Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients.

OBJECTIVES: The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD. METHODS: This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination. RESULTS: A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartile-range: 427-1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2-3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3-3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients 'ever colonized' with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization. CONCLUSIONS: COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142).

Impact of contact investigation and tuberculosis screening among high-risk groups in Denmark.

SETTING: The objective of tuberculosis (TB) screening in low-incidence countries is to identify TB patients earlier, ideally to improve health outcomes and reduce Mycobacterium tuberculosis transmission. In this retrospective study, we compare hospitalisation (morbidity) and smear positivity rates (infectiousness) in TB patients identified through active case finding (ACF) with patients identified through passive case finding (PCF). METHODS: ACF patients were identified by screening socially marginalised persons or through contact investigation. Logistic regression was used to model the associations between case-finding group (ACF/PCF) and hospitalisation, and between case-finding group and smear positivity rates. RESULTS: A total of 108 patients were identified through ACF and 332 through PCF. Thirty (27.8%) ACF patients and 153 (46.1%) PCF patients were hospitalised. In the adjusted models, ACF patients (OR 0.24, P 0.001) and ACF subgroups identified using mobile X-ray screening, spot sputum culture screening and contact investigation were significantly less likely to be hospitalised than PCF patients. Thirty-one (34.4%) ACF patients and 127 (50.4%) PCF patients were smear-positive. ACF patients (OR 0.30, P 0.001) and ACF subgroups identified through contact investigation and spot sputum culture screening were less likely to be smear-positive than PCF patients. CONCLUSIONS: These findings suggest that ACF reduces morbidity and infectiousness among TB patients, thereby potentially improving health outcomes and reducing transmission of M. tuberculosis.

Standardised mortality rates in females and males with COPD and asthma.

Mortality studies of males and females with chronic obstructive pulmonary disease (COPD) and asthma have suggested that females have a poorer prognosis than males, but the results are either not unanimous or based on poorly characterised patients. The current study analysed the mortality of 279 asthma patients and 869 COPD patients, who were seeking pension due to disability, and compared mortality rates with expected rates derived from the general population. The mean follow-up period was 13.3 yrs (range 2.5-22.4 yrs) during which time 96 (34.4%) and 671 (77.2%) deaths were identified among asthma and COPD patients, respectively. The average age at study entry was 46.8 and 56.6 yrs, and the average forced expiratory volume in one second (FEV1) was 68.8 and 44.1 % predicted in the two diagnostic groups. After adjustment for predictors of survival (age, FEV1 % predicted, chronic bronchitis, body mass index, smoking status, oral prednisolone, ischaemic heart disease, and cor pulmonale), the relative risk of death was 1.21 (95% confidence interval: 0.77-1.89) and 0.98 (0.83-1.16) in females compared with males, in asthma and COPD patients, respectively. The standardised mortality rate (SMR) for males was 1.54 (1.10-2.09) and 2.7 (2.5-3.0), and for females 1.91 (1.44-2.49) and 4.8 (4.2-5.4), in asthma and COPD patients, respectively. Direct comparison of the SMR of males and females showed that females had higher mortality than males, with a rate ratio of 1.24 (0.82-1.84) and 1.8 (1.5-2.0), in asthma and COPD patients, respectively. Poisson regression analysis with control for the confounders did not change this result. Females and males with the same level of obstructive lung disease appear to have the same level of mortality. However, using standardised mortality rates, females have a higher mortality than males, suggesting that the protective effect of being female is lost in chronic obstructive pulmonary disease patients.

Short-term reproducibility of computed tomography-based lung density measurements in alpha-1 antitrypsin deficiency and smokers with emphysema.

PURPOSE: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. MATERIAL AND METHODS: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. RESULTS: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. CONCLUSION: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency.

The protein and molecular characteristics of variants of the alpha1-antitrypsin (AAT) gene are described, and available data on the genetic epidemiology of AAT deficiency are presented.

Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries.

BACKGROUND: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. METHODS: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. RESULTS: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. CONCLUSIONS: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.

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.

Risk of hospital admission for obstructive pulmonary disease in alpha(1)-antitrypsin heterozygotes of phenotype PiMZ.

