Katharine C. Pike

Patterns of fetal and infant growth are related to atopy and wheezing disorders at age 3 years

Background Little is known about whether patterns of early growth are associated with altered respiratory and immune development. This study relates prenatal and infant growth patterns to wheeze and atopy at age 3 years. Methods Birth weight and length were measured in 1548 children born at term. Conditional fetal head and abdominal circumference growth velocities were calculated from antenatal ultrasound measurements. Conditional postnatal growth velocities were calculated from infant weight, length and adiposity data. Measures of size and conditional growth were related to parentally-reported infant and early childhood wheeze and to atopic status at age 3 years. Results The risk of atopy increased by 46% per SD increase in abdominal circumference growth velocity from 11 to 19 weeks gestation but by 20% per SD decrease in abdominal growth velocity from 19 to 34 weeks (p=0.007 and p=0.011, respectively). The risk of atopic wheeze increased by 20% per SD decrease in 19–34-week abdominal growth (p=0.046). The risk of non-atopic wheeze increased by 10% per SD decrease in 11–19-week head circumference growth. Greater relative infant weight and adiposity gains were associated with both atopic and non-atopic wheeze. Conclusions A rapid growth trajectory during 11–19 weeks gestation followed by late gestation growth faltering is associated with atopy, suggesting that influences affecting fetal growth may also alter immune development. A lower early fetal growth trajectory is associated with non-atopic wheeze, possibly reflecting an association with smaller airways. An association between postnatal adiposity gain and wheeze may partly reflect prenatal influences that cause fetal growth to falter but are then followed by postnatal adiposity gain.

Long term respiratory consequences of intrauterine growth restriction

Epidemiological studies demonstrate that in-utero growth restriction and low birth weight are associated with impaired lung function and increased respiratory morbidity from infancy, throughout childhood and into adulthood. Chronic restriction of nutrients and/or oxygen during late pregnancy causes abnormalities in the airways and lungs of offspring, including smaller numbers of enlarged alveoli with thicker septal walls and basement membranes. The structural abnormalities and impaired lung function seen soon after birth persist or even progress with age. These changes are likely to cause lung symptomology through life and hasten lung aging.

The relationship between maternal adiposity and infant weight gain, and childhood wheeze and atopy

Background Obesity and asthma have increased in westernised countries. Maternal obesity may increase childhood asthma risk. If this relation is causal, it may be mediated through factors associated with maternal adiposity, such as fetal development, pregnancy complications or infant adiposity. We investigated the relationships of maternal body mass index (BMI) and fat mass with childhood wheeze, and examined the influences of infant weight gain and childhood obesity. Methods Maternal prepregnancy BMI and estimated fat mass (from skinfold thicknesses) were related to asthma, wheeze and atopy in 940 children. Transient or persistent/late wheeze was classified using questionnaire data collected at ages 6, 12, 24 and 36 months and 6 years. At 6 years, skin-prick testing was conducted and exhaled nitric oxide and spirometry measured. Infant adiposity gain was calculated from skinfold thickness at birth and 6 months. Results Greater maternal BMI and fat mass were associated with increased childhood wheeze (relative risk (RR) 1.08 per 5 kg/m2, p=0.006; RR 1.09 per 10 kg, p=0.003); these reflected associations with transient wheeze (RR 1.11, p=0.003; RR 1.13, p=0.002, respectively), but not with persistent wheeze or asthma. Infant adiposity gain was associated with persistent wheeze, but not significantly. Adjusting for infant adiposity gain or BMI at 3 or 6 years did not reduce the association between maternal adiposity and transient wheeze. Maternal adiposity was not associated with offspring atopy, exhaled nitric oxide, or spirometry. Discussion Greater maternal adiposity is associated with transient wheeze but not asthma or atopy, suggesting effects upon airway structure/function but not allergic predisposition.

Validation of novel wheeze phenotypes using longitudinal airway function and atopic sensitization data in the first 6 years of life: Evidence from the Southampton Women's survey†

In 1995 the Tucson Childrens Respiratory Study (TCRS) identified clinically distinct phenotypes amongst early wheezers; the Avon Longitudinal Study of Parents And Children (ALSPAC) has recently re‐examined these.

