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, , 81-89. Pulmonary emphysema exists in two main pathological forms, centrilobular and panlobular (panacinar) emphysema, the lesions predominantly affecting the upper and lower zones of the lungs respectively. There is disagreement among authors as to the clinical and physiological differences between these two forms, and direct evidence of the pathological type is seldom available during life. Patients with emphysema can, however, be divided on radiological criteria into an `upper zone' and a `lower zone' group, and it can be argued that these groups relate respectively to the centrilobular and panlobular forms of the disease. The evidence is far from conclusive but it was thought that a comparison of the two radiological groups would be of value. Patients in whom there was no obvious zonal preponderance were not included in the study. Fifty patients with definite radiological evidence of pulmonary emphysema have been studied, those with α-antitrypsin deficiency being excluded. Thirty-one patients (62%) had emphysema which predominantly affected the upper zones of the lungs; the lower zones were the more severely affected in the remainder. Bullae were found in approximately equal proportions in each group. All the patients were, or had been, cigarette smokers. There was no significant difference between the mean ages of the two groups; only seven patients were free from exertional dyspnoea, all being in the upper zone group. Chronic bronchitis occurred with equal frequency in the two groups but started on average about 10 years earlier in those with lower zone disease; the latter patients had rather more severe airflow obstruction and more severe blood-gas abnormalities. The presence or absence of chronic bronchitis per se, however, did not appear to have any significant effect upon the common respiratory function tests. No data emerged from this study which suggested that there were differing aetiological factors in the two groups. [ABSTRACT FROM PUBLISHER]

, , 584-587. Three methods of measuring the vital capacity have been compared in six normal subjects and in six with pulmonary emphysema, according to a randomized design. The methods were () the inspiratory vital capacity (IVC), () the expiratory vital capacity (EVC), and () the forced vital capacity (FVC). In normal subjects, there was a small but significant difference between the methods. The residual standard deviation derived from analysis of variance was 94 ml (coefficient of variation 1.7%). A slight but significant rise in vital capacity with repeated effort was observed. In emphysematous subjects, there was no significant difference between the IVC and EVC methods. The FVC gave values which were, on average, approximately 0.5 litre less than those obtained by the other methods. The standard deviation in all three methods was substantially greater than for the normal subjects. The FVC is not a suitable method for the measurement of vital capacity in patients with pulmonary emphysema. The EVC is satisfactory, provided it is used with caution, but in practice the IVC is the preferred method. [ABSTRACT FROM PUBLISHER]

Continuous measurements of transcutaneous oxygen tension (tcPO2) were made in 23 patients with radiological evidence of emphysema, at rest and during a maximal progressive exercise test. tcPO2 during the final phase of exercise was compared with tcPO2 at rest; the mean change (exercising minus resting value) in tcPO2 (delta tcPO2) was -0.8 mm Hg (SD 10.5, range -18 to +25) (-0.1 kPa (SD 1.4, range -2.4 to +3.3]. delta tcPO2 was correlated with: resting arterial oxygen tension (PaO2) (r = 0.606, p less than 0.005); resting arterial carbon dioxide tension (PaCO2) (r = -0.691, p less than 0.001); FEV1 % predicted (r = 0.688, p less than 0.001); vital capacity % predicted (r = 0.543, p less than 0.01); and transfer factor (TLCO) % predicted (r = 0.604, p less than 0.005). There was no significant difference between the delta tcPO2 of 10 patients who regularly produced sputum and of 13 patients with no sputum. delta tcPO2 appears to be more closely related to the severity of emphysema than to the presence or absence of chronic bronchitis. Pretreatment with fenoterol aerosol resulted in an increased work load in three out of 10 patients. Overall there was no change in delta tcPO2. In all except one patient there was a rise in tcPO2 after the end of exercise. In the 11 patients whose tcPO2 fell during exercise, tcPO2 returned to the resting value within two minutes of the cessation of exercise; this was followed by a further rise beyond the resting value, and a single postexercise arterial sample is therefore a poor indicator of the response of PaO2 to exercise. Measurement of TcPO2 is of value in following rapid changes in PaO2 during and after exercise and avoids the necessity for an indwelling arterial cannula. [ABSTRACT FROM AUTHOR]

In patients with radiological evidence of pulmonary emphysema the bronchodilator drugs fenoterol and ipratropium bromide produced a considerable increase in vital capacity and reduction in residual volume. The response to fenoterol was virtually complete 15 minutes after administration, but after ipratropium bromide vital capacity was still increasing at 60 minutes. The change in vital capacity was slightly greater with a combination of the two drugs than with either used alone. Changes in FEV1 and peak flow rate were small. [ABSTRACT FROM PUBLISHER]

Fifty-six male patients with pulmonary emphysema and normal serum alpha 1-antitrypsin were followed for a minimum period of three years (range 3-13 yr) to observe the effects of the radiological distribution of emphysema on the annual rate of change of lung function indices. The subjects were placed in three categories--upper zone (UZ), lower zone (LZ), and generalised (G). The influence of smoking was taken into account with subjects in each radiographic category being divided into ex-smokers (group EX-S) and continuing smokers (group S). The rate of decline of FEV1, VC, TCO, and KCO was greater in group S than EX-S in all three x-ray categories. In group S, FEV1, VC, TCO, and KCO declined significantly faster in UZ emphysema than in G emphysema. In group EX-S, FEV1, TCO, and PaO2 declined significantly faster in UZ than G emphysema but VC remained unaltered. KCO and PaCO2 did not change significantly in any radiographic category in either group S or EX-S. Patients with G and LZ emphysema underwent very similar physiological changes over the course of time. Those with UZ emphysema, however, complained of exertional dyspnoea at an earlier age; a number of their lung function indices deteriorated at a faster rate than in patients from the other two categories, suggesting that UZ emphysema is a different disease entity. [ABSTRACT FROM AUTHOR]

Transcutaneous oxygen tension (tcPO2) measured with a heated electrode was compared with arterial oxygen tension (PaO2) in three groups of adult patients-group A: 20 patients with chronic respiratory disease; group B: eight hypothermic patents studied immediately after cardiopulmonary bypass surgery; and group C: 14 patients in an intensive care unit who had in all 35 comparisons of tcPO2 and PaO2. For group A, the relationship of the two methods is given by the regression equation (in mmHg): tcPO2 = 0.88 PaO2 + 5.0 (standard error = 5.2: r = 0.93: p less than 0.001) and for group C tcPO2 = 0.69 PaO2 + 14.9 (standard error =12.0, r = 0.90: p less than 0.001). A method of in vivo calibration using a single arterial blood sample improved the reliability of the method in group C. In the group B patients there was no correlation between tcPO2 and PaO2 even when supplementary heating was applied to the skin. Continuous monitoring can reveal large fluctuations in arterial PO2 which would be missed by the use of intermittent arterial samples. The transcutaneous electrode can be employed usefully in intensive care monitoring of adult patients and in physiological studies where repeated arterial samples would otherwise be required. [ABSTRACT FROM AUTHOR]

Eleven patients who had received surgical treatment for bullous emphysema had regular assessment of lung function for a minimum of four years (mean 8.8, range 4-20 years). For each patient we estimated the annual rate of change in FEV1 and "relaxed" vital capacity (before and after bronchodilator aerosol) and in carbon monoxide transfer factor (TLCO), transfer coefficient (KCO), and arterial carbon dioxide and oxygen tensions (Paco2 and Pao2). Among the 11 who had undergone operation, all lung function variables declined at a faster rate in those who continued to smoke than in ex-smokers, the difference in rate being significant (p less than 0.05) for FEV1 (before bronchodilator), TLCO and KCO. In ex-smokers the rate of change in most lung function indices was not significantly different from zero--that is, no change; in smokers all lung function indices except Paco2 declined at a rate significantly greater than zero. These findings suggest that long term results of surgical treatment for bullous emphysema are likely to be greatly improved if patients abandon smoking. [ABSTRACT FROM AUTHOR]

