Diagnostic Accuracy of Specific IgE Against Wheat and Rye in Flour-Induced Occupational Asthma.

BACKGROUND: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures. OBJECTIVE: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard. METHODS: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. RESULTS: Compared with SIC, sIgE levels of 0.35 kUA/L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE. CONCLUSION: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of TH2 biomarkers.

Comparison of high- and low-molecular-weight sensitizing agents causing occupational asthma: an evidence-based insight.

INTRODUCTION: The many substances used at the workplace that can cause sensitizer-induced occupational asthma are conventionally categorized into high-molecular-weight (HMW) agents and low-molecular-weight (LMW) agents, implying implicitly that these two categories of agents are associated with distinct phenotypic profiles and pathophysiological mechanisms. AREAS COVERED: The authors conducted an evidence-based review of available data in order to identify the similarities and differences between HMW and LMW sensitizing agents. EXPERT OPINION: Compared with LMW agents, HMW agents are associated with a few distinct clinical features (i.e. concomitant work-related rhinitis, incidence of immediate asthmatic reactions and increase in fractional exhaled nitric oxide upon exposure) and risk factors (i.e. atopy and smoking). However, some LMW agents may exhibit 'HMW-like' phenotypic characteristics, indicating that LMW agents are a heterogeneous group of agents and that pooling them into a single group may be misleading. Regardless of the presence of detectable specific IgE antibodies, both HMW and LMW agents are associated with a mixed Th1/Th2 immune response and a predominantly eosinophilic pattern of airway inflammation. Large-scale multicenter studies are needed that use objective diagnostic criteria and assessment of airway inflammatory biomarkers to identify the pathobiological pathways involved in OA caused by the various non-protein agents.

Upper airway disease diagnosis as a predictive biomarker of therapeutic response to biologics in severe asthma.

Asthma is a heterogeneous disease sharing airway instability but with different biology, risk factors, and response-to-therapy patterns. Biologics have revolutionized the one-size-fits-to-all approach to personalized medicine in severe asthma (SA), which relies on the identification of biomarkers that define distinct endotypes. Thus, blood eosinophils and, to some extent, exhaled nitric oxide (FeNO) can predict the response to approved anti-type 2 (T2) biologics (anti-IgE, anti-IL-5, and anti-IL-4R alpha), whereas age at onset and comorbidities such as anxiety/depression, obesity, reflux, and upper airway disease (UAD) also influence therapeutic responses in SA. In this article, focusing on the predictive value of biomarkers for the therapeutic response to biologics in SA, we first summarize the level of prediction achieved by T2 biomarkers (blood eosinophils, FeNO) and then review whether data support the predictive value of upper airway diagnosis on such outcomes. Post hoc analysis of most studies with T2 biologics suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) and, to a lower extent, allergic rhinitis may help in predicting clinical response. Considering that T2 biologics are now also approved for the treatment of severe CRSwNP, diagnosis of upper airway disease is a key step in determining eligibility for such therapy.

Pilot study on the use of basophil activation tests and skin tests for the prevention of allergic transfusion reactions.

Background and objectives: Management of severe allergic transfusion reactions (ATR) is challenging. In this study, we investigate the usefulness of skin tests and basophil activation tests (BAT) in chronically transfused patients for the prevention of future ATR. Materials and methods: BAT and skin tests were carried with the supernatant of red blood cell (RBC) units for a sickle-cell disease patient under chronic exchange transfusion who has presented a severe ATR, in order to prevent potential future ATR. If the results for both BAT and skin tests were negative, the RBC units could be transfused to the patient. If either one of the results was positive, the tested RBC unit was discarded for the patient. Results: 192 RBC units were tested with both tests. The level of results concordance between the two tests was 95%. Out of the 169 negative units with both tests, 118 units were transfused to the patient for which he presented no ATR. Conclusion: In our study, combining both BAT and skin tests was associated with a good negative predictive value since we were able to safely transfuse our patient. Further studies are still necessary to confirm this result but this pilot study indicates that skin tests and BAT might help prevent ATR. When BAT is not available, skin tests may also be useful in preventing ATR.

