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Adnan Custovic

Publications and source records attributed to Adnan Custovic.

45 records · Page 3Linked to original sources

Early pet exposure: friend or foe?

PURPOSE OF REVIEW: Sensitization to pets is a risk factor for asthma and it was assumed that pet ownership was a risk factor for sensitization. Epidemiological studies failed to confirm this, some even suggesting that keeping pets decreased the risk of sensitization and asthma. In the last year, 10 studies have been published which have, at least in part, attempted to address the question. The results, however, are heterogeneous and it is still not clear how we should advise our patients on this issue of pet ownership. RECENT FINDINGS: Results of studies of the association between exposure to cat or cat allergen and the development of sensitization are such that almost any view on the relationship could be supported by evidence from the literature. For dogs, there are fewer data, but there is little to suggest that keeping a dog increases the risk of sensitization to dog. The majority of studies reviewed find either no association or a reduced risk of asthma amongst pet owners, but only one of these selectively excludes those who deliberately avoid pets from the analysis. There is evidence to suggest that amongst non-pet owners, the risk of sensitization and of asthma increases in areas with a high proportion of pet owners. There is evidence emerging that the effect of exposure to pets may be different in different relative risk groups, based on parental allergy. There is also evidence that asthma is more severe amongst pet sensitized pet owners. SUMMARY: There are several large birth cohort studies being conducted around the world designed to measure the development of asthma and allergies in children with prospective and objective measures of environmental exposures. The results of such studies are required before the association between pets and asthma can be determined.

Adolescent↗

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 child's 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.

Airway Resistance↗

Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study.

OBJECTIVE: To investigate the importance of sensitisation and exposure to allergens and viral infection in precipitating acute asthma in adults resulting in admission to hospital. DESIGN: Case-control study. SETTING: Large district general hospital. PARTICIPANTS: 60 patients aged 17-50 admitted to hospital over a year with acute asthma, matched with two controls: patients with stable asthma recruited from the outpatient department and patients admitted to hospital with non-respiratory conditions (inpatient controls). MAIN OUTCOME MEASURES: Atopic status (skin testing and total and specific IgE), presence of common respiratory viruses and atypical bacteria (polymerase chain reaction), dust samples from homes, and exposure to allergens (enzyme linked immunosorbent assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). RESULTS: Viruses were detected in 31 of 177 patients. The difference in the frequency of viruses detected between the groups was significant (admitted with asthma 26%, stable asthma 18%, inpatient controls 9%; P=0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised and exposed to either mite, cat, or dog allergen than patients with stable asthma (37%) and inpatient controls (15%; P<0.001). Being sensitised and exposed to allergens was an independent associate of the group admitted to hospital (odds ratio 2.3, 95% confidence interval 1.0 to 5.4; P=0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably increased the risk of being admitted with asthma (8.4, 2.1 to 32.8; P=0.002). CONCLUSIONS: Allergens and viruses may act together to exacerbate asthma.

Acute Disease↗

The effect of allergen exposure in early childhood on the development of atopy.

While there is good evidence for the association between allergen exposure and disease severity in sensitized individuals, and allergen exposure and development of sensitization, the relationship between allergen exposure and development of allergic disease is as yet unresolved. A protective effect of cat ownership on sensitization and allergic disease has been reported. The dose-response relationship between allergen exposure and sensitization may be different for different allergens (eg, linear for mite, bell-shaped for cat). Exposure to a high level of cat allergen may result in a modified Th2 response characterized by the presence of IgG4 antibody to cat proteins without IgE response, which could be regarded as a form of tolerance. The long-term prospective follow-up of well-defined cohorts with objective exposure and outcome measures will elucidate the complex relationship between environmental allergen exposures, sensitization, and asthma.

Allergens↗

Controlling indoor allergens.

OBJECTIVES: Reading of this article reinforces the reader's knowledge of the role of allergen exposure in relation to asthma and its severity, as well as the relevance of allergen avoidance in the treatment of asthma. DATA SOURCES: Initial literature search for existing evidence-based guidelines, reviews, and meta-analyses was carried out, and further literature searches were performed to review individual randomized controlled trials. Evidence level was graded according to the Scottish Intercollegiate Guidelines Network recommendations. RESULTS: There is good evidence for the link between mite and cockroach allergen exposure and sensitization, and between sensitization and asthma. For pet allergens, some studies found that exposure to pets in early life was associated with specific immunoglobulin E sensitization and allergic disease later in childhood, whereas others reported a protective effect. The effectiveness of allergen reduction in the treatment of asthma is suggested by studies in which the patients improve substantially when moved into the low-allergen environment of hospitals or high-altitude sanatoria. Because of limitations in the design of the most clinical of studies, we do not yet have a conclusive answer on the effectiveness of domestic aeroallergen avoidance. CONCLUSIONS: Minimizing the impact of identified environmental risk factors is an important first step to reduce the severity of asthma. Although environmental control is difficult, it should be an integral part of the overall management of sensitized patients. However, what is unclear is which patients would benefit and by how much, and whether the intervention is cost-effective. These questions will be answered satisfactorily only by large randomized trials.

