The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has defined stage 1 chronic obstructive pulmonary disease (COPD) as forced expiratory volume in one second/forced vital capacity (FEV1/FVC)% <70% and a FEV1% predicted of >80%. Stage 2 has been defined as FEV1/FVC <70% and a FEV1% pred of <80%. The authors examined the extent of COPD misdiagnosis using this definition in healthy, never-smoker, asymptomatic adults aged >70 yrs in Bergen, Norway. A respiratory questionnaire was mailed to a random sample of 2,871 persons aged>70 yrs. In a random, well-defined subgroup of 208 never-smoker respondents with no current respiratory disease and significant dyspnoea or heart disease/hypertension complicated with dyspnoea, 71 were able to perform an acceptable spirometry. Approximately 35% of these healthy, elderly never-smokers had an FEV1/FVC% of <70% and would be classified as having at least a stage 1 COPD. This percentage increased with age and in those aged >80 yrs ∼50% would be classified as having COPD and approximately one-third would have an FEV1of <80% pred (stage 2 COPD). The estimated 5th percentile of FEV1was consistently <80% pred.The Global Initiative for Chronic Obstructive Lung Disease criteria will probably lead to a significant degree of over-diagnosis of chronic obstructive pulmonary disease in those aged >70 yrs. The criteria used to define the various stages of chronic obstructive pulmonary disease need to be age-specific.

There is evidence of a hereditary component in chronic obstructive pulmonary disease (COPD). A number of genetic association studies have been performed to find susceptibility genes of COPD.The current authors performed a case-control, genetic-association study and a meta-analysis of 16 studies, involving seven polymorphisms in three well-studied genes: microsomal epoxide hydroxylase (EPHX1); tumour necrosis factor; and b 2 -adrenoreceptor. A total of 492 Caucasian smokers and former smokers were recruited from hospital databases and population cohort studies.In the present study, a protective effect of the EPHX1 Tyr113His polymorphism was found (homozygous odds ratio (OR) 0.5). In the meta-analysis, homozygotes for this single nucleotide polymorphism (SNP) also had a pooled OR of 0.5. The same effect has been found in several lung cancer studies. Effects for other candidate SNPs were weak or statistically insignificant, and probable genotyping error was common.In conclusion, the present data and meta-analysis support a role for microsomal epoxide hydroxylase in the aetiology of chronic obstructive pulmonary disease.

The objectives of this study were to examine within and between individual variation detected during forced expiratory (FE) and forced inspiratory (FI) manoeuvers in a general population and to investigate the dependence of these variables on age, body size, and gender. A random sample of asymptomatic never smokers who had never been exposed occupationally to quartz or asbestos and who were living on the south-western coast of Norway were examined by spirometry; 81% of the individuals invited to attend did so. Of the 488 subjects between 18 and 73 years of age, 98% contributed three acceptable recordings for forced expiratory vital capacity (FVC) and one-second forced expiratory volume (FEV1), 94% contributed three acceptable recordings for forced inspiratory vital capacity (FIVC) and 85% contributed three acceptable recordings for one-second forced inspiratory volume (FIV(1)). The within-subject variation increased with body height and was considerably larger for FIV(1) than for FVC, FEV(1) or FIVC. A four-parameter model of pulmonary function measurement divided by height squared, including a gender term and a linear and quadratic term of age, fit the median of the observed values well. The residuals had a close-to-normal distribution, and the fifth-percentile values were estimated as the lower limit of normal. The peak value of dynamic lung volumes was observed into the middle of the fourth decade of life, and the decline thereafter did not differ greatly between the genders or among the different indices. The forced inspiratory volumes are the first reported in any reference population.

H Hi ig gh h--d do os se e i in nh ha al le ed d s st te er ro oi id ds s i in n a as st th hm ma at ti ic cs s:: m mo od de er ra at te e e ef ff fi ic ca ac cy y g ga ai in n a an nd d s su up pp pr re es ss si io on n o of f t th he e h hy yp po ot th ha al la am mi ic c--p pi it tu ui it ta ar ry y--a ad dr re en na al l ( (H HP PA A) ) a ax xi is s J. Boe*, P. Bakke**, T. Rødølen + , E. Skovlund ++ , A. Gulsvik**, The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l·min -1 ) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2 -agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone.We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.

Chronic obstructive pulmonary disease (COPD) is characterised by chronic and progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell activation.Genetic association between nine CTLA4 single nucleotide polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896 individuals) from the International COPD Genetics Network (ICGN) population. We then replicated the associations in 342 COPD subjects with chronic bronchitis and 511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based association tests were used to analyse the ICGN cohort, and a logistic regression model was used for the Bergen cohort.Six CTLA4 SNPs were significantly associated with chronic bronchitis in the ICGN cohort (0.0079fpf0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325fpf0.0408). One of these replicated SNPs (rs231775) encodes the Thr to Ala substitution at amino acid position 17. Haplotype analyses supported the results of single SNP analyses.Thus, CTLA4 is likely to be a genetic determinant of chronic bronchitis among COPD cases.