Irreversible Airflow Obstruction Research Articles

Left ventricular function in patients with advanced stages of chronic obstructive pulmonary disease in correlation with GOLD classification system

Background: Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, with irreversible airflow obstruction, disease with high morbidity and early mortality rate. COPD is not just a disorder limited to the lungs. As the disease progresses, extra pulmonary co morbidities occur, where cardiovascular diseases are the most common. They mostly affect the right side of the heart, but sometimes changes also occur on the left side of the heart, as a result of long-term strain from the right ventricle (RV) and pulmonary hypertension which follows COPD. Material and methods: The design of our study was prospective-clinical crosssectional study with 2 years follow up. In the study were included 94 patients with previously confirmed chronic obstructive pulmonary disease with spirometry and classified by Tiffeneau index in four gold classes. We have analyzed the values of some echocardiographic parameters that were selected as indicators of left heart function, and also we have analyzed them in relation to the progression of COPD from milder to more severe Golden classes, such as: left ventricular diastolic dimension (LvdD - mm), left ventricular ejection fraction (EF %), myocardial performance index (MPI) of the left ventricle, global longitudinal strain (Gl strain - %) of LV, diastolic function (E/e'). Echo analysis was done by Vivid 7 echo machine with a special feature to left heart chamber characteristics and function. Results: All echocardiographic parameters analyzed in our study, underline their significance in disease progression in patients with COPD and increasing Gold classes. A varies of statistical methods and parameters were used to evaluate: left ventricular diastolic dimension(mm), Ejection fraction of left ventricle (%), MPI of the left ventricle obtain by Tissue Doppler, GL strain of left ventricle (%) and E/e' in correlation of disease progression and GOLD class. Echo-parameters MPI of the left ventricle and Global longitudinal strain LV (%), progressively grow with the rise of the gold class (form I to IV). On the contrary the values of the parameters LvdD and EF% gradually decrease with the progression of the disease and gold class. Echocardiographic parameter GL strain LV % has the highest value and statistically by decreasing the values of this parameter the risk of disease progression from gold stage I/II to Gold stage III/IV is 1.570 times higher, with high statistical significance(p<0,01). The calculated value of the parameter EF% is lower than 0,75, which indicates that the model of prediction is not the best one but it's acceptable. Conclusion: COPD is a progressive disease that affects the dimensions of the right and left heart chambers, as well as the function of both chambers and the development of pulmonary hypertension. Monitoring echocardiographic parameters intended for assessment cardiac dimension and function can help tо predict disease progression for timely inclusion of specific therapeutic strategies. We suggest screening of all COPD patients for cardiac assessment using echocardiography as a non-invasive and repeatