Physical activity and sedentary behaviour: applying lessons to chronic obstructive pulmonary disease.

In health and disease, the benefits of regular participation in moderate to vigorous intensity physical activity are well documented. However, individuals with chronic conditions, such as those with chronic obstructive pulmonary disease (COPD), typically do very little activity at a moderate or vigorous intensity. Much of their day is instead spent in sedentary behaviour, such as sitting or reclining, which requires very little energy expenditure. This high level of time spent in sedentary behaviour can have serious health consequences, including increased risk of diabetes, cardiovascular disease and premature mortality. There is emerging evidence to suggest that participation in light intensity physical activities (e.g. standing or slow walking) may have benefits for cardio-metabolic health. Given the low aerobic capacity of individuals with moderate to severe COPD, increasing light intensity activity (through reducing sedentary time) may be a feasible additional strategy to improve health in this population, alongside traditional recommendations to increase the time spent in moderate to vigorous intensity physical activity. This review provides an overview of physical activity and sedentary behaviour, with a particular emphasis on these behaviours for people with COPD. It provides suggestions for the measurement of these behaviours within the clinical setting, as well as for interventions that may be effective at increasing physical activity and reducing sedentary behaviour in this population.

Relationship between body composition, peripheral muscle strength and functional exercise capacity in patients with severe chronic obstructive pulmonary disease.

The influence of body composition and peripheral muscle strength on 6-minute walk distance was assessed by performing dual energy X-ray absorptiometry scanning, spirometry and dynamometry testing in 13 men and 13 women with severe chronic obstructive pulmonary disease. Multivariate modelling showed that 76% of the variance in 6-minute walk distance could be explained by an equation incorporating lung function, quadriceps strength and lean leg mass. These findings indicate an important role for lower limb strength measures in pulmonary rehabilitation training programmes.

Measurement properties of the 6-min walk test in individuals with exercise-induced pulmonary arterial hypertension.

BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPAH) is associated with reduced peak exercise cardiac output (CO) and aerobic capacity (peak ). We investigated the validity of the encouraged 6-min walk test (6MWT) to identify exercise limitation and estimate aerobic capacity in subjects with EIPAH. METHODS: Seventeen subjects with EIPAH (56 ± 14 years, 15 women) and 20 healthy controls (57 ± 13 years, 19 women) underwent two encouraged 6MWTs and a symptom-limited cardiopulmonary exercise test (CPET). To measure central haemodynamics, subjects with EIPAH performed the CPET with a pulmonary artery catheter in situ. RESULTS: Compared with controls, subjects with EIPAH had reduced peak (1.2 ± 0.4 vs 1.7 ± 0.5, L/min, P < 0.01), 6-min walk distance (6MWD) (575 ± 86 vs 669 ± 76 m, P < 0.001) and 6-min walk work (6MWW) (39 ± 11 vs 45 ± 7 km.kg, P < 0.01). In subjects with EIPAH, there was a moderate correlation between 6MWD and peak (r= 0.72, P < 0.01) and a strong correlation between 6MWW and peak (r= 0.86, P < 0.001). There were significant correlations between 6MWD and peak CO (r= 0.59, P < 0.05), and between peak and peak CO (r= 0.55, P < 0.05). Peak heart rate was similar in the CPET and 6MWT in subjects with EIPAH (133 ± 15 vs 133 ± 19 beats/min, P= 0.8). CONCLUSIONS: The encouraged 6MWT identifies reduced exercise capacity and provides a valid estimate of aerobic capacity in EIPAH.

Estimating peak work rate during incremental cycle ergometry from the 6-minute walk distance: differences between reference equations.

BACKGROUND: Prescription of an appropriate exercise training intensity is critical to optimise the outcomes of pulmonary rehabilitation; however, prescribing cycle ergometry training is challenging if peak work is unknown. Recently two studies reported regression equations which allow estimation of peak cycle work rate from the 6-minute walk distance (6MWD) in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To compare estimates of peak work and target training work rate (60% peak) obtained from these equations. METHODS: Sixty-four (38 male) subjects, mean ± SD age 70 ± 8 years and FEV(1) 49 ± 18% predicted with COPD performed the 6-minute walk test according to a standardised protocol. Estimates of peak work were obtained using the published equations and agreement was examined using Bland and Altman plots. RESULTS: Mean 6MWD was 376 ± 86 m compared to 464 ± 110 m and 501 ± 83 m in samples used to derive the equations. There was substantial variation in estimates of peak work between equations (range 1-75 Watts difference) with a coefficient of variation of 35%. Differences were greater in men than in women (p < 0.001). The Luxton equation predicted higher peak work than the Hill equation in younger subjects and at work rates over 50 Watts. Estimated training work rate differed by more than 20 Watts in 18 subjects (28%). CONCLUSIONS: This comparison of reference equations for predicting peak cycle work rate from 6MWD indicates substantial variation between methods that differs systematically across the range of work rates. Further research is required to validate the equations and assess their utility for exercise prescription in pulmonary rehabilitation.

Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis.

One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case-control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1(*)07 and DQA1(*)02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.

Comparison of incremental and constant load tests of inspiratory muscle endurance in COPD.

The aim of the present study was to determine the relative value of incremental and constant load tests in detecting changes in inspiratory muscle endurance following high-intensity inspiratory muscle training (H-IMT) in chronic obstructive pulmonary disease. In total, 16 subjects (11 males; forced expiratory volume in one second (FEV(1)) 37.4+/-12.5%) underwent H-IMT. In addition, 17 subjects (11 males; FEV(1) 36.5+/-11.5%) underwent sham inspiratory muscle training (S-IMT). Training took place three times a week for 8 weeks. Baseline and post-training measurements were obtained of maximum threshold pressure sustained during an incremental load test (P(th,max)) and time breathing against a constant load (t(lim)). Breathing pattern was unconstrained. H-IMT increased P(th,max) and t(lim) relative to baseline and to any change seen following S-IMT. The effect size for P(th,max) was greater than for t(lim). Post-training tests were accompanied by changes in breathing pattern, including decreased duty cycle, which may have served to decrease inspiratory work and thereby contribute to the increase in P(th,max) and t(lim) in both groups. When assessing inspiratory muscle function in chronic obstructive pulmonary disease via tests in which the pattern of breathing is unconstrained, the current authors recommend incremental load tests be used in preference to constant load tests. However, to attribute changes in these tests to improvements in inspiratory muscle endurance, breathing pattern should be controlled.

High-intensity inspiratory muscle training in COPD.

The aim of the present study was to investigate the effects of an interval-based high-intensity inspiratory muscle training (H-IMT) programme on inspiratory muscle function, exercise capacity, dyspnoea and health-related quality of life (QoL) in subjects with chronic obstructive pulmonary disease. A double-blind randomised controlled trial was performed. Sixteen subjects (11 males, mean forced expiratory volume in one second (FEV(1)) 37.4+/-12.5%) underwent H-IMT performed at the highest tolerable inspiratory threshold load (increasing to 101% of baseline maximum inspiratory pressure). Seventeen subjects (11 males, mean FEV(1 )36.5+/-11.5%) underwent sham inspiratory muscle training (S-IMT) at 10% of maximum inspiratory pressure. Training took place three times a week for 8 weeks and was fully supervised. Pre- and post-training measurements of lung function, maximum inspiratory pressure, maximum threshold pressure, exercise capacity, dyspnoea and QoL (Chronic Respiratory Disease Questionnaire; CRDQ) were obtained. H-IMT increased maximum inspiratory pressure by 29%, maximum threshold pressure by 56%, 6-min walk distance by 27 m, and improved dyspnoea and fatigue (CRDQ) by 1.4 and 0.9 points per item, respectively. These changes were significantly greater than any seen following S-IMT. In conclusion, high-intensity inspiratory muscle training improves inspiratory muscle function in subjects with moderate-to-severe chronic obstructive pulmonary disease, yielding meaningful reductions in dyspnoea and fatigue.

Benefits of an education programme on the self-management of aerosol and airway clearance treatments for children with cystic fibrosis.

Adherence to recommended aerosol medicines and airway clearance techniques (ACT) for children with cystic fibrosis (CF) requires self-management skills. A multi-centre, randomized, controlled trial was conducted to investigate the effectiveness of a self-management education programme called 'Airways' for six- to 11-year old children with CF and their caregivers. Assessments were conducted immediately before and after the intervention period, and six and 12 months after the post-intervention assessment. The pen and paper education programme was completed by the child and caregiver together at home. Participants in the intervention and control groups had similar baseline characteristics. A per-protocol analysis was conducted and for variables that changed significantly, an additional intention-to-treat analysis was performed that included data from participants in the intervention group who withdrew from the study during the intervention period. The intervention group increased the percentage of prescribed aerosols taken (P < 0.001) and this was maintained at 12-month follow-up (P < 0.001). There was no change in the percentage of prescribed ACT performed, although when the child was unwell, caregivers in the intervention group increased the frequency and/or duration of ACT (P = 0.028) in the per-protocol analysis but not in the intention-to-treat analysis. Children in the intervention group increased their knowledge of ACT (P < 0.001) which was maintained at 12-month follow-up (P < 0.001) and felt more positively about their chest treatment regimens immediately following the intervention (P = 0.017) but not at 12-month follow-up. There were no significant changes in the control group for these variables over time. No significant changes occurred in the caregivers' reports of self-management behaviours and self-efficacy in either group. The positive results suggest that 'Airways' is a valuable educational tool for primary school-aged children with CF and their caregiver.

