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N Scichilone

Publications and source records attributed to N Scichilone.

18 recordsLinked to original sources

Airway hyperresponsiveness in the elderly: prevalence and clinical implications.

Airway hyperresponsiveness is associated with an increased risk of developing respiratory symptoms. The assessment of airway hyperresponsiveness can provide valuable information regarding the natural course of respiratory diseases. However, little information is available for populations of more advanced age, and data are conflicting. It was assessed whether age influences the occurrence of airway hyperresponsiveness by reviewing those studies that specifically addressed this issue, and attempting to identify the factors responsible for discrepancies between studies. Eighteen studies, published between 1983 and 2002, are included in this review. Overall, the results of the analysis are in favour of a positive association between age and airway hyperresponsiveness, the prevalence of which appears to increase in the elderly. The most important determinants were reduced lung function, probably due to geometric factors, and a history of smoking, primarily because of the length of exposure, although acute effects were also demonstrated. Atopy should also be considered as an independent determinant of airway hyperresponsiveness in the elderly population. In addition, inflammatory and neuronal mechanisms could be involved. Finally, the role of sex requires further investigation. Assessing the impact of age on the occurrence of airway hyperresponsiveness has important implications: the age-associated alterations to the lung provide a model for evaluating the contribution of structural changes to the pathogenesis of airway hyperresponsiveness. From a clinical standpoint, evaluation of the magnitude of airway hyperresponsiveness could permit the early identification of individuals who are at risk, even at more advanced age. Assessment of airway hyperresponsiveness in the aged should be considered as an additional tool in the diagnostic work-up in the subset of elderly subjects with long-term smoking exposure and/or documented atopy.

Aged↗

Monitoring response to treatment in asthma management: food for thought.

Asthma is a chronic inflammatory disorder of the airways that is characterized by episodic symptoms. In this regard, asthma management has classically involved periodic re-assessment by the health-care provider, during which therapy is altered mainly based on clinical and physiological parameters, such as assessment of symptoms, spirometry and peak expiratory flow monitoring. In this context, various markers of airway inflammation (e.g. eosinophils in the induced sputum, nitric oxide in the exhaled air) have been proposed to assess the severity of asthma and to adjust the therapy accordingly. The evaluation of airway hyper-responsiveness with different stimuli has also been suggested as a new tool to monitor asthma. However, the lack of definite relationships between airway inflammation and asthmatic symptoms strongly limit the use of markers of asthma severity in the clinical setting. Therefore, the need of new tools to assess the severity of asthma is raised. The ideal measurement employed to establish the proper asthmatic therapy should be safe, non-invasive, easy to perform, reproducible and accurate, and have the capability to monitor the changes induced by the therapeutic interventions. A careful review of the available techniques, and the evaluation of their sensitivity and specificity in the clinical setting is warranted.

Asthma↗

Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD.

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.

Adult↗

Increased airway inflammatory cells in endurance athletes: what do they mean?

BACKGROUND: Inflammatory cells are increased in the airways of endurance athletes, but their role in causing exercise-induced respiratory symptoms and bronchoconstriction, or their possible long-term consequences, are uncertain. AIM: To put the results of athlete studies in perspective, by analysing the pathogenesis of airway cell changes and their impact on respiratory function. RESULTS: Athletes of different endurance sports at rest showed increased airway neutrophils. Elite swimmers and skiers also showed large increases in airway eosinophils and lymphocytes, possibly related to chronic, exercise-related exposure to irritants or cold and dry air, respectively. Post-exercise studies reported variable responses of airway cells to exercise, but found no evidence of inflammatory cell activation in the airways, at variance with exercise-induced neutrophil activation in peripheral blood. The increase in airway inflammatory cells in athletes can result from hyperventilation-induced increase in airway osmolarity stimulating bronchial epithelial cells to release chemotactic factors. Hyperosmolarity may also inhibit activation of inflammatory cells by causing shedding of adhesion molecules, possibly explaining why airway inflammation appears 'frustrated' in athletes. Data on exhaled nitric oxide are few and variable, not allowing conclusions about its usefulness as a marker of airway inflammation in athletes, or its role in modulating bronchial responsiveness. CONCLUSIONS: The acute and long-term effects of exercise on airway cells need further study. Airway inflammatory cells are increased but not activated in athletes, both at rest and after exercise, and airway inflammation appears to regress in athletes quitting competitions. Altogether, these findings do not clearly indicate that habitual intense exercise may be detrimental for respiratory health. Rather, airway changes may represent chronic adaptive responses to exercise hyperventilation. An improved understanding of the effects of exercise on the airways will likely have a clinical impact on sports medicine, and on the current approach to exercise-based rehabilitation in respiratory disease.

