Biomedical subjects

Ashley Woodcock

Publications and source records attributed to Ashley Woodcock.

At least 19 recordsLinked to original sources

PubMed2006

Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study.

BACKGROUND: Wheezing and asthma often begins in early childhood, but it is difficult to predict whether or not a wheezy infant will develop asthma. Some researchers suggest that treatment with inhaled corticosteroids at the first signs of wheezing in childhood could prevent the development of asthma later in life. However, other investigators have reported that although such treatment could help control symptoms, the benefits can disappear within months of stopping treatment. We tested our hypothesis that to prevent loss of lung function and worsening asthma later in childhood, anti-inflammatory treatment needs to be started early in life. METHODS: We did a randomised, double-blind, controlled study of inhaled fluticasone propionate 100 mug twice daily in young children who were followed prospectively and randomised after either one prolonged (>1 month) or two medically confirmed wheezy episodes. The dose of study drug was reduced every 3 months to the minimum needed. If the symptoms were not under control by 3 months, open-label fluticasone propionate 100 mug twice daily was added to the treatment. Children were followed-up to 5 years of age, at which point we gave their parents or guardians questionnaires, and measured the children's lung function (specific airways resistance [sR(aw)], forced expiratory volume in 1s [FEV1]) and airway reactivity (eucapnic voluntary hyperventilation [EVH] challenge). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN86717853. FINDINGS: We followed 1073 children prospectively, of whom 333 were eligible, and 200 of these began treatment (130 male, median age 1.2 years [range 0.5-4.9]; 101 placebo, 99 treatment); 173 (85 treatment, 88 placebo) completed the follow-up at age five years. The groups did not differ significantly in the proportion of children with current wheeze, physician-diagnosed asthma or use of asthma medication, lung function, or airway reactivity (percentage change in FEV1, adjusted mean for placebo 5.5% [95% CI -2.5 to 13.4]) vs for treatment 5.0% [-2.2 to 12.2], p=0.87). There were no differences in the results after adjustment for open-label fluticasone propionate, nor between the two groups in the time before the open-label drug was added (estimated hazard ratio 1.12 [95% CI 0.73-1.73], p=0.60), or the proportion needing the open-label drug (43 [42.57%] placebo, 41 [41.41%] treatment). INTERPRETATION: The early use of inhaled fluticasone propionate for wheezing in preschool children had no effect on the natural history of asthma or wheeze later in childhood, and did not prevent lung function decline or reduce airway reactivity.

Administration, Inhalation↗

PubMed2006

Inhaled steroid/long-acting beta 2 agonist combination products provide 24 hours improvement in lung function in adult asthmatic patients.

BACKGROUND: The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES: The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS: Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS: In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION: Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

Administration, Inhalation↗

PubMed2006

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.

Asthma↗

PubMed2006

Endotoxin exposure, CD14, and allergic disease: an interaction between genes and the environment.

RATIONALE: High endotoxin exposure may reduce the risk of allergic sensitization. OBJECTIVE: To determine the relationship between a promoter polymorphism in the CD14 gene (CD14/-159 C to T) and endotoxin exposure in relation to the development of allergic sensitization, eczema, and wheeze within the setting of a birth cohort. METHODS: We genotyped 442 children (CD14/-159 C to T; rs2569190). We assessed children for allergic sensitization (IgE > 0.2 kU/L to at least one of seven allergens), eczema (physical examination), and parentally reported wheeze. Endotoxin was measured in house dust. MAIN RESULTS: Genotype frequencies were consistent with other populations (TT, 25%; CT, 47%; CC, 28%). Sensitization (present in 33% of children) was not associated with genotype. For children with TT and CT genotypes, there was no association between endotoxin and sensitization (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.71-1.23; p = 0.7; and OR, 0.90; 95% CI, 0.77-1.04; p = 0.16, respectively) or endotoxin and eczema (OR, 0.99; 95% CI, 0.81-1.20; p = 0.89; and OR, 1.38; 95% CI, 0.83-2.30; p = 0.22, respectively). In children with the genotype CC, increasing endotoxin load was associated with a marked and significant reduction in the risk of sensitization (OR, 0.70; 95% CI, 0.55-0.89; p = 0.004) and eczema (OR, 0.73; 95% CI, 0.56-0.95; p = 0.02). However, we observed an increased risk of nonatopic wheeze with increasing endotoxin exposure in children with the CC genotype (OR, 1.42; 95% CI, 1.01-1.99; p = 0.04) but not other genotypes. No effect was seen for atopic wheeze. CONCLUSIONS: Increasing endotoxin exposure is associated with reduced risk of allergic sensitization and eczema but with increased risk of nonatopic wheeze in children with the CC genotype at -159 of the CD14 gene. The impact of environmental endotoxin may be enhanced in individuals with this genotype.

