Interrelationships among asthma, atopy, rhinitis and exhaled nitric oxide in a population-based sample of children

BACKGROUND: Exhaled nitric oxide (eNO) has attracted increasing interest as a non-invasive marker of airway inflammation in asthma. However, little evidence exists on the influences exerted on eNO by the interrelations among atopic status, asthma and rhinitis. METHODS: Among the 1156 children who participated in a large-scale epidemiological survey on asthma and allergies (ISAAC II: International Study of Asthma and Allergies in Childhood Phase II) in the city of Clermont-Ferrand, 53 asthmatics without corticosteroid treatment and 96 non-asthmatics were invited to perform eNO and skin prick tests (SPTs) to 12 common allergens. RESULTS: Atopic asthmatic children had higher eNO than non-atopic asthmatic children (28.9+/-9.1 vs. 17.1+/-13.1 p.p.b.; P=0.0004) with a significant increase when one SPT or more are positive (26.5+/-7.8 vs. 17.1+/-13.1 p.p.b.; P=0.03). Similarly, non-asthmatic, atopic subjects had higher eNO than non-atopic subjects with a significant increase when two SPTs or more are positive (19.4+/-9.8 vs. 11.7 +/-6.7 p.p.b.; P=0.003). In the case of equal levels of positive SPTs (0, 1, >/=2), asthmatic children always had higher eNO than non-asthmatic ones. Furthermore, among non-asthmatic children, the eNO level increased only in atopics who had rhinitis (20.7+/-13 vs. 12.5+/-6.4 p.p.b. in atopic controls (subjects without rhinitis and asthma) and 12.3+/-6.6 p.p.b. in non-atopic controls; P=0.001), whereas among asthmatic children, eNO level increased in atopics independently of rhinitis (28.2+/-9.5 p.p.b. in those with rhinitis and 30.9+/-8.1 p.p.b. in those without) as well as in non-atopics with rhinitis (22.5+/-17.2 p.p.b.). CONCLUSIONS: Our data suggest that besides atopy and asthma, allergic rhinitis should also be taken into account in the assessment of eNO.     

Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge

BACKGROUND: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen-induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. METHODS: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite (Dermatophagoides pteronyssinus), of whom 26 had non-asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. RESULTS: At baseline eNO was significantly lower in non-asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non-asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P < 0.006). However, the increase in eNO after bronchial allergen challenge in non-asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non-asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). CONCLUSION: The difference in eNO between non-asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non-asthmatic rhinitis.     

Nasal nitric oxide: longitudinal reproducibility and the effects of a nasal allergen challenge in patients with allergic rhinitis

BACKGROUND: Exhaled nitric oxide (eNO) is a validated noninvasive marker of airway inflammation in asthma. In patients with allergic rhinitis (AR), increased levels of nasal nitric oxide (nNO) have also been measured. However, the applicability of nNO as a marker of upper airway inflammation awaits validation. AIM: To test the longitudinal reproducibility of standardized nNO measurements in patients with AR and the effects of nasal allergen challenge. METHODS: Twenty patients with clinically stable, untreated AR participated in a combined study design. First, reproducibility of nNO was tested over 1, 7, and 14-21 days. Subsequently, the effect of nasal allergen challenge on nNO was studied in a placebo-controlled, parallel design. Nasal NO was measured with a chemoluminescence analyzer. Ten subjects randomly underwent a standardized nasal allergen challenge; 10 subjects received placebo. Response to nasal challenge was monitored by composite symptom scores. RESULTS: There was a good reproducibility of nNO up to 7 days [coefficient of variation (CV) over 1 (16.45%) and 7 days (21.5%)], decreasing over time [CV (14-21 days): 38.3%]. As compared with placebo, allergen challenge caused a significant increase in symptom scores (P < 0.001), accompanied by a decrease in nNO at 20 min postchallenge (P = 0.001). Furthermore, there was a gradual increase in nNO at 7 h, reaching significance at 24-h postallergen (P = 0.04). CONCLUSIONS: Similar to eNO in asthma, nNO is a noninvasive marker, potentially suitable to monitor upper airway inflammation following allergen-induced late response. Present data show a good reproducibility of nNO measurements, decreasing over time, probably because of subclinical seasonal influences.     

