Chronic Obstructive Pulmonary Disease Individuals Research Articles

Role of oscillometry to diagnose obstructive airway diseases in patients who are unable to perform spirometry correctly

BackgroundObstructive airway diseases (OAD) are an important contributor to the burden of respiratory diseases in India. The current gold standard to diagnose OAD is spirometry. However, spirometry is a forceful manoeuvre and many patients are unable to perform it as per correct standard acceptable criteria. Therefore, patients are sometimes misdiagnosed or undiagnosed leading to a delay in treatment. Therefore, a study was conducted with an aim to assess the role of forced oscillometry in diagnosing obstructive disease. MethodsA cross -sectional study was carried out from Jun 2019-Jun 2021 at a tertiary care chest centre, where consecutively 102 patients who were unable to perform spirometry correctly or had a contraindication to it were evaluated by oscillometry for OAD. ResultsOut of 102 patients who could not perform spirometry, OAD was detected in 84.4 %. 42.2 % of patients were diagnosed with asthma and similarly 42.2 % of patients were diagnosed to have Chronic obstructive pulmonary disease (COPD). The Mean (R5) Rrs at 5 Hz of the study population were 6.69 cmH2O/L/s for asthma, 5.91 cmH2O/L/s for COPD, and 3.16 cmH2O/L/s in a healthy population respectively. Mean R19 for Asthma, COPD and healthy individuals were 4.45 cmH20/L/s, 3.92 cmH20/L/s and 2.547 cmH20/L/s respectively. (X5) Xrs at 5 Hz of the study population were -3.16 cmH2O/Ls in asthma, −3.33 cmH2O/L/s in COPD, and −0.975 cmH2O/L/s in healthy individuals, respectively. ConclusionOscillometry is a pulmonary function test which can be performed easily and it can help in diagnosing OAD.

Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury

BACKGROUND: Vascular disorders are a prominent pathological feature across many pulmonary diseases, such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and COVID-19. Paracrine signals are enriched throughout the lung tissue and are critical in maintaining functional microvascular homeostasis. In this study, we applied comprehensive computational tools to analyze single-cell RNA-seq (scRNAseq) datasets in healthy and diseased lungs and identified a local component in human lung microvascular niche VEGF-D exhibiting barrier protective property in ALI/ARDS animal models. METHODS: Leveraging scRNAseq-based ligand-receptor analysis, we studied the cell-cell crosstalk signals in the human lung microvascular niche among healthy adults and in IPF and COPD individuals. The impact of identified ligands on vascular barrier function and anti-inflammation was further assessed in vitro assays and lipopolysaccharide (LPS)-induced lung injury models. RESULTS: scRNAseq datasets reveal over 24 cell populations in the human lung microvascular niche. We applied Connectome to map the averaged gene expression per cell type to known ligand-receptor interactions cataloged in the NicheNet database. Using microvascular ECs, such as EC Aerocyte and EC General Capillary, as signal receivers (Senders) and the putative adjacent cell types (alveolar fibroblast, ATI, ATII, pericyte, plasma cell, etc.) in the microvascular niche as signal senders (Ligands), we identified several specific and abundant ligand-receptor pairs based on their expression levels in the niche, including SLIT2-ROBO4, ANGPT1-TEK, ADM-RAMP2, VEGFD-VEGFR2, BMP5-BMPR2, etc. Interestingly, these highly produced ligands were significantly reduced in patients with IPF or COPD. Upon treatment with these ligands on human lung endothelial cells, we found that VEGF-D could significantly increase the barrier function, unlike its analogs, VEGF-A and VEGF-C. Additionally, VEGF-D exerts barrier-protective properties against tumor necrosis factor-α, interleukin 1-β, and thrombin challenges. The blockage of VEGFR2 through either siRNA or pharmacological inhibitor SU5614 attenuates the impact of VEGF-D. Furthermore, intravenous administration of VEGF-D significantly reduced vascular permeability and immune cell infiltration in the LPS-induced lung injury model. CONCLUSIONS: This study highlights the cell-cell crosstalk signals in lung microvascular niche between healthy and diseased individuals and determines a novel and potentially therapeutic role of VEGF-D in improving lung vascular integrity during acute lung injury. NIH K99HL159261 (Y.Y.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease

Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10−5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10−8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.