Irritant-Induced Asthma.

Irritant-induced asthma (IIA) is a phenotype of asthma caused by the inhalation of irritant agents. Definite, probable, or possible IIA have been described, depending on the concentration of the inhaled irritants and the onset of respiratory symptoms respective to the time of exposure. Definite IIA represents approximately 4% to 14% of all cases of new-onset work-related asthma. Agents responsible for IIA can be encountered as fumes, gases, aerosols, or dusts. The most frequent are chlorine, nitrogen oxides, sulfur dioxide, ammonia, acetic acid, solvents, and cleaning materials. Although the diagnosis of definite IIA is based on a suggestive clinical history along with evidence of reversible airflow limitation and/or nonspecific bronchial hyperresponsiveness, possible IIA cannot be diagnosed with certainty because the relationship between exposure and the onset of symptoms is difficult to establish. This article reviews the epidemiology, pathophysiology, diagnostic approach, and management of IIA.

Which patients with asthma are most likely to benefit from allergen immunotherapy?

If allergen immunotherapy (AIT) is to be considered as a treatment option for allergic asthma, it must undergo the same developmental steps as other antiasthmatic drugs. The bronchial allergen challenge model has demonstrated excellent negative predictive value for the development of new therapies for asthma. Subcutaneous immunotherapy appears to have a clinical and significant effect on the early asthmatic response to mite, cat, and birch and grass pollens in children and adults. Use of AIT in children with asthma is widely practiced but not supported by as strong a level of evidence as in adults. House dust mite sublingual immunotherapy tablets demonstrate efficacy in asthma exacerbations and other outcomes when used as add-on therapy in adult patients. Using a biologic to improve the patient's lung functions and asthma control before initiating AIT can transform unsuitable candidates for AIT into appropriate candidates. Because AIT is a form of personalized medicine, phenotyping the most suitable patient is necessary. Field studies of adults and children have suggested that polysensitized patients with rhinitis and Global Initiative for Asthma class 2 to class 4 asthma appear the most likely to be good responders. We hypothesized that AIT responders are those who demonstrate a high eosinophilic response to natural or experimental exposure.

An unequal endotoxin distribution in typical house types of Ho Chi Minh city.

BACKGROUND: Endotoxin exposure may cause asthma exacerbations and contribute to non-atopic respiratory diseases. Viet Nam, a country with multiple house types, is lacking data on indoor contamination by endotoxin in regard with house types. OBJECTIVE: The comparison of measured settled dust endotoxin levels among house types in Ho Chi Minh city will allow to classify the house types regarding health risks. METHODS: This study is a cross-sectional study. Five identified house types were selected: apartment (APA), rental (REN), rural (RUR), slum (SLU) and tube house (TUB). One hundred house's endotoxin contamination was evaluated by questionnaire and dust sampling. Endotoxin concentration was measured by kinetic chromogenic Limulus assay. RESULTS: dotoxin concentration (geometric mean 126.0 EU/mg, 95%CI 118.3-133.7) is particularly high in settled house dust compared to western countries and is significantly associated with the house type. The highest level was found in RUR in each room (p = 0.002 for living room; p < 0.0001 for bedrooms and for kitchens). Concerning levels in the different rooms, APA and TUB form a low group while REN and SLU (p < 0.001) form a median group and RUR the highest (p < 0.001). Differences in endotoxin levels were associated to the presence of dog, chicken and farm animals, wood cooking, air-conditioning usage. CONCLUSIONS: Further understanding of the relevant factors to endotoxin levels would contribute to prevent asthma exacerbations and chronic respiratory diseases. Public health interventions to reduce exposure to endotoxin include improving housing conditions, eliminating risk factors and a priority to high-risk house types.

Helminth infection induces non-functional sensitization to house dust mites.