Nasal and bronchial response to exercise in patients with asthma and rhinitis: the role of nitric oxide

BACKGROUND: Physical exercise is associated with a decrease in nasal resistance in rhinitis and an increase in bronchial resistance in asthma. The objective was to evaluate the relationship between the levels of nasal nitric oxide (nNO) and exhaled bronchial nitric oxide (eNO) with bronchial responses to exercise in patients with rhinitis and asthma. METHODS: We submitted 24 subjects with asthma and rhinitis to an exercise test. A decrease in FEV(1)> or =15% was considered positive. The volume of the nasal cavity and the minimal cross-sectional area (MCA) was evaluated by means of acoustic rhinometry (AR), and nNO and eNO were evaluated by chemoluminiscence. The measurements were recorded at baseline, 15 and 50 min after the end of the exercise test. RESULTS: The exercise test was positive in 17 cases. Fifteen minutes after exercise test, the nasal volume increased by 57% (P < 0.0001) and was still increased by 30% after 50 min (P < 0.0001). There was no correlation between decrease in FEV(1) and increase in nasal volume. The baseline value of nNO was 1185 +/- 439 ppb, and the value at 15 and 50 min was 1165 +/- 413 and 1020 +/- 368 ppb, the latter value being significantly lower (P < 0.01) than the baseline. The baseline value of eNO was 21 +/- 19 ppb, with no significant differences at 15 and 50 min. There was no significant correlation between either the decrease in FEV(1) and the nasal response, or the baseline eNO and nNO values. CONCLUSIONS: The nasal and bronchial response to exercise is completely different in rhinitis and asthma; in the former, an increase in nasal volume occurs, while in the latter there is a drop in FEV(1). There is no relationship between the values of nasal or exhaled NO and the nasal and bronchial response after exercise.     

Nasal and exhaled nitric oxide in response to occupationallatex exposure

BACKGROUND: Latex sensitivity is an increasing problem among health-care workers. Allergic responses are associated with changes in nitric oxide (NO) generation and the changes secondary to latex have not been described. METHODS: A total of 22 subjects comprising equal numbers of control volunteers and subjects with self-reported latex sensitivity were recruited to undergo latex skin prick testing. Symptom scores, exhaled nitric oxide (eNO), and nasal nitric oxide (nNO) were studied 1) before and after a controlled latex challenge (n=16), and 2) at the beginning and end of the working week, during exposure to latex (n=18). RESULTS: Latex challenge caused a significant fall in nNO levels in latex-sensitive subjects, compared to normal control subjects (P=0.04). eNO levels also decreased in the latex-sensitive subjects after latex challenge, but to a lesser degree. There were no significant differences between the beginning and end of the working week in terms of eNO or nNO in either group, although symptom scores showed a nonsignificant increase in latex-sensitive subjects. CONCLUSION: Fall in nasal NO after latex challenge is associated with reported symptomatic latex sensitivity, and this corresponds to latex skin prick test positivity. Neither nNO nor eNO showed a clear relationship to routine workplace exposure.     

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of lower airway inflammation in asthma. To investigate the existence of lower airways inflammation in allergic rhinitis eNO measurements were performed in 32 patients with symptomatic and asymptomatic seasonal allergic rhinitis early in and out of pollen seasons and in 80 healthy volunteers. To further define how exhaled NO is modified by therapy, NO levels were detected following 1-month treatment with either inhaled steroids or non-steroids therapy with nedocromil. Exhaled NO (mean +/- SE) was significantly elevated in patients with seasonal allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb, respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher increase during the allergen exposure in season. Higher levels of exhaled NO were detected in patients with symptoms, either from the upper or lower airways, and with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients was reduced only by inhaled steroids and not by nedocromil. These findings possibly suggest the existence of lower airway inflammation in both symptomatic and asymptomatic patients with seasonal allergic rhinitis in and out of pollen season. Thus, exhaled NO may be used as a non-invasive index for early detection of lower airway inflammation and for monitoring the optional treatment in patients with seasonal allergic rhinitis.     

Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic rhinitis sensitized to the same pollen allergen.

BACKGROUND: Some studies have reported that the levels of exhaled nitric oxide (ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and it has been postulated that atopic status might be the determinant of enhanced nitric oxide production in asthma. OBJECTIVES: The aim of this study was to determine differences in ENO levels between asthmatics and subjects with allergic rhinitis sensitized to the same allergen, and to correlate these levels with airway responsiveness. METHODS: Nineteen patients with asthma and 18 subjects with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the study. ENO values and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured during the pollen season. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV1 (PC20). ENO was measured with the single-exhalation method. RESULTS: The geometric mean (95% confidence interval) ENO values were significantly higher in asthmatics than in subjects with allergic rhinitis: 72.4p.p.b. (54.9-93.3p.p.b) vs. 44.7p.p.b. (30.9-64.6p.p.b., P = 0.03). In asthmatics, a significant correlation was found between ENO and PC20 AMP values (p = -0.57, P=0.02), whereas no correlation was detected between ENO and PC20 methacholine (p = -0.35, P = 0.14). CONCLUSIONS: Our results suggest that atopy is not the only determinant of increased ENO levels detected in subjects with asthma, and that responsiveness to AMP may be a more sensitive marker for assessing airway inflammation in asthma compared to methacholine.     

Evaluation of antigen specific IgE responses in Japanese asthmatics and non-asthmatics]

BACKGROUND: An increase in the prevalence of asthma does not seem to be comparable to the dramatic increase of atopy for the last two decades in Japan. Atopy is considered an important risk factor for asthma. It is, however, suggested that asthma itself may be responsible for the increased overall IgE responsiveness. We examined the significance of IgE responsiveness in asthma. METHODS: We studied 265 healthy controls and 275 patients with asthma. Total serum IgE levels and levels of antigen-specific IgE antibody to mite (D. farinae), cat, dog, timothy, and Candida spp. were determined. We defined atopy by positive RAST (>0.35UA/ml) or MAST scores (>1.0 lumicount) to at least one inhaled allergen. Frequencies of atopic subjects and frequencies of subjects sensitized to each allergen in atopic subjects were compared between the asthmatics and controls. All comparisons were made in younger (<41 yrs) and older (> = 41 yrs) groups, separately. RESULTS: In younger non-asthmatics, 76.5% (104/136) were atopic. The frequency of atopy was significantly higher in asthmatic subjects compared to non-asthmatics in both younger and older groups. In atopic subjects, older asthmatics were sensitized to animals more frequently than older controls. Although the frequency of subjects sensitized to mite did not differ between asthmatics and controls both in younger and older atopic subjects, asthmatics sensitized to mite had higher titers of specific IgE antibody to mite compared to those of controls sensitized to mite. Even non-atopic asthmatics had higher levels of total IgE compared to non-atopic controls. CONCLUSION: Our data may indicate that sensitization to animals and severer sensitizations to mite are risk factors for asthma. However, given the high prevalence of atopy in younger healthy controls, and increased levels of total serum IgE even in non-atopic asthmatics, our findings may reflect the increased overall IgE responsiveness that is inherent in asthma.     