Promising Intestinal Microbiota Associated with Clinical Characteristics of COPD Through Integrated Bioinformatics Analysis.

Chronic obstructive pulmonary disease (COPD), an incurable chronic respiratory disease, has become a major public health problem. The relationship between the composition of intestinal microbiota and the important clinical factors affecting COPD remains unclear. This study aimed to identify specific intestinal microbiota with high clinical diagnostic value for COPD. The fecal microbiota of patients with COPD and healthy individuals were analyzed by 16S rDNA sequencing. Random forest classification was performed to analyze the different intestinal microbiota. Spearman correlation was conducted to analyze the correlation between different intestinal microbiota and clinical characteristics. A microbiota-disease network diagram was constructed using the gut MDisorder database to identify the possible pathogenesis of intestinal microorganisms affecting COPD, screen for potential treatment, and guide future research. No significant difference in biodiversity was shown between the two groups but significant differences in microbial community structure. Fifteen genera of bacteria with large abundance differences were identified, including Bacteroides, Prevotella, Lachnospira, and Parabacteroides. Among them, the relative abundance of Lachnospira and Coprococcus was negatively related to the smoking index and positively related to lung function results. By contrast, the relative abundance of Parabacteroides was positively correlated with the smoking index and negatively correlated with lung function findings. Random forest classification showed that Lachnospira was the genus most capable of distinguishing between patients with COPD and healthy individuals suggesting it may be a potential biomarker of COPD. A Lachnospira disease network diagram suggested that Lachnospira decreased in some diseases, such as asthma, diabetes mellitus, and coronavirus disease 2019 (COVID-19), and increased in other diseases, such as irritable bowel syndrome, hypertension, and bovine lichen. The dominant intestinal microbiota with significant differences is related to the clinical characteristics of COPD, and the Lachnospira has the potential value to identify COPD.

COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors

IntroductionEnvironmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.MethodsWe delineated...

Restoring the epigenetic landscape of lung microbiome: potential therapeutic approach for chronic respiratory diseases.

Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis, present significant threats to global health. Recent studies have revealed the crucial role of the lung microbiome in the development of these diseases. Pathogens have evolved complex strategies to evade the immune response, with the manipulation of host cellular epigenetic mechanisms playing a pivotal role. There is existing evidence regarding the effects of Pseudomonas on epigenetic modifications and their association with pulmonary diseases. Therefore, this study aims to directly assess the connection between Pseudomonas abundance and chronic respiratory diseases. We hope that our findings will shed light on the molecular mechanisms behind lung pathogen infections. We analyzed data from 366 participants, including individuals with COPD, acute exacerbations of COPD (AECOPD), bronchiectasis, and healthy individuals. Previous studies have given limited attention to the impact of Pseudomonas on these groups and their comparison with healthy individuals. Two independent datasets from different ethnic backgrounds were used for external validation. Each dataset separately analyzed bacteria at the genus level. The study reveals that Pseudomonas, a bacterium, was consistently found in high concentrations in all chronic lung disease datasets but it was present in very low abundance in the healthy datasets. This suggests that Pseudomonas may influence cellular mechanisms through epigenetics, contributing to the development and progression of chronic respiratory diseases. This study emphasizes the importance of understanding the relationship between the lung microbiome, epigenetics, and the onset of chronic pulmonary disease. Enhanced recognition of molecular mechanisms and the impact of the microbiome on cellular functions, along with a better understanding of these concepts, can lead to improved diagnosis and treatment.

Association between α-klotho levels and adults with COPD in the United States.

