Caroline J. Lodge

Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery

Background Surgical management of colon cancer for patients with Lynch syndrome who carry a mismatch repair (MMR) gene mutation is controversial. The decision to remove more or less of the colon involves the consideration of a relatively high risk of metachronous colorectal cancer (CRC) with the impact of more extensive surgery. Objective To estimate and compare the risks of metachronous CRC for patients with Lynch syndrome undergoing either segmental or extensive (subtotal or total) resection for first colon cancer. Design Risk of metachronous CRC was estimated for 382 MMR gene mutation carriers (172 MLH1, 167 MSH2, 23 MSH6 and 20 PMS2) from the Colon Cancer Family Registry, who had surgery for their first colon cancer, using retrospective cohort analysis. Age-dependent cumulative risks of metachronous CRC were calculated using the Kaplan–Meier method. Risk factors for metachronous CRC were assessed by a Cox proportional hazards regression. Results None of 50 subjects who had extensive colectomy was diagnosed with metachronous CRC (incidence rate 0.0; 95% CI 0.0 to 7.2 per 1000 person-years). Of 332 subjects who had segmental resections, 74 (22%) were diagnosed with metachronous CRC (incidence rate 23.6; 95% CI 18.8 to 29.7 per 1000 person-years). For those who had segmental resections, incidence was statistically higher than for those who had extensive surgery (P <0.001). Cumulative risk of metachronous CRC was 16% (95% CI 10% to 25%) at 10 years, 41% (95% CI 30% to 52%) at 20 years and 62% (95% CI 50% to 77%) at 30 years after segmental colectomy. Risk of metachronous CRC reduced by 31% (95% CI 12% to 46%; p=0.002) for every 10 cm of bowel removed. Conclusions Patients with Lynch syndrome with first colon cancer treated with more extensive colonic resection have a lower risk of metachronous CRC than those receiving less extensive surgery. This finding will better inform decision-making about the extent of primary surgical resection.

The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies

The impact of early childhood traffic‐related air pollution (TRAP) exposure on development of asthma and allergies remains unclear. Birth cohort studies are the best available study design to answer this question, but the evidence from such studies has not been synthesized to date. We conducted a systematic review and meta‐analyses of published birth cohort studies to understand the association between early childhood TRAP exposure, and subsequent asthma, allergies and sensitization. Increased longitudinal childhood exposure to PM2.5 and black carbon was associated with increasing risk of subsequent asthma in childhood (PM2.5: OR 1.14, 95%CI 1.00 to 1.30 per 2 μg/m3 and black carbon: OR 1.20, 95%CI 1.05 to 1.38 per 1 × 10−5 m−1). Also, early childhood exposure to TRAP was associated with development of asthma across childhood up to 12 years of age. The magnitude of these associations increased with age, and the pattern was prominent for PM2.5. Increasing exposure to PM2.5 was associated with sensitization to both aero‐ and food allergens. There was some evidence that TRAP was associated with eczema and hay fever. In summary, exposure to TRAP was related to asthma and allergic diseases. However, the substantial variability across studies warrants long‐term birth cohort studies with regular repeated follow‐ups to confirm these findings.

Breastfeeding and asthma and allergies: a systematic review and meta‐analysis

To systematically review the association between breastfeeding and childhood allergic disease.

House dust mite sensitization in toddlers predicts current wheeze at age 12 years

BACKGROUND Identification of children at risk of developing asthma provides a window of opportunity for risk-reducing interventions. Allergen sensitization might identify high-risk children. OBJECTIVE We sought to determine whether skin prick tests (SPTs) to individual allergens up to age 2 years predict wheeze at age 12 years. METHODS In a birth cohort of 620 children oversampled for familial allergy, sensitization was assessed by using SPTs (monosensitized, polysensitized, or either) to 6 allergens at ages 6, 12, and 24 months. Wheeze and eczema were recorded 18 times during the first 2 years. Current wheeze was recorded at age 12 years. Adjusted associations were evaluated by multiple logistic regression. RESULTS A positive SPT to house dust mite (HDM) at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31 [95% CI 1.59-6.91]; 2 years, 6.37 [95% CI, 3.48-11.66]). Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51% to 91%) probability of wheeze at age 12 years compared with a 36% (95% CI, 23% to 50%) probability among those not sensitized. Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45% to 84%) probability of wheeze at age 12 years compared with a 35% (95% CI, 25% to 45%) probability among those not sensitized. Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was 64% (95% CI, 35% to 87%) if HDM sensitized and 50% (95% CI, 26% to 74%) if not. CONCLUSION HDM sensitization at age 1 or 2 years in wheezing and eczematous children at increased familial allergy risk predicts asthma and may inform management of these high-risk groups.

