Component-resolved diagnosis in childhood and prediction of asthma in early adolescence: A birth cohort study.

INTRODUCTION: Component-resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD. METHODS: One thousand one hundred one twenty-five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics. RESULTS: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82. CONCLUSIONS: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models.

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

Sensitization trajectories to multiple allergen components in a population-based birth-cohort.

BACKGROUND: The characteristics of allergic sensitization profiles can differ between populations and geographic regions, contributing differently to the association with allergic diseases. Consequently, the sensitization trajectories found in previous studies conducted in Northern Europe may not apply in Southern European countries. OBJECTIVE: To identify trajectories of allergic sensitization profiles during childhood and evaluate the association with allergic outcomes, using data from a Portuguese birth cohort. METHODS: A random sample from Generation XXI was screened for allergic sensitization at 10 years of age. Among 452 allergic sensitized children, 186 were tested with ImmunoCAP™ ISAC multiplex array that detects 112 molecular components, at three follow-ups (4, 7, and 10 years old). Information on allergic outcomes (asthma, rhinitis, atopic dermatitis) was obtained at the 13-year-old follow-up. Latent class analysis (LCA) was used to identify clusters of participants with similar sensitization profiles. Then, sensitization trajectories were defined based on the most prevalent transitions between clusters over time. Logistic regression was applied to estimate the association between sensitization trajectories and allergic diseases. RESULTS: Five trajectories were proposed: "no/few sensitizations," "early persistent house dust mites (HDM)," "early HDM and persistent/late grass pollen," "late grass pollen," and "late HDM." The "early HDM and persistent/late grass pollen" trajectory was associated with rhinitis and "early persistent HDM" with asthma and rhinitis. CONCLUSION: Distinct sensitization trajectories pose different risks in the development of allergic diseases. These trajectories present some differences from those in Northern European countries and are important for planning adequate prevention health plans.

Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

Eosinophil cationic protein (ECP) correlates with eosinophil cell counts in the induced sputum of elite swimmers.

Introduction: Swimming practice has been associated with eosinophilic inflammation, however, the underlying mechanisms are not fully understood. The eosinophil cationic protein (ECP) in induced sputum may be used as a potential biomarker to assess airway eosinophilic inflammation among elite swimmers. The objective of this study is to characterize ECP levels in sputum supernatant in elite swimmers and evaluate ECP as an eosinophilic inflammatory marker. Material and methods: Elite swimmers annually screened in our department (n = 27) were invited to participate in this cross-sectional study. Swimmers who agreed to participate (n = 24, 46% girls) performed lung function and skin-prick tests. Induced sputum was also collected and analyzed for differential cell counts and ECP measurements in sputum supernatant (ImmunoCAPTM 100, ECP, Thermo Fisher Scientific, Uppsala, Sweden). Results: The median ECP level was 15.60 µg/L (6.02-38.75 µg/L) and higher levels were found among boys (27.90 (11.20-46.30) µg/L vs 6.65 (2.82-22.80) µg/L, P = .02). In addition, ECP levels in the sputum supernatant were positively correlated with eosinophil cell counts in the induced sputum (r = 0.583, P = .08). Conclusions: ECP levels correlated positively with eosinophil counts in the induced sputum in elite swimmers. The measurement of ECP in sputum supernatant may be a useful marker to assess and manage eosinophilic inflammatory changes in the airways of elite swimmers.

Insights on chronic hypersensitivity pneumonitis' treatment: Factors associated with a favourable response to azathioprine.

BACKGROUND: The use of immunosuppressive and antifibrotic agents for the treatment of chronic hypersensitivity pneumonitis (CHP) appears promising, but there is still no evidence supporting the clinical decision regarding the implementation of each specific pharmacological strategy. METHODS: Patients diagnosed with CHP and treated with azathioprine (AZA) were retrospectively selected from a single centre for Interstitial Lung Diseases. Baseline clinical data, as well as functional, imaging, bronchoalveolar lavage (BAL) and histology features were assessed. Longitudinal data on functional parameters were collected and comparatively analysed with patients' characteristics. RESULTS: In this cohort of 80 patients, of those who reached 12 months of treatment, 78.3% presented a preserved forced vital capacity, with 59 being eligible to be classified as AZA responders (n = 36) or non-responders (n = 23). BAL lymphocytosis was associated with a favourable response to AZA treatment (OR 1.051; 95% CI 1.015-1.089), although it didn't identify all responders. CONCLUSIONS: AZA revealed to be effective in disease stabilisation in most patients, while ineffective for a subset. BAL lymphocytosis appears as a potentially valuable strategy to identify AZA responders, although with limited accuracy. Further studies are needed to clarify other response markers to immunosuppressive agents, in order to optimize the therapeutic options for this condition.

