Biomedical subjects

Adnan Custovic

Publications and source records attributed to Adnan Custovic.

17 recordsLinked to original sources

PubMed2025

Gene-environment interaction analysis in atopic eczema: evidence from large population datasets and modelling in vitro.

BACKGROUND: Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modelling to independently assess findings. RESULTS: The discovery analysis showed suggestive evidence for interaction (p<0.05) between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total (maxN=25,339). In replication analysis (maxN=252,040) dog exposure*rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction=0.91 [0.83-0.99] P=0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction=0.84[0.75-0.94] P=0.003), but replication analysis was under-powered ORinteraction=1.09[0.82-1.46]). Rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. CONCLUSIONS: Interaction analysis and functional assessment provide evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G*E studied here implies that only weak effects are likely to occur.

Atopic eczema↗

PubMed2003

Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.

BACKGROUND: The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed covers involving 1122 adults with asthma. The primary outcomes were the mean morning peak expiratory flow rate over a four-week period during the run-in phase and at six months and the proportion of patients who discontinued inhaled corticosteroid therapy as part of a phased-reduction program during months 7 through 12. Der p1 was measured in mattress dust in a 10 percent random subsample of homes at entry and at 6 and 12 months. RESULTS: The prevalence of sensitivity to dust-mite allergen was 65.4 percent in the group supplied with allergen-impermeable bed covers (active-intervention group) and 65.1 percent in the control group supplied with non-impermeable bed covers. The concentration of Der p1 in mattress dust was significantly lower in the active-intervention group at 6 months (geometric mean, 0.58 microg per gram vs. 1.71 microg per gram in the control group; P=0.01) but not at 12 months (1.05 microg per gram vs. 1.64 microg per gram; P=0.74). The mean morning peak expiratory flow rate improved significantly in both groups (from 410.7 to 419.1 liters per minute in the active-intervention group, P<0.001 for the change; and from 417.8 to 427.4 liters per minute in the control group, P<0.001 for the change). After adjustment for base-line differences (by analysis of covariance), there was no significant difference between the groups in the peak expiratory flow rate at six months (difference in means, active-intervention group vs. control group, -1.6 liters per minute [95 percent confidence interval, -5.9 to 2.7] among all patients [P=0.46] and -1.5 liters per minute [95 percent confidence interval, -6.9 to 3.9] among mite-sensitive patients [P=0.59]). There was no significant difference between the groups in the proportion in whom complete cessation of inhaled corticosteroid therapy was achieved (17.4 percent in the active-intervention group and 17.1 percent in the control group) or in the mean reduction in steroid dose, either among all patients or among mite-sensitive patients. CONCLUSIONS: Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.

Adrenal Cortex Hormones↗

PubMed2003

Childhood asthma.

Asthma is the most common chronic disease of childhood. Despite increasing evidence indicating that genetic and environmental factors have significant effects on airway development and function in early life, our understanding of the natural history of the disease is limited. The development of objective outcome measures will enable us to distinguish between children with transient early wheeze and those who will progress to persistent asthma, and to investigate factors affecting airway function throughout early childhood. A thorough knowledge of lung physiology in early life and its relationship with environmental exposures and prior or subsequent development of asthma would have a profound effect on our understanding of the natural history of asthma and the design of future strategies for disease prevention.

Allergens↗

PubMed2003

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 child's behavior, particularly if parents do not have the experience of having the illness themselves.

Asthma↗

PubMed2003

Primary and secondary prevention of allergic airway disease.

The incidence of atopic conditions is continuing to rise. The number of primary prevention cohorts is increasing and results are becoming available. There is a lack of true secondary prevention trials, however. This article reviews the results currently available from primary and secondary prevention studies.

Humans↗

PubMed2003

High-efficiency particulate arrest-filter vacuum cleaners increase personal cat allergen exposure in homes with cats.

