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The role of house dust mite elimination in the management of childhood asthma: an unresolved issue.

Indoor allergens are likely to be direct environmental causes of asthma and mite exposure, and sensitization is the most important environmental risk factor for childhood asthma in temperate zones. Analagous to occupational asthma, allergen avoidance in asthmatic children sensitized and exposed to mite allergens is associated with a reduction in airway hyperresponsiveness and symptoms associated with improvement in lung function. The long-term effect of this strategy needs to be prospectively evaluated considering both the timing and duration of exposure, as well as the timing and duration of removal. In order to be successful, it is important to achieve and maintain a major reduction on allergen levels, for a long period of time.

Air Pollutants↗

The use of mutually exclusive categories for atopic sensitization: a contrasting effect for family size on house dust mite sensitization compared with ryegrass sensitization.

Our aim was to examine the relative importance of family size on sensitization to two different allergens: ryegrass and house dust mite (HDM), using a mutually exclusive classification for allergen-specific sensitization. An 8-year follow-up birth cohort study of children born between 1988-89 was conducted. The follow-up sample consisted of 498 children residing in Northern Tasmania in 1997 (84% of eligible). Outcome measures included skin prick test (SPT) reaction to nine aeroallergens and parental questionnaire. Family size was defined as sibling number in 1997. Children with a positive SPT to either Der p or Der f house dust mite but not ryegrass were classified as HDM-exclusive (n = 84). Children with a positive SPT to ryegrass but not HDM were classified as ryegrass-exclusive (n = 43). Family size was associated with reduced ryegrass-exclusive sensitization [AOR 0.57 (0.39, 0.84) per increase in sibling number] but not HDM-exclusive sensitization [AOR 0.97 (0.77,1.23)]. The difference in the family size effect on these sensitization outcomes was significant (p = 0.02). Similarly, family size tended to be associated with reduced asthma among ryegrass-exclusive sensitized children [AOR 0.45 (0.18,1.12)] but not HDM-exclusive sensitized children [(AOR 1.46(0.80-2.65)]. Large family size was strongly associated with reduced sensitization for ryegrass allergens but not HDM allergens using mutually exclusive sensitization categories. If this difference is confirmed in other studies, the contrasting effect of family size may reflect differences between these allergens with regard to level or timing of early life exposure, differences in allergen -specific potentiation for sensitization or unidentified confounding. The use of mutually exclusive categories for allergen sensitization will assist future work on child atopic disease.

Allergens↗

The effect of montelukast on allergen-induced cutaneous responses in house dust mite allergic children.

The benefits of a leukotriene modifier on allergen-induced cutaneous responses have not been studied in children. We hypothesized that a leukotriene-receptor antagonist would provide protection against allergen-induced early and/or late phase cutaneous responses in susceptible children. In a randomized, double-blind, placebo-controlled, cross-over study in 6- to 15-year-old house dust mite allergic children, we compared the benefit of either montelukast or a matching placebo for 2 days on cutaneous responses induced by intradermal injection of house dust mite extract. Responses were measured as the mean of the longest diameter and its longest perpendicular of the induration response after 10, 20 min, 4 h and 6 h of the challenge. A total of 30 children were randomized to placebo or montelukast. The mean decline from baseline was significantly greater (p = 0.04) in the montelukast-treated children [-5.20 mm (-12.03-1.63)][median (95% CI)] than in the placebo-treated children [0.13 mm (-6.46-6.73] at 6th hour of the challenge, as was the mean diameter (p = 0.04), but did not differ in the remaining time points. We concluded that in house dust mite allergic children, montelukast 5 mg provided significant improvement in allergen-induced cutaneous late-phase responses, suggesting its contribution to allergic skin responses and its potential therapeutic value.

Acetates↗

Predictive features for persistence of atopic dermatitis in children.

