part of the assessment and follow-up of patients with pulmonary disease. Many factors can influence the results produced by a laboratory. This audit was performed to examine the extent of variation in the pulmonary function test results amongst all laboratories in the West Midlands. This was followed by an attempt to determine the cause of this variation. METHODS: Phase 1. Three normal healthy subjects each underwent a set of pulmonary function tests in all 22 laboratories in the West Midlands. Information regarding technicians' qualifications, training and seniority, protocol and equipment used were obtained in the form of a questionnaire. Phase 2. All 22 laboratories were asked to calculate the predicted values on the same nine sets of demographic data. These data included both sexes, ethnic minorities and range of ages. In addition technical aspects of each laboratory were investigated including the assessment of volume and gas analysers with standard gases containing known concentrations of helium and carbon monoxide. RESULTS: Phase 1. Significant variations (P < 0.05) were observed in all measured values of pulmonary function tests of the three subjects. Significant variations (P < 0.05) were also observed in all predicted values except total lung capacity. Phase 2. There were significant variations (P < 0.05) amongst laboratories in calculating the predicted values of all components of pulmonary function tests. No significant differences were observed in the measurement of volume or concentration of carbon monoxide or helium.

Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton.

Alpha 1-Antitrypsin (alpha 1AT) deficiency is characterized by reduced serum levels of alpha 1AT and a risk for the development of emphysema and liver disease. However, whereas there is an increased risk for emphysema associated with at least 10 alpha 1AT deficiency and null alleles, the hepatic disease is observed only in a subset of these alleles, suggesting that it is not the reduced serum levels of alpha 1AT per se which cause the liver disease. The present study characterizes the alpha 1AT deficiency allele Mmalton, an allele that like the common Z deficiency mutation (Glu342----Lys) is associated with both alpha 1AT deficiency and hepatic disease. Capitalizing on the identification of the homozygous inheritance of the rare Mmalton alpha 1AT deficiency allele, it was demonstrated that although caused by a very different mutation, the Mmalton allele shares with the Z allele the association of liver disease with the same type of abnormalities of alpha 1AT biosynthesis. Cloning of the Mmalton gene and sequence analysis demonstrated that it differs from the normal alpha 1AT M2 allele by deletion of the entire codon (TTC) for residue Phe52. Liver biopsy of the Mmalton homozygote revealed inflammation, mild fibrosis, and intrahepatocyte accumulation of alpha 1AT. Evaluation of de novo alpha 1AT biosynthesis in alpha 1AT-synthesizing cells of this individual demonstrated normal levels of alpha 1AT mRNA transcripts but abnormal intracellular accumulation of newly synthesized alpha 1AT at the level of the rough endoplasmic reticulum with consequent reduced alpha 1AT secretion. Finally, retroviral gene transfer of a normal alpha 1AT cDNA and an alpha 1AT cDNA with the Mmalton Phe52 deletion into murine cells demonstrated that the Mmalton cells reproduced the abnormal accumulation of newly synthesized alpha 1AT, thus directly demonstrating that the deletion mutation is responsible for the intracellular accumulation of the newly synthesized alpha 1AT. Thus, not only is the liver disease associated with alpha 1AT deficiency restricted to a subset of alpha 1AT deficiency alleles, it appears to be restricted to those alleles associated with intracellular accumulation of newly synthesized alpha 1AT, suggesting that it is the abnormal intrahepatocyte alpha 1AT accumulation which incites the liver injury.

Obstructive sleep apnoea during pregnancy requiring tracheostomy.

The case is presented as an unusual example of the benefit of tracheostomy during pregnancy in a patient with obstructive sleep apnoea syndrome.

Ambulatory pH monitoring of gastro-oesophageal reflux in "morning dipper" asthmatics.

A causal relation between gastro-oesophageal reflux and nocturnal asthma has been postulated. Forty four adult asthmatics underwent ambulatory monitoring of their oesophageal pH over 24 hours to find out if there was such a relation. Of these 21 showed significant "morning dipping" in which the peak expiratory flow falls during the night. Asthmatics with morning dipping had a history of nocturnal wheeze and a higher incidence of reflux symptoms, but measurement of oesophageal pH showed no significant difference in the amount or pattern of reflux when compared with "non-dippers." Overall, 15 asthmatics had gastro-oesophageal reflux, and these participated in a randomised, double blind crossover trial of ranitidine versus placebo. No significant difference was found in the peak expiratory flow rates or subjective evaluation of well being of the patients.