BACKGROUND: IgE characterizes the humoral response of allergic sensitization but less is known about what modulates its function and why some patients present clinical symptoms for a given IgE level and others do not. An IgE response also occurs during helminth diseases, independently of allergic symptoms. This response could be a model of non-functional IgE. OBJECTIVE: To study the IgE response against environmental allergens induced during natural helminth infection. METHODS: In 28 non allergic subjects from the periphery of Ho Chi Minh city with (H+, n = 18) and without helminth infection (H-, n = 10), we measured IgE and IgG4 against several components of Dermatophagoïdes pteronyssinus (Dpt) and Ascaris (a marker of immunization against nematodes), and determined the IgE component sensitization profile using microarray ISAC biochips. The functional ability of IgE to induce degranulation of cultured mast cells was evaluated in the presence of Dpt. RESULTS: Non allergic H+ subjects exhibited higher levels of IgE against Dpt compared to H- subjects. Dpt IgE were not functional in vitro and did not recognize usual Dpt major allergens. IgE recognized other component allergens that belong to different protein families, and most were glycosylated. Depletion of IgE recognizing carbohydrate cross-reactive determinant (CCD) did not induce a reduction in Dpt IgE. The Dpt IgG4 were not significantly different. CONCLUSION: Helminth infections induced IgE against allergens such as Dpt and molecular components that belong to different sources as well as against CCD (such as ß-1,2-xylose and/or ⍺-1,3-fucose substituted N-glycans). Dpt IgE were not able to induce degranulation of mast cells and were not explained by sensitization to usual major allergens or N-glycans.

Hookworm treatment induces a decrease of suppressive regulatory T cell associated with a Th2 inflammatory response.

BACKGROUND: Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment. METHODOLOGY: Twenty hookworm infected (HW+) and 14 non-infected subjects HW-from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1ß, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFß. RESULTS: HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP3lo resting Treg (rTreg). CD45RA-FoxP3lo non-suppressive Treg cells were also increased. No preferential Th1/Th2 orientation was observed, nor difference for IL-10 between two groups. After treatment, Treg, TregICOS+, TregCD62L+, Treg PD1- and rTreg decreased while IL-4 and IL-6 cytokines increased. CONCLUSION: During HW infection, Treg are increased and characterized by a heterogeneous population: a highly suppressive as well as a non-suppressive T cells phenotype. After treatment, Treg with immune-suppressive phenotype exhibited a decrease parallel to an inflammatory Th2 response.

Covid-19 and blood groups: ABO antibody levels may also matter.

BACKGROUND: Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. METHODS: After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. RESULTS: We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. CONCLUSION: In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.

A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer.

OBJECTIVES: We aimed to explore cytokine profile in patients as it relates to Coronavirus Disease 2019 (COVID-19) severity, and to establish a predictive cytokine score to discriminate severe from non-severe cases and provide a prognosis parameter for patients that will require intensive care unit (ICU) transfer. METHODS: Serum samples of 63 patients diagnosed with SARS-CoV-2 infection were collected early after hospital admission (day 0-3). Patients were categorized in five groups based on the clinical presentation, the PaO2/FiO2 ratio and the requirement of mechanical ventilation. RESULTS: Three cytokines, IL-6, IL-8 and IL-10, were markedly higher in severe forms (n = 44) than in non-severe forms (n = 19) (p < 0.005). A score combining levels of these three cytokines (IL-6*IL-8*IL-10) had the highest performance to predict severity: sensitivity of 86.4% (95% CI, 72.4-94.8) and specificity of 94.7% (95% CI, 74.0-99.9) for a cutoff value of 2068 pg/mL. Elevated levels of IL-6, IL-8 and IL-10 were also found in critically ill patients. The combination of IL-6*IL-10 serum levels allowed the highest predictability for ICU transfer: AUC of 0.898 (p < 0.0001). CONCLUSION: The combinatorial IL-6*IL-8*IL-10 score at presentation was highly predictive of the progression to a severe form of the disease, and could contribute to improve patient triage and to adapt therapeutic strategy within clinical trials more accurately and efficiently.

SARS-CoV-2 Pneumonia in Hospitalized Asthmatic Patients Did Not Induce Severe Exacerbation.