Neighbourhood green and blue spaces and allergic sensitization in children: A longitudinal study based on repeated measures from the Generation XXI cohort.

Evidence on the effect of natural environments on atopy in children is limited and inconsistent, disregarding the time-varying and cumulative exposures throughout the life course. To assess critical periods of exposure as well as the effect of longitudinal trajectories of exposure to green and blue spaces on the development of allergic sensitization in children at the age of 10 years. A longitudinal study was conducted involving 730 children enrolled in Generation XXI, a population-based birth cohort from the Porto Metropolitan Area (Portugal). Food and aeroallergens sensitization were evaluated at 10 years of age using Phadiatop Infant, Phadiatop fx1 and fx22 ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden). Residential Normalized Difference Vegetation Index (NDVI) and distance to the nearest blue space (sea, river) were assessed using a Geographic Information System. Latent class linear mixed models were fitted to determine longitudinal trajectories of exposure. Associations were estimated using Cox proportional hazards regression models and expressed using hazard ratios (HR) and 95% confidence intervals (95% CI). Residing in neighbourhoods surrounded by more vegetation at 10 years, as well as lifetime exposure to a trajectory of higher levels of NDVI, were associated with a lower risk of allergic sensitization [HR (95% CI) = 0.095 (0.011, 0.823) and HR (95% CI) = 0.539 (0.301, 0.965), respectively]. Our findings support a role for both longitudinal, but particularly late-childhood, exposure to green spaces, in the prevention of allergic sensitization in children.

Cytokine gene polymorphisms in Pigeon Breeder's Disease expression.

BACKGROUND: Exaggerated immunological response to repeated inhalation of organic or chemical dusts may lead to Hypersensitivity Pneumonitis among sensitized individuals. Only a few exposed individuals became ill and disease expression pattern is highly variable which suggest that genetic factors may play a role. AIM: To investigate interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-ß, and IL-10 gene polymorphisms in a cohort of pigeon breeder's disease (PBD) patients in comparison with exposed but healthy controls and the association with different patterns of disease. METHODS: We evaluated 40 PBD patients and 70 exposed controls. IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 polymorphisms were determined by polymerase chain reaction-sequence specific primer amplification. RESULTS: Polymorphism analysis of IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 genotypes and allele frequencies showed no differences between patients and controls. IFN-γ T/T genotype frequency was increased among patients with chronic presentation (RR=2.33, p=0.047) compared with those with acute/subacute presentation. Also, chronic presenting patients had an increased frequency of IFN-γ T allele (50% vs 22.5%, RR=1.76, p=0.011). No differences were found in TNF-α, IL-6, TGF-ß, and IL-10 genotypes neither allelic frequencies between both groups of patients. IL-6 C/C genotype was more frequent in patients who showed chronic evolution (RR=2.54, p=0.017), when comparing with patients with disease resolution. CONCLUSION: IFN-γ T/T and the IL-6 C/C genotypes seem to play a role in HP expression due to avian exposure, as their frequencies are increased in chronic presentations or in those with chronic evolution one year after the initial diagnosis, respectively. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (3): e2020004).

What is the effect of a Mediterranean compared with a Fast Food meal on the exercise induced adipokine changes? A randomized cross-over clinical trial.

