Molecular T2 asthma phenotypes are stable but heterogeneous: the usefulness of periostin for endotyping.

Background: The stability of molecular T2/non-T2 phenotypes remains uncertain. The objectives of this study were to assess the stability of these phenotypes and the correlation between serum periostin and asthma T2 phenotypes and endotypes. Methods: Demographics, clinical data, and blood samples were collected. Patients diagnosed with moderate-to-severe asthma were classified into T2 or non-T2 according to previously defined thresholds of blood eosinophilia and serum total IgE levels. Asthma endotype was also determined. After at least 1 year of follow-up, the stability of T2 phenotypes and endotypes was assessed. Results: A total of 53 patients (72% women), mean age 47 years (range 16-77), were included. In the initial and second evaluations, the T2 phenotype was found in 41.5% and 43.4% of patients and the non-T2 phenotype was found in 58.4% and 56.7%, respectively. The mean [standard deviation (SD), range] serum periostin level was 52.7 (26.2, 22.6-129.7) ng/mL in patients with T2 phenotype, and 39.3 (25.6, 7.7-104.) ng/mL in non-T2 patients (P = 0.063). Periostin levels correlated to endotypes (P = 0.001): 45.7 (27.9) ng/mL in allergic asthma (n = 16 patients), 64.7 (24.9) in aspirin-exacerbated respiratory disease (n = 14), 59.0 (27.6) ng/mL in late-onset eosinophilic asthma (n = 4), and 28.3 (13.3) ng/mL in non-eosinophilic asthma (n = 18). Conclusions: T2 and non-T2 asthma phenotypes assessed by accessible methods in daily practice are stable over time yet widely heterogeneous. Serum periostin does not discriminate between T2 and non-T2 phenotypes. Nevertheless, its correlation to asthma endotypes may contribute to guide therapies targeting T2 cytokines in a more personalized approach.

[Girl with hypersensitivity pneumonitis. A case report]. / Niña con neumonitis por hipersensibilidad. Reporte de un caso.

BACKGROUND: Hypersensitivity pneumonitis entails several inflammatory lung diseases that preferentially affect the alveolar and perialveolar tissue. It is a very rare disease in children, with a complicated diagnosis due to the fact that antigen exposure usually goes unnoticed. CASE REPORT: A 12-year-old girl with dry cough, dyspnea, wheezing, and tachypnea, with partial improvement after treatment with inhaled bronchodilators and corticoids. The spirometry showed a restrictive pattern and reduced lung diffusion capacity; in the CT scan, centrilobular ground-glass opacities were observed, and a lymphocyte count of CD4/CD8 of 2.46 (lymphocytosis) was obtained from the bronchoalveolar lavage. IgG positivity to bird feathers was obtained. CONCLUSIONS: The treatment of hypersensitivity pneumonitis is based on avoiding exposure to the causative agent, which is determined by the prognosis; for which taking an extensive medical history is of paramount importance. Corticosteroids can be prescribed based on the clinical response, the pulmonary function, and the radiological improvement.

Antecedentes: La neumonitis por hipersensibilidad agrupa varias enfermedades inflamatorias pulmonares que afectan preferentemente el tejido alveolar y perialveolar. En niños se trata de una enfermedad muy rara, con diagnóstico complicado debido a que la exposición antigénica suele pasar desapercibida. Caso clínico: Niña de 12 años que presentaba tos seca, disnea, sibilancias y taquipnea con mejoría parcial al tratamiento con broncodilatadores y corticoides inhalados. En la espirometría presentó un patrón restrictivo y una capacidad de difusión pulmonar reducida; en la tomografía computarizada se observaron opacidades centrolobulillares en vidrio esmerilado y del lavado broncoalveolar se obtuvo un cociente de linfocitosis CD4/CD8 de 2.46. Se obtuvo IgG positiva a plumas de aves. Conclusiones: El manejo de la neumonitis por hipersensibilidad se basa en evitar la exposición al agente causante, lo que determina el pronóstico; de ahí que resulta de vital importancia realizar una historia clínica exhaustiva. Pueden indicarse corticosteroides en función de la respuesta clínica, la función pulmonar y la mejoría radiológica.

Fish muscle processing into seafood products reduces ß-parvalbumin allergenicity.

Fish is one of the eight major foods causing type-I food allergy, and the prevalence of its allergy is increasing in part due to changes in consumption habits. One of the main drivers for these changes has been the processing developments transforming the fish muscle into seafood products. Most fish allergic patients react to the Ca2+-binding protein ß-parvalbumin (ß-PV) abundant in muscle. Here we have analyzed the effect of processing in the content and allergenic properties of the ß-PV. We found that the transformation process decreases the ß-PV content (4.7 ± 0.3 mg/g muscle, 0.24 ± 0.03 mg/g surimi, ≤0.003 ± 0.001 mg/g in seafood products), reduces the specific-IgE binding and prevents allergy relevant properties such the protease resistance and amyloid aggregation. These results suggest seafood products as potentially tolerable foods for fish allergic patients, but milk and egg allergic patients should be aware of the presence relevant additives.

