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- Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitisPublication . Mota, P.C.; Soares, M.L.; Ferreira, A.C.; F. Santos, Rita; Cavaleiro Rufo, J; Vasconcelos, D.; Carvalho, A.; Guimarães, S.; Vasques-Novo, F.; Cardoso, C.; Melo, N.; Alexandre, A.T.; Coelho, D.; Novais-Bastos, H.; Morais, A.Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fH. A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73–27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.
- The impact of war on asthma, a systematic review and meta-analysis: An EAACI task force reportPublication . Rufo, João Cavaleiro; Paciência, Inês; Jutel, Marek; Moreira, André; Annesi-Maesano, Isabella; Suojalehto, Hille; Zemelka-Wiącek, Magdalena; Trikamjee, Thulja; Demir, Semra; Eguíluz-Gracia, Ibon; Carvalho, Daniela; Backland, Anaïs; Lawson, Josh; Cavaleiro Rufo, JoãoWartime events have been followed by an increase in asthma prevalence, which is believed to result from a combination of environmental hazards and psychological trauma. This systematic review and meta-analysis aimed to investigate this relationship by pooling available data on various wartime exposures, such as occupational, environmental, and psychological factors. MEDLINE, Scopus, and Cochrane databases were searched for articles that measure the effect of war-related exposures on asthma. Risk of bias was assessed using the Effective Public Health Practice Project tool. The retrieved effects were then used to fit meta-analytical models. A total of 48 studies, corresponding to 90 effect measures, were included. War-related post-traumatic stress disorder showed the strongest association with asthma outcomes (OR [95% CI]=2.25 [1.04, 4.89]), followed by experiencing at least one life-threatening event (1.96 [1.18, 3.26]) and depression (1.56 [1.02, 2.37]). Although environmental exposures were also associated with an increased asthma risk in subgroup analysis (1.64 [1.32, 2.04]), this effect was mitigated when psychological variables were included in the models. The study's results show that wartime events and conflicts may increase asthma prevalence and outcomes associated with asthma. The management of asthma symptoms, lung function, and mental health seems fundamental in individuals who have experienced psychological trauma in war zones.
- Editorial comments on “Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity”Publication . Rufo, João Cavaleiro; Chauhan, Jitesh; Kalayci, Ömer; Eigenmann, Philippe; Cavaleiro Rufo, JoãoThe clinical associations between asthma and obesity remain poorly understood. The increasing prevalence ofboth conditions occurring may represent a modern clinical paradox. It is unclear whether reduced physical activ-ity in children with asthma leads to obesity, or if asthma-like symptoms in obese children result directly from theassociated excessive abdominal fat, impaired lung function, and heightened Th2 inflammation. Determining theetiology of both diseases and their interconnection is therefore an important research avenue.A recent study has sought to investigate this through a cross-sectional analysis of Australian children, bothwith and without asthma, examining their levels of physical activity. Interestingly, the study found no evidencethat asthma hindered physical activity.1 On the other hand, although most studies have shown obesity is linkedto a higher risk of asthma, the exact mechanism remains unclear. Many studies refer to obesity as an exacerbationfactor for asthma symptoms rather than a direct contributor to the underlying pathophysiological mechanisms ofasthma. 2 This highlights the need for continued research to untangle the complex interplay between these twoconditions.In 2019, a study investigating the associations between exposure to endocrine-disrupting chemicals andchildhood asthma identified a specific pattern of volatile organic compounds that were significantly linked to theearly onset “obese-asthma” phenotype, but not to asthma or obesity independently. 3 This suggests that asthmaand obesity may share common risk factors that trigger disease onset of both conditions during early childhood.Supporting this hypothesis, subsequent research has identified 29 genes associated with the obese-asthma phe-notypes, including GBP5 and SOCS, which further highlights the genetic underpinnings of this dual condition. 4In this issue, Manell et al. offer valuable insights by investigating novel plasma protein biomarkers specificallyassociated with the coexistence of asthma and obesity in an adolescent population. 