Peter N. Black

A differential effect of 2 probiotics in the prevention of eczema and atopy: A double-blind, randomized, placebo-controlled trial

BACKGROUND The role of probiotics in prevention of allergic disease is still not clearly established, although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years. OBJECTIVE To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years. METHODS Double-blind, randomized placebo-controlled trial of infants at risk of allergic disease. Pregnant women were randomized to take Lactobacillus rhamnosus HN001 (L rhamnosus), Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding, and their infants were randomized to receive the same treatment from birth to 2 years (n = 474). The infants cumulative prevalence of eczema and point prevalence of atopy, using skin prick tests to common allergens, was assessed at 2 years. RESULTS Infants receiving L rhamnosus had a significantly (P = .01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30-0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58-1.41). There was no significant effect of L rhamnosus (HR, 0.74; 95% CI, 0.46-1.18) or B animalis subsp lactis (HR, 0.82; 95% CI, 0.52-1.28) on atopy. L rhamnosus (71.5%) was more likely than B animalis subsp lactis (22.6%) to be present in the feces at 3 months, although detection rates were similar by 24 months. CONCLUSION We found that supplementation with L rhamnosus, but not B animalis subsp lactis, substantially reduced the cumulative prevalence of eczema, but not atopy, by 2 years. Understanding how Lactobacilli act to prevent eczema requires further investigation.

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.

Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review

Abstract Objective: To assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease. Design: Systematic review of randomised controlled trials that compared at least two months of regular oral mucolytic drugs with placebo. Studies: Twenty three randomised controlled trials in outpatients in Europe and United States. Main outcome measures: Exacerbations, days of illness, lung function, adverse events. Results: Compared with placebo, the number of exacerbations was significantly reduced in subjects taking oral mucolytics (weighted mean difference −0.07 per month, 95% confidence interval −0.08 to −0.05, P<0.0001). Based on the annualised rate of exacerbations in the control subjects of 2.7 a year, this is a 29% reduction. The number needed to treat for one subject to have no exacerbation in the study period would be 6. Days of illness also fell (weighted mean difference −0.56, −0.77 to −0.35, P<0.0001). The number of subjects who had no exacerbations in the study period was greater in the mucolytic group (odds ratio 2.22, 95% confidence interval 1.93 to 2.54, P<0.0001). There was no difference in lung function or in adverse events reported between treatments. Conclusions: In chronic bronchitis and chronic obstructive pulmonary disease, treatment with mucolytics is associated with a reduction in acute exacerbations and days of illness. As these drugs have to be taken long term, they could be most useful in patients who have repeated, prolonged, or severe exacerbations of chronic obstructive pulmonary disease. What is already known on this topic Mucolytic drugs have properties that may be beneficial in chronic obstructive pulmonary disease These drugs are not prescribed in the United Kingdom and Australasia, although they are widely used in many other countries Drugs that reduce exacerbations may reduce the morbidity and healthcare costs associated with progressively severe disease What this study adds Regular use of mucolytic drugs for at least two months significantly reduces exacerbations and days of illness compared with placebo in patients with chronic bronchitis and chronic obstructive pulmonary disease Exacerbations that do occur may not be as severe, and the benefit may be greater in those with more severe disease Reductions are modest and treatment may not be cost effective

Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon‐γ and breast milk transforming growth factor‐β and immunoglobin A detection

Background This study explored the effects of maternal probiotic supplementation on immune markers in cord blood (CB) and breast milk.

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.

Transforming growth factor-β1 genotype and susceptibility to chronic obstructive pulmonary disease

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 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). 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-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.

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.

A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years

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 until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 109 cfu/day) halved the cumulative prevalence of eczema by age 2 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 109 cfu/day) had no effect.

Risk factors for obesity in 7-year-old European children: the Auckland Birthweight Collaborative Study

Objective: To identify risk factors associated with obesity in primary school children, with a particular focus on those which can be modified. To identify critical periods and growth patterns in the development of childhood obesity. Methods: 871 New Zealand European children were enrolled in a longitudinal study at birth and data were collected at birth, 1, 3.5 and 7 years of age. Data collected at 7 years included weight, height, bioelectrical impedance analysis (BIA), television viewing time and a 24 h body movement record (actigraphy). The outcome measure was percentage body fat (PBF), which was calculated at 3.5 and 7 years using BIA. Univariate and multiple regression analyses were carried out using PBF as a continuous variable. Results: Multivariable analysis found maternal overweight/obesity, maternal age, female gender, sedentary activity time and hours of television viewing to be independently associated with PBF at 7 years. Growth variables (birth weight, rapid weight gain in infancy, early (1–3.5 years) and middle childhood (3.5–7 years)) were also independently associated with adiposity at 7 years. There was a strong correlation between PBF at 3.5 years and PBF at 7 years. Conclusions: Many primary school aged children start on the trajectory of obesity in the preschool years, which suggests interventions need to start early. Maternal overweight/obesity, television watching, sedentary activity time and rapid weight gain in infancy, early and middle childhood are risk factors for childhood obesity, and are all potentially modifiable.

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 α5 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 α5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.