Whether subjects heterozygous for alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for development of obstructive pulmonary disease (OPD) has been discussed for the past three decades. Both cohort and case-control studies have reached different conclusions, with the major problems being small sample sizes. A cohort of heterozygotes with the phenotype PiMZ was retrieved from the Danish Alpha(1)-Antitrypsin Deficiency Registry. Ten matched controls for each PiMZ subject were identified from the files of the Danish Central Population Registry. Cases and controls were subsequently linked to the files of the Danish Hospital Discharge Registry, and relative risk for OPD was calculated. In the cohort of 1,551 PiMZ subjects (11,678 person-years), we identified 47 subjects with a discharge diagnosis of OPD, as compared with 206 subjects with this diagnosis in the control group (109,748 person-years), yielding a relative risk (RR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.0). This increased risk was present in both men and women and in all age groups; however, it was significant only in the age group from 40 to 79 yr. Of the 1,551 PiMZ subjects, 565 (36%) were first-degree relatives of PiZ index cases, and it appeared that only this group was at increased risk of hospital admission for OPD (RR: 3.4, 95% CI: 2.2 to 5.3). We conclude that alpha(1)-AT heterozygotes of phenotype PiMZ are at increased risk of hospital admission for OPD if they are first-degree relatives of PiZ index cases only, and that other, yet unknown genetic or environmental factors contribute to the development of lung disease.

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

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.

Transmitting genetic risk information in families: attitudes about disclosing the identity of relatives.

Attitudes about disclosing the identities of family members to a physician to ensure diffusion of genetic risk information within affected families were examined in a questionnaire study of Danish patients with alpha1-antitrypsin deficiency (A1AD), their relatives, and a control group of Danish citizens. The questionnaires were returned by 1,761 (82%) of 2,146 recipients; 1,609 (75%) agreed to participate and completed the questionnaire. Only 2.8% objected to disclosing the identity of children, 9.1% objected to disclosing the identity of parents, and 6.7% objected to disclosing the identity of siblings. When genetic tests are offered to a sister, 75.4% of screened individuals with severe A1AD (phenotype "piZ") and 66.8% of piZ probands thought that the physician should say who is ill. Important reasons for informing a sister at risk were, for 58%, the opportunity to prevent disease and, for 41% of piZ-probands, the opportunity to maintain openness in the family and to avoid uncertainty. Stepwise logistic regression of background variables showed that relatives were those for whom most respondents approved the disclosure of the parents' and siblings' identities to enable the physician to examine them for the presence of A1AD. Women were less prone to disclose the identity of siblings. The results indicate that the genetic counselor should inquire about relatives' identities, to ensure that they are properly informed about the known risk of severe genetic disorder, such as A1AD, for which disability can be prevented by a change of lifestyle or by careful management. Disease prevention is essential, but openness and avoidance of uncertainty in affected families are also important. Our findings imply that fully informing all relatives about the disorder and about who is actually ill should be the principal rule.

Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based study.

OBJECTIVE: We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barrett's esophagus, making them potential candidates for endoscopic surveillance. METHODS: Rates of esophageal and gastric cancers were collected from the Danish Cancer registry for the period 1970-1991. The registry was used to identify all cases of esophageal adenocarcinoma in the period 1987-1992. Medical records were retrieved and details concerning previous diagnosis of reflux disease and Barrett's esophagus were recorded. RESULTS: The age- and gender-adjusted incidence of esophageal adenocarcinoma increased eightfold, from 0.3/10(5)/yr in 1970 to 2.3/10(5)/yr in 1990. This increase could not be explained by changes in classification or diagnostic routines. Medical data were retrieved for 524 of the 578 cases of esophageal adenocarcinoma reported during the period 1987-1992. A history of reflux symptoms or a diagnosis compatible with reflux was reported in 113 of 524 patients. A total of 119 patients (23%) had previously been investigated for dyspepsia or reflux symptoms, most often by endoscopy. A previous diagnosis of Barrett's esophagus was found in only 1.3% of the cancer patients. CONCLUSIONS: The rate of esophageal adenocarcinoma in Denmark has increased eightfold over a 20-yr period, and this increase is not explained by changes in classification or diagnostic routines. More than 98% of esophageal adenocarcinomas were found in patients who could not have entered endoscopic surveillance, as Barrett's esophagus had not been diagnosed before the cancer diagnosis. Endoscopic surveillance to detect dysplasia may be an option for the individual patient with Barrett's esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population.

