HIV seroprevalence by anonymous testing in patients with Mycobacterium tuberculosis and in tuberculosis contacts.

Having witnessed a large increase in Mycobacterium tuberculosis notifications in south London, we wanted to ascertain the prevalence of HIV and tuberculosis co-infection in our patients. All patients with tuberculosis and their contacts were anonymously tested for HIV in blood and saliva, respectively. 11.4% of patients (from various demographic groups) with tuberculosis who attend chest clinics in south London are HIV positive. In addition, 5% of individuals seen in the tuberculosis contact screening clinics and 4% new entrants are HIV positive. All patients with Mycobacterium tuberculosis, irrespective of background, should be urged to have an HIV test.

Palliation and life quality in lung cancer; how good are clinicians at judging treatment outcome?

A recent trial by the MRC Lung Cancer Working Party used physician assessments to compare two palliative schedules of radiotherapy in lung cancer. A prospective study has been undertaken on a subset of these trial patients to see how physician assessments of symptomatic relief and general condition correlate with patient perception of therapeutic response. In 40 patients followed up monthly from presentation until close to death, good agreement was found between doctors and patients on change in specific physical symptoms and overall physical condition. Doctors were poor judges of life quality at presentation but appeared able to identify relative improvement or deterioration in overall quality of life. In conclusion, physician assessments may constitute valid end-points for radiotherapy trials comparing palliative schedules in lung cancer.

Urinary desmosine, elastolysis, and lung disease.

Desmosine is an amino acid specific to elastin. Animal studies suggest that urinary desmosine (UD) represents endogenous elastin degradation. Therefore, UD has previously been used to investigate endogenous elastolysis, but was not elevated in subjects with chronic obstructive airways disease (COAD), although accelerated pulmonary elastolysis is thought to contribute to COAD. We have investigated whether this reflects large day-to-day and between-subject variation in UD and whether, in man, dietary desmosine contributes significantly to that in urine. Mean 24-hour UD output (over 5 consecutive days) from 10 asymptomatic subjects (5 males) was higher in males than females (77.4 +/- 9.6 and 40.2 +/- 5.0 nmol/24 hours, respectively; mean +/- SD, P less than .001), but not significantly different when expressed in terms of creatinine (micrograms desmosine/100 mg creatinine: males, 2.5 +/- 0.4; females, 3.1 +/- 0.8; mean +/- SD). The lowest between-subject variation was observed when the mean of 5 days' 24-hour UD values was analyzed on the basis of gender (coefficient of variation [CV], 12.5%); when gender was not considered, the least between-subject variation was found for the mean of 5 days' desmosine/creatinine analysis (CV, 24.5%). Approximately 1% of dietary desmosine (ingested as [3H]elastin and [3H] desmosine) was excreted in the urine within 24 hours, contributing approximately 15% of UD while on a normal diet. Although ingestion of a low elastin diet (less than 1/10 desmosine/24 hours than a normal diet) resulted in lower within-subject variation in 24-hour UD excretion (mean CV decreased from 31.5% to 20.2%), the between-subject CV and UD levels did not alter.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effect of cigarette smoking on the neutrophil elastase inhibitory capacity of peripheral lung lavage from asymptomatic volunteers.

Cigarette smoke-induced emphysema is thought to involve reduction of antielastolytic capacity, resulting in elevated elastase activity and lung tissue damage. Peripheral lavage collected from ten asymptomatic subjects immediately before and 20 min after smoking two high tar cigarettes was analysed for neutrophil elastase (NE) inhibitory capacity (IC), alpha 1-proteinase inhibitor (PI) function, elastolytic activity and immunoreactive levels of PI and bronchial inhibitor (BI). The only change found was a small fall in mol immunoreactive PI/mol albumin after smoking (approximately 17%, p less than 0.05) which did not affect NEIC, since PI contributed less than 50% of the NEIC. There was often more NEIC than mol BI + functional PI, suggesting the presence of other NE inhibitors. Thoracic computerized tomography scans of eight of these subjects highlighted two with emphysematous regions of lung; lavage from these two subjects contained either undetectable BI or inactive BI and this suggests a protective role for BI in emphysema.

Fibreoptic bronchoscopy: an assessment of immediate cytological diagnosis using methylene blue stain.

