Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST).

BACKGROUND: The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. METHODS: This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. RESULTS: At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. CONCLUSIONS: Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.

Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells.

AIMS/HYPOTHESIS: IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1beta-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45beta (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study was to investigate if Gadd45b prevents IL-1beta-induced beta cell MAPK signalling and apoptosis. MATERIALS: Rat insulinoma INS-1E cells and mouse beta-TC3 cells stably expressing Gadd45b were generated. The effects of Gadd45b expression on signalling by JNK, ERK and p38 were assessed by Western blotting and kinase assays. Apoptosis rate was measured by terminal deoxynucleotidyl-mediated dUTP-biotin nick end-labelling (TUNEL) and an ELISA designed to detect apoptotic nucleosomes. Expression of endogenous Gadd45b mRNA was measured by RT-PCR. RESULTS: In INS-1E and beta-TC3 cells, expression of Gadd45b inhibited IL-1beta-induced activation of JNK and ERK, but augmented IL-1beta-mediated p38 activity. IL-1beta-induced nitric oxide production and decreases in insulin content and secretion were reduced by GADD45beta. IL-1beta-induced apoptosis was reduced by GADD45beta by up to 77%. Although IL-1beta stimulated the time-dependent induction of endogenous Gadd45b in INS-1E cells and rat islets, expression levels were lower in these cells than in IL-1beta-exposed NIH-3T3 and 3DO T cells. CONCLUSIONS/INTERPRETATION: Inadequate induction of Gadd45b, which encodes a novel beta cell JNK and ERK inhibitor, may in part explain the pro-apoptotic response of beta cells to IL-1beta.

Unchanged acetylation of isoniazid by alcohol intake.

SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.

[Smoking cessation in patients with severe irreversible chronic obstructive pulmonary disease, "smoker's lung"]. / Rygestop hos patienter med svaer grad af irreversibel kronisk obstruktiv lungesygdom, "rygerlunger".

A one year prospectively recorded material of 80 patients with severe chronic obstructive pulmonary disease (COPD) (FEV-1 < 40% predicted), only one never smoker and 26 ex-smokers, were included in the study. The 53 smokers were offered a smoking cessation program. Fifty-three of the total were alive after one year, including 16 of the ex-smokers. Twenty-one (57%) of the 37 surviving smokers had quit smoking (carbon monooxide in expired air < 10 ppm), whereas 16 (43%) still were smoking. FEV-1 increased by median 100 ml among both the quitters (p < 0.01), and the ex-smokers (p < 0.02), whereas FEV-1 declined by 50 ml (p > 0.05) among those who continued to smoke. There were more deaths among the sustainers than among the quitters (p < 0.05). Taking into consideration the many sources of bias in this small, uncontrolled study it seems as if smoking cessation prevents loss of lung function and perhaps even death among patients with advanced degree of smoker's lung.

Radiographic spectrum of adult pulmonary tuberculosis in a developed country.

SETTING: Bispebjerg Hospital, Department of Pulmonary Medicine P. The referral centre of adult tuberculosis in the municipality of Copenhagen, Denmark. OBJECTIVE: To evaluate the radiographic spectrum of pulmonary tuberculosis (TB) in adults in a low-prevalence country and to correlate radiographic appearances with bacteriological results, clinical and demographic data. DESIGN: Retrospective review of medical files on 548 cases with pulmonary TB according to the criteria of WHO. RESULTS: Usual radiographic pattern of reactivating TB, with upper lobe involvement, was found in 92% (n = 504), eight percent (n = 44) showed unusual X-ray patterns for adults, such as isolated lower lobe infiltrations (n = 19), hilar adenopathy (n = 10), miliary TB (n = 7), tuberculoma (n = 2), pleural effusion (n = 1) and normal chest X-ray (n = 3). Eight-nine percent of cases with cavitary lesions were positive by microscopy. CONCLUSION: The risk of missing a diagnosis of pulmonary TB may be high if patients present with an X-ray unusual for TB, but this is fortunately seen only in 8% of cases of pulmonary tuberculosis. Unusual X-ray is more commonly found in patients with concomitant disease, such as diabetes and cancer. If chest X-ray shows cavities, but the smear is negative for Mycobacterium, TB is unlikely and further diagnostic procedures should be performed without waiting for culture results.

Tracheobronchopathia osteochondroplastica.