Cancer risk in close relatives of women with early-onset breast cancer--a population-based incidence study.

Inherited susceptibility to breast cancer is associated with an early onset and bilateral disease. The extent of familial risks has not, however, been fully assessed in population-based incidence studies. The purpose of the study was to quantify the risks for cancers of the breast, ovary and other sites of close relatives of women in whom breast cancer was diagnosed at an early age. Records collected between 1943 and 1990 at the Danish Cancer Registry were searched, and 2860 women were found in whom breast cancer was diagnosed before age 40. Population registers and parish records were used to identify 14 973 parents, siblings and offspring of these women. Cancer occurrence through to 31 December 1993 was determined within the Cancer Registry's files and compared with national incidence rates. Women with early-onset breast cancer were at a nearly fourfold increased risk of developing a new cancer later in life (268 observed vs. 68.9 expected). The excess risk was most evident for second cancer of the breast (181 vs. 24.5) and for ovarian cancer (20 vs. 3.3). For mothers and sisters, risks for cancers of the breast and ovary were significantly increased by two- to threefold. Bilateral breast cancer and breast-ovarian cancer were very strong predictors of familial risks, with one in four female relatives predicted to develop breast and/or ovarian cancer by age 75. Mothers had a slightly increased risk of colon cancer, but not endometrial cancer. The risk for breast cancer was also increased among fathers (standardized incidence ratio 2.5; 95% CI 0.5-7.4) and especially brothers (29; 7.7-74), although based on small numbers. The risk for prostatic cancer was unremarkable. In this large population-based survey, the first-degree relatives of women who developed breast cancer before age 40 were prone to ovarian cancer as well as male and female breast cancer, but not other tumours that may share susceptibility genes with breast cancer.

Self-reported smoking habits, biochemical markers, and nicotine dependence in a sample of the Danish population.

This study reports the smoking habits in a Danish population, evaluates plasma cotinine and thiocyanate levels in the detection of 'slips' (subjects participating in smoking cessation trials who begin to smoke a few cigarettes per week) and provides distribution scores on questionnaire measures of nicotine dependence. A total of 599 subjects with a mean age of 41 years participated in the study. Of these 46% were current smokers with no difference in the proportion of males(46%) and females(45%) and with a mean cigarette consumption of 12.7 daily. Plasma samples were analyzed for cotinine and thiocyanate, and the smokers completed two questionnaires to measure nicotine dependence: the Fagerström Tolerance Questionnaire and the modified Horn-Russell scale. The mean plasma cotinine was 207 micrograms/l for smokers, 14.4 micrograms/l for occasional smokers and 8.0 micrograms/l for non-smokers (ex-smokers and never-smokers). For plasma thiocyanate the levels were 130 mg/l, 54.8 mg/l, and 54.3 mg/l, respectively. The mean Horn-Russell score was 7.4 and the mean Fagerström score was 5.9. The two tests correlated with a t-value of 0.61 (p < 0.001) and the scores in both tests increased with increasing cigarette consumption. In conclusion, 75% of the smokers consumed 10 or more cigarettes per day and males smoked more cigarettes than females. It was impossible to distinguish occasional smokers (slips) from non-smokers using plasma cotinine or thiocyanate levels. We suggest that studies are needed to evaluate if light smokers benefit from nicotine replacement therapy because they achieve plasma cotinine levels which are similar to those seen when using patches for nicotine replacement therapy.

Clinical features and prognosis of life time non-smokers with severe alpha 1-antitrypsin deficiency.

BACKGROUND: The hereditary disorder alpha 1-antitrypsin deficiency is characterised by development of severe emphysema at an early age with smoking being the most significant additional risk factor. The purpose of the present paper was to analyse potential risk factors other than smoking for emphysema and to estimate the prognosis of life time non-smokers. METHODS: Patients were identified through the files of the Danish alpha 1-antitrypsin deficiency register which contains information on more than 700 persons with the condition. Many of the patients, the non-index cases, were identified from family studies. RESULTS: There were 75 life time non-smokers with PiZ (27 index cases and 48 non-index cases) aged 20 years or more at entry. Twenty one subjects died during the follow up period. The Standardised Mortality Ratio (SMR) was 3.0 (95% confidence intervals (CI) 1.9 to 4.6). There was no significant difference in SMR between males and females. The SMR was 8.8 (95% CI 5.0 to 14) for the index cases and 0.96 (95% CI 0.3 to 2.3) for the non-index cases based on five deaths. The overall mean % predicted forced expiratory volume in one second (FEV1) at entry was 83% with a significant difference between index cases (54%) and non-index cases (100%) (p < 0.001). The difference in the ratio of FEV1 to forced vital capacity (FVC) was also highly significant with values of 0.57 and 0.79 for index and non-index cases, respectively (p < 0.001). In the non-index group only three had an FEV1% predicted of less than 70%. CONCLUSIONS: Occupational exposure to airway irritants did not have any significant influence on the development of emphysema. Only a few life time non-smokers develop severe emphysema; most never develop pulmonary symptoms and thus remain undetected unless family members of index cases are screened.

