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Serum IgE levels, atopy, and asthma in young adults: Results from a longitudinal cohort study
Allergy
Abstract
To explore the natural history of asthma and its relation to allergic responses, we examined the relation between total serum IgE in early adulthood and a history of respiratory symptoms, airway hyperresponsiveness (AHR), and atopy during childhood. We studied 180 subjects aged 18-20 years who had been studied since the age of 8-10 years. We measured wheeze in the previous year by questionnaire, AHR by histamine inhalation test, atopy by skin prick tests, and serum IgE levels by immunoassay. Subjects with AHR in early adulthood had higher IgE levels (mean 257.0 IU/ml) than subjects with past AHR (mean 93.3 IU/ml) or with lifelong normal responsiveness (mean 67.6 IU/ml) (P < 0.001). Subjects who had symptoms had higher IgE levels (mean 125.9 IU/ml) than those who were lifelong asymptomatic (mean 63.1 IU/ml) (P < 0.001). Recent wheeze, AHR, and allergic sensitization all had a positive relation to serum IgE, but IgE was not more predictive of AHR than skin prick tests. The finding that young adults who are sensitized to common allergens are highly likely to have AHR even in the absence of symptoms is further evidence of the fundamental role of IgE-mediated responses in the natural history of AHR throughout childhood and into adulthood.
... To the Editor, Wheezing episodes are common in young infants affecting every third child before the age of 3. 1,2 While wheezing episodes in early life are mostly triggered by viral lower respiratory tract infection, the development of asthma and airway hyperresponsiveness seems to be promoted by immunoglobulin E (IgE)-mediated lung inflammation. [3][4][5] Although the development of an asthma phenotype does not necessarily require an atopic status, early childhood asthma is mostly associated with atopy while nonatopic, intrinsic asthma is a rather rare condition. 3,4 Considering the critical role of IgE in the development of impaired lung function in early childhood, several studies tried to differentiate children with transient wheezing episodes from those with persistent wheeze based on early childhood serum IgE levels providing evidence that persistently wheezing children seem to have elevated IgE levels already very early in life. ...
... [3][4][5] Although the development of an asthma phenotype does not necessarily require an atopic status, early childhood asthma is mostly associated with atopy while nonatopic, intrinsic asthma is a rather rare condition. 3,4 Considering the critical role of IgE in the development of impaired lung function in early childhood, several studies tried to differentiate children with transient wheezing episodes from those with persistent wheeze based on early childhood serum IgE levels providing evidence that persistently wheezing children seem to have elevated IgE levels already very early in life. 6 Notably, although not every child with persistent or late-onset wheeze will be diagnosed with asthma, none of the earlier studies focusing on IgE, wheeze, and asthma distinguished between persistent wheeze and asthma (eg, 4,6 ). ...
... 3,4 Considering the critical role of IgE in the development of impaired lung function in early childhood, several studies tried to differentiate children with transient wheezing episodes from those with persistent wheeze based on early childhood serum IgE levels providing evidence that persistently wheezing children seem to have elevated IgE levels already very early in life. 6 Notably, although not every child with persistent or late-onset wheeze will be diagnosed with asthma, none of the earlier studies focusing on IgE, wheeze, and asthma distinguished between persistent wheeze and asthma (eg, 4,6 ). ...
... In a study by Satwani et al., serum total IgE levels were associated with severity of bronchial asthma [22]. In a study by Peat et al., subjects who had respiratory symptoms had higher total serum IgE levels than those who were lifelong asymptomatic [23]. In a study by Louis et al., variation in total serum IgE was weakly associated with asthma control but not with exacerbation [24]. ...
... In a study by Hourihane et al., peanut-specific IgE levels did not predict clinical severity, and skin-prick test weal size correlated weakly with severity [28]. In a study by Peat et al., total serum IgE was not more predictive of airway hyperresponsiveness than skin-prick tests [23]. In a study by Moore et al., the severe asthma group had less atopy by skin tests, but total IgE did not differentiate disease severity [29]. ...
Introduction
Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases.
Aim
To determine the relationship between the concentration of specific IgE antibodies in serum and types of asthma.
Material and methods
The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of asthma, skin-prick tests).
Results
sIgE antibodies against any allergen were detected in 9.9% (classes 1–6)/7.6% (classes 2–6) of healthy respondents. Comparing sIgE antibodies of respondents with intermittent asthma to sIgE antibodies of respondents with persistent asthma, no statistically significant differences were identified. Relating to allergens of D. pteronyssinus, cat dander, and A. alternata, sIgE antibodies were more frequently detected in respondents with atopic asthma and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.005 to p < 0.001). Relating to allergens of D. pteronyssinus, cat dander, and timothy grass, sIgE antibodies were more frequently detected in respondents with atopic asthma and a weakly positive skin-prick test as compared to healthy respondents with weakly positive skin-prick test (p < 0.05 to p < 0.001).
Conclusions
Regarding subjects with a negative or weakly positive skin test, when sIgE antibodies to the same allergen are detected, asthma is much more likely to occur.
... Indeed, two-thirds of asthmatics are allergic and more than 50% of patients with severe asthma have allergy [4]. Bronchial hyperresponsiveness was shown to be associated with serum IgE levels [5], and transferable by IgE-rich serum from asthmatic to non-asthmatic individuals [6]. Furthermore, serum IgE levels play an important role in smooth muscle hyperreactivity [5,7,8] and incubation of IgE-rich serum from atopic individuals causes hyperreactivity in isolated airway preparations from non atopic patients [9]. ...
... Bronchial hyperresponsiveness was shown to be associated with serum IgE levels [5], and transferable by IgE-rich serum from asthmatic to non-asthmatic individuals [6]. Furthermore, serum IgE levels play an important role in smooth muscle hyperreactivity [5,7,8] and incubation of IgE-rich serum from atopic individuals causes hyperreactivity in isolated airway preparations from non atopic patients [9]. Moreover, IgE was proposed to induce smooth muscle contractile function through binding to the smooth muscle membrane and cause subsequent hyperpolarization [10]. ...
Previous studies have shown that enhanced accumulation of contractile proteins such as smooth muscle myosin light chain kinase (smMLCK) plays a major role in human airway smooth muscle cells (HASM) cell hypercontractility and hypertrophy. Furthermore, serum IgE levels play an important role in smooth muscle hyperreactivity. However, the effect of IgE on smMLCK expression has not been investigated. In this study, we demonstrate that IgE increases the expression of smMLCK at mRNA and protein levels. This effect was inhibited significantly with neutralizing abs directed against FcεRI but not with anti-FcεRII/CD23. Furthermore, Syk knock down and pharmacological inhibition of mitogen activated protein kinases (MAPK) (ERK1/2, p38, and JNK) and phosphatidylinositol 3-kinase (PI3K) significantly diminished the IgE-mediated upregulation of smMLCK expression in HASM cells. Taken together, our data suggest a role of IgE in regulating smMLCK in HASM cells. Therefore, targeting the FcεRI activation on HASM cells may offer a novel approach in controlling the bronchomotor tone in allergic asthma.
... Serum IgE levels have been shown earlier to modulate smooth muscle function. Bronchial hyperresponsiveness was shown to be associated with serum IgE levels [9]. IgE was also shown to cause smooth muscle contractile function through binding to the smooth muscle membrane and subsequent hyperpolarization [10]. ...
... Serum IgE levels were shown to affect ASM cell function and tend to correlate with AHR [9]. Cumulative data in last decade has defined a direct role of IgE in ASM cell activation. ...
Airway remodeling is not specifically targeted by current asthma medications, partly owing to the lack of understanding of remodeling mechanisms, altogether posing great challenges in asthma treatment. Increased airway smooth muscle (ASM) mass due to hyperplasia/hypertrophy contributes significantly to overall airway remodeling and correlates with decline in lung function. Recent evidence suggests that IgE sensitization can enhance the survival and mediator release in inflammatory cells. Human ASM (HASM) cells express both low affinity (FcεRII/CD23) and high affinity IgE Fc receptors (FcεRI), and IgE can modulate the contractile and synthetic function of HASM cells. IgE was recently shown to induce HASM cell proliferation but the detailed mechanisms remain unknown. We report here that IgE sensitization induces HASM cell proliferation, as measured by 3H-thymidine, EdU incorporation, and manual cell counting. As an upstream signature component of FcεRI signaling, inhibition of spleen tyrosine kinase (Syk) abrogated the IgE-induced HASM proliferation. Further analysis of IgE-induced signaling depicted an IgE-mediated activation of Erk 1/2, p38, JNK MAPK, and Akt kinases. Lastly, lentiviral-shRNA-mediated STAT3 silencing completely abolished the IgE-mediated HASM cell proliferation. Collectively, our data provide mechanisms of a novel function of IgE which may contribute, at least in part, to airway remodeling observed in allergic asthma by directly inducing HASM cell proliferation.
... By contrast, persistent and late-onset wheezing were found to be associated with an increased risk of persistent asthma and allergies (Martinez et al. 1995). The same applies to asthma in older children and adolescents; asthma in these groups has been demonstrated to be closely associated with atopic diathesis, reflected in IgE responses (Burrows et al. 1989, Sears et al. 1991, Peat et al. 1996). Neonatal chronic lung disease is defined here because in a notable portion of children born preterm it causes long-term pulmonary consequences, including asthmalike symptoms. ...
... In the study of late pulmonary sequelae of BPD, Northway et al. (1990) analysed the frequency of atopy between groups of preterm children and controls but did not link the result to respiratory findings. The significant association found here between atopy, asthma and wheezing in the full-term group is in agreement with the results of several previous studies in which unselected populations of older children and young adults were evaluated (Burrows et al. 1989, Sears et al. 1991, Peat et al. 1996, Strachan et al. 1996). In infants, however, as Martinez et al. (1995) have demonstrated, a considerable proportion of wheezing is nonatopic and transient, is related to a diminished airway function at birth and becomes symptomatic especially during viral infections. ...
... Therefore, it is now widely accepted that ASM actively participates in the pathogenesis of allergic asthma, by virtue of its role in airway inflammation, airway hyperresponsiveness and airway remodeling. Several studies have led to novel insights into immune processes and the role of IgE in atopic diseases such as asthma [5]. Bronchial hyperresponsiveness has been shown to be associated with increased serum IgE levels and could be transferred from asthmatic to non-asthmatic subjects by IgE-rich serum adminis- tration [5]. ...
... Several studies have led to novel insights into immune processes and the role of IgE in atopic diseases such as asthma [5]. Bronchial hyperresponsiveness has been shown to be associated with increased serum IgE levels and could be transferred from asthmatic to non-asthmatic subjects by IgE-rich serum adminis- tration [5]. The biological activities of IgE are mediated through the high affinity (FceRI) and the low affinity (FceRII or CD23) IgE receptors [6,7]. ...
The high affinity IgE receptor (FcepsilonRI) is a crucial structure for IgE-mediated allergic reactions. We have previously demonstrated that human airway smooth muscle (ASM) cells express the tetrameric (alphabetagamma2) FcepsilonRI, and its activation leads to marked transient increases in intracellular Ca(2+) concentration, release of Th-2 cytokines and eotaxin-1/CCL11. Therefore, it was of utmost importance to delineate the factors regulating the expression of FcepsilonRI in human (ASM) cells.