Air Pollution, Indoor↗

Seasonal variability in exercise test responses in Ghana.

Exercise-induced bronchospasm (EIB) is widely used in epidemiological studies to investigate the prevalence of asthma. We aimed to determine seasonal variations in the prevalence of EIB in Ghanaian school children from urban-rich (UR), urban-poor (UP), and rural (R) schools. We have previously reported the prevalence of EIB in 9-16-year-old children to be 3.1% in the dry season, with UR children having a significantly higher prevalence of both EIB and atopy compared to UP or R children. In the current study, the prevalence of EIB was assessed in the same 1,095 children in the wet season (5 months following the initial study) using the same methodology. Exercise provocation consisted of free running outdoors for 6 min. In the wet season, 17/1,095 children [mean 1.55%, 95% confidence interval (CI): 0.91-2.47] had a positive response to exercise, compared to our previous report of 34 children (mean 3.1%, 95% CI: 2.15-4.32) with EIB in the dry season (dry vs. wet season, difference 1.55, 95% CI: 0.41-2.69). The proportion of children with a positive response to exercise in the UR school fell from 4.2% (25/599) to 1.3% (8/599) (difference 2.9, 95% CI: 1.2-4.5). In the wet season, there was no difference in the prevalence of EIB among the UR, UP, and R children. Only five of 1,095 subjects (mean 0.5%, 95% CI: 0.15-1.07) demonstrated EIB in both seasons. In conclusion, although exercise challenge remains a useful tool for determining asthma prevalence in epidemiological studies, seasonal variations in the pattern of responses may occur and the results should be interpreted with caution.

Adolescent↗

Clostridium difficile, atopy and wheeze during the first year of life.

Differences have been suggested to occur in the composition of intestinal microflora from allergic and non-allergic children. In this study we used a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the measurement of Clostridium difficile-specific immunoglobulin G (IgG) (CDIgG). CDIgG was excellent in differentiating between adults with or without Cl. difficile colitis (absorbance levels, positive vs. negative controls: geometric mean (GM) 0.301, 95% CI: 0.289-0.314 vs. GM 0.167, 95% CI: 0.155-0.181; mean difference 1.8-fold, 95% CI: 1.65-1.95; p < 0.0001). We used this technique to investigate whether there are any differences between atopic wheezy infants and non-atopic non-wheezy controls. In a prospective cohort study (n = 390) 10 patients were identified at 1 year of age (atopic, history of recurrent wheeze) and matched (gender, month of birth, exposure to Der p 1, Fel d 1 and Can f 1) with a control group of infants (non-atopic, no history of wheeze). The patients had significantly higher Cl. difficile-specific IgG absorbance levels (GM 0.298, 95% CI: 0.249-0.358) compared with controls (GM 0.235, 95% CI: 0.201-0.274; mean difference 1.27-fold, 95% CI: 1.07-1.50; p = 0.01). These results suggest that there may be differences in the composition of intestinal microflora between allergic and non-allergic infants at 1 year of age, with allergic children having higher Cl. difficile IgG antibody levels.

Antibody Specificity↗

Array-based diagnostic gene-expression score for atopy and asthma.

Whether gene expression is useful in discriminating different atopic phenotypes is unclear. The aim of the study was to evaluate a gene-expression score for the diagnosis of atopy and asthma and to assess disease activity as a guide for therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects, 8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to cDNA membranes. A composite atopy gene expression (CAGE) score was determined by using 10 genes dysregulated in atopic individuals according to a specific algorithm. The CAGE score was better than total IgE in differentiating atopic from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between the CAGE score and total IgE (P <.001) was found, and there was a trend for correlation with asthma severity (P =.051). The CAGE score was able to quantify phenotype-specific alteration in gene expression of atopic individuals. The CAGE score might be used as a diagnostic tool or to monitor the effects and side effects of therapy.

Adolescent↗

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.

Asthma↗