Allergen exposure plays an important role in atopic dermatitis (AD). Because immunological mechanisms underlying asthma and AD have great similarities, we evaluated whether features such as allergen sensitization, immune response, disease severity and duration or allergen exposure could be considered predictive for AD persistence. Seventy-one AD children (age range 14-158 months) were enrolled and followed for 3 consecutive years for AD severity using the SCORAD index (SI). At enrollment, reactivity to inhalant and food allergens using the skin prick test (SPT) and house dust mite (HDM) atopy patch test (APT), and HDM allergens in house dust were evaluated. After 3 years, 38 children outgrew their AD (AD- group), while in 33 AD persisted (AD+ group). At enrollment, AD+ children had a higher SI, higher rate of positivity to SPT and APT for mites (p = 0.001), and higher environmental exposure to HDM allergens (p = 0.035). The AD+ children developed more respiratory symptoms in comparison to AD- children (p < 0.001). None of the AD- children presented APT positivity. In our study population, positivity of SPT and APT for HDM, environmental allergen exposure levels and severity of the disease at enrollment presented a significant predictive power towards AD persistence. Subjects with positive skin reactivity to HDM should be considered at risk of AD persistence and of possible development of allergic respiratory disorders.

Adolescent↗

Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children.

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.

Adolescent↗

Bronchial hyper-responsiveness and atopy in urban, peri-urban and rural South African children.

Twenty years ago, the prevalence of atopic sensitization and bronchial hyper-responsiveness (BHR) in Xhosa children in a rural location in South Africa was very low. The aim of this study was to document the current prevalence of these two indices by comparing traditional rural Xhosa children, recently urbanized Xhosa children and established city white children, and to consider factors that may account for the observed increase in all of these groups. One thousand four hundred and fifty-seven school children aged 10-14 years from the rural Transkei, from a recently urbanized peri-urban area and from urban Cape Town areas were studied using a questionnaire. Four hundred and eighteen children had histamine challenges, and 492 tests for atopy were also conducted. As determined by bronchial challenge with histamine, 17% of rural and 34.4% of recently urbanized Xhosa children had increased BHR, a marked increase from the 0.03% and 3.17% prevalence of increased BHR previously found using the exercise challenge. The prevalence of increased BHR in white urban children was 33%. Sensitization to one or more aero-allergens, as indicated by CAP RAST tests, was present in 36.6% of the rural Xhosa children with normal BHR and in 62.5% of those with increased BHR, a striking increase from that of previous studies. Atopic sensitization to one or more aero-allergens, as indicated by a skin prick test (SPT), was found in 42.3% of the recently urbanized Xhosa children and 45% of urbanized white children. We have also documented sensitization to house dust mites in the rural Xhosa children for the first time. Passive cigarette smoking was not identified as a risk factor for increased BHR or atopy. Wood smoke in the indoor environment did not play a role in the rural Xhosa children's BHR. Ascaris infection does not appear to play any modifying role in the development of increased BHR in the rural or urban children. We have found that increases in BHR in the rural and recently urbanized Xhosa children develop independently of increases in atopy. Our results challenge the 'hygiene' hypothesis as a complete explanation for the recent dramatic worldwide increases in allergic diseases.

Adolescent↗

House dust-mite allergen and cat allergen variability within carpeted living room floors in domestic dwellings.

Exposure to allergens from house dust-mites (Der p 1) and domestic cats (Fel d 1) is associated with symptom severity in atopic subjects with asthma and rhinitis. Assessment of allergen exposure in the domestic environment is normally determined by measurement from a single floor site. We determined the variability of these allergens and protein throughout the whole living room floor area. Dust samples were collected from 1 m2 areas from 16 carpeted living room floors in Wellington, New Zealand, and analyzed for concentrations of Der p 1 and Fel d 1. Mean coefficients of variation for Der p 1 and Fel d 1 were 53.1% (range: 28.5-136.8) and 65.6% (range: 28.5-131), respectively. This study has demonstrated a large variation of house dust-mite and cat allergens within living room floors and thus a single sampling site may not be representative for assessment of an individual's exposure risk. House dust-mite and cat allergen levels from the center of the room, in front of a couch or chair, or from a corner of the room are similar to mean levels from the whole room, these sites may thus be representative of the whole living room floor in large-scale epidemiological studies.

Air Pollution, Indoor↗

Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites.

Although elevated levels of serum immunoglobulin E (IgE) are considered the hallmark of atopic diseases, their clinical value in evaluating subjects with allergic disorders is under debate. To evaluate possible relationships between serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal control reference values detected in our laboratory, children with allergic asthma had higher blood eosinophil counts (expressed both as percentage and as absolute number) and higher fractional exhaled nitric oxide (FeNO) levels but similar values in pulmonary function parameters. In the allergic asthmatic population, serum levels of total, Dp-specific or Df-specific IgE correlated positively with eosinophil counts (Rho > or = 0.30, p < 0.01, each correlation) and FeNO levels (Rho > or = 0.33, p < 0.01, each correlation) but not with pulmonary function parameters (p > 0.1, each correlation). Finally, significant correlations, although moderate, were found in the allergic asthmatic population between eosinophil counts and FeNO levels (Rho > or = 0.42, p < 0.001, each correlation). Thus, in atopic children sensitized to HDM with mild intermittent asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes or the degree of airflow limitation.