Incubation of human bronchial and tracheal smooth muscle (B/TSM) cells with TNF-alpha, IL-1beta or IL-4 resulted in a significant increase in FcepsilonRI-alpha chain mRNA expression (p<0.05); and TNF-alpha, IL-4 enhanced the FcepsilonRI-alpha protein expression compared to the unstimulated control at 24, 72 hrs after stimulation. Interestingly, among all other cytokines, only TNF-alpha upregulated the FcepsilonRI-gamma mRNA expression. FcepsilonRI-gamma protein expression remained unchanged despite the nature of stimulation. Of note, as a functional consequence of FcepsilonRI upregulation, TNF-alpha pre-sensitization of B/TSM potentially augmented the CC (eotaxin-1/CCL11 and RANTES/CCL5, but not TARC/CCL17) and CXC (IL-8/CXCL8, IP-10/CXCL10) chemokines release following IgE stimulation (p<0.05, n = 3). Furthermore, IgE sensitization of B/TSM cells significantly enhanced the transcription of selective CC and CXC chemokines at promoter level compared to control, which was abolished by Lentivirus-mediated silencing of Syk expression.
Our data depict a critical role of B/TSM in allergic airway inflammation via potentially novel mechanisms involving proinflammatory, Th2 cytokines and IgE/FcepsilonRI complex.
... Ludviksdottir and colleagues 15 reported a similar relationship in asthmatic adults. There is a well established relationship between atopy and increased AR in both children 26 27 and adults, 27 and our data suggest that increased NO production in the airways may be associated with a mechanism linking these two factors. This may involve inflammatory processes and would support the hypothesis that FE NO is a marker of allergic airway inflammation. ...
... 36 However, atopy and increased AR can coexist in adults in the absence of symptoms. 27 The association between raised FE NO levels and the development of asthma later in life can only be addressed by longitudinal data. This cohort will be reassessed 5 years after the present data were obtained. ...
... The implication is that skin test positivity, a high serum total IgE level, and peripheral blood eosinophilia are different expressions of the atopic phenotype. This conclusion is in accord with other studies in children (26) and young adults (27), in which many young adults without a positive skin test have had high serum total IgE levels. ...
... In contrast to the findings of most other studies (27)(28)(29), we observed no relationship between high serum total IgE levels and BHR in our middle-aged population. Higher serum total IgE levels are known to be associated with smoking, male gender, and younger age. ...
To assess the simultaneous effects of symptoms related to asthma, smoking, and Immunoglobulin E (IgE) on the concentrations of methacholine at which different individuals fall below 80% the FEV1 values obtained with saline, we used parametric survival methods that fit the dose-response nature of bronchial responsiveness (BR). A general population-based sample of 1,615 adults (aged 20 to 44 yr) from five cities in Spain participating in the European Community Respiratory Health Survey was studied. The total number of subjects whose FEV1 values dropped below 80% was 237 (14.7%). We found that individuals with symptoms related to asthma, whether they were smokers or nonsmokers, responded at lower concentrations of methacholine than individuals without symptoms. The greatest decrease in the concentrations of methacholine at which different percentages of individuals responded was due to symptoms among the nonsmokers (relative percentiles ranging from 0.53 to 0.76, and a 90% confidence band not containing a value one). Among individuals without symptoms, smokers responded at moderately but significantly lower concentrations than nonsmokers, whereas an apparent protective effect of smoking was seen in symptomatic individuals, owing in part to a self-selection bias. The higher the concentration of IgE, the lower were the concentrations of methacholine needed to obtain a given level of BR. Moreover, the magnitude of the decrease in methacholine concentrations leading to a response was constant over all percentages of individuals responding. The analytical methods used in the study permit the incorporation of complexities in the relationships between BR and symptoms, smoking, and IgE, and are generally applicable to situations in which a dose-response relationship occurs.
... Previous research on the connection between skin, allergy, and respiratory symptoms has shown that they are often associated with one another, as all commonly have a component of immunoglobulin E (IgE)-mediated reactions, also known as type-1 hypersensitivity reactions. Past investigations have found that higher levels of serum IgE are associated with respiratory and skin symptoms, such as airway hyperresponsiveness, allergic sensitization, asthma, rhinoconjunctivitis, and contact urticaria [50,51]. A survey of 453 individuals determined that among those occupationally sensitized to a specific allergen (laboratory animals), 16% of them reported having skin disorders, rhinitis, and asthma [52]. ...
Healthcare facility staff use a wide variety of cleaning and disinfecting products during their daily operations, many of which are associated with respiratory or skin irritation or sensitization with repeated exposure. The objective of this study was to characterize the prevalence of cleaning and disinfection product use, glove use during cleaning and disinfection, and skin/allergy symptoms by occupation and identify the factors influencing glove use among the healthcare facility staff. A questionnaire was administered to the current employees at a midwestern Veterans Affairs healthcare facility that elicited information on cleaning and disinfection product use, glove use during cleaning and disinfection, skin/allergy symptoms, and other demographic characteristics, which were summarized by occupation. The central supply/environmental service (2% of the total survey population) and nursing occupations (licensed practical nurse: 3%, nurse: 26%, nursing assistant: 3%, other nurses: 10% of the total survey population, respectively) had the highest prevalence of using cleaning or disinfecting products, specifically quaternary ammonium compounds, bleach, and alcohol. Glove use while using products was common in both patient care and non-patient care occupations. The factors associated with glove use included using bleach or quaternary ammonium compounds and using cleaning products 2–3 or 4–5 days per week. A high frequency of glove use (≥75%) was reported by workers in most occupations when using quaternary ammonium compounds or bleach. The use of alcohol, bleach, and quaternary ammonium compounds was associated with skin disorders (p < 0.05). These research findings indicate that although the workers from most occupations report a high frequency of glove use when using cleaning and disinfection products, there is room for improvement, especially among administrative, maintenance, and nursing workers. These groups may represent populations which could benefit from the implementation of workplace interventions and further training regarding the use of personal protective equipment and the potential health hazards of exposure to cleaning and disinfecting chemicals.
... I mmunoglobulin E (IgE) is best known for its pathological effects in allergic diseases and the beneficial role of IgE in host defense against parasitic infections, in particular, against helminth infections. 1 Normal levels of IgE are highly variable within the population, 2 and there have been few studies on patients with a low or undetectable serum total IgE. Selective IgE deficiency (IgED) is currently defined as a significant reduction in serum levels of IgE (less than or equal to 2 kIU/L) in a patient whose other immunoglobulin levels are normal or diminished (mixed IgED). ...
Selective immunoglobulin E (IgE) deficiency (IgED) is defined as serum levels of IgE more than or equal to 2 kIU/L and is associated with immune dysregulation and autoimmunity. This study aimed to investigate a prevalence of atherosclerotic cardiovascular disease (ASCVD) in population
with IgED. Within the electronic patient record (EPR) database of Leumit Health Care Services (LHS) in Israel, data capture was performed using IBM Cognos 10.1.1 BI Report Studio software. The case samples were drawn from the full study population (n = 18,487), having any allergy-related symptoms
and/or those requesting antiallergy medications and performed serum total IgE measurement during 2012 at LHS. All subjects aged more than or equal to 40 years old, with serum total IgE less than 2 kIU/L were included in case group. Control group was randomly sampled from the remained subjects,
with a case-control ratio of 10 controls for each case (1:10). The comorbid cardiovascular diseases during less than or equal to 10 years before serum total IgE testing were identified and retrieved using specific International Classification of Diseases, 9th Revision, Clinical Modification
diagnostic codes. There were 103 in case and 1030 subjects in control group. Compared with control group patients, the case group had significantly more arterial hypertension [34 (37.7%) versus 187 (18.2%), p < 0.001], ischemic heart disease (IHD) [26 (25.2%) versus 87 (8.4%), p < 0.001],
carotid stenosis [5 (4.9%) versus 7 (0.7%), p = 0.003], cerebrovascular disease (CVD) [3 (2.9%) versus 5 (0.5%), p = 0.029], and peripheral vascular disease (PVD) [4 (3.9%) versus 9 (0.9%), p = 0.024]. IgED is associated with higher prevalence of arterial hypertension and ASCVD.
... While the natural history of asthma and its relation to allergic responses from age 8-10 years into adulthood has been well studied [3], early life events play a critical role in determining the pattern of immune maturation and the development of allergic disease and particularly asthma [4]. However, current understanding of these events is limited by the nature of the available data. ...
Background
The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life.
Methods
Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640), had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), 5 years (n = 370) and 8 years (n = 275). We measured interleukin (IL-) 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ), at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression.
Results
HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years.
Conclusion
HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.
... 또한 다양한 버섯들의 열수추출물이 암세포 성장을 억제 시킨다는 많은 보고가 있다 (Moradali et al., 2007). 이와 (Peat et al., 2008). 몇몇 연구에 의하면 버섯의 특정 성분이 알러지성 천식 및 아토피 등의 면역과민 반응을 완화시키는 결 과를 보고하였다 (Furue and Kitoh, 1981;Han et al., 2010). ...
This study was carried out to evaluate the immunomodulatory capacity of edible mushrooms, including Sarcodon aspratus, Letinus edodes and Grifola frondosa in mice. BALB/c mice were administered 50, 500, and 1000 mg/kg body weight of various mushrooms five times a week over 4 weeks through oral administration. The control mice were administered distilled water. No significant changes in body weight were observed. IL-4 and production was evaluated with splenic T lymphocytes stimulated in vitro with phytohemagglutinins for 48 hr. The mice group administered Sarcodon aspratus, Grifola frondosa tend to higher ratio of versus IL-4 than the other groups. In addition, the ratio of plasma IgG2a versus IgG1 was also elevated in mice treated with Sarcodon aspratus. These results indicated that Sarcodon aspratus can enhance type-1 helper T cell-mediated cellular immunity. And also, S. aspratus seems to be one of the most useful mushrooms for immunomedicine.
... J Pneumol 27(5) -set-out de 2001 vação nas pesquisas desenvolvidas neste campo, ao longo das últimas décadas. Várias teorias têm sido apontadas como justificativas, mas a explicação mais conclusiva para esse fenômeno ainda não foi definida (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) . Fatores genéticos e ambientais parecem estar envolvidos, mas cada vez mais os últimos têm aparecido como os principais implicados (3,4,(11)(12)(13)(14)(15)(16)(17)(18)(19) . ...
Introdução: Considerável aumento na prevalência da asma e da atopia vem sendo mundialmente observado ao longo das últimas décadas, porém, em nosso país, os dados epidemiológicos ainda são insuficientes. Objetivo: Este estudo foi realizado a fim de determinar a prevalência de asma e atopia em um grupo de escolares e comparar tais dados com outros dois levantamentos previamente realizados em Porto Alegre, Rio Grande do Sul. Métodos: A prevalência de asma foi identificada através de um questionário aplicado a 855 alunos de cinco escolas de Porto Alegre. Foram considerados atópicos aqueles escolares que, submetidos a testes cutâneos, apresentaram pelo menos uma reação cutânea positiva. Assinatura do termo de consentimento pós-informação de um dos pais foi exigida para a realização dos testes cutâneos. Resultados: Foi identificada prevalência de 42,5% de asma cumulativa e 22% de asma ativa, com predominância nas meninas. Atopia foi identificada em 50,1% da amostra. Tais resultados foram significativamente superiores aos 6,7% (1980) e 16% (1989) de asma cumulativa, 10,9% (1989) de asma ativa e 15,8% (1980) de atopia encontrados nos dois estudos previamente realizados. Conclusões: Altas prevalências de asma e atopia foram identificadas em nossos estudantes. Futuros estudos deverão ser realizados a fim de elucidar o fenômeno aqui demonstrado.
