Bacterial lysate add-on therapy in adult and childhood asthma: a systematic review and meta-analysis.

Background: It has been proposed that bacterial lysates may serve as a suitable immunomodulatory oral medication to improve and control asthma symptoms. However, the difference in its efficacy in adults and children remains unclear. Methods: Randomized controlled trials (RCTs) evaluating OM-85 add-on therapy in asthma patients up to December 2021 were searched using PubMed, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, and WP (WeiPu) database. Risk of bias was evaluated using the Cochrane risk of bias assessment tool. Results: A total of 36 studies were included. The results showed that OM-85 add-on treatment provided a 24% improvement in asthma symptom control [relative rates (RR) =1.24, 95% confidence intervals (CI): 1.19-1.30], and also significantly improved lung function, increased numbers of T-lymphocytes and the subtypes, and elevated levels of interferon-γ (IFN-γ), interleukin-10 (IL-10), and IL-12. Levels of serum immunoglobulin E (IgE), eosinophil cationic protein (ECP) and pro-inflammatory cytokines (including IL-4 and IL-5) were suppressed in the OM-85 add-on treatment group. Moreover, OM-85 add-on treatment showed more prominent effects in asthmatic children than in asthmatic adults. Conclusions: OM-85 add-on therapy showed important clinical benefits for patients with asthma, especially asthmatic children. Further studies focusing on the immunomodulatory function of OM-85 in personalized asthma treatment are warranted.

Efficacy and safety of Sanfeng Tongqiao Diwan in the treatment of upper airway cough syndrome: a randomized, double-blind, placebo-controlled clinical study.

Background: Sanfeng Tongqiao Diwan has shown the potential to alleviate acute, recurrent, and chronic rhinitis in adults based on available studies. However, the evidence for its application in upper airway cough syndrome (UACS) is unclear. The purpose of this study was thus to investigate the efficacy and safety of Sanfeng Tongqiao Diwan in the treatment of UACS. Methods: This was a single-center, randomized, double-blind, placebo-controlled clinical trial. A total of 60 patients who satisfied the inclusion criteria were randomly divided into experimental and placebo groups in a 1:1 ratio. The experimental group was given Sanfeng Tongqiao Diwan, and the placebo group was given a simulant for 14 consecutive days. The follow-up period was 15 days. The primary outcome was the total effective rate. The secondary outcomes included clinical efficacy, Visual Analogue Scale (VAS) of related symptoms, and Leicester Cough Questionnaire in Mandarin-Chinese (LCQ-MC) scores before and after the treatment. Additionally, the safety was also evaluated. Results: The total effective rate in the experimental group was 86.6% (26/30), which was significantly higher than the 7.1% (2/28) in the placebo group (difference 79.6; 95% CI: 57.0 to 89.1; P<0.001). Nasal congestion, runny nose, cough, postnasal drip, and overall symptoms in the experimental group were significantly lower than those in the placebo group after treatment (3.7±1.5 vs. 5.0±1.1, 3.6±1.3 vs. 5.9±1.1, 3.8±1.2 vs. 6.8±1.3, 3.5±1.4 vs. 6.1±1.5, 3.8±2.0 vs. 7.3±1.4, respectively; all P values <0.001). After treatment, the LCQ-MC score in the experimental group was significantly higher than that in the placebo group (all P values <0.001). The blood eosinophil count in the placebo group was significantly higher after treatment than before treatment (P=0.037). No abnormalities were found in liver or renal indicators during the treatment period in the 2 groups, and no adverse reactions occurred. Conclusions: Sanfeng Tongqiao Diwan improved the symptoms and living quality of patients with UACS and showed acceptable safety. The results of this trial represent rigorous clinical evidence for the application of Sanfeng Tongqiao Diwan and further support a new option in UACS treatment. Trial Registration: Chinese Clinical Trial Registry ChiCTR2300069302.

Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis.

Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.

Allergic disease and sensitization disparity in urban and rural China: A EuroPrevall-INCO study.