Asthma, Exercise-Induced↗

Do GOLD stages of COPD severity really correspond to differences in health status?

The purpose of this study was to assess whether different stages of chronic obstructive pulmonary disease (COPD) severity defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria correlate with meaningful differences in health status. A total of 381 COPD patients, aged 73+/-6 yrs, were classified in the five GOLD stages. Disease-specific (St George Respiratory Questionnaire (SGRQ)) and generic indexes of health status were measured in all patients. Multivariate analysis of covariance or Kruskal Wallis tests were used to compare health status indexes across the spectrum of GOLD stages of COPD severity. GOLD stages of COPD severity significantly differed in SGRQ components and Barthel's index, but not in the indexes assessing cognitive and affective status and quality of sleep. The largest variation in health status was observed at the transition from stage IIa to stage IIb, while there were no other significant differences between consecutive stages. Both female sex and comorbidity were associated with a greater impact of COPD on the health status. In conclusion, the upper limit of stage IIb (forced expiratory volume in one second of 49%) marks a threshold for dramatic worsening of health status. Progression of chronic obstructive pulmonary disease severity from stage 0 to stage IIa does not correspond to any meaningful difference in health status.

Aged↗

Effect of age and asthma duration upon elastase and alpha1-antitrypsin levels in adult asthmatics.

In asthmatic subjects an imbalance between elastase and alpha1-antitrypsin (alpha1-PI) exists. This study aims to evaluate whether ageing per se affects the levels of elastase. Both young and elderly asthmatics with comparable severity and duration of disease, as well as young and elderly healthy subjects, underwent an induced sputum procedure to measure levels of elastase and alpha1-PI. The percentage of sputum neutrophils and eosinophils was higher in young and elderly asthmatics than in young and elderly controls. The levels of both total and active elastase were significantly higher in young and elderly asthmatics than in young and elderly controls, and directly correlated with the percentage of neutrophils. In addition, in both young and elderly asthmatics the levels of total and active elastase were negatively correlated with forced expiratory volume in one second values, but positively correlated with the duration of the disease. This study indicates that ageing per se does not necessarily lead to a progressive elastase/alpha1-antitrypsin imbalance in asthma, and suggests that an important variable in the development of airway remodelling in both young and elderly asthmatics is represented by the duration of the disease.

Adult↗

Questionnaires, spirometry and PEF monitoring in epidemiological studies on elderly respiratory patients.

Questionnaires are the most used subjective instrument of measurement in respiratory epidemiology. The standardisation of the questionnaires aims to limit bias by maximising validity and reliability, and comparability. Within the European Union project BIOMED1, a compendium of respiratory standard questionnaires (CORSQ) was developed for adults covering 18 topics from general information to early life events, through environmental risk factors and respiratory symptoms and diseases. Reliable spirometry data needs a rigorous quality control programme, as in the "Salute Respiratoria nell'Anziano" (Sa.R.A.) project, Italian for "Respiratory Health in the Elderly". Reproducibility rates were 95.8% for forced expiratory volume in one second (FEV1). Male sex and age were independent risk factors for a poorer reproducibility, as well as cognitive and physical impairment (shorter 6-min walking distance) and lower educational level for a poorer acceptability. Reference values for people aged 65-85 yrs have been produced; these results suggest that the effect of aging should be corrected for physical and mental disability. A revision of interpretative strategies included in current guidelines is needed. Peak expiratory flow monitoring has several methodological problems: reliability and sensitivity of the measurement in order to detect changes in airway calibre; compliance with long-term monitoring; choice of the best variability index; difference between asthmatic and nonasthmatic subjects; age-related differences. Despite these methodological problems, peak expiratory flow monitoring has been successfully used in the evaluation of the effects of air pollution in normal and asthmatic subjects, and in the elderly.