Chronic obstructive pulmonary disease (COPD) is accompanied by increased inflammation, persistent lung function decline, and extensive lung injury. Klotho, a well-known antiaging protein, has anti-inflammatory and antioxidative effects. However, the effects of klotho on COPD have yet to be thoroughly elucidated. This study examined the association among COPD adults and their α-klotho level. Data were collected from the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES). A total of 676 participants were analyzed and divided into COPD (n = 403) and non-COPD (n = 273) groups. The two groups were compared with respect to clinical characteristics. Logistic regression analysis and a generalized additive model were used to estimate the association between COPD incidence and serum α-klotho concentration. All COPD participants were stratified according to the levels of α-klotho (Q1: <687 pg./mL; Q2: 687-900 pg./mL; Q3: ≥900 pg./mL), and clinical characteristics were compared. Non-COPD individuals had higher α-klotho levels than did COPD individuals (863.09 ± 267.13 vs. 817.51 ± 302.20, p < 0.05). Logistic regression analysis revealed that the Q2 and Q3 layers had a lower risk of COPD than did the Q1 layer, with odds ratios (ORs) of 0.73 (0.50, 0.99) for Q2 and 0.58 (0.41, 0.86) for Q3 (p < 0.001). The generalized additive model showed that the risk of COPD gradually decreased with increasing α-klotho concentration when the α-klotho concentration < 1,500 pg./mL, while the risk of COPD increased as the α-klotho concentration increased to ≥1,500 pg./mL. Compared with individuals in the Q2 or Q3 groups, individuals with COPD in the Q1 group were more likely to be current smokers, have lower levels of erythrocytes, and have higher levels of creatinine and leukocytes. Increased α-klotho levels were negatively correlated with the risk of COPD in participants over 40 years old with α-klotho <1,500 pg./mL. When α-klotho was ≥1,500 pg./mL, the risk of COPD increased as α-klotho levels increased. Pulmonary ventilation function and the number of hemocytes differed among COPD patients with different levels of α-klotho.

Morphometric analysis of airways in pre-COPD and mild COPD lungs using continuous surface representations of the bronchial lumen.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent respiratory disease that presents a high rate of underdiagnosis during onset and early stages. Studies have shown that in mild COPD patients, remodeling of the small airways occurs concurrently with morphological changes in the proximal airways. Despite this evidence, the geometrical study of the airway tree from computed tomography (CT) lung images remains underexplored due to poor representations and limited tools to characterize the airway structure. Methods: We perform a comprehensive morphometric study of the proximal airways based on geometrical measures associated with the different airway generations. To this end, we leverage the geometric flexibility of the Snakes IsoGeometric Analysis method to accurately represent and characterize the airway luminal surface and volume informed by CT images of the respiratory tree. Based on this framework, we study the airway geometry of smoking pre-COPD and mild COPD individuals. Results: Our results show a significant difference between groups in airway volume, length, luminal eccentricity, minimum radius, and surface-area-to-volume ratio in the most distal airways. Discussion: Our findings suggest a higher degree of airway narrowing and collapse in COPD patients when compared to pre-COPD patients. We envision that our work has the potential to deliver a comprehensive tool for assessing morphological changes in airway geometry that take place in the early stages of COPD.

Evaluation of the antioxidant and anti-inflammatory effect of sublingual glutathione on COPD patients.

Glutathione (GSH) is a potent antioxidant and anti-inflammatory, proven effective in reducing treatment duration, prescribed doses, and hospitalization for several diseases. This study assessed the therapeutic response of chronic obstructive pulmonary disease (COPD) patients by measuring oxidative superoxide dismutase (SOD3), glutathione peroxidase 1 (GPX1), and inflammatory biomarkers such as tumor necrosis factor-alpha (TNF-α) and Interleukin-8 (IL-8) after sublingual administration of glutathione supplements. A cohort of 50 COPD individuals was involved and divided into two groups of 25 each. The first group received conventional therapy involving the administration of formoterol fumarate (12 µg inhaler) twice daily. The second group received the conventional treatment alongside sublingual glutathione (300 mg twice daily) for two months. The levels of serum IL-8, TNF-α, SOD3, and GPX1 were assessed before therapy, as well as at one and two months after treatment, in both cohorts. Both groups exhibited a notable reduction in the inflammatory mediators IL-8 and TNF-α when compared to their respective pre-treatment levels (P value <0.05). However, it is worth noting that the observed difference between the groups was not statistically significant (P value >0.05). The levels of SOD3 and GPX1 exhibited a substantial rise in both groups; however, they were found to be greater in group 2 compared to group 1 (P value >0.05). The administration of glutathione resulted in enhanced levels of antioxidant biomarkers among individuals diagnosed with COPD, accompanied by a minor and statistically insignificant decrease in the levels of the anti-inflammatory mediators IL-8 and TNF-alpha.

Combined effect of ozone and household air pollution on COPD in people aged less than 50 years old

ObjectivesAir pollution has been suggested as an important risk factor for chronic obstructive pulmonary disease (COPD); however, evidence of interactive effects on COPD between different factors was sparse, especially for...

Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions.

Chronic obstructive pulmonary disease (COPD) is characterized by nonresolving inflammation fueled by breach in the endothelial barrier and leukocyte recruitment into the airspaces. Among the ligand-receptor axes that control leukocyte recruitment, the full-length fractalkine ligand (CX3CL1)-receptor (CX3CR1) ensures homeostatic endothelial-leukocyte interactions. Cigarette smoke (CS) exposure and respiratory pathogens increase expression of endothelial sheddases, such as a-disintegrin-and-metalloproteinase-domain 17 (ADAM17, TACE), inhibited by the anti-protease α-1 antitrypsin (AAT). In the systemic endothelium, TACE cleaves CX3CL1 to release soluble CX3CL1 (sCX3CL1). During CS exposure, it is not known whether AAT inhibits sCX3CL1 shedding and CX3CR1+ leukocyte transendothelial migration across lung microvasculature. We investigated the mechanism of sCX3CL1 shedding, its role in endothelial-monocyte interactions, and AAT effect on these interactions during acute inflammation. We used two, CS and lipopolysaccharide (LPS) models of acute inflammation in transgenic Cx3cr1gfp/gfp mice and primary human endothelial cells and monocytes to study sCX3CL1-mediated CX3CR1+ monocyte adhesion and migration. We measured sCX3CL1 levels in plasma and bronchoalveolar lavage (BALF) of individuals with COPD. Both sCX3CL1 shedding and CX3CR1+ monocytes transendothelial migration were triggered by LPS and CS exposure in mice, and were significantly attenuated by AAT. The inhibition of monocyte-endothelial adhesion and migration by AAT was TACE-dependent. Compared with healthy controls, sCX3CL1 levels were increased in plasma and BALF of individuals with COPD, and were associated with clinical parameters of emphysema. Our results indicate that inhibition of sCX3CL1 as well as AAT augmentation may be effective approaches to decrease excessive monocyte lung recruitment during acute and chronic inflammatory states.NEW & NOTEWORTHY Our novel findings that AAT and other inhibitors of TACE, the sheddase that controls full-length fractalkine (CX3CL1) endothelial expression, may provide fine-tuning of the CX3CL1-CX3CR1 axis specifically involved in endothelial-monocyte cross talk and leukocyte recruitment to the alveolar space, suggests that AAT and inhibitors of sCX3CL1 signaling may be harnessed to reduce lung inflammation.

The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease.

Excessive activation of M1 macrophages affects the chronic inflammatory response of the airways and leads to the development of chronic obstructive pulmonary disease (COPD). Therefore, it needs to be closely monitored and investigated. MAPK signaling pathway is involved in the activation of M1 macrophages, and N6-methyladenosine (m6A) is involved in the pathogenesis of COPD. However, it is unknown whether activation of the MAPK signaling pathway is mediated by m6A in M1 macrophages in COPD. The GEO data were analyzed using bioinformatics techniques to assess the differences between COPD and healthy individuals in the levels of M1 macrophages, their secreted cytokines, and m6A regulators. The MAPK signaling pathway was significantly enriched in the list of differentially regulated genes between COPD and healthy individuals. We further analyzed the correlation between M1 macrophages, m6A, and the MAPK signaling pathway. Next, blood samples from COPD and healthy individuals were collected and analyzed by using flow cytometry, ELISA, and RT-PCR. Western blotting was performed using CSE-induced THP-1 cells. COPD and healthy mice were used for Me-RIP sequencing and flow cytometry experiments. Validation of the results of the above bioinformatics analysis by molecular biology experiments and sequencing techniques. We found that GEO data and blood specimens from COPD patients showed increased M1 macrophages, higher levels of IL-6 and TNF-α, and higher mRNA expression of key mediators of the MAPK signaling pathway (p38, ERK, and JNK). Western blotting showed increased expression of p38, ERK, and JNK in the CSE group. In contrast, the expression of m6A regulators was low. Also, M1 macrophages in COPD mice were hyperactivated and had reduced m6A modifications of p38, ERK, and JNK compared with control. m6A may be involved in M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby influencing the development of COPD.