5 The cross-sectional studyinvolved 390 children and adolescents, aged 10 to 19, who were categorized into four groups: healthy controls,individuals with asthma, individuals with obesity, and those with both obesity and asthma (OA).A proximity extension assay was used to assess the relative plasma concentrations of 113 proteins associatedwith inflammation and immune response. The study identified five plasma proteins—CCL8, IL-33, IL-17C, FGF-23,and CLEC7A—that were significantly and specifically elevated in the OA group compared to controls. However,after adjusting for age, sex, and sIgE levels, only CCL8 and CLEC7A remained significantly elevated. This suggeststhat the high levels observed for IL-33, IL-17C, and FGF-23 in the OA group may be partially attributable to atopy.Drawing on previously published evidence and considering the role of CCL8 in mucosal chemotaxis and Th2inflammation, Manell et al. propose that viral defense at mucosal barriers may play an important role in obesity-related asthma in children and adolescents. 5 While the exact pathophysiological mechanism behind CCL8 over-expression remains unclear, it is noteworthy that prior studies have confirmed no association between CCL8and atopy. 6 This, along with the evidence that CCL8 levels are regulated in obese individuals without asthma,strengthens the argument for this chemokine as a promising biomarker for obese-asthma phenotypes.Additionally, FGF-23, IL-17C, and IL-33, which are linked to mucosal host defense against viral infections andTh17 cell activation, were also regarded as potential biomarkers for concomitant asthma and obesity, though toa lesser extent. 5 Conversely, the elevated levels of CLEC7A in the OA group appear to be additive, reflecting thecombined effects of asthma and obese observed separately.
- Potenciais riscos para a saúde dos trabalhadores decorrentes da exposição a corantes sintéticos e naturais na indústria têxtilPublication . Ramos, Cristiana; Martins, Rosário; Rufo, João; Freitas, Marisa; Martins, Rosario; Cavaleiro Rufo, João; Freitas, MarisaA Indústria Têxtil (IT) apresenta um elevado impacte ambiental, sendo a etapa de tingimento particularmente crítica devido à poluição causada pelos componentes utilizados, nomeadamente pelos corantes sintéticos. A reintrodução de corantes naturais pode constituir uma alternativa face ao uso de corantes sintéticos, no entanto, o conhecimento dos seus potenciais efeitos para a saúde dos trabalhadores é ainda limitado, devido a escassez de investigação sobre o tema. Aprofundar o conhecimento sobre os potenciais riscos associados à exposição dos trabalhadores a corantes sintéticos e naturais, através da integração de dados de efeitos na saúde reportados pelos trabalhadores, monitorização ambiental e avaliação toxicológica in vitro. O estudo foi desenvolvido na área de tingimento de 3 empresas do setor têxtil e com uma amostra de 33 profissionais. Foi solicitado aos profissionais o preenchimento de um questionário para a caracterização dos potenciais efeitos na saúde. Nas áreas de pesagem de corantes, foi realizada a monitorização ambiental de parâmetros físico químicos, nomeadamente de PM10 e PM2,5. A avaliação da toxicidade in vitro de corantes sintéticos e naturais realizou-se em linhas celulares representativas da pele (HaCaT, 3T3-L1 e B16F10). Os resultados relativos aos potenciais efeitos na saúde reportados pelos trabalhadores demonstraram que 30.3% apresentam tosse matinal, dos quais 20% referiram agravamento no local de trabalho. Além disso, 42.4% dos trabalhadores manifestam ter eczema, sendo que 57.1% destes referiram agravamento no local de trabalho. A monitorização ambiental revelou concentrações elevadas de PM10 e PM2.5 nas áreas de pesagem de corantes e picos de concentração associada à pesagem dos corantes da classe reativos. Os ensaios de viabilidade celular revelaram que a maioria dos corantes sintéticos induziu citotoxicidade para as linhagens HaCaT e B16F10 (500µg/mL e 250µg/mL). Os corantes naturais apresentaram uma taxa de viabilidade celular maior (entre os 80%). Este estudo preliminar proporciona uma visão dos potenciais riscos à saúde enfrentados pelos trabalhadores expostos a corantes sintéticos e naturais. A monitorização ambiental nas áreas de pesagem de corantes, combinada com a recolha sistemática de sintomas reportados pelos trabalhadores, torna-se importante para compreensão dos riscos e apoio no desenvolvimento de estratégias de prevenção.