Adult↗

The lack of the bronchoprotective and not the bronchodilatory ability of deep inspiration is associated with airway hyperresponsiveness.

In healthy subjects, deep inspiration (DI) acts both as a bronchodilator and a bronchoprotector. The latter is impaired in asthmatics. We have now evaluated whether the lack of bronchoprotection is related to bronchial hyperresponsiveness (BHR), and whether the bronchodilatory effect is also lost in asthmatics. Ten healthy subjects (PC20 > 75 mg/ml), 12 asthmatics with moderate to severe BHR (PC20 < 1 mg/ml), 14 asthmatics with mild to borderline BHR (1 < PC20 < 25 mg/ml), and 10 rhinitics with mild to borderline BHR (1 < PC20 < 25 mg/ml) underwent single-dose methacholine provocations inducing at least 20% reduction in FEV1 after 20 min of DI inhibition. To measure the bronchodilatory effect, DIs were taken immediately after the postmethacholine spirometry, and lung function was again tested. To measure the bronchoprotective effect, DIs were taken before the administration of spasmogen. All four groups achieved the same reductions in FEV1 and FVC, in the absence of deep breaths (analysis of variance [ANOVA], p = 0.49). Only healthy subjects showed bronchoprotection (percent bronchoprotection, mean +/- SEM; healthy: 79 +/- 4.0; asthmatics with moderate to severe BHR: 12 +/- 14.5; asthmatics with mild to borderline BHR: -7 +/- 19.7; rhinitics with mild to borderline BHR: 2 +/- 14.0). In contrast, DIs were able to partially reverse bronchial obstruction in all four groups, albeit percent bronchodilation in healthy subjects was somewhat stronger. The dissociation between bronchoprotection and bronchodilation suggests that the two effects involve different mechanisms.

Adult↗

High-resolution computed tomographic evaluation of airway distensibility and the effects of lung inflation on airway caliber in healthy subjects and individuals with asthma.

The effects of a deep inspiration (DI) in individuals with asthma differ from those observed in healthy subjects. It has been postulated that the beneficial effect of lung inflation is mediated by airway stretch. One hypothesis to explain the defects in the function of lung inflation in asthma is that a DI may be unable to stretch the airways. This may result from attenuation of the tethering forces between the airways and the surrounding parenchyma. In the current study, we used high-resolution computed tomography (HRCT) to examine the ability of a DI to distend the airways of subjects with asthma (n = 10) compared with healthy subjects (n = 9) at baseline and after increasing airway tone with methacholine (MCh). We found that both at baseline and after the induction of smooth muscle tone with MCh, a DI distended the airways of healthy and asthmatic subjects to a similar extent, indicating that abnormal interdependence between the lung parenchyma and the airways is unlikely to play a major role in the loss or attenuation of the beneficial effect of lung inflation that characterizes asthma. Furthermore, we observed that after constriction had already been induced by MCh, following a DI, bronchodilation occurred in the healthy subjects but further bronchoconstriction occurred in the subjects with asthma. Our findings suggest that an abnormal excitation contraction mechanism in the airway smooth muscle of subjects with mild asthma counteracts the bronchodilatory effect of a DI. Therefore, the mechanism for reduced bronchodilation after DIs in subjects with mild asthma could be intrinsic to the airway smooth muscle.

Adult↗

Evaluation of health outcomes in elderly patients with asthma and COPD using disease-specific and generic instruments: the Salute Respiratoria nell'Anziano (Sa.R.A.) Study.