... The study of environmental factors that modify serum IgE in young infants is an important area of research as at this stage in life the immune system is maturing and hence relatively plastic to external influences. There have been many studies demonstrating the association between increased serum IgE levels and a greater likelihood of asthma symptoms (Peat et al. 1996;Sherrill et al. 1999;Sunyer et al. 2000;Simpson et al. 2005), although few data sets with IgE measurements from the first 2 years of life (excluding birth). We are not aware of any other comparable population-based studies of serum IgE in infants aged 12-15 months that we can contrast our results with. ...
Immunoglobulin E (IgE) plays a key role in allergy disease pathogenesis, but little is known about the environmental factors associated with higher IgE levels in infants. The aim of this study was to determine the risk factors for elevated serum total IgE infants living in Havana.
Eight hundred and seventy-seven infants provided blood samples. Data on allergic disease symptoms and a wide range of exposures were collected.
The median IgE was 35IU/ml (interquartile range 13-96). The risk of having an IgE level above the median was higher for children who had been breastfed for 4 months or more (adjusted odds ratio (OR) 1.28; 95% confidence interval (CI): 1.02-1.61) and for children who reported cockroaches in their home (OR 1.30; 95% CI: 1.03-1.63). The risk was lower for children whose mother was in paid employment (OR 0.73; 95% CI: 0.54-0.97 compared with those who did not), for children living in homes where gas and electricity were used for cooking (OR 0.45; 95% CI: 0.32-0.62 compared with electricity only) and for children with domestic pets at birth (OR 0.83; 95% CI: 0.70-1.00). There was no association between paracetamol use and serum IgE levels.
Associations between gas fuel use and maternal employment indicate that IgE levels in early life are lower in children who may be living in relative affluence. The discrepancy in the effect of early exposure to pets or cockroaches may reflect differences in these allergens, or be confounded by relative affluence. Further investigation of this cohort will determine how these effects translate into the expression of allergic disease in later life.
... Wyniki niektórych badań sugerują, że występowanie u pacjenta objawów wskazujących na alergię (czyli istotny osobniczy wywiad w kierunku alergii) jest w mniejszym stopniu związane z ryzykiem rozwoju astmy zawodowej niż nadwrażliwość na pospolite aeroalergeny, potwierdzona jedynie dodatnimi wynikami punktowych testów skórnych, bez klinicznych objawów uczulenia (5). Z innej jednak strony należy podkreślić, że cechy atopii wykrywa się u około 40-60% badanej populacji, a dodatnie wyniki PTS stwierdzane są u 40% populacji generalnej (6,7). ...
Respiratory diseases are a cause of long-term sickness absence, and even of partial or complete inability to work. This paper presents the first in Poland description of principles of good practice in occupational health service provided for people with respiratory diseases. The issues concerning the certification of the ability to work in this group of patients are discussed. The key-principles of preventive care of workers with obstructive and interstitial lung diseases with particular attention paid to the control of major risk factors are also presented. The importance of possible contraindications for job performance by workers affected by these diseases, as well as the responsibilities of occupational health physicians were highlighted. M
... The fascination with allergy and the role it played in populations throughout the world was to continue for the rest of her life. A partnership between Dr Jennifer Peat, Dr Cheryl Salome and many others developed into the epidemiology team which answered so many questions about the changing prevalence of asthma over time, perceived differences in prevalence across Australia, the reproducibility of lung function tests in the field as well as the validity of measurements and new instruments to measure clinical and patient focussed outcomes [8][9][10][11][12][13]. Her work revolutionised epidemiology studies in respiratory health, she answered the important questions on methodology as well as answering the ''big picture'' questions concerning differences between populations over time. ...
... Par exemple, Peat et coll. [81] ont montré que des adultes jeunes sensibilisés à des allergènes courants ont un risque augmenté de développer une hyperréactivité bronchique, même en l'absence de symptomatologie. De plus, des études longitudinales montrent que l'augmentation du taux d'IgE sériques est en rapport avec l'aggravation du déficit fonctionnel ventilatoire de sujets nonfumeurs, ex-fumeurs [82], ou fumeurs actifs [83]. ...
Introduction
IgE is known to provide the biological basis for allergy and immediate hypersensitivity. However, recent data provide some evidence that IgE responses are involved in other inflammatory processes apart from allergy, including several respiratory diseases.
State of the art
IgE binds to mast cells and basophils but also to other inflammatory cells, which are involved in non-allergic processes. IgE has a role in antigen presentation and is implicated in a number of other immune mechanisms. In the airways, IgE plays an important role in bronchial hyperactivity, even in the absence of an allergen.
Epidemiological studies have demonstrated that IgE response is related not only to allergy but also to asthma symptoms, in the presence or absence of atopy, as well as exposure to cigarette smoke. IgE response is altered in several respiratory diseases including extrinsic and intrinsic asthma and allergic bronchopulmonary aspergillosis.
Conclusion and Perspectives
Since anti-IgE monoclonal antibodies are now available for administration to humans, a better understanding of the IgE response may allow the identification of novel therapeutic targets in the field of respiratory disease.
... For instance, serum levels would possibly rise due to inflammation. Only few longitudinal studies investigated this [13,[20][21][22][23] , and most of those were limited in size or did not investigate the effect of total IgE independently from atopic status. Using the ECRHS data, a significant association between new-onset asthma and total IgE was found by Anto et al. [13] . ...
Background:
Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey.
Methods:
Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE ≥0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre.
Results:
Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person-years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05–2.88] and the sum of allergenspecific IgEs (OR 1.18, 95% CI 1.00–1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91–1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account.
Conclusions:
After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults.
... In most economically-developed countries, at least 20% of the population suffers from IgE-mediated (Type I) allergic diseases, typically manifesting as asthma or seasonal rhinitis/conjunctivitis. In the majority of patients, this is related to sensitisation to airborne allergens [1,2] but the mechanisms by which exposure triggers an allergic response remain incompletely understood. Nor is it clear why the incidence of allergic asthma and rhinitis in economically-developed countries, including Australia, is so high. ...
Pollens are important triggers for allergic asthma and seasonal rhinitis, and proteases released by major allergenic pollens can injure airway epithelial cells in vitro. Disruption of mucosal epithelial integrity by proteases released by inhaled pollens could promote allergic sensitisation.
Pollen diffusates from Kentucky blue grass (Poa pratensis), rye grass (Lolium perenne) and Bermuda grass (Cynodon dactylon) were assessed for peptidase activity using a fluorogenic substrate, as well as by gelatin zymography. Following one- or two-dimensional gel electrophoresis, Coomassie-stained individual bands/spots were excised, subjected to tryptic digestion and analysed by mass spectrometry, either MALDI reflectron TOF or microcapillary liquid chromatography MS-MS. Database searches were used to identify allergens and other plant proteins in pollen diffusates.
All pollen diffusates tested exhibited peptidase activity. Gelatin zymography revealed high Mr proteolytic activity at approximately 95,000 in all diffusates and additional proteolytic bands in rye and Bermuda grass diffusates, which appeared to be serine proteases on the basis of inhibition studies. A proteolytic band at Mr approximately 35,000 in Bermuda grass diffusate, which corresponded to an intense band detected by Western blotting using a monoclonal antibody to the timothy grass (Phleum pratense) group 1 allergen Phl p 1, was identified by mass spectrometric analysis as the group 1 allergen Cyn d 1. Two-dimensional analysis similarly demonstrated proteolytic activity corresponding to protein spots identified as Cyn d 1.
One- and two-dimensional electrophoretic separation, combined with analysis by mass spectrometry, is useful for rapid determination of the identities of pollen proteins. A component of the proteolytic activity in Bermuda grass diffusate is likely to be related to the allergen Cyn d 1.
... When comparing the severity of asthma with serum IgE levels in bronchial asthma, the present data indicated that the more severity of the asthma, the greater is the elevation in serum IgE. The most important risk factor for the development of extrinsic asthma is atopy (Lebowitz et al., 1984;Peat et al., 1996). An atopic individual responds to antigenic stimuli to which normal people will not respond. ...
Bronchial asthma is a major public health concern affecting 100-150 million people worldwide. Elevated total serum immunoglobulin E (IgE) is considered as an objective marker of allergy and has been associated with a number of respiratory disorders. The present study tests the hypothesis that serum IgE levels reflect the severity of asthma. The serum IgE levels were investigated in 132 asthma patients and their severities of asthma were determined by pulmonary function tests. Serum IgE levels were also compared with the severity of asthma by history. The data indicated that 27% patients developed symptoms of bronchial asthma before 30 years of age; 17% patients between 31 to 45 years and only 5% patients developed asthmatic symptoms after the age of 45 years. Serum IgE levels significantly increased in all groups of asthma when compared to control subjects (p<0.001). The IgE levels were proportionately higher in patients with more severe airflow obstruction. The present study suggests that the serum IgE level may reflect the severity of bronchial asthma assessed by pulmonary function tests and clinical history.
... Although it is established that asthma and seasonal rhinitis/ conjunctivitis complications are related in the majority of cases to airborne allergens sensitisation [38,39], the mechanism by which exposure to these allergens triggers an allergic response remains incompletely understood. It is however supposed that the biological function of an allergen might be an important factor for its allergenicity. ...
We intend to solve whether or not Phl p 1 can be regarded as a protease. A group reported that Phl p 1 has papain-like properties and later on, that this allergen resembles cathepsin B, while another one demonstrated that Phl p 1 lacks proteinase activity and suggested that the measured activity may rise either from a recombinant Phl p 1 contaminant or as a result of an incompletely purified natural allergen. A third group reported Phl p 1 to act by a non-proteolytic activity mechanism. We report the purification of the natural Phl p 1 by means of hydrophobic interaction, gel filtration and STI-Sepharose affinity chromatographies. The Phl p 1 purity was assessed by silver-stained SDS-PAGE and by 'in-gel' and 'gel-free' approaches associated to mass spectrometry analyses. The proteolytic activity was measured using Boc-Gln-Ala-Arg-AMC and Z-Phe-Arg-AMC as substrates. While amidolytic activity could be measured with Phl p 1 after rechromatography on gel filtration, it however completely disappeared after chromatography on STI-Sepharose. The contaminant activity co-eluting with Phl p 1 was not affected by cysteine proteases inhibitors and other thiol-blocking agents, by metalloproteases inhibitors and by aspartic proteases inhibitors. However, it was completely inhibited by low molecular weight and proteinaceous serine proteases inhibitors. TLCK, but not TPCK, inhibited the contaminant activity, showing a trypsin-like behavior. The pH and temperature optimum were 8.0 and 37°C, respectively. These data indicated that Phl p 1 is not a protease. The contaminant trypsin-like activity should be considered when Phl p 1 allergenicity is emphasized.
... From atopic serum sensitization studies, it was suggested that serum IgE levels play an important role in smooth muscle hyperreactivity [50,53]. Indeed, the bronchial hyperresponsiveness has been shown to be associated with serum IgE levels and transferable by IgE-rich serum from asthmatic to non-asthmatic individuals [53,54]. Moreover, IgE was proposed to cause smooth muscle contractile function through binding to the smooth muscle membrane and cause subsequent hyperpolarization [55]. ...
