Efficacy of allergen immunotherapy in reducing the likelihood of developing new allergen sensitizations: a systematic review.

BACKGROUND: Guidelines and position papers indicate that allergen immunotherapy (AIT) is the only disease-modifying treatment, including prevention of the onset of new allergen sensitizations. However, this preventive effect was shown by only a few observational studies. Our aim was to systematically review the efficacy of AIT in preventing the onset of new allergen sensitizations. METHODS: Computerized bibliographic searches of Medline, EMBASE, and the Cochrane Library (through June 2015) were supplemented with manual searches of reference lists. Observational studies or randomized controlled trials with a long-term observation period were included. Paired reviewers extracted data about study characteristics and assessed biases. The end point was the risk difference in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy. The strength of the evidence was graded based on the risk of bias, consistency, and magnitude of effect, according to the GRADE Working Group's guide. RESULTS: Eighteen studies (1049 children, 10 057 adults) met the inclusion criteria. The risk of bias was high in all but one study. Low evidence supports the position that AIT prevents the onset of new allergen sensitizations, with 10 of 18 studies reporting a reduction in the onset of new sensitizations in patients treated with AIT vs placebo. Small studies and studies with a shorter follow-up showed the highest benefit of AIT. CONCLUSIONS: The overall evidence provides a low-grade level of the evidence supporting the efficacy of AIT in preventing the onset of new allergen sensitizations, but high-quality studies could change this estimate.

Differences in the behavior of advanced glycation end products and advanced oxidation protein products in patients with allergic rhinitis.

BACKGROUND: The presence of oxidative stress in patients with asthma is well documented; however, the role of oxidative stress in allergic rhinitis has received less attention, although it is likely to be similar to that observed in patients with asthma. Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) are compounds formed by the transformation of macromolecules, including proteins, which can serve as densitometric markers of oxidative stress and inflammation in several diseases. OBJECTIVE: The aim of this study was to investigate the role of AGEs and AOPPs as new markers of oxidative stress and inflammation in patients affected by allergic rhinitis. METHODS: AGE and AOPP levels were determined in the sera of 25 patients with allergic rhinitis and 64 healthy controls. AGEs and AOPPs were detected using spectrofluorimetry and spectrophotometry, respectively. RESULTS: AGE levels in patients were significantly higher than those in controls (P < .0001). These levels were not affected by the presence of asthma. No statistically significant differences were found between AOPP levels in patients or controls (P = .38). CONCLUSIONS: Formation of AGEs and AOPPs may be accelerated in immunological and respiratory disorders such as asthma. Depending on the marker evaluated, the presence or absence of oxidative stress in allergic rhinitis is controversial. To our knowledge, this is the first study showing the possible involvement of AGEs in allergic rhinitis. The different behavior observed for these 2 biomarkers is very likely due to the activation of specific related biochemical pathways (eg, the myeloperoxidase pathway) associated with the condition under study.

Differences in the Behavior of Advanced Glycation End Products and Advanced Oxidation Protein Products in Patients With Allergic Rhinitis

Antecedentes: La presencia de estrés oxidativo en pacientes con asma bronquial ha sido bien documentada, sin embargo el papel del estrés oxidativo en las rinitis alérgicas no ha sido estudiado. Los productos finales de la glicación avanzada (AGEs), y los productos de la oxidación avanzada de proteínas (AOPPs) son compuestos formados por la transformación de macromoléculas, incluyendo proteínas, que pueden servir como marcadores densitométricos del estrés oxidativo y de la inflación en diferentes enfermedades. Objetivos: El motivo de este estudio fue investigar el papel de AGEs y AOPPs como nuevos marcadores del estrés oxidativo en la rinitis alérgica. Métodos: Estos marcadores fueron analizados en 25 pacientes con rinitis alérgica y en 64 sujetos sanos, mediante métodos de espectrofluorometría y espectrofotometría respectivamente. Resultados: Los resultados confirman la existencia de niveles elevados de AGEs en pacientes respecto a los controles sanos (p<0.0001). Estos niveles no se vieron influenciados por la presencia de asma. No encontramos diferencias significativas entre los niveles de AOPPs en pacientes y controles (p=0.38). Conclusiones: La formación de AGEs y AOPPs podría dispararse en alteraciones inmunológicas y patologías respiratorias tales como el asma bronquial. La presencia o no de estrés oxidativo en la rinitis alérgica es tema de controversia y depende del marcador evaluado. Este es el primer estudio que demuestra la posible implicación de AGEs en la rinitis alérgica. El diferente comportamiento observado para estos dos biomarcadores podría ser debido a las vías bioquímicas específicas (por ejemplo la vía de la mieloperoxidasa) relacionadas con la condición patológica bajo estudio (AU)

