Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization?

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clear; efficacy may depend on the timing, dose, duration, and specific probiotic used. Using a double-blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high-risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema at 2 and 4 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no significant effect. OBJECTIVE: To determine whether differences in effects of HN001 and HN019 on eczema persist to age 6 years, and to investigate effects on sensitization. METHODS: Standard procedures were used to assess eczema (The UK Working Party's Criteria), eczema severity (SCORAD), atopic sensitization [skin prick tests (SPT), total and specific IgE] and standard questions used for asthma, wheeze, and rhinoconjunctivitis. RESULTS: HN001 was associated with significantly lower cumulative prevalence of eczema (HR = 0.56, 95% CI 0.39-0.80), SCORAD ≥ 10 (HR = 0.69, 0.49-0.98) and SPT sensitization (HR = 0.69, 95% CI 0.48-0.99). The point prevalence of eczema (RR = 0.66, 95% CI 0.44-1.00), SCORAD ≥ 10 (RR = 0.62, 95% CI 0.38-1.01) and SPT sensitization (RR = 0.72, 95% CI 0.53-1.00) were also reduced among children taking HN001. HN019 had no significant effect on any outcome. CONCLUSION AND CLINICAL RELEVANCE: This study provides evidence for the efficacy of the probiotic L. rhamnosus HN001 in preventing the development of eczema and possibly also atopic sensitization in high risk infants to age 6 years. The absence of a similar effect for HN019 indicates that benefits may be species specific.

Coherent anti-Stokes Raman scattering and spontaneous Raman spectroscopy and microscopy of microalgae with nitrogen depletion.

Microalgae are extensively researched as potential feedstocks for biofuel production. Energy-rich compounds in microalgae, such as lipids, require efficient characterization techniques to investigate the metabolic pathways and the environmental factors influencing their accumulation. The model green alga Coccomyxa accumulates significant amounts of triacylglycerols (TAGs) under nitrogen depletion (N-depletion). To monitor the growth of TAGs (lipid) in microalgal cells, a study of microalgal cells (Coccomyxa sp. C169) using both spontaneous Raman and coherent anti-Stokes Raman scattering (CARS) spectroscopy and microscopy were carried out. Spontaneous Raman spectroscopy was conducted to analyze the components in the algal cells, while CARS was carried out to monitor the distribution of lipid droplets in the cells. Raman signals of carotenoid are greater in control microalgae compared to N-depleted cells. Raman signals of lipid droplets appear after N-depletion and its distribution can be clearly observed in the CARS microscopy. Both spontaneous Raman spectroscopy and CARS microscopy were found to be suitable analysis tools for microalgae.

Surface-enhanced Raman spectroscopy using gold-coated horizontally aligned carbon nanotubes.

Gold-coated horizontally aligned carbon nanotube (Au-HA-CNT) substrates were fabricated for surface-enhanced Raman spectroscopy (SERS). The Au-HA-CNT substrates, which are granular in nature, are easy-to-prepare with large SERS-active area. Enhancement factors (EFs) of ∼10(7) were achieved using the Au-HA-CNTs as substrates for rhodamine 6G (R6G) molecules. Maximum enhancement was found when the polarization direction (E-field) of the incident laser beam was parallel to the aligned direction of the HA-CNTs. Simulations using the finite-difference time-domain (FDTD) method were carried out for the granular Au-HA-CNT samples. Enhancement mechanisms and determination of EFs were analyzed. Biological samples, including (13)C- and deuterium (D)-labeled fatty acids and Coccomyxa sp. c-169 microalgae cells, were also measured using this SERS substrate. The limits of detection (LODs) of D- and (13)C-labeled fatty acids on the SERS substrate were measured to be around 10 nM and 20 nM, respectively. Significantly enhanced Raman signals from the microalgae cells were acquired using the SERS substrate.

Chromosome 4q31 locus in COPD is also associated with lung cancer.

