Effect of photobiomodulation in an experimental in vitro model of asthma-Copd overlap.

The objective of the study was to evaluate the effect of photobiomodulation (PBM) with laser on the inflammatory process in an experimental in vitro model of ACO. The groups were: (1) human bronchial epithelial cells (BEAS-2B); (2) BEAS-2B cells treated with dexamethasone; (3) BEAS-2B cells irradiated with laser; (4) BEAS-2B cells stimulated with cigarette smoke extract (CSE) + House Dust Mite (HDM); (5) BEAS-2B cells stimulated with CSE + HDM and treated with dexamethasone; (6) BEAS-2B cells incubated with CSE + HDM and irradiated with laser. After 24 h, cytokines were quantified. There was a reduction in TNF-α, IL-1ß, IL-6, IL-4, IL-5, IL-13, IL-17, IL-21, IL-23, and an increase in IL-10 and IFN-γ in cells from the laser-irradiated ACO group compared to only ACO group. With these results, we can suggest that photobiomodulation acts in the modulation of inflammation observed in ACO, and may be a treatment option.

Altered levels of IFN-γ, IL-4, and IL-5 depend on the TLR4 rs4986790 genotype in COPD smokers but not those exposed to biomass-burning smoke.

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with tobacco smoking and biomass-burning smoke exposure. Toll-like receptor 4 (TLR4) single-nucleotide polymorphisms (SNPs) may contribute to its pathogenesis. The study aimed to assess the association of rs4986790 and rs4986791 in the TLR4 gene in a Mexican mestizo population with COPD secondary to tobacco smoking (COPD-TS) and biomass-burning smoke (COPD-BBS) and to evaluate whether the genotypes of risk affect cytokine serum levels. Materials and methods: We enrolled 2,092 participants and divided them into two comparisons according to their environmental exposure. SNPs were genotyped using TaqMan probes. Serum cytokine levels (IL-4, IL-5, IL-6, IL-10, and INF-γ) were quantified by ELISA. Results: The rs4986790 AA genotype in COPD-TS was associated with a higher COPD risk (OR = 3.53). Haplotype analysis confirmed this association, identifying a block containing the rs4986790 allele (A-C, OR = 3.11). COPD-TS exhibited elevated IL-6, IL-4, and IL-5 levels compared with smokers without COPD (SWOC), whereas COPD-BBS displayed higher IFN-γ, IL-6, and IL-10 levels. The AA carriers in the COPD-TS group had elevated IL-4, IL-5, and IFN-γ compared with carriers of AG or GG. Conclusion: The rs4986790 common allele and the A-C haplotype (rs4986790-rs4986791) were associated with a higher COPD risk in smokers; COPD patients carrying the AA genotype showed increased pro-inflammatory cytokines.

Dietary patterns and risk of Chronic Obstructive Pulmonary Disease (COPD) and clinical outcomes in diagnosed patients: A scoping review.

BACKGROUND & AIMS: Limited research exists on the association between dietary patterns (DP) and COPD risk or health-related outcomes. We reviewed existing literature to identify DP as a potential factor influencing COPD development and associated health outcomes in diagnosed individuals. METHODS: We followed the Joanna Briggs Institute methodology for this scoping review, conducting searches on PubMed, Scopus, Embase, and Web of Science to identify studies meeting our inclusion criteria (P, population - adults from the general population with or without COPD diagnosis; C, concept - DP; C, context - any setting). Two reviewers screened titles and abstracts, confirmed eligibility through full-text examination, extracted data using Redcap®, and assessed bias risk with the Newcastle Ottawa Scale. RESULTS: We analyzed 24 studies with sample sizes ranging from 121 to 421,426 individuals aged 20 to 75. Eighty-three percent investigated the role of DP in the COPD etiology, while 16.7 % examined health-related COPD outcomes. Food frequency questionnaires predominated (75 %) in exploring 23 distinct DP. Sixty-seven percent employed a priori-defined DP, focusing on the Mediterranean Diet (MedDiet) and Healthy Eating Index (HEI), while 33.3 % utilized a posteriori-defined DP, mainly represented by the Prudent and Traditional DP. Sixty percent of the studies reported significant associations between DP and COPD risk/odds. However, studies examining DP and COPD patient outcomes produced varied results. CONCLUSIONS: Most studies focused on assessing COPD risk using a priori-defined DP, particularly emphasizing the Med Diet and HEI. Overall, the studies found that healthy DPs are associated with reduced risk of COPD and improved outcomes in diagnosed patients.