Adolescent↗

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: a pilot study.

Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 +/- 1.1% at T0 and 3.5 +/- 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 +/- 0.5% at T0 and 1.5 +/- 1.0% at T1 (ns). Cys-LTs mean level was 14.24 +/- 4.53 pg/ml at T0 and 4.65 +/- 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 +/- 0.19 pg/ml at T0 and 2.41 +/- 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 +/- 3.18 pg/ml at T0 to 7.36 +/- 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.

Adolescent↗

The determinants of dust mite allergen and its relationship to the prevalence of symptoms of asthma in the Asia-Pacific region.

The role that house dust mites play in the primary causation of asthma is controversial. Approximately thirty-six 10-yr-old children in each of 10 centres in the Asia-Pacific region participated. Researchers collected dust from mattresses and living room floors using standardized procedures. Der p1 and Der f1 were analysed using a double monoclonal antibody enzyme-linked immunosorbent assay. Geometric mean allergen levels were calculated for each centre. An ecological analysis was conducted to show the regression of the geometric mean allergen level, using the highest household level, against asthma symptom and severity prevalence data from the International Study of Asthma and Allergies in Childhood, Phase I. Among children aged 13-14 yr, the change in asthma symptom prevalence was associated with per unit change in Der p1 microg/g (1.08, 95% CI 0.10-2.06) and Der 1 microg/g (Der p1 + Der f1) (0.64, 95% CI 0.02-1.26). The change in having four or more attacks of asthma in the last 12 months was associated with per unit change in Der p 1 microg/g (0.29, 95% CI -0.02 to 0.60) and Der 1 microg/g (0.20, 95% CI 0.01-0.38). There was no effect for total Der p1 or Der f1 (total or microg/g). Among children aged 6-7 yr, neither allergen was related to symptoms or severity prevalence. While our findings suggest that Dermatophagoides pteronyssinus may have a role in the primary causation of asthma, the complexity of this association reinforces the need for prospective studies.

Adolescent↗

Prevention of sensitization to house dust mite by allergen avoidance in school age children: a randomized controlled study.

BACKGROUND: Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders. OBJECTIVE: To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children. METHODS: As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5-7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust-mite allergen. Control group children were given non-specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed. RESULTS: Ten children in the prophylactic group and 19 in the control group were lost to follow-up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child. CONCLUSION: Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.

Air Pollution, Indoor↗

Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey.

BACKGROUND: There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese. OBJECTIVE: To determine the association of body mass index with respiratory symptoms and atopy in young adults METHOD: Information collected from 15,454 participants in the European Community Respiratory Health Survey, a multicentre cross-sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy. RESULTS: Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20-24.99 (OR in men 1.85, 95% confidence interval 1.41-2.42; OR in women 2.03, 95% confidence interval 1.59-2.58). Similar associations were observed for other symptoms suggestive of asthma. Body mass index was not associated with 'hayfever or nasal allergies', specific IgE to house dust mite, grass or cat or with total IgE in men or women. CONCLUSION: Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.

Adult↗

Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease.

BACKGROUND: Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. OBJECTIVE: To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. METHODS: PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). RESULTS: Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. CONCLUSION: We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.

Adolescent↗

Associations of Fc epsilon R1-beta polymorphisms with immunoglobin E antibody responses to common inhalant allergens in a rural population.

