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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.

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.

Fifty-six male patients with pulmonary emphysema were followed for a minimum period of three years (range 3-13), to observe the effects of smoking and smoking withdrawal. The subjects were divided into smokers (Group S) and ex-smokers (Group EX-S). Forced expiratory volume in one second (FEV1) and vital capacity (VC) declined at a significantly (p less than 0.001) faster rate in those who continued to smoke than in ex-smokers. No significant difference between the two groups was observed for kCO (permeability coefficient) and PaO2 (arterial oxygen tension). There was a significant (p less than 0.001) difference between the two groups in the annual change in body weight. We conclude that all patients with emphysema, even those with advanced disease, should be encouraged to stop smoking.

, , 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]