Phenotypes of regulatory T cells in different stages of COPD.

BACKGROUND: Previous studies have shown that failure to control inflammatory processes mediated by regulatory T (Treg) cells contributes to chronic obstructive pulmonary disease (COPD) development and progression. The activity of Treg cells depends on their phenotypic characteristics: resting Treg (rTreg, CD3+CD4+CD25+FOXP3+CD25++CD45RA+) and activated Treg (aTreg, CD3+CD4+CD25+FOXP3+CD25+++CD45RA-) cells exhibit immunosuppressive activity, while cytokine-secreting T cells (FrIII, CD3+CD4+CD25+FOXP3+CD25++CD45RA-) exhibit proinflammatory activity. Previous findings have shown an increased density of cytokine-secreting T cells in COPD patients experiencing exacerbation. However, the methods for evaluating COPD under stable conditions are lacking. AIM: To evaluate Treg cell phenotypes in patients with different stages of COPD under stable conditions. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from non-obstructed smokers and ex-smokers (NOS group, n = 19) and COPD patients at different stages (COPD I-II group, n = 25; COPD III-IV group, n = 25). The phenotypic characteristics of Treg cells and Th17 cells and their respective intracellular cytokines were analyzed by flow cytometry. RESULTS: Both obstructed groups showed an increase in the proportion of rTregs, while the COPD III-IV group showed additional increases in total Treg and Th17 cells and in IL-10+ cells. There was an increase in proinflammatory mediators (CD3+CD4+IL-17+ cells; CD3+CD4+RORγt+ cells) in the COPD I-II group. In contrast, the NOS group demonstrated high proportions of proinflammatory Treg cells and proinflammatory CD8+ T cells (CD3+CD8+IL-17+). CONCLUSION: Despite the increase in both total Treg cells and the rTreg phenotype from the early stages of COPD, there was a decrease in cells expressing IL-10, suggesting a failure in controlling the inflammatory process. These events precede the progression of the inflammatory process mediated by Th17 cells.

Anxiety Inventory for Respiratory Disease: Cross-Cultural Adaptation and Semantic Validity of the Brazilian Version for Individuals with Chronic Obstructive Pulmonary Disease.

Background: Most instruments available to screen for anxiety in people with chronic obstructive pulmonary disease (COPD) are not disease specific. Therefore, the Anxiety Inventory for Respiratory Disease (AIR) was developed to measure anxiety for this patient group; however, it requires cross-cultural adaptation for use in non-English speaking countries. Purpose: To carry out cross-cultural adaptation of the AIR scale for Brazilian patients with COPD and to analyze its semantic validity. Patients and Methods: This methodological study followed six stages: 1) Initial translation by two independent translators fluent in English; 2) Synthesis of translations; 3) Back translation by two English first language translators; 4) Expert committee review (eight healthcare professionals, a methodologist, the translators, and back-translators); 5) Pre-final version evaluation with 30 patients with COPD through a cognitive interview; and 6) Submission of documents. Semantic validity was analyzed by agreement rate and content validity index (CVI) for the committee equivalence assessments. Results: 1) Initial translation: the two translated versions presented eight divergences; 2) Synthesis of translations: the differences were discussed to reach consensus; 3) Back-translation: there were no important inconsistencies; 4) Expert Committee: the experts proposed eight and the instrument developer proposed three changes, which were analyzed and voted on, resulting in the pre-final version; 5) Evaluation of the pre-final version: data collection allowed for other changes and the formulation of instructions by applying the adapted instrument in an interview format. Patients rated the questions as clear or very clear; 6) The expert committee and the developer approved the final documents. The agreement rate and CVI were ≥ 0.80 for all items of the scale final version. Conclusion: The process of cross-cultural adaptation followed all necessary stages and the semantic validity results were adequate, providing the Brazilian version of the AIR to assess anxiety symptoms in patients with COPD.

