Differing associations of BMI and body fat with asthma and lung function in children.

BACKGROUND: Current evidence suggests that in children there is a significant, albeit weak, association between asthma and obesity. Studies generally use body mass index (BMI) in evaluating body adiposity, but there are limitations to its use. METHOD: Children from a population-based study attending follow-up (age 11 years) were weighed, measured and had percent body (PBF) and truncal (PTF) fat assessed using bioelectrical impedance. They were skin prick tested and completed spirometry. Parents completed a validated respiratory questionnaire. Children were defined as normal or overweight according to BMI and PBF cut-offs. We tested the association between these adiposity markers with wheeze, asthma, atopy, and lung-function. RESULTS: Six hundred forty-six children (339 male) completed follow-up. BMI z-score, PBF, and PTF were all positively associated with current wheeze (odds ratio [95% CI]: 1.27 [1.03, 1.57], P = 0.03; 1.05 [1.00, 1.09], P = 0.03; 1.04 [1.00, 1.08], P = 0.04, respectively). Similar trends were seen with asthma. However, when examining girls and boys separately, significant positive associations were found with PBF and PTF and asthma but only in girls (gender interaction P = 0.06 and 0.04, respectively). Associations between being overweight and wheezing and asthma were stronger when overweight was defined by PBF (P = 0.007, 0.03) than BMI (P > 0.05). Higher BMI was significantly associated with an increase in FEV(1) and FVC, but only in girls. Conversely, increasing body fat (PBF and PTF) was associated with reduced FEV(1) and FVC, but only in boys. No associations between adiposity and atopy were found. CONCLUSION: All adiposity measures were associated with wheeze, asthma, and lung function. However, BMI and PBF did not have the same effects and girls and boys appear to be affected differently.

Effect of addition of salmeterol versus doubling the dose of fluticasone propionate on specific airway resistance in children with asthma.

Based primarily on extrapolation from adult studies, current pediatric asthma guidelines advise the addition of long-acting beta2-agonists for children symptomatic on low/moderate-dose inhaled corticosteroids before increasing the corticosteroid dose. This study was designed to compare the effect of combination salmeterol/fluticasone propionate (SFC) with doubling the dose of fluticasone propionate (FP) on specific airway resistance (sR(aw)) in moderate/severe persistent asthmatic children. A double-blind, randomized, controlled study was performed; children with asthma (4-11 years old; sR(aw) > 1.3 kPa·s) were randomized after a 2-week run-in (FP, 100 µg, b.i.d.) to either SFC (50 µg/100 µg b.i.d.) or FP (200 µg b.i.d.) via Diskus (GlaxoSmithKline, Stockley Park, U.K.) for 6 weeks. Lung function (sR(aw)-plethysmography and forced expiratory volume in 1 second [FEV1]) was measured before run-in, at randomization, after 3 weeks, at the end of 6-week treatment, and after 48-hour washout. Symptom scores and rescue medication use were recorded throughout. Thirty-five children entered run-in and 24 were randomized (mean age, 7.3 ± 2.2 years; 50% boys). All children showed an improvement in sR(aw). After adjusting for age, gender, and baseline sR(aw,) children receiving SFC had a significantly greater improvement in sR(aw) compared with those receiving FP (adjusted means ratio [95% confidence interval {CI}], 0.81 [0.68-0.97]; p = 0.021). There was a significant interaction between treatment and gender (sR(aw), adjusted geometric mean [95% CI ]kPa·s, SFC versus FP: boys, 1.25 [1.10-1.41] [n = 7] versus 1.87 [1.61-2.17] [n = 5]; girls, 1.29 [1.10-1.52] [n = 5] versus 1.29 [1.13-1.47] [n = 7]; p = 0.008). There were no differences in FEV1, symptoms, or rescue medication use between the groups. Addition of salmeterol provides greater improvement in sR(aw) than doubling the dose of FP in children with moderate/severe persistent asthma.

Day-care attendance, position in sibship, and early childhood wheezing: a population-based birth cohort study.

