[Diagnostic value of a novel test paper detection of ECP in nasal secretion for allergic rhinitis].

Objective:To explore the diagnostic value of a novel test paper, which detect eosinophil cationic protein（ECP） of nasal secretion in allergic rhinitis（AR）. Methods:Nasal secretion and serum samples from 107 patients with allergic rhinitis（AR group） and 40 healthy volunteers（control group） were selected. The nasal symptoms were also evaluated in AR group. The degree of ECP coloration was evaluated by nasal secretion eosinophil cationic protein-myeloperoxid（ECP-MPO） test paper, and the concentration of ECP in nasal secretion and the concentration of cytokines in serum were detected at the same time. The difference and correlation among these indexes were analyzed. The best cutoff value and test efficiency of ECP chromogenic grade and concentration of nasal secretion were calculated by receiver operating characteristic curve（ROC）. Results:The concentration of ECP in nasal secretion of AR patients was significantly higher than that of healthy controls（P<0.05）. The color grade of nasal secretion detected by the test paper was positively correlated with the concentration of ECP in nasal secretion（P<0.05）, and there was significant difference among different grades（P<0.05）. There was a satisfying symmetry between the ECP color grade of nasal secretion and the serum specific IgE（sIgE） level as well as a high diagnostic consistency between them（P<0.05）. The area under the curve（AUC） of ECP concentration ROC in nasal secretion was 0.807 2, corresponding to 64% sensitivity and 85% specificity when the cutoff value was set at 0.980 5; when the cutoff value was set at 1, the AUC of nasal secretion ECP color grading was 0.941 9, corresponding to 92% sensitivity and 94% specificity. No clear correlation between the concentration of ECP in nasal secretion and serum cytokines was found（P>0.05）. Conclusion:The results of this novel test paper is in good agreement with those of serological allergens. It could serve as a preliminary test to evaluate the severity of allergy with satisfactory sensitivity and specificity, and is especially suitable in clinical practice for primary hospital.

Small airway dysfunction in patients with cough variant asthma: a retrospective cohort study.

BACKGROUND: Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA. METHODS: A total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test. RESULTS: The number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively). CONCLUSIONS: The eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.

Salbutamol combined with budesonide in treatment of pediatric bronchial asthma and its effect on eosinophils.

BACKGROUND: The aim of this study was to investigate and discuss the salbutamol combined with budesonide in treatment of pediatric bronchial asthma (BA) and its effect on eosinophils (EOS). METHODS: Ninety-eight BA children admitted and treated in our hospital from July 2016 to June 2017 were collected and divided into control group (N.=49) and observation group (N.=49) according to random number table. The children in control group were treated with budesonide and those in observation group were treated with salbutamol combined with budesonide. The clinical efficacy, pulmonary functions and levels of T-lymphocyte subsets (including cluster of differentiation 3 (CD3)+, CD4+, CD8+ and CD4+/CD8+) in the immune system between two groups were compared after the treatment; the levels of eosinophil cationic protein (ECP) and eotaxin in the children were compared before the treatment and at 1, 4 and 8 weeks after the treatment; the changes in EOS counts in blood and induced sputum of the children before and after the treatment were compared, and the EOS apoptosis rate was compared at 1, 4 and 8 weeks after the treatment. RESULTS: The effective rate of treatment in observation group was significantly higher than that in control group (P<0.05). After the treatment, the indexes of pulmonary function in observation group were obviously better than those in control group (P<0.05). Compared with those in control group, the levels of CD3+, CD4+ and CD4+/CD8+ of the children in observation group were elevated remarkably, while the CD8+ level was lowered (P<0.05). The levels of ECP and eotaxin in the two groups were decreased after the treatment compared with those before the treatment, and the levels in observation group were superior to those in control group (P<0.05). After the treatment, the EOS counts of both groups of children were lower than those before the treatment, and the decrease in observation group was more notable than that in control group. At 1, 4 and 8 weeks after the treatment, the EOS apoptosis rate in observation group was obviously higher than that in control group (P<0.05). CONCLUSIONS: The treatment of salbutamol combined with budesonide for pediatric BA has significant therapeutic effects; it can restore the pulmonary functions rapidly and improve the immunity of the lung, reduce the levels of eotaxin, ECP and EOS of the child patients and promote EOS apoptosis.

Serum eosinophil cationic protein: a prognostic factor for early postoperative recurrence of nasal polyps.

