Adnan Custovic - Academia.edu (original) (raw)

Papers by Adnan Custovic

The Journal of allergy and clinical immunology, Jan 7, 2017

The relationship between allergy and autoimmune disorders is complex and poorly understood. To in... more The relationship between allergy and autoimmune disorders is complex and poorly understood. To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at...

The Journal of allergy and clinical immunology, Jan 20, 2016

The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mec... more The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. To assess whether the trajectory to asthma begins already at birth and epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. We used Methylated CpG Island Recovery Assay (MIRA)-chip to survey DNA methylation in cord blood mononuclear cells (CBMC) from 36 children (18 non-asthmatic, 18 asthmatic by age 9) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n=60) and in two replication cohorts (The Manchester Asthma and Allergy Study, n=30, and the Childhood Origins of ASThma Study, n=28) was analyzed by bisulfite sequencing or Illumina 450K arrays. CBMC-derived IL-1β was measured by ELISA. Neonatal immune cells harbored 589 differentially methylated regions (DMRs) that distingu...

American Journal of Physiology Lung Cellular and Molecular Physiology, Apr 1, 2001

B-cell isotype switching and the production of IgE is regulated by a variety of gene products thr... more B-cell isotype switching and the production of IgE is regulated by a variety of gene products through different mechanisms. A better understanding of these processes has the potential to identify markers of disease and new therapeutic targets. The aim of the study was to investigate human B-cell isotype control and IgE production in atopy and asthma with cDNA array technology. Eighteen atopic asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were included. Peripheral blood mononuclear cells were separated by gradient centrifugation, mRNA was purified, and the reverse-transcribed probes were hybridized to cDNA membranes. Group differences were assessed with the Mann-Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had significantly altered expression in atopy and asthma compared with that in the healthy subjects. The differentially expressed genes include surface molecules involved in T- and B-cell interaction and activation, cytokines, intracellular signaling products, and transcription factors. In conclusion, both atopic nonasthmatic and atopic asthmatic individuals had activated proinflammatory pathways, a minimal requirement for B-cell isotype switching, and a clear net pro-IgE cytokine climate.

Pediatric Allergy and Immunology, Oct 1, 2002

Differences have been suggested to occur in the composition of intestinal microflora from allergi... more 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 atopicwheezyinfantsandnon-atopicnon-wheezycontrols.Inaprospective cohort study (n5390) 10 patients were identified at 1 year of age (atopic, history ofrecurrent wheeze) andmatched (gender,month ofbirth,exposure toDer p1,Fel d1andCanf1)withacontrol groupofinfants (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 5 0.01). These results suggest that there may be differences inthecompositionofintestinalmicroflorabetweenallergic andnon-allergic infants at 1 year of age, with allergic children having higher Cl. difficile IgG antibody levels.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Drugs of Today, Dec 1, 2008

Drugs of Today, Dec 1, 2008

Environmental Health Perspectives 2013 121 1232 1238, Jun 18, 2013

Findings from previous studies on the effects of air pollution exposure on lung function during c... more Findings from previous studies on the effects of air pollution exposure on lung function during childhood have been inconsistent. A common limitation has been the quality of exposure data used, and few studies have modeled exposure longitudinally throughout early life. oBjectives: We sought to study the long-term effects of exposure to particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) and to nitrogen dioxide (NO 2 ) on specific airway resistance (sR aw ) and forced expiratory volume in 1 sec (FEV 1 ) before and after bronchodilator treatment. Subjects were from the Manchester Asthma and Allergy Study (MAAS) birth cohort (n = 1,185). Methods: Spirometry was performed during clinic visits at ages 3, 5, 8, and 11 years. Individuallevel PM 10 and NO 2 exposures were estimated from birth to 11 years of age through a microenvironmental exposure model. Longitudinal and cross-sectional associations were estimated using generalized estimating equations and multivariable linear regression models. results: Lifetime exposure to PM 10 and NO 2 was associated with significantly less growth in FEV 1 (percent predicted) over time, both before (-1.37%; 95% CI: -2.52, -0.23 for a 1-unit increase in PM 10 and -0.83%; 95% CI: -1.39, -0.28 for a 1-unit increase in NO 2 ) and after bronchodilator treatment (-3.59%; 95% CI: -5.36, -1.83 and -1.20%; 95% CI: -1.97, -0.43, respectively). We found no association between lifetime exposure and sR aw over time. Cross-sectional analyses of detailed exposure estimates for the summer and winter before 11 years of age and lung function at 11 years indicated no significant associations. conclusions: Long-term PM 10 and NO 2 exposures were associated with small but statistically significant reductions in lung volume growth in children of elementary-school age. citation: Mölter A, Agius RM, de Vocht F, Lindley S, Gerrard W, Lowe L, Belgrave D, Custovic A, Simpson A. 2013. Long-term exposure to PM 10 and NO 2 in association with lung volume and airway resistance in the MAAS birth cohort. Environ Health Perspect 121:1232-1238. http://dx.