Asthma↗

PubMed2006

Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease.

BACKGROUND: Codeine is the standard antitussive treatment to which novel agents are compared. Little is known about the objective effect of any treatments on cough in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To quantify the effect of codeine on objective cough frequency (quantified as time spent coughing: cough seconds, cs/h), citric acid cough threshold, and subjective measures in a double-blind, placebo-controlled crossover study in COPD. METHODS: We studied 21 patients with physician-diagnosed, stable disease who complained of cough (76.9% male; mean age, 67.7 years; mean predicted FEV(1), 53.4%; median smoking history, 43.5 pack-years). Each subject performed a cough challenge (single breath, citric acid), 10-hour daytime ambulatory and overnight cough recordings, subjective cough scores, and visual analog scales at baseline and on 2 study days, 1 week apart. Codeine phosphate 60 mg or matched placebo were given, in random order, at the start of each cough recording (0 and 12 hours). RESULTS: Median time spent coughing at baseline was 8.27 cs/h (interquartile range [IQR], 5.94-11.67); after placebo treatment, 7.22 cs/h (IQR 4.42-10.40); and after codeine treatment, 6.41 cs/h (IQR 3.86-9.10). Codeine treatment had a significant effect on time spent coughing compared with baseline (P = .02) but not compared with placebo (P = .52). There were no significant differences in cough challenge thresholds (log concentration of tussive agent causing 2 coughs or log concentration of tussive agent causing 5 coughs) or subjective cough measures for codeine compared with placebo. CONCLUSION: In this study, codeine was no more effective than placebo in patients with COPD complaining of cough. CLINICAL IMPLICATIONS: Codeine is the antitussive agent to which we compare new treatments; however, in a group of stable patients with COPD, it had no effect on cough frequency over placebo.

Aged↗

PubMed2006

Dust mite allergen avoidance as a preventive and therapeutic strategy.

Asthma is a global health problem with genetic and environmental components. Indoor allergens have a major impact on asthma, and exposure in sensitized subjects can compromise lung function. A reduction in allergen exposure would seem a logical facet to treatment. Methods for reducing mite allergen levels that are effective in the laboratory may not work in the home and may not result in a clinical benefit. Six ongoing studies are investigating the effects of environmental control on the primary prevention of asthma and allergies. Although the Isle of Wight and Canadian studies provide encouraging results at age 8 and 7 years, respectively, it will be some time before a definitive public health message emerges. For secondary prevention, there is little evidence to support the use of mite-proof encasings as a single intervention in adults. In children, however, single or multifaceted interventions appear to be of some benefit.

Adult↗

PubMed2006

Intranasal air sampling in homes: relationships among reservoir allergen concentrations and asthma severity.

BACKGROUND: The relationship among inhaled allergen exposure, sensitization, and asthma severity is unknown. OBJECTIVES: To investigate the relationship among personal allergen exposure, reservoir dust allergen concentrations, and physiological measures of asthma severity; to examine the numbers of particles inspired that react with autologous IgE and IgG4. METHODS: A total of 117 patients with asthma wore 5 nasal air samplers (NASs) at home: 1 each for exposure to mite, cat and dog allergens, NAS-IgE, and NAS-IgG4. NASs were processed by HALOgen assay for allergen measurement and incubated with autologous serum for detection of NAS-IgE and NAS-IgG4. Reservoir allergen concentrations were measured by ELISA. Subjects' asthma severity was ascertained by measurement of lung function, exhaled nitric oxide, and nonspecific bronchial reactivity to histamine. RESULTS: Nasal air sampler counts correlated with reservoir concentrations for cat (r=0.31; P=.001) and dog (r=0.20; P=.03) but not mite allergen (r=0.001; P=1.0). There was no significant relationship between sensitization with exposure measured by NAS to any allergen and PD20FEV1 (F[3,60]=1.60; P=.20); however, sensitization with exposure in dust reservoirs had significant effects on PD20FEV1 for any allergen (F[3,59]=3.12; P=.03), cat (F[3,59]=3.77; P=.01), and mite (F[3,59]=2.78; P=.05), but not dog (F[3,59]=1.06; P=.37). We repeated the analysis with separate variables for sensitization and exposure, controlling for the confounders; sensitization but not exposure conferred lower PD20FEV1 values. However, increasing cat allergen exposure was associated with improving bronchial reactivity in not cat-sensitized patients. NAS-IgE and NAS-IgG4 counts bore no relationship to any measure of asthma severity. CONCLUSION: Nasal air samplers confer no advantage over reservoir dust analysis for studies of asthma severity. CLINICAL IMPLICATIONS: In common with other measures of exposure, single nasal air samples do not provide a useful measure of home allergen exposure for the individual patient with allergic asthma.

Adolescent↗

PubMed2006

Atopic wheezing and early life antibiotic exposure: a nested case-control study.

Several factors including early-life antibiotic usage have been implicated in the rising prevalence of allergic sensitization and asthma. A nested case-control study comparing antibiotic exposure of 37 sensitized children with recurrent wheeze (age 3-5 yr) and 37 non-sensitized children who had never wheezed was carried out within a population-based birth cohort (matching for age, sex, parental atopy, allergen exposure, and pet ownership). We collected data on antibiotic prescriptions during first 3 yr of life (timing, type, indication) from the primary care medical records. Significantly, more cases than controls received one or more antibiotic courses during the first year of life (92% vs. 70%, p = 0.04). The median time to first antibiotic course was shorter for the cases than the controls (6 vs. 8 months, p = 0.03). The total number of antibiotic receipts was greater amongst cases in each of the first 3 yr of life, but this reached significance only when the whole three-year period was considered (249 vs. 182 courses, p = 0.05). The increased ratio of antibiotic receipt in cases over controls was highest in the first year of life (1.32, 95% CI 0.99-1.78). Significantly more cases than controls were prescribed antibiotics for lower respiratory tract infection during the first 3 yr (p = 0.007), but not during the first year of life (p = 0.52). Antibiotics use by class was similar in the two groups. Our data support the hypothesis that early life exposure to broad-spectrum antibiotics may have a causative role in sensitisation and the expression of wheeze.

Anti-Bacterial Agents↗

PubMed2006

Cough in COPD: correlation of objective monitoring with cough challenge and subjective assessments.

BACKGROUND: The relationships between objective cough rates, cough reflex sensitivity, subjective estimates of cough frequency, and cough-related quality of life in patients with COPD are poorly understood. SUBJECTS: Twenty-six patients with stable COPD who complained of cough (76.9% men; mean +/- SD age, 68.7 +/- 6.9 years; mean FEV(1), 54.2 +/- 12.0% of predicted; median smoking history, 42.4 pack-years [range, 13 to 135 pack-years]). METHODS: Subjects performed a cough challenge test, ambulatory daytime and overnight sound recordings, scored the severity of cough (0 to 5 score and visual analog scale) for each recording period, and completed a cough-specific quality of life questionnaire (CQLQ). Coughs were counted manually and quantified in terms of cough seconds per hour (cs/h): the number of seconds within the recording that contain cough. RESULTS: Overall median time spent coughing was 7.5 cs/h (range, 2.7 to 23.1 cs/h; daytime median, 12.4 cs/h [range, 3.3 to 40.4 cs/h]; overnight, 1.9 cs/h [0.0 to 19.0 cs/h]) [p = <0.01]. Median log concentration of citric acid eliciting five coughs (C5) was - 0.9 mol/L (range, - 1.5 to 0.0 mol/L). Day time but not overnight time spent coughing was significantly correlated with log C5 (log C5 r = - 0.49, p = 0.02, and r = - 0.20, p = 0.37, respectively). Subjective cough scores and visual analog scales were moderately associated with objective time spent coughing: daytime (r = 0.37, p = 0.03, and r = 0.41, p = 0.03) and overnight (r = 0.48, p = <0.01, and r = 0.5, p = 0.01), respectively. CONCLUSIONS: Subjective measures of cough and cough reflex sensitivity are statistically related to time spent coughing in patients with COPD, but with low-to-moderate levels of correlation. These measures have insufficient predictive value to substitute for objective time spent coughing; however, in conjunction with the CQLQ, they may provide a qualitative dimension to the assessment of cough.

Aged↗

PubMed2005

IgE antibody quantification and the probability of wheeze in preschool children.