BACKGROUND: The objective of this work was to assess the efficacy of serum eosinophil cationic protein (ECP) concentration in predicting early postoperative recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: We prospectively enrolled CRSwNP patients to receive bilateral functional endoscopic sinus surgery (FESS) and followed them for 1 year. Serum ECP level was measured within 1 week before surgery. Demographics and associated medical factors were analyzed with the surgical outcome, and nasal polyp histology was microscopically examined. RESULTS: Overall, 58 patients met the inclusion criteria and underwent FESS. After at least a 1-year follow-up period, 9 patients had postoperative recurrence, with significantly higher serum ECP levels (p = 0.030). Receiver operating characteristic curve analysis showed the optimal cutoff level of serum ECP concentration for predicting the postoperative recurrence of nasal polyps was 21.8 µg/L (p = 0.030). Regardless of atopy status and histology type, logistic regression analysis showed that a higher ECP level was the sole significant factor related to early postoperative recurrence of nasal polyps (odds ratio, 54.8; p = 0.014). Cox proportional hazard regression analysis revealed that the hazard ratio of CRSwNP patients with an ECP level of >21.8 µg/L resulting in early postoperative recurrence was 7.6 (p = 0.011). CONCLUSION: Serum ECP appears to be a feasible predictor for early postoperative recurrence of nasal polyps. CRSwNP patients with preoperative serum ECP levels of ≥21.8 µg/L had an approximately 55-fold increased risk of early recurrence. CRSwNP patients with higher preoperative serum ECP levels should be closely monitored within the first year after surgery.

A randomized trial of Lactobacillus rhamnosus IDCC 3201 tyndallizate (RHT3201) for treating atopic dermatitis.

BACKGROUND: Probiotic therapies, mainly live bacteria, have been proven to be effective in treating atopic dermatitis (AD) with some controversies. Killed probiotics or postbiotics would have immunomodulatory effect in allergic diseases including AD. This study was performed to evaluate the therapeutic effect and safety of tyndallized Lactobacillus rhamnosus (IDCC 3201, isolated from the feces of a Korean breastfed infant, repeated heat-treated and incubated, RHT3201) in children with AD. METHODS: In a randomized, double-blind, placebo-controlled study, RHT3201 at a dose of 1.0 × 1010  CPU/d or placebo was given in children (aged 1-12 years) with moderate AD for 12 weeks. SCORing of AD (SCORAD) scores, allergic inflammatory markers, and safety parameters were evaluated. RESULTS: For evaluating the therapeutic effects of RHT3201, 33 subjects in each group were analyzed. The change of SCORAD total score at 12 weeks (primary outcome) from baseline was significantly greater in the RHT3201 group (-13.89 ± 10.05) compared to the control group (-8.37 ± 9.95). Levels of eosinophil cationic protein (ECP) and interleukin (IL)-31 showed tendency to decrease in the RHT3201 group and significant decreases in subgroup analysis in AD for ≥50 months. For safety analysis, a total of 100 subjects (50 in the treated group and 50 in the control group) were evaluated, and there were no significant differences in safety parameters between two groups. CONCLUSION: In children with moderate AD, oral administration of RHT3201 showed the therapeutic effect on AD, the effects in part correlated with decrement of ECP and IL-31, and the effect was more remarkable in subgroup analysis.

An update on non-invasive urine diagnostics for human-infecting parasitic helminths: what more could be done and how?

Reliable diagnosis of human helminth infection(s) is essential for ongoing disease surveillance and disease elimination. Current WHO-recommended diagnostic assays are unreliable in low-endemic near-elimination settings and typically involve the invasive, onerous and potentially hazardous sampling of bodily fluids such as stool and blood, as well as tissue via biopsy. In contrast, diagnosis by use of non-invasive urine sampling is generally painless, more convenient and low risk. It negates the need for specialist staff, can usually be obtained immediately upon request and is better accepted by patients. In some instances, urine-based diagnostic assays have also been shown to provide a more reliable diagnosis of infection when compared to traditional methods that require alternative and more invasive bodily samples, particularly in low-endemicity settings. Given these relative benefits, we identify and review current research literature to evaluate whether non-invasive urine sampling is currently exploited to its full potential in the development of diagnostic tools for human helminthiases. Though further development, assessment and validation are needed before their routine use in control programmes, low-cost, rapid and reliable assays capable of detecting transrenal helminth-derived antigens and cell-free DNA show excellent promise for future use at the point-of-care in high-, medium- and even low-endemicity elimination settings.