The airway smooth muscle (ASM) is no longer considered as merely a contractile apparatus and passive recipient of growth factors, neurotransmitters and inflammatory mediators signal but a critical player in the perpetuation and modulation of airway inflammation and remodeling. In recent years, a molecular link between ASM and IgE has been established through Fc epsilon receptors (FcεRs) in modulating the phenotype and function of these cells. Particularly, the expression of high affinity IgE receptor (FcεRI) has been noted in primary human ASM cells in vitro and in vivo within bronchial biopsies of allergic asthmatic subjects. The activation of FcεRI on ASM cells suggests a critical yet almost completely ignored network which may modulate ASM cell function in allergic asthma. This review is intended to provide a historical perspective of IgE effects on ASM and highlights the recent updates in the expression and function of FcεRI, and to present future perspectives of activation of this pathway in ASM cells.
... Elevated total serum IgE levels may also contribute indirectly to pulmonary inflammation. Peat and colleagues found a strong correlation between total serum IgE levels and airway hyperresponsiveness (AHR) (26), and others have reported a close association between total serum IgE levels, AHR, and reduced FEV 1 / FVC when IgE was at least moderately elevated (27). After studying 562 eleven-year-olds with asthma, Sears et al. concluded that IgE has a major effect on lung function (28). ...
Haselkorn T, Szefler SJ, Simons FER, Zeiger RS, Mink DR, Chipps BE, Borish L, Wong DA, for the TENOR Study Group. Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR.
Pediatr Allergy Immunol 2010: 21: 1157–1165.
© 2010 John Wiley & Sons A/S
In children and adolescents with difficult‐to‐treat asthma, few data exist characterizing the relationships between basic patient characteristics (e.g., age, sex) and atopic indicators in asthma. These associations were examined in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR), an observational study of a large cohort of patients with severe or difficult‐to‐treat asthma. To characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and airflow in young patients with severe or difficult‐to‐treat asthma. A total of 1261 patients from the TENOR study were stratified into four age groups at baseline (6–8, 9–11, 12–14, and 15–17 yr). The objective was to characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and ratio of pre‐bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV 1 /FVC) in young patients with severe or difficult‐to‐treat asthma. The chi‐square test for categorical variables and analysis of variance for continuous variables were used to identify significant differences among age groups. Multivariable linear regression was used to evaluate the association between IgE and FEV 1 /FVC. Allergic rhinitis was reported in approximately two‐thirds of patients. Up to 25% of patients had atopic dermatitis, which differed across age groups in boys (p < 0.05). Positive allergen skin test rate differed across age groups in boys (p < 0.05). Rates of asthma triggers were higher and differed across age groups in girls (p < 0.05), particularly around menarche (12–14 yr). IgE levels were higher in boys and differed across age groups in boys (p < 0.01) and girls (p < 0.05). IgE was associated with a lower FEV 1 /FVC after adjusting for age and sex (p < 0.01). Severe or difficult‐to‐treat asthma in children and adolescents is characterized by high frequencies of comorbid allergic diseases, allergen sensitization, and high IgE levels. This burden is amplified by the association of more airflow limitation with higher IgE levels, suggesting the need for allergy evaluations.
Asthma is characterized by airflow limitations resulting from bronchial closure, which can be either reversible or fixed due to changes in airway tissue composition and structure, also known as remodeling. Airway remodeling is defined as increased presence of mucins-producing epithelial cells, increased thickness of airway smooth muscle cells, angiogenesis, increased number and activation state of fibroblasts, and extracellular matrix (ECM) deposition. Airway inflammation is believed to be the main cause of the development of airway remodeling in asthma. In this chapter, we will review the development of the adaptive immune response and the impact of its mediators and cells on the elements defining airway remodeling in asthma.
IgE Abs are a common mediator of allergic responses and are generally produced in type 2 immune responses to allergens. Allergen stimulation of IgE-bound FcεRI on mast cells or basophils induces the production of chemical mediators and cytokines. In addition, IgE binding to FcεRI without allergen promotes the survival or proliferation of these and other cells. Thus, spontaneously produced natural IgE can increase an individual's susceptibility to allergic diseases. Mice deficient in MyD88, a major TLR signaling molecule, have high serum levels of natural IgE, the mechanism for which remains unknown. In this study, we demonstrated that the high serum IgE levels were maintained from weaning by memory B cells (MBCs). IgE from plasma cells and sera from most Myd88-/- mice, but none of the Myd88+/- mice, recognized Streptococcus azizii, a commensal bacterium overrepresented in the lungs of Myd88-/- mice. IgG1+ MBCs from the spleen also recognized S. azizii. The serum IgE levels declined with the administration of antibiotics and were boosted by challenge with S. azizii in Myd88-/- mice, indicating the contribution of S. azizii-specific IgG1+ MBCs to the natural IgE production. Th2 cells were selectively increased in the lungs of Myd88-/- mice and were activated upon addition of S. azizii in the lung cells ex vivo. Finally, lung nonhematopoietic cells, and CSF1 overproduced therefrom, were responsible for natural IgE production in Myd88-/- mice. Thus, some commensal bacteria may prime the Th2 response and natural IgE production in the MyD88-defective lung environment in general.
The purpose of this study was a toxicological interpretation of exposure to chlorine with unusual course. Medical, clinical and court records, as well as reviews of the literature, served as the basis for this interpretation. The first case of poisoning concerns a 52-year-old man who for a short time (probably several hours), during the industrial cleaning of facilities with sodium hypochlorite, was exposed to chlorine in a presumed high concentration. The man was obese and suffered from hypertension and moderate atherosclerosis, and therefore could be more susceptible to the toxic effects of chlorine. After exposure no pulmonary edema or symptoms typical for acute respiratory distress syndrome were present. The second case concerns the chronic poisoning of a 56-year-old man who worked for eight years, 8 h a day, 5 days a week, in a room which was next to a chlorination room. In this chamber technical sodium hypochlorite was stored and dosed. In both cases, determining a cause and effect relationship between exposure to toxic and allergic agents in the form of active chlorine, and the onset of symptoms may be difficult. The findings described above in the first and second case are particularly important in cases of compensation claims and may have a completely different etiology than previously described in medical literature.
Résumé
Une hyper-IgE peut être retrouvée dans un grand nombre de situations pathologiques. Le rôle des IgE est essentiellement associé à la survenue des manifestations allergiques qui peuvent s’accompagner d’une augmentation de leur taux sérique. Une élévation des IgE totales a aussi été décrite en association avec la survenue de certains déficits immunologiques rares d’origine génétique appelés syndromes d’hyper-IgE. D’autres circonstances, telles que des maladies infectieuses, tumeurs ou maladies auto-immunes peuvent également conduire à une synthèse d’IgE en excès. Du fait de la diversité de ces situations, la discussion de la valeur pronostique des IgE totales est utile pour l’interniste.
Background:
Allergic rhinitis (AR) is a common disorder. The diagnosis is based on the concordance between allergy sensitization and history. Serum allergen specific immunoglobulin E (sIgE) assessment allows characterization of the relevant sensitizing allergens. Presently, Allergic Rhinitis and its Impact on Asthma (ARIA) classification subdivides AR based on symptoms severity and duration. However, the relationship between sIgE levels and symptom severity is still a matter of debate.
Objective:
Therefore, this study aimed at relating sIgE levels with symptom severity assessed by ARIA classification in a group of patients with AR.
Methods:
We enrolled 217 patients with AR (123 women; median age, 39.5 years). The sIgE levels (expressed in kUA/L) to house-dust mite were detected by the fluorescence enzyme immunoassay in peripheral blood samples. The IgE calibrators were traceable to the second international reference preparation 75/502 of human serum IgE from the World Health Organization. Symptom severity was assessed by ARIA classification.
Results:
We found a significant difference in sIgE levels in patients with mild intermittent versus mild persistent symptoms (p < 0.05), mild intermittent versus moderate-to-severe persistent symptoms (p < 0.001), moderate-to-severe intermittent versus moderate-to-severe persistent symptoms (p < 0.01), and mild persistent versus moderate-to-severe persistent symptoms (p < 0.05).
Conclusion:
Analysis of these findings indicated that the sIgE level to house-dust mite might be a reliable biomarker for symptom severity in patients with AR. This outcome might be clinically relevant, particularly in candidates for immunotherapy.
Background:
Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization.
Methods:
All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1516 participated in all three examinations.
Results:
Prevalence of any positive SPT increased from 20.6% at age 7-8 years to 30.6% at 11-12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7-8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7-8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6-2.8), urban living, OR 1.9 (95% CI 1.2-2.9), and male sex, OR 1.3 (95% CI 1.0-1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7-1.0), and furry animals at home, OR 0.7 (95% CI 0.7-0.9). Incidence after age 11-12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon.
Conclusion:
The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12 years, the factors urban living, number of siblings, and male sex lost their importance.
Background Airway hyperresponsiveness to non-specific stimuli is one characteristic feature of airway diseases such as bronchial asthma and chronic bronchitis. Until now, studies aiming to demonstrate a relationship between in vivo conditions associated with airway hyperreactivity and in vitro airway responsiveness have been inconclusive. Objective Since serum immunoglobulin (Ig) E is believed to be one determinant of airway reactivity in vivo, we studied whether in vitro airway reactivity in lung resection material from patients with elevated levels of serum IgE was increased as compared with patients with undetectable IgE. By this approach, we aimed to elucidate the role of circulating IgE for bronchial smooth muscle reactivity in vitro. Methods Bronchial rings from nine patients with total serum IgE levels above 200 U/mL and 10 patients with total serum IgE levels below 10 U/mL were passively sensitized, i.e. incubated overnight with buffer or sensitizing serum containing high levels of total IgE (> 250 U/mL). Afterwards, contractile responses to histamine were assessed in the organ bath. Results Histamine responsiveness was significantly increased in airways obtained from patients with IgE levels above 200 U/mL as compared with airways from patients with IgE levels below 10 U/mL (P < 0.05). Passive sensitization of bronchi from patients with low IgE significantly increased histamine responsiveness, as compared with non-sensitized controls from the same patients (P < 0.05). In contrast, passive sensitization of airways from patients with elevated IgE did not further increase responsiveness. There was no difference in histamine reactivity between non-passively sensitized and passively sensitized tissue preparations from patients with IgE above 200 U/mL and passively sensitized tissues from patients with IgE below 10 U/mL. Conclusion Our findings reveal that elevated levels of serum IgE predict airway hyperresponsiveness to histamine in vitro. At the same time, they indicate that the in vitro model of passive sensitization, in addition to its ability to induce allergen responses, also mimics conditions of non-specific airway hyperreactivity, which are relevant under in vivo conditions.
In early life, asthma symptoms can occur intermittently or may not be severe enough to limit normal activities, which makes it difficult for the clinician to make reliable predictions and administer therapy with some precision. In the case of pediatric asthma, the identification of children who will experience the development of a clinically important illness that will impair their quality of life can be a complex process. The usual methods for describing this information include the prognostic statistics of sensitivity, specificity, likelihood ratio, and positive predictive value. The sensitivity, specificity, and likelihood ratio of various early markers of asthma have been calculated from several cohort studies.
