Because of the limited number of donor organs available, the selection of patients for lung transplantation is crucial. One important issue in setting priorities is the life expectancy without transplantation. The purpose of this study was to estimate survival based on lung function, in alpha 1-antitrypsin deficient patients. Data from the Danish alpha 1-antitrypsin deficiency registry were analysed. The basic element of the analysis was two year intervals, characterized by date of spirometry and known mortality status 2 yrs later. We found a simple exponential relationship between lung function (forced expiratory volume one second (FEV1)) and two year survival on conservative treatment. The formula implies an almost 100% two year survival until FEV1 falls below one third of predicted normal; at this level two year mortality increases and will reach 50% at a FEV1 of 15% predicted. In conclusion, the two year mortality of emphysema patients due to alpha 1-antitrypsin deficiency increases exponentially with decreasing FEV1 and the results imply that only a few patients who underwent lung transplantation would have had a better two year prognosis without this procedure.
Molecular genotyping of Mycobacterium tuberculosis has proved to be a powerful tool in tuberculosis surveillance, epidemiology, and control. Based on results obtained through 15 years of nationwide IS6110 restriction fragment length polymorphism (RFLP) genotyping of M. tuberculosis cases in Denmark, a country on the way toward tuberculosis elimination, we discuss M. tuberculosis transmission dynamics and point to areas for control interventions. Cases with 100% identical genotypes (RFLP patterns) were defined as clustered, and a cluster was defined as cases with an identical genotype. Of 4,601 included cases, corresponding to 76% of reported and 97% of culture-verified tuberculosis cases in the country, 56% were clustered, of which 69% were Danes. Generally, Danes were more often in large clusters (= 50 persons), older (mean age, 45 years), and male (male/female ratio, 2.5). Also, Danes had a higher cluster frequency within a 2-year observation window (60.8%), and higher clustering rate of new patterns over time, compared to immigrants. A dominant genotype, cluster 2, constituted 44% of all clustered and 35% of all genotyped cases. This cluster was primarily found among Danish males, 30 to 59 years of age, often socially marginalized, and with records of alcohol abuse. In Danes, cluster 2 alone was responsible for the high cluster frequency level. Immigrants had a higher incidence of clustered tuberculosis at a younger age (0 to 39 years). To achieve tuberculosis elimination in Denmark, high-risk transmission environments, like the cluster 2 environment in Danes, and specific transmission chains in immigrants in the capital area, e.g., homeless/socially marginalized Somalis/Greenlanders, often with alcohol abuse, must be targeted, including groups with a high risk of reactivation.
Sixty-five patients with severe alpha 1-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 ex-smokers (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 greater than 0.01). At the time of diagnosis smokers and ex-smokers had a lower FEV1 (44 and 38% predicted) than never-smokers (85% predicted) (p less than 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 greater than 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.
The referral centre of tuberculosis in the municipality of Copenhagen, Denmark was the setting for this study, which aimed to assess the diagnostic strategy (chest X-ray and clinical mycobacteriology) in pulmonary tuberculosis. Patient records and chest X-rays were examined for all patients who had sputum or gastric lavage examined for Mycobacterium tuberculosis (Mtb) from 1 January 1992 to 30 April 1994. All chest X-rays were re-evaluated by a trained lung specialist, who did not know the results of sputum culture. Evaluation was referred to one of seven X-ray categories, and compared to the results of culture. Culture of sputum or gastric lavage were positive for Mtb in 54 (14%) of 392 patients; in 61% of 59 patients with X-ray changes thought to be due to tuberculosis (TB); in 20% of 51 patients with X-ray changes compatible with TB; in 14% of 35 patients with previous TB and radiographically active TB; in 2% of 103 patients with previous TB, but not radiographically active TB; in 1% of 112 patients with X-ray changes thought to be due to other disease; and none out of 32 patients with normal X-ray. Even in this highly selected material, it is relatively expensive to find the very few cases of active TB in patients with chest X-ray changes not suspected to be due to TB. It is recommended that: (1) examination of sputum for Mtb should always be preceded by X-ray of the chest in a low-prevalence country; (2) routine culture of sputum for Mtb is restricted to patients with X-ray changes typical or compatible with active TB; and (3) exceptions to this general rule should be made on the basis of the individual's clinical history.
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.
Comment In: Eur Respir J. 1997 Oct;10(10):2191-39387938
SETTING: Denmark, a high-income country with a low prevalence of tuberculosis. OBJECTIVE AND DESIGN: Molecular epidemiological studies of Mycobacterium tuberculosis strains are conducted worldwide, and distinct strains have been associated with large outbreaks of tuberculosis. This is the first systematic population-based search for distinct strains of M. tuberculosis in Denmark among 4102 strains DNA fingerprinted nationwide from 1992 to 2001. RESULTS: A specific strain of M. tuberculosis has emerged rapidly in Denmark: in 1992, the Danish Cluster 2 strain accounted for 5.8% of all culture-positive Danish-born cases, increasing to 29.0% in 2001. The Cluster 2 cases were on average younger (41.8 vs. 51.4 years), more likely to be male (81.4% vs. 64.1%), and more likely to have pulmonary involvement only (90.3% vs. 64.6%) than other Danish-born cases. During the first 4 observation years, they were mainly found in the capital city, Copenhagen, but were later increasingly observed in the provinces. CONCLUSION: The reasons for the increasing dominance and change in geographical distribution of Cluster 2 strains in Denmark is unknown, but may be partly explained by the fact that Cluster 2 is associated with younger males with pulmonary disease manifestation. We consider it as an outbreak and believe the situation requires increased focus on early tuberculosis diagnosis and control of transmission in Denmark.