Exhaled breath condensate pH determinants in school-aged children: A population-based study.

BACKGROUND: Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. METHODS: A cross-sectional analysis of exhaled breath condensates from 613 children, aged 7-12 years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5 school days. Post-deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. RESULTS: Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [ß = -0.09 (-0.15, -0.02)] and PM 2.5 concentration [ß = -0.16 (-0.32, -0.01)], and in the alkaline group by relative humidity [ß = 0.07 (0.02, 0.13)] and concentration of endotoxins [ß = -0.06 (-0.1, -0.01)]. CONCLUSION: Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis.

BACKGROUND: Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. OBJECTIVE: To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. METHODS: A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. RESULTS: Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1ß (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. CONCLUSIONS: SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

Mast Cell Activation Syndromes: Comparison Between Two Scoring Models to Predict for Mast Cell Clonality.

BACKGROUND: The Red Española de Mastocitosis (Spanish Network on Mastocytosis) score (REMAs) and the National Institutes of Health idiopathic clonal anaphylaxis score (NICAS) were developed for more efficient screening of mast cell (MC) clonality in MC activation syndromes. In a limited idiopathic anaphylaxis case series, the NICAS showed higher accuracy compared with the REMAs. OBJECTIVE: To compare the performance of the REMAs against the NICAS in the diagnosis of MC clonality. METHODS: We compared the diagnostic value of the REMAs against the NICAS in 182 patients (63% men, median age 56 years) who presented with anaphylaxis triggered by Hymenoptera venom allergy (45%), drugs (15%), food (11%), idiopathic anaphylaxis (20%), and mixed causes (10%). KIT mutation was assessed in parallel in whole blood and bone marrow (BM) and, when negative, in highly purified BM MC. TPSAB1 was genotyped in a subset of 71 patients. RESULTS: We found higher accuracy and rates of correctly classified patients for the REMAs (82% and 84%) compared with the NICAS (75% and 75%; P = .02 and P = .03, respectively), particularly among men (P = .05), patients with systemic mastocytosis (P = .05), those presenting anaphylaxis owing to any cause featuring urticaria (P = .04), cardiovascular symptoms (P = .02), and/or presyncope (P = .02) and those with a blood-negative/BM-positive KIT mutational profile (P = .002), but not hereditary α-tryptasemia-associated genotypes. Combined assessment of the REMAs and KITD816V in blood yielded an overall improved classification efficiency of 86% versus 84% for REMAs. CONCLUSIONS: The combined use of the REMAs and blood detection of KITD816V is recommended, but more sensitive blood-based molecular assays to detect KITD816V are needed.

Anisakis Allergy: Raising Awareness.

INTRODUCTION: Ingestion of Anisakis is a common cause of allergic reactions to seafood in countries in which undercooked/raw seafood is part of gastronomic traditions. Despite current trends for the ingestion of raw/marinated/undercooked fish, the prevalence rate of anisakiasis and allergy to Anisakis is still considered to be low in Portugal. We aimed to review the current pathogenic mechanisms, the clinical and diagnostic approach of Anisakis allergy, and Anisakis-related eviction measures, while raising awareness to this problem. MATERIAL AND METHODS: Literature search in the MEDLINE and Scopus databases, regarding Anisakis allergy. CONCLUSION: Assessment of sensitization to Anisakis should be included in the workup study of urticaria/angioedema and anaphylaxis, as there is a rise in consumption of raw and undercooked fish. Ingestion of previously frozen and properly cooked fish appears to be safe for most patients who are allergic to Anisakis.

Introdução: A ingestão de Anisakis é uma causa frequente de alergia a pescado, em países onde o hábito de ingerir estes alimentos crus/pouco cozinhados faz parte das tradições gastronómicas. Apesar do aumento na frequência de ingestão de peixe cru/marinado/pouco cozinhado que se verifica em Portugal, a prevalência de anisaquíase e alergia ao Anisakis continua a ser considerada como sendo baixa. O nosso objectivo foi rever os mecanismos fisiopatológicos da alergia a Anisakis, a abordagem clínica e diagnóstica, e as medidas de evicção de Anisakis. Em simultâneo, pretendemos consciencializar para este problema de saúde crescente. Material e Métodos: Foi efetuada uma pesquisa e revisão bibliográfica nas bases de dados MEDLINE e Scopus, sobre alergia ao Anisakis e anisaquíase. Conclusão: A avaliação da sensibilização ao Anisakis deve ser incluída no estudo inicial da urticária/angioedema e anafilaxia, dado que o consumo de peixe cru e malcozinhado está a aumentar. A ingestão de peixe previamente congelado e sujeito a uma cocção correta parece ser segura para a grande maioria dos doentes alérgicos ao Anisakis.

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication.

Reported cases of anaphylaxis following COVID-19 vaccination raised concerns about the safety of these vaccines, namely in patients suffering from clonal mast cell (MC) disorders-a heterogenous group of disorders in which patients may be prone to anaphylaxis caused by vaccination. This study aimed to assess the safety of COVID-19 vaccines in patients with clonal MC disorders. We performed an ambidirectional cohort study with 30 clonal MC disorder patients (n = 26 in the prospective arm and n = 4 in the retrospective arm), that were submitted to COVID-19 vaccination. Among these, 11 (37%) were males, and median age at vaccination date was 41 years (range: 5y to 76y). One patient had prior history of anaphylaxis following vaccination. Those in the prospective arm received a premedication protocol including H1- and H2-antihistamines and montelukast, while those in the retrospective arm did not premedicate. Overall, patients received a total of 81 doses, 73 under premedication and 8 without premedication. No MC activation symptoms were reported. COVID-19 vaccination seems to be safe in patients with clonal mast cell disorders, including those with prior anaphylaxis following vaccination. Robust premedication protocols may allow for vaccination in ambulatory settings.