Levels of serum eosinophil cationic protein are associated with hookworm infection and intensity in endemic communities in Ghana.

BACKGROUND: The eosinophil cationic protein (ECP) is a cytotoxic protein mainly secreted by eosinophils granulocytes and plays a role in host defense against parasitic infections. Infection with Necator americanus (hookworm) is traditionally diagnosed by the Kato-Katz method which is inherently tedious, subjective and known to underestimate infection intensity. This study aimed to assess levels of serum ECP in relation to hookworm infection intensity. METHODS: Stool samples from 984 (aged 4 to 80 years) participants in a cross-sectional study conducted in the Kintampo North Municipality of Ghana were examined using the Kato-Katz and formol-ether concentration methods. Serum ECP levels were measured by ECP assay kit and compared between 40 individuals infected with hookworm only, 63 with hookworm- Plasmodium falciparum co-infection, 59 with P. falciparum infection and 36 with no infection. RESULTS: Hookworm infection prevalence was 18.1% (178/984). ECP levels were significantly higher in individuals infected with hookworm only (ß = 2.96, 95%CI = 2.69, 3.23, p<0.001) or co-infected with P. falciparum (ß = 3.15, 95%CI = 2.91, 3.39, p<0.001) compared to the negative control. Levels of ECP were similar between those with only P. falciparum infection and the uninfected control (p>0.05). Increased hookworm intensity was associated with a significant increase in ECP level (ß = 4.45, 95%CI = 2.25, 9.11, rs = 0.193, n = 103, p<0.01). ECP threshold of 84.98ng/ml was associated with a positive predictive value (PPV) of 98% (95% CI = 92, 100), and negative predictive value (NPV) of 76% (95% CI = 62, 87) in classifying hookworm infection status with an AUROC of 96.3%. CONCLUSION: Serum ECP level may be a good biomarker of hookworm infection and intensity and warrant further investigations to help improve current hookworm diagnosis.

Development of an effective sample transfer device for biomarker detection in nasal secretions.

Nasal secretions (NS) reflect inflammatory activity of the nasal mucosa and thus can be utilized for disease diagnosis and determining treatment effects in Allergic rhinitis (AR). However, non-standardized collection of samples can affect the measured concentration of inflammatory biomarker in NS. In this study, we aimed to develop and evaluate new devices capable of standardizing the collection, storage, and preprocessing methods of NS samples. First, we chose the best swab as polyester (PE) and selected a stimulation method, twirling for 10 s at 1 Hz, to efficiently release AR biomarkers from a PE swab. Storage of sample solutions at -20 °C was optimal for the stability of biomarkers for the detection of AR. The new swab sample transfer device showed excellent concentration recovery efficiency (90-100%) for tryptase (Trp) and eosinophil cationic protein (ECP) without crosstalk between the two biomarkers. Finally, we compared the concentration of Trp in human NS samples of AR patients (n = 6) pre-processed by the new device with that by centrifuge as a standard method. As a result, the concentrations of Trp in NS were very similar in both groups. Therefore, this device can be utilized as an effective sample transfer and pre-processing device for point-of-care testing of AR.

Home and day-care microenvironment exposure to Blomia tropicalis allergens and their associations with salivary eosinophilic cationic protein (ECP) among preschool children in Singapore.

To date, exposure studies linking dust-mite allergens with asthma and allergic morbidities have typically relied on sampling from representative locations in the home for exposure assessment. We determine the effects of differing microenvironments allergen exposures on asthma and asthma severity among 25 case and 31 control preschool children in Singapore. Blo t 5 allergen levels in various niches from the children's home and day-care microenvironments as well as their Blo t 5 time-weighted concentrations were determined. Eosinophilic cationic protein (ECP) levels from the children's saliva as markers for airway inflammation were obtained. Salivary ECP levels were higher in children with asthma than those without and the strength of association increased with higher salivary ECP levels. Although there was no relationship between time-weighted Blo t 5 concentrations with salivary ECP levels among the controls, a positive statistically significant relationship was noted among cases, demonstrating the effects of cumulative exposure on asthma severity. Avoidance measures to reduce Blo t 5 allergen exposure should include all microenvironments that asthmatic children are exposed throughout the day.

Serum eosinophilic cationic protein is correlated with food impaction and endoscopic severity in eosinophilic esophagitis.