BACKGROUND: Adipose tissue-derived adipokines are pro-inflammatory cytokines involved in metabolic-related diseases and can be influenced by diet and exercise. We aimed to compare the effect of a Mediterranean (MdM) compared with Fast Food (FFM) meal on the exercise induced adipokines changes. METHODS: In a double blinded cross over trial, 46 participants were randomly assigned to one of two standardized iso-energy pre-exercise meals: FFM or MdM-type. Three hours after each meal, participants completed a treadmill exercise test (EC). Serum adiponectin, resistin, PAI-1, lipocalin-2/NGAL and adipsin were determined by Luminex magnetic bead immunoassay. Wilcoxon signed rank test compared changes before/after meal and before/after EC and a linear mixed model evaluated the effect of meals on the adipokine response to exercise, adjusted for confounders. RESULTS: Thirty-nine participants (mean age of 25, with a standard deviation of 5 years) completed the trial (56% females). For both interventions, a significant reduction of adipsin after each meal and a significant increase of lipocalin, PAI-1, adipsin and resistin, after exercise was observed. When exercise was preceded by a MdM meal a higher increase in adipsin levels was seen. CONCLUSION: Acute exercise induced an increase of circulatory levels of adipsin, resistin, lipocalin and PAI-1, but not adiponectin. A pre-exercise Mediterranean meal potentiated the increase of adipsin after the exercise test, which possibly relates to the immune regulatory role of adipsin. These changes suggest a cross-talk between the immune and metabolic immediate response to exercise and its modulation by the pre-exercise diet composition.

NK and NKT cells in the diagnosis of diffuse lung diseases presenting with a lymphocytic alveolitis.

BACKGROUND: Diffuse lung diseases (DLD) are characterized by different immunophenotypes in the bronchoalveolar lavage fluid (BALF). We aimed to evaluate the diagnostic value of BALF NK and NKT cell counts of patients with DLD and lymphocytic alveolitis. METHODS: We assessed 202 patients with DLD, who underwent BALF immunophenotyping. Samples were routinely processed by flow cytometry and lymphocyte subsets were compared between patients with sarcoidosis (n = 106), hypersensitivity pneumonitis (HP; n = 53), and other DLDs (n = 43). We compared absolute counts and percentages of NK and NKT cells between patients with HP versus the remaining DLD patients. To assess the accuracy of BALF lymphocyte subsets in the diagnosis of HP, we calculated the respective areas under the receiver operating characteristic curves (AUC-ROC). RESULTS: Patients with HP had significantly higher numbers of BALF NK cells, and its percentage was significantly associated with a higher odds of HP, even after adjustment for the NKT and CD8+ cells. For the absolute number of BALF NK cells, we found an AUC-ROC of 0.76 (95%CI = 0.68-0.84) when comparing patients with HP versus the remaining DLD. The cut-offs of 2000 NK cells/mL and of 2.4% NK cells in the BALF had a specificity and a negative predictive value over 80% for the diagnosis of HP. BALF NK cells absolute counts were significantly higher in HP patients with a restrictive pattern. No such differences were observed for NKT cells. CONCLUSIONS: BALF NK immunophenotyping may be a helpful adjunct to the diagnostic work-up of DLD, particularly in the differential diagnosis of HP.

Meal-exercise challenge and physical activity reduction impact on immunity and inflammation (MERIIT trial).

BACKGROUND: The effect of a pre-exercise meal as countermeasure to exercise induced immunodepression is poorly known. Also, sedentary behavior is associated with increased cardiometabolic risk but studies on immune changes are lacking. Therefore, we aimed to assess: 1) the impact of a pre-exercise Mediterranean meal (MdM) compared with a fast-food type meal (FFM) on exercise-induced immunological changes and 2) the impact of an induced acute period of sedentary behavior on neuro-immune-endocrine status. METHODS: /Design: This is a two steps clinical trial including: (a) randomized crossover clinical trial, comparing the effect a high-fat/low-nutrient dense meal, FFM, with an isoenergetic similar high-nutrient dense meal, MdM, in the immune response to an exercise challenge (EC) and (b) a pilot trial assessing the neuro-immune-endocrine change induced by acute decreasing by half the usual physical activity level. RESULTS: A total of 46 participants (26 females), median aged 25 years were included. Of those 39-completed protocol, including overweight, physical active and inactive and participants with asthma. There were no differences in the EC between interventions. Dietary factors and physical activity were closely monitored during interventions and kept similar. During physical inactivity induction, 31% reached the target of 50% reduction in mean step number and 77% reached a 30% reduction. CONCLUSION: The use of a pre-exercise meal to modulate immune response and the understanding of the immunological impact of physical inactivity might help to establish future recommendations on how to practice exercise in a safer way and to recognize the potential impact of inactivity.

Chitosan Coated Textiles May Improve Atopic Dermatitis Severity by Modulating Skin Staphylococcal Profile: A Randomized Controlled Trial.