Maternal complications in pregnancy and wheezing in early childhood: a pooled analysis of 14 birth cohorts

BACKGROUND Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient. METHODS A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring. Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index ≥ 30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12-24 months of age. Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model. RESULTS The study included 85509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98-1.06) and 1.20 (95% CI: 0.98-1.47) for hypertensive disorders; 1.09 (95% CI: 1.01-1.18) and 1.23 (95% CI: 1.07-1.43) for preeclampsia; 1.04 (95% CI: 0.97-1.13) and 1.24 (95% CI: 0.86-1.79) for diabetes; 1.08 (95% CI: 1.05-1.11) and 1.19 (95% CI: 1.12-1.26) for overweight; 1.12 (95% CI: 1.08-1.17) and 1.16 (95% CI: 0.97-1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P=0.027). CONCLUSIONS Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring.

Exhaled nitric oxide monitoring does not reduce exacerbation frequency or inhaled corticosteroid dose in paediatric asthma: a randomised controlled trial

Inhaled corticosteroid therapy (ICS) for asthma is currently modified according to symptoms and lung function. Fractional exhaled nitric oxide (FENO) has been demonstrated to be a non‐invasive marker of eosinophilic inflammation. Studies of FENO‐driven asthma management show variable success.

The bronchodilator response in preschool children: A systematic review

The bronchodilator response (BDR) is frequently used to support diagnostic and therapeutic decision‐making for children who wheeze. However, there is little evidence‐based guidance describing the role of BDR testing in preschool children and it is unclear whether published cut‐off values, which are derived from adult data, can be applied to this population.

Maternal body mass index: relation with infant respiratory symptoms and infections

Maternal obesity is increasingly prevalent in many westernized countries. Many studies report associations between maternal obesity and childhood wheeze or asthma but few have considered maternal obesity in relation to respiratory infections or symptoms other than wheeze during infancy. This study assesses the relationship between maternal BMI and reported wheeze, cough and respiratory infections during the first year of life.

Ciprofloxacin during upper respiratory tract infections to reduce Pseudomonas aeruginosa infection in paediatric cystic fibrosis: a pilot study

Objectives: Acute viral respiratory illnesses are associated with acquisition of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients. This study aimed to pilot a protocol for a randomized controlled trial to determine whether oral antipseudomonal antibiotics used at the onset of such episodes might delay onset of infection with this organism. Methods: A total of 41 children with CF aged 2–14 years, without chronic Pseudomonas infection, were randomized to receive ciprofloxacin (n = 28) or placebo (n = 13) at the onset of acute viral respiratory infections on an intention to treat basis, during a study period of up to 32 months. Results: There were no unexpected adverse events believed related to the use of the study medication. The rate of withdrawal from the study was low (approximately 7%) and did not differ between groups. Randomization was effective and acceptable to participants. Primary and secondary outcome measures all favoured active treatment, but there were no significant between group differences. The median rate of Pseudomonas isolates was 0/patient/year (interquartile range 0–0.38) in both the active and placebo groups. Kaplan–Meier survival curves showed no significant difference in time to first Pseudomonas isolate between groups. Conclusions: This study demonstrated the clinical feasibility of using oral ciprofloxacin in CF patients at times of viral infection. Within this sample size, no significant association was found between active treatment and decreased growth of Pseudomonas in follow-up microbiological samples. A definitive study would require at least 320 children to demonstrate significant differences in the rate of pseudomonal isolates.

Nutritional outcomes in cystic fibrosis – are we doing enough?

Although outcome data for individuals with cystic fibrosis (CF) have shown consistent improvements throughout the twentieth century, more recent national registry data suggests that outcomes have reached a plateau. Median values for nutritional outcomes in CF currently cluster around the fiftieth centile for the normal population. These data suggest that up to half of CF patients have sub-optimal body mass index (BMI) which might have a significant adverse impact on their respiratory status. BMI might be underestimating the extent to which more important lean body mass might also be reduced. Nutritional decline is a particular problem during adolescence and commonly persists into early adult life. Current treatment strategies to optimize nutrition include the use of high energy diets, proton pump inhibitors and optimal use of enzyme preparations including higher strength preparations to decrease pill burden. Whilst these are all of potential benefit, poor adherence to nutritional care recommendations is probably the greatest impediment to future health improvement. More effective strategies to impact on treatment adherence are needed.