Environmental Health Perspectives 2013 121 1232 1238, Jun 18, 2013

Findings from previous studies on the effects of air pollution exposure on lung function during c... more Findings from previous studies on the effects of air pollution exposure on lung function during childhood have been inconsistent. A common limitation has been the quality of exposure data used, and few studies have modeled exposure longitudinally throughout early life. oBjectives: We sought to study the long-term effects of exposure to particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) and to nitrogen dioxide (NO 2 ) on specific airway resistance (sR aw ) and forced expiratory volume in 1 sec (FEV 1 ) before and after bronchodilator treatment. Subjects were from the Manchester Asthma and Allergy Study (MAAS) birth cohort (n = 1,185). Methods: Spirometry was performed during clinic visits at ages 3, 5, 8, and 11 years. Individuallevel PM 10 and NO 2 exposures were estimated from birth to 11 years of age through a microenvironmental exposure model. Longitudinal and cross-sectional associations were estimated using generalized estimating equations and multivariable linear regression models. results: Lifetime exposure to PM 10 and NO 2 was associated with significantly less growth in FEV 1 (percent predicted) over time, both before (-1.37%; 95% CI: -2.52, -0.23 for a 1-unit increase in PM 10 and -0.83%; 95% CI: -1.39, -0.28 for a 1-unit increase in NO 2 ) and after bronchodilator treatment (-3.59%; 95% CI: -5.36, -1.83 and -1.20%; 95% CI: -1.97, -0.43, respectively). We found no association between lifetime exposure and sR aw over time. Cross-sectional analyses of detailed exposure estimates for the summer and winter before 11 years of age and lung function at 11 years indicated no significant associations. conclusions: Long-term PM 10 and NO 2 exposures were associated with small but statistically significant reductions in lung volume growth in children of elementary-school age. citation: Mölter A, Agius RM, de Vocht F, Lindley S, Gerrard W, Lowe L, Belgrave D, Custovic A, Simpson A. 2013. Long-term exposure to PM 10 and NO 2 in association with lung volume and airway resistance in the MAAS birth cohort. Environ Health Perspect 121:1232-1238. http://dx.

Primary Care Respiratory Journal, 2004

The incidence of allergic conditions continues to increase world wide. The underlying mechanisms ... more The incidence of allergic conditions continues to increase world wide. The underlying mechanisms and in particular the causes are however poorly understood. This article presents the evidence for the hygiene hypothesis which has been proposed in the debate on the causation of allergic disease.

Primary Care Respiratory Journal, 2004

The incidence of allergic conditions continues to increase world wide. The underlying mechanisms ... more The incidence of allergic conditions continues to increase world wide. The underlying mechanisms and in particular the causes are however poorly understood. This article presents the evidence for the hygiene hypothesis which has been proposed in the debate on the causation of allergic disease.

Current Allergy and Asthma Reports, Aug 11, 2009

For about 20 years, investigators have been attempting to design studies to reduce exposure to al... more For about 20 years, investigators have been attempting to design studies to reduce exposure to allergens in order to prevent the development of allergic sensitization and thus prevent the onset of allergic disease, particularly asthma. Seven such studies-environmental control studies-have attempted to accomplish this by changing the domestic environment into which a high-risk child is born. Some of these studies also included a dietary intervention aimed at reducing the risk of development of sensitization to food allergens. In this review, we summarize the seven studies, compare study designs, and evaluate the effectiveness of the environmental control measures adopted. We present published results, focusing on the most recent. There is great heterogeneity of results that cannot be explained by the variety of study designs alone. We propose that the next generation of primary prevention studies will be informed by epidemiologic studies of geneenvironment interactions and will investigate the effects of tailor-made measures targeting individuals with specifi c susceptibilities who may benefi t from specifi ed interventions.