The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children

BACKGROUND: Exhaled nitric oxide (NO) has been proposed as novel a non-invasive marker of airway inflammation. OBJECTIVE: The level of exhaled NO was determined in a random sample of school children (7-12 years old) with the aim of investigating the relationship between exhaled NO and sensitization to common allergens. RESULTS: In the 450 children tested by skin prick tests (SPT), the prevalence of sensitization was 29.5% (overall), 21.9% (sensitization to indoor allergens), and 15.0% (sensitization to outdoor allergens). Regression analysis showed that levels of exhaled nitric oxide were closely associated with various measures of sensitization to aeroallergens. Sensitization to indoor allergens was associated with higher levels of exhaled NO (eNO) than sensitization to outdoor allergens when assessed by IgE but not when assessed by SPT. Children with reported wheeze in the past 12 months had much stronger associations between sensitization and eNO than children without wheeze. CONCLUSION: We conclude that allergic sensitization is strongly associated with increased levels of exhaled NO, especially in children with wheeze.     

Cytokine synthesis in occupational allergy to caddisflies in hydroelectric plant workers

BACKGROUND: Workers in hydroelectric plants appear to be readily sensitized to caddisfly allergens. This sensitization probably occurs de novo from occupational exposure. In some workers, sensitization occurs on a non-atopic background. Cytokine synthesis of IFN-gamma, IL-5 and IL-13 in atopic and non-atopic caddisfly-allergic workers was examined to determine if responses were similar or different. METHODS: Peripheral blood mononuclear cells were isolated from atopic caddisfly-allergic workers, non-atopic caddisfly-allergic workers and non-atopic caddisfly-exposed but non-allergic workers. Stimulation with caddisfly antigens was carried out and synthesis of IFN-gamma, IL-5 and IL-13 was determined by sandwich ELISA. RESULTS: Both caddisfly-allergic and non-allergic subjects responded to stimulation with caddisfly extract. The response in non-atopic caddisfly-non-allergic subjects was TH1 predominant, while that in atopic caddisfly-allergic subjects was TH2 predominant. The response in non-atopic caddisfly-allergic subjects was between that of the atopic caddisfly-allergic workers and the non-atopic caddisfly-non-allergic workers and the trend was to a TH2 response. Work-related symptoms were similarly intermediate between the atopic caddisfly-allergic and non-atopic caddisfly-non-allergic group. Differences were significant for IFN-gamma/IL-5 ratios but not IFN-gamma/IL-13 ratios for atopic and non-atopic caddisfly-allergic individuals, compared to non-atopic caddisfly-non-allergic workers. However, a linear relationship existed between IFN-gamma synthesis and IL-5 and IL-13 synthesis in non-atopic caddisfly-allergic workers but not in atopic caddisfly-allergic subjects. CONCLUSIONS: Caddisfly allergy in hydroelectric workers may be a useful model for the development of allergy to a previously unencountered allergen, and points to some interesting differences between atopic and non-atopic subjects who become sensitized to environmental allergens.     

Allergen-induced interleukin-9 production in vitro: correlation with atopy in human adults and comparison with interleukin-5 and interleukin-13

BACKGROUND: The contribution of IL-9 to human atopy is supported by genetic studies. However, IL-9 production in response to allergen in vitro has been reported only in children. OBJECTIVE: Study IL-9 induction by allergen in adults, compare it with IL-5 and IL-13 and evaluate its association with atopy. METHODS: Peripheral blood mononuclear cell (PBMC) from control adults and from atopic patients were cultured with various allergens or phytohaemagglutinin (PHA) and secreted IL-5, IL-9 and IL-13 were measured by ELISA. RESULTS: IL-9 was produced in response to Dermatophagoides pteronyssinus (Der p) by PBMC from Der p-hypersensitive adults at levels equivalent to those induced by PHA but with slower kinetics. The induction of IL-9 was allergen specific, reflecting donor RAST profile. In Der p-triggered reactions of non-atopic and atopic subjects, IL-9 showed the highest selectivity for atopics, IL-5 and IL-13 being produced more frequently in non-atopic donors. Significant correlations with specific IgE titres were found for IL-9 with all allergens tested (Der p and two peptides of Bet v 1 birch allergen). For IL-5 and IL-13, they were in the same range for Der p but more variable for birch allergens. Patterns of cytokine production by individual patients in response to allergen reflected these differences: for Der p, IL-5, IL-9 and IL-13 productions were strongly correlated but for birch IL-5 differed from the latter two. The in vitro production of IL-9 reflected clinical hypersensitivity profiles and was higher in individuals with asthma than in those with disease limited to rhinitis and/or conjunctivitis. CONCLUSIONS: Allergen-triggered IL-9 production in vitro is an excellent marker for atopy in adults given its virtual absence in allergen-stimulated PBMC from non-atopic individuals and its correlation with allergen-specific IgE and asthma.     

