HIV testing of patients diagnosed with tuberculosis increased in Denmark during the period from 2007 to 2009.

We examined the trends of HIV testing among patients notified with TB in Denmark during a 3-year period from 2007 to 2009. We were able to obtain HIV testing status for 96%. There was a significant increase of patients examined for HIV infection during the 3-year period. HIV prevalence among HIV-tested TB patients in Denmark is much higher than in the average population. It seems there is an increasing awareness in Denmark towards testing TB cases for HIV co-infection.

Clustered tuberculosis in a low-burden country: nationwide genotyping through 15 years.

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.

Attitudes toward an unsolicited approach in relation to status of genetic disease: exemplified by alpha(1)-antitrypsin deficiency.

Knowledge of a genetic disease in an individual raises the questions of whether and how this information should be communicated to his or her family. The aim of the present study was to provide factual information about attitudes towards an unsolicited approach from a physician regarding genetic counseling within affected families. We performed a questionnaire study among patients with alpha(1)-antitrypsin deficiency, their examined and unexamined relatives, and a control group of Danish citizens. Of 2,146 subjects, the questionnaires were returned by 1,761 (82%), and 1,609 (75%) wanted to participate. Stepwise logistic regression showed that phenotype/subgroup, having descendants, and being female were significantly related to the approval of an unsolicited approach and the informing of relatives. Provided it was difficult for the index case to inform relatives about their risk and about his/her disease, then a total of 75.8% would not proscribe an unsolicited approach by the physician. Most of those for proscribing an unsolicited approach found that relatives should be informed in advance by the index case. The control group of randomly chosen Danes was the most skeptical towards an unsolicited approach. Most individuals found that genetic risk information should be shared with relatives at-risk. A flexible information policy by the health care system based on active approach towards relatives is acceptable to 75 to 95% of individuals in order to ensure diffusion of genetic risk information within families segregating for a genetic disease with a modifiable outcome.

Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects.

In obstructive lung disease the annual change in lung function is usually estimated from serial measurements of forced expiratory volume in 1 s (FEV1). Frequent measurements in each patient may not improve this estimate because data are not statistically independent; i.e., the measurements are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self-administered spirometry. FEV1 measurements fulfilling standard criteria were detrended, and the autocorrelation profile and the power spectrum were calculated. On average the subjects were followed for >3 yr and performed >1,000 acceptable spirometries. The autocorrelation of FEV1 measurements in the emphysematous patients was approximately 0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of -0.1 at approximately 8 mo and then increased toward zero over the following 12 mo. The autocorrelation function in the two normal subjects showed a similar pattern, but with a faster decay toward zero. In the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We conclude that serial spirometric measurements show long-range correlations. The practical implication is that FEV1 need not be measured more often than once every 3 mo in studies of the long-term trends in lung function.

Multidrug-resistant tuberculosis in Denmark 1993-1995.

SETTING: All bacteriologically confirmed new cases of tuberculosis and treatment relapses in Denmark are examined for drug resistance. In the years 1993-1995, nine cases of multidrug-resistant tuberculosis (MDR-TB), all acquired outside Denmark, were identified among 1354 cases of tuberculosis. OBJECTIVE: To examine incidence, treatment and prognosis for patients with tuberculosis due to MDR Mycobacterium tuberculosis. DESIGN: Retrospective evaluation of routine data. RESULTS AND CONCLUSION: Multidrug resistance was present in less than one present of patients with tuberculosis. One patient died from tuberculosis without revision of treatment, and eight patients responded favourably to a regimen of pyrazinamide, streptomycin or amikacin, ofloxacin and cycloserine. In two patients, this regimen was supplemented with para-aminosalicylic acid and thiacetazone respectively. All patients needed prolonged hospitalization and had observed treatment. It is possible to cure such patients, but it is a lengthy and expensive process. It is expected that similar cases will be imported into the country and that they will occur within Denmark in the future.

Tuberculosis treatment in Denmark: treatment outcome for all Danish patients in 1992.