BACKGROUND: Polymorphisms within the beta subunit of the high-affinity receptor for IgE (Fc epsilon R1-beta ) on chromosome 11q13 have been related to atopy and asthma and the lymphotoxin alpha (LT alpha) gene on chromosome 6 is implicated in asthma. OBJECTIVE: To elucidate the association of polymorphisms in the Fc epsilon R1-beta and LT alpha genes to IgE responses and asthma in a family-orientated rural population. METHODS: A total of 461 adult farmers, who participated in an epidemiological follow-up study on respiratory symptoms among farmers on the Swedish island of Gotland, were examined. The traits assessed included serum total IgE, IgE antibody responses to 21 common inhalant allergens and asthma. RESULTS: The 237G mutation was only detected in seven persons. Atopy was found to be associated with the RsaI-ex7 AB-genotype (OR = 1.9; P = 0.04). The RsaI-ex7 B allele had a significant influence on IgE responses to pollens and dust mites (OR = 5.5; P = 0.03 and OR = 5.2; P = 0.049, respectively). The influence of this allele was stronger when the association towards single dust mite species (Lepidoglyphus destructor) was estimated (OR = 7.1, P = 0.03) and the association increased even more when the major allergen of L. destructor (rLep d 2) was analysed (OR = 11.2, P = 0.02). These associations were independent of sex, age and smoking, and the estimates of RsaI-in2 independent of RsaI-ex7. RsaI-in2, RsaI-ex7 and LT alpha genotypes were unassociated with total serum IgE. No significant difference in the distribution of RsaI-in2, RsaI-ex7 and LT alpha genotypes was found among subjects with atopy or asthma compared to healthy controls. CONCLUSION: This study supports the notion that polymorphisms in the Fc epsilon R1-beta gene have significant effects on IgE responsiveness. Secondly, dust mites in rural populations influence the expression of genes on chromosome 11q13.

Adolescent↗

Personal exposure to house dust mite allergen in bed: nasal air sampling and reservoir allergen levels.

BACKGROUND: Assessment of personal exposure to dust mite allergen has relied on proxy measures. Only recently has a means to directly measure inhaled allergen particle number become available (the intra-nasal air sampler). OBJECTIVE: To quantify inspired dust mite group 1 and group 2 allergen-bearing particles in bed in undisturbed conditions prior to sleep by nasal air sampling and to investigate the relationship between inhaled particles and reservoir allergen levels. METHODS: Twelve volunteers wore nasal samplers in bed for 6 evenings, nose-breathing in undisturbed conditions. Allergen-bearing particles ('halos') were detected by immunostaining for Der p 1, Der p 2, or Der p 1 and Der p 2 together, and counted by light microscopy. Count data were square root transformed for analysis of variance. Mattress dust samples were assayed for Der p 1 and Der p 2 concentrations. RESULTS: Square root detransformed mean particle counts per 30-min sample were: Der p 1, 4.22; Der p 2, 5.9; Der p 1 + Der p 2, 4.87; and for all samples, 5.01, with no difference between the groups. With replicate samples, halo number correlated significantly with mattress allergen concentrations (Der p 1 r = 0.80, P < 0.01; Der p 2 r = 0.68, P < 0.02). CONCLUSION: Nasal air sampling can be used to quantify nocturnal Der p exposure in undisturbed conditions in an area with moderate exposure to mite allergen and can provide a direct measure of inhaled mite allergen. The choice of either Der p 1 or Der p 2 is appropriate for this purpose.

Adult↗

House dust mites and their allergens at selected locations in the homes of house dust mite-allergic patients.

BACKGROUND: Knowledge of the occurrence of house dust mites (HDM) and their allergens in domestic locations is important when planning intervention. OBJECTIVE: The aim of this study was to describe the distribution of HDMs and their allergens before intervention in multiple locations in the homes of newly diagnosed HDM-allergic patients with a known high Der 1 concentration in their mattress dust. METHODS: Dust was collected from ten locations in the homes of eight HDM-allergic patients. Dust was analysed for allergen content with ELISAs for Der f 1, Der p 1 and Der m 1; and HDM were counted. Total allergen concentrations ( micro g Der 1/g dust) were expressed as the sum of Der f 1, Der p 1 and Der m 1. RESULTS: On mattresses the median concentration was 86 micro g Der 1/g dust (range 30-288) and 188 mites/g dust (range 12-1910). Der 1 exceeded 10 micro g/g dust in mattresses (8/8), duvets/pillows (3/8), a bedroom carpet (1/1), a living room carpet (1/6), upholstered furniture (2/8) and a curtain (1/5). Uncarpeted floors, upholstered furniture, bookshelves and walls had significantly lower Der 1 concentration than the mattresses. The relative contribution of Der p 1, Der f 1 or Der m 1 to Der 1 was related to homes, rather than to the location. Der m 1 only occurred in minute amounts. CONCLUSION: For HDM intervention, our results indicate that priority should be given to the removal of allergens from mattresses, and in addition from carpets, duvets/pillows and upholstered furniture. Dust from walls, uncarpeted floors, bookshelves and curtains appear to contribute insignificantly to the domestic HDM allergen load.