Nucleic acid sensor STING drives remodeling and its inhibition enhances steroid responsiveness in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is progressive and irreversible chronic lung inflammatory disease. Cigarette smoke, the main cause of COPD, is often associated with double-stranded DNA release which potentially activates DNA-sensing pathways, such as STING. This study, therefore, analyzed the role of STING pathway in inducing pulmonary inflammation, steroid resistance, and remodeling in COPD. Primary cultured lung fibroblasts were isolated from healthy non-smoker, healthy smoker, and smoker COPD individuals. The expression of STING pathway, remodeling, and steroid resistance signatures were investigated in these fibroblasts upon LPS stimulation and treatment with dexamethasone and/or STING inhibitor, at both mRNA and protein levels using qRT-PCR, western blot, and ELISA. At baseline, STING was elevated in healthy smoker fibroblasts and to a higher extent in smoker COPD fibroblasts when compared to healthy non-smoker fibroblasts. Upon using dexamethasone as monotherapy, STING activity was significantly inhibited in healthy non-smoker fibroblasts but showed resistance in COPD fibroblasts. Treating both healthy and COPD fibroblasts with STING inhibitor in combination with dexamethasone additively inhibited STING pathway in both groups. Moreover, STING stimulation triggered a significant increase in remodeling markers and a reduction in HDAC2 expression. Interestingly, treating COPD fibroblasts with the combination of STING inhibitor and dexamethasone alleviated remodeling and reversed steroid hyporesponsiveness through an upregulation of HDAC2. These findings support that STING pathway plays an important role in COPD pathogenesis, via inducing pulmonary inflammation, steroid resistance, and remodeling. This raises the possibility of using STING inhibitor as a potential therapeutic adjuvant in combination with common steroid treatment.

Effects of a Single Session of Systemic Vibratory Therapy on Flexibility, Perception of Exertion and Handgrip Strength in Chronic Obstructive Pulmonary Disease Individuals: A Quasi-Experimental Clinical Trial.

Whole-body vibration exercises (WBVE), that are generated in systemic vibratory therapy (SVT), may benefit individuals with chronic obstructive pulmonary disease (COPD). This study evaluated acute effects of SVT on the flexibility, on the perception of exertion to perform the anterior trunk flexion (ATF), and on the handgrip strength (HG). Thirty-eight individuals, separated into two groups, performed a single session of SVT (five bouts, 25 Hz, 2.5 of amplitude) on a side-alternating vibrating platform (SAVP), in two postures: sitting (Sitting group-SitG, n = 21) or standing (Stand group-StandG, n = 17). In both positions, the feet were on the base of the SAVP. The HG and the AFT were performed before and after the session, and the perception of effort (RPE) was measured during the ATF. The ATF in the SitG (p ≤ 0.05) and in the StandG (p ≤ 0.05) was significantly improved, but in the comparison between both groups, no significant reduction was found (p = 0.14). The RPE was not influenced by the session. A significant increase of the HG in StandG post session (33.49 ± 10.30 kgf) p = 0.03 was found, but not in the SitG (p = 0.12) or between the two groups (p = 0.55). SVT, in a single acute session, would be capable of promoting some functional benefits for the COPD individuals without altering the perception of exertion to perform the ATF. 49219115.3.0000.5259, RBR-72dqtm.

Alterations in mRNA Expression Levels of Tight Junction Proteins in the Blood Cells of Smokers with or without COPD.

This study aimed to assess the role of Tight junction proteins (TJPs) and claudins in smokers with and without COPD compared to healthy individuals. Chronic obstructive pulmonary disease (COPD) is a complex chronic respiratory disease, including various inflammatory mediators. The prime etiological element in the development of COPD is cigarette smoking. The lung airway epithelium comprises beneficial immunological barriers to draw in insults, such as environmental particulates, cigarette smoke, etc. Tight junctions (TJ) connected by transmembrane proteins determine epithelial permeability. Cigarette smoke is indicated to defect TJ integrity. The possible involvement of the airway epithelium in the pathogenesis of COPD has recently become apparent; however, its detailed mechanisms remain elusive. The integrity of airway epithelium is crucial for airway homeostasis; defective airway barrier activity contributes to COPD. In the present study, the objective was to investigate mRNA expression levels of TJP's like TJP-1, TJP-2, TJP-3, Tight junction-associated proteins-1, claudin-1, claudin-3, claudin-4, claudin-7, claudin-10, claudin-15, claudin-19, and claudin-25 from blood samples of smokers with COPD and compared them with smokers without COPD and healthy individuals. The mRNA expressions were evaluated by the quantitative PCR method. The gene expressions of these TJPs were significantly down-regulated, specifically in COPD patients with a history of smoking (Smokers with COPD). Besides, FEV% was also established for these patients. Similarly, smokers with COPD showed a significant increase in the expression levels of transcription factors, like ZEB-1, ZEB-2, PDGFA, and HDGF, compared to COPD patients without a history of smoking (smokers without COPD) and the healthy subjects. In conclusion, cigarette smoke disrupts TJ of the human airway epithelium, and the transcriptional factors counteract this smoke-induced COPD. Thus, TJPs may serve as protective elements for airway epithelial homeostasis during COPD.