In Search of an Association Between Genotype and Phenotype in Hereditary Angioedema due to C1-INH Deficiency.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is caused by mutations affecting the SERPING1 gene. Adult patients (≥ 18 years old) diagnosed with C1-INH-HAE were clustered according to a modified SERPING1 gene mutation classification [5]. Demographic, clinical, and laboratory data were studied. Published manuscripts on the genotype/phenotype relationship were reviewed. Eighty-eight patients participated in the study, with 78 having a classifiable mutation. We compared the data in the 3 largest groups: class 0 only (n = 32), class II only (n = 18), class III only (n = 22). Antigenic C4 and C1 inhibitors were higher in class II (p = 0.008 and p = 0.02, respectively), and facial attacks in the last 6 months were more frequent in class III (p = 0.04)). All the other differences were non-significant. Twelve manuscripts on phenotype/genotype correlation were found: missense mutations in SERPING1 gene were associated with delay in disease onset and lower severity score in some studies, whereas the CC F12-C46T/C polymorphism produced earlier disease onset. Our study shows minimal differences regarding clinical phenotype in patients with class 0, II, and III SERPING1 gene mutations, with a tendency to class III having a more severe phenotype. The study should be performed in a larger sample to confirm if they are significant.We propose that larger multicenter, international studies are performed, comparing different SERPING1 gene mutation classifications, combining polymorphisms in other involved genes (kallikrein-kinin system, regulation of vasculature, plasminogen activation) and using different variables and clinical scores to assess C1-INH-HAE disease activity and/or severity in order to study possible genotype/phenotype relationships.

Quercus ilex pollen allergen, Que i 1, responsible for pollen food allergy syndrome caused by fruits in Spanish allergic patients.

BACKGROUND: Pollen food allergy syndrome (PFAS) related to PR10 from vegetables is common in northern Europe, whereas in Mediterranean countries PFAS has been preferentially associated with profilins. However, there are pollen-allergic patients reactive to Bet v 1 in birch-free regions. Since it cannot be the primary sensitizer, there has to be another culprit. Quercus ilex is a good candidate as it belongs to the order Fagales. This order includes trees with highly sensitizing pollen such as alder, hazel, hornbeam, oak and chestnut because of the presence of PR10 allergens. PR10 allergens have indeed been described in other Quercus species. OBJECTIVE: Our goals were to determine the rate of sensitization to Q. ilex in central Spain and the associated frequency of PFAS; secondly to identify and clone the Q. ilex allergen PR10. METHODS: We included 224 allergic patients with respiratory symptoms to estimate the rate of sensitization. A skin prick test (SPT) and ImmunoCAP were performed. A total of 38 Q. ilex-sensitized patients were tested using Western blotting to determine the rate of Que i 1. Peptides from Que i 1 were analysed by MALDI-TOF/TOF and Orbitrap LC-MSMS. The Que i 1 sequence was first obtained from the Holm oak transcriptome then cloned and expressed in bacteria. RESULTS: 59.8% of pollen-allergic children were sensitized to Q. ilex. We described and cloned the Q. ilex PR10, Que i 1, which has a sensitization rate of 60.5% and was recognized by 65.4% patients reporting PFAS. CONCLUSION AND CLINICAL RELEVANCE: Sensitization to Q. ilex pollen has increased significantly since 1995. This sensitization could be important, as the presence of PFAS in this population is higher than in patients not sensitized to Q. ilex. The first Q. ilex allergen has been described and is related to PFAS in Spanish patients sensitized to PR10 but not exposed to birch pollen.

Tranexamic acid plus bemiparin sodium as long-term prophylaxis in a patient with FXII-HAE during pregnancy: a case report

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[When education in asthma is crucial. About a case]. / Cuando la educación en asma es crucial. A propósito de un caso.

BACKGROUND: Childhood asthma causes frequent hospitalizations and visits to the emergency room because of exacerbations that could be avoided if the disease is managed properly. CLINICAL CASE: A 6-year-old girl who has had asthma since her first 16 months of life. She had been taken 130 times to the emergency room; she had been hospitalized 22 times, and she had received numerous medical consultations for asthma. She had never received structured health education, therefore, she was misusing the inhalation devices, and the controller treatment for bronchial inflammation was clearly below the dose according to the level of severity of the disease. There was an intervention focused on health education, an increase in the dose of anti-inflammatory drugs to treat bronchial asthma, and instruction in the proper use of inhaled medications. Since the intervention was made, the patient achieved better control without requiring visits to the emergency room, hospital admissions, or systemic corticosteroids after two years of follow-up. CONCLUSION: The lack of health education about asthma causes insufficient control of the disease. In the therapeutic approach to patients with severe uncontrolled asthma, it is essential to apply structured procedures of health education.

Antecedentes: El asma infantil ocasiona frecuentes hospitalizaciones y visitas a urgencias por exacerbaciones que podrían ser evitadas con el manejo apropiado de la enfermedad. Caso clínico: Niña de seis años con asma desde los 16 meses de vida. Fue llevada 130 veces al servicio de urgencia, 22 veces fue hospitalizada y recibió otras numerosas consultas médicas por asma. Nunca había recibido educación sanitaria estructuradamente, de manera que utilizaba los dispositivos de inhalación inadecuadamente y el tratamiento controlador de la inflamación bronquial estaba claramente por debajo de la dosis correspondiente al grado de gravedad de su asma. Se realizó una intervención centrada en la educación sanitaria, incremento de la dosis de medicamentos antiinflamatorios bronquiales e instrucción en el uso adecuado de la medicación inhalada. A partir de la intervención, la paciente alcanzó un mejor control sin requerir nuevamente visitas a urgencias, ingresos hospitalarios ni corticoides sistémicos, tras dos años de seguimiento. Conclusiones: La falta de educación sanitaria en asma ocasiona control insuficiente de la enfermedad. En el acercamiento terapéutico al paciente con asma grave no controlada resulta imprescindible aplicar procedimientos estructurados de educación sanitaria.