Evaluating the impact of short-term nitrate-rich dietary supplementation on endothelial function in COPD: A randomized crossover study.

AIM: This study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration. METHODS: In this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series. RESULTS: Seventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m2, FEV1, 0.79 (0.67-1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels. CONCLUSIONS: Acute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect.

Immunosenescence and Inflammation in Chronic Obstructive Pulmonary Disease: A Systematic Review.

Background/Objectives: Chronic Obstructive Pulmonary Disease (COPD) is a disease of premature aging, characterized by airflow limitations in the lungs and systemic chronic inflammation. This systematic review aimed to provide a systematic overview of immunosenescence and inflammation in Chronic Obstructive Pulmonary Disease (COPD). Methods: The PubMed, Science Direct, Scopus, Cochrane Library, and Web of Science databases were searched for studies on markers of immunosenescence. Observational studies comparing patients with COPD to individuals without disease were evaluated, considering the following markers: inflammation and senescence in COPD, naïve, memory, and CD28null T cells, and telomere length in leukocytes. Results: A total of 15 studies were included, eight of which were rated as high quality. IL-6 production, telomere shortening, and the higher frequencies of CD28null T cells were more prominent findings in the COPD studies analyzed. Despite lung function severity being commonly investigated in the included studies, the importance of this clinical marker to immunosenescence remains inconclusive. Conclusions: The findings of this systematic review confirmed the presence of accelerated immunosenescence, in addition to systemic inflammation, in stable COPD patients. Further studies are necessary to more comprehensively evaluate the impact of immunosenescence on lung function in COPD.

Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD.

Introduction: Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model. Methods: We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p < 0.05). Results: This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells. Conclusion: This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD.

Curve-Modelling and Machine Learning for a Better COPD Diagnosis.

Background: Development of new tools in artificial intelligence has an outstanding performance in the recognition of multidimensional patterns, which is why they have proven to be useful in the diagnosis of Chronic Obstructive Pulmonary Disease (COPD). Methods: This was an observational analytical single-centre study in patients with spirometry performed in outpatient medical care. The segment that goes from the peak expiratory flow to the forced vital capacity was modelled with quadratic polynomials, the coefficients obtained were used to train and test neural networks in the task of classifying patients with COPD. Results: A total of 695 patient records were included in the analysis. The COPD group was significantly older than the No COPD group. The pre-bronchodilator (Pre BD) and post-bronchodilator (Post BD) spirometric curves were modelled with a quadratic polynomial, and the coefficients obtained were used to feed three neural networks (Pre BD, Post BD and all coefficients). The best neural network was the one that used the post-bronchodilator coefficients, which has an input layer of 3 neurons and three hidden layers with sigmoid activation function and two neurons in the output layer with softmax activation function. This system had an accuracy of 92.9% accuracy, a sensitivity of 88.2% and a specificity of 94.3% when assessed using expert judgment as the reference test. It also showed better performance than the current gold standard, especially in specificity and negative predictive value. Conclusion: Artificial Neural Networks fed with coefficients obtained from quadratic and cubic polynomials have interesting potential of emulating the clinical diagnostic process and can become an important aid in primary care to help diagnose COPD in an early stage.

Mapping the Common Barriers to Optimal COPD Care in High and Middle-Income Countries: Qualitative Perspectives from Clinicians.

Purpose: Chronic obstructive pulmonary disease (COPD) poses a significant global health burden despite being largely preventable and treatable. Despite the availability of guidelines, COPD care remains suboptimal in many settings, including high-income countries (HICs) and upper-middle-income countries (UMICs), with varied approaches to diagnosis and management. This study aimed to identify common and unique barriers to COPD care across six countries (Australia, Spain, Taiwan, Argentina, Mexico, and Russia) to inform global policy initiatives for improved care. Methods: COPD care pathways were mapped for each country and supplemented with epidemiological, health-economic, and clinical data from a targeted literature review. Semi-structured interviews with 17 respiratory care clinicians were used to further validate the pathways and identify key barriers. Thematic content analysis was used to generate the themes. Results: Six themes were common in most HICs and UMICs: "Challenges in COPD diagnosis", "Strengthening the role of primary care", "Fragmented healthcare systems and coordination challenges", "Inadequate management of COPD exacerbations", "Limited access to specialized care" and, "Impact of underfinanced and overloaded healthcare systems". One theme, "Insurance coverage and reimbursement challenges", was more relevant for UMICs. HICs and UMICs differ in patient and healthcare provider awareness, primary care involvement, spirometry access, and availability of specialized care. Both face issues with healthcare fragmentation, guideline adherence, and COPD exacerbation management. In addition, UMICs also grapple with resource limitations and healthcare infrastructure challenges. Conclusion: Many challenges to COPD care are the same in both HICs and UMICs, underscoring the pervasive nature of these issues. While country-specific issues require customized solutions, there are untapped possibilities for implementing global respiratory strategies that support countries to manage COPD effectively. In addition to healthcare system-level initiatives, there is a crucial need for political prioritization of COPD to allocate the essential resources it requires.