Current Allergy and Asthma Reports, Aug 11, 2009

For about 20 years, investigators have been attempting to design studies to reduce exposure to al... more For about 20 years, investigators have been attempting to design studies to reduce exposure to allergens in order to prevent the development of allergic sensitization and thus prevent the onset of allergic disease, particularly asthma. Seven such studies-environmental control studies-have attempted to accomplish this by changing the domestic environment into which a high-risk child is born. Some of these studies also included a dietary intervention aimed at reducing the risk of development of sensitization to food allergens. In this review, we summarize the seven studies, compare study designs, and evaluate the effectiveness of the environmental control measures adopted. We present published results, focusing on the most recent. There is great heterogeneity of results that cannot be explained by the variety of study designs alone. We propose that the next generation of primary prevention studies will be informed by epidemiologic studies of geneenvironment interactions and will investigate the effects of tailor-made measures targeting individuals with specifi c susceptibilities who may benefi t from specifi ed interventions.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients... more Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients with asthma. 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. 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). 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. 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.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients... more Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients with asthma. 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. 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). 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. 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.

Journal of Allergy and Clinical Immunology, Nov 1, 2007

The Journal of Allergy and Clinical Immunology, Jan 3, 2011

Journal of Investigational Allergology Clinical Immunology Official Organ of the International Association of Asthmology and Sociedad Latinoamericana De Alergia E Inmunologia, 2012

Immunoglobulin (Ig) E-mediated sensitization to domestic inhalant allergens (eg, dust mite, cockr... more Immunoglobulin (Ig) E-mediated sensitization to domestic inhalant allergens (eg, dust mite, cockroach, cat, and dog) is the most important risk factor for asthma. The severity of asthma increases among atopic patients exposed to high levels of sensitizing allergen. In addition, synergism between high allergen exposure and respiratory virus infection increases the risk of asthma exacerbation. However, opinions on the role of allergen avoidance in the management of asthma are diverse, partly because most currently used allergen avoidance measures are usually tested in highly artificial experimental conditions, often with no assessment of their effect on personal inhaled allergen exposure or their clinical effectiveness. While there is little evidence for the clinical benefits of single avoidance measures (eg, bedding encasings, vacuum cleaners, and air filters), multifaceted intervention in carefully selected patients may be of benefit. Until conclusive evidence is available, a pragmatic approach in clinical practice should involve the following: (a) interventions tailored to the patient's sensitization and allergen exposure (if exposure cannot be estimated, specific IgE antibody level or the results of skin testing can be used as a marker); (b) a multifaceted allergen avoidance regime, based on removal of the accumulating allergen; (c) initiation of the intervention as early as possible. Currently, no evidence-based advice on the use of allergen avoidance for prevention of allergic disease can be given; however, it is increasingly clear that no single strategy will be applicable to all children, only to those with specific genetic susceptibility.

J Allerg Clin Immunol, 1996

Allergy, Jan 25, 2016

IgE sensitization tests, such as skin prick testing and serum specific IgE, have been used to dia... more IgE sensitization tests, such as skin prick testing and serum specific IgE, have been used to diagnose IgE-mediated clinical allergy for many years. Their prime drawback is that they detect sensitization which is only loosely related to clinical allergy. Many patients therefore require provocation tests to make a definitive diagnosis; these are often expensive and potentially associated with severe reactions. The likelihood of clinical allergy can be semi-quantified from an IgE sensitization test results. This relationship varies though according to the patients' age, ethnicity, nature of the putative allergic reaction and co-existing clinical diseases such as eczema. The likelihood of clinical allergy can be more precisely estimated from an IgE sensitization test result, by taking into account the patient's presenting features (pre-test probability). The presence of each of these patient specific factors may mean that a patient is more or less likely to have clinically alle...