Supply of Antioxidants vs. Recruit Firefighters' Cellular Immune Status: A Randomized Double-Blinded Placebo-Controlled Parallel-Group Trial.

Background: Physical exercise can affect the immune system. We studied the effect of antioxidants on hematological and immune biomarkers after heavy training. Methods: 24 well-trained and well-fed male firefighters were randomly divided into supplemented and placebo groups, and tested for immunology-related variables using venous blood samples in the fasting state, pre- (M1) and post- (M2) five weeks of daily micronutrient supplementation (15 mg of beta-carotene, 200 mg of vitamin C, 136 mg of vitamin E, 200 µg of selenium, 15 mg of zinc, 100 mg of magnesium). Total leukocytes and a differential count for five populations were determined using standard procedures (MAXM­Beckman Coulter Diagnostics; Brea, CA, USA). Lymphocyte subsets were determined through immunophenotyping. Results: Although all values were within the normal range for healthy adults and athletes in the supplemented group (SG), mean CD3+CD8+, CD8+ and CD16+CD56+ decreased (p < 0.05; small to moderate effects), while mean CD4+, CD19+ and CD4+/CD8+ increased (p < 0.05; small effects) after five-weeks. Regarding the placebo group (PG), higher total leukocyte count (p < 0.05; trivial effect) and natural killer cells percentage (CD16+CD56+; p < 0.05; moderate effect) were observed when comparing M1 and M2. Conclusions: Antioxidants supplementation did not alter well-fed male firefighters recruit firefighters' immune cell response during the five-week physical training program.

Mastocytosis presenting with mast cell-mediator release-associated symptoms elicited by cyclo oxygenase inhibitors: prevalence, clinical, and laboratory features.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently avoided in mastocytosis, because of a potential increased risk for drug hypersensitivity reactions (DHRs) due to inhibition of cyclo-oxygenase (COX), subsequent depletion of prostaglandin E2 and release of leukotrienes. OBJECTIVES: Here, we aimed at determining the prevalence of mast cell (MC) mediator release symptoms triggered by NSAIDs in mastocytosis patients and the associated clinical and laboratory features of the disease. METHODS: Medical records from 418 adults to 223 pediatric mastocytosis patients were retrospectively reviewed. Patients were classified according to tolerance patterns to NSAIDs and other COX inhibitors (COXi) and compared for epidemiological, clinical and laboratory findings. RESULTS: Overall, 87% of adults and 91% of pediatric patients tolerated NSAIDs and other COXi. Among adult and pediatric patients presenting DHRs, 5% and 0% reacted to multiple NSAIDs, 4% and 0.7% were single reactors, and 3% and 8% were single reactors with known tolerance to paracetamol but unknown tolerance to other COXi, respectively. Among adults, hypersensitivity to ≥2 drugs was more frequent among females (p = 0.009), patients with prior history of anaphylaxis to triggers other than NSAIDs or other COXi and Hymenoptera venom (p = 0.009), presence of baseline flushing (p = 0.02), baseline serum tryptase ≥48 ng/ml (p = 0.005) and multilineage KIT mutation (p = 0.02). In contrast, tolerance to NSAIDs and other COXi was more frequent among males (p = 0.02), in patients with anaphylaxis caused by Hymenoptera venom (p = 0.02), among individuals who had skin lesions due to mastocytosis (p = 0.01), and in cases that had no baseline pruritus (p = 0.006). Based on these parameters, a score model was designed to stratify mastocytosis patients who have never received NSAIDs or other COXi apart from paracetamol, according to their risk of DHR. CONCLUSIONS: Our results suggest that despite the frequency of MC mediator related symptoms elicited by NSAIDs and other COXi apart from paracetamol is increased among mastocytosis patients versus the general population, it is lower than previously estimated and associated with unique disease features. Patients that tolerated NSAIDs and other COXi following disease onset should keep using them. In turn, adults with unknown tolerance to such drugs and a positive score should be challenged with a preferential/selective COX-2 inhibitor, while the remaining may be challenged with ibuprofen.

Case Report: Mastocytosis: The Long Road to Diagnosis.

Mastocytosis is a heterogeneous group of disorders characterized by expansion and accumulation of clonal mast cells. Patients mainly present with either cutaneous lesions, anaphylaxis, or both. Its low prevalence and unusual features often hinder its diagnosis for several years. We report the case of an 18-year-old male who was referred to our department with a long-standing history of atypical skin lesions, allergic rhinitis, exercise-induced bronchoconstriction and what was believed to be food-related flushing and anaphylaxis, that was later diagnosed with mastocytosis. This case illustrates the need to consider investigating for mastocytosis when recurrent anaphylaxis is present, especially in the presence of atypical skin lesions, even if normal serum basal tryptase levels and allergic sensitization are present.