SETTING: Denmark. OBJECTIVE: To evaluate tuberculosis (TB) treatment outcome using treatment indicators recommended by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). DESIGN: Retrospective cohort analysis of all TB patients notified in 1992 (n = 350). TB related information was registered and analyzed using hospital case records and laboratory data from Statens Serum Institut, Copenhagen. RESULTS: Among the 350 TB patients, cure rate was 25.7%, treatment completion rate 36.0%, death rate 12.9%, failure rate 0.9%, defaulter rate 3.1% and transfer out rate 2.3%. The remaining 19.1% 'other cases' did not fulfil any of the WHO indicators, but could be included in the treatment completion rate. During the 4 year follow-up period, 3% of all patients relapsed and 15% died. CONCLUSION: The aim set by the WHO of a cure rate of at least 95% was not achieved. The two main reasons were 1) the fact that sputum samples were not taken late during treatment, and 2) the death rate. In the future sputum examination for M. tuberculosis late during treatment will be encouraged to obtain evidence of cure, but only if the patient can produce sputum, as examination of saliva is of no interest. Death from causes other than TB accounted for 8.3%, making it impossible to attain the desired cure rate in Denmark, and possibly also in other industrialized countries with many elderly TB patients. Additional information on risk factors and methodological issues in performing a TB cohort analysis in a low incidence country is presented.

A dominant Mycobacterium tuberculosis strain emerging in Denmark.

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.

Performance of whole blood IFN-gamma test for tuberculosis diagnosis based on PPD or the specific antigens ESAT-6 and CFP-10.

OBJECTIVE: To evaluate the QuantiFERON-TB test in BCG-vaccinated, non-BCG-vaccinated and tuberculosis (TB) patient donor groups, and to compare its diagnostic performance with that of a blood test based on the Mycobacterium tuberculosis specific antigens ESAT-6 and CFP-10. DESIGN: Analysis of the IFN-gamma responses of whole blood cells from BCG-vaccinated or non-BCG-vaccinated donors or patients with tuberculosis, stimulated with PPD, ESAT-6 or CFP-10 antigens, and evaluation of the specificity and sensitivity of the test. RESULTS: None of the non-vaccinated donors showed positive responses to M. tuberculosis-PPD, ESAT-6 or CFP-10. In BCG-vaccinated donors, 9/19 (47%) donors responded to the QuantiFERON-TB test based on M. tuberculosis-PPD, whereas 2/19 (10.5%) responded to either ESAT-6 or CFP-10. Comparable levels of sensitivity were obtained with the QuantiFERON-TB test based on M. tuberculosis-PPD (79%) and ESAT-6 or CFP-10 antigens (72%). CONCLUSION: Our results demonstrate that the whole blood test based on M. tuberculosis-PPD did not efficiently distinguish BCG-vaccinated donors from individuals with disease due to M. tuberculosis. The introduction of new recombinant antigens specific for M. tuberculosis, such as ESAT-6 or CFP-10, should increase the specificity of the whole blood test and enable discrimination between TB infection, atypical mycobacterial reactivity and reactivity due to BCG vaccination. Such a test would provide a quantum improvement over the current practice of using the tuberculin skin test for TB control and elimination.

A prospective evaluation of the clinical value of nation-wide DNA fingerprinting of tuberculosis isolates in Denmark.