Involvement of GPR43 Receptor in Effect of Lacticaseibacillus rhamnosus on Murine Steroid Resistant Chronic Obstructive Pulmonary Disease: Relevance to Pro-Inflammatory Mediators and Oxidative Stress in Human Macrophages.

BACKGROUND: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. OBJECTIVE: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. METHODS: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. RESULTS: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. CONCLUSIONS: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.

Analysis of Endocrine and Inflammatory Markers in Preserved Ratio Impaired Spirometry.

Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine. Differences were observed in the nutritional status, lung function, and comorbidity. There were no differences in IL-6, IL-8, IL-10, IL-12, and TNF levels between PRISm and COPD groups. Both PRISm and COPD patients have lower dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. Correlation analysis of PRISm and COPD patients revealed positive correlations between serum levels of DHEA-S and DHEA, with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), which negatively correlated with IL-8 levels. The results indicated that despite differences in lung function parameters, the PRISm and COPD groups exhibited similarities in endocrine profile alterations. This study represents the first attempt to link endocrine with immune markers and lung function in individuals with PRISm.

sRAGE levels are decreased in plasma and sputum of COPD secondary to biomass-burning smoke and tobacco smoking: Differences according to the rs3134940 AGER variant.

The receptor for advanced glycation end products (RAGE) and its gene (AGER) have been related to lung injury and inflammatory diseases, including chronic obstructive pulmonary disease (COPD). We aimed to evaluate the association of rs2071288, rs3134940, rs184003, and rs2070600 AGER single-nucleotide variants and the soluble-RAGE plasma and sputum levels with COPD secondary to biomass-burning smoke (BBS) and tobacco smoking. Four groups, including 2189 subjects, were analyzed: COPD secondary to BBS exposure (COPD-BBS, n = 342), BBS-exposed subjects without COPD (BBES, n = 774), tobacco smoking-induced COPD (COPD-TS, n = 434), and smokers without COPD (SWOC, n = 639). Allelic discrimination assays determined the AGER variants. The sRAGE was quantified in plasma (n = 240) and induced-sputum (n = 72) samples from a subgroup of patients using the ELISA technique. In addition, a meta-analysis was performed for the association of rs2070600 with COPD susceptibility. None of the studied genetic variants were found to be associated with COPD-BBS or COPD-TS. A marginal association was observed for the rs3134940 with COPD-BBS (p = 0.066). The results from the meta-analysis, including six case-control studies (n = 4149 subjects), showed a lack of association of rs2070600 with COPD susceptibility (p = 0.681), probably due to interethnic differences. The sRAGE plasma levels were lower in COPD-BBS compared to BBS and in COPD-TS compared to SWOC. The sRAGE levels were also lower in sputum samples from COPD-BBS than BBES. Subjects with rs3134940-TC genotypes exhibit lower sRAGE plasma levels than TT subjects, mainly from the COPD-BBS and SWOC groups. The AGER variants were not associated with COPD-BBS nor COPD-TS, but the sRAGE plasma and sputum levels are related to both COPD-BBS and COPD-TS and are influenced by the rs3134940 variant.

Rate of severe exacerbations, healthcare resource utilisation and clinical outcomes in patients with COPD in low-income and middle-income countries: results from the EXACOS International Study.