OBJECTIVES: To compare the effects of asthma and COPD on health status (HS) in elderly patients, and to assess the correlation between disease-specific and generic instruments assessing HS. DESIGN: Multicenter, cross-sectional, observational study. SETTING: The Salute Respiratoria nell'Anziano (respiratory health in the elderly) Study network of outpatient departments. PATIENTS: One hundred ninety-eight asthma patients and 230 COPD patients > or = 65 years old. MEASUREMENTS: HS was assessed by the Saint George's Respiratory Questionnaire (SGRQ) and five generic outcomes: Barthel's index, 6-min walk test, mini mental state examination, geriatric depression scale (GDS), and quality-of-sleep index. Independent correlates of SGRQ scores were assessed by logistic regression. Patients were considered to have a "good" HS or "poor" HS according to whether they did or did not perform worse than 75% of the corresponding population of asthma or COPD patients, on at least two of the five generic outcomes. RESULTS: On average, COPD patients had poorer HS than asthma patients on the SGRQ. Only polypharmacy (more than three respiratory drugs) and diagnosis of COPD qualified as independent correlates of the SGRQ score. The SGRQ "Activity" and "Impacts" scores shared the following independent correlates: polypharmacy, Barthel's index < 92, and GDS > 6. Further correlates were waist/hip ratio > 1 for the Activity score, and age and occiput-wall distance > 9 cm for the Impacts score. All sections of the SGRQ except for the Symptoms score could significantly distinguish patients with good HS and poor HS. CONCLUSIONS: Individual dimensions of HS recognize different determinants. COPD outweighs asthma as a cause of distressing respiratory symptoms. A high degree of concordance exists between SGRQ and generic health outcomes, except for the Symptoms dimension in COPD patients.

Aged↗

Potent bronchoprotective effect of deep inspiration and its absence in asthma.

In the absence of deep inspirations, healthy individuals develop bronchoconstriction with methacholine inhalation. One hypothesis is that deep inspiration results in bronchodilation. In this study, we tested an alternative hypothesis, that deep inspiration acts as a bronchoprotector. Single-dose methacholine bronchoprovocations were performed after 20 min of deep breath inhibition, in nine healthy subjects and in eight asthmatics, to establish the dose that reduces forced expiratory volume in 1 s by >15%. The provocation was repeated with two and five deep inspirations preceding methacholine. Additional studies were carried out to assess optimization and reproducibility of the protocol and to rule out the possibility that bronchoprotection may result from changes in airway geometry or from differential spasmogen deposition. In healthy subjects, five deep inspirations conferred 85% bronchoprotection. The bronchoprotective effect was reproducible and was not attributable to increased airway caliber or to differential deposition of methacholine. Deep inspirations did not protect the bronchi of asthmatics. We demonstrated that bronchoprotection is a potent physiologic function of lung inflation and established its absence, even in mild asthma. This observation deepens our understanding of airway dysfunction in asthma.

Adult↗

Spontaneous gastroesophageal reflux and airway patency during the night in adult asthmatics.

Controversies still exist on the role of nighttime gastroesophageal reflux (GER) in precipitating nocturnal asthma. We tested the relationship between GER and nocturnal bronchoconstriction by continuously and simultaneously monitoring both respiratory resistances and esophageal pH in seven asthmatics with moderate to severe GER disease. Twenty-nine GER episodes were found during the study night lasting more than 5 min (LGER) and 72 not longer than 5 min (SGER). Both long (LGER) and short (SGER) gastroesophageal refluxes were able to maintain significantly higher lower respiratory resistances (RLR) at the resolution of each GER episode (RLR(e)) with respect to baseline values. RLR, expressed as the area under the RLR curve along each GER episode (AUCR(LR)) and as RLR(e), showed significant correlations with GER duration. Moreover, a significant correlation was found between RLR measured 10 min after GER resolution and GER duration during each episode. We conclude that GER itself is able to elicit nocturnal bronchoconstriction in asthmatics with moderate to severe GER disease and that bronchoconstriction severity and duration are related to GER duration.

Adult↗

Deep inspiration-induced bronchoprotection is stronger than bronchodilation.