SETTING: Denmark, a country with a low incidence of tuberculosis (TB). OBJECTIVE: To evaluate the value of the nation-wide DNA fingerprinting of Mycobacterium tuberculosis isolates performed in Denmark since 1992. DESIGN: Prospective study of consecutive patients with culture-verified TB from five large TB Departments in Denmark during a 7-month period in 1998. Results of IS6110 RFLP and spoligotyping were compared to those in the nation-wide Danish DNA-fingerprint database which covers approximately 95% of all culture-verified TB cases from 1992 onwards. Questionnaires asking about contact tracing and epidemiological links were sent to the patients' treating physicians. RESULTS: Of the 177 patients included in the study, 57 were Danes, one was from Iceland, 111 were immigrants, and eight were from Greenland. Responses to the questionnaires were obtained from 163 patients (92%). Four cases of unsuspected transmission were detected: one of nosocomial spread of TB, one of occupational acquisition of TB and two of transmission in an international school, leading to further contact tracing among 75 schoolchildren. These four cases were all the result of short-term contacts. In 22 cases, contact with one or more TB patient(s) was reported. In six of these, the DNA-fingerprint result revealed that the presumed contact could not be the source of infection, even though in two of the cases the known TB contact was from the household. CONCLUSION: Nation-wide DNA fingerprinting of TB isolates provides information that could not have been obtained otherwise, and contribute to the understanding of TB transmission in Danish society. In some cases the results lead to further contact tracing. Short-term contact can apparently result in transmission of TB.

Tuberculosis in a cohort of Vietnamese refugees after arrival in Denmark 1979-1982.

SETTING: Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. OBJECTIVE: To study the occurrence of tuberculosis (TB) in a cohort of immigrants from a high incidence country during the years following arrival in a low incidence country. DESIGN: Follow-up analysis in a cohort of 1983 Vietnamese refugees who arrived in Denmark during the period 1979-1982. The civil registration number could be identified for 1936 (98%) individuals from the original cohort. Date of possible death, emigration and the development of tuberculosis were determined by checking the refugees' civil registration number in the National Civil Register and the National Infectious Disease Registry for Tuberculosis. RESULTS: Tuberculosis notification for the 1936 individuals fell from 1.14% for the first 12 months to a mean of 0.08% per year during the following 5-year period. During the 16 years of follow up, 36 of the refugees developed tuberculosis, of whom 14 (39%) had had abnormal chest X-ray on arrival and 14 (39%) (including one with normal chest X-ray) had been identified as having active tuberculosis through screening on arrival. CONCLUSION: Decline in tuberculosis incidence for immigrants is very rapid if the tuberculosis infection rate is low following arrival. With a very limited TB screening programme (chest X-ray on arrival) and a passive diagnosis policy without preventive chemotherapy, it is possible to control tuberculosis among high prevalence immigrants in a low incidence country.

Diagnostic strategy for pulmonary tuberculosis in a low-incidence country: results of chest X-ray and sputum cultured for Mycobacterium tuberculosis.

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.

Intermediate alpha 1-antitrypsin deficiency PiSZ: a risk factor for pulmonary emphysema?

It is well documented that the severe hereditary disorder alpha 1-antitrypsin deficiency (alpha 1ATD) PiZZ is a strong risk factor for emphysema, especially among smokers, but the role of intermediate alpha 1ATD PiMZ and PiSZ in the development of emphysema remains uncertain. In this study, we have evaluated mortality and lung function of 94 persons with intermediate alpha 1ATD PiSZ of whom 66 were non-index cases, i.e. persons ascertained through family studies. The index cases and the non-index cases were similar with respect to sex, age and follow-up time, but differed in smoking habits and FEV1. Among the smokers there was no significant difference in pack-years between index cases and non-index cases. The overall Standardized Mortality Ratio (SMR) was 1.6 (95% confidence intervals (CI): 0.8-2.7). For the index cases the SMR was 4.3 (95% CI: 1.9-8.5) and for the non-index cases it was 0.8 (95% CI: 0.3-1.8). In the index group six patients died of pulmonary emphysema, one of pulmonary fibrosis, and one of colon cancer. In the non-index group two died of pulmonary emphysema, two of pneumonia, and one of cerebral haemorrhage. The mean initial FEV1% predicted among the index cases was 59% compared with 94% among the non-index cases. Based on the analysis of the non-index cases it is concluded that only a small fraction of persons with the PiSZ phenotype are at increased risk of developing pulmonary emphysema, and at an older age than persons with the PiZ phenotype.

Patient-administered sequential spirometry in healthy volunteers and patients with alpha 1-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.

