Asthma, obesity and diet

El asma y la obesidad son dos trastornos de gran impacto en la salud pública que han aumentado su prevalencia en los últimos años. Numerosos estudios han relacionado ambas entidades. La mayoría de los estudios prospectivos demuestran que la obesidad es un factor de riesgo para el diagnóstico “de novo” de asma. Además, los resultados de diversos estudios sugieren que así como la ganancia de peso aumenta el riesgo de asma, la pérdida mejora su evolución. En general, los estudios prospectivos encuentran una asociación positiva entre el índice de masa corporal (IMC) basal y el posterior desarrollo de asma, lo que sugiere que es el exceso de peso el que podría favorecer el desarrollo de asma, aunque estos resultados no son tan concluyentes cuando se estudia la asociación entre hiperreactividad bronquial con el IMC. Existen distintos factores que podrían explicar esta asociación. La obesidad es capaz de reducir la compliance pulmonar, los volúmenes pulmonares y el diámetro de de las vías respiratorias periféricas, así como alterar los volúmenes sanguíneos pulmonares y la relación ventilación- perfusión. Además, el aumento del funcionamiento normal del tejido adiposo en sujetos obesos conduce a un estado proinflamatorio sistémico, que produce un aumento de las concentraciones séricas de numerosas citoquinas, fracciones solubles de sus receptores y quimiocinas. Muchos de estos mediadores son sintetizados y secretados por células del tejido adiposo y reciben el nombre genérico de adipocinas, entre las que se incluyen IL-6, IL-10, eotaxina, TNF- , TGF- 1, PCR, leptina y adiponectina. Por último, se han identificado regiones específicas del genoma humano que están relacionadas tanto con el asma como con la obesidad. La mayoría de los estudios apuntan a que la obesidad es capaz de aumentar la prevalencia y la incidencia de asma, aunque este efecto parece ser moderado. El tratamiento de los asmáticos obesos debe incluir un programa de control de peso.Asthma and obesity have a considerable impact on public health and their prevalence has increased in recent years. Numerous studies have linked both disorders. Most prospective studies show that obesity is a risk factor for asthma and have found a positive correlation between baseline body mass index (BMI) and the subsequent development of asthma, although these results are not conclusive when studying the association between airway hyperresponsiveness with BMI. Furthermore, several studies suggest that whereas weight gain increases the risk of asthma, weight loss improves the course of the illness. Different factors could explain this association. Obesity is capable of reducing pulmonary compliance, lung volumes and the diameter of peripheral respiratory airways as well as affecting the volume of blood in the lungs and the ventilation-perfusion relationship. Furthermore, the increase in the normal functioning of adipose tissue in obese subjects leads to a systemic proinflammatory state, which produces a rise in the serum concentrations of several cytokines, the soluble fractions of their receptors and chemokines. Many of these mediators are synthesized and secreted by cells from adipose tissue and receive the generic name of adipokines, including IL-6, IL-10, eotaxin, TNF- , TGF- 1, PCR, leptin y adiponectin. Finally, specific regions of the human genome which are related to both asthma and obesity have been identified. Most studies point out that obesity is capable of increasing the prevalence and incidence of asthma, although this effect appears to be modest. The treatment of obese asthmatics must include a weight control progra

Differences in Inflammatory Cytokine Profile in Obesity-Associated Asthma: Effects of Weight Loss