BACKGROUND: IgE-mediated sensitization is usually considered a dichotomous variable (either sensitized or not). Quantitative IgE antibody analysis may better predict the expression of wheeze. OBJECTIVE: Within the context of a population-based birth cohort, we investigated the association among wheeze, lung function, and specific IgE antibody levels. METHODS: Children (n = 521) were followed to age 5 years with repeated questionnaires, skin testing, and measurement of lung function (specific airway resistance) and specific serum IgE (ImmunoCAP). RESULTS: Using specific IgE as a continuous variable, the risk of current wheeze increased significantly with increasing IgE to mite, cat, and dog (P < .0001). When IgE levels to these 3 allergens were summed, the probability of current wheeze increased 1.33-fold (95% CI, 1.21-1.47; P < .0001) per logarithmic unit increase, corresponding to an odds ratio of 3.1 at 10 and 4.25 at 30 kU(A)/L (kilo units of Allergen per liter). Similarly, increasing sum of mite-specific, cat-specific, and dog-specific IgE was associated with reduced lung function (P = .004). Among sensitized children (n = 184), the sum of mite, cat, and dog IgE was the strongest associate of current wheeze (odds ratio, 1.28; 95% CI, 1.13-1.46; P < .001), corresponding to an odds ratio of 2.56 at 10 and 3.32 at 30 kU(A)/L. There was no association between current wheeze and the size of skin test wheal. Furthermore, the sum of IgE to mite, cat, and dog at age 3 years increased the risk of persistent wheeze by age 5 years (2.15-fold/logarithmic unit increase in the specific IgE). CONCLUSION: IgE-mediated sensitization is not an all or nothing phenomenon. The probability of wheeze and reduced lung function increases with increasing specific IgE antibody levels.

Airway Resistance↗

PubMed2005

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.

ADAM Proteins↗

PubMed2005

Potential roles in rhinitis for protease and other enzymatic activities of allergens.

Exposure to airborne pollen, fungal allergens, and dust mite allergens is associated with the development of allergic rhinitis. Biologic function of allergens is considered to be a key determinant for allergenicity, and many clinically important allergens have been shown to possess enzymatic activity. It is proposed that by enabling allergens to breach the integrity of the airway epithelial barrier, proteolytic activity plays an adjuvant pro-allergic role influencing immunogenicity. In this review, current evidence regarding enzymatic activity of aeroallergens is described, and the potential role of aeroallergens in allergic rhinitis is discussed.

Allergens↗

PubMed2005

The effect of reducing the fine-particle mass of salmeterol from metered-dose inhalers on bronchodilatation and bronchoprotection against methacholine challenge: a randomized, placebo-controlled, double-blind, crossover study.

OBJECTIVE: This study examined the clinical relevance of fine-particle mass (FPM) delivered from metered dose inhalers (MDIs) to bronchodilatation and bronchoprotection against methacholine challenge by comparing a marketed chlorofluorocarbon (CFC) formulation of salmeterol with an investigational hydrofluoroalkane (HFA)formulation. METHODS: This was a randomized, double-blind, placebo-controlled, 3-way crossover study in patients with mild to moderate asthma who had a forced expiratory volume in 1 second (FEV (1)) of > or =60% predicted and a base-line provocation dose of inhaled methacholine required to produce a 20% decrease in FEV(1) (PD (20) [methacholine]) of < or =3.2 mg. On separate occasions, patients received 2 inhalations of salmeterol 25 microg from either the CFC MDI (FPM 14 microg), the investigational HFA MDI (FPM 7 microg), or placebo via CFC MDI. Serial measurements of FEV(1) were made over 90 minutes after dosing, followed by methacholine challenge. Efficacy end points were PD(20) (methacholine) and FEV(1) AUC (inc) (incremental area under the FEV(1) curve) over 15 to 90 minutes. The study was designed to demonstrate non-inferiority of the investigational HFA formulation to the CFC formulation in terms of protection against methacholine-induced bronchial hyperresponsiveness; for PD(20) (methacholine), noninferiority was predefined as 1.0 doubling dose of methacholine. RESULTS: The study enrolled 40 patients (65% men; mean age, 36.9 years). Both active treatments were significantly better than placebo in terms of PD(20) (methacholine) (P < 0.001). In the per-protocol population, the mean (SE) difference in bronchoprotection between the CFC MDI and placebo was 2.7888 (0.3432) doubling doses of methacholine (n = 32), and the difference between the investigational HFA MDI and placebo was 1.8268 (0.3418) doubling doses(n = 33). The adjusted mean (SE) treatment difference between the CFC MDI and HFA MDI was 0.9621 (0.3454) doubling doses. The upperlimit of the 95% CI (0.2714-1.6527) was greater than the predefined limit for noninferiority. There was no significant difference in FEV(1) AUC(inc) between formulations (mean treatment difference, 1.895 L . min; 95% CI, -4.893 to 8.684); however, both active treatments were significantly different from placebo (P < 0.001). CONCLUSIONS: FPM from different MDI formulations may affect the bronchoprotective properties of salmeterol. In this study, the formulation with the smaller FPM was associated with less-effective bronchoprotection, although there was no difference in bronchodilatation. This study did not demonstrate noninferiority of the investigational HFA formulation to the CFC formulation in terms of protection against methacholine-induced bronchial hyperresponsiveness.