Background: The presence of oxidative stress in patients with asthma is well documented; however, the role of oxidative stress in allergic rhinitis has received less attention, although it is likely to be similar to that observed in patients with asthma. Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) are compounds formed by the transformation of macromolecules, including proteins, which can serve as densitometric markers of oxidative stress and inflammation in several diseases. Objective: The aim of this study was to investigate the role of AGEs and AOPPs as new markers of oxidative stress and inflammation in patients affected by allergic rhinitis. Methods: AGE and AOPP levels were determined in the sera of 25 patients with allergic rhinitis and 64 healthy controls. AGEs and AOPPs were detected using spectrofluorimetry and spectrophotometry, respectively. Results: AGE levels in patients were significantly higher than those in controls (P<.0001). These levels were not affected by the presence of asthma. No statistically significant differences were found between AOPP levels in patients or controls (P=.38). Conclusions: Formation of AGEs and AOPPs may be accelerated in immunological and respiratory disorders such as asthma. Depending on the marker evaluated, the presence or absence of oxidative stress in allergic rhinitis is controversial. To our knowledge, this is the first study showing the possible involvement of AGEs in allergic rhinitis. The different behavior observed for these 2 biomarkers is very likely due to the activation of specific related biochemical pathways (eg, the myeloperoxidase pathway) associated with the condition under study (AU)

Clinical importance of eosinophil count in nasal fluid in patients with allergic and non-allergic rhinitis.

Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNF's accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNF's median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNF's median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNF's median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNF's median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was < or = 5.0, AUC = 0.94. ECNF's median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was < or = 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNF's performance was moderately accurate in distinguish patients with AR and NAR.

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.

Is there a role for antileukotrienes in urticaria?

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, i.e. leukotriene receptor antagonists and synthesis inhibitors, are a new class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma. We searched the MedLine database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin or food additive hypersensitivity or with autoreactivity to intradermal serum injection when taken with an antihistamine but not in moderate chronic idiopathic urticaria. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angio-oedema, and exercise-induced anaphylaxis.

Determinants of bronchial hyperresponsiveness in subjects with rhinitis.

Subjects with rhinitis but without asthma may have coexisting bronchial hyperresponsiveness, although the reasons for this are uncertain. To evaluate the factors that determine BHR in rhinitis we examined 410 patients with symptomatic rhinitis with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)>or=80% of the predicted value. In all subjects a skin prick test (SPT) was performed, a determination of total serum IgE and an eosinophils count in the blood. Of the 410 subjects we found that 161 (39.3%) exhibited a methacholine PD20 of 800 mg or less (Group A), whereas 249 (60.7%) had a methacholine PD20 more of 800 mg (Group B). Despite the matched mean values for FEV1 and FVC, compared with Group B, Group A had a lower predicted forced expiratory flow between 25% and 75%(FEF25%-75%) (86.7 +/- 12.0 vs. 93.7 +/- 7.3, P < 0.0001). A great portion of the subjects of the Group Ain respect to subjects of the Group B were exposed to passive smoke (37.8% vs. 22.0%, P = 0.0008), reported having mothers with asthma (34.1% vs. 6.0%, P < 0.0001), presented a positive skin prick test (93.7% vs. 67.0%, P < 0.0001), had higher levels of total serum IgE (geometric mean of Log10 2.46 +/- 0.27 kU/L vs. 2.06 +/- 0.38 kU/L, P < 0.0001) and higher blood eosinophil counts (geometric mean of Log10 2.67 +/- 0.07 x 10(-3) mL vs. 2.57 +/- 0.09 x 10(-3) mL, P < 0.0001), and reported increased nasal obstruction (2.0 (95% CI 1.8 to 2.2) vs. 0.6 (95% CI 0.5 to 0.7), P < 0.0001). Logistic regression demonstrates that nasal obstruction (OR 2.19, 95% CI 1.72 to 2.80) and the presence of positive SPT (OR 6.15, 95% CI 2.42 to 15.61) were the most available predictors to discriminate between subjects with BHR and subjects without BHR. In addition, BHR was positively related to blood eosinophil counts (OR= 2.80, 95% CI 1.54 to 5.07), FEF25%-75% values (OR= 2.72, 95% CI 1.23 to 5.99) and familiarity (mother) for asthma (OR = 2.45, 95% CI 1.10 to 5.46). Whereas passive smoke and total serum IgE were not positively related to BHR. Increased nasal obstruction and the presence of positive SPT were the most available predictors to discriminate between subjects with and without BHR. Finally, BHR was positively related to blood eosinophil counts, FEF25%-75% values and to familiarity (mother) for asthma.