Chronic obstructive pulmonary disease (COPD) is the single greatest risk factor for lung cancer in smokers and is found in 50-90% of lung cancer cases. The link between COPD and lung cancer may stem in part from the matrix remodelling and repair processes underlying COPD, and the development of epithelial-mesenchymal transition (EMT) that underlies lung carcinogenesis. The Hedgehog-interacting protein (HHIP), which mediates the epithelial response (EMT) to smoking, has been implicated in COPD and lung cancer. Recent genome-wide and candidate gene studies of COPD implicate genetic variants on the chromosomal 4q31 (HHIP/glycophorin A (GYPA)) locus. In a case-control study of smokers with normal lung function, COPD and lung cancer (subphenotyped for COPD), we show the GG genotype of the rs 1489759 HHIP single-nucleotide polymorphism (SNP) and the CC genotype of the rs 2202507 GYPA SNP confers a "protective" effect on COPD (OR 0.59, p = 0.006 for HHIP and OR = 0.65, p = 0.006 for GYPA) and lung cancer (OR = 0.70 (p = 0.05) for HHIP and OR 0.70 (p = 0.02) for GYPA). This study suggests that, in smokers, genetic variants of the 4q31 locus conferring a protective effect for COPD are also protective in lung cancer. We conclude that genetic susceptibility to lung cancer includes COPD-related gene variants.

A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers.

BACKGROUND: Epidemiological and family studies suggest that lung cancer results from the combined effects of age, smoking and genetic factors. Chronic obstructive pulmonary disease (COPD) is also an independent risk factor for lung cancer and coexists in 40-60% of lung cancer cases. METHODS: In a two-stage case-control association study, genetic markers associated with either susceptibility or protection against lung cancer were identified. In a test cohort of 439 Caucasian smokers or ex-smokers, consisting of healthy smokers and lung cancer cases, 157 candidate single nucleotide polymorphisms (SNPs) were screened. From this, 30 SNPs were identified, the genotypes (codominant or recessive model) of which were associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping of this 30-SNP panel in a second validation cohort of 491 subjects and using the same protective and susceptibility genotypes from our test cohort, a 20-SNP panel was selected on the basis of independent univariate analyses. RESULTS: Using multivariate logistic regression, including the 20 SNPs, it was also found that age, history of COPD, family history of lung cancer and gender were significantly and independently associated with lung cancer. CONCLUSIONS: When numeric scores were assigned to both the SNP and demographic data, and sequentially combined by a simple algorithm in a risk model, the composite score was found to be linearly related to lung cancer risk with a bimodal distribution. Genetic data may therefore be combined with other risk variables from smokers or ex-smokers to identify individuals who are most susceptible to developing lung cancer.

Falling asleep: the determinants of sleep latency.

BACKGROUND: Difficulty falling asleep (prolonged sleep latency) is a frequently reported problem in school-aged children. AIMS: This study aimed to describe the distribution of sleep latency and factors that influence its duration. METHODS: 871 children of European mothers were recruited at birth. 591 (67.9%) children took part in the follow-up at 7 years of age. Sleep and daytime activity were measured objectively by an actigraph worn for 24 h. RESULTS: Complete sleep data were available for 519 children (87.8%) with a mean age of 7.3 years (SD 0.2). Median sleep latency was 26 minutes (interquartile range 13-42). Higher mean daytime activity counts were associated with a decrease in sleep latency (-1.2 minutes per 102 movement count per minute, p = 0.05). Time spent in sedentary activity was associated with an increase in sleep latency (3.1 minutes per hour of sedentary activity, p = 0.01). CONCLUSIONS: These findings emphasise the importance of physical activity for children, not only for fitness, cardiovascular health and weight control, but also for promoting good sleep.

Interventions to reduce the frequency of exacerbations of chronic obstructive pulmonary disease.

Frequent exacerbations of chronic obstructive pulmonary disease (COPD) are associated with impaired quality of life, and hospital admissions for exacerbations account for a large proportion of the expenditure of COPD. An important objective when treating COPD is to reduce the frequency of exacerbations. Studies published in the last few years have increased our knowledge on how to prevent exacerbations, but a number of questions remain unanswered. Tiotropium, inhaled steroids and long-acting inhaled beta agonists reduce the frequency of exacerbations, but further studies are necessary to determine if combining tiotropium with the other inhaled medicines is more effective than using them separately. There is evidence that mucolytics and prophylactic antibiotics reduce exacerbations, but there is uncertainty how these treatments should be used. Both influenza and pneumococcal vaccination are recommended in guidelines, although evidence for the latter remains controversial. Other interventions including oral bacterial extracts and self-management programmes warrant further study.

COPD prevalence is increased in lung cancer, independent of age, sex and smoking history.