A case of tracheobronchopathia osteochondroplastica (TO) was diagnosed in a 68-year-old male with prolonged cough. A bronchoscopy revealed multiple nodular excrescences along the anterolateral wall of the trachea and main bronchi. Tissue specimens showed pronounced change of bronchial cartilage with massive mineralization diagnostic for TO. The literature on the subject is reviewed here. The aetiology and pathogenesis is unknown. The severity of TO range from no symptoms to severe dyspnoea, haemoptysis or pneumonitis. Treatment is seldom necessary. However, in severe cases, bronchoscopic removal of obstructing excrescences and surgery has been performed with therapeutic effect. Differential diagnosis of nodular excrescences includes amyloidosis, endobronchial sarcoidosis, calcificating lesions of tuberculosis, papilomatosis and tracheobronchial calcinosis. Awareness of the condition as a differential diagnosis to neo-plasms is important, to avoid unnecessary surgery or chemotherapy.

Liver cancer among employees in Denmark.

To test the hypothesis that occupational exposure to chemical agents-particularly organic solvents in certain industries-may cause primary liver cancer (PLC), a nested case-control study of PLC cases from the Danish Cancer Registry and an age- and sex-stratified random sample of controls from the Central Population Register in Denmark were linked with files of a national supplementary pension fund. Employment histories since April 1964 were obtained for 973 cases histologically classified as hepatocellular carcinoma, cholangiocarcinoma, or combined hepatocellular and cholangiocarcinoma and 15,348 controls. Men from 35 different industrial branches, women from 7 branches, and both men and women from 3 branches had an excess risk of PLC, with an odds ratio of (OR) > 1.0; 29 branches had an OR of liver cancer in excess of 3.0. Women from bookprinting and offset printing industries had an OR above 10. Only male farmers had an OR below unity (0.41). Employees from breweries, restaurants, hotels, motels, and distilleries had an increased OR of both PLC and esophageal cancer.

Liver injury during antituberculosis treatment: an 11-year study.

SETTING: Bispebjerg Hospital, Department of Pulmonary Medicine, tuberculosis referral center for the Municipality of Copenhagen. OBJECTIVE: To evaluate routine procedure for the management of liver injury during antituberculosis treatment. DESIGN: From 1983-1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with standard Danish treatment for tuberculosis. From 1983-1986 they received a three-drug (9-month) regimen and from 1986-1993 a four-drug (6-month) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinamide. Data from a retrospective chart review. RESULTS: An increase in aspartate aminotransferase (AST) of more than twice the upper limit of normal (ULN) was recorded in 127 patients (16%). 66 had elevated AST before treatment; most of these were men with a daily alcohol consumption in excess of 60 g. In the remaining 61 patients (8%) AST increased during antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 x ULN (range 2-25 x ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reintroduce it fully in 14 (12 excessive alcohol consumers). Only 16 patients (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P < 0.05), seven were jaundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was confirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepatotoxicity. CONCLUSION: In spite of an increase in AST levels to approximately 6 x ULN during antituberculosis treatment, the drugs can be continued or reintroduced in full in most cases. Risk factors of hepatotoxicity included old age, female sex and extensive tuberculosis, and not alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.

Antipyrine clearance and metabolite excretion in Saudi patients with non-alcoholic chronic liver disease.

In this report, we examined the hepatic microsomal enzyme activity in 34 Saudi patients with chronic liver disease (CLD) and in 21 healthy Saudi subjects by measuring antipyrine clearance (APCI) and the fraction (%) of antipyrine (AP) dose excreted in urine unchanged (fAP) and in the form of its main metabolites: 3-hydroxymethylantipyrine (fHMAP), norantipyrine(fNORAP), and 4-hydroxyantipyrine (f4OHAP). While APCI, fHMAP, fNORAP, f4OHAP were significantly reduced in patients with CLD, fAP was significantly higher in these patients. Correlation was observed between serum albumin and APCI, fHMAP, fNORAP, or f4OHAP and between each two of the last three variables. We conclude that Saudis with CLD have uniform rather than selective reduction of hepatic microsomal enzyme activity and that serum albumin is a sensitive indicator of this activity.

Relationship between antipyrine metabolism and acetylation phenotype in health and chronic liver diseases.