Ann Woolcock graduated in medicine from the University of Adelaide and pursued postgraduate studies in respiratory medicine with Professor John Read at the University of Sydney. Her MD thesis, awarded in 1967, was on the mechanical behaviour of the lungs in asthma. From 1966 to 1968 she worked with Professor Peter Macklem at McGill University in Canada, then returned to the University of Sydney to continue researching asthma. Her work in asthma and epidemiology showed that asthma was caused by allergens but that there is a genetic component. Her clinical research was a major contribution to better outcomes in asthma, in particular, the demonstration and practical measurement of airway hyperresponsiveness and her subsequent research that examined its contribution to asthma severity and the ways in which treatments were able to reduce it. In 1989 she wrote, with others, the world's first national guidelines for asthma management, the Australian Asthma Management Plan. In 1984, she was appointed to a personal chair of Respiratory Medicine at the University of Sydney. She founded the Institute of Respiratory Medicine in 1985, based at Sydney's Royal Prince Alfred Hospital. After her death, the Institute was renamed the Woolcock Institute of Medical Research in her honour.
The interactions between genetic and environmental factors play a major role in the development of childhood asthma. We hypothesized that a pre-existing Th2/asthmatic response can promote Th2 responses to newly encountered Ags (i.e., phenotype spread). To test this hypothesis, we developed a mouse model in which the requirements for the induction and inhibition of phenotype spread to a clinically relevant neo-allergen (i.e., ragweed) were investigated. Our results indicate that 1) phenotype spread to the neo-allergen can be induced only within the first 8 h after a bronchial challenge with the first Ag (OVA); 2) Th2 differentiation of naive CD4(+) T cells occurs in bronchial lymph nodes; 3) trafficking of naive CD4(+) T cells to local lymph nodes and IL-4 produced by OVA-activated Th2 cells play essential roles in the differentiation of naive CD4(+) T cells to Th2 cells; and 4) suppression of the production of chemokines involved in the homing of naive CD4(+) T and Th2 cells to bronchial lymph nodes by a TLR9 agonist inhibited phenotype spread and abrogated the consequent development of experimental asthma. These findings provide a mechanistic insight into Th2 phenotype spread and offer an animal model for testing relevant immunomodulatory interventions.
In Burkina Faso, W. indica L. syn. W. americana is used by traditional healers for curative and preventive management of asthma. Based on an ethnopharmacological approach, this study aimed to characterize W. indica on the chemical and pharmacological level according to the traditional use against asthma. Methodology: First, interviews of traditional healers confirmed the literature data concerning traditional use of the plant against asthma. Second, chemical investigations were conducted alternatively with biological investigation. Moreover, an in situ characterization of mains chemical groups was performed in different parts of the plant; then, a general acute toxicity of hydro alcoholic extract was evaluated in mice. Results and discussion: Alkaloids and polyphenols are presents in different parts of W. indica. Several compounds have been isolated from hydro alcoholic roots extract (HA). One compound have been identified as (-)-epicatechin. In vitro, HA, its fractions n-hexane (F1), dichloromethane (F2), ethyl acetate (F3), residual fraction (F4) and (-)-epicatechin isolated from F3 dose-dependently inhibited the activity of 5-LOX, LOX-IB de soja and PLA2. Inhibition of PDE4A1α by fractions was not dose-dependent. On tissue level, HA, F3 and fractions from F3 inhibited contraction induced by acetylcholine on rat trachea ex vivo. This effect was dose-dependent with IC50 of 1051 µg/mL for HA, between 181 and 477µg/mL for F3 and its fractions. HA is moderately toxic in mice (LD50 =210 mg/Kg, intraperitoneal route). This study is the first pharmacological investigation of traditional use of W. indica against asthma. Our results validate the use of W. indica in traditional for management of asthma. These effects should be, at least in part, attributed to the presence of (-)-epicatechin in roots of W. indica. Conclusion: The pharmacological validation of traditional use of W. indica against asthma must be completed in the future research by isolation and biological assays of other compounds which could participate to activity of W. indica.
Multiple Antigen Simultaneous Test (MAST)-immunoblot assay is a practical and economical test, which has been recently introduced nationwide. Authors investigated test efficiency of a MAST-immunoblot assay, Polycheck Allergy (PA).
Selective IgE deficiency (IgED) is currently defined as a significant decrease in serum levels of IgE (<2 kIU/L) in a patient whose other immunoglobulin levels are normal. There are no published large-scale epidemiological studies regarding the prevalence of and clinical features of IgED. In the population-based case-control study, we investigated clinical and laboratory characteristics of patients with IgED. Case samples were drawn from all subjects (n = 18487), with serum total IgE measurement during 2012 at Leumit Health Care Services (Israel) and had serum total IgE of <2 kIU/L. The control group was randomly sampled from the remaining 18,261 subjects with a case-control ratio of four controls for each case (1:4). Comorbid diseases were identified by specific International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes given by the corresponding board-certificated physicians. Two hundred twenty-six subjects showed serum total IgE levels of <2 kIU/L; 68 (30.9%) were between the ages of 4 and 12 years (children) and 250 (69.1%) were ≥12 years old (adults). Matched control groups were selected for each age group. The children group was characterized by higher prevalence of asthma and hyperreactive airways disease; and both children and adult groups had significantly higher prevalence of chronic sinusitis, otitis media, autoimmune, and oncological diseases than their respective controls. Undetectable serum total IgE may serve as a marker of immune dysregulation and autoimmunity.
The impact of pollen on human health is primarily evident in allergic diseases. Sensitized patients can respond to pollen by symptoms of nose, eyes and bronchi. Pollen threshold levels for sensitization are unknown; instead most studies focus on the prevalence of sensitization for different pollen species. The pollen thresholds for symptom development vary among the different studies. Factors that influence the threshold level of a pollen species for symptom development are discussed. (i) Differences in response are observed among individual patients, but also among (ii) ethnic populations, (iii) changes in response to pollen concentrations during the pollen season occur, (iv) the amount of allergens carried by the pollen grains can differ in per region, from day to day and from year to year, and finally (v) threshold levels are affected by environmental factors, like weather conditions (temperature, pressure and storms), and air pollutants.The diversity of factors that influence the health impact of pollen has hampered the definition of a straight forward relationship between pollen and the severity of symptoms. However, within the public, the policymakers and the pharmaceutical industry there is a need for a definition of threshold pollen levels. A first approach to meet this need could be to define preliminary threshold values for different regions, followed by a validation of these preliminary threshold levels with patient symptom scores that can be collected by using new information and communication technology (ICT). Finally, the possible role of pollen in non allergic diseases is discussed, especially non-allergic respiratory diseases, cardio- and cerebrovascular diseases, and psychiatric diseases, including suicide and suicide attempt.
Asthma is a common syndrome characterized by intermittent, reversible, airflow obstruction that is associated with airway hyperresponsiveness, mucus hypersecretion, and inflammation. With the advent of fiberscopic bronchoscopy, it has become possible to classify the nature of the cellular inflammation present in the airways of asthmatics. The balance of CD4 lymphocyte subsets, Th1 and Th2, is now recognized to be important in the pathogenesis of asthma. CD4 Th2 lymphocytes are central to the disease process and exert their effects through inflammatory cytokines that they release in response to activation by antigen. Th1 cells appear to be protective against the development of the disease. The treatment of asthma has traditionally been focused on decreasing inflammation and maximizing bronchodilation. Steroids and β-agonists have long since been the mainstay of therapy; however, there are now under investigation novel therapies targeted to inhibit specific proinflammatory mediators. Additionally, immunotherapy with repeated low-dose antigen exposure has had some promising results. The future of the treatment of asthma will be dependent on continued investigation into its pathogenesis.
Zusammenfassung Schimmelpilze, deren Sporen und/oder andere Schimmelpilzbestand-teile werden über die Luft eingeatmet und können schleimhautreizende (Mucous Membrane Irritation MMI, gelegentlich auch als Mucous Mem-brane Irritation Syndrome, MMIS bezeichnet) und/oder allergische Be-schwerden auslösen. Von Betroffenen werden oft neben den genann-ten Beschwerden unspezifische Symptome wie Kopfschmerzen und Müdigkeit in Zusammenhang mit Schimmelpilzexpositionen gebracht. Allergische Beschwerden äußern sich vor allem als heuschnupfenähn-liche Symptome und als Asthma bronchiale mit Luftnot und Husten. Bei sehr hohen Schimmelpilzkonzentrationen, die im Regelfall außerhalb von entsprechenden Arbeitsplätzen im Innenraum nicht vorkommen, können zudem schwerwiegende toxische Wirkungen (Organic Dust Toxic Syndrome, ODTS) beobachtet werden. In seltenen Fällen können Schim-melpilze bei bestimmten Risikogruppen (stark abwehrgeschwächte Menschen) Infektionen hervorrufen. Schimmelpilzbefall von Innenräumen ist aus hygienisch-präventiver Sicht als bedenklich einzustufen, auch wenn es zurzeit nicht möglich ist, im Einzelfall konkrete Beschwerden mit einem Schimmelpilzbefall im Innenraum in einen eindeutigen kausalen Zusammenhang zu bringen. Abstract Environmental medical relevance of mould in living environment Fungi, their spores and/or other fungal components are inhaled and can induce irritating symptoms of the mucous membranes (mucous mem-brane irritation, MMI, sometimes called as mucous membrane irritation syndrome, MMIS) and/or allergic reactions. In addition, unspecific com-plaints like headache and fatigue are often attributed to mould exposures by affected persons. Symptoms of allergic disorders are mainly similar to hay fever or asthma bronchiale with dyspnoea and cough. Severe toxic effects (organic dust toxic syndrome, ODTS) can be observed in case of very high mould concentrations usually not occurring indoors except for certain workplaces. Rarely, fungi can induce infections in certain risk groups like strongly immunosuppressed persons. Indoor air mould exposure is critical from a hygienic preventative point of view despite the fact that is is currently impossible to identify in indi-vidual cases a definitively causal relationship between indoor mould exposure and specific health disorders.
To determine the magnitude of immunoglobulin E (IgE) variability in a cohort of patients with severe asthma considered for omalizumab therapy.
Retrospective chart review identified 65 patients with two or more IgE determinations out of the 124 patients referred to the Cleveland Clinic Respiratory Institute for treatment with omalizumab from 2003 to 2011. Patients with conditions known to affect IgE concentrations were excluded. Demographic data, pulmonary function testing, medications, smoking status, and atopy were recorded. The range of variability and percent variability in relation to baseline serum IgE were calculated.
The median difference of serum IgE between the minimal and maximal values was 94.9 IU/ml (IQR 26.3-324.1 IU/ml). Percent variability from minimum value had a median of 75.5% (IQR 23.3-152.6%). There was no correlation between age, body mass index, lung function, and IgE variability. Greater variability was associated with female gender (p = .06). There was no association with peripheral eosinophilia, systemic corticosteroid use, and leukotriene modifier use at presentation. The observed variability would have affected omalizumab dosing in 20 out of 42 patients. Six patients who may have qualified at different time points would not have been deemed candidates based on an IgE concentration <30 IU/ml or >700 IU/ml.
Serum IgE concentration may have clinically significant variability over time, affecting candidacy and dosing of omalizumab. Our findings imply that repeating serum IgE determinations merits consideration for patients whose initial concentrations are <30 or >700 IU/ml. Prospective studies are warranted to delineate the factors that contribute to IgE variability.