Adult↗

PubMed2004

Behavior problems antecede the development of wheeze in childhood: a birth cohort study.

RATIONALE: It is not clear to what extent behavior problems observed in children with asthma antecede asthma development, or are a consequence of the disease. OBJECTIVES: We investigated psychologic factors at age 3 years and subsequent development of wheeze by age 5 in an unselected birth cohort study. Children were recruited prenatally, followed prospectively, and reviewed at age 3 and 5 years. The rate of significant behavior problems at age 3 (above the clinically relevant cut-off on the Eyberg Child Behavior Inventory) was compared between children who had never wheezed (n = 397) and those developing late-onset wheezing (after age 3 years; n = 39). Late-onset wheezers were more likely to be above cut-offs for behavior problems at 3 years (before wheeze onset), compared with children who never wheezed, on Intensity (23.1% vs. 6.0%, p < 0.001) and Problem scores (10.8% vs. 1.3%, p < 0.001). Families of late-onset wheezers had poorer scores on family functioning variables, but we found no evidence of increased anxiety or depression scores in parents. In the multivariate analysis, significant and independent associates of late-onset wheeze were as follows: maternal asthma (odds ratio [OR] 5.4, 95% confidence intervals [CI] 2.1-13.8, p < 0.001), maternal smoking when child was 3 years (OR 3.3, CI 1.2-8.7, p = 0.02), expressiveness (OR 0.71, CI 0.55-0.9, p = 0.005), and significant behavior problems at age 3 years (OR 3.5, CI 1.2-9.9, p = 0.02). CONCLUSIONS: Behavior problems in early life are associated with increased risk of subsequent development of wheeze.

Age of Onset↗

PubMed2004

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.

Age Factors↗

PubMed2004

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.

Allergens↗

PubMed2004

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.

Air Pollution, Indoor↗

PubMed2004

Tobacco smoke exposure, wheeze, and atopy.

We investigated the effect of in utero and postnatal environmental tobacco smoke (ETS) exposure on respiratory symptoms and atopy in the first 3 years of life in children at high risk of allergic disease (both parents atopic). Three hundred and sixty-nine children were followed from birth and reviewed at ages 1 and 3 years (respiratory questionnaire, skin testing). Parental smoking questionnaires were administered, and plasma cotinine in cord and peripheral blood (at age 1 year) was measured (capillary column gas-liquid chromatography). Wheezing starting in the first year of life was significantly more common in children of smoking mothers (54.2% vs. 39.5%, P = 0.017), but not wheezing starting after age 1 year (10.8% vs. 10.9%, smoking and nonsmoking mothers, P = 0.99). Detectable cord cotinine was not associated with wheeze. More frequent wheeze in infancy was significantly more common in those with detectable 1-year cotinine (e.g., wheeze without colds, 17.8% vs. 5.6%, P = 0.02; wheeze most days, 6.5% vs. 0%, P = 0.04). ETS exposure was not associated with atopy. In the multivariate regression analysis, maternal smoking during pregnancy and/or in the first year of life remained associated with wheeze in the first year of life (odds ratio, 1.88; 95% confidence interval, 1.14-3.12; P = 0.01). ETS exposure in "high-risk" infants increases the risk of wheezing starting in the first year of life, but not after age 1 year. However, ETS exposure has little or no effect on the development of atopy. Measurement of plasma cotinine was no more useful than tobacco exposure assessment by questionnaire in our cohort.

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