Malnutrition associated with readmission in elderly patients with chronic obstructive pulmonary disease.

Malnutrition associated with readmission in elderly patients with chronic obstructive pulmonary disease.

Characterization of pulmonary vascular remodeling and MicroRNA-126-targets in COPD-pulmonary hypertension

BackgroundDespite causing increased morbidity and mortality, pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) patients (COPD-PH) lacks treatment, due to incomplete understanding of its pathogenesis. Hypertrophy of pulmonary arterial walls and pruning of the microvasculature with loss of capillary beds are known features of pulmonary vascular remodeling in COPD. The remodeling features of pulmonary medium- and smaller vessels in COPD-PH lungs are less well described and may be linked to maladaptation of endothelial cells to chronic cigarette smoking (CS). MicroRNA-126 (miR126), a master regulator of endothelial cell fate, has divergent functions that are vessel-size specific, supporting the survival of large vessel endothelial cells and inhibiting the proliferation of microvascular endothelial cells. Since CS decreases miR126 in microvascular lung endothelial cells, we set out to characterize the remodeling by pulmonary vascular size in COPD-PH and its relationship with miR126 in COPD and COPD-PH lungs.MethodsDeidentified lung tissue was obtained from individuals with COPD with and without PH and from non-diseased non-smokers and smokers. Pulmonary artery remodeling was assessed by ⍺-smooth muscle actin (SMA) abundance via immunohistochemistry and analyzed by pulmonary artery size. miR126 and miR126-target abundance were quantified by qPCR. The expression levels of ceramide, ADAM9, and endothelial cell marker CD31 were assessed by immunofluorescence.ResultsPulmonary arteries from COPD and COPD-PH lungs had significantly increased SMA abundance compared to non-COPD lungs, especially in small pulmonary arteries and the lung microvasculature. This was accompanied by significantly fewer endothelial cell markers and increased pro-apoptotic ceramide abundance. miR126 expression was significantly decreased in lungs of COPD individuals. Of the targets tested (SPRED1, VEGF, LAT1, ADAM9), lung miR126 most significantly inversely correlated with ADAM9 expression. Compared to controls, ADAM9 was significantly increased in COPD and COPD-PH lungs, predominantly in small pulmonary arteries and lung microvasculature.ConclusionBoth COPD and COPD-PH lungs exhibited significant remodeling of the pulmonary vascular bed of small and microvascular size, suggesting these changes may occur before or independent of the clinical development of PH. Decreased miR126 expression with reciprocal increase in ADAM9 may regulate endothelial cell survival and vascular remodeling in small pulmonary arteries and lung microvasculature in COPD and COPD-PH.

Physical activity pattern of patients with interstitial lung disease compared to patients with COPD: A propensity-matched study.

Physical activity (PA) is reduced in patients with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). Evidence about the PA pattern of patients with ILD is scarce. If PA of patients with ILD would be comparable to COPD, it is tempting to speculate that existing interventions focusing on enhancing PA could be as effective in ILD as already shown in COPD. Therefore, we aimed to compare PA and the correlates with PA in matched patients with ILD, COPD, and healthy subjects. Patients with ILD (n = 45), COPD (n = 45) and healthy subjects (n = 30) were propensity matched. PA level, pattern, and PA correlations with lung function and physical performance (6-minute walking distance and quadriceps force) were compared between groups. Daily number of steps was similar in both patient groups (mean±SE: 5631±459 for ILD, 5544±547 for COPD, p = 0.900), but significantly lower compared to healthy subjects (10031±536, p<0.001 for both). Mean intensity of PA tended to be lower in the ILD group (mean±SE metabolic equivalents of task per day: 1.41±0.04) compared to COPD (1.52±0.05, p = 0.074) and healthy individuals (1.67±0.04, p<0.001). The pattern of PA over one day was found to be similar between the three groups. Lastly, the correlation between PA and 6-minute walking distance was significantly weaker in patients with ILD compared to patients with COPD (respectively r = 0.348 and r = 0.739; p<0.05 for both). For a given functional reserve, patients with ILD perform an equal amount of steps but perform PA at lower intensity compared to patients with COPD. Both groups are less active compared to healthy control subjects. Functional exercise capacity was shown to be only moderately related to PA. This can potentially influence the effectiveness of PA interventions that can be expected.