INTRODUCTION: The EXAcerbations of Chronic obstructive lung disease (COPD) and their OutcomeS (EXACOS) International Study aimed to quantify the rate of severe exacerbations and examine healthcare resource utilisation (HCRU) and clinical outcomes in patients with COPD from low-income and middle-income countries. METHODS: EXACOS International was an observational, cross-sectional study with retrospective data collection from medical records for a period of up to 5 years. Data were collected from 12 countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Guatemala, Hong Kong, Mexico, Panama, Russia and Taiwan. The study population comprised patients ≥40 years of age with COPD. Outcomes/variables included the prevalence of severe exacerbations, the annual rate of severe exacerbations and time between severe exacerbations; change in lung function over time (measured by the forced expiratory volume in 1 s (FEV1)); peripheral blood eosinophil counts (BECs) and the prevalence of comorbidities; treatment patterns; and HCRU. RESULTS: In total, 1702 patients were included in the study. The study population had a mean age of 69.7 years, with 69.4% males, and a mean body mass index of 26.4 kg/m2. The mean annual prevalence of severe exacerbations was 20.1%, and 48.4% of patients experienced ≥1 severe exacerbation during the 5-year study period. As the number of severe exacerbations increased, the interval between successive exacerbations decreased. A statistically significant decrease in mean (SD) FEV1 from baseline to post-baseline was observed in patients with ≥1 severe exacerbation (1.23 (0.51) to 1.13 (0.52) L; p=0.0000). Mean BEC was 0.198 x109 cells/L, with 64.7% of patients having a BEC ≥0.1 x109 cells/L and 21.3% having a BEC ≥0.3 x109 cells/L. The most common comorbidity was hypertension (58.3%). An increasing number of severe exacerbations per year was associated with greater HCRU. DISCUSSION: The findings presented here indicate that effective treatment strategies to prevent severe exacerbations in patients with COPD remain a significant unmet need in low-income and middle-income countries.

Physical inactivity and sedentary behavior in individuals with stable COPD non-infected by SARS-CoV-2 during the COVID-19 pandemic / Inatividade física e comportamento sedentário em indivíduos com DPOC estável não infectados pelo SARS-CoV-2 durante a pandemia de COVID-19

Objective: to identify factors associated to sedentary behavior and physical inactivity in individuals with stable chronic obstructive pulmonary disease (COPD) non-infected by SARS-CoV-2 during the COVID-19 pandemic, and to identify possible favorable conditions during social isolation in individuals who performed pulmonary rehabilitation in the pre-pandemic period. Method: time/day in sedentary activities and moderate/vigorous physical activities (SA and MVPA, respectively), history of previous rehabilitation, laboural activity, symptoms, insecurity and quality of life (Medical Outcomes Study 36-item Short-Form Health Survey [SF-36]) were assessed during strict social isolation due to the COVID-19 pandemic. Individuals were classified as sedentary if presenting time/day in SA >8.5 h/day and physically inactive if presenting time/day in MVPA <150 min/week. Result: The sample consisted of 33 individuals (69±7 years; 20 male). Regarding the SF-36, non-sedentary individuals presented better functional capacity than sedentary individuals (65 [38-73] vs. 33 [20-63] points; p=0.01) whereas physically active individuals presented better physical and social function than physically inactive individuals (100 [100-100] vs. 50 [25-100] points, p=0.049; and 100 [100-100] vs. 75 [69-100] points, p=0.022, respectively). Having a professional activity and working outside were associated with non-sedentary behavior (X2=5.93; p=0.025 and X2=7.03; p=0.009, respectively). Having undergone rehabilitation previously to the pandemic was associated with less insecurity to walk outside (X2=4.95; p=0.034) and better perception of symptoms' worsening (X2=5.46; p=0.033). Conclusion: non-sedentarism was associated with functional capacity and laboural activity; active lifestyle was associated with physical and social function; and previous rehabilitation was associated with better symptoms' recognition and less insecurity