The authors examined the activity of N-acetyltransferase and that of microsomal P-450 isoenzymes in health and hepatic disease state by determining the acetylation phenotype and the total (CLAP) and metabolic clearances of antipyrine to form norantipyrine or N-demethylantipyrine (MCLnora), 3-hydroxymethylantipyrine (MCLhma), and 4-hydroxyantipyrine (MCLha) in 21 healthy subjects and in 33 patients with chronic liver diseases (CLD) and investigated the relationship between the activities of these two enzyme systems. The acetylation phenotype was determined according to the urinary caffeine metabolites test. The mean and (SEM) of CLAP, MCLhma, MCLha, and MCLnora in healthy subjects were 2.42 (0.264), 0.193 (0.031), 0.322 (0.045), and 0.288 (0.04) L/h, and those observed in patients with CLD were 0.98 (0.1), 0.076 (0.015), 0.131 (0.026), 0.103 (0.022) L/h, respectively. The prevalence of fast acetylation among the healthy subjects and patients with CLD was 38% and 39%, respectively. Although all metabolic clearances appear to be reduced in healthy slow acetylators, the reduction was only significant in MCLnora, indicating a direct association between the activity of N-acetyltransferase and that of P-450 IIIA3 responsible for the N-demethylation of antipyrine. Conversely, slow acetylators with CLD exhibited significantly higher CLAP and near-significantly larger metabolic clearances including MCLnora, which suggests that P-450 activity in fast acetylators is more sensitive to chronic liver diseases than in slow acetylators.

Nasal or oral oil application on infants: a possible risk factor for adult bronchiectasis.

Lipid pneumonia has been observed in infants exposed by inhalation of oil or butter applied into the nose or throat as part of an old custom. We performed a case-control study to test the hypothesis, that this ancient tradition may be a predisposing factor to bronchiectasis. A case group of 59 patients with bronchiectasis and three control groups -46 patients with COPD, 32 asthmatics, and 71 healthy Saudis-were questioned about possible risk factors of bronchiectasis including nasal or oral application of oil/butter at infancy. The risk of witnessed exposure to this old folk remedy was significantly higher among the cases than the controls (OR = 3.9 (1.7-8.8), (95% confidence interval) p < 0.001). Application of oil or butter into the nasal or oral cavity of infants may be a risk factor for bronchiectasis.

[Exposure to passive smoking of hospital employees and attitude to smoking at workplaces in 1992]. / Hospitalsansattes udsaettelse for passiv rygning og holdning til rygning på arbejdspladsen 1992.

The aim of the study was to investigate exposure to passive smoking at work and the attitudes towards smoking at work among Danish hospital employees. It was carried out as a cross-sectional questionnaire study in collaboration with Bispebjerg Hospital and Tobaksskaderådet, to which 3154 (84%) employees responded. Results showed that 40% of the employees were exposed to passive smoking at work. Fifty-seven percent of the non-smokers and 14% of the smokers had symptoms associated with exposure to tobacco smoke. Every third employee complained of headache, coughing, eye irritation or breathlessness, and most were worried about the possible long term impact on health of passive smoking. In conclusion, surprisingly many employees are unwillingly exposed to the effects of passive smoking during working hours. Rules on smoking restriction are needed at the Danish health institutions to ensure the right to work in an environment free of tobacco smoke.

[Smoking habits among hospital employees in 1992]. / Rygevaner blandt hospitalsansatte 1992.

The aim of the study was to investigate the smoking habits of employees of a Danish hospital on the basis of a questionnaire given in October 1992 and compare the results with two similar previous studies of smoking habits among the Danish population (1991) and physicians and nurses (1989). It was performed as a cross-sectional questionnaire study in collaboration with Bispebjerg Hospital and Tobaksskaderådet. Three thousand one hundred and fifty-four (84%) employees responded. The results showed that 37% of male and 33% of female employees were daily smokers. The prevalence of smokers and the distribution of smoking habits according to social class of the employees were equal to the general population except for male physicians and female nurses where the prevalence of smokers was lower than the corresponding social classes. Female doctors smoked as much as class I from the population study. Twenty-two percent of male and 17% of female employees smoked 15 cigarettes a day or more (heavy smokers). Eighty-seven percent of the smokers smoked at work, and one-third smoked more than five cigarettes on each workday. It is concluded that the smoking habits of Danish hospital employees correspond to the smoking habits of the general population. Rules on smoking restriction in Danish hospitals are needed. The smoking habits of female doctors calls for attention.

Hepatotoxicity caused by the combined action of isoniazid and rifampicin.

A 35 year old black Somalian woman with miliary tuberculosis developed hepatotoxicity after a few days of treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol. After withdrawal of all drugs the liver profile returned to normal and remained so after challenge with isoniazid. Hepatotoxicity recurred when rifampicin was added, but it was well tolerated when reintroduced without isoniazid.