BACKGROUND: There are conflicting data on the effect of day-care attendance and position in sibship on the development of wheezing. OBJECTIVE: To investigate the relationship between day-care attendance and position in sibship with early childhood wheeze. METHODS: Prospective population-based birth cohort. At age 5 years, we collected information on parentally reported symptoms (n = 922); lung function was ascertained using plethysmography (n = 745) and allergic sensitization by skin testing (n = 815). Participants were assigned into categories according to the age of entry to day-care (0-6, 6-12, >12 mo) and number of older siblings (0, 1, 2, >2). RESULTS: Current wheeze was reported by 203 participants (22%); 224 (28%) were sensitized. In the multivariate model, sensitization (odds ratio, 2.47; 95% CI, 1.66-3.67), male sex (1.49, 1.01-2.20), maternal asthma (1.72, 1.10-2.68), and maternal smoking during pregnancy (2.15, 1.26-3.66) significantly increased the risk of wheezing. Entering day-care between 6 and 12 or after 12 months of age was significantly and inversely associated with current wheeze (0.25, 0.11-0.60; and 0.65, 0.44-0.98, respectively). Entry into nursery between 6 and 12 months reduced the risk of persistent wheezing (P = .04). We found no association between day-care attendance and lung function. Entering nursery in the first 6 months of life was associated with increased risk of atopy (2.47, 1.23-4.95). Having older siblings was associated only with rhinoconjunctivitis (0.72, 0.54-0.97). CONCLUSION: Day-care attendance was associated with a reduced risk of current wheezing in 5-year-old children. The protective effect appeared strongest for children who entered day-care between the ages of 6 and 12 months.

Exhaled breath condensate pH and childhood asthma: unselected birth cohort study.

RATIONALE: Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients with asthma. OBJECTIVES: To investigate the relationship between EBC-pH and symptoms suggestive of childhood asthma in an epidemiologic setting and examine its relation to lung function, airway hyperresponsiveness (AHR), and airway inflammation. METHODS: Within the context of a prospective population-based birth cohort, EBC was collected from 630 children at age 8 yr using the RTube (pH measured after deaeration with argon). Lung function was measured by spirometry (FEV1; n = 521) and plethysmography (sRaw; n = 567), and AHR by methacholine challenge (n = 498). Airway inflammation was assessed using exhaled nitric oxide (eNO; n = 305). RESULTS: EBC-pH values ranged widely (4.40-8.29), and did not differ between 54 children with parentally reported asthma and 562 nonasthmatic subjects (median [interquartile range]: 7.75 [7.45-7.85] vs. 7.77 [7.59-7.87]; p = 0.35). There was a trend for lower EBC-pH among current wheezers (n = 98; 7.72 [7.50-7.83]) compared with nonwheezers (n = 532; 7.77 [7.60-7.87]; p = 0.07). Wheeze frequency, severity, and use of antiasthma medication were not associated with EBC-pH. There was no consistent association between EBC-pH and lung function, airway reactivity, and airway inflammation (FEV1, sRaw, PD20 methacholine, or eNO). There was no significant difference in EBC-pH between current wheezers receiving asthma medication who had positive methacholine challenge compared with children without any of these features. CONCLUSIONS: In the epidemiologic setting, EBC-pH does not differ between children with and without parentally reported symptoms suggestive of asthma. We found no consistent association between EBC-pH and lung function, AHR, and airway inflammation in this sample from the general population.

Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function.