BACKGROUND: Studies in comparison with allergic diseases and sensitization between rural and urban environments in westernized countries might be biased and not adequately reflect countries undergoing rapid transition. METHODS: A total of 5542 schoolchildren from urban area and 5139 from rural area were recruited for the EuroPrevall-INCO survey. A subsequent case-control sample with 196 children from urban area and 202 from rural area was recruited for a detailed face-to-face questionnaire and assessment of sensitization. Skin prick tests and serum-specific IgE measurements were used to assess sensitizations against food and aeroallergens. Logistic regression analysis was used to determine associations between risk/protective factors, food adverse reactions (FAR), allergic diseases, and sensitizations. RESULTS: Prevalence of self-reported allergic diseases, including asthma (6.6% vs.2.5%), rhinitis (23.2% vs.5.3%), and eczema (34.1% vs.25.9%), was higher in urban than in rural children. Urban children had a significantly higher prevalence of FAR and related allergic diseases, and lower food/inhalation allergen sensitization rate, than those of rural children. In urban children, frequent changing places of residency (odds ratio 2.85, 95% confidence interval: 1.45-5.81) and antibiotic usage (3.54, 1.77-7.32) in early life were risk factors for sensitization, while sensitization and family history of allergy were risk factors for allergic diseases. In rural children, exposure to rural environments in early life was protective against both allergen sensitizations (0.46, 0.21-0.96) and allergic diseases (0.03, 0.002-0.19). CONCLUSION: We observed a disparity in rates of allergic diseases and allergen sensitization between rural and urban children. In addition to family history, the development of allergic diseases and allergen sensitization were associated with specific urban/rural environmental exposures in early life.

Suppression function against environmental dust exposure after Dermatophagoides pteronyssinus immunotherapy is associated with production of specific and cross-reactive immunoglobulin G4.

BACKGROUND: Whether Dermatophagoides pteronyssinus (Der-p) allergen immunotherapy (AIT) can induce Dermatophagoides farina (Der-f)-specific immunoglobulin (sIg) G4 production, and tolerance to environmental allergens has not been fully investigated. OBJECTIVE: We aimed to determine serum Der-p-sIgG4 and Der-f-sIgG4 levels in asthma and/or rhinitis patients undergoing Der-p AIT and their ability to reduce immune responses triggered by indoor dust extracts. METHODS: We performed a real-world prospective trial and enrolled patients with allergic rhinitis and/or asthma in Guangzhou, China. These patients received either Der-p AIT (SCIT group) or routine medications (non-SCIT group) for 156 weeks. Clinical outcomes were assessed by the combined symptom medication score (SMS) and FEV1 % changes. House dust samples were collected to analyse allergen levels. Serum levels of Der-p-sIgG4 and Der-f-sIgG4, serum inhibitory capacity against Der-p, Der-f and indoor dust extract by sIgE-facilitated allergen binding to B cells (IgE-FAB), and serum blocking indoor dust extract-induced basophil activation inhibition assays (BATI) in peripheral blood monocytes were carried out at weeks 0, 4, 12, 16, 52, 104 and 156 after the initiations of the treatments. RESULTS: Our study enrolled a total of 60 participants, with 30 patients in each group. Patients in the SCIT group had significantly improved SMS when compared with the baseline and the patients in the non-SCIT group. Median levels of Der-p 1 and Der-f 1 in indoor dust extract were 1.86 µg/g and 4.74 µg/g, respectively. Serum Der-p-sIgG4 and Der-f-IgG4 levels in SCIT patients showed a significant increase from weeks 12 to 156. Serum in these SCIT patients could significantly block Der-p, Der-f and indoor dust extract formation of allergen-sIgE complex and reduced the threshold of IgE-FAB from 16 weeks after the initiation of the treatment. The capacity to inhibit Der-p, Der-f and indoor dust extract BATI was observed in SCIT serum after 12 weeks. Der-p-sIgG4 and Der-f-sIgG4 had a significant correlation with IgE-FAB and BATI in SCIT patients at all time points. CONCLUSION: Single Der-p immunotherapy induced both Der-p-sIgG4 and Der-f-sIgG4 production, which might cross-reactively induce tolerance against environmental allergen exposure in patients with asthma and/or rhinitis.

Clinical relevance of serum Krebs von den Lungen-6 levels in patients with coronavirus disease 2019.