We have previously shown that in healthy subjects, deep inspiration (DI) has not only a bronchodilatory but also a bronchoprotective effect that is absent in asthmatic subjects. We conducted the study reported here to test the hypothesis that the bronchoprotective effect is stronger than the bronchodilatory effect, and to determine the extent to which these two effects are related. Ten healthy subjects underwent provocations in which single doses of methacholine, previously shown to reduce FEV(1) by 10% to 20% (Dose 1) and by 20% to 40% (Dose 2) were administered after a 20-min period devoid of DI. To measure the bronchodilator effect, DIs were performed immediately after the first spirometry after methacholine, and were followed by another lung function test. To measure their bronchoprotective effect, DIs were performed before administration of a single dose of methacholine, and the FEV(1) after methacholine was compared with that of another single-dose challenge in which DIs were not included. From these outcomes, bronchodilation and bronchoprotection indices were constructed and compared with each other. At Dose 1 (mild obstruction), the ability of DIs to reverse methacholine-induced obstruction was equal to their ability to prevent it (bronchodilation index [BDI] versus bronchoprotection index [BPI]: 1.62 +/- 0.21 versus 2.02 +/- 0.40 [mean +/- SEM], p = 0.26). At Dose 2, the relative potency of both the bronchodilating and bronchoprotective effects of DIs increased, but bronchoprotection was significantly stronger (BDI versus BPI: 3.40 +/- 0.43 versus 6.98 +/- 1.42, p = 0.02). Correlation analysis of the two indices indicated that as the BPI increased, the BDI reached a plateau. We conclude that in healthy humans, the bronchoprotective effect of lung inflation is stronger than the bronchodilatory effect.

Adult↗

Prevalence of nocturnal asthma in a general population sample: determinants and effect of aging.

Nocturnal asthma (NA) is important because of clinical and prognostic implications. Previous data on prevalence may be overestimated, because they are derived from selected series. Observations on monitoring of peak expiratory flow in elderly asthmatics suggested that prevalence of NA may increase with age. This study was designed to estimate the prevalence of NA-related symptoms in a sample drawn from a general population and evaluate the role of aging. Subjects (1,100, mean age 41.9, SD 22.8 years) were randomly selected from the lists of seven general practitioners. A questionnaire on nighttime and morning NA-associated symptoms was used and frequency of occurrence was rated as never, sometimes (less than once a week), and often (once a week or more). In the overall sample, symptoms were experienced "sometimes" by 2.3%-4.9% of subjects, whereas the response "often" was given by 0.9%-1.6% of subjects. Among subjects with a diagnosis of asthma, symptoms occurred sometimes in 16.7%-23.7% and often in 5%-15%. Symptoms reported the morning after were significantly more frequent among patients aged 65 years and older (p < 0.005), whereas the difference for nighttime symptoms was not statistically significant in different age groups, confirming an age-related blunted sensitivity. Logistic regression analysis shows that a diagnosis of asthma is the most important correlate of symptoms, with odds ratio (OR) up to 14.78 for cough; advanced age also proved to be an independent risk factor (OR 3.35-4.97). In conclusion, although the prevalence of NA was previously overestimated, our results indicate its importance, particularly among elderly patients who are exposed to a prominent risk of underdiagnosis and undertreatment.

Adult↗

Effect of age upon airway obstruction and reversibility in adult patients with asthma.