BACKGROUND/AIMS: The aim of the present study was to analyze the diagnostic accuracy of serum eosinophilic cationic protein (ECP) for eosinophilic esophagitis (EoE) and the correlation of ECP with clinical, histopathological, laboratory, and endoscopic features of EoE. MATERIALS AND METHODS: Fifteen patients with EoE and 14 healthy controls were included in the study. Demographic parameters were recorded. EoE Endoscopic Reference Score (EREFS) was calculated according to endoscopic features, and esophageal biopsies were obtained by a single experienced endoscopist in a patient group. Serum ECP levels (µg/mL), absolute eosinophil count (U/mm3), and maximum peak of eosinophils/high-power field in esophageal biopsies were analyzed. RESULTS: The median age of all participants was 33.0 (min-max: 18-46) years. There were 27 (93.1%) male patients. Serum ECP level was significantly higher in patients with EoE than in healthy volunteers (20.4 vs. 8.8, p<0.0001). According to the receiver operating characteristic (ROC) curve analysis, ECP had 80% sensitivity and 92.8% specificity to diagnose EoE with a cut-off value of 13.9 µg/mL (area under the ROC curve 0.895; p<0.0001; 95% CI: 0.725-0.978). EREFS (p<0.0001) and the presence of food impaction (p=0.04) were significantly correlated with ECP. CONCLUSION: Serum ECP is an accurate non-invasive biomarker for EoE with high specificity and sensitivity. In addition, ECP is strongly correlated with EREFS and the symptom of food impaction.

Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: An experimental exposure study in human volunteers.

3D printers are increasingly run at home. Nanoparticle emissions from those printers have been reported, which raises the question whether adverse health effects from ultrafine particles (UFP) can be elicited by 3D printers. We exposed 26 healthy adults in a single-blinded, randomized, cross-over design to emissions of a desktop 3D printer using fused deposition modeling (FDM) for 1 hour (high UFP-emitting acrylonitrile butadiene styrene [ABS] vs low-emitting polylactic acid [PLA]). Before and after exposures, cytokines (IL-1ß, IL-6, TNF-α, INF-γ) and ECP in nasal secretions, exhaled nitric oxide (FeNO), urinary 8-isoprostaglandin F2α (8-iso PGF2α ), and self-reported symptoms were assessed. The exposures had no significant differential effect on 8-iso PGF2α and nasal biomarkers. However, there was a difference (P < .05) in the time course of FeNO, with higher levels after ABS exposure. Moreover, indisposition and odor nuisance were increased for ABS exposure. These data suggest that 1 hour of exposure to 3D printer emissions had no acute effect on inflammatory markers in nasal secretions and urine. The slight relative increase in FeNO after ABS printing compared to PLA might be due to eosinophilic inflammation from inhaled UFP particles. This possibility should be investigated in further studies using additional biomarkers and longer observation periods.

Blood eosinophils, fraction of exhaled nitric oxide, and serum eosinophil cationic protein as surrogate markers for sputum eosinophils in asthma: influence of treatment with inhaled corticosteroids

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Predictors of response to therapy with omalizumab in patients with severe allergic asthma - a real life study.

OBJECTIVES: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. METHODS: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician's global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders. RESULTS: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV1 and FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV1 (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709). CONCLUSION: Lower baseline FEV1 and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.

Evaluation of the PPAR-γ Agonist Pioglitazone in Mild Asthma: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. METHODS: Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency's reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. RESULTS: There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). CONCLUSIONS: We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma. TRIAL REGISTRATION: ClinicalTrials.gov NCT01134835.

Evaluation of biomarkers for ulcerative colitis comparing two sampling methods: fecal markers reflect colorectal inflammation both macroscopically and on a cellular level.