RATIONALE: Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. OBJECTIVES: Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene and early-life lung function. METHODS: Children were genotyped for 17 SNPs in ADAM33. Lung function at age 3 (n = 285) and 5 years (n = 470) was assessed using plethysmographic measurement of specific airway resistance (sRaw). At age 5, we also measured FEV(1). SNPs were analyzed individually using logistic regression, followed by linkage disequilibrium mapping to identify the causal locus. MAIN RESULTS: Carriers of the rare allele of F+1 SNP had reduced lung function at age 3 years (p = 0.003). When the recessive model was considered, four SNPs (F+1, S1, ST+5, V4) showed association with sRaw at age 5 years (p < 0.04). Using linkage disequilibrium mapping, we found evidence of a significant causal location between BC+1 and F1 SNPs, at the 5' end of the gene. Four SNPs were associated with lower FEV(1) (F+1, M+1, T1, and T2; p < or = 0.04). The risk of transient early wheezing more than doubled among children homozygous for the A allele of F+1 (odds ratio, 2.39; 95% confidence intervals, 1.18-4.86; p = 0.02), but there was no association between any SNP and allergic sensitization or physician-diagnosed asthma. CONCLUSIONS: Polymorphisms in ADAM33 predict impaired early-life lung function. The functionally relevant polymorphism is likely to be at the 5' end of the gene.

Wheeze phenotypes and lung function in preschool children.

Distinct phenotypes can be identified in childhood wheezing illness. Within the context of a birth cohort study, we investigated the association between preschool lung function and phenotypes of wheeze. From parentally reported history of wheeze (interviewer-administered questionnaire, age 3 and 5 years), children were classified as never wheezers, transient early wheezers, late-onset wheezers, or persistent wheezers. Lung function (specific airway resistance [sRaw]; kPa/second) was assessed at age 3 (n = 463) and 5 years (n = 690). Persistent wheezers had markedly poorer lung function compared with other groups. In children who had wheezed by age 3, the risk of persistent wheeze increased with increased sRaw (odds ratio [OR] 5.2, 95% confidence interval [CI] 1.3-22.0; p = 0.02). In a multivariate model, increasing sRaw (OR 5.5, 95% CI 1.2-25.9; p = 0.03) and the child's sensitization (OR 2.8, 95% CI 1.3-5.8; p = 0.008) were significant independent predictors of persistent wheezing. We found no association between lung function at age 3 and late-onset wheeze in children who had not wheezed previously (OR 0.6, 95% CI 0.07-5.3; p = 0.64). In conclusion, poor lung function at age 3 predicted the subsequent persistence of symptoms in children who had wheezed within the first 3 years, but was not associated with the onset of wheeze after age 3 in children who had not wheezed previously.

Lung function at age 3 years: effect of pet ownership and exposure to indoor allergens.

OBJECTIVE: To investigate the effect of pet ownership and exposure to indoor allergens on lung function in 3-year-old children. DESIGN: Birth cohort study. SETTING: Community. PARTICIPANTS: Children recruited prenatally and followed prospectively to age 3 years. MAIN OUTCOME MEASURES: Specific airway resistance (sRaw) (measured with body plethysmograph) at age 3 years; skin-prick tests; data on cat and dog ownership collected prospectively; allergen levels measured in dust collected from homes (high exposure defined as mite allergens >2 microg/g in mattress, and dog >10 microg/g and cat >8 microg/g allergens on the living room floor). RESULTS: There was no effect of cat or dog ownership at birth or age 3 years on lung function, and no association between lung function and mite, dog, or cat allergen exposure. Sensitized children exposed to high levels of sensitizing allergen had significantly poorer lung function (n = 49, sRaw kiloPascal per second [kPa/s]; geometric mean [GM], 1.20; 95% confidence interval [CI], 1.13-1.28) than children who were not sensitized and not exposed (n = 114; GM, 1.08; 95% CI, 1.04-1.12); not sensitized, but exposed (n = 282; GM, 1.07; 95% CI, 1.05-1.10); or sensitized and not exposed (n = 53; GM, 1.12; 95% CI, 1.06-1.18; P = .005). In a multivariate model, independent significant associates of lung function were maternal and paternal asthma, and the combination of sensitization and exposure to sensitizing allergen, with significant interaction between them. Lung function was substantially worse in sensitized and highly exposed children with both asthmatic parents (GM, 2.23; 95% CI, 1.68-2.97), compared with those with neither (GM, 1.09; 95% CI, 1.04-1.16) or just 1 of these features. CONCLUSIONS: Pet ownership, sensitization without exposure, or exposure in nonsensitized individuals have no effect on lung function. However, the combination of specific sensitization and exposure to sensitizing allergen is associated with significantly poorer lung function in early life.

Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years.

We investigated whether environmental control during pregnancy and early life affects sensitization and lung function at the age of 3 years. High-risk children (n = 251) were prenatally randomized to stringent environmental control (active) or no intervention (control). Questionnaires, skin testing, IgE, and specific airway resistance (sRaw) measurement were completed at the age of 3 years. Children in the active group were significantly more frequently sensitized compared with control subjects (at least one allergen by skin tests: risk ratio, 1.61; 95% confidence interval [CI], 1.02-2.55; p = 0.04; mite by IgE: risk ratio, 2.85; 95% CI, 1.02-7.97; p = 0.05). However, sRaw was significantly better in the active group (kiloPascal/second, geometric mean [95% CI]: 1.05 [1.01-1.10] vs. 1.19 [1.13-1.25], p < 0.0001, active vs. control). Maximal flow at functional residual capacity was measured using rapid thoracic compression at the age of 4 weeks in a subgroup. Prospective lung function data (at infancy and 3 years) were obtained in 32 children (14 active and 18 control). There was no difference in infant lung function between the groups, but at 3 years, sRaw was significantly lower in the active compared with control children (p = 0.003). Stringent environmental control was associated with increased risk of mite sensitization but better results for some measurements of lung function in high-risk children at the age of 3 years.

Urinary eosinophilic protein X, atopy, and symptoms suggestive of allergic disease at 3 years of age.

BACKGROUND: Urinary eosinophilic protein X (U-EPX) measurement is easy to perform in children. However, its use for prediction, diagnosis, and monitoring of asthma and atopy is unclear. OBJECTIVE: We sought to investigate the relationship between U-EPX and clinical phenotypes suggestive of allergic diseases. METHODS: U-EPX measurement (RIA), respiratory questionnaires, and skin testing were completed at age 3 years in 903 children followed prospectively from birth. Specific airway resistance was measured in 503 currently asymptomatic children by using whole-body plethysmography during tidal breathing. RESULTS: Nonatopic children with wheezing or eczema had slightly increased U-EPX levels compared with nonatopic asymptomatic children. U-EPX levels (geometric mean EPX/creatinine ratio) were as follows: nonatopic asymptomatic children (n = 313), 61.3 microg/mmol (95% CI, 56.4-66.6 microg/mmol); nonatopic children with wheezing (n = 148), 71.2 microg/mmol (95% CI, 63.2-80.1 microg/mmol); nonatopic children with eczema (n = 90), 65.7 microg/mmol (95% CI, 56.7-76.2 microg/mmol); and nonatopic children with wheezing and eczema (n= 86), 79.7 microg/mmol (95% CI, 67.4-94.3 microg/mmol). Children who had persistent atopy early in life had significantly higher U-EPX levels at age 3 years (nonatopic at 1 and 3 years [n = 263], 63.4 microg/mmol [95% CI, 58.4-69.0 microg/mmol]; atopic at 1 but not 3 years [n = 24], 65.1 microg/mmol [95% CI, 43.8-96.7 microg/mmol]; nonatopic at 1 year and atopic at 3 years [n = 62], 90.0 microg/mmol [95% CI, 74.6-108.4 microg/mmol]; atopic at 1 and 3 years [n = 35], 111.5 microg/mmol [95% CI, 89.2-139.3 microg/mmol]; P <.002). Atopy alone and with wheezing, eczema, or both was associated with significantly increased U-EPX levels (P <.0001). Wheezing appeared to be associated with higher U-EPX levels compared with eczema in both atopic and nonatopic children. The highest U-EPX level was found in atopic children with a history of wheezing and eczema (P <.0001). There was no relationship between U-EPX level and lung function. CONCLUSION: U-EPX level reflects the presence of atopy and associated symptoms and might be useful for monitoring the progression of allergic disease.