[When can tuberculosis be eradicated in Denmark?]. / Hvornår kan tuberkulose vaere udryddet i Danmark?

Eradication is here defined as a tuberculosis (tbc.) incidence below one case of contagious tbc. per million per year and a Mycobacterium tuberculosis (Mt) infection prevalence of 1% or lower and declining. The situation is evaluated separately for Danes and foreigners. Late cases of tbc due to Mt infection more than five years earlier will decline with declining Mt infection prevalence over 50 years. Early tbc. due to Mt infection within five years can with good case finding, effective treatment, and contact examination be kept at a level of 33% of late cases. Relapses are now 15% of all cases and will also decline relatively. HIV/tbc. will only be a limited problem for a few years due to a low Mt infection prevalence. Continued limited immigration will only have minor influence on tbc. among Danes. Tbc. in immigrants already living in Denmark will decline over 10-20 years to around 20/100,000 but can not be eradicated in first generation immigrants. MT resistance will not be of importance for eradication. It is estimated that only major social disasters will be able to prevent eradication of tbc. among Danes by 2040.

[Extrapulmonary tuberculosis in Denmark. A review of the incidence, localization and therapy]. / Ekstrapulmonal tuberkulose i Danmark. En oversigt over forekomst, lokalisation og behandling.

In Denmark, just under 20% of tuberculosis (TB) cases amongst Danes and 25-30% of cases amongst people of foreign nationalities are made up of isolated extrapulmonary (EP) TB. The incidence among Danes is falling, whereas an increasing amount of EP TB cases are found among foreigners due to continued immigration, and these now constitute 50% of all cases of EP TB. EP TB is found among older Danes and younger foreigners. The HIV/AIDS epidemic has not had any effect on the incidence of TB and EP TB in Denmark. EP TB is most frequently found in lymph nodes and the urogenital system. Since the disease is rare, it may be overlooked; it should be considered as a differential diagnosis in unresolved cases, particularly in immigrants from countries with a high prevalence of TB. Treatment is as for pulmonary TB, namely "four drug" therapy for six months. Surgical intervention is rarely required. Supplementation with oral steroids may be useful in very special cases.

[Therapeutic strategies for patients with tuberculosis]. / Behandlingstilbud til tuberkulosepatienter.

OBJECTIVES: To determine the effectiveness of strategies used to promote adherence to anti-tuberculosis treatment. SEARCH STRATEGY: MEDLINE 1966-1996 (August), Cochrane Collaboration Trials Registers (October 1996), LILACS 1982-1996 (September); reference lists in articles on adherence, contact with experts in the fields of TB and adherence research. SELECTION CRITERIA: Randomised or pseudo-randomised controlled trials of interventions to promote compliance with curative or preventive chemotherapy for TB, with at least one measure of adherence. DATA COLLECTION AND ANALYSIS: Data on study methods, participants, interventions and outcomes were collected for each study and methodological quality was assessed. Estimates of effect were assessed for categorical outcomes using the Peto odds ratio, with 95% confidence intervals. MAIN RESULTS: Strategies found to be of benefit were reminder cards sent to defaulters, assistance of patients by lay health workers, monetary incentives offered to patients, and increased supervision of TB clinic staff. It is not possible to determine from current trials whether health education by itself leads to better adherence to treatment. Even though directly-observed therapy (DOT) is widely advocated as the most cost-effective means of ensuring completion of TB treatment, no completed trials could be found which confirm or refute this view. CONCLUSIONS: RCT evidence exists that certain strategies improve adherence to anti-tuberculous therapy, and these should be adopted into clinical practice depending on their appropriateness to practice circumstances. Further innovations should be tested to find solutions that will be useful in low income countries. Randomised trials evaluating the independent effects of directly-observed therapy (DOT) are awaited.

[Multiresistant tuberculosis in Denmark 1993-1996]. / Multiresistent tuberkulose i Danmark i årene 1993-1996.