Subtelomeric deletion of 18p in an adult with paranoid schizophrenia and mental retardation.

Chromosome anomalies are responsible for a significant proportion of patients with mental retardation, and congenital anomalies. Development of new molecular cytogenetic techniques has provided a powerful tool for detection of patients with subtle chromosome abnormalities. Particularly, investigation of the gene-rich subtelomeric regions has generated interest regarding the implications and prevalence of cryptic chromosomal rearrangements. Here we describe an adult with a submicroscopic deletion of 18pter, detected by subtelomeric FISH probe. The patient is a 42-year-old man with a history of developmental delay, moderate mental retardation, and symptoms of paranoid schizophrenia since adolescence. His physical examination is remarkable for only a few dysmorphic findings typically seen in 18p- syndrome (round face, hypertelorism, down-slanted palpebral fissures, temporal narrowing, small hands and feet). He lacks significant short stature, skin changes, and associated anomalies involving internal organs. All known patients with deletions of the short arm of chromosome 18 have either loss of large parts of 18p or of the entire p-arm, or have complex chromosomal rearrangement involving other chromosomes. To our knowledge, this is the first description of a cryptic subtelomeric deletion of 18p and the first case of such a chromosomal anomaly in a patient with schizophrenia. Small subtelomeric chromosomal deletions would be missed by standard G-banded karyotyping. Therefore, FISH analysis using subtelomeric probes should be considered for diagnostic evaluation of patients with psychiatric symptoms and mental retardation in whom the karyotype is normal.

Gelofusine allergy--the need for identification jewellery.

A case of anaphylactoid reaction due solely to the use of Gelofusine in a patient with non-haemorrhagic hypovolaemia is presented, with a discussion on the management and the use of allergy identification jewellery.

A novel method of shortening an aortic graft.

We describe a simple method of shortening the abdominal aortic graft during an emergency procedure which is easy to perform and does not unduly delay the completion of the operation.

A novel variant of the MHC-linked hsp70, hsp70-hom, is associated with rheumatoid arthritis.

The three major histocompatibility complex (MHC)-linked hsp70s have been screened for variation in their 28 kDa C-terminal regions by direct nucleotide sequencing of the corresponding DNA fragments. No amino acid variation was detected in the major heat-inducible hsp70 (encoded by hsp70-1 and hsp70-2), although previously unreported silent mutations were identified in all three of the MHC-linked hsp70 genes. A novel coding polymorphism, a G to A transition, was identified at nucleotide 2763 of hsp70-hom (hom-2763). This dimorphism results in a glutamic acid to lysine alteration at position 602 in the C-terminal domain of hsp70-hom. The frequencies of the A-2763 and G-2763 alleles were calculated to be 27% and 73%, respectively. The hom-2763 dimorphism was characterised in 81 HLA-homozygous cell lines using an ARMS-PCR assay and A-2763 was found to be in strong linkage disequilibrium with DRB1*04 (Pc=1.31 x 10(-7), following Bonferoni's correction). Analysis of 60 rheumatoid arthritis (RA) families, each with an affected sib-pair, revealed an association between hsp70-hom A-2763 and RA using both the transmission disequilibrium test (TDT) and the transmission to sib-pair (Tsp) test (P=0.0038 and P=0.013, respectively). This association may be due to linkage disequilibrium with HLA-DR alleles, but could represent an additional risk factor for RA in the MHC class III region.

The active cycle of breathing techniques--to tip or not to tip?

The active cycle of breathing techniques (ACBT) in gravity-assisted drainage positions is an effective airway clearance regimen for individuals who produce excess bronchial secretions. This study compared the ACBT in positions with and without a head-down tilt. Nineteen subjects (11 men), mean age 37.1 years (range 18-76 years), with bronchiectasis who produced more than 20 g of sputum per day and had a mean forced expiratory volume in 1 s (FEV1) of 56.9% predicted (range 23-90% pred.) were studied. There was no significant difference in the wet weight of sputum expectorated when using the ACBT in gravity-assisted drainage positions with or without a head-down tilt. Mean (SD) score for perception of breathlessness, measured on a visual analogue scale, increased significantly following treatment with a head-down tilt [2.3 (1.6) to 3.3 (2.0) cm, P = 0.02]. There was no significant difference in oxygenation or lung function (FEV1). Eighteen subjects preferred the ACBT without a head-down tilt. The ACBT in the horizontal position is a simple airway clearance regimen suitable for individuals who produce greater than 20 g of sputum per day. Subjects were less breathless and preferred the ACBT in the horizontal position, thus providing a treatment alternative that may improve adherence in individuals who are required to carry out daily airway clearance treatments.

A genome-wide search for human type 1 diabetes susceptibility genes.