A method of examining cytological material during fibreoptic bronchoscopy using a methylene blue (MB) stain was assessed in 164 consecutive fibreoptic bronchoscopies where cytology specimens were taken. The MB method provided an immediate positive diagnosis in 86% of bronchoscopically visible tumours. Subsequent histology provided a positive diagnosis in 69%, conventional brush cytology in 81% and trap cytology in 77%. The MB method produced no false positive diagnosis of malignancy and the tumour cell type identified by MB stain agreed with the histological cell type in 72% of cases. This technique is considered to be sufficiently specific to provide a method of controlling the quality of specimens taken at bronchoscopy, for further analysis in the laboratory.

Comparison of human lung surface protein profiles from the central and peripheral airways sampled using two regional lavage techniques.

This study describes two new techniques of lung lavage which selectively remove material from the central airways, or from the lung below the seventh generation. Bronchograms confirmed that discrete regions of the lung were washed by central lavage (CL; maximum airway diameter approximately 6.5 mm) and peripheral lavage (PL; maximum airway diameter approximately 1.3 mm), and that both could be clearly distinguished from conventional bronchoalveolar lavage (BAL). These techniques were used to establish whether or not large-airway proteins made a major contribution to the protein profile of BAL. Twenty consecutive patients undergoing routine fibreoptic bronchoscopy were investigated. More bronchial mucus proteinase inhibitor per unit albumin and per unit total measured antiproteinase was present in CL than PL or BAL. In contrast alpha 1-proteinase inhibitor per unit albumin and as a percentage of total measured antiproteinase was lower in CL than in other lavage types. There were no differences in elastase activity, irrespective of the way in which the data were expressed. As no differences were found between BAL and PL for any of the variables measured, it was concluded that in the subjects studied the contribution of CL proteins to BAL was minimal.

The elastase: anti-elastase profile in lung lavage from sarcoidosis patients.

One feature of pulmonary sarcoidosis is an increase of lymphocyte numbers in bronchoalveolar lavage fluid (BALF). In some patients the number of polymorphonuclear neutrophils (PMN) also rises. It has been suggested that the prognosis for the latter subjects is likely to be worse than that for the former, but the damaging agent (or agents) released by the PMN have not yet been identified. Therefore, in the current study, the activity of one neutrophilic enzyme, elastase, which is known to damage the pulmonary interstitium, has been assessed in sarcoid BALF and compared to BALF from subjects matched for age, sex and smoking status. As BALF also contains locally-produced and serum-derived inhibitors of elastase, levels of which may change in subjects with sarcoidosis, the serine protease inhibitory capacity and the levels of three anti-elastases have been measured in the samples. Levels of the serum-derived antiproteases, alpha 1 proteinase inhibitor (alpha 1PI) and alpha 2 macroglobulin (alpha 2M) were found to be significantly increased. However, alpha 1PI/albumin and alpha 2M/albumin ratios were unchanged, suggesting that the increased levels were due to an increased permeability of the alveolar-capillary barrier. The total protease inhibitory capacity was elevated and this could be entirely explained by the raised levels of alpha 1PI and alpha 2M. Levels of the locally-produced inhibitor were unaltered. The elastolytic capacity of sarcoid BALF was unchanged. Thus, the elastase: anti-elastase balance was shifted against elastolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of elastolytic activity in lung lavage from current, ex- and non-smokers.

Cigarette smokers have an increased risk of developing a wide variety of lung diseases compared to non-smokers, and there have been many studies of the possible biochemical changes underlying this increased susceptibility. However, although epidemiological and physiological studies have shown that in the ex-smoker, the risk of smoking-related lung diseases falls between that of current and non-smokers, the biochemical and cellular mechanisms responsible for this intermediate status have not been investigated. In the present study, therefore, the extracellular elastolytic activities in lung lavage fluid from current, ex- and non-smokers have been compared. Elastolytic enzyme activity was investigated, since it is significantly elevated in lung lavage from smokers, and because it has been implicated in the development of pulmonary emphysema. In the subjects studied, extracellular elastolytic activities in lung lavage from ex-smokers were intermediate between those from current and non-smokers. There was no correlation between the time of abstinence from smoking, or the number of pack-years smoked and the extracellular elastolytic activities in ex-smokers' lung lavage. Elastolytic activity may remain elevated in ex-smokers' lungs for a number of reasons, including the persistence of particulate matter which may activate phagocytic cells on the lung surface. The possible significance of the raised elastolytic activity remains to be fully determined.

Measurement of lung tissue mass, thoracic blood and interstitial volumes by transmission/emission scanning using [99mTc]pertechnetate.