Infections with multiresistant tubercle bacilli have also become a problem in the rich part of the world. The reasons are lack of compliance in patients with life style problems and ineffectiveness of the health system due to lack of fundings. During a four year period, 1993-1996 ten patients were seen in Denmark with tuberculosis due to multiresistant Mycobacterium tuberculosis. Nine were infected abroad, one developed MDR-TB during treatment in Denmark. It is possible to cure these patients, but it is expensive and takes a long time. In the future more cases created within Denmark are likely to be seen due to lack of funding for the tuberculosis programme and, depending on immigration, further cases created abroad are expected.

[Survival of patients with severe alpha 1-antitrypsin deficiency]. / Overlevelse for patienter med svaer alpha 1-antitrypsinmangel.

Previous estimates of survival of patients with alpha-1-antitrypsin deficiency (alpha 1ATD) have been based on selected patients. In this paper we have compared the survival of 397 patients with severe alpha-1-antitrypsin deficiency either ascertained because of pulmonary impairment (index cases) or ascertained through family studies (non-index cases). The patients were drawn from the nationwide Danish alpha 1ATD register. The overall median survival was 54.5 years with no significant difference between males and females. Survival for index cases was less than for the non-index cases regardless of smoking history (49.4 years and 69.3 years respectively). When we analyzed index cases and non-index cases separately there was no difference between the survival of smokers and never-smokers in the index group. In the non-index group smokers had a shorter survival than never-smokers. The survival of non-index never-smokers was similar to the survival of the normal Danish population. We conclude that the prognosis of severe alpha 1ATD is better than previously assumed, and that although smoking is a major risk factor the development of emphysema in patients with severe alpha 1ATD is multifactorial.

[Pulmonary function and survival of patients with alpha 1-antitrypsin deficiency, residents of Copenhagen]. / Lungefunktion og overlevelse hos patienter med alfa 1-antitrypsinmangel bosiddende i København.

From 1976 to 1987 alpha 1-antitrypsine deficiency type PiZZ was diagnosed in 89 patients living in the Copenhagen urban area (mean age: 45 years). Spirometry was performed yearly in 66 of these patients (mean observation period was 50 months). At the time of diagnosis basic FEV1 was significantly lower in smokers and ex-smokers than in patients who had never smoked (45%, 44% and 84% of predicted normal, respectively). However, the decline in FEV1 was similar (3% per year) in all three categories of smokers. Our results indicate that both smokers and non-smokers are at risk of developing pulmonary emphysema, however, the disease usually appears later in life or not at all in non smokers.

[New therapeutic possibilities in alpha 1-antitrypsin deficiency]. / Nye behandlingsmuligheder ved alfa 1-antitrypsinmangel.

The alpha-1-antitrypsin gene is localized to chromosome 14. Numerous genetic variations may occur and some of these result in severely reduced concentration in the serum. The commonest cause of severe deficiency of alpha-1-antitrypsin is the gene-variant Z in the homozygotic form which occurs in one out of 2,000 Danes. Severe deficiency in alpha-1-antitrypsin results in liver symptoms in approximately 10% of the children. Some of these will develop cirrhosis of the liver. In adults at the ages of about 30 to 40 years, gradual development of emphysema occurs and this is earliest and most pronounced in smokers. Adults have also increased frequency of cirrhosis but this is much less pronounced than the development of emphysema. In addition to a number of theoretical therapeutic possibilities, liver transplantation is now possible and this is employed particularly in children with cirrhosis. In young persons with terminal pulmonary insufficiency with anticipated survival for less than one year, heart/lung transplantation or possibly isolated lung transplantation may be considered. An alpha-1-antitrypsin concentrate has been produced. Intravenous dosage once monthly can provide a concentration in the serum for three to four weeks which, as a rule, suffices to prevent emphysema. It is not yet known whether this treatment has any prophylactic effect in cases of developed emphysema. It is to be anticipated that treatment instituted prior to development of emphysema will prevent development of pulmonary disease but the treatment is rather expensive and must, probably, continue throughout life. No controlled investigation of the effect of treatment is available and the range of indications is not defined.