Exhaled monoxides in asymptomatic atopic subjects

BACKGROUND: Atopy is a genetically determined condition and some atopic people develop airway hyperresponsiveness and sometimes asthma later in life. Since airway inflammation may be present before the onset of clinical symptoms of asthma, early and noninvasive detection of inflammation would be useful in atopic subjects. Mediators produced by activated inflammatory cells may lead to induction of inducible nitric oxide synthase producing nitric oxide (NO) and inducible heme oxygenase releasing carbon monoxide (CO) in the airways. Both monoxides are present in exhaled air and their levels are elevated in asthma reflecting airway inflammation. OBJECTIVE: We have measured exhaled NO and CO levels in atopic and nonatopic healthy non-smoking subjects to determine whether inflammation is present in the airways. METHODS: Exhaled NO was measured by a chemiluminescence analyser and exhaled CO electrochemically and NO in asymptomatic atopic and age-matched nonatopic normal subjects. RESULTS: Exhaled NO and CO levels were both significantly elevated in 15 atopic subjects compared with 40 nonatopic individuals (means +/- SEM: 18.3+/-3.0 p.p.b. vs. 6.3+/-0.3 p.p.b., P< 0.0001 and 4.7+/-0.3 p.p.m. vs 2.8+/-0.2 p.p.m., P = 0.0005, respectively). CONCLUSION: Increase in exhaled monoxide levels may be an early and noninvasive marker of airway inflammation in asymptomatic atopic subjects.     

Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: results from a pooled study

BACKGROUND: Recent studies in a few industries have shown that the likelihood of IgE-mediated sensitization increases with increasing exposure. The shape of the exposure-response relationships and modification by age, sex, and smoking habit has hardly been studied. OBJECTIVE: The purpose of this study was to determine exposure sensitization relationships for rat sensitization and to evaluate the influence of atopy, smoking habits, and sex. METHODS: Data from 3 cross-sectional studies in The Netherlands, the United Kingdom, and Sweden were used and involved 1062 animal laboratory workers. Selection criteria were harmonized, and this resulted in a study population of 650 animal laboratory workers (60.6% female) with less than 4 years of exposure. Air allergen levels were assessed previously and converted on the basis of an interlaboratory allergen analysis comparison. Available sera were analyzed for the presence of specific antibodies against common allergens (house dust mite, cat, dog, and grass and birch pollen) and work-related allergens (rat and mouse urinary proteins). Questionnaire items on work-related respiratory symptoms, hours worked with rats per week, job performed, smoking habits, and sex were used in this analysis RESULTS: The prevalence of work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as specific IgE to 1 of the common allergens). The sensitization rate increased with increasing air allergen exposure. Atopic workers exposed to low levels of allergen had a more than 3-fold increased sensitization risk compared with nonexposed atopic workers. For atopic subjects, the risk increased little with increasing exposure, whereas for nonatopic subjects, a steadily increasing risk was observed. Smoking and sex did not modify the sensitization risk. CONCLUSION: Rat urinary allergen-sensitization risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitization risk at low allergen exposure levels.     