- Movement behaviours, air pollution and health in school-aged children: a cross-sectional study to guide the co-creation of healthier environments – the MOVE-AIR projectPublication . Martins, Clarice; Rufo, João Cavaleiro; Fonseca, Hélder; Padrão, Ana; Baptista, Liliana C.; Santos, Maria Paula; Sousa, Miguel; Zacca, Rodrigo; Silva, José Pedro; Ribeiro, Ana Isabel; Cavaleiro Rufo, JoãoThe MOVE-AIR study was designed to explore the moderating role of movement behaviours on the association between air pollutants and health outcomes in Portuguese children. Secondarily, it aims to characterise the settings (both indoor and outdoor) where children are exposed to air pollutants and to co-create solutions with participants to mitigate the exposure to air pollutants in children’s daily life. This study aims to describe the MOVE-AIR study protocol in detail. Data from 52 primary school children aged 9–11 years will be assessed for indoor and outdoor air pollutants (particulate matter (PM)2.5 and PM10, and carbon dioxide), geo-tracked for distinct settings (ie, home/school, indoor/outdoor) along the day, through an optical monitoring sensor with Global Positioning System incorporated. Health-related biological outcomes, such as interleukin-6, tumour necrosis factor alpha and oxidative parameters, including total antioxidant status and total oxidant status, will be evaluated and the Oxidative Stress Index will be calculated. Children’s cardiopulmonary fitness will be assessed through the shuttle run test, and movement behaviours will be evaluated through accelerometers (wGT3X). Children’s sex, age and parental socioeconomic status will be provided by parents through a questionnaire. The influence of movement behaviours in the link between pollution and health will be analysed through moderating regression models using process for SPSS R software (V.30.0.0). A subsample of class teachers, school leaders, parents and children will be invited to a co-creation process to create solutions to mitigate their daily exposure to air pollutants. The results will contribute to further understanding the moderating role of movement behaviours in the association between air pollution and health, adding a biological layer to the mechanistic links underlying these potential relationships that have not been explored in this target population. Finally, enhancing our comprehension of the living environments and contexts where children are more exposed to air pollution can help to cooperatively create solutions to mitigate their daily exposure to those harmful pollutants.
- Fungal-mediated biodegradation of microplastics: Evaluation of degradative potential and pathogenic traitsPublication . Barbosa, Joel; Fernandes, Virgínia Cruz; Rufo, João; Vieira, Mónica; Prudêncio, Cristina; Pereira, Clara; Fernandes, Virgínia; Cavaleiro Rufo, João; Almeida Vieira, Mónica Andreia; Prudêncio, CristinaThe increasing accumulation of plastics and micro-plastics in the environment represents a major global concern due to their persistence, widespread distribu-tion, and potential impact on ecosystems and human health1. Microbial biodegradation has emerged as a promising and sustainable strategy for plastic reme-diation, particularly through the use of fungi with en-zymatic degradative capacity. This project aims to test the biodegradative potential of different fungal spe-cies against the widely used microplastics Polypropyl-ene, Polystyrene and Poly(ehylene-co-cinyl acetate), under optimized growth conditions. The fungi, Mucor spp, Rhizopus spp, Scedosporium spp. and Nigrospora spp. were specifically selected because they have nev-er previously been investigated as plastic degraders, thereby offering the opportunity to identify novel bio-degradation capabilities. Aspergillus flavus will also be included as a control, since this species has recognized degradative capacity against some types of microplas-tics2.To identify growth conditions that maximize bio-degradation, preliminary studies using Scedosporiumspp. were performed under different glucose concen-trations and medium replacement intervals. Low-glu-cose media combined with fortnightly medium renew-al promoted the highest degradative activity and were selected for the subsequent biodegradation assays. Biodegradation will be assessed through microplastic mass loss determination, Fourier-transform infrared spectroscopy (FTIR), and Raman spectroscopy, allow-ing the identification of structural and chemical mod-ifications on microplastic surfaces. Fungal adherence to microplastics will be evaluated by microscopic ob-servation and surface colonization analysis, providing insight into biofilm formation and the role of fungal activity in the degradation process. Additionally, fun-gal pathogenicity-related traits, including biofilm for-mation and antifungal susceptibility, will be evaluated to determine whether long-term exposure to micro-plastics influences fungal virulence. This study may support the development of sustainable plastic bio-degradation strategies and improve understanding of fungal adaptation to plastic-rich environments.