Chronic obstructive pulmonary disease (COPD) is a common comorbid disease in lung cancer, estimated to affect 40-70% of lung cancer patients, depending on diagnostic criteria. As smoking exposure is found in 85-90% of those diagnosed with either COPD or lung cancer, coexisting disease could merely reflect a shared smoking exposure. Potential confounding by age, sex and pack-yr smoking history, and/or by the possible effects of lung cancer on spirometry, may result in over-diagnosis of COPD prevalence. In the present study, the prevalence of COPD (pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2+ criteria) in patients diagnosed with lung cancer was 50% compared with 8% in a randomly recruited community control group, matched for age, sex and pack-yr smoking exposure (n = 602, odds ratio 11.6; p<0.0001). In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer (n = 127), we found a nonsignificant increase in COPD prevalence following diagnosis (56-61%; p = 0.45). After controlling for important variables, the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers; this is much greater than previously reported. We conclude that COPD is both a common and important independent risk factor for lung cancer.

Lung cancer gene associated with COPD: triple whammy or possible confounding effect?

Recently, several large genome-wide association studies have identified a putative "lung cancer" locus in the nicotinic acetylcholine receptor subunit genes (nAChR) on 15q25. However, these findings may be confounded by the presence of chronic obstructive pulmonary disease (COPD), which is also strongly associated with smoking exposure and lung cancer. This is likely as the prevalence of COPD in lung cancer cohorts is as much as two-fold greater than that reported in smoking control populations (50 versus 20%). The present authors compared the genotype frequencies of the most strongly associated single nucleotide polymorphism (rs16969968) in the alpha5 subunit of the nAChR gene cluster between three matched smoking cohorts. The AA genotype was found to be more frequent and was seen in 437 (16%) lung cancer cases and 445 (14%) COPD cases compared with 475 (9%) healthy smoking controls. More importantly, when 429 lung cancer cases were divided according to spirometry results (performed within 3 months of diagnosis, prior to surgery and in the absence of effusions or collapse), the AA genotype was present in 19 and 11% of cases with and without COPD, respectively. These findings suggest that the association between the alpha5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.

Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon-gamma and breast milk transforming growth factor-beta and immunoglobin A detection.

BACKGROUND: This study explored the effects of maternal probiotic supplementation on immune markers in cord blood (CB) and breast milk. METHODS: CB plasma and breast milk samples were collected from a cohort of women who had received daily supplements of either 6 x 10(9) CFU/day Lactobacillus rhamnosus HN001 (n=34), 9 x 10(9) CFU/day Bifidobacterium lactis HN019 (n=35) or a placebo (n=36) beginning 2-5 weeks before delivery and continuing for 6 months in lactating women. CB plasma and breast milk (collected at 3-7 days, 3 months and 6 months postpartum) were assayed for cytokines (IL-13, IFN-gamma, IL-6, TNF-alpha, IL-10, TGF-beta1) and sCD14. Breast milk samples were also assayed for total IgA. RESULTS: Neonates of mothers who received a probiotic had higher CB IFN-gamma levels (P=0.026), and a higher proportion had detectable blood IFN-gamma levels, compared with the placebo group (P=0.034), although levels were undetectable in many infants. While this pattern was evident for both probiotics, when examined separately only the L. rhamnosus HN001 group showed statistically significant higher IFN-gamma levels (P=0.030) compared with the placebo group. TGF-beta1 levels were higher in early breast milk (week 1) from the probiotic groups (P=0.028). This was evident for the B. lactis HN019 group (P=0.041) with a parallel trend in the L. rhamnosus HN001 group (P=0.075). Similar patterns were seen for breast milk IgA, which was more readily detected in breast milk from both the B. lactis HN019 (P=0.008) and the L. rhamnosus HN001 group (P=0.011). Neonatal plasma sCD14 levels were lower in the B. lactis HN019 group compared with the placebo group (P=0.041). CONCLUSION: The findings suggest that supplementation with probiotics in pregnancy has the potential to influence fetal immune parameters as well as immunomodulatory factors in breast milk.

Changes in elastic fibres in the small airways and alveoli in COPD.

Small airways are the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD). This is attributed to loss of elastin in alveoli and fibrosis in small airways. In the present study, it was hypothesised that changes to elastic fibres in alveoli might be paralleled by a similar reduction in elastic fibres in small airways. Tissue blocks from patients who had lobectomy for bronchial carcinoma were studied. Patients were classified as COPD (forced expiratory volume in one second (FEV(1)) < 80% predicted, FEV(1)/forced vital capacity (FVC) < 0.7) or controls (FEV(1) > or = 80% pred, FEV(1)/FVC > or = 0.7). Elastic fibres were visualised using Elastic van Gieson staining and the volume fraction (v/f) of elastic fibres was determined as a percentage of tissue volume using point counting. Elastic fibre networks were also visualised by confocal microscopy. The v/f for elastic fibres in alveoli was 18.6% for COPD and 32.8% in controls. In the airways the v/f was 14.6% for COPD and 25.5% in controls. FEV(1)% predicted was correlated with v/f in both alveoli and small airways. The volume fraction of elastic fibres was reduced to a similar extent in small airways and alveoli in chronic obstructive pulmonary disease and both were correlated with the extent of airflow obstruction. Loss of elastic fibres in small airways may contribute to the development of airflow obstruction in chronic obstructive pulmonary disease.

Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice.

BACKGROUND: It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. OBJECTIVE: We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. METHODS: C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. RESULTS: Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. CONCLUSION: Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Risk factors for asthma at 3.5 and 7 years of age.

BACKGROUND: It has been suggested that factors in early life including exposure to allergens and microbes may influence the development of asthma. OBJECTIVE: To identify risk factors for asthma in early childhood. Methods Eight-hundred and seventy-one children of European mothers were enrolled at birth, of whom 385 (44.2%) were born small for gestational age (SGA) and 486 were appropriate for gestational age (AGA). Data were collected at birth, 12 months, 3.5 years of age (y) and 7 y. The outcome of interest (current wheeze) was defined as a positive response to the question: 'Has your child had wheezing or whistling in the chest in the last 12 months?' RESULTS: Participation rate was 85.4% at 1 y, 63.1% at 3.5 y and 68.0% at 7 y. The prevalence of asthma was 23.8% at 3.5 y and 18.1% at 7 y. Antibiotic use in the first year of life and day care in the first year of life were associated with increased risk of wheeze at 7 y [odds ratio (OR)=4.3 95% confidence interval (CI) (1.8-10.1) and OR=2.8 95% CI (1.2-6.5), respectively], but not at 3.5 y. Exposure to dogs was a risk factor for asthma at both ages [OR=2.1 95% CI (1.1-3.8)] as was sleeping on a used cot mattress in the first year of life [OR=1.8 95% CI (1.0-3.2)]. CONCLUSIONS: There was a significant association between antibiotic use and day care in the first year of life and wheezing at 7 y but not at 3.5 y. This strengthens the argument that these factors increase the risk of asthma. We have also made the novel observation that sleeping on a used mattress in the first year of life is a risk factor for wheezing at 3.5 and 7 y. Capsule summary This prospective study of 871 children made the novel observation that sleeping on a used mattress in the first year of life was a risk factor for wheezing at 3.5 and 7 y.

Inhaled corticosteroids for stable chronic obstructive pulmonary disease.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much controversy. Major international guidelines recommend selective use of ICS. Recently published meta-analyses have reported conflicting findings on the effects of inhaled steroid therapy in COPD. OBJECTIVES: The objective of the review is to determine the efficacy of regular use of inhaled corticosteroids in patients with stable COPD. SEARCH STRATEGY: A pre-defined search strategy was used to search the Cochrane Airways Group specialised register for relevant literature. Searches are current as of October 2006. SELECTION CRITERIA: We selected randomised trials comparing any dose of any type of inhaled steroid with a placebo control in patients with COPD. Acute bronchodilator reversibility to short term beta2-agonists and bronchial hyperresponsiveness were not exclusion criteria. The a priori primary outcome was change in lung function. Data on mortality, exacerbations, quality of life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and safety were also analysed. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Forty-seven primary studies with 13,139 participants met the inclusion criteria. Medium term use of ICS (> two months and up to six months) resulted in a small improvement in FEV1 in some studies. Long term use of ICS (> six months) did not significantly reduce the rate of decline in FEV1 in COPD patients (weighted mean difference (WMD) 5.80 ml/year with ICS over placebo, 95% CI -0.28 to 11.88, 2333 participants). There was no statistically significant effect on mortality in COPD patients (OR 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (WMD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (WMD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.49, 95% CI 1.78 to 3.49, 4380 participants) and hoarseness. The few long term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over 3 years. AUTHORS' CONCLUSIONS: Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life), against the known increase in local side effects (oropharyngeal candidiasis and hoarseness). The risk of long term adverse effects is unknown.

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments. AUTHORS' CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma.

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.

Accuracy of information on medicines in hospital discharge summaries.