BACKGROUND: Atopic dermatitis (AD) patients may benefit from using textiles coated with skin microbiome-modulating compounds. Chitosan, a natural biopolymer with immunomodulatory and antimicrobial properties, has been considered potentially useful. OBJECTIVE: This randomized controlled trial assessed the clinical utility of chitosan-coated garment use in AD. METHODS: Of the 102 patients screened, 78 adult and adolescents were randomly allocated to overnight use of chitosan-coated or uncoated cotton long-sleeved pyjama tops and pants for 8 weeks. The primary outcome was change in disease severity assessed by Scoring Atopic dermatitis index (SCORAD). Other outcomes were changes in quality of life, pruritus and sleep loss, days with need for rescue medication, number of flares and controlled weeks, and adverse events. Changes in total staphylococci and Staphylococcus aureus skin counts were also assessed. Comparisons were made using analysis of variance supplemented by repeated measures analysis for the primary outcome. Interaction term between time and intervention was used to compare time trends between groups. RESULTS: Chitosan group improved SCORAD from baseline in 43.8%, (95%CI: 30.9 to 55.9), P = 0.01, placebo group in 16.5% (-21.6 to 54.6); P = 0.02 with no significant differences between groups; Dermatology Quality of life Index Score significantly improved in chitosan group (P = 0.02) and a significant increase of skin Coagulase negative Staphylococci (P = 0.02) was seen. CONCLUSIONS: Chitosan coated textiles may impact on disease severity by modulating skin staphylococcal profile. Moreover, a potential effect in quality of life may be considered. TRIAL REGISTRATION: ClinicalTrials.gov NCT01597817.

Serum metalloproteinases 1 and 7 in the diagnosis of idiopathic pulmonary fibrosis and other interstitial pneumonias.

INTRODUCTION: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) has important therapeutic and prognostic implications and would be greatly aided by reliable diagnostic biomarkers as IPF has sometimes overlapping features with other interstitial lung diseases (ILD). OBJECTIVES: To explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of IPF with other ILD. METHODS: MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, and compared using the Mann-Whitney U test. RESULTS: MMP-1 was significantly higher in IPF than non-IPF UIP (P = .042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). The Area Under the Curve for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff = 3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values = 52.3% and Negative Predictive Values = 82.4%. CONCLUSIONS: MMP-1 and particularly MMP-7 serum levels were significantly higher in IPF than in non-IPF UIP, the main entity in differential diagnosis. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF diagnosis needs to be considered and further explored.

Differential responses of adiposity, inflammation and autonomic function to aerobic versus resistance training in older adults.

BACKGROUND: Increased body fat, autonomic dysfunction and low-grade chronic inflammation are interrelated risk factors implicated in the etiology of several chronic conditions normally presented by older adults. OBJECTIVE: This study aims to assess the effectiveness of different training protocols on reducing body fat, improving autonomic function, and decreasing low-grade systemic inflammation in community-dwelling elderly adults. METHODS: Fifty participants (11 men, 68±5.5years) were randomly allocated into resistance or aerobic training or control groups. Evaluations were done at baseline and following the 8-month intervention period on their body composition (assessed by DXA), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], tumor necrosis-alpha [TNF-α], interferon-gamma [IFN-γ], interleukins-6 and -10 [IL-6, IL-10]), lipoproteic profile, fasting glycemia, blood pressure, heart rate variability (HRV; frequency and time domains) and aerobic fitness (assessed by six-minute walk distance [6MWD]). A paired t-test was used to detect changes (%Δ=[(post-test score-pretest score)/pre-test score]×100) within groups, while between-group differences were analyzed using the one-way ANOVA or General Linear Models. RESULTS: A significant change (Δ%) both in total (-5.4±6.3% and -3.3±2.9%, respectively) and central body fat (8.9±11.3% and -4.8±4.5%) was observed in resistance and aerobic training groups, respectively; along with a change in resting systolic and diastolic blood pressures (-9.2±9.8% and -8.5±9.6%), heart rate (-4.6±6.5%), hs-CRP (-18.6±60.6%), and 6MWD (9.5±6.9%) in response to aerobic training. CONCLUSIONS: The present findings provide further evidence for the benefits of aerobic and resistance training on reducing body fat. Aerobic training was demonstrated to reduce hs-CRP and blood pressure in community-dwelling elderly participants with no serious medical conditions.

Neurogenic inflammation in allergen-challenged obese mice: A missing link in the obesity-asthma association?

AIM: A number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. METHODS: High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. RESULTS: Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R(2) = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). CONCLUSIONS: Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.