- Antimicrobial properties of PLA scaffolds functionalized via LbL method with Manuka and multifloral honeyPublication . Alves, Inês; Ferraz, Ricardo; Prudêncio, Cristina; Rufo, João; Prudêncio, Cristina; Cavaleiro Rufo, JoãoTissue engineering and chronic wound management face obstacles due to the global rise of resistances. Natural bioactive agents, such as Manuka honey, offer a unique therapeutic profile by combining antimicrobial activity with the ability to modulate the biochemical wound environment and promote cellular regeneration. However, the seamless integration of these biological compounds into synthetic matrices, such as polylactic acid (PLA), remains a challenge. This study aims to develop PLA scaffolds functionalised with honey using the Layer-by-Layer (LbL) technique and evaluate their inhibitory capacity against microbial growth. Two honey types are com-pared, MGO 263+/UMF10+ Manuka honey and a Portuguese multifloral honey. Concentrations of 15%, 20%, 25%, 30% and 35% will be tested by diluting the honey in 3M sodium acetate buffer and adjusting pH to 5.5. The method has currently been successfully optimized for the 15% concentration. The LbL process consist-ed of three immersion cycles, alternating with coating in the honey solutions, washing in acetate buffer and short periods of drying. As a negative control, PLA scaffolds were subjected only to the washing steps. Biological activity was assessed against Escherichia coliand Staphylococcus aureus. In the disc diffusion test, the plates were inoculated uniformly and the scaffolds arranged in quadrants, including positive controls of ciprofloxacin for E. coli andpenicillin G for S. aureus. After incubation, inhibition was quantified by two per-pendicular measurements of the halo. Quantification of Colony-Forming Units (CFU) was performed after recovery of the microorganisms from the scaffolds by vortexing and centrifugation in saline solution. The study is currently in the optimization phase. Sterilization has been successfully achieved by im-mersing the scaffolds in 70% ethanol for 2 hours with gentle stirring, followed by vacuum drying in a Petry dish for 24 hours. Microscopic observation of the scaf-folds showed a clear coating layer in functionalized samples. This research seeks to validate LbL functionalisation as a simple strategy for developing bioactive scaffolds. The present work establishes a foundation for subsequent phases involving various honey concentrations, with the goal of demonstrating a synergistic effect between the PLA scaffold and nat-ural antimicrobial agents.
- Profiling airway microbiome composition through volatilomicsPublication . Neto, Filipa; Ferraz, Ricardo; Vieira, Mónica; Prudêncio, Cristina; Rufo, João; Almeida Vieira, Mónica Andreia; Cavaleiro Rufo, JoãoThe airway microbiome is known to mediate respi-ratory health. However, current available methods for microbiome analysis are time-consuming and/or rep-resent significant costs for a generalized application in clinical practice. Volatilomics has been suggested as a rapid and low-cost approach to screen microbial pro-files in human samples. Therefore, we aimed to study the efficacy of volatilomics in discriminating microbi-al isolates collected from human breath condensate samples. Bacterial strains showing significant growth under conditions simulating the respiratory environ-ment were isolated. Each strain was standardised to an inoculum of 10⁸ CFU/mL and analysed using an elec-tronic nose equipped with a six-sensor matrix. Data were explored through principal component analysis, cluster analysis, pattern analysis, random forests and recursive partitioning regression. One sensor was re-moved from the analysis due to high collinearity. Prin-cipal component analysis was able to separate strains and the control mainly through the second principal component (p = 0.024), characterized by high MQ3 and MQ8 sensor responses. Sensor profile maps showed distinct volatile patterns across strains (Fig-ure 1), suggesting the presence of distinct microbial signatures. However, reproducibility was low between replicas and time since culture. Recursive partitioning for separating sterile controls from inoculated sam-ples showed the highest accuracy (AUC = 0.73). These results show the potential of separation of microbial strains based on volatilomics. Nonetheless, relative robustness was only achieved for the discrimination of sterile vs inoculated samples.