Kaj Viskum

Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT study group

Patients with severe hereditary alpha1-antitrypsin deficiency (alpha1-ATD) face a high risk of developing emphysema at a young age. Intravenous augmentation therapy with purified human alpha1-antitrypsin (alpha1-AT) is now available. However, a controlled trial to show its efficacy has never been carried out. The aim of this study was to compare the decline in forced expiratory volume in one second (deltaFEV1) between Danish patients who had never received augmentation therapy and German patients treated with weekly infusion of alpha1-AT. From the files of the Danish alpha1-ATD register, 97 exsmokers, with a PiZ phenotype and for whom results of at least two lung function measurements with an interval of at least 1 yr were available, were identified. From a German group of patients treated with weekly infusions of alpha1-AT, 60 mg x kg(-1) body weight, 198 exsmokers, with biannual lung function measurements were identified. The deltaFEV1 was compared between the two treatment groups by random effects modelling. The deltaFEV1 in the treated group was significantly lower than in the untreated group, with annual declines of 53 mL x yr(-1) (95% confidence interval (95% CI) 48-58 mL x yr(-1)) and 75 mL x yr(-1) (95% CI 63-87 mL x yr(-1)), respectively (p=0.02). The two groups differed with respect to gender and initial FEV1% predicted. Gender did not have any influence on the deltaFEV1. Stratification by initial FEV1% pred showed a significant effect of the treatment only in the group of patients with an initial FEV1% pred of 31-65%, and deltaFEV1 was reduced by 21 mL x yr(-1). This nonrandomized study suggests that weekly infusion of human alpha1-antitrypsin in patients with moderately reduced lung function may slow the annual decline in forced expiratory volume in one second.

A quantitative and qualitative study of blood monocytes in patients with bronchogenic carcinoma

SummaryAbsolute circulating number and functions of blood monocytes (i.e., pinocytosis, phagocytosis, and chemotaxis) were studied in 25 patients with untreated bronchogenic carcinoma and in 28 control subjects. The absolute circulating monocyte count was increased in 20 (80%) of the patients. There was no difference in the pinocytic and phagocytic activity of patient and control monocytes. In contrast, patient monocytes showed depressed chemotactic responsiveness. This defect was more severe in small cell anaplastic carcinoma than in the other histologic types of bronchogenic carcinoma (P=0.001), and may explain the difference in macrophage infiltration seen in solid tumours of the lung. There was no correlation between chemotaxis and clinical stage. Depressed chemotaxis may be related to a plasma factor, since patient plasma inhibited the chemotaxis of control monocytes as well as the activity of chemotactic agents. The defective chemotaxis and the presence of plasma inhibitory activity may interfere with the ability of blood monocytes to accumulate as macrophages in tumour sites.

Decline in pulmonary function in patients with α1-antitrypsin deficiency

Sixty-five patients with severe alpha1-antitrypsin (AAT) deficiency (phenotype PiZ) were followed with spirometry at regular intervals of one year and a median observation period of four years.The annual decline in pulmonary function was adjusted for sex, age and height by division with the predicted normal pulmonary function. The median decline in FEV1 was 1.9% predicted/year. The rate of decline was independent of age and pulmonary function, except for patients with FEV1 below 25% of predicted normal.There was a tendency towards a slower median decline in FEV1 in exsmokers (1.7% predicted/year) compared to smokers (3.8% predicted/year) and never-smokers (3.7% predicted/year), however, this difference was not significant (p > 0.1). At the time of diagnosis smokers and ex-smokers had a lower FEV1 (44 and 38% predicted) than never-smokers (85% predicted) (p < 0.02), and smokers and ex-smokers were generally younger (median age 44 and 42 years, respectively) than never smokers (median age 55 years) (p > 0.1).Our data indicate that smokers as well as nonsmokers with severe AAT deficiency are at risk of developing pulmonary emphysema. The disease seems to appear later in nonsmokers, though once initiated it progresses at the same rate.

Bacillarity at autopsy in pulmonary tuberculosis. Mycobacterium tuberculosis is often disseminated.

The aim of this investigation was to quantify dissemination of Mycobacterium tuberculosis infection in patients with pulmonary tuberculosis and to show the pattern of eradication during treatment. The study is based on 98 out of the 113 patients with pulmonary tuberculosis who died during their admission to hospital in the Municipality of Copenhagen from 1963 to 1971. These patients had cultures for M. tuberculosis performed from different organs at autopsy: 78% treated <=100 days had dissemination of bacteria, cultured with decreasing frequency in the lungs, spleen, liver, and kidneys, respectively. In comparison, 23% treated >100 days had dissemination of bacteria, among which 50% occurred in patients with records of poor treatment compliance, 14% in patients with good treatment compliance. 81% of all patients had at least one chest x‐ray judged to be without a miliary pattern. This study emphasizes that M. tuberculosis is often disseminated to organs other than the lungs in severe pulmonary tuberculosis. Eradication of bacteria in these organs can take several months. This observation adds to our understanding of the natural history of tuberculosis: M. tuberculosis is a resilient organism that can adapt to a wide variety of environmental conditions.

Criteria for alpha 1-antitrypsin substitution.

The pharmacology and safety of substitution treatment intraveneously withα1-antitrypsin (AAT) in patients deficient of AAT has been thoroughly investigated. The clinical efficacy of the treatment has so far not been established. The difficulties and uncertainties involved in defining the right persons for treatment, and determining the right time for a possible start of treatment are discussed. A controlled trail with participation of several European countries is suggested.

Patient-administered sequential spirometry in healthy volunteers and patients with α1-antitrypsin deficiency

The launching of cheap, pocket-sized spirometers, with data storage capability, has made patient-administered sequential spirometry (PASS) an attractive method of monitoring ventilatory capacity. At present, little information is available on the quality of PASS, compared to laboratory spirometry. The aim of this study was to investigate whether patients could perform PASS without loss of reliability and reproducibility as compared with traditional laboratory spirometry. Ten healthy volunteers performed spirometry for 1 month and 10 emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria on full data documentation, a traditional direct recording spirometer, the Vitalograph R-model, was used. A decompression device was used for calibration and a 3.8% annual drift in volume registration was noted. This drift was largest for the first year. After training, all patients were able to perform unsupervised spirometry, producing technically correct forced expiratory curves. Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for laboratory spirometry. After adjustment for the diurnal variation, the residual variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6% (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the same pattern. In conclusion, PASS is possible in highly motivated individuals without loss of reliability and reproducibility when compared to laboratory spirometry.

Spontaneous regression of a pleural thickening with the histological appearance of an inflammatory pseudotumour

The inflammatory nature of a tumour-like lesion not formerly observed in the parietal pleura was confirmed histologically using immunohistochemical analysis and clinically by spontaneous regression. A study of the literature revealed that the histological picture of the lesion was consistent with that of the rarely described inflammatory pseudotumour.