The relationship between atopy, asthma, and eosinophilic inflammation is less clear in early childhood than later in life.
We sought to determine the relationships between asthma, atopy, and serum eosinophil cationic protein (ECP), a biomarker of eosinophil activation, in 6-year-old children.
Serum ECP levels were available from 968 six-year-old children who were part of a longitudinal birth cohort being assessed for asthma and atopy. Detailed clinical history and examination, lung function testing, methacholine challenge, and skin prick testing to 4 common allergens were undertaken. Subgroups of the children were compared by using t tests, ANOVA, chi 2 tests, and regression analysis.
One hundred ninety-one (19.7%) children had current asthma, with 114 (59.7%) of these being atopic. The mean serum ECP level for the entire group was 18.0 mug/L (range, 2.0-146.0 mug/L), with no difference between male and female patients. Serum ECP was higher in atopic children (20.5 +/- 18.4), those with asthma (22.4 +/- 19.6), and those with asthma and atopy (26.6 +/- 22.4; all P < .001 compared with children with no asthma or atopy [16.1 +/- 15.9]). Serum ECP levels were highest in children with severe asthma ( P < .001), especially in those with concurrent atopy. Severity of atopy, judged on the basis of wheal size or derived variables combining wheal size and the number of positive skin tests, was a major determinant of serum ECP. Heightened methacholine responsiveness was not associated with increased serum ECP levels.
The higher serum ECP levels seen in 6-year-old children with current asthma and more severe atopy suggest that atopy and eosinophilic inflammation are important in driving this clinical phenotype and that this might represent asthma that persists.
Clinical research findings indicate that there are synergistic interactions between allergy and viral infection that cause increased severity of asthma exacerbations. This article summarizes the current literature linking these 2 risk factors for asthma exacerbation, and reviews experimental data suggesting potential mechanisms for interactions between viral infection and allergy that cause asthma exacerbations. In addition, the authors discuss clinical evidence that treatment of allergic inflammation could help to reduce the frequency and severity of virus-induced exacerbations of asthma.
Omalizumab is the first of a new generation of targeted asthma therapies. This monoclonal antibody against IgE is now licensed for use in atopic asthma. The majority of asthmatics are well controlled with conventional therapies. However, there remains a cohort of patients with severe refractory asthma, despite currently available treatments ( approximately 5-10% of asthmatics), which account for approximately 50% of direct expenditure on asthma care. This article examines the evidence for both clinical and cost-effectiveness of omalizumab in patients with severe asthma and gives a 5-year view on the likely role of omalizumab in clinical practice.
A new europium fluorescent chelate, 4,4'-bis(1",1",1",2",2",3",3"-heptafluoro-4",6"-hexanedione-6"-yl) - chlorosulfo-o-terphenyl (BHHCT)-Eu3+, was used as a label for highly sensitive time-resolved fluoroimmunoassay of human IgE. Two assay formats were employed in the analysis. In the first format, an immunoconjugate of rabbit anti-human IgE antibody-human IgE-biotinylated goat anti-human IgE antibody-BHHCT-Eu(3+)-labeled SA (or BHHCT-Eu(3+)-labeled BSA-SA; BSA, bovine serum albumin; SA, streptavidin) was used for measurement. The method gives the detection limits of 3.6 x 10(-2) IU/ml (labeled SA) and 1.1 x 10(-2) IU/ml (labeled SA-BSA). In the second format, an immunoconjugate of goat anti-human IgE antibody-human IgE-rabbit anti-human IgE antibody-biotinylated goat anti-rabbit IgG antibody-BHHCT-Eu(3+)-labeled SA (or BHHCT-Eu(3+)-labeled BSA-SA) was used for measurement. The detection limits of these methods are 3.0 x 10(-3) IU/ml (labeled SA) and 1.5 x 10(-3) IU/ml (labeled BSA-SA). The above detection limits are one to two orders of magnitude lower than those of the conventional radioimmunoassay and enzyme immunoassay. The CV of the present method is less than 7%, and the recovery is in the range of 85-105% for serum samples.
In recent years the morbidity and mortality of asthma has increased, although the etiology is still poorly understood. Most patients with asthma suffer acute attacks that are commonly treated in hospital emergency rooms (ER). In the present study, asthma in adults was studied with acute attacks as a marker for the disease; 102 patients first observed at a university hospital ER with acute airway obstruction were compared to 118 patients observed at the same ER with any diagnosis other than shortness of breath to evaluate allergy as a risk factor for asthma in adults. Sera were assayed for IgE antibody (Ab) to dust mites, cockroach, cat dander, and grass and ragweed pollen. The results demonstrate that in adults younger than 50 years of age, the prevalence of IgE Abs was fourfold greater among subjects with asthma than among control subjects (46/67 versus 12/81; odds ratio, 10.1; 95% confidence interval, 4.9 to 20.7). The population attributable risk for the presence of IgE Ab to one of the five allergens was greater than 50%. Among individuals older than 50 years of age, the prevalence of serum IgE Abs was not significantly increased among patients with acute airway obstruction. In the whole group, the prevalence of IgE Abs to different allergens demonstrated significant seasonal and socioeconomic differences, suggesting that the associated risk is related to exposure to those allergens. The results establish that, with acute attacks of asthma as a marker for adult asthma, the presence of serum IgE Abs to common inhalant allergens is a major risk factor.(ABSTRACT TRUNCATED AT 250 WORDS)
A group of 323 subjects who had wheezed in childhood and 48 control subjects of the same age were studied prospectively from 7 to 28 years of age. A classification system based on wheezing frequency was found to correlate well with clinical and spirometric features of airway obstruction. The amount of wheezing in early adolescence seemed to be a guide for severity in later life with 73% of those with few symptoms at 14 continuing to have little or no asthma at 28 years. Similarly 68% of those with frequent wheezing at 14 still suffered from recurrent asthma at 28 years. Most subjects with frequent wheezing at 21 continued to have comparable asthma at 28 years. Of those with infrequent wheezing at 21, 44% had worsened at 28 years. Women fared better than men between 21 and 28 with 19% having worse symptoms compared with 28% of men. Treatment at all ages was generally inadequate. The number of smokers among those with asthma was of concern.
A rapid, simple method for measuring bronchial responsiveness to inhaled histamine is described. The method was used to obtain dose response curves in 50 atopic subjects with varying respiratory and nasal symptoms. The cumulative dose of histamine which caused a 20% fall in the one second forced expiratory volume (PD20-FEV1) varied between 0.046 and greater than 3.9 mumol and correlated with the severity of symptoms. The reproducibility of the PD20-FEV1, determined from duplicate measurements in 15 subjects with varying degrees of bronchial responsiveness was found to be satisfactory. When the PD20-FEV1 from this rapid method was compared with that obtained from the dosimeter method no significant difference was found. The dose delivered by this method was shown to be cumulative.
To assess the prevalence and distribution of allergic skin-test reactions in a general population sample, allergy prick tests were applied to 3101 subjects older than 2 years of age. Test materials included allergens common to the Tucson environment, and subjects were randomly stratified by age, sex, and socioeconomic status. No difference in the prevalence of measurable reactions was found among male subjects versus female subjects. A definite age relation was apparent, however, with the peak prevalence of reactivity (more than 40%) occurring during the third decade, and falling rapidly past age 50. When present, reactions tended to be multiple, highly reproducible, and more frequent among those in the higher socioeconomic strata. The prick test was judged to be a useful tool for the assessment of atopy.
Four out of five commercially available benzylpenicillin preparations elicited homologous passive cutaneous anaphylactic (PCA) reaction in sensitized guinea pigs with anti-benzylpenicilloyl (anti-BPO) reaginic sera. The same preparations could not evoke PCA reaction in sensitized guinea pigs with anti-BPO γ1 homocytotropic antibodies. The PCA reactions were completely inhibited by a prior injection of BPO-ε-aminocaproic acid (BPO-EACA). Chromatographic analysis of one of the benzylpenicillin preparations on Sephadex G 10 revealed that the reagin-mediated PCA reaction was not evoked with the fractions from the main peak of the benzylpenicillin but with fractions eluted earlier. None of the fractions gave positive γ1-mediated PCA reactions. These results indicated that some commercial benzylpenicillin preparations contained minute amounts of the impurities that could elicit the homologous PCA reaction in guinea pigs sensitized with anti-BPO reaginic sera. It was also indicated that the PCA elicitation activity of the benzylpenicillin preparation in the system of reagin-mediated PCA differed from that of γ1-mediated PCA.
To assess the prevalence and distribution of allergic skin-test reactions in a general population sample, allergy prick tests were applied to 3101 subjects older than 2 years of age. Test materials included allergens common to the Tucson environment, and subjects were randomly stratified by age, sex, and socioeconomic status. No difference in the prevalence of measurable reactions was found among male subjects versus female subjects. A definite age relation was apparent, however, with the peak prevalence of reactivity (more than 40%) occurring during the third decade, and falling rapidly past age 50. When present, reactions tended to be multiple, highly reproducible, and more frequent among those in the higher socioeconomic strata. The prick test was judged to be a useful tool for the assessment of atopy.
Accurate measurement of low IgE concentrations is technically difficult. In this paper results obtained by a direct sandwich and three inhibition methods of radioimmunoassays are compared. For values above 50 U/ml good correlation was obtained with all methods. Below 50 U/ml, however, the inhibition methods tended to yield falsely high values. For very low concentrations, 1–10 U/ml the best correlation was obtained between the direct sandwich test (PRIST*) and the inhibition test using a correction factor to allow for the non-specific effect of serum.
The four methods were used to quantify IgE in cord serum samples from healthy individuals. The mean value obtained by PRIST was 0.4 U/ml and by the inhibition test, using a correction factor, 0.6 U/ml respectively. Because of its greater simplicity the direct sandwich test is recommended.
Because there is no "gold standard" for defining asthma for epidemiology, we have defined current asthma as bronchial hyperresponsiveness (BHR) plus recent wheeze (in the 12 months prior to study). To describe the characteristics of groups categorized by these measurements, we studied two samples of children aged 7 to 12 yr: 210 from a population sample and 142 self-identified asthmatics. Bronchial responsiveness to histamine was measured by the rapid method, respiratory symptom history, and asthma medication use by self-administered questionnaire to parents and atopy by skin prick tests to 14 allergens. Children recorded daily Airflometer readings and symptom scores for 2 wk. Children with current asthma had more severe bronchial responsiveness, greater Airflometer variability, more symptoms, more atopy (particularly to house dust mites), and used more asthma medication than children with BHR or recent wheeze alone. Children with BHR, but not with recent wheeze, were intermediate between the current asthma and normal groups in terms of bronchial responsiveness, Airflometer variability, and atopy. Children with recent wheeze and normal responsiveness differed from the normal group only in symptoms and medication use. Our definition of current asthma discriminates a group of children that is clearly different in terms of both clinical features and physiologic measures. As such, it is the most useful definition to date for measuring the prevalence of clinically important asthma in populations.
