Given the phenotypic similarities between rheumatoid arthritis (RA)–associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10⁻¹⁷). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10⁻³⁵) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10⁻⁴⁹). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10⁻⁵), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10⁻⁶). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.)

Matrix metalloproteinases (MMPs) participate from the initial phases of cancer onset to the settlement of a metastatic niche in a second organ. Their role in cancer progression is related to their involvement in the extracellular matrix (ECM) degradation and in the regulation and processing of adhesion and cytoskeletal proteins, growth factors, chemokines and cytokines. MMPs participation in cancer progression makes them an attractive target for cancer therapy. MMPs have also been used for theranostic purposes in the detection of primary tumor and metastatic tissue in which a particular MMP is overexpressed, to follow up on therapy responses, and in the activation of cancer cytotoxic pro-drugs as part of nano-delivery-systems that increase drug concentration in a specific tumor target. Herein, we review MMPs molecular characteristics, their synthesis regulation and enzymatic activity, their participation in the metastatic process, and how their functions have been used to improve cancer treatment.

Question addressed by the study: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.Methods: Through a case–control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.Results: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24–0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19–0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26–0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001).Answer to the question: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to a severe clinical course. The host genetic background influence on the susceptibility and outcome of multiples infectious diseases has been previously reported. Herein, we aimed to describe relevant identified genetic variants and those potentially related to the inter-individual variability of COVID-19 susceptibility and/or severity considering the physiopathological pathway of the disease TheHLA-A*25:01, -B*15:27,-B*46:01,-C*01:02, and-C*07:29alleles have been associated with COVID-19 susceptibility; whileHLA-A*02:02,-B*15:03, and-C*12:03have been identified as low-risk alleles. Variants in cytokine genes such asIL1B,IL1R1,IL1RN,IL6,IL17A,FCGR2A, andTNFcould be related to disease susceptibility and cytokine storm, and/or COVID-19 complications (e.g., venous thrombosis). Several variants inACE2andTMPRSS2affecting the expression of the receptors related to COVID-19 have been associated with the disease susceptibility and risk factors. Finally, two GWAS have identified theloci3p21.31 (LZTFL1,SLC6A20,CCR9,FYCO1,CXCR6, andXCR1) and 9q34.2 (ABO) with COVID-19 severity. Heterogeneous results in the association of genetic variants with COVID-19 susceptibility and severity were observed. The mechanism of identified risk-genes and studies in different populations are still warranted.

Pigeon breeders disease (PBD) is caused by the exposure of a susceptible host to avian antigens. However, genetic factors determining individual predisposition are unknown. In this work, polymorphisms of the major histocompatibility complex (MHC) class II alleles and tumor necrosis factor alpha (TNF- α ) promoter were evaluated in 44 patients with PBD, 99 healthy unrelated controls (HC), and 50 exposed but asymptomatic subjects (EAS). MHC typing was performed by PCR-specific sequence oligonucleotide analysis, and TNF- α polymorphism at − 238 and − 308 positions by amplification refractory mutation system-PCR. PBD patients showed a significant increase of the alleles HLA-DRB1*1305 (p < 0.001, OR = 15.4, 95% CI = 3.18–102.6 [HC], and OR = 17.05, 95% CI = 2.25–357.8 [EAS]) and HLA-DQB1*0501 (p < 0.05, OR = 2.93, 95% CI = 1.21–7.15 [HC], and OR = 2.96, 95% CI = 1.0–9.14 [EAS]). A decrease of HLA-DRB1*0802 was also noticed in patients when compared with both control groups (p < 0.05). Haplotype analysis revealed an increase of DRB1*1305–DQB1*0301 and a decrease of DRB1*0802–DQB1*0402. PBD patients had an increased frequency of TNF-2^{− 308} compared with both control groups (p < 0.05). Patients exhibiting the TNF-2^{− 308} allele were younger (33.9 ± 14.6 versus 44.2 ± 10.4 yr; p < 0.05), and displayed more lymphocytes in their bronchoalveolar lavages (88.0 ± 12.1 versus 68.9 ± 17.2; p < 0.05). These results suggest that genetic factors located within the MHC region contribute to the development of PBD.

The tobacco industry promotes electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) as a safer alternative to conventional cigarettes with misleading marketing sustained by studies with conflict of interest. As a result, these devices sell without regulations and warnings about their adverse effects on health, with a growing user base targeting young people. This systematic review aimed to describe the adverse effects on the respiratory system in consumers of these devices. We conducted a systematic review and bibliometric analysis of 79 studies without conflict of interest evaluating ENDS and HTP effects in the respiratory system in experimental models, retrieved from the PubMed database. We found that the damage produced by using these devices is involved in pathways related to pulmonary diseases, involving mechanisms previously reported in conventional cigarettes as well as new mechanisms particular to these devices, which challenges that the tobacco industry’s claims. The present study provides significant evidence to suggest that these devices are an emerging public health problem and that they should be regulated or avoided.