We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis. In addition to IDDM1 (in the major histocompatibility complex on chromosome 6p21) and IDDM2 (in the insulin gene region on chromosome 11p15), eighteen different chromosome regions showed some positive evidence of linkage to disease. Linkages to chromosomes 11q (IDDM4) and 6q (IDDM5) were confirmed by replication, and chromosome 18 may encode a fifth disease locus. There are probably no genes with large effects aside from IDDM1. Therefore polygenic inheritance is indicated, with a major locus at the major histocompatibility complex.

The effects of mild obesity on lung function.

Lung volumes and blood gas tensions were measured in 144 males awaiting coronary artery surgery. Patients were divided into three groups according to their body mass index. Functional residual capacity (FRC), expiratory reserve volume (ERV) and arterial oxygen tension (PaO2) were reduced in the 91 patients with Grade I obesity (mean +/- SD weight, 81.1 +/- 9.0 kg) compared with the results obtained in the 28 patients of normal weight (Grade 0, 70.8 +/- 8.8 kg). The magnitude of the reduction was greater in the Grade II obesity patients (90.1 +/- 8.8 kg, n = 25). Mean values were: FRC 3.45, 3.17, 2.66 l; ERV 1.10, 0.77, 0.59 l and PaO2 11.05, 10.47, 9.99 kPa in patients with Grades 0, I and II obesity respectively. The alveolar-arterial oxygen difference (A-aPO2) was significantly higher in the obese patients. Mean A-aPO2 was 2.47, 3.14 and 3.88 kPa in patients with Grades 0, I and II, respectively. We conclude that obesity, even when mild, significantly impairs lung function.

Survey of genitourinary organisms in a population of sexually active adolescent males admitted to a chemical dependency unit.

Sixty-two males consecutively admitted to an adolescent chemical dependency unit for treatment over a one-year period were studied. When interviewed, all denied having urogenital symptoms. Forty-eight reported having had sexual intercourse. Of these 48, 34 were screened (urethral swab) for Neisseria gonorrhoeae, Chylamydia trachomatis, Ureaplasma urealyticum, and Gardnerella vaginalis. Eighteen of the 34 males who had complete screening were found to harbor one or more organisms: 3 had Chlamydia, 13 had Ureaplasma, and 11 had Gardnerella. In addition, 61 of the original 62 subjects were tested for serum antibodies to Treponema pallidum and for pyuria. No subjects were found to have syphilis. Pyuria was present in all subjects with Chlamydia but in only two with Ureaplasma or Gardnerella.

Physiotherapy after coronary artery surgery: are breathing exercises necessary?

One hundred and ten men undergoing coronary artery bypass grafting took part in a prospective randomised study comparing three physiotherapy protocols. All patients were taught self supported huffing and coughing by a physiotherapist and encouraged to move about. This comprised the sole treatment for the 37 control patients (group 3). Additional physiotherapy included breathing exercises for the 35 patients in group 1 and use of an incentive spirometer for the 38 patients in group 2. Functional residual capacity (FRC) was measured daily at the bedside until the fifth postoperative day and arterial blood gas tensions were measured on the second and fourth postoperative days. After surgery patients developed a severe restrictive ventilatory defect and profound arterial hypoxaemia. There were no differences between the three groups. Mean FRC on day 2 was 1.90 litres (61% of the preoperative value), increasing to 2.32 1 by day 5 (76% of the preoperative value). The mean arterial oxygen tension was 7.37 kPa on day 2 and 8.58 kPa on day 4. Four patients in group 1, two in group 2, and five in group 3 developed a chest infection. It is concluded that the addition of breathing exercises or incentive spirometry to a regimen of early mobilisation and huffing and coughing confers no extra benefit after uncomplicated coronary artery bypass grafting.

Lung function after coronary artery surgery using the internal mammary artery and the saphenous vein.

Lung volumes and arterial blood gas tensions in patients undergoing coronary artery surgery were compared in 77 patients given an internal mammary artery graft (group 1) and 33 patients given a saphenous vein graft only (group 2). Patients in both groups developed a severe restrictive ventilatory defect after surgery, more pronounced in those receiving an internal mammary artery graft. Mean (SEM) vital capacity in groups 1 and 2 was reduced to 36% (1.2%) and 45% (2.0%) of preoperative values on the second postoperative day (1.56 and 1.85 1 respectively), with some recovery by day 4 to 56% (1.2%) and 63% (2.1%) of preoperative values. The mean (SEM) arterial oxygen tension was 7.34 (0.13) kPa for group 1 and 7.46 (0.20) kPa for group 2 on day 2, rising to 8.39 (0.13) and 9.01 (0.23) kPa on day 4. Analgesic requirements were greater in the group receiving an internal mammary artery graft. Possible explanations for the differences between the effects of the two grafts include the higher frequency of pleurotomy, the placing of pleural drains, and additional surgical trauma when internal mammary artery grafts are used.