Browsing by Author "Delgado, Luís"
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- Comprehensive assessment of environmental fungus-reactive T cells response in hypersensitivity pneumonitis patientsPublication . Santos, Rita F.; Coelho, Andreia L.; Rufo, João C.; Coelho, David; Gonçalves, Melany; Gonçalves, Samuel L.; Cunha, Cristina; Carvalho, Agostinho; Delgado, Luís; Morais, António; Saraiva, Margarida; Novais-Bastos, HélderHypersensitivity pneumonitis (HP) is an interstitial lung disease that results in parenchymal and small airways inflammation and culminates in breathlessness, negatively impacting patient’s quality of life and survival. HP is initiated by an exaggerated immune response triggered by the inhalation of a variety of environmental antigens. The identification of the triggering antigen is a cornerstone of the diagnostic algorithm, and importantly, exposure avoidance ameliorates the clinical outcomes. However, the inciting antigen is not identified in a large proportion of patients. A difficult to identify, but common inciting antigen, is exposure to household fungi.
- Disentangling the heterogeneity of allergic respiratory diseases by latent class analysis reveals novel phenotypesPublication . Amaral, Rita; Bousquet, Jean; Pereira, Ana M.; Araújo, Luís M.; Sá‐Sousa, Ana; Jacinto, Tiago; Almeida, Rute; Delgado, Luís; Fonseca, João A.Background Refined phenotyping of allergic diseases may unravel novel phenotypes. Conjunctivitis as an independent disorder has never been approached. Aim To identify distinct classes of allergic respiratory diseases using latent class analysis (LCA) and distinguish each class using classification and regression tree (CART) analysis. Methods Seven hundred and twenty‐eight adults from the Portuguese general population study ICAR had a structured medical interview combined with blood collection, skin prick tests, spirometry with bronchodilation, and exhaled nitric oxide. LCA was applied to 19 variables. The CART algorithm selected the most likely variables distinguishing LCA‐classes. Results A six‐class model was obtained. Class 1 (25%): nonallergic participants without bronchial or ocular symptoms. Classes 2 (22%) and 3 (11%): nasal and ocular (low levels) symptoms without nasal impairment, monosensitized (Class 2) or polysensitized (Class 3). Class 4 (13%): polysensitized participants with high levels of nasal and ocular symptoms, and nasal impairment. Classes 5 (16%) and 6 (14%): high level of nasal, bronchial and ocular symptoms with nasal impairment (non‐allergic or polysensitized, respectively). Participants in classes 5 and 6 had more bronchial exacerbations and unscheduled medical visits (P < 0.001). Ocular symptoms were significantly higher in classes with nasal impairment, compared to those without impairment (P < 0.001) or no nasal symptom (P < 0.001). CART highlighted ocular symptoms as the most relevant variable in distinguishing LCA‐classes. Conclusion Novel severe phenotypes of participants with co‐occurrence of ocular, nasal and bronchial symptoms, and exacerbation‐prone were identified. The tree algorithm showed the importance of the ocular symptoms in the expression of allergic diseases phenotypes.
- Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association?Publication . Ramalho, Renata; Almeida, Joana; Beltrão, Marília; Pirraco, Ana; Costa, Raquel; Sokhatska, Oksana; Guardão, Luísa; Palmares, Carmo; Guimarães, João Tiago; Delgado, Luís; Moreira, André; Soares, RaquelA 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. 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. 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, R2 = 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). 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.
- Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotypePublication . Ramalho, Renata; Almeida, Joana; Fernandes, Rúben; Costa, Raquel; Pirraco, Ana; Guardão, Luísa; Delgado, Luís; Moreira, André; Soares, RaquelAims Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice. Main methods Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1 +) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings Obesity and allergen-sensitization together increased the number of LYVE-1 + lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.
- Unveiling common molecular pathways linked to ILDs with progressive fibrosing phenotype: the role of MUC5BPublication . Santos, Rita F.; Gonçalves, Melany; Mota, Patrícia Caetano; Cardoso, Catarina Gouveia; Coelho, Andreia L.; Sokhatska, Oksana; Beltrão, Marília; Guimarães, Susana; Delgado, Luís; Soares, Miguel; Morais, António; Saraiva, Margarida; Bastos, Hélder NovaisProgressive fibrosing ILDs (PF-ILDs) comprise a heterogeneous group of lung disorders associated with high morbidity and mortality, that exhibit a continuous worsening phenotype despite standard treatment. Among PF-ILDs are pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (HP), involving complex interactions between host genetics and different environmental triggers, shaping the immune milieu that ultimately drives the fibrotic cascade in a susceptible patient. The MUC5B promoter variant rs35705950 is the common genetic variant associated with the greatest risk of developing IPF. As IPF and fibrotic HP present phenotypic resemblances, we aim to analyze the role of rs35705950 MUC5B single nucleotide polymorphism (SNP) in common molecular pathways linked to PF-ILDs. Herein, taking advantage of our extensive ILD patients’ cohort, we found that MUC5B rs35705950 GT and TT genotypes frequency was dramatically increased in IPF and fibrotic HP compared to healthy controls.