OBJECTIVE: In a cross-sectional study we evaluated the effect of aging (separately from that of duration of disease) on airway obstruction and reversibility by comparing two groups of non-smoker patients with asthma. METHODS: We compared two groups of patients: group A, which had 50 subjects (8 men and 42 women) aged 59.7+/-4.6 years (mean +/- SD), and group B, comprised of 51 subjects (19 men and 32 women) who were 35.7+/-7.4 years old. The groups were selected because of comparable baseline degree of obstruction (FEV1 % of predicted, 67.8+/-20.3 in group A; 73.0+/-19.6 in group B, NS) and duration of the disease (14.0+/-11.7 years vs 11.2+/-9.1, NS). Spirometric examination, with a bronchodilator test, was performed and subjects not reaching 85% of predicted were submitted to a 4-week course of inhaled steroids. RESULTS: Although a higher number of subjects from group B responded to the acute bronchodilator test (p < 0.001), the maximum response achievable with treatment (steroid or bronchodilator) (deltaFEV1 expressed as the percent of predicted) was not statistically different between groups (12.0+/-17.5 vs 16.0+/-23.9). The mean FEV1 attainable after treatment (deltaFEV1%PT) was significantly lower in the older group (p = 0.0006). Within groups, the baseline FEV1% did not correlate with age; it was inversely correlated with the duration of the disease (p < 0.03 and p < 0.01, respectively). In both groups deltaFEV1 was inversely related with the baseline FEV1, whereas FEV1%PT was correlated with the duration of the disease, with a slope nearly doubled in group B (p < 0.001). CONCLUSIONS: Both the process of aging and the prolonged exposure to disease effects are important factors in determining the functional characteristics of chronic asthma: In particular, aging is associated not only with a reduced acute responsiveness to bronchodilators, but also with a reduced slope of the duration-FEV1%PT relationship that suggests a slowing of the rate of loss of reversibility of uncertain biological meaning.

Adult↗

Airways hyperresponsiveness and the effects of lung inflation.

Lung inflation has a beneficial effect on the airways of healthy subjects. It acts as a bronchoprotector, that is to prevent bronchoconstriction, and as a bronchodilator, in that it reverses bronchial obstruction. The bronchoprotective effect of deep inspiration is more potent than the bronchodilatory one, and the two phenomena appear to advocate different mechanisms. Asthmatics and rhinitics with airways hyperresponsiveness show an impairment in bronchoprotection induced by deep breaths, whereas the bronchodilatory effect, although reduced, is still effective. The lack of the bronchoprotective effect of deep inspiration may contribute to the development of airways hyperresponsiveness. The mechanisms through which lung inflation exerts its beneficial role in healthy subjects, and the factors impairing such an effect in those with airways hyperresponsiveness, are currently under investigation.

Asthma↗

Relationship between specific serum IgE to Ascaris lumbricoides and onset of respiratory symptoms in Bangladesh immigrants.

The role of helminths in asthma and/or rhinitis and in allergic sensitization is still unclear. We assessed the relationship between Ascaris-specific IgE, respiratory symptoms and allergic sensitization in Bangladesh immigrants. 246 individuals were examined from 1996 to 2001. Serum total IgE, Ascaris IgE, specific IgE to inhalant allergens, skin prick tests (SPT) and parasitological evaluation of the stool were performed. Total serum IgE were significantly higher in Ascaris-IgE positive (> 0.35 kU/L) individuals (806.5 [409.0-1436.0] kU/L vs. 207.0 [127.0-332.5] kU/L; P < 0.0001) and in subjects with respiratory symptoms (413.0 [239.0-1096.0] kU/L vs. 259.5 [147.0-387.0] kU/L), (P < 0.0001), but not in SPT positive subjects (413.0 [179.0-894.0] kU/L vs. 404.6 [305.0-1201.0] kU/L (P = 0.5). Ascaris-specific IgE were detected in 48 subjects with respiratory symptoms (40.0%) and in 46 subjects without respiratory symptoms (36.5%) (P = 0.5). The SPT positivity was similar between Ascaris-IgE seropositive (38.2%) and Ascaris-IgE seronegative (38.1%) subjects (P = 0.9). Total IgE and length of stay in Italy correlated with SPT positivity (OR 5.6 [CI 95% 1.5-19.8], P = 0.007, and OR 1.5 [CI 95% 1.3-1.7], P< 0.0001), and with respiratory symptoms (OR 13.7 [CI 95% 3.0-62.4];, P = 0.0007, and OR 2.4 [CI 95% 1.9-3.0], P < 0.0001). Ascaris-IgE were negatively associated with SPT positivity (OR 0.3 [CI 95% 0.1-0.8], P = 0.02) and with respiratory symptoms (OR 0.1 [CI 95% 0.04-0.7], P = 0.01). Our findings favour the role of environmental factors in the development of respiratory symptoms in immigrants, irrespective of Ascaris-IgE.

Adult↗