B. Simpson

Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial

BACKGROUND Asthma places huge demands on health-care services, and its prevalence is increasing. Reduction of exposure to environmental allergens could offer a realistic chance for primary prevention. Our aim was to ascertain whether or not living in a low-allergen environment reduces the risk of asthma and atopic diseases in infants. METHODS We assigned infants to four risk groups according to parental atopic status. We enrolled 291 high-risk couples (both parents atopic, no pets) into a prospective, prenatally randomised, cohort study, and allocated them to environmental manipulation, in which measures to reduce prenatal and postnatal allergen exposure were undertaken (active HRA) (n=145) or no intervention (control HRC) (n=146). Two further prospective groups were studied: 161 high-risk infants with pets in the home (HRP group) and 168 low-risk infants, whose parents were both non-atopic (LR group). The main outcome measures were signs and symptoms of atopic disease at 1 year of age. FINDINGS 103 families dropped out or were lost to follow up. At age 1 year we followed-up 133 HRA, 118 HRC, 140 HRP, and 126 LR infants. Children in the HRA group were less likely to have respiratory symptoms during the first year of life than those in the HRC group. The most pronounced differences were in the relative risks for severe wheeze with shortness of breath (relative risk 0.44 [95% CI 0.20-1.00]), prescribed medication for the treatment of wheezy attacks (0.58 [0.36-0.95]), and wheezing after vigorous playing, crying, or exertion (0.18 [0.04-0.79]). Probability of respiratory symptoms in HRC and HRP infants was similar, whereas it was much lower in the LR than in the HRC group. Cat ownership was significantly associated with sensitisation to cats (24.6 [3.04-199.05]; p=0.003). INTERPRETATION Environmental manipulation reduces some respiratory symptoms in the first year of life in high-risk infants. Further follow up is needed, however, to ascertain whether living in a low-allergen environment reduces allergy and asthma in later life.

Manchester Asthma and Allergy Study: Low-allergen environment can be achieved and maintained during pregnancy and in early life☆☆☆★

BACKGROUND Early exposure to dust mite allergens may be critical for primary sensitization. Reducing exposure may offer a realistic chance for primary prevention of sensitization and asthma, but it is essential to implement measures that can achieve and maintain the low-allergen environment. OBJECTIVE Our purpose was to assess the effectiveness of mite allergen avoidance measures in achieving and maintaining a low-allergen environment during pregnancy and in the first year of life. METHODS The Manchester Asthma and Allergy Study is a prospective, prenatally randomized study that follows the development of asthma and atopy in a cohort of infants at high risk (both parents atopic) who are randomly allocated to full mite allergen avoidance or to a normal regimen. Avoidance measures comprise (1) mite-proof covers (mattress, pillow, and quilt) for parental bed, (2) high-filtration vacuum cleaner, (3) vinyl flooring in infants bedroom, (4) new crib and portable crib mattresses encased in mite-proof material, (5) benzyl benzoate (Acarosan) applied on carpets and soft furniture, (6) bed linens washed in hot water weekly, and (7) washable soft toys. Dust samples from the parental bed, bedroom floor, living room floor, infants mattress, and nursery floor were collected between the 10th and 14th weeks of pregnancy, immediately after birth, and then at age 6 months and 1 year, and Der p 1 levels were determined by mAb-based ELISA. RESULTS Recovered Der p 1 from maternal mattress was reduced by 97. 25% (95% confidence interval [CI] 95.25%-98.41%) during the second and third trimesters of pregnancy, with the effect persisting for 6 months (98% reduction, 95% CI 97.25%-99.1%) and 12 months (97.6% reduction, 95% CI 95.7%-98.6%) after the birth (active vs control, P <.000001). Total Der p 1 from bedroom floor in the active group was reduced by 53.7% (95% CI 25.7%-71.2%) in samples collected within 4 weeks of the childs birth, with the percentage reduction being 62. 8% (95% CI 39.3%-77.2%) at 6 months and 26.5% (95% CI -24% to 57.1%) at 1 year (active compared vs control, P <.007). Der p 1 levels in crib mattress and nursery floor in the active group were extremely low (crib mattresses geometric mean [95% CI] 2.3 ng [1.6-3.4] at birth, 6.8 ng [4.5-10] at age 6 months, and 15.6 ng [9.8-24.8] at age 1 year [active vs control, P =.001]; nursery 1 ng [0.9-1.1] at birth, 1.7 ng [1.2-2.5] at age 6 months, and 2 ng [1.3-3.5] at age 1 year [active vs control, P <.00001]). The total amount of allergen recovered at age 1 year was 29-fold (95% CI 15.1- to 56.7-fold) higher in the control group than in the active group. CONCLUSIONS The avoidance measures used in this study achieved and maintained a low mite allergen environment during pregnancy and in the first year of life in homes of infants at risk of atopy.

The CREATE Project : development of certified reference materials for allergenic products and validation of methods for their quantification

Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE‐binding potencies as their focus. Unfortunately, each company is using their own in‐house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.