The Journal of allergy and clinical immunology, Jan 7, 2017

The relationship between allergy and autoimmune disorders is complex and poorly understood. To in... more The relationship between allergy and autoimmune disorders is complex and poorly understood. To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at...

The Journal of allergy and clinical immunology, Jan 20, 2016

The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mec... more The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. To assess whether the trajectory to asthma begins already at birth and epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. We used Methylated CpG Island Recovery Assay (MIRA)-chip to survey DNA methylation in cord blood mononuclear cells (CBMC) from 36 children (18 non-asthmatic, 18 asthmatic by age 9) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n=60) and in two replication cohorts (The Manchester Asthma and Allergy Study, n=30, and the Childhood Origins of ASThma Study, n=28) was analyzed by bisulfite sequencing or Illumina 450K arrays. CBMC-derived IL-1β was measured by ELISA. Neonatal immune cells harbored 589 differentially methylated regions (DMRs) that distingu...

American Journal of Physiology Lung Cellular and Molecular Physiology, Apr 1, 2001

B-cell isotype switching and the production of IgE is regulated by a variety of gene products thr... more B-cell isotype switching and the production of IgE is regulated by a variety of gene products through different mechanisms. A better understanding of these processes has the potential to identify markers of disease and new therapeutic targets. The aim of the study was to investigate human B-cell isotype control and IgE production in atopy and asthma with cDNA array technology. Eighteen atopic asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were included. Peripheral blood mononuclear cells were separated by gradient centrifugation, mRNA was purified, and the reverse-transcribed probes were hybridized to cDNA membranes. Group differences were assessed with the Mann-Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had significantly altered expression in atopy and asthma compared with that in the healthy subjects. The differentially expressed genes include surface molecules involved in T- and B-cell interaction and activation, cytokines, intracellular signaling products, and transcription factors. In conclusion, both atopic nonasthmatic and atopic asthmatic individuals had activated proinflammatory pathways, a minimal requirement for B-cell isotype switching, and a clear net pro-IgE cytokine climate.

Pediatric Allergy and Immunology, Oct 1, 2002

Differences have been suggested to occur in the composition of intestinal microflora from allergi... more 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 atopicwheezyinfantsandnon-atopicnon-wheezycontrols.Inaprospective cohort study (n5390) 10 patients were identified at 1 year of age (atopic, history ofrecurrent wheeze) andmatched (gender,month ofbirth,exposure toDer p1,Fel d1andCanf1)withacontrol groupofinfants (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 5 0.01). These results suggest that there may be differences inthecompositionofintestinalmicroflorabetweenallergic andnon-allergic infants at 1 year of age, with allergic children having higher Cl. difficile IgG antibody levels.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Drugs of Today, Dec 1, 2008

Drugs of Today, Dec 1, 2008

Environmental Health Perspectives 2013 121 1232 1238, Jun 18, 2013

Findings from previous studies on the effects of air pollution exposure on lung function during c... more Findings from previous studies on the effects of air pollution exposure on lung function during childhood have been inconsistent. A common limitation has been the quality of exposure data used, and few studies have modeled exposure longitudinally throughout early life. oBjectives: We sought to study the long-term effects of exposure to particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) and to nitrogen dioxide (NO 2 ) on specific airway resistance (sR aw ) and forced expiratory volume in 1 sec (FEV 1 ) before and after bronchodilator treatment. Subjects were from the Manchester Asthma and Allergy Study (MAAS) birth cohort (n = 1,185). Methods: Spirometry was performed during clinic visits at ages 3, 5, 8, and 11 years. Individuallevel PM 10 and NO 2 exposures were estimated from birth to 11 years of age through a microenvironmental exposure model. Longitudinal and cross-sectional associations were estimated using generalized estimating equations and multivariable linear regression models. results: Lifetime exposure to PM 10 and NO 2 was associated with significantly less growth in FEV 1 (percent predicted) over time, both before (-1.37%; 95% CI: -2.52, -0.23 for a 1-unit increase in PM 10 and -0.83%; 95% CI: -1.39, -0.28 for a 1-unit increase in NO 2 ) and after bronchodilator treatment (-3.59%; 95% CI: -5.36, -1.83 and -1.20%; 95% CI: -1.97, -0.43, respectively). We found no association between lifetime exposure and sR aw over time. Cross-sectional analyses of detailed exposure estimates for the summer and winter before 11 years of age and lung function at 11 years indicated no significant associations. conclusions: Long-term PM 10 and NO 2 exposures were associated with small but statistically significant reductions in lung volume growth in children of elementary-school age. citation: Mölter A, Agius RM, de Vocht F, Lindley S, Gerrard W, Lowe L, Belgrave D, Custovic A, Simpson A. 2013. Long-term exposure to PM 10 and NO 2 in association with lung volume and airway resistance in the MAAS birth cohort. Environ Health Perspect 121:1232-1238. http://dx.