BACKGROUND: On the basis of experimental chamber studies, vacuum cleaners with double-thickness bags and integral high-efficiency particulate arrest (HEPA) air filters are claimed to reduce airborne allergen levels and are currently recommended to allergic patients. OBJECTIVES: The objective of this study was to investigate the effect of vacuum cleaning on personal inhaled cat allergen exposure in homes with cats. METHODS: Five unused new vacuum cleaners were compared with an old non-HEPA filter vacuum cleaner. Each vacuum cleaner was tested in an experimental chamber and in 5 homes with cats. Inhaled cat allergen was measured by nasal air sampling. RESULTS: New vacuum cleaners failed to leak any allergen in the experimental chamber. There was a significant increase in inhaled cat allergen during vacuum cleaning in homes (F = 48.39, df = 1.4, P =.002) with no difference between the old vacuum cleaner and the unused new vacuum cleaners (5-fold and 3-fold increase compared to baseline, respectively; F = 0.005, df = 1.4, P =.95). CONCLUSIONS: The use of new HEPA-filter vacuum cleaners increases inhaled cat allergen in homes with cats. The use of HEPA-filter modern vacuum cleaners to reduce pet allergen exposure in the homes of pet owners should not be justified merely on the basis of experimental chamber data.

Air Pollution, Indoor↗

PubMed2003

Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma.

BACKGROUND: Exposure to high levels of allergens in sensitized asthmatic patients causes worsening of pulmonary function in experimental studies. Chronic exposure to lower, naturally occurring levels of allergens might increase the severity of asthma. OBJECTIVE: We sought to study the associations between sensitization and exposure to common indoor allergens (dust mite, cat, and dog) in the home on pulmonary function, exhaled nitric oxide (eNO), and airway reactivity in asthmatic patients. METHODS: Dust samples were collected from the living room carpet and mattress of 311 subject's homes, and Der p 1, Fel d 1, and Can f 1 concentrations were measured by using ELISAs. Spirometry, nonspecific bronchial reactivity, and eNO were measured. RESULTS: Subjects both sensitized and exposed to high levels of sensitizing allergen had significantly lower FEV(1) percent predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6%-10.6%; P =.03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P =.001), and more severe airways reactivity (PD(20) GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P <.001) compared with subjects not sensitized and exposed. No significant effect of the interaction between sensitization and exposure was found for FEV(1) percent predicted and eNO values. However, there was a significant effect of the interaction between sensitization and exposure to any allergen (P =.05) and between sensitization and exposure to cat allergen (P =.04) for nonspecific bronchial reactivity. CONCLUSION: Asthmatic subjects who are exposed in their homes to allergens to which they are sensitized have a more severe form of the disease.

Adolescent↗

PubMed2003

Current mite, cat, and dog allergen exposure, pet ownership, and sensitization to inhalant allergens in adults.

BACKGROUND: Simultaneous exposure to more than one allergen might modify the effect of individual allergens. OBJECTIVE: The purpose of this study was to investigate the effect of current exposures to mite, cat, and dog allergen and pet ownership on sensitization in adults. METHODS: Questionnaires, skin tests, and home visits (Der p 1, Fel d 1, and Can f 1, ELISA; mattresses, living room floors) were performed in 2502 adults. Allergen exposure was treated as a continuous variable and divided into quartiles. To investigate the interaction between allergens, quartiles for 3 allergens were added, creating arbitrary combined exposure categories. RESULTS: In the univariate analysis, mite sensitization was associated with Der p 1 in mattresses (odds ratio [OR], 1.10; 95% CI, 1.01 to 1.19; P =.03) and with Can f 1 in living room floors (OR, 1.08; 95% CI, 1.00 to 1.17; P =.05). In a multivariate regression analysis, Der p 1 in mattresses remained an independent associate of mite sensitization (OR, 1.12; 95% CI, 1.02 to 1.23; P =.03) and pollen sensitization (OR, 1.23; 95% CI, 1.11 to 1.36; P =.0001). The proportion of subjects sensitized to mite increased significantly with the increasing combined exposure categories (P <.0001). The highest prevalence of sensitization to cat and dog was in the medium combined exposure categories. Cat ownership was associated with a reduced prevalence of sensitization to cats (P =.002) and a reduced prevalence of sensitization to dog (P =.003) but had no effect on sensitization to mite and pollen. CONCLUSIONS: Sensitization to dust mites increased with the increasing combined exposure. Cat ownership was associated with a lower prevalence of sensitization to cat and dog but not to mite and grass pollen.

Administration, Inhalation↗

PubMed2003

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMedDate not supplied

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↗