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.

Risk of malignant neoplasms in patients with pulmonary sarcoidosis.

BACKGROUND: For over 20 years the association between sarcoidosis and malignancy, particularly lymphoma and lung cancer, has been disputed with misclassification being the major concern. The aim of the present study was to analyse the incidence of malignancies in a cohort of patients with sarcoidosis by linkage to a nationwide population based cancer register. METHODS: The cohort comprised 254 patients followed for a median of 25 years until death, emigration, or 31 December 1992, whichever came first. The expected number of cancer cases was calculated using the annual age and sex specific cancer rates from the Danish Cancer Registry. RESULTS: Thirty six cancers were registered, three of which were misclassified as sarcoidosis, leaving 33 cancers compared with 23 expected (standardised incidence ratio (SIR) = 1.4; 95% CI 0.99 to 2.0). Five lung cancers were observed compared with 2.5 expected, yielding an SIR of 2.0 (95% CI 0.7 to 4.7). There was no incidence of lymphoma and only one case of leukaemia. There was a significant excess number of pharyngeal cancers based on two cases (SIR = 15.4; 95% CI 1.7 to 56). CONCLUSIONS: This study does not support the theory of an association between sarcoidosis and malignancy, and the main reason other studies have shown such an association is most likely to have been due to selection bias and misclassification.

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.

Body mass index and mortality in patients with severe alpha 1-antitrypsin deficiency.

It appears that patients with advanced stages of chronic obstructive pulmonary disease, and particularly emphysema, lose weight and have higher mortality even after controlling for lung function. In the present study, mortality of alpha 1-antitrypsin-deficiency patients PiZ as a function of body mass index (BMI) with control for FEV1, sex and smoking habits was studied. A total of 342 patients participated with a mean follow-up time of 7.6 yr. Ninety patients had BMI under 20 kg m-2, which was the cut-off defining underweight patients. The patients were divided into three groups according to their initial FEV1 % predicted: < 30%, 30-64% and > or = 65%. The underweight patients had significantly higher mortality in the two groups with the lowest FEV1 % predicted. A Cox regression model was applied to control for potential confounders. The risk ratio for the underweight patients was 1.6 (P = 0.03) after controlling for FEV1, age, sex and smoking habits. It is concluded that low body weight is an independent predictor of mortality, but the reason is still unclear.

[Cancer in the parents of children with cancer]. / Cancer hos foraeldre til børn med cancer.

Certain types of cancer in children and young adults have been linked with an increased risk of cancer in close relatives. However, the relation between childhood cancer and familial risk remains to be fully assessed in population-based studies. We conducted a nationwide study in Denmark of 11,380 parents of children with cancer. The children were identified from records in the Danish Cancer Registry; their parents were identified from population registers. The occurrence and rate of cancer in the parents were determined with use of the Cancer Registry's files and compared with national incidence rates for various categories of tumour. Overall, 1445 cancers were diagnosed in the parents, as compared with 1496 expected from national incidence rates, to yield standardized incidence ratios of 0.97 (95 percent confidence interval, 0.92 to 1.02) for all parents, 0.99 for mothers, and 0.94 for fathers. The lower rate of cancer among fathers reflected their lower standardized incidence ratio for lung cancer (0.76; 95 percent confidence interval, 0.63 to 0.91), as calculated from 114 observations. Genetic determinants are important in several types of childhood cancer, but the genetic susceptibility to tumours does not generally extend to the parents of children with cancer, not do the patterns of incidence point to the influence of shared environmental factors. Thus, cancer in children should not be viewed as a general marker for an increased risk of cancer in the patient's parents.