Objetivo: identificar fatores associados ao comportamento sedentário e inatividade física em indivíduos com doença pulmonar obstrutiva crônica (DPOC) estável não-infectados pelo SARS-CoV-2 durante o isolamento social causado pela pandemia de COVID-19, e identificar eventuais condições favoráveis durante o isolamento social em indivíduos que realizaram reabilitação pulmonar pré-pandemia. Método: tempo/dia em atividades sedentárias e em atividades físicas moderadas/vigorosas (AS e AFMV, respectivamente), reabilitação prévia, atividade laboral, sintomas, insegurança e qualidade de vida (Medical Outcomes Study 36-item Short-Form Health Survey [SF-36]) foram avaliados durante a vigência de isolamento social devido à pandemia de COVID-19. Foram considerados sedentários aqueles que apresentassem tempo/dia em AS >8,5 h/dia e fisicamente inativos os que apresentassem tempo/dia em AFMV <150 min/semana. Resultado: a amostra consistiu em 33 indivíduos (69±7 anos; 20 homens). Pelo SF-36, indivíduos não-sedentários apresentaram melhor capacidade funcional do que sedentários (65 [38-73] vs. 33 [20-63] pontos; p=0,01) enquanto indivíduos fisicamente ativos apresentaram melhor função física e social do que os fisicamente inativos (100 [100-100] vs. 50 [25-100] pontos, p=0,049; e 100 [100-100] vs. 75 [69-100] pontos, p=0,022, respectivamente). Ter atividade profissional e trabalhar fora de casa associou-se com comportamento não-sedentário (X2=5,93; p=0,025 e X2=7,03; p=0,009, respectivamente). Ter participado de reabilitação pulmonar pré-pandemia associou-se com menos insegurança para caminhar em lugares públicos (X2=4,95; p=0,034) e melhor percepção de piora dos sintomas respiratórios (X2=5,46; p=0,033). Conclusão: não-sedentarismo associou-se com capacidade funcional e atividade laboral; ser fisicamente ativo associou-se com função física e social; e ter realizado reabilitação prévia com menos insegurança e melhor percepção dos sintomas

Proteomic Networks and Related Genetic Variants Associated with Smoking and Chronic Obstructive Pulmonary Disease.

Background: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with interconnections that may not be captured when considering single molecular features. Methods: Leveraging proteomic data from 3,173 COPDGene Non-Hispanic White (NHW) and African American (AA) participants, we applied sparse multiple canonical correlation network analysis (SmCCNet) to 4,776 proteins assayed on the SomaScan v4.0 platform to derive sparse networks of proteins associated with current vs. former smoking status, airflow obstruction, and emphysema quantitated from high-resolution computed tomography scans. We then used NetSHy, a dimension reduction technique leveraging network topology, to produce summary scores of each proteomic network, referred to as NetSHy scores. We next performed genome-wide association study (GWAS) to identify variants associated with the NetSHy scores, or network quantitative trait loci (nQTLs). Finally, we evaluated the replicability of the networks in an independent cohort, SPIROMICS. Results: We identified networks of 13 to 104 proteins for each phenotype and exposure in NHW and AA, and the derived NetSHy scores significantly associated with the variable of interests. Networks included known (sRAGE, ALPP, MIP1) and novel molecules (CA10, CPB1, HIS3, PXDN) and interactions involved in COPD pathogenesis. We observed 7 nQTL loci associated with NetSHy scores, 4 of which remained after conditional analysis. Networks for smoking status and emphysema, but not airflow obstruction, demonstrated a high degree of replicability across race groups and cohorts. Conclusions: In this work, we apply state-of-the-art molecular network generation and summarization approaches to proteomic data from COPDGene participants to uncover protein networks associated with COPD phenotypes. We further identify genetic associations with networks. This work discovers protein networks containing known and novel proteins and protein interactions associated with clinically relevant COPD phenotypes across race groups and cohorts.

Adaptation to Living at High Altitude in Patients with COPD. Comparative Study of Exercise Capacity and Ventilatory Variables between Patients Residing at High and Low Altitudes in the Andes.