1. We have developed a method for non-invasive measurement of lung tissue mass, thoracic blood and interstitial volumes by a combination of transmission and emission scanning with technetium isotope (99mTc). 2. In a lung model we demonstrated that emission counts could be successfully corrected for attenuation with data obtained by transmission scanning, despite an uneven distribution of radioactivity and attenuation in the model. 3. In dogs we compared regional transthoracic tissue thickness, measured by transmission scanning, and regional 'thickness' of blood measured by transmission/emission scanning with direct gravimetric measurements made post mortem. Scanning and direct measurements correlated significantly. 4. In man we used a [99mTc]pertechnetate (99mTcO4) flood source to obtain antero-posterior transmission scans with a gamma-camera. The thickness of attenuating tissue was estimated in each pixel. Scans were obtained of thoracic blood (by labelling erythrocytes with 99mTcO4) and of interstitium (with 99mTc-labelled diethylenetriaminepenta-acetic acid and subtraction of the blood image). We used a computer program to correct the emission scans for attenuation using the transmission scan derived tissue thickness, pixel by pixel. Finally we took a lateral chest radiograph to estimate chest wall thickness. 5. In normal man lung tissue thickness at hilar level was 3.1 +/- 0.5 cm (n = 8). Thoracic blood thickness increased from the apex downwards in the upright lung, being 1.2 +/- 0.1 cm at the hilar level and 2.0 +/- 0.3 cm at the lung base. Interstitial thickness was 0.8 +/- 0.3 cm at the hilum and 0.85 +/- 0.2 at the base. These values compare well with data in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Transmission electron microscopy of percutaneous fine needle aspirates from lung: a study of 70 cases.

Seventy consecutive lung fine needle aspirates (FNA) from 69 patients were examined by cytology/cell block histology, by transmission electron microscopy (TEM), and, where available, at histological follow up to determine the value of TEM in interpreting lung FNAs. Of 70 FNAs, 50 were suitable for TEM. Transmission electron microscopy was helpful in classifying seven of 10 poorly differentiated tumours, and two case histories are reported. In 26 of 30 well differentiated tumours TEM confirmed diagnosis by light microscopy. Two TEM false negatives, but no TEM false positives, were recorded. It is concluded that transmission electron microscopy of cells aspirated from lung can be helpful when unequivocal diagnosis has not been achieved.

Effects of cigarette smoking and drugs on respiratory tract proteases and antiproteases.

Increased pulmonary proteolytic (elastolytic) activity is thought to be the primary cause of emphysema and may also play a rôle in the pathology of bronchitis. These diseases are common amongst tobacco smokers. Serum-derived alpha 1-proteinase inhibitor (alpha 1PI) and locally produced protease inhibitors normally protect the pulmonary epithelium from proteolytic attack, but tobacco smoke can inactivate these antiproteases by oxidative and non-oxidative mechanisms. Bronchoalveolar lavage fluid (BALF) samples lung surface components and most studies show that there is elevated elastolytic activity in smokers' BALF. Whether antiproteolytic capacity is reduced in these samples remains debatable. A selective lavage technique is described which independently samples central and peripheral epithelium from the same subject. Analysis demonstrates a protease-antiprotease imbalance which can differ in central and peripheral lavage and which could be significant in the development of obstructive airways disease. Therapeutic approaches include augmenting antiprotease potential using genetically engineered, oxidant-resistant alpha 1PI or synthetic peptide inhibitors.

Acid-stable low molecular mass proteinase inhibitors in human lung lavage.

An acid-stable, low molecular mass proteinase inhibitor, bronchial mucus proteinase inhibitor (BMPI), has been isolated from sputum and partially characterised. A single band with a modal molecular mass of 18 700 was observed following SDS-polyacrylamide gel electrophoresis. BMPI inhibited human leukocyte elastase, cathepsin G, trypsin and chymotrypsin, but not porcine pancreatic elastase. Although BMPI had a molecular mass close to the similarly isolated inhibitor of Girard et al. (Girard, F., Tournier, J.M., Polu, J.M. & Sadoul, P. (1980), Bull. Eur. Physiopathol. Respir. 16 (Suppl.) 237-245), and although it showed immunological cross reactivity to the low molecular mass inhibitor of Kramps et al. (Kramps, J.A., Franken, C., Meyer, C.J.L.M. & Dijkman, J.H. (1981) J. Histochem. Cytochem. 29, 712-719), it was found to have an amino-acid profile different to any previously described inhibitor. BMPI was detectable in bronchoalveolar lavage fluid collected from healthy and diseased human lungs. The median molar ratio of BMPI/alpha 1-proteinase inhibitor (alpha 1 PI) observed in these lavage samples was 0.7, which is generally higher than those derived from the data of other authors. This suggests that BMPI is a different protein to those previously described, although its exact relationship to other low molecular mass proteinase inhibitors remains to be determined.