Environmental Health Perspectives 2013 121 1232 1238, Jun 18, 2013

Findings from previous studies on the effects of air pollution exposure on lung function during c... more Findings from previous studies on the effects of air pollution exposure on lung function during childhood have been inconsistent. A common limitation has been the quality of exposure data used, and few studies have modeled exposure longitudinally throughout early life. oBjectives: We sought to study the long-term effects of exposure to particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) and to nitrogen dioxide (NO 2 ) on specific airway resistance (sR aw ) and forced expiratory volume in 1 sec (FEV 1 ) before and after bronchodilator treatment. Subjects were from the Manchester Asthma and Allergy Study (MAAS) birth cohort (n = 1,185). Methods: Spirometry was performed during clinic visits at ages 3, 5, 8, and 11 years. Individuallevel PM 10 and NO 2 exposures were estimated from birth to 11 years of age through a microenvironmental exposure model. Longitudinal and cross-sectional associations were estimated using generalized estimating equations and multivariable linear regression models. results: Lifetime exposure to PM 10 and NO 2 was associated with significantly less growth in FEV 1 (percent predicted) over time, both before (-1.37%; 95% CI: -2.52, -0.23 for a 1-unit increase in PM 10 and -0.83%; 95% CI: -1.39, -0.28 for a 1-unit increase in NO 2 ) and after bronchodilator treatment (-3.59%; 95% CI: -5.36, -1.83 and -1.20%; 95% CI: -1.97, -0.43, respectively). We found no association between lifetime exposure and sR aw over time. Cross-sectional analyses of detailed exposure estimates for the summer and winter before 11 years of age and lung function at 11 years indicated no significant associations. conclusions: Long-term PM 10 and NO 2 exposures were associated with small but statistically significant reductions in lung volume growth in children of elementary-school age. citation: Mölter A, Agius RM, de Vocht F, Lindley S, Gerrard W, Lowe L, Belgrave D, Custovic A, Simpson A. 2013. Long-term exposure to PM 10 and NO 2 in association with lung volume and airway resistance in the MAAS birth cohort. Environ Health Perspect 121:1232-1238. http://dx.

Primary Care Respiratory Journal, 2004

The incidence of allergic conditions continues to increase world wide. The underlying mechanisms ... more The incidence of allergic conditions continues to increase world wide. The underlying mechanisms and in particular the causes are however poorly understood. This article presents the evidence for the hygiene hypothesis which has been proposed in the debate on the causation of allergic disease.

Primary Care Respiratory Journal, 2004

The incidence of allergic conditions continues to increase world wide. The underlying mechanisms ... more The incidence of allergic conditions continues to increase world wide. The underlying mechanisms and in particular the causes are however poorly understood. This article presents the evidence for the hygiene hypothesis which has been proposed in the debate on the causation of allergic disease.

Current Allergy and Asthma Reports, Aug 11, 2009

For about 20 years, investigators have been attempting to design studies to reduce exposure to al... more For about 20 years, investigators have been attempting to design studies to reduce exposure to allergens in order to prevent the development of allergic sensitization and thus prevent the onset of allergic disease, particularly asthma. Seven such studies-environmental control studies-have attempted to accomplish this by changing the domestic environment into which a high-risk child is born. Some of these studies also included a dietary intervention aimed at reducing the risk of development of sensitization to food allergens. In this review, we summarize the seven studies, compare study designs, and evaluate the effectiveness of the environmental control measures adopted. We present published results, focusing on the most recent. There is great heterogeneity of results that cannot be explained by the variety of study designs alone. We propose that the next generation of primary prevention studies will be informed by epidemiologic studies of geneenvironment interactions and will investigate the effects of tailor-made measures targeting individuals with specifi c susceptibilities who may benefi t from specifi ed interventions.