González-García, Mauricio and Luis Ernesto Téllez. Adaptation to living at high altitude in patients with COPD. Comparative study of exercise capacity and ventilatory variables between patients residing at high and low altitudes in the Andes. High Alt Med Biol. 00:000-000, 2024. Introduction: Although some variables related to oxygen transport and utilization such as ventilation, pulmonary vascular responses to hypoxia, heart rate (HR), cardiac output, hemoglobin (Hb), and oxygen saturation (SpO2) are used to compare adaptation to altitude between populations, peak oxygen consumption (VO2) constitutes an integrative measure of total oxygen transport that may reflect successful adaptation to altitude. We designed this study to make a direct comparison of VO2 in a cardiopulmonary exercise test (CPET) between chronic obstructive pulmonary disease (COPD) patients residing at high altitude (Bogotá, Colombia: 2,640 m) (COPD-HA) and those living at low altitude (Bucaramanga, Colombia: 959 m) (COPD-LA). Methods: All patients performed a CPET with measurements of VO2, minute ventilation (VE), HR, oxygen pulse (VO2/HR), ventilatory equivalents (VE/VCO2), and SpO2. Unpaired T-test or Mann-Whitney U test were used for comparisons between COPD-HA and COPD-LA. Results: We included 71 patients with COPD, 53 COPD-HA, and 18 COPD-LA. There were no differences between groups in age, sex, or forced expiratory volume in 1 second. The means ± SD of Hb, g/dl was slightly higher in COPD-HA (15.9 ± 1.9 vs. 14.7 ± 1.8, p = 0.048), without differences in VO2, % pred (71.6 ± 17.9 vs. 69.0 ± 17.0, p = 0.584), VO2/HR, % pred (92.1 ± 22.0 vs. 89.7 ± 19.8, p = 0.733) or VE/MVV, % (75.5 ± 14.1 vs. 76.5 ± 14.3, p = 0.790) at peak exercise between groups. Median (IQR) of VE/VCO2 nadir [38.0 (37.0-42.0) vs. 32.5 (31.0-39.0), p = 0.005] was significantly higher, and SpO2, % at rest [88.0 (86.0-91.0) vs. 95.0 (94.0-96.0), p < 0.001] and at peak exercise [84.0 (77.0-90.0) vs. 93.0 (92.0-95.0), p < 0.001] were significantly lower in COPD-HA. Conclusions: Despite higher desaturation at rest and during exercise in COPD-HA, there were no differences in VO2 peak between COPD-HA and COPD-LA, suggesting a potential altitude adaptation in those patients chronically exposed to hypoxia.

Role of the Fungus Pneumocystis in IL1ß Pathway Activation and Airways Collagen Deposition in Elastase-Induced COPD Animals.

Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus Pneumocystis, which is linked to severe COPD in human patients. Recent evidence has demonstrated that Pneumocystis significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by Pneumocystis infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1ß pro-inflammatory pathway during Pneumocystis infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with Pneumocystis exhibited elevated inflammation levels, including a synergistic increase in IL-1ß and Cox-2. Furthermore, protein levels of the IL-1ß-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with Pneumocystis, while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with Pneumocystis compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with Pneumocystis compared with the other experimental animal groups and correlated with the increase of Tgfß1 mRNA levels. These findings emphasize the role of Pneumocystis as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.

Respiratory Oscillometry and Functional Performance in Different COPD Phenotypes.

Purpose: Chronic obstructive pulmonary disease (COPD) phenotypes may introduce different characteristics that need to be known to improve treatment. Respiratory oscillometry provides a detailed analysis and may offer insight into the pathophysiology of COPD. In this paper, we used this method to evaluate the differences in respiratory mechanics of COPD phenotypes. Patients and Methods: This study investigated a sample of 83 volunteers, being divided into control group (CG = 20), emphysema (n = 23), CB (n = 20) and asthma-COPD overlap syndrome (ACOS, n = 20). These analyses were performed before and after bronchodilator (BD) use. Functional capacity was evaluated using the Glittre­ADL test, handgrip strength and respiratory pressures. Results: Initially it was observed that oscillometry provided a detailed description of the COPD phenotypes, which was consistent with the involved pathophysiology. A correlation between oscillometry and functional capacity was observed (r=-0.541; p = 0.0001), particularly in the emphysema phenotype (r = -0.496, p = 0.031). BD response was different among the studied phenotypes. This resulted in an accurate discrimination of ACOS from CB [area under the receiver operating curve (AUC) = 0.84] and emphysema (AUC = 0.82). Conclusion: These results offer evidence that oscillatory indices may enhance the comprehension and identification of COPD phenotypes, thereby potentially improving the support provided to these patients.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.