Animals↗

Allergen-induced bronchial inflammation in house dust mite-allergic patients with or without asthma.

BACKGROUND: It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite-allergic individuals. The level of allergen-specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem to differ significantly between asthmatic and non-asthmatics individuals. AIM: It was hypothesized that the presence or absence of asthmatic symptoms in house dust mite-allergic patients is associated with quantitative or qualitative differences in the cellular bronchial inflammatory response during the late phase of the allergic reaction. This hypothesis was tested in the bronchial allergen challenge model. MATERIAL AND METHODS: Whole lung challenges with house dust mite extract were performed in 52 house dust mite-allergic subjects, of whom 26 had asthma and 26 had perennial rhinitis without asthmatic symptoms. Primary outcomes were parameters for bronchial inflammation in serial samples of induced sputum (cell differentials, eosinophil cationic protein (ECP), interleukin-8 (IL-8), myeloperoxydase (MPO)). In addition, lung function, non-specific bronchial hyper-responsiveness and serial blood samples (eosinophils and IL-5) were analysed. RESULTS: At baseline sputum eosinophils and ECP were similar in both groups but neutrophils and IL-8 were higher in asthmatics. The early bronchoconstriction after allergen challenge was similar in asthma and non-asthmatic rhinitis (median decrease in FEV1: asthma -31.7% vs. non-asthmatics -29.1%, P > 0.1). The late phase bronchoconstriction was significantly greater in asthma (median decrease in FEV1: asthma -27.6% vs. non-asthmatics -18.9%, P = 0.02). Induction of bronchial hyper-responsiveness was similar in both groups. Bronchial allergen challenge elicited significant increases in sputum eosinophils and ECP, which were indistinguishable for both groups (P > 0.1 and P = 0.07, respectively). In contrast, higher numbers of neutrophils persisted in asthma 24h after challenge and were accompanied by significant increases in IL-8 and MPO, which were absent in non-asthmatics (difference between groups P = 0.007 and P = 0.05, respectively). CONCLUSION: Allergen challenge inducedvery similar increases in eosinophils and ECP in induced sputum in allergic asthmatics and in allergic non-asthmatic patients. The difference in bronchial inflammation between asthma and non-asthmatic rhinitis appeared to be more closely related to indices for neutrophilic inflammation.

Adolescent↗

Safety of inhalant allergen immunotherapy with mass units-standardized extracts.

BACKGROUND: Allergen-specific immunotherapy (SIT) is an effective treatment for patients with respiratory allergies. However, subcutaneous injection of allergens can provoke systemic side-effects. OBJECTIVE: This study was carried out to determine the incidence and risk factors o fsystemic reactions caused by SIT treatment, using extracts of different inhalant allergens, adsorbed in aluminium hydroxide and biologically standardized with the major allergens quantified in mass units. METHODS: Five hundred and fifty-five subjects with allergic rhinitis and/or asthma were evaluated on clinical history and skin prick test (SPT) reactions to common inhalant allergens. Subcutaneous SIT was administered to all patients, according to the suggested precautionary guidelines and administration schedule. Patients were treated with house dust mite, grass pollen, Parietaria judaica pollen and olive pollen extracts, each receiving one or two extracts. RESULTS: A total of 36,359 injections were administered in the 555 patients. We observed 34 episodes of serious systemic side-effects (0.093% of all injections), in 29 patients (5.2% of all patients), and no fatalities. About 55% of patients reported mild rhinitis and asthma. The majority (59%) of the serious systemic reactions (SSR), and all the anaphylactic reactions, were immediate (i.e. occurred within 30 min after the injection). Asthmatic subjects were at higher risk of SSR than patients with rhinitis (P = 0.01). Most of the side-effects observed occurred during the dose-increase phase (P < 0.05). There was no association of SSR with age, gender, SPT reactivity or allergen type. CONCLUSION: SIT performed in patients with respiratory allergies by specialized staff with the allergen extracts studied, standardized in mass units, provoked a low rate of SSR. The significant risk factors for systemic reactions were asthma and the build-up period.

Adolescent↗