Current Allergy and Asthma Reports, Aug 11, 2009

For about 20 years, investigators have been attempting to design studies to reduce exposure to al... more For about 20 years, investigators have been attempting to design studies to reduce exposure to allergens in order to prevent the development of allergic sensitization and thus prevent the onset of allergic disease, particularly asthma. Seven such studies-environmental control studies-have attempted to accomplish this by changing the domestic environment into which a high-risk child is born. Some of these studies also included a dietary intervention aimed at reducing the risk of development of sensitization to food allergens. In this review, we summarize the seven studies, compare study designs, and evaluate the effectiveness of the environmental control measures adopted. We present published results, focusing on the most recent. There is great heterogeneity of results that cannot be explained by the variety of study designs alone. We propose that the next generation of primary prevention studies will be informed by epidemiologic studies of geneenvironment interactions and will investigate the effects of tailor-made measures targeting individuals with specifi c susceptibilities who may benefi t from specifi ed interventions.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients... more Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients with asthma. 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. 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). 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. 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.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients... more Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients with asthma. 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. 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). 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. 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.

Journal of Allergy and Clinical Immunology, Nov 1, 2007

The Journal of Allergy and Clinical Immunology, Jan 3, 2011

Journal of Investigational Allergology Clinical Immunology Official Organ of the International Association of Asthmology and Sociedad Latinoamericana De Alergia E Inmunologia, 2012

Immunoglobulin (Ig) E-mediated sensitization to domestic inhalant allergens (eg, dust mite, cockr... more Immunoglobulin (Ig) E-mediated sensitization to domestic inhalant allergens (eg, dust mite, cockroach, cat, and dog) is the most important risk factor for asthma. The severity of asthma increases among atopic patients exposed to high levels of sensitizing allergen. In addition, synergism between high allergen exposure and respiratory virus infection increases the risk of asthma exacerbation. However, opinions on the role of allergen avoidance in the management of asthma are diverse, partly because most currently used allergen avoidance measures are usually tested in highly artificial experimental conditions, often with no assessment of their effect on personal inhaled allergen exposure or their clinical effectiveness. While there is little evidence for the clinical benefits of single avoidance measures (eg, bedding encasings, vacuum cleaners, and air filters), multifaceted intervention in carefully selected patients may be of benefit. Until conclusive evidence is available, a pragmatic approach in clinical practice should involve the following: (a) interventions tailored to the patient's sensitization and allergen exposure (if exposure cannot be estimated, specific IgE antibody level or the results of skin testing can be used as a marker); (b) a multifaceted allergen avoidance regime, based on removal of the accumulating allergen; (c) initiation of the intervention as early as possible. Currently, no evidence-based advice on the use of allergen avoidance for prevention of allergic disease can be given; however, it is increasingly clear that no single strategy will be applicable to all children, only to those with specific genetic susceptibility.

J Allerg Clin Immunol, 1996

Allergy, Jan 25, 2016

IgE sensitization tests, such as skin prick testing and serum specific IgE, have been used to dia... more IgE sensitization tests, such as skin prick testing and serum specific IgE, have been used to diagnose IgE-mediated clinical allergy for many years. Their prime drawback is that they detect sensitization which is only loosely related to clinical allergy. Many patients therefore require provocation tests to make a definitive diagnosis; these are often expensive and potentially associated with severe reactions. The likelihood of clinical allergy can be semi-quantified from an IgE sensitization test results. This relationship varies though according to the patients' age, ethnicity, nature of the putative allergic reaction and co-existing clinical diseases such as eczema. The likelihood of clinical allergy can be more precisely estimated from an IgE sensitization test result, by taking into account the patient's presenting features (pre-test probability). The presence of each of these patient specific factors may mean that a patient is more or less likely to have clinically alle...