Extracellular elastolytic activity in human lung lavage: a comparative study between smokers and non-smokers.

Unrestrained proteolysis in the lung is believed to initiate emphysema, a disease common among tobacco smokers. However, few studies have found extracellular protease activity in human lung lavage. In this investigation, elastase and serine protease activities were measured in bronchoalveolar lavage supernatants (BAL) from patients undergoing routine investigations. Significantly more elastolytic activity (against insoluble [3H]-elastin) was recovered in the lavage of smokers than that of non-smokers. However, no significant difference was found when the levels of serine proteolytic activity (against N-succinyl-L-trialanyl-p-nitroanilide) were compared. The elastolytic component of the protease activity rose from 5% in non-smokers' BAL to over 30% in that of smokers, suggesting that elastase activity is selectively enhanced by smoking. In lavages from most smokers, 80% or more of the elastase activity was serine-dependent, whereas lavages from non-smokers contained variable proportions of serine elastase. Both alpha 1-proteinase inhibitor (alpha 1-PI) and a low molecular weight antiprotease, bronchial mucus proteinase inhibitor (BMPI) were detectable in the lavage samples, the latter contributing up to 76% of the total antiprotease quantified in the lavage. Functional antiprotease was detected in 85% of the lavages. Since there were no differences in either antiprotease levels or functional inhibitory capacities between lavages from smokers and controls, it is concluded that the imbalance in the protease/antiprotease profile of the smokers' lung results from an enhancement of proteases, specifically of elastolytic activity, rather than a reduction in inhibitory capacity.

Predicted normal values for maximal respiratory pressures in caucasian adults and children.

Maximal respiratory pressures at the mouth (PEmax and PImax) have been measured in 370 normal caucasian children and adults. Age, height, and weight were recorded for all subjects and incorporated in a stepwise multiple regression analysis to determine prediction equations for the maximal respiratory pressures in the children and adults for both sexes. In men PImax and PEmax were significantly correlated only with age (p less than 0.001 and less than 0.035 respectively), whereas in women they were correlated with height (p less than 0.035 and less than 0.03). In both boys and girls PImax was related to weight (p less than 0.0001 and less than 0.01 respectively) and PEmax to age (p less than 0.001 for both). The values for PImax and PEmax in adults were lower than in previously reported series, but in children the values obtained were similar to those reported for several smaller series.

Sternomastoid muscle function and fatigue in normal subjects and in patients with chronic obstructive pulmonary disease.

Four normal subjects and 5 patients with chronic obstructive pulmonary disease (COPD) (mean FEV1, 1.03 L) had frequency:force curves of their sternomastoid muscle measured before and 5 min after a 12-min walk on a flat treadmill, a progressive exercise test (normal subjects only), and a 10-min period of sustained maximal voluntary ventilation (SMVV). Before each test, all subjects had a normal frequency:force curve, and the ratio of the force response at 20 Hz to that at 50 Hz was normal. After SMVV, all the normal subjects and 4 of the 5 patients developed a greater than 15% fall in 20:50 ratio, and this was taken to indicate the presence of low frequency fatigue (LFF). During SMVV, all the subjects achieved minute ventilation greater than 70% of predicted maximal breathing capacity (MBC). During the 12-min walk, all the patients exceeded 70% MBC, and 4 developed LFF. The normal subjects performing progressive exercise also exceeded 70% MBC, and all showed LFF. The 12-min walk did not cause LFF in the normal subjects, but no subject reached 70% of MBC. Despite the presence of LFF in the sternomastoid muscle, the patients were all able to walk the same distance during a second 12-min walk. In both the normal and patient groups, the ventilatory response to CO2 was not changed by the presence of LFF. There were no changes in maximal inspiratory and expiratory mouth pressures or spirometry with LFF. High, sustained levels of minute ventilation cause sternomastoid LFF, but the clinical significance of this phenomenon is not yet certain.