The clinical relevance of Krebs von den Lungen-6 (KL-6) levels in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to evaluate the correlation between KL-6 levels, laboratory parameters, and clinical outcomes. We enrolled 364 patients with confirmed COVID-19 who were hospitalized within 1 week of symptom onset. Their serum KL-6 level was measured on admission. Demographic data, symptoms, comorbidities, and laboratory parameters were recorded at the time of admission. Days to nucleic acid conversion and days of hospitalization were defined as clinical outcomes for evaluating the clinical relevance of serum KL-6 levels in COVID-19. Patients with elevated KL-6 levels were significantly older; had more reported instances of fever, cough, fatigue, and wheezing; and a longer hospital stays than those with normal KL-6 levels; the difference was statistically significant (p < 0.001). Furthermore, KL-6 levels was associated with the days of hospitalization and various laboratory parameters that influence the severity and prognosis of COVID-19. Elevated KL-6 levels have also been shown to be an independent risk factor for prolonged hospitalization. Our data suggest that serum KL-6 levels on admission can serve as an indicator for assessing the clinical outcomes of COVID-19.

FEF25-75% Is a More Sensitive Measure Reflecting Airway Dysfunction in Patients with Asthma: A Comparison Study Using FEF25-75% and FEV1.

BACKGROUND: Reduced forced expiratory flow between 25% and 75% of vital capacity percent predicted (FEF25-75%) representing small airway dysfunction (SAD) was associated with asthma development and progression. OBJECTIVE: To investigate whether FEF25-75% was superior to forced expiratory volume in 1 second in predicted (FEV1%) in reflecting asthma features in adult patients. METHODS: A retrospective spirometry dataset comprising 1801 adult patients with confirmed asthma and a subgroup of 332 patients having detailed clinical data were used to explore the association of FEF25-75% and/or FEV1% with clinical features of asthma. RESULTS: Of the 1801 subjects, FEV1% and FEF25-75% ranged from 136.8% to 10.2% and 127.3% to 3.1%, respectively. FEF25-75% < 65% was present in 1,478 (82.07%) of patients. FEF25-75% was strongly correlated with matched FEV1% (r = 0.900, P < .001). FEF25-75% and FEV1% were both correlated with airway hyperresponsiveness (r = 0.436, P < .001; r = 0.367, P < .001), asthma control test score (r = 0.329, P < .001; r = 0.335, P < .001), and sputum eosinophil count (r = -0.306, P < .001; r = -0.307, P < .001). Receiver-operating characteristic curves showed that FEF25-75% had greater value in predicting severe asthma (area under the curve: 0.84 vs 0.81, P = .018), airflow obstruction (0.97 vs 0.89, P < .001), and severe bronchial hyperresponsiveness (0.74 vs 0.69, P = .012) as compared with FEV1%. Patients with SAD (FEF25-75% < 65%) in the presence of normal FEV1% exhibited higher sputum eosinophil counts and had an increased dosage of daily inhaled corticosteroids (P < .001 and P = .010) than patients with normal lung function and their FEF25-75% values correlated with sputum eosinophil count (r = -0.419, P = .015), but not FEV1%. CONCLUSION: FEF25-75% represented small airway function and was more sensitive at reflecting airway hyperresponsiveness, inflammation, and disease severity as compared with FEV1% in patients with asthma. Our data suggest further assessment of FEF25-75% in asthma management, particularly for those with SAD who present normal FEV1%.

Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS: A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS: Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION: These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.

Effect of Dermatophagoides pteronyssinus Immunotherapy on Upper and Lower Airway Eosinophilic Inflammatory Response to Nasal Allergen Challenge.

PURPOSE: It remains unknown whether allergen-specific immunotherapy (AIT) could attenuate airway inflammatory response triggered by allergen exposure. METHODS: We performed Dermatophagoides pteronyssinus (Der-p) nasal provocation tests (NPTs) in allergic rhinitis (AR) and/or asthma patients without AIT (non-AIT), or at 16, 52, 104, or 156 weeks after Der-p AIT. Rhinitis and asthma visual analog scale (VAS; VAS of nasal symptoms [VAS-NS], VAS of asthma symptoms), the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal lavage, sputum induction, fractional exhaled nitric oxide (FeNO), nasal airway resistance, pulmonary function, and airway hyperresponsiveness were performed before and after NPT. RESULTS: Non-AIT subjects demonstrated significantly higher VAS-NS before and after NPT compared to AIT subjects (P < 0.05). NPT response was positive in 14 (100%) non-AIT, 7 (70%) 16 weeks-AIT, 6 (60%) 52 weeks-AIT, 6 (60%) 104 weeks-AIT, and 2 (20%) 156 weeks-AIT subjects. The NPT grade significantly correlated with AIT duration and baseline RQLQ score (r =- 0.561, P < 0.001 and r = 0.525, P < 0.001, respectively). Sputum and nasal lavage eosinophil count, and FeNO in non-AIT subjects were significantly increased 6 hours after NPT (P < 0.05). AIT subjects did not change their sputum or nasal lavage eosinophil count before and after NPT. Subjects with 156 weeks-AIT demonstrated significantly lower levels of sputum and nasal lavage eosinophil count before and after NPT when compared with non-AIT patients (P < 0.05). Sputum eosinophil counts positively correlated with nasal lavage eosinophil counts at baseline and 6 hours after NPT (r = 0.719, P = 0.006 and r = 0.823, P < 0.001, respectively) in non-AIT patients. CONCLUSION: Our results show that AIT can attenuate both upper and lower airway immune response to nasal allergen exposure in patients with AR and/or asthma.