Obesity and asthma are associated with systemic inflammation maintained by mediators released by adipose tissue and lung. This study investigated the inflammatory serum mediator profile in obese subjects (O) (n = 35), non-obese asthma (NOA) patients (n = 14), obese asthmatics (OA) (n = 21) and healthy controls (HC) (n = 33). The effect of weight loss after bariatric surgery (BS) was examined in 10 OA and 31 O subjects. We analyzed serum markers including leptin, adiponectin, TGF-?1, TNFR2, MCP-1, ezrin, YKL-40, ST2, IL-5, IL-9, and IL-18. Compared with HC subjects, the O group showed increased levels of leptin, TGF-?1, TNFR2, MCP-1, ezrin, YKL-40, and ST2; the OA group presented increased levels of MCP-1, ezrin, YKL-40, and IL-18, and the NOA group had increased levels of ezrin, YKL-40, IL-5, and IL-18. The higher adiponectin/leptin ratio in NOA with respect to OA subjects was the only significant difference between the two groups. IL-9 was the only cytokine with significantly higher levels in OA with respect to O subjects. TNFR2, ezrin, MCP-1, and IL-18 concentrations significantly decreased in O subjects after BS. O, OA, and NOA showed distinct patterns of systemic inflammation. Leptin and adiponectin are regulated in asthma by obesity-dependent and-independent mechanisms. Combination of asthma and obesity does not result in significant additive effects on circulating cytokine levels. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Efficacy and Safety of Reslizumab in Patients with Severe Asthma with Inadequate Response to Omalizumab : A Multicenter, Open-Label Pilot Study

Funding: This study was endorsed by the Asthma Research Program of the Spanish Respiratory Society (PII de Asma de SEPAR) supported by a grant from Teva Pharmaceutical Industries.Background: Patients with severe allergic and eosinophilic asthma could qualify for different biologic therapies. Objective: To evaluate the efficacy and safety of weight-based intravenous reslizumab dosing in patients who have previously failed therapy with omalizumab. Methods: We carried out a 24-week prospective, multicenter, open-label, single-group, self-controlled study in patients with severe eosinophilic asthma who had previously failed to respond to omalizumab. The main objective was to determine whether treatment with reslizumab significantly improved asthma symptoms assessed by the Asthma Control Test (ACT) at week 24. Secondary objectives were to evaluate symptoms at weeks 4 and 12, change in FEV at week 24, and the incidence of severe exacerbations over the study period. Results: Twenty-nine patients (62.1% women, median age, 50.8 years) were included in the study. The median ACT score significantly increased from 13.0 (interquartile range, 8.0-18.0) at baseline to 21.0 (interquartile range, 14.0-24.0) at 24 weeks (P =.002). Only 2 of 29 patients developed at least 1 severe exacerbation during follow-up and none of them required hospitalization. Overall, 15 of 25 patients (60%) were considered as being controlled (ACT score of ≥20 and no exacerbations) at week 24. The percentage of patients who were receiving daily systemic corticosteroids significantly decreased from 72.4% to 52.0% (P =.019). Adverse events were mostly moderate and within the range of previously reported side effects with reslizumab. Conclusion: Reslizumab is an effective and safe option for patients with severe eosinophilic asthma and a history of omalizumab failure

How reliably can algorithms identify eosinophilic asthma phenotypes using non-invasive biomarkers?

Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non-invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely-eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset.We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity.No correlation was found between both classifications 0.025 (CI = 0.013-0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population.In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation.© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

peer reviewedBackground: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non–oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non–OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction. © 202

Platelet-Activating Factor (PAF) in Allergic Rhinitis: Clinical and Therapeutic Implications

Platelet-activating factor (PAF) is a lipid mediator involved in several allergic reactions. It is released from multiple cells of the immune system, such as eosinophils, neutrophils, and mast cells, and also exerts its effect on most of them upon specific binding to its receptor, becoming a pleiotropic mediator. PAF is considered a potential relevant mediator in allergic rhinitis, with a key role in nasal congestion and rhinorrhoea due to its effect on vascular permeability. Interestingly, despite its potential relevance as a therapeutic target, no specific PAF inhibitors have been studied in humans. However, rupatadine, a second-generation antihistamine with dual antihistamine and anti-PAF effects has shown promising results by both blocking nasal symptoms and inhibiting mast cell activation induced by PAF, in comparison to antihistamine receptor drugs. In conclusion, the inhibition of PAF may be an interesting approach in the treatment of allergic rhinitis as part of a global strategy directed at blocking as many relevant inflammatory mediators as possible

Statement of the Spanish Society of Allergology and Clinical Immunology on Provocation Tests With Aspirin/Nonsteroidal Anti-inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated