Search

Background: Only a few long term smokers develop symptomatic chronic obstructive pulmonary disease (COPD) and this may be due, at least in part, to genetic susceptibility to the disease. Transforming growth factor beta1 (TGF-beta1) has a number of actions that make it a candidate for a role in the pathogenesis of COPD. We have investigated a single nucleotide polymorphism at exon 1 nucleotide position 29 (T-->C) of the TGF-beta1 gene that produces a substitution at codon 10 (Leu-->Pro).Methods: The frequency of this polymorphism was determined in 165 subjects with COPD, 140 healthy blood donors, and 76 smokers with normal lung function (resistant smokers) using the polymerase chain reaction and restriction enzyme fragment length polymorphism.Results: The distribution of genotypes was Leu-Leu (41.8%), Leu-Pro (50.3%), and Pro-Pro (7.9%) for subjects with COPD, which was significantly different from the control subjects (blood donors: Leu-Leu (29.3%), Leu-Pro (52.1%) and Pro-Pro (18.6%), p=0.006; resistant smokers: Leu-Leu (28.9%), Leu-Pro (51.3%) and Pro-Pro (19.7%), p=0.02). The Pro10 allele was less common in subjects with COPD (33%) than in blood donors (45%; OR=0.62, 95% CI 0.45 to 0.86, p=0.005) and resistant smokers (45%; OR=0.59, 95% CI 0.40 to 0.88, p=0.01).Conclusions: The proline allele at codon 10 of the TGF-beta1 gene occurs more commonly in control subjects than in individuals with COPD. This allele is associated with increased production of TGF-beta1 which raises the possibility that TGF-beta1 has a protective role in COPD. [ABSTRACT FROM AUTHOR]

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 × 109 cfu/day) halved the cumulative prevalence of eczema at 2 and 4 years. Bifidobacterium animalis subsp lactis HN019 ( HN019) (9 × 109 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 × 109 CFU/day Lactobacillus rhamnosus HN001 ( n=34), 9 × 109 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-γ, IL-6, TNF-α, IL-10, TGF-β1) and sCD14. Breast milk samples were also assayed for total IgA. Results Neonates of mothers who received a probiotic had higher CB IFN-γ levels ( P=0.026), and a higher proportion had detectable blood IFN-γ 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-γ levels ( P=0.030) compared with the placebo group. TGF-β1 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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% Cl 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 21 3Gly 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.To examine factors associated with a diagnosis of AD at 3·5 years of age, especially those factors implicated by the hygiene hypothesis.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≤ 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.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;≥ 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.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. [ABSTRACT FROM AUTHOR]

Allergic sensitization to inhaled allergens and foods is common and is linked to the development of asthma, allergic rhinitis and eczema. In view of the morbidity associated with these diseases it is not clear why the genetic predisposition to atopy is so common. Children who are atopic are less likely to develop oral tolerance to ingested foods and as a result are more likely to have manifestations of food allergy including wheezing, skin rashes and gastrointestinal symptoms. Oral tolerance also develops to micro-organisms in the gastrointestinal tract. Children who are atopic may be protected against enteric infections in early childhood because they are less likely to be tolerant of these organisms. This may explain why individuals who are atopic are less likely to have evidence of previous infection with hepatitis A and other enteric organisms although they are just as likely to have been infected with respiratory pathogens. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the average doses of inhaled beclomethasone, fluticasone and budesonide prescribed in primary care reflect the relative potencies of these medicines. Methods: Retrospective analysis of 95,540 prescriptions for inhaled steroids written by 293 general practitioners in Auckland, New Zealand, between November 1995 and June 1998. In addition, 177 general practitioners were presented with two case histories describing patients with uncontrolled asthma who were not on treatment with inhaled steroids. They were asked which medicine they would prescribe and in what dose. Results: The average daily doses prescribed were 600 μg for fluticasone, 747 μg for beclomethasone and 1184 μg for budesonide. The average dose of fluticasone was 80% of that for beclomethasone. In May 1997, when 4.5% of the prescriptions for inhaled steroids were for fluticasone, the average doses of fluticasone and beclomethasone were 632 μg and 760 μg, respectively. By May 1998, when 23% of prescriptions were for fluticasone, the average doses of fluticasone and beclomethasone were little changed at 610 μg and 726 μg, respectively. In response to the two case histories, the average doses of fluticasone chosen were 71% and 77% of the doses of beclomethasone. Conclusions: The average prescribed dose of fluticasone was 80% of that for beclomethasone, even though fluticasone is at least twice as potent as beclomethasone. Similar findings were observed when the general practitioners responded to the case histories. The high doses of fluticasone prescribed may be due to a failure to appreciate that fluticasone is twice as potent as beclomethasone and to the availability of high strength preparations of fluticasone, i.e. 250 μg per actuation. [ABSTRACT FROM AUTHOR]