Influence of SERPINA1 Gene Polymorphisms on Anemia and Chronic Obstructive Pulmonary Disease.

Anemia is one of the predominant hematological conditions, whereas chronic obstructive pulmonary disease (COPD) is a predominant respiratory disease. These two diseases were found to be interlinked, but the physiological pathways are still unclear. The current study has been aimed at analysing the genetic interrelationship between anemia and COPD in accordance with different altitudes. Methodology. The genetic analysis was performed in the SERPINA1 gene of anemia, COPD, and healthy individuals for the analysis of single nucleotide polymorphism at rs28949274 and rs17580 locations. Result and Discussion. The single nucleotide polymorphism at the locations rs28949274 and rs17580 was present in both anemic and COPD patients. The COPD patients were more prone to mutations (63% had rs28949274, and 11% had rs17580 polymorphisms) than the anemic patients (40% had rs28949274, and 1% had rs17580 polymorphisms). On the basis of altitude, high-altitude individuals were found to be more susceptible to both the polymorphisms. Based on the current findings, we suggest that the SERPINA1 gene has a positive correlation with anemia as well as COPD, and the increase in altitude also influences the diseased conditions in a positive manner.

Low bone mineral density and chronic obstructive pulmonary disease – A missed correlation

Chronic obstructive pulmonary disease (COPD) is a disorder involving various other systems in the body apart from lungs. Such co-existence leads to worsening of disease control and associated increase in the morbidity as well as mortality of the diseased patients. They COPD patients are more prone for association with low fat free mass and low bone mineral density owing to pronounced persistent inflammation and various other associated risk factors. Low bone mineral density in those patients lead to the development of osteoporosis in those patients. Osteoporosis also worsens COPD and reduce their symptom free survival and reduction in day-to-day activities. However, the occurrence of osteoporosis in COPD patients is not well represented. The main objective is to study the occurrence of low bone mineral density leading to osteoporosis and osteopenia in COPD individuals and to propose various risk Factors leading to its development. This cross-sectional prevalence study was done in a tertiary care hospital in the department of Respiratory medicine over a period of 2 years. 100 diagnosed patients of COPD by spirometry (FEV/FVC &amp;#60; 0.70) according to GOLD guidelines were included in the study. Spirometry was done to group the patients in various grades of airflow obstruction severity and DXA scan of lumbar spine was done with the help of bone densitometer to determine the T-scores and to look for the presence of any reduction in Bone Mineral Density (BMI) satisfying WHO osteoporosis diagnostic guidelines. Among the 100 patients of COPD, 52 patients (52%) had osteoporosis and 22 patients (22%) had osteopenia. Majority of the patients (96.1%) who had osteoporosis were confined to stages 3 and 4 GOLD grading of severity of airflow obstruction. Patients in stages III and IV of airflow obstruction severity were found to have reduction in their bone mineral density. Underweight COPD patients were found to have higher cases of osteoporosis. On analysis; female sex, severe degree of airflow obstruction, Underweight, intake of higher doses of inhalational and oral or systemic corticosteroids, frequent exacerbations and deficiency of 1,25-Dihydrocholecalciferol were observed as risk factors for osteoporosis in COPD patients. In this study, the prevalence of osteoporosis and osteopenia were 52% and 22% respectively in the COPD patients. The risk of acquiring osteoporosis increased with the airflow obstruction severity. Thus, a high index of clinical suspicion and early diagnosis of it is essential to evaluate for osteoporosis in COPD and to treat it early to prevent further disability, morbidity and mortality and to improve the quality of life in COPD patients.