Carlos Robalo Cordeiro

In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) has suffered a variety of alterations. Chemotherapy (CTX), immunotherapy (IT) and tyrosine kinase inhibitors (TKI) have shown remarkable results. However, not all patients with NSCLC respond to these drug treatments or receive durable benefits. In this framework, metabolomics has been applied to improve the diagnosis, treatment, and prognosis of lung cancer and particularly lung adenocarcinoma (AdC). In our study, metabolomics was used to analyze plasma samples from 18 patients with AdC treated with CTX or IT via ¹H-NMR spectroscopy. Relevant clinical information was gathered, and several biochemical parameters were also evaluated throughout the treatments. During the follow-up of patients undergoing CTX or IT, imaging control is recommended in order to assess the effectiveness of the therapy. This evaluation is usually performed every three treatments. Based on this procedure, all the samples were collected before the beginning of the treatment and after three and six treatments. The identified and quantified metabolites in the analyzed plasma samples were the following: isoleucine, valine, alanine, acetate, lactate, glucose, tyrosine, and formate. Multivariate/univariate statistical analyses were performed. Our data are in accordance with previous published results, suggesting that the plasma glucose levels of patients under CTX become higher throughout the course of treatment, which we hypothesize could be related to the tumor response to the therapy. It was also found that alanine levels become lower during treatment with CTX regimens, a fact that could be associated with frailty. NMR spectra of long responders’ profiles also showed similar results. Based on the results of the study, metabolomics can represent a potential option for future studies, in order to facilitate patient selection and the monitoring of therapy efficacy in treated patients with AdC. Further studies are needed to improve the prospective identification of predictive markers, particularly glucose and alanine levels, as well as confer guidance to NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease; IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may support clinical decisions. These tools evolved to play a crucial role in the diagnosis and management of a wide range of human diseases. This is not the case, however, with hypersensitivity pneumonitis, where there is still great room for research in the path to find consensual diagnostic biomarkers. Gaps in the current evidence include lack of validation, validation against healthy controls alone, small sampling and heterogeneity in diagnostic and classification criteria. Furthermore, discriminatory accuracy is currently limited by overlapping mechanisms of inflammation, damage and fibrogenesis between ILDs. Still, biomarkers such as BAL lymphocyte counts and specific serum IgGs made their way into clinical guidelines, while others including KL-6, SP-D, YKL-40 and apolipoproteins have shown promising results in leading centers and have potential to translate into daily practice. As research proceeds, it is expected that the emergence of novel categories of biomarkers will offer new and thriving tools that could complement those currently available.

Annual vaccination is fundamental for individual and group protection against seasonal influenza infection. International and Portuguese healthcare organizations have established influenza vaccination coverage rate (VCR) targets for risk groups, namely 75% in people ≥ 65 years old. The Vacinómetro® initiative has been monitoring influenza VCR among target risk groups in Portugal since 2009,: Group 1, ≥ 65 years old; Group 2, patients with chronic conditions; Group 3, healthcare workers in direct contact with patients; and Group 4, 60-64 years old. Besides VCR, social-demographic and health-related variables have been evaluated. During the study period (2009/2010 - 2019/2020), the VCR increased in the 4 target risk groups: from 58.6% to 76.0% in Group 1 (reaching the WHO target); 33.3% to 72.0% in Group 2; 25.0% to 58.9% in Group 3; and 36.6% to 42.8% in Group 4. "Physician recommendation" was the main driver for vaccination whereas "lack of habit" was the main barrier to vaccination. Vacinómetro® data demonstrate that free-of-charge vaccination has a positive impact on VCR. The observed positive trends in influenza VCR demonstrate that public health measures implemented in Portugal to facilitate access to influenza vaccine result in increased vaccine uptake. Strategies to promote population literacy and the physician's awareness should be continued and reinforced. Free-of-charge vaccination criteria extended to more risk groups would also contribute to higher influenza VCR in Portugal.

Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score ≥4 and all patients with DILI had a RUCAM score ≥ 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age ≥ 55 years (OR:3.67; 95% CI:1.82–7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23–5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CI:1.25–4.84; p = 0.009), and carriers of p.Val444Ala variant for ABCB11 gene (OR:2.06; 95%CI:1.02–4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILI, with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years.

Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this disease are the diagnosis of 61% of patients in advanced stages and the reduced five-year survival rate of around 4%. Noninvasively collected samples are gaining significant interest as new areas of knowledge are being sought and opened up. Metabolomics is one of these growing areas. In recent years, the use of metabolomics as a resource for the study of lung cancer has been growing. We conducted a systematic review of the literature from the past 10 years in order to identify some metabolites associated with lung cancer. More than 150 metabolites have been associated with lung cancer-altered metabolism. These were detected in different biological samples by different metabolomic analytical platforms. Some of the published results have been consistent, showing the presence/alteration of specific metabolites. However, there is a clear variability due to lack of a full clinical characterization of patients or standardized patients selection. In addition, few published studies have focused on the added value of the metabolomic profile as a means of predicting treatment response for lung cancer. This review reinforces the need for consistent and systematized studies, which will help make it possible to identify metabolic biomarkers and metabolic pathways responsible for the mechanisms that promote tumor progression, relapse and eventually resistance to therapy.

Introduction and objectives Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial lung disease of unknown cause, which predominantly manifests in older males. IPF diagnosis is a complex, multi-step process and delay in diagnosis cause a negative impact on patient survival. Additionally, a multidisciplinary team of pulmonologists, radiologists and pathologists is necessary for an accurate IPF diagnosis. The present study aims to assess how diagnosis and treatment of IPF are followed in Portugal, as well as the knowledge and implementation of therapeutic guidelines adopted by the Portuguese Society of Pulmonology. Materials and methods Seventy-eight practicing pulmonologists were enrolled (May–August 2019) in a survey developed by IPF expert pulmonologists comprised of one round of 31 questions structured in three parts. The first part was related to participant professional profile, the second part assessed participant level of knowledge and practice agreement with national consensus and international guidelines for IPF as well as their access to radiology and pathology for IPF diagnosis, and the third part was a self-evaluation of the guidelines adherence for diagnosis and treatment in their daily practice. Results: Participants represented a wide spectrum of pulmonologists from 14 districts of Portugal and autonomous regions of Azores and Madeira. The majority were female (65%), with 5–19 years of experience (71%) and working in a public clinical center (83%). Importantly, the majority of pulmonologists follow their IPF patients (n = 45) themselves, while 26% referred IPF patients to ILD experts in the same hospital and 22% to another center. Almost all pulmonologists (98%) agreed or absolutely agreed that multidisciplinary discussion is recommended to accurately diagnose IPF. No pulmonologists considered pulmonary biopsy as absolutely required to establish an IPF diagnosis. However, 87% agreed or absolutely agree with considering biopsy in a possible/probable UIP context. If a biopsy is necessary, 96% of pulmonologists absolutely agree or agree with considering criobiopsy as an option for IPF diagnosis. Regarding IPF treatment, 98% absolutely agreed or agreed that antifibrotic therapy should be started once the IPF diagnosis is established. Finally, 76% stated that 6 months is the recommended time for follow-up visit in IPF patients. Conclusions: Portuguese pulmonologists understand and agree with national consensus and international guidelines for IPF treatment but their implementation in Portugal is heterogeneous.