Allergen Immunotherapy-Induced Immunoglobulin G4 Reduces Basophil Activation in House Dust Mite-Allergic Asthma Patients.

It is unclear if allergen immunotherapy (AIT) can reduce allergy effector cell activation. We evaluated the basophil response during Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) and its relationship to allergen-specific immunoglobulin G4 (sIgG4) in allergic rhinitis and/or asthma patients. The study included 55 subjects, of which 35 cases received Der p SCIT and 20 controls received standard medications. Symptom and medication scores (SMSs), sIgG4 levels, specific immunoglobulin E (sIgE) levels, allergen-induced basophil activation tests (BATs) in whole blood, and BAT inhibition assays in serum were determined at weeks 0, 4, 12, 16, 52, and 104 of SCIT. Levels of Der p sIgG4 in SCIT patients significantly increased after 12 weeks of treatment compared to week 0. Serum obtained from SCIT patients significantly inhibited basophil activation after 12 weeks of treatment. Removal of immunoglobulin G4 (IgG4) antibodies at week 104 reduced the ability of serum to block basophil activation. An increase of Der p sIgG4 rather than reduction of Der p sIgE correlated with the reduction of basophil activation during SCIT. The sIgG4 antibodies may compete with sIgE binding to allergens to form an immunoglobulin E (IgE)-allergen complex. SCIT reduced the sensitivity of allergen-triggered basophil activation in Der p allergic rhinitis and/or asthma patients through induction of sIgG4.

Characteristics of COVID-19 Patients Based on the Results of Nucleic Acid and Specific Antibodies and the Clinical Relevance of Antibody Levels.

Combination of nucleic acid and specific antibody testing is often required in the diagnosis of COVID-19, but whether patients with different nucleic acid and antibody results have different laboratory parameters, severities and clinical outcomes, has not yet been comprehensively investigated. Thus, according to different groups of nucleic acid and antibody results, we aimed to investigate the differences in demographic characteristics, and laboratory parameters among the different groups and predict their clinical outcomes. In our study, nasopharyngeal swab nucleic acids and antibodies were detected by reverse-transcription polymerase chain reaction and chemiluminescence, respectively. Patients with confirmed COVID-19 with different severities, were divided into the PCR+Ab+, PCR+Ab-, and PCR-Ab+ groups. Demographic characteristics, symptoms, comorbidities, laboratory parameters, and clinical outcomes were compared among the three groups. The correlation of antibodies with laboratory parameters and clinical outcomes was also explored, and antibodies were used to predict the timing of nucleic acid conversion. We found that a total of 364 COVID-19 patients were included in the final analysis. Of these, a total of 184, 37, and 143 patients were assigned to the PCR+Ab+, PCR+Ab-, and PCR-Ab+ groups, respectively. Compared to patients in the PCR+Ab- or PCR- Ab+ groups, patients in the PCR+Ab+ group presented worse symptoms, more comorbidities, more laboratory abnormalities, and worse clinical outcomes (P < 0.05). In addition, the levels of IgG, IgM, and IgA were all significantly correlated with the days of hospitalization, days of PCR turning negative, and multiple laboratory parameters (P < 0.05). Meanwhile, combined IgM, IgA, and IgG predicted the days of PCR turning negative within 1 week. The best performance was achieved when the cut-off values of IgM, IgG, and IgA were 3.2, 1.8 and 0.5, respectively, with a sensitivity of 73% and specificity of 82%. In conclusion, COVID-19 patients who were both positive for nucleic acids and antibodies presented with worse clinical features, laboratory abnormalities, and clinical outcomes. The three specific antibodies were positively correlated with clinical outcomes and most laboratory parameters. Furthermore, antibody levels can predict the time of nucleic acid conversion.