Objectives: To assess the evidence for the effects of physical training on pulmonary function, symptoms, cardiopulmonary fitness, and quality of life in subjects with asthma.Methods: A search was conducted for randomised controlled trials of subjects with asthma undertaking physical training using the Cochrane Airways Group register of controlled clinical trials, Medline, Embase, Sportdiscus, Science citation index, and Current contents index. Studies were included in the review if the subjects had asthma, were 8 years of age or older, and had undertaken physical training for at least 20 minutes per session, twice a week, for a minimum of four weeks. The eligibility of trials for inclusion in the review and the quality of the trials were independently assessed by two reviewers.Results: Eight studies with a total of 226 subjects met the inclusion criteria for this review. Physical training had no effect on resting lung function but led to an improvement in cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.6 ml/kg/min (95% confidence interval 3.9 to 7.2). None of the studies measured quality of life.Conclusions: Physical training improves cardiopulmonary fitness without changing lung function. It is not clear if the improvement in fitness translates into a reduction in symptoms or an improvement in the quality of life. There is a need for further randomised controlled trials of the effects of physical training in the management of asthma. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life-threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to an intensive care unit (ICU) for asthma. Methods: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house-dust mite (Dermatophagoides pteronyssinus), and a seven-grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma. Results: Twenty of 37 patients (54%) admitted to the ICU had a positive skin test for one or more fungal allergens compared with 15/50 patients (30%) in each of the other groups (P=0.005). The ICU patients were no more likely to have positive skin tests for the grass mix, cat dander, or house-dust mite than the other patients. Conclusions: A positive skin test for fungal allergens is a risk factor for admission to an ICU with an acute attack of asthma. [ABSTRACT FROM AUTHOR]

Fatty acyl-CoA thioesters are essential intermediates in lipid metabolism. For many years there have been numerous conflicting reports concerning the possibility that these compounds also serve regulatory functions. In this review, we examine the evidence that long-chain acyl-CoA is a regulatory signal that modulates gene expression. In the bacteria Escherichia coli, long-chain fatty acyl-CoA bind directly to the transcription factor FadR. Acyl-CoA binding renders the protein incapable of binding DNA, thus preventing transcription activation and repression of many genes and operons. In the yeast Saccharomyces cerevisiae, genes encoding peroxisomal proteins are activated in response to exogenously supplied fatty acids. In contrast, growth of yeast cells in media containing exogenous fatty acids results in repression of a number of genes, including that encoding the delta9-fatty acid desaturase (OLE1). Both repression and activation are dependent upon the function of either of the acyl-CoA synthetases Faa1p or Faa4p. In mammals, purified hepatocyte nuclear transcription factor 4alpha (HNF-4alpha) like E. coli FadR, binds long chain acyl-CoA directly. Coexpression of HNF-4alpha and acyl-CoA synthetase increases the activation of transcription of a fatty acid-responsive promoter, whereas coexpression with thioesterase decreases the fatty acid-mediated response. Conflicting data exist in support of the notion that fatty acyl-CoA are natural ligands for peroxisomal proliferator-activated receptor alpha (PPARalpha). [ABSTRACT FROM AUTHOR]

The effect of intradermal injection of leukotriene B4 alone and in combination with prostaglandin D2 and E2 and the effect of inhaled leukotriene B4 in combination with prostaglandin D2 were studied in six non-asthmatic men. The intradermal injection of leukotriene B4 (1 microgram) alone caused no immediate or late response in five of the six subjects but greatly potentiated the flare response to intradermal prostaglandin D2 (0.5 microgram) and E2 (0.5 microgram) in all subjects. In contrast, inhaled prostaglandin D2 (6 micrograms) alone and in combination with inhaled leukotriene B4 (12 micrograms) caused no change in the response to inhaled histamine, measured 30 minutes and three and six hours after the inhalation. These findings provide no support for the suggestion that leukotriene B4 has an important role in causing bronchial hyperresponsiveness. The possibility that higher doses of inhaled leukotriene B4 may alter bronchial responsiveness cannot, however, be ruled out. [ABSTRACT FROM AUTHOR]

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 ∼107 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 13C- 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 13C-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. [ABSTRACT FROM AUTHOR]

Only a few long term smokers develop symptomatic chronic obstructive pulmonary disease (COPD) and this may be due, at least in part, to genetic susceptibility to the disease. Transforming growth factor β1 (TGF-β1) has a number of actions that make it a candidate for a role in the pathogenesis of COPD. We have investigated a single nucleotide polymorphism at exon 1 nucleotide position 29 (T→C) of the TGF-β1 gene that produces a substitution at codon 10 (Leu→Pro). The distribution of genotypes was Leu-Leu (41.8%), Leu-Pro (50.3%), and Pro-Pro (7.9%) for subjects with COPD, which was significantly different from the control subjects (blood donors: Leu-Leu (29.3%), Leu-Pro (52.1%) and Pro-Pro (18.6%), p = 0.006; resistant smokers: Leu-Leu (28.9%), Leu-Pro (51.3%) and Pro-Pro (19.7%), p = 0.02). The Prom allele was less common in subjects with COPD (33%) than in blood donors (45%; OR = 0.62, 95% CI 0.45 to 0.86, p = 0.005) and resistant smokers (45%; OR= 0.59, 95% CI 0.40 to 0.88, p = 0.01). The proline allele at codon 10 of the TGF-β1 gene occurs more commonly in control subjects than in individuals with COPD. This allele is associated with increased production of TGF-β1 which raises the possibility that TGF-β1 has a protective role in COPD. [ABSTRACT FROM AUTHOR]