Specific airway resistance in 3-year-old children: a prospective cohort study

BACKGROUND The development of a method to assess lung function in young children may provide new insight into asthma development. Plethysmographic measurement of specific airway resistance (sR(aw)) is feasible in this age group. We aimed to identify risk factors associated with low lung function in early childhood in a prospective birth cohort. METHODS Children were prenatally assigned to risk group according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic) and followed prospectively until age 3 years. We measured sR(aw) in 503 symptom-free children using whole-body plethysmography during tidal breathing. FINDINGS 803 of 868 children attended the clinic, of whom 503 obtained satisfactory sR(aw) readings. 200 who wheezed at least once during first 3 years of life had significantly higher sR(aw) than the 303 who had never wheezed (mean difference 5.8%, 95% CI 2.2-9.3, p=0.002). For children who had never wheezed there were significant differences in sR(aw) between risk groups (p<0.001). Children at high risk (n=87) had a higher sR(aw) (geometric mean 1.17 kPa/s, 1.12-1.22) than children at medium risk (n=162; 1.02 kPa/s, 1.00-1.05) and at low risk (54; 1.04 kPa/s, 0.99-1.11). Atopic children (n=62) had significantly higher sR(aw) (1.15 kPa/s, 1.09-1.21) than those who were not atopic (232; 1.05 kPa/s, 1.02-1.07, p=0.002). For non-atopic children, those at high risk (58) had higher sR(aw) (1.13kPa/s, 1.07-1.18) than those at medium risk (125, 1.01kPa/s, 0.98-1.05) or at low risk (49, 1.04 kPa/s, 0.97-1.10, p=0.003). We showed a significant interaction between history of maternal asthma and childs atopic status (p=0.006). INTERPRETATION Even in the absence of respiratory symptoms, children of atopic parents and those with personal atopy have impaired lung function in early life.

NAC Manchester Asthma and Allergy Study (NACMAAS): risk factors for asthma and allergic disorders in adults

Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates.

The National Asthma Campaign Manchester Asthma and Allergy Study

The NACManchester Asthma and Allergy Study is a prospective study of the development of asthma and allergies in childhood. The subjects (995 children at age 3 years) were recruited in utero by screening parents in the antenatal clinic using skin prick testing and a questionnaire regarding allergic diseases. Children were assigned to risk groups according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic). A subgroup of those at high risk (with no pets in the home) was randomized to stringent environmental control (allergen impermeable covers for the parental and infant bed, hot washing of bedding weekly, HEPA vacuum cleaner, hard floor for the nursery), and the remainder followed a normal regime. The children have been followed prospectively. The environmental influences are very clearly defined. Measurements of environmental exposures include levels of house dust mite; cat and dog allergens during pregnancy and early life; pet ownership and exposure; childcare arrangements; number of siblings; vaccination uptake; thorough dietary questionnaire; and endotoxin exposure. Further unique objective outcome in the cohort is the assessment of lung function in preschool children using specific airways resistance, which at age 3 years clearly reflects both genetic and environmental influences.

Relationship between mite, cat, and dog allergens in reservoir dust and ambient air.

Background: Standardized methods to measure allergen exposure are essential to assess the relationship between exposure, sensitization, and asthma. Most studies have measured allergen levels in reservoir dust, although air samples may be more representative as a measure of inhaled allergen. The aim of this study was to define the relationship between mite, cat, and dog allergen content in the reservoir dust and the levels in the ambient air.

Stringent environmental control in pregnancy and early life: the long‐term effects on mite, cat and dog allergen

Background As part of a primary prevention of asthma study, we measured the effect of environmental control measures on Der p 1, Fel d 1 and Can f 1 over a 3.5‐year period.

Childhood asthma, behavior problems, and family functioning

BACKGROUND Studies of families of asthmatic children indicate associations between psychological factors and asthma symptoms. OBJECTIVE We investigated relations between psychosocial factors and the development of respiratory symptoms within a large prospective cohort study. METHODS The children were prenatally assigned to high, medium, or low risk for asthma development on the basis of parental atopy and family history of allergic disease. When the children were 3 years of age, parents completed the Eyberg Child Behavior Inventory (ECBI), Family Relationships Index (FRI), Hospital Anxiety and Depression Scale (HAD), and General Health Questionnaire (GHQ). RESULTS Data from 663 participants were analyzed. ECBI intensity scores were significantly higher for children with parentally reported respiratory symptoms. Symptomatic low-risk children (both parents nonatopic, no family history of allergic disease) were particularly likely to have elevated behavior problem ratings. None of the other family psychosocial variables showed this pattern. Child behavior problems were, however, significantly positively correlated with the other family psychosocial variables. Logistic regression indicated that behavior problem scores were associated with 3 or more attacks of wheeze (P =.03, OR = 1.023), irrespective of risk group. CONCLUSIONS Children at 3 years of age with symptoms suggestive of asthma are at elevated risk of behavior problems. Children from families without a history of asthma and allergic diseases may be particularly vulnerable to behavioral disturbance. Families may benefit from additional advice on management of their childs behavior, particularly if parents do not have the experience of having the illness themselves.

Dietary intake in sensitized children with recurrent wheeze and healthy controls : a nested case-control study

Background:  The rising prevalence of asthma and allergic disease remains unexplained. Several risk factors have been implicated including diet, in particular poly‐unsaturated fats and antioxidant intake.