BACKGROUND: At Auckland Hospital, patients have been given handwritten summaries on discharge from hospital with a copy posted to the general practitioner. A typed summary is often not completed so the list of medicines on the handwritten summary needs to be accurate and complete. METHODS: We selected 100 patient charts from the general medical service and 100 charts from the general surgical service and recorded the medicines on admission, on the inpatient medication chart and on the discharge summary. We noted errors in the recording of medicines on the discharge summary and rated the severity of errors. RESULTS: Surgical patients were discharged on 7.88 (95% confidence interval (CI) 7.40-8.64) medicines and medical patients on 8.58 (95% CI 7.87-9.29) medicines. During the admission there were 0.59 (95% CI 0.38-0.80) changes to the medicines for the surgical patients and 1.70 (95% CI 1.39-2.01) for the medical patients (P < 0.0001). There were 0.81 (95% CI 0.65-1.02) errors per surgical discharge summary and 1.42 (95% CI 1.20-1.67) errors per medical summary (P = 0.006). Four errors were graded as having the potential to cause readmission to hospital, 24 as potentially serious, 83 as potentially troublesome and 111 as minor. DISCUSSION: Error rates were high and although the majority were minor, a number of them had the potential to cause serious consequences. There were more medication changes in the medical patients and this may contribute to higher error rates in this group. There is a need to improve the accuracy of recording medicines on discharge summaries. Strategies to improve this problem are discussed.

Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is predominantly the consequence of chronic smoking exposure, but its development may be influenced by genetic variants that affect lung remodelling, inflammation, and defence from oxidant stress. A study was undertaken to determine whether genetic variants within genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase may be associated with the development of impaired lung function. METHODS: In a case-control study, the allele and genotype frequencies of functional polymorphisms from SOD1 (CuZnSOD), SOD2 (MnSOD), SOD3 (extracellular SOD), and catalase (CAT) were compared in chronic smokers with normal lung function (resistant smokers) and in those with COPD. RESULTS: Significantly higher frequencies of the G allele and CG/GG genotype of the 213 SOD3 polymorphism were found in resistant smokers (odds ratios (ORs) 4.3 (95% CI 1.5 to 13.3) and 4.2, 95% CI 1.4 to 13.3), Bonferroni corrected p = 0.02 and p = 0.02, respectively) than in those with COPD. There were no differences between the COPD and resistant smokers for the SOD1, SOD2, or CAT polymorphisms tested. CONCLUSIONS: The 213Gly variant of the SOD3 gene may, through antioxidant or anti-inflammatory effects, confer a degree of resistance in some smokers to the development of COPD.

Physical training for asthma.

BACKGROUND: Physical training programmes have been designed for asthmatic subjects with the aim of improving physical fitness, neuromuscular coordination and self-confidence. Habitual physical activity increases physical fitness and lowers ventilation during mild and moderate exercise thereby reducing the likelihood of provoking exercise induced asthma. Exercise training may also reduce the perception of breathlessness through a number of mechanisms including strengthening respiratory muscles. Subjectively, many asthmatics report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. OBJECTIVES: The purpose of this review was to assess evidence for the efficacy and effectiveness of physical training in asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register, SportDiscus and the Science Citation Index up to May 2005. SELECTION CRITERIA: Randomised trials in asthmatic subjects undertaking physical training. Subjects had to be eight years and older. Physical training had to be undertaken for at least 20 to 30 minutes, two to three times a week, over a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion and quality of trials were assessed independently by two reviewers. MAIN RESULTS: Thirteen studies (455 participants) were included in this review. Physical training had no effect on resting lung function or the number of days of wheeze. The results of this review have shown that lung function and wheeze is not worsened by physical training in patients with asthma. Physical training improved cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.4 ml/kg/min (95% confidence interval 4.2 to 6.6) and maximum expiratory ventilation 6.0 L/min (95% confidence interval 1.5 to 10.4). There were no data concerning quality of life measurements. AUTHORS' CONCLUSIONS: In people with asthma, physical training can improve cardiopulmonary fitness without changing lung function. It is not known whether improved fitness is translated into improved quality of life. It is comforting to know that physical training does not have an adverse effect on lung function and wheeze in patients with asthma. Therefore, there is no reason why patients with asthma should not participate in regular physical activity.

Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age.

BACKGROUND: The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. OBJECTIVES: To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. METHODS: The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight < or = 10th centile; controls were appropriate for gestational age, with birthweight > 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. RESULTS: Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L(-1), and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: < 6 months, adjusted OR 6.13, 95% CI 1.45-25.86; > or = 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for environmental factors and a personal history of atopy. AD at 3.5 years was associated with owning a cat at 3.5 years (adjusted OR 0.45, 95% CI 0.21-0.97) but not with owning a dog at 3.5 years, pets at 1 year, nor with older siblings. Furthermore, AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, damp, mould, immunizations, body mass index or antibiotic use in first year of life. CONCLUSIONS: A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with those factors implicated by the hygiene hypothesis. This study suggests that breastfeeding should not be recommended for the prevention of AD.