Atenolol and sustained release nifedipine alone and in combination in hypertension. A randomised, double-blind, crossover study.

In this randomised, double-blind, crossover trial, the efficacy in hypertension of atenolol and nifedipine as single agents or in combination was compared. 81 patients with mild to moderate essential hypertension (sitting diastolic blood pressure 100-120 mm Hg, aged 20-70 years) from 6 outpatient clinics entered the study. By use of a Latin-square design, patients received, in randomised fashion, sustained release nifedipine 20mg twice daily, atenolol 50mg in the morning and then placebo in the evening, or sustained release nifedipine 20mg plus atenolol 50mg in the morning and then placebo in the evening. Each schedule was followed for 4 weeks. All treatments lowered systolic and diastolic blood pressure in the supine and standing positions compared with pretreatment values. The combination regimen significantly reduced supine and standing systolic (p less than 0.01 and p less than 0.001, respectively) and diastolic (p less than 0.001) blood pressure compared with nifedipine alone, and it also significantly reduced supine and standing systolic (p less than 0.01 and p less than 0.03, respectively) and diastolic (p less than 0.01) blood pressure compared with atenolol alone. Heart rate was significantly decreased by atenolol and the combination compared with nifedipine alone. 15 patients withdrew because of side effects: 9 during nifedipine treatment, 2 during atenolol treatment and 4 during combination treatment. Side effects were typical of those associated with nifedipine or atenolol. Flushes and hot sweats, which were frequent with nifedipine, were significantly less (p less than 0.001) with atenolol or the combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of temperature on Vitalograph spirometer readings.

Spirometric variables were obtained from nine symptomless subjects, who performed forced expiratory manoeuvres with three Vitalograph spirometers at three different ambient temperatures (36.5 degrees C, 24.1 degrees C, and - 7.3 degrees C) over three days according to a Latin square design. Analysis of variance showed no significant difference between values at different ambient temperatures when measured at ATPS. Correction of the results to BTPS resulted in a significant difference in values at the three ambient temperatures for all measurements other than the Vmax25. The mean error introduced by conversion to BTPS varied from 7% (SD 5%) for the FVC at 24.1 degrees C to 30% (21%) for Vmax50 at - 7.3 degrees C. Possible explanations for these observations include the increasing compliance of the spirometer bellows with increasing temperature, relatively slow cooling of gases within the spirometer, and a combination of these effects. We conclude that there is no evidence that conversion to BTPS improves the accuracy of measurements made on a Vitalograph spirometer. Further studies on other spirometers are needed to see whether conversion to BTPS is always appropriate.

An evaluation of the vitalograph pulmonary monitor.

The Vitalograph pulmonary monitor has recently been altered by the manufactures to read in litres per minute. In 200 pairs of measurements comparing the monitor to the Wright peak flow meter (PFM) the mean difference between the instrument was 0.57 litres/min and there was a strong positive correlation (r = 0.92). The mean within subject coefficient of variation was 5.8% (range 2.6% to 10.7%). There was a statistical difference (P less than 0.05) in measurements obtained with different monitors but in practical terms this difference was small. The monitor is pocket-sized and light and is therefore suitable for following changes in peak expiratory flow away from the physiology laboratory.

Sleep apnoea in acromegaly.

Day time somnolence or excessive snoring, or both, occurred in five out of 11 patients with acromegaly. All five had episodes of sleep apnoea, and three had the sleep apnoea syndrome. Growth hormone concentrations were higher (p less than 0.025) in these patients than in the six patients without these symptoms. One patient with daytime somnolence and one asymptomatic patient had flow loop evidence of upper airways obstruction. Two of the patients with the sleep apnoea syndrome had cardiomegaly. Sleep apnoea appears to be common and clinically important in acromegaly, and it may be central, obstructive, or mixed. Polygraphic nocturnal monitoring is indicated to assess these patients properly.