There has been a worldwide increase in multiple drug-resistant tuberculosis (MDR-TB) which has in the past been associated with a poor prognosis. In the U.K., about half of the cases live in the London area and we have set out to obtain further information on their treatment and outcome. We examined the risk factors, drug resistance, drug treatment, sputum conversion, and outcome in patients with MDR-TB at three hospitals in South London and diagnosed during the period June 1995-January 1999. Human Immunodeficiency Virus (HIV)-positive patients were excluded. There were 760 patients resident in Lambeth, Southwark and Lewisham Health Authority (LSLHA) who were notified as tuberculosis (TB) during the time period and who were of negative or unknown HIV status. (The population of LSLHA is approx.750,000.) There was a total of 13 patients with MDR-TB, known or presumed to be HlV negative. Their median age was 28 years (range 15-53); nine (69%) were born outside the U.K. and 11 had pulmonary disease; they had organisms resistant to a median of two first-line drugs (range 2-4) and to a median of four of all drugs tested (range 2-10). They received treatment with a median of six drugs (range 3-9). Eight were followed up for at least 3 years (range 3-6) after the completion of treatment; at their last assessment none had features of active TB and all were sputum negative (smear and culture). Two returned to their countries of origin during treatment; they were sputum negative at that time. Two patients are well and continue on treatment in the U.K. One patient (known HIV negative) died following treatment failure. In conclusion, we obtained disease-free survival in eight cases of MDR-TB, known or presumed to be HIV negative and followed up for 3 years or more. The prognosis for patients treated at specialised centres is good (and better than is generally believed). We describe a new protocol for the detection and management of MDR-TB.

Background: Alpha-1-antitrypsin (AT) deficiency is a hereditary disorder associated with pulmonary emphysema. AT replacement therapy has been available for many years with only one randomised controlled trial, showing no improvement in the rate of decline in lung function. We aimed to obtain further data on the natural history of the disorder and thus to refine the criteria for future clinical trials., Methods: Homozygotes for Pi type Z were identified among chest clinic patients and close relatives. Clinical and lung function data were obtained by means of a standardised questionnaire administered yearly for a maximum of 15 years., Results: Baseline study: forced expiratory volume in 1 s (FEV1) and vital capacity (VC) were studied in 194 Pi type Z patients at registration. Past or present smoking history had the strongest relationship to reduction in FEV1 (P < 0.001), but among those who had smoked, estimated total lifetime tobacco consumption (kg) was not significantly related to FEV1. No effecton FEV1 was produced by gender, age of starting to smoke, asthma, occupation or intra-family factors in sib pairs concordant for smoking. Follow-up study: In 71 patients, the average number of annual lung function assessments per subject was 8.0 (range 6-13) and average follow-up time 97 years (range 4.2-14.9). FEV1 slope tended to be steeper in current smokers than in ex-smokers (0.05 < P < 0.1) and greatest in patients with initial FEV1 in the range 30-65% predicted. Effects on VC were less severe. Much deterioration takes place before emphysematous patients come to clinical attention. FEV1 slopes calculated using only the first four assessments have a significantly greater variance than when calculated on all assessments (F = 3.79; P < 0.01). FEV1 and VC slopes using post-bronchodilator values are greater than when using pre-bronchodilator values., Conclusions: Future trials of AT replacement therapy need rigorous standardisation of lung function testing (including bronchodilator protocol) together with an adequate period of assessment. Only randomised controlled trials should be considered valid. Therapy should ideally be started earlier than normally envisaged and before the onset of clinical emphysema.

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

alpha 1-Antitrypsin (AT) is the principal serum inhibitor of proteolytic enzymes such as neutrophil elastase. AT can exist as over 90 different genetically determined variants known as the Pi system; the three most important variants are type M (90% of population) and types S and Z, two of the commoner abnormal variants. Homozygotes of type Z have a severe reduction in the serum AT concentration and may develop pulmonary emphysema or hepatic cirrhosis. Heterozygotes of type SZ have a less severe reduction in serum AT concentration and the association with clinical disease is less clear. The S and Z variants are found mainly among those of European stock. The gene frequency for Pi type Z is highest on the north-western seaboard of the continent and the mutation seems likely to have arisen in southern Scandinavia. The distribution of type S is quite different; the gene frequency is highest in the Iberian peninsula and the mutation is likely to have arisen in that region. A population survey for determining the number of type Z homozygotes in a given community is important for planning purposes now that AT replacement therapy is potentially available.