BACKGROUND: Viral infections are known to exacerbate asthma in adults. Previous studies have found few patients with asthma among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known. OBJECTIVE: To assess the frequency of asthma exacerbation in patients with asthma hospitalized for SARS-CoV-2 pneumonia and compare symptoms and laboratory and radiological findings in patients with and without asthma with SARS-CoV-2 pneumonia. METHODS: We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 had asthma. To assess the patients' asthma status, 3 periods were defined: the last month before the onset of COVID-19 symptoms (p1), prehospitalization (p2), and during hospitalization (p3). Severe asthma exacerbations were defined according to Global INitiative for Asthma guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled ß2 agonist. RESULTS: We found no significant difference between patients with and without asthma in terms of severity (length of stay, maximal oxygen flow needed, noninvasive ventilation requirement, and intensive care unit transfer); 52.2% of the patients with asthma had Global INitiative for Asthma step 1 asthma. One patient had a severe exacerbation during p1, 2 patients during p2, and 5 patients were treated with systemic corticosteroids and inhaled ß2 agonist during p3. CONCLUSIONS: Our results demonstrate that patients with asthma appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation.

Validation of Strasbourg environmental exposure chamber (EEC) ALYATEC® in mite allergic subjects with asthma.

Objective: Environmental Exposure Chamber (EEC) should have standardized and controlled allergenic and non-allergenic exposures to perform reproducible clinical studies. The aim was to demonstrate that mite exposure in the Alyatec® EEC could induce early (EAR) and/or late asthmatic reactions (LAR) in at least 60% of subjects allergic to mite.Methods: The EEC has a volume of 147-m3 with 20 seats. The nebulized particle number, airborne Der p1, endotoxins, and volatile organic compound (VOC) concentrations were measured. Twenty-four asthmatics allergic to mite were randomly exposed to 15, 25, and 46 ng/m3 Der p1. Specificity was assessed in not mite-sensitized asthmatics.Results: No significant endotoxin or VOC contamination was measured. The mean inter-assay CVs were 12.5% for the airborne particle number and 28.7% for airborne Der p1 concentrations. For the three Der p1 concentrations, at least 88% of the subjects developed EAR and/or LAR, and at least 46% developed a dual response. No reaction occurred with placebo or in the control group. No severe bronchial reaction occurred.Conclusions: The Alyatec® EEC demonstrated a tight control of allergenic and non-allergenic exposures. The EEC was clinically validated, with airborne Der p1 levels close to levels found in natural settings.

The protective effect of rural life on mite sensitization disappears among urban migrants in the South of Vietnam.

BACKGROUND: Rapid urbanization combined with rural migration to urban areas in southern Vietnam could be risk factors for allergen sensitization, contributing to chronic respiratory diseases (CRD). We aimed to evaluate the prevalence of mite sensitization and its relation to house dust characteristics among rural and urban native and migrating populations with CRD. METHODS: Rural (n = 19) and urban (n = 46) dwellings were defined on the basis of a home typology. Controls were western Belgian houses (n = 14). Besides the house characteristics, both endotoxin and mite allergens were measured in the settled dusts. The sensitization to mite allergens was defined by positive skin prick test (SPT) and concentration of specific IgE (sIgE)≥ 0.7 U/mL. The prevalence of mite sensitization was evaluated among 610 patients with CRD and compared according to both their home types and places of birth and residences. RESULTS: The concentration of endotoxin (but not mite allergen) was higher in rural compared to urban dusts (440 (95%CI: 314-566) versus 170 (95%CI: 115-226) EU/mg; p < 0.0001). The prevalence of positive sIgE to Der p1 and Der p2 was significantly lower in rural (9% and 5%) compared to urban (15% and 9%) population, consistent with the positive SPT to mite (14% and 21%, respectively). Among the urban migrants, the risk of mite sensitization (SPT) was higher compared to the rural natives (OR: 1.79 (1.02-3.15), p < 0.05) and not different to the urban ones (OR: 1.35 (0.82-2.23) p NS). CONCLUSION: In Vietnam, associated with higher endotoxin (but not allergen) dust concentrations, the risk of mite sensitization was lower in rural compared to the native urban population, but this protective effect could disappear among rural to urban migrants.