Sputum Autoantibodies Are More Relevant in Autoimmune Responses in Asthma than Are Serum Autoantibodies.

PURPOSE: The data on the differences between sputum autoantibodies (Sp-Abs) and serum autoantibodies (Se-Abs) in reflection of autoimmune responses to lungs is still lacking. METHODS: Ten types of Abs were investigated in matched Se and Sp samples collected from recruited subjects. Correlations between Ab levels and airway inflammatory parameters and measures of pulmonary function were assessed. The network-based and inter-correlated analysis was performed to explore the patterns of Sp- and Se-Ab profiles. RESULTS: Fifty stable asthmatic patients and 24 healthy volunteers were recruited for our study, 15 with mild asthma, 18 with moderate asthma and 17 with severe asthma. The concentrations of Sp-Ab against U1 small nuclear ribonucleoprotein (Sp-anti-U1-SnRNP), Sp-Ab against Smith antigen and Se-Ab against thyroid peroxidase (anti-TPO) in severe asthmatics and Sp-anti-U1-SnRNP in moderate asthmatics were significantly higher compared to healthy controls and mild asthmatic subjects (P < 0.05). Sp-anti-U1-SnRNP levels were positively correlated with the dose of inhaled corticosteroids, Sp eosinophil counts and fractional exhaled nitric oxide (r = 0.326, P = 0.022; r = 0.356, P = 0.012; r = 0.241, P = 0.025, respectively) and negatively correlated with Sp neutrophil counts (r = -0.308, P = 0.031) with adjustment for age. Spearman's correlation matrix showed multiple inter-correlations among Sp-Abs and Se-Abs (P < 0.05) while only the levels of Ab against DNA topoisomerase and anti-TPO in Se were correlated with those Sp-Ab counterparts (P < 0.05). The network-based analysis defined 2 clusters: clusters 1 and 2 contained 10 Sp-Abs and 10 Se-Abs, respectively. CONCLUSIONS: This study observes that Sp-Abs are more associated with clinical parameters and the severity of disease in asthma compared to Se-Abs. Targeting on Sp-Abs which are the hallmark of the localized autoimmune event might help us better understand the role of autoimmunity in the pathological mechanism of asthma.

Functional and Immunoreactive Levels of IgG4 Correlate with Clinical Responses during the Maintenance Phase of House Dust Mite Immunotherapy.

Allergen-specific immunotherapy for house dust mite allergy is effective, but there are no validated biomarkers reflecting or predicting the clinical efficacy. We aimed to investigate the relationship between clinical outcomes and functional responses of allergen-specific IgG4 (sIgG4) and specific IgE (sIgE) during Dermatophagoides pteronyssinus s.c. allergen immunotherapy (SCIT) in allergic rhinitis and/or asthma patients. Combined symptom medication scores (SMS), D. pteronyssinus-sIgG4 levels, D. pteronyssinus-sIgE levels, and the serum inhibitory capacity against D. pteronyssinus-sIgE facilitated allergen binding to B cells (IgE-FAB) were determined during the updosing (week 0, 4, 12, and 16) and maintenance (week 52, 104, and 156) phase of SCIT. We found that SCIT patients had a significant improvement in SMS from week 52 to 156 compared with medication-treated control subjects (p < 0.05). Levels of D. pteronyssinus-sIgG4 in SCIT patients showed a significant increase from week 12 to 156 (p < 0.05). Serum obtained from SCIT patients significantly inhibited D. pteronyssinus-sIgE binding to B cells after 16 wk (p < 0.01). Significantly lower levels of D. pteronyssinus-sIgE were observed in SCIT patients after 52 wk (p < 0.05). A significant relationship was demonstrated between SMS and IgE-FAB or D. pteronyssinus-sIgG4 during the maintenance phase according to linear regression analysis. In conclusion, D. pteronyssinus-sIgG4 level and D. pteronyssinus IgE-FAB are associated with clinical efficacy in the maintenance phase rather than the updosing phase of SCIT. Immunologic tolerance can be induced with SCIT when maintenance phase is achieved.