The relationship of bronchial responsiveness (BR), assessed by methacholine challenge, to serum IgE, baseline ventilatory function, and symptoms or diagnoses suggesting an atopic disorder were examined in 522 11-year-old New Zealand children. BR was assessed by the presence or absence of a PC20 25 mg/ml or less and by calculating a continuous index of the decline of the FEV1 during the methacholine test. The latter facilitated multivariate analyses and revealed significant relationships to predictor variables even in those considered "nonresponsive" by PC20 criteria. There was a close relationship of BR to the baseline FEV1/vital capacity ratio, seen even in patients with known asthma, but this relationship was seen only in subjects with at least moderate levels of serum IgE. There was a less close relation of BR to percent predicted FEV1, but this persisted even after accounting for the FEV1/vital capacity ratio and was present regardless of the level of serum IgE. Reported asthma was associated with increased BR independent of all other factors, but other diagnoses and symptoms contributed relatively little to the prediction of BR once the serum IgE and lung function were taken into account. The overall results are compatible with the concept that IgE is a critical factor in the development of bronchial responsiveness in childhood.
In order to examine further the relation between atopy, as defined by skin-prick tests, and respiratory illness, we studied three populations of schoolchildren aged 8-11 years and living in different climatic areas of New South Wales, Australia. Skin-prick tests were performed using 13 commercial allergen extracts. Respiratory and allergic symptoms were assessed using a self-administered questionnaire to parents and bronchial hyper-responsiveness (BHR) was measured by histamine inhalation test. We defined current asthma as BHR together with symptoms of wheeze in the 12 months prior to study. Children with one or more positive skin weals of greater than or equal to 3 mm had significantly more recent wheeze, hayfever, eczema and BHR than children with smaller weals (P less than 0.001). In each area, 95-97% of all atopic children were sensitized to one of the following seven allergens: house dust, Dermatophagoides farinae, D. pteronyssinus, cat dander, plantain, rye grass, and Alternaria tenuis. Thus, these seven selected allergen extracts and a skin weal of 3 mm could be used to detect clinically relevant atopy in these populations of children. Sensitivity to house dust mite had the strongest independent association with current asthma in all three areas. The associations of other allergen sensitivities with BHR or current asthma were area dependent, indicating the influence of local allergen levels on respiratory illness in children. The potency of house dust mite sensitivity in increasing the risk of children having BHR and current asthma is confirmed.
A group of 26 Australian asthmatic children with laboratory-proven bronchial hyper-reactivity to the allergens of rye grass pollen and/or the house dust mite has been studied over a 9-year period. Clinical symptoms and drug scores were used to evaluate the severity of the patients' asthma and, wherever possible, blood samples were obtained before, during and after the rye grass pollen seasons. The cumulative symptom and drug scores for the 20 patients with bronchial hyper-reactivity to rye grass pollen extract tended to increase during and fall after each pollen season but the peaks were of decreasing amplitude over the 9 years. Since a proportion of these patients underwent hyposensitization to rye grass during year 1, longitudinal comparisons were made between year 2 and year 9. Comparing the individuals at the same three seasonal time-points revealed significantly lower drug scores in year 9 compared with year 2, and in parallel with this, significantly lower total IgE, IgE anti-rye and IgG anti-rye antibodies at all three assessment points. In the 14 patients with bronchial hyper-reactivity to house dust mite the severity of the asthma and the median levels of IgE and IgG mite specific antibodies all decreased over the study period. Despite the progressive improvement in asthma and diminishing immune responses to both rye grass and house mite in the patients, no immunological feature could be identified that correlated significantly with clinical outcome.
Although asthma diagnosed by a physician is known to be related to serum IgE levels, it is not known whether there is a relation between the level of IgE and airway hyperresponsiveness to a methacholine challenge. The characteristics of asymptomatic persons that predispose them to airway hyperresponsiveness are also unknown.
We studied the relation between the serum total IgE level and airway hyperresponsiveness in the presence or absence of asthma and other atopic diseases in a birth cohort of children. Data from a questionnaire regarding respiratory symptoms, plus measurements of the serum total IgE level and airway responsiveness to inhaled methacholine, were obtained for 562 11-year-olds in New Zealand.
The boys had a higher prevalence than the girls of current diagnosed asthma (13 percent vs. 6 percent), current symptoms of wheezing (22 percent vs. 15 percent), and airflow obstruction at base line (6 percent vs. 1 percent) and had a wider distribution of IgE levels, although mean IgE levels (120.8 IU per milliliter in the boys and 98.1 IU per milliliter in the girls) did not differ significantly between the sexes. The prevalence of diagnosed asthma was strongly related to the serum IgE level (P for trend less than 0.0001). No asthma was reported in children with IgE levels less than 32 IU per milliliter, whereas 36 percent of those with IgE levels greater than or equal to 1000 IU per milliliter were reported to have asthma. This relation with the serum IgE level was not explained by a concomitant diagnosis of allergic rhinitis or eczema. Airway hyperresponsiveness to a methacholine challenge also correlated very highly (P less than 0.0001) with the serum IgE level. This relation remained significant even after the exclusion of children with diagnosed asthma (P less than 0.0001) and of all children with a history of wheezing, allergic rhinitis, or eczema (P less than 0.0001).
Even in children who have been asymptomatic throughout their lives and have no history of atopic disease, airway hyperresponsiveness appears to be closely linked to an allergic diathesis, as reflected by the serum total IgE level.
To describe bronchial responsiveness in populations, the dose-response slope (DRS), which is the linear slope of the dose-response curve, may be a more useful measure of severity than the provoking dose that causes a 20% fall in FEV1 (PD20 FEV1). To examine the distribution of DRS measurements and their relation to respiratory symptoms in children, we have analyzed data collected during a population study designed to measure the prevalence of bronchial hyper-responsiveness and respiratory symptoms. In this study, respiratory symptom history was measured by a self-administered questionnaire to parents and bronchial responsiveness was measured using the rapid inhalation method. Of 1,217 children studied, DRS values were obtained for 1,203 children who had technically satisfactory bronchial challenge data. In asymptomatic children, DRS values were distributed symmetrically on a logarithmic scale. The geometric mean DRS was reliable measure of the central position of the curve, and 1.96 standard deviations only slightly underestimated the 95% interval. In children with recent wheeze, the distribution was skewed toward larger DRS values. Mean DRS values were significantly different between groups determined according to symptom frequency. It appears that DRS values are more useful than PD20 FEV1 values in epidemiologic studies of respiratory illness in children because a value that relates well to symptom history can be calculated for the entire sample. The major advantages are that the measurement more clearly discriminates between symptom severity groups and that a value that represents abnormal responsiveness can be calculated.
We studied 143 young subjects by skin-prick testing to common allergens and by the measurement of non-specific bronchial responsiveness (NSBR). A logistic regression model showed a prevalence odds ratio (POR) for bronchial hyper-responsiveness (PD20 less than 10 mumol methacholine) in house dust positive subjects of 4.10 (95% CI 1.77-9.51, P less than 0.001), and in mould positive subjects 5.72 (95% CI 2.06-15.9, P less than 0.001): the PORs for epithelia (2.05, P = 0.12) and grasses (1.78, P = 0.19) were not significant. If bronchial reactivity was assessed as measurable (PD20 less than 102 mumol methacholine) or not, the POR for house-dust-positive subjects was 4.83 (95% CI 2.23-10.5, P less than 0.001), for moulds was 10.5 (95% CI 2.33-47.5, P less than 0.001), for epithelia was 4.79 (95% CI 1.91-12.0, P less than 0.001), and for grasses was 2.21 (95% CI 1.11-4.4, P = 0.022). The results show the risk of bronchial hyper-responsiveness is greater in subjects sensitive to house dust and mould than in those reactive to grasses, and suggests that the presence or absence of increased NSBR in atopic individuals may depend on the antigens to which they become sensitized.
A group of 20 mite allergic asthmatic children aged 6-12 years old, living in São Paulo, Brazil, was studied regarding their degree of sensitization to house dust mites and exposure to mite allergens in their homes. In 18 out of 20 houses at least one dust sample was obtained which contained greater than 10 micrograms Der p I/g of dust. The highest levels of Dermatophagoides pteronyssinus allergens, Der p I and Group II, were measured in bedding samples (geometric mean 38.4 and 36.6 micrograms/g, respectively), followed by bedroom floor, TV room and kitchen. Mite allergen levels in Brazilian houses were as high as those reported to be associated with sensitization and acute attacks of asthma in other parts of the world. In keeping with previous reports that D. farinae is rarely found in Brazil, Der f I was undetectable or found in very low levels (less than 0.5 micrograms/g). Levels of cat allergen Fel d I of greater than 8 micrograms/g of dust were obtained only in 2 houses only. Cockroach allergen Bla g I was detected in five out of 20 houses. Levels of IgE antibodies to D. pteronyssinus were greater than 200 RAST U/ml in 19 out of 20 children (geometric mean 1588 RAST U/ml). IgE antibodies to cat, cockroach, A. fumigatus, ragweed and rye grass pollens were undetectable or less than 80 RAST U/ml. IgE antibodies to the mite Blomia tropicalis were also measured, and levels greater than 200 RAST U/ml were observed in 13 out of 20 sera.(ABSTRACT TRUNCATED AT 250 WORDS)
Over the last 20 yrs our understanding of the relationship of allergens to asthma has changed completely. This is due to several interrelated developments: firstly, it is clear that bronchial hyperreactivity can be increased by allergen exposure and that it is at least in part reversible; secondly, it is now generally accepted that asthma involves inflammation of the bronchi in which eosinophils play an important role; thirdly, there are a large number of studies demonstrating an epidemiological relationship between immediate hypersensitivity to dust mites and asthma; finally, it has been shown that natural exposure to dust mite allergens is very different from bronchial provocation. Together these findings have lead to the view that indoor allergens can play a major role in causing bronchial inflammation with consequent bronchial reactivity and that this is usually not apparent to the patient. Recently three studies in the USA have established that immunoglobulin E (IgE) antibodies to common inhalants can also be important risk factors for acute asthma. In these studies both dust mites and pollens were significant, but cat and cockroach allergy were also important. The results imply that the management of all asthma requires evaluation of the role of immediate hypersensitivity and that treatment of inflammation in the lungs should include both anti-inflammatory drugs and allergen avoidance.
Children with asthma commonly have positive skin tests for inhaled allergens, and in the United Kingdom the majority of older children with asthma are sensitized to the house-dust mite. In a cohort of British children at risk for allergic disease because of family history, we investigated prospectively from 1978 to 1989 the relation between exposure to the house-dust mite allergen (Der p I) and the development of sensitization and asthma.
Of the 67 children studied in 1989, 35 were atopic (positive skin tests), and 32 were nonatopic. Of the 17 with active asthma, 16 were atopic (P less than 0.005), all of whom were sensitized to the house-dust mite, as judged by positive skin tests and levels of specific IgE antibodies (P less than 0.001). For house-dust samples collected from the homes of 59 of the children in 1979 and from 65 homes in 1989, the geometric means for the highest Der p I exposure were, respectively, 16.1 and 16.8 micrograms per gram of sieved dust. There was a trend toward an increasing degree of sensitization at the age of 11 with greater exposure at the age of 1 (P = 0.062). All but one of the children with asthma at the age of 11 had been exposed at 1 year of age to more than 10 micrograms of Der p I per gram of dust; for this exposure, the relative risk of asthma was 4.8 (P = 0.05). The age at which the first episode of wheezing occurred was inversely related to the level of exposure at the age of 1 for all children (P = 0.015), but especially for the atopic children (r = -0.66, P = 0.001).
In addition to genetic factors, exposure in early childhood to house-dust mite allergens is an important determinant of the subsequent development of asthma.