What do we know about fish allergy at the End of the Decade?

Fish allergy is one of the most common food allergies. It is usually considered to be IgE-mediated and correlates well with diagnostic tests such as prick tests and/or determination of specific IgE. Avoidance is the recommended treatment and is generally extended to all fish species. However, new clinical presentations have been described. These include non-IgE-mediated disease, monosensitization, and new syndromes that are sometimes associated, surprisingly, with cross-reactivity. Advances in molecular allergy have provided insights into new allergens and have increased our understanding of cross-reactivity. This paper focuses on recent publications providing information for clinicians involved in the management of fish allergy

La alergia al pescado es una de las alergias alimentarias más frecuentes. Constituye habitualmente una alergia IgE mediada que se identifica correctamente mediante las pruebas cutáneas y/o la IgE específica in vitro. El tratamiento recomendado es la evitación de la ingesta habitualmente de todo tipo de pescados. Sin embargo, hay otras formas de presentación como la alergia no-IgE mediada, monosensibilizaciones y nuevos síndromes asociados a otros tipos de reactividad cruzada. Los avances en el diagnóstico molecular han descrito nuevos alérgenos y aumentado nuestro conocimiento sobre la reactividad cruzada. Este artículo analiza las publicaciones recientes que proporcionan nueva información para el tratamiento de la alergia a pescados

Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers.

AIMS: In drug development, the anti-inflammatory properties of new molecules in the lung are currently tested using the inhaled lipopolysaccharide (LPS) model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective of the present study was to compare inflammatory responses in healthy volunteers after the inhalation of LPS of varying droplet size. METHODS: Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 µm), MB2 (3.2 µm) and Pari (7.9 µm)]. Participants inhaled three boluses of a 20 µg (technetium 99 m-labelled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma-scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges. RESULTS: MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts pixel-1 , respectively, vs. 67.9 (±20.6) counts pixel-1 ; P < 0.01]. MB2 and Pari caused higher levels of blood C-reactive protein and more total cells and neutrophils in sputum compared with Microcirrus (P < 0.05). C-reactive protein levels correlated positively with lung deposition (P < 0.01). CONCLUSIONS: Inhalation of large droplets of LPS gave rise to greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.

A new, faster, and safe nasal provocation test method for diagnosing mite allergic rhinitis.

BACKGROUND: Diagnosing house dust mite (HDM) allergic rhinitis is difficult. The nasal provocation test (NPT) has been shown to be the most pertinent, but several methods are available. According to guidelines, the NPT requires a skin end-point titration and an objective measurement of nasal patency. Hence, NPT is time consuming and its use is limited. OBJECTIVE: To evaluate the sensitivity, specificity, and safety of a new, more rapid, and simple alternative NPT (NPT-R) to HDM. METHODS: Eighty-eight patients with from rhinitis (49 allergic to HDM and 39 controls with and without atopy) were included. Allergic rhinitis to HDM was confirmed by a "classic" NPT based on the Lebel score and rhinomanometry. After a period of 4 weeks, NPT-R was performed and only the clinical score was measured. RESULTS: The study population was young (mean ± SD, 27.7 ± 8.5 years old), composed mostly of women (61 vs 27 men), and 24% reported asthma. The sensitivity and specificity of NPT-R were 83.7% and 100%, respectively. The correlation between the NPTs was statistically significant (0.833, P < .0001, n = 88) and the 2 NPTs were completely safe. Performing NPT-R was more rapid (mean ± SD, 22 ± 8 minutes) than the classic NPT (97 ± 20 minutes). CONCLUSION: The NPT-R is safe and easier and faster than the classic NPT. This new method appears to be a very useful tool in the diagnosis of HDM allergic rhinitis when the diagnosis is uncertain or before initiating immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01485523.