Sleep apnoea in Scheie's syndrome.

An 18-year-old student presented with a two-year history of daytime sleepiness and noisy breathing during sleep. Both he and his brother, aged 25 years, had Scheie's syndrome, a mucopolysaccharidosis characterised by small stature, micrognathia, corneal clouding, hepatosplenomegaly, raised urinary mucopolysaccharides, and undetectable levels of alpha-L-iduronidase assayed in cultured fibroblasts. Both brothers had sleep apnoea (apnoea index, 59 and 35 respectively) during which there was a significant fall in heart rate and arterial oxygen saturation. One brother had EEG changes suggestive of cerebral hypoxia and the other had ventricular extrasystoles at the end of several episodes. Tracheostomy in the younger brother produced a dramatic symptomatic improvement and reduced the number and severity of apnoeic episodes (post-tracheostomy apnoea index 2.4).

Demeclocycline in the treatment of the syndrome of inappropriate secretion of antidiuretic hormone.

Fourteen patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been treated with demethylchlortetracycline (demeclocycline) 1200 mg daily. In 12 patients the underlying lesion was malignant. The serum sodium returned to normal (greater than 135 mmol/l) in all patients after a mean of 8.6 days (SD +/- 5.3 days). Blood urea rose significantly from the pretreatment level of 4.2 +/- 2.3 mmol/l to 10.1 +/- 5.1 mmol/l at ten days (P less than 0.001). The average maximum blood urea was 13.4 +/- 6.8 mmol/l. In four patients the urea rose above 20 mmol/l, and in two of these demecyocycline was discontinued because of thie rise. The azotaemia could be attributed to a combination of increased urea producation and a mild specific drug-induced nephrotoxicity. Discontinuation of demeclocycline in six patients led to a fall in serum sodium, in one case precipitously, and return of the urea towards normal levels. Demeclocycline appears therefore to be an effective maintenance treatment of SIADH, and the azotaemia that occurs is reversible and probably dose dependent.

Work-related respiratory disease in employees leaving an electronics factory.

Examination of the records of employees leaving an electronics factory over three-and-a-half years showed that a significantly greater proportion left the shop floor (where soldering took place) because of ill health than left the stores and office areas. This difference was largely due to work-related respiratory disease in those whose job was soldering. Shop floor workers leaving for health reasons also had increased sickness certification due to respiratory illness compared to stores and office workers. These findings suggest that work-related respiratory illness is a significant cause of morbidity and loss of employment in solderers working at the factory and that this has been a longstanding problem with its onset before the first recorded cases of occupational asthma caused by solder flux containing colophony.

An evaluation of the mini-Wright peak flow meter.

The mini-Wright peak flow meter (MPFM) has been evaluated, and the results obtained from it show a strong positive correlation (r=0.970) with the Wright's peak flow meter (PFM). MPFM measurements, however, were biased to be about 38 1/min higher than PFM measurements (95% confidence limits 31.01/min to 45.01/min). Between instrument variation was found (F--ratio 3.67 with 9 and 81 degrees of freedom: P less than 0.001). In practice this did not appreciably affect individual measurements greatly as 95% confidence limits on any individual measurements were increased from +/-24 1/min to +/-27 1/min. There was no significant day-to-day variability in measurements obtained with individual instruments. The MPFM is a pocket-sized, simple, cheap, and robust instrument for following changes in ventilatory function. In clinical trails and surveys, however, both the bias in favour of the MPFM compared to the PFM and inter-machine variation must be taken into account. As the manufacturers have altered the scale to remove the bias since this study was performed, it will be important to know whether the original or the modified meter is being used in future studies.

Hyponatraemia and mesothelioma.

Hyponatraemia was found in 18 (62%) of 29 patients with histologically proven mesothelioma. The mechanism for the development of the hyponatraemia is discussed. It is suggested that patients with mesothelioma should be monitored for electrolyte abnormalities. If hyponatraemia is found the syndrome of inappropriate secretion of antidiuretic hormone should be suspected as treatment with demethylchlortetracycline may improve the quality of life in an otherwise fatal illness.