Recent studies have suggested that inflammation may play an important role in the characteristic bronchial hyperresponsiveness and symptoms of chronic asthma. The mechanisms by which inflammatory cells, mediators, and nerves interact to produce the features of asthma are still uncertain, however. Although mast cells play an important role in the immediate response to allergen (and probably exercise), pharmacologic evidence argues against a critical role in the late response or bronchial hyperresponsiveness in which other cells, such as macrophages and eosinophils, may play a more important role. Many mediators have been implicated in asthma, but only PAF causes a prolonged increase in bronchial responsiveness. PAF attracts eosinophils into tissues and potently activates these cells, which may lead to epithelial damage, a key feature of asthmatic airways. PAF is also a potent inducer of microvascular leakage in airways, which may result in submucosal edema and plasma exudation into the airway lumen in the future. PAF antagonists will reveal whether PAF plays an important role in the eosinophilic inflammation of asthma. Neural mechanisms may also make an important contribution. Inflammatory mediators may influence neurotransmitter release from airway nerves, and neurotransmitters may be proinflammatory. Neural control is complex and cholinergic, adrenergic, and NANC mechanisms may contribute to bronchial hyperresponsiveness. Many neuropeptides, which may be the transmitters of NANC nerves, have been identified in airways. Neuropeptides in airway sensory nerves, such as substance P, have potent proinflammatory effects and, if these are released by an axon reflex, may amplify the inflammatory response in asthma. Since asthma may be chronic eosinophilic bronchitis, it is logical that the primary treatment should involve drugs that suppress this inflammatory response. At present, corticosteroids appear to be the most effective therapy; they have potent effects against eosinophils and macrophages (but not on mast cells) and reduce bronchial hyperresponsiveness and symptoms. By contrast, bronchodilators, such as beta-agonists, although they reduce symptoms, do not reduce the chronic inflammatory response or bronchial hyperresponsiveness and may mask the underlying inflammation. New therapies should be directed toward controlling eosinophil infiltration and activation in airways.
The interrelationships between smoking history, objective markers of allergy and inflammation, and methacholine responsiveness were examined among 778 middle-aged and elderly men (age range 41 to 86 yr). Methacholine responsiveness was analyzed using dose-response slope to describe each subject's responsiveness. Current smokers were observed to have significantly greater total serum IgE concentration ([IgE]), blood total leukocyte count, and blood eosinophil count than nonsmokers. Current smokers with at least one positive skin test reaction to common aeroallergens displayed significantly greater methacholine dose-response slope than smokers with negative skin test results (p less than 0.01). Among nonsmokers, skin test positivity was associated with slightly but not significantly greater methacholine responsiveness. Among subjects with negative skin test results, smoking was not associated with greater methacholine responsiveness. Blood eosinophil count and serum total [IgE] displayed weak but statistically significant direct relationships to methacholine dose-response slope (p less than 0.01), and these relationships were not significantly modified by smoking status. In a multivariate model, the cigarette smoking/skin test positivity interaction, total serum [IgE], and blood eosinophil count displayed significant, independent relationships to methacholine dose-response slope, although only a small portion of the variance of dose-response slope was accounted for by these covariates. These data suggest that smoking and atopy may act synergistically to increase the degree of nonspecific airway responsiveness displayed by middle-aged and elderly individuals. Allergic airway inflammation, as reflected by total serum [IgE] and blood eosinophil count, may also influence nonspecific airway responsiveness in this age group.
The associations between skin sensitivity to various common allergens and the development of childhood asthma were ascertained in a longitudinal study of a birth cohort of New Zealand children up to the age of 13 years. Of 714 children skin-tested, 45.8% were sensitive to at least one of 11 allergens, the most common responses being to rye grass pollen (32.5%), house dust mite (30.1%) and cat dander (13.3%). Allergen-specific relative risk analysis, controlled for the effect of sensitivity to other allergens, demonstrated that sensitivity to house dust mite and to cat dander were highly significant independent risk factors associated with the development of asthma (whether defined as recurrent typical respiratory symptoms, increased airway responsiveness, or the concurrent presence of both), whereas grass sensitivity was not a significant independent risk factor for asthma.
We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma.
Do subjects living in high altitude where house-dust mites are known to be uncommon exhibit a lower prevalence of asthma and allergy to house-dust mites? To answer this question, we compared the prevalence rates of asthma and skin reactions to house-dust mites in two towns with contrasted environments: Marseille, located on the seashore, and Briançon, 1350 m in altitude. The study population consisted of a random sample of 4,008 people in Marseille and 1,055 people in Briançon. All subjects received a home questionnaire, and a sample of patients and asymptomatic subjects had a skin-prick test evaluation. The cumulative prevalence of asthma was equal to 4.1 percent in Marseille and 2.4 percent in Briançon, a difference which was significant (p = 0.01). The prevalence of positive skin tests to housedust mites in asymptomatic subjects was equal to 27.5 percent in Marseille and 10.2 percent in Briançon (p less than 0.001). This study supports the hypothesis that exposure to environmental factors may have a major influence on developing allergic diseases.
Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longitudinal study of aging. Among the participants of the latter study, there is a unimodal, skewed distribution of dose-response slope. Dose-response slope is proposed as a quantitative measure of nonspecific airway responsiveness that avoids censoring and that may be particularly useful in epidemiologic studies.
A cohort of 1333 subjects, aged 3 years and older, was followed for a mean of 8.1 years to assess changes in allergen skin test reactivity. The overall prevalence of reactivity to the five antigen mixtures was 39.1% during the initial survey and 50.7% after the follow-up period. The greatest increase in prevalence occurred among children and teenagers (22.2% and 19.5%) with only minimal increases after the age of 65 years (6.0%). No difference in prevalence between male and female subjects was apparent, either initially or at the end of the follow-up period. In-migration to the Tucson area was a major factor in determining changes in reaction prevalence. Among subjects more than 35 years of age, recent in-migrants accounted for most of the increased prevalence. Comparisons of atopy among consistent smoking groups confirmed the previous observation that smokers are less atopic than either nonsmokers or exsmokers, probably because of a self-selection process. In contrast, exsmokers were generally the most atopic, both initially and at the end of the longitudinal observation period. The high overall prevalence of allergen reactivity in this population is believed to be due in large measure to high year-round concentrations of multiple aeroallergens in the Tucson environment.
The bronchial response to inhaled histamine has been suggested as an epidemiological tool for assessing the prevalence of asthma, though the exact relationship between reactivity and asthma is unknown. Tests of bronchial reactivity to histamine were carried out in 511 subjects aged 18-64 years, randomly selected from the population in two areas of the South of England, who had returned questionnaires on respiratory symptoms. Bronchial reactivity to less than or equal to 8 mumol histamine was present in 14% and was associated with positive skin test responses to common allergens and with smoking history. Both of these relationships were in turn dependent on age, skin sensitivity being the more important determinant of reactivity in the young and smoking the more important in older subjects. Bronchial reactivity was least prevalent in the 35-44 year age group. No independent effect on reactivity of sex, social class, or area of residence was detected, and no significant effect from recent respiratory tract infections. Interpretation of the bronchial response to histamine in selected groups of subjects must take account of age, atopic state, and smoking history.
A coastal population mainly reactive to house dust mite was compared with an inland population mainly reactive to other allergens
to investigate whether exposure to house dust mite plays a part in initiating childhood asthma. Respiratory symptoms, asthma,
bronchial hyperresponsiveness, hay fever and atopy were all more common in the dry inland area than in the humid coastal area.
In both areas 38% of children were atopic. Coastal children had more skin reactivity to house dust mites and inland children
were more reactive to grass pollen extracts. The findings suggest that the clinical presentation of asthma may be related
more to the total burden of aeroallergens than to exposure to a particular allergen.
An allergic population of 341 patients was studied using 14 different allergen extracts in skin prick tests and radioallergosorbent tests (RAST) in an attempt to identify important allergen sources in the Sydney area and to examine relationships between these diagnostic methods and a number of clinical parameters. A computer based statistical analysis of the data revealed that: (a) male patients showed a significantly higher frequency of skin test reactivity to extracts of house dust and the house dust mite Dermatophagoides farinae; (b) the incidence of positive prick test reactions declined with age; (c) cross-reactive allergenic determinants were found in taxonomically-related extracts (e.g. between different house dust mites, pollens, and fungi); (d) a clear correlation emerged between relative potency using a histamine standard and RAST score which supports the continued use of histamine as a standard in skin prick testing; and (e) important associations between certain allergens and clinical diagnosis emerged (e.g. positive skin test reactions to house dust mites and epithelia but not pollens were associated with asthma).
Serum IgE concentrations, IgE antibody titers to mite allergen, the number ofblood cosinophils, the number of positive scratch tests, and the bronchial reactivity to acetylcholine were examined on the following 3 groups: (1) asthmatic subjects who had been in remission for 3 years or more; (2) asthmatics currently having asthma attacks; (3) normal healthy control subjects. Mean values were all higher in the asthmatic groups than in the controls. Differences between the 2 asthmatic groups were insignificant except for the acetylcholine inhalation tests, in which asthmatics in remission had lower bronchial reactivity than active asthmatics. In the former group, decreases in bronchial reactivity to acetylcholine after remission were observed in 7 of the 9 subjects. No correlation was obtained between bronchial reactivity and serum IgE. Of 7 asthmatics in remission having high serum IgE levels, 6 showed low bronchial responsiveness to acetylcholine, while the remaining one retained marked bronchial hyperreactivity. These results indicated that the atopic disposition of asthmatic subjects persisted but the bronchial reactivity to acetylcholine might decrease after long-term remission.
We studied the relationship between specific IgE antibodies, nonspecific bronchial reactivity to methacholine, and the type of asthmatic reaction in patients with red cedar asthma. The level of circulating specific IgE antibodies (expressed as RAST ratios) was not related to the type of asthmatic reaction, the degree of nonspecific bronchial hyperreactivity [expressed by the provocative concentration of methacholine producing a 20% decrease in the forced expiratory volume in 1 sec (PC20)] or the index of reactivity to plicatic acid. On the other hand, methacholine PC20 was found to correlate with the index of reactivity to plicatic acid in the late asthmatic reaction (LAR) and both the immediate and late components of the dual asthmatic reaction (DAR). Development of the LAR is associated with increase in nonspecific bronchial hyperreactivity. Repeated inhalation challenge with plicatic acid in eight patients with LAR resulted in DAR in all. The results suggest that the mechanism responsible for the LAR is associated with an increase in nonspecific bronchial reactivity; furthermore, the immediate component of DAR could also be related to heightened bronchial hyperreactivity.
This is a prospective study of wheezing children, who were followed up from the ages of seven to 21 years. Allergy factors were documented in all subjects. Hay fever and positive reactions to skin allergy tests were more prevalent in 21-year-old subjects with severe asthma. However, 50% of subjects who had ceased wheezing has hay fever, and 65% had at least one positive skin test reaction. The number of asthmatic subjects with hay fever and positive skin test reactions progressively increased between the ages of seven and 21 years. Eczema was significantly associated only with severe asthma. More 21-year-old subjects with severe asthma wee breast-fed in infancy for longer periods than in the control group and in groups with mild to moderate asthma. Further investigation is needed before the hypothesis that breast feeding protects against the development of allergic phenomena can be accepted.
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