OBJECTIVE: Simple, objective and inexpensive tools for the assessment of mucosal inflammation in ulcerative colitis (UC) are highly desirable. The aim of this study was to evaluate a broad spectrum of activity markers comparing two sampling methods: fecal samples and the mucosal patch technique. METHODS: Twenty patients with active UC and 14 healthy controls were characterized by means of clinical indices and endoscopy together with histology and immunohistochemistry on colorectal sections. Neutrophil myeloperoxidase (MPO), calprotectin, eosinophil cationic protein (ECP), eosinophil protein X (EPX/EDN) and IL-1ß were analyzed in fecal samples and rectal fluid collected by the patch technique. Nitric oxide (NO) was analyzed in rectal gas samples. Expression of activity markers on colorectal neutrophils and eosinophils were analyzed by flow cytometry. RESULTS: All fecal and patch markers were increased in UC patients compared with healthy controls. Fecal markers and the level of neutrophil activation correlated to disease activity, whereas patch markers did not. The best markers in terms of discriminative power were fecal MPO and IL-1ß. Fecal marker levels were related to sigmoidal histology scores and to neutrophil number and activation. Patch markers were related to rectal inflammation only. CONCLUSIONS: The levels of inflammation markers in feces and patch fluid distinctly reflected active inflammation in UC. The degree of disease activity was however best assessed by fecal markers, particularly MPO and IL-1ß. Fecal markers reflect colorectal inflammation both macroscopically and on a cellular level, and may be useful for the evaluation of subclinical inflammation. The applicability of patch markers is restricted to rectal inflammation.

Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea.

OBJECTIVE: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. METHODS: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. RESULTS: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups. CONCLUSION: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.

New data analysis in a population study raises the hypothesis that particle size contributes to the pro-asthmatic potential of small pet animal allergens.

BACKGROUND: The size of inhaled particles influences where they deposit and theoretically should be important for the development of airway inflammation and responsiveness. Our aim was to assess if sensitization to smaller-sized aeroallergens relates to higher prevalence of treated asthma, increased airway responsiveness, and airway and systemic inflammation. METHODS: Molecular-based IgE antibody determination was done in 467 subjects. Sensitized subjects were grouped based on the particle size of the aeroallergen: (1) Large particles only (mainly pollen); (2) Medium-sized particles (sensitized to mainly mite and mold and possibly to large particles); and 3) Small particles (sensitized to pet allergens and possibly to medium- and/or large-sized particles). Airway responsiveness to methacholine, exhaled nitric oxide (FENO), and serum eosinophil cationic protein (S-ECP) were measured. Asthma and rhinitis were questionnaire-assessed. RESULTS: Subjects sensitized to small particles had higher prevalence of treated asthma (35% versus 10%, P < 0.001), higher FENO50 (32 versus 17 ppb, P < 0.001), higher S-ECP (10 versus 7.5 ng/mL, P = 0.04), and increased bronchial responsiveness (dose-response slope, 5.6 versus 7.5, P < 0.001) compared with non-atopics. This was consistent after adjusting for potential confounders. Sensitization to only large or to medium and possibly also large aeroallergen particles was not related to any of these outcomes after adjustments. CONCLUSIONS: Sensitization to smaller particles was associated with a higher prevalence of asthma under treatment, higher airway responsiveness, and airway and systemic inflammation. Mapping of IgE sensitization to small particles might help to detect subjects having increased airway and systemic inflammation and bronchial responsiveness, indicating increased risk of developing asthma.

Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design.

BACKGROUND: Patients with allergic asthma have exacerbations which are frequently caused by rhinovirus infection. The antiviral tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is induced by interferon-γ and suppressed by Th2 mediators interleukin (IL)-4 and IL-13. We hypothesised that local IDO activity after viral airway infection is lower in patients with allergic asthma than in healthy controls. OBJECTIVE: To determine whether IDO activity differs between patients with allergic asthma and healthy individuals before and after rhinovirus infection. METHODS: Healthy individuals and patients with allergic asthma were experimentally infected with low-dose (10 TCID50) rhinovirus 16. Blood, bronchoalveolar lavage fluid and exhaled breath condensate (for mass spectrometry by UPLC-MS/MS) were obtained before and after rhinovirus challenge. RESULTS: IDO activity was not induced by rhinovirus infection in either group, despite increases in cold scores. However, baseline pulmonary IDO activity was lower in patients with allergic asthma than in healthy individuals. In contrast, systemic tryptophan and its catabolites were markedly higher in patients with allergic asthma. Moreover, systemic quinolinic acid and tryptophan were associated with eosinophil cationic protein (r=0.43 and r=0.78, respectively) and eosinophils (r=0.38 and r=0.58, respectively) in bronchoalveolar lavage fluid and peak asthma symptom scores after rhinovirus challenge (r=0.53 and r=0.64, respectively). CONCLUSIONS: Rhinovirus infection by itself induces no IDO activity, but the reduced pulmonary IDO activity in patients with allergic asthma at baseline may underlie a reduced control of viral infections. Notably, the enhanced systemic catabolism of tryptophan in patients with allergic asthma was strongly related to the outcome of rhinovirus challenge in asthma and may serve as a prognostic factor.