Breastfeeding and childhood acute otitis media: a systematic review and meta-analysis

To synthesise the evidence on the association between duration and exclusivity of breastfeeding and the risk of acute otitis media (AOM).

Perinatal Cat and Dog Exposure and the Risk of Asthma and Allergy in the Urban Environment: A Systematic Review of Longitudinal Studies

Background. The literature is contradictory concerning pet exposure and the risk of development of asthma and other allergic diseases. Using longitudinal studies, we aimed to systematically review the impact of pet ownership in the critical perinatal period as a risk factor for allergies in childhood. Methods. Medline database was searched for urban cohort studies with perinatal exposure to cats and/or dogs and subsequent asthma or allergic disease. Results. Nine articles, comprising 6498 participants, met inclusion criteria. Six found a reduction in allergic disease associated with perinatal exposure to dogs or, cats or dogs. One study found no association. Two found increased risk only in high-risk groups. Conclusion. Longitudinal studies in urban populations suggest that perinatal pets, especially dogs, may reduce the development of allergic disease in those without a family history of allergy. Other unmeasured factors such as pet-keeping choices in allergic families may be confounding the association seen in these high-risk families, and further study is required.

Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis

Background and objective While paracetamol exposure in pregnancy and early infancy has been associated with asthma, it remains unclear whether this is confounded by respiratory tract infections, which have been suggested as an alternative explanation. We undertook a systematic review and meta-analysis of longitudinal studies that reported the association between paracetamol exposure during pregnancy or infancy and the subsequent development of childhood asthma (≥5 years). Methods Two independent researchers searched the databases EMBASE and PUBMED on 12 August 2013 for relevant articles using predefined inclusion and exclusion criteria. Study quality was assessed and results were pooled using fixed effect models or random effect models when moderate between-study heterogeneity was observed. We explicitly assessed whether the observed associations are due to confounding by respiratory tract infections. Results Eleven observational cohort studies met the inclusion criteria. Any paracetamol use during the first trimester was related to increased risk of childhood asthma (5 studies, pooled OR=1.39, 95% CI 1.01 to 1.91) but there was marked between-study heterogeneity (I2=63%) and only one of these studies adjusted for maternal respiratory tract infections. Increasing frequency of use of paracetamol during infancy was associated with increased odds of childhood asthma (3 studies, pooled OR=1.15, 95% CI 1.00 to 1.31 per doubling of days exposure), but in these same three studies adjusting for respiratory tract infections reduced this association (OR=1.06, 95% CI 0.92 to 1.22). Discussion The association during early pregnancy exposure was highly variable between studies and exposure during infancy appears to be moderately confounded by respiratory tract infections. There is insufficient evidence to warrant changing guidelines on early life paracetamol exposure at this time.

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question.

Childhood Wheeze Phenotypes Show Less Than Expected Growth in FEV1 across Adolescence

RATIONALE Better characterization of childhood wheeze phenotypes using newer statistical methods provides a basis for addressing the heterogeneity of childhood asthma. Outcomes of these phenotypes beyond childhood are unknown. OBJECTIVES To determine if adolescent respiratory symptoms, lung function, and changes in lung function over adolescence differ by childhood wheeze phenotypes defined through latent class analysis. METHODS A prospective birth cohort (Melbourne Atopy Cohort Study) followed 620 high allergy-risk children, recording respiratory symptoms and spirometry at 12 and 18 years. Regression analyses identified relationships between wheeze phenotypes (never/infrequent, early transient, early persistent, intermediate onset, and late onset) and lung function, change in lung function (12-18 yr), respiratory symptoms, and asthma. The baseline classification was never/infrequent wheeze. MEASUREMENTS AND MAIN RESULTS Deficits in expected growth of lung function, measured by change in prebronchodilator FEV1 between 12 and 18 years, were found for early persistent (reduced 290 ml; 95% confidence interval [CI], 82-498), intermediate-onset (reduced 210 ml; 95% CI, 62-359), and late-onset wheeze (reduced 255 ml; 95% CI, 69-442). Intermediate-onset wheezers had persistent FEV1 deficit after bronchodilator at 18 years (reduced 198 ml; 46,350). Current asthma risk was increased for all phenotypes except early transient, which was also not associated with lung function deficits at 12 or 18 years. CONCLUSIONS Persistent wheeze phenotypes in childhood were associated with reduced growth in prebronchodilator FEV1 over adolescence. Intermediate-onset wheezers showed irreversible airflow limitation by 18 years. Conversely, early transient wheeze was a benign condition with no sequelae for respiratory health by age 18.

Breastfeeding and the risk of dental caries: a systematic review and meta-analysis.

To synthesise the current evidence for the associations between breastfeeding and dental caries, with respect to specific windows of early childhood caries risk.