Exhaled nitric oxide is associated with allergic inflammation in children

Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 ± 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 ± 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 ± 31.92 ppb) and in those with allergic rhinitis (43.59 ± 29.84 ppb) than in healthy controls (27.01 ± 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization.     

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

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

Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma

Background and objectives The determinants of variability in the clinical expression of atopy are still to be documented. The goals of this study were to determine, in subjects with a clinical diagnosis of symptomatic asthma or rhinitis, what is the possible contribution of different types of indoor and outdoor allergens to the development of their disease, by looking at the prevalence and degree of sensitization to these allergens according to age and gender. Subjects and methods We analysed allergy skin prick tests to common airborne indoor and outdoor allergens in 3371 consecutive patients, grouped according to diagnosis of allergic asthma, rhinitis, or both. For each of these three groups, we calculated the prevalence of sensitization to indoor/outdoor allergens, the atopic index (Al), the number of positive responses to allergy skin prick test and the mean wheal diameter (MWD) of these responses. Results The prevalence of atopy and the values of Al and MWD peaked in subjects aged 16 to 25 years, declining afterwards; in subjects ± 18 years old, atopic indices were slightly higher in men than in women. In atopic subjects, the prevalence of sensitization was, in decreasing order: housedust (84.2%), cat hair-epithelium (76.5%), dog hair-dander (63.0%), house dust mite (54.2%), grasses (51.9%), trees (47.2%) and ragweed pollens (44.9%) and finally, moulds (25.4%). Among subjects sensitized only to outdoor allergens (n= 195), 73.8% had a rhinitis, 11.8% had asthma and 14.4% had both diagnoses; for those sensitized only to indoor allergens (n= 710), these values were respeetively 48.6, 24.5 and 26.9%, and for those sensitized to both indoor and outdoor allergens (n= 1793), the comparable values were 55.5, 14.6 and 29.9%. Conclusion These data show that in our population of subjects with respiratory allergic symptoms, indoor allergen sensitization is strongly associated with asthma, while exclusive sensitization to pollens is associated primarily with rhinitis. Sensitization was more prevalent for indoor allergens than for outdoor allergens in all groups determined according to diagnosis or age. Indices of atopy were higher in men in the group ± 18 years old. Prevalence and degree of sensitization were shown to peak in young adults, regardless of the allergen, and to diminish with age. This study stresses the role of indoor allergens in the development of asthma and shows the variability of allergic manifestations according to the type of sensitization.     

Increased nitric oxide production in the respiratory tract in asymptomatic pacific islanders: an association with skin prick reactivity to house dust mite

BACKGROUND: Exhaled nitric oxide (NO) is increased in asthma and may also be increased in subclinical airway inflammation. The relationship between atopy and subclinical airway inflammation in the pathogenesis of asthma remains unclear. We have evaluated the relationship between exhaled NO levels and skin prick test reactivity to 8 common allergens in 64 asymptomatic adult Pacific Islanders. Pacific Islanders were studied as a racial group with major morbidity from asthma. OBJECTIVE: Our purpose was to determine whether asymptomatic subjects with skin prick test reactivity to common allergens have elevated NO levels. METHODS: All subjects underwent full lung function testing and skin prick testing. Exhaled and nasal NO levels were measured by chemiluminescence (Logan LR2000 analyzer) with use of the single-breath and breath-holding techniques, respectively. RESULTS: House dust mite (HDM) reactivity was seen in 38 of 64 (56%). Exhaled NO levels (median 8.9 ppb, range 2.9-47.3 ppb) and nasal NO levels (527.5 +/- 181.5 ppb) lay above the normal European range in 30% and 25% of subjects, respectively. HDM reactivity was associated with higher exhaled NO levels (P <. 0005) and higher nasal NO levels (P =.01). In HDM-sensitive subjects the wheal size for HDM correlated with exhaled NO levels (r = 0.35, P =.04) and nasal NO levels (r = 0.40, P =.01). On multivariate analysis, exhaled NO levels were independently and positively related to the severity of HDM reactivity (P =.01) and nasal NO levels (P <.02), equation R(2) = 0.27. CONCLUSION: NO levels are elevated in a significant proportion of asymptomatic Pacific Islanders and are associated with HDM sensitivity. This may denote subclinical airway inflammation in this population and suggests that exposure to HDM in atopic individuals might play an important role in the early pathogenesis of asthma.     

Prevalence of symptoms, sensitization to rats, and airborne exposure to major rat allergen (Rat n 1) and to endotoxin in rat-exposed workers: a cross-sectional study

OBJECTIVE: To analyse the relation between airborne exposure to major rat allergen and to endotoxins in exclusively rat-exposed workers and the prevalence of rat-related symptoms and sensitization. METHODS: A total of 113 workers answered a standardized questionnaire on their atopy status, occupational exposure to rats, and possible work-related symptoms. Specific IgE against rat urinary proteins (RUP) was measured for 73 subjects. Individual airborne exposure to Rat n 1 and endotoxin were determined with static (n = 256) samplings. Rat n 1 was measured with enzyme-linked immunosorbent assay (ELISA) and endotoxin by the Limulus method. RESULTS: Forty-four of 113 subjects (38.9%) reported at least one rat-related symptom: asthma (4.4%), rhinitis (34%) and conjunctivitis (16%). Twelve per cent were sensitized to RUP (specific IgE > 0.35 KU/L). But only 30.8% of all symptomatic subjects were sensitized to rat allergens. Airborne Rat n 1 levels were not related to symptoms in workers. Symptomatic patients not sensitized to rats were exposed to higher endotoxin levels, but airborne exposure to endotoxins did not significantly protect against or increase sensitization to RUP or rat-related symptoms. CONCLUSION: Most symptomatic workers were not sensitized to rat allergen; but no significant relation between rat-related symptoms and endotoxin levels was found. This suggests that more studies are needed to determine causes other than rat allergens or endotoxins that may be responsible for symptoms in rat-exposed workers.     

Early-onset atopy is associated with enhanced lymphocyte cytokine responses in 11-year-old children

BACKGROUND: Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR); the underlying mechanism is unclear but may involve T cell responses. OBJECTIVE: To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy. METHODS: In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. Individuals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined. RESULTS: The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023). CONCLUSIONS: Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization.     

Clinical Characteristics According to Sensitized Allergens in Adult Korean Patients With Bronchial Asthma

Purpose

Allergic sensitization is a risk factor for the development of bronchial asthma. This study was conducted to investigate clinical manifestations according to sensitized allergens in adult Korean patients with bronchial asthma.

Methods

In total, 523 adult patients who were diagnosed with bronchial asthma between March 2002 and March 2008 were included in the study. All patients underwent skin prick tests for approximately 45 allergens or a specific IgE test. Sensitized allergens were grouped into the following categories: house dust mites, fungus, pollen, and animal dander. Atopy was defined as a positive skin prick test response or the presence of a specific IgE to one or more allergens.

Results

Of the 523 patients, 295 (56%) were sensitized to one or more allergens. A younger median age, greater proportion of males, higher eosinophil counts, and higher total IgE levels were observed in the atopic asthma group compared to the non-atopic asthma group. The PC20 value was negatively correlated with eosinophil counts and total IgE in the atopic asthma group. In the subgroup analysis, patients sensitized to Cladosporium showed poorer pulmonary function and a higher response to bronchodilators. In addition, patients sensitized to Alternaria showed severer bronchial hyperresponsiveness than non-atopic patients with asthma. Finally, a gradual increase in the number of sensitized allergens was noted with increasing age, eosinophil counts, and total IgE levels.

Conclusions

We suggest the need for identifying the existence of atopy and exact offending allergens at the time of asthma diagnosis, since significant differences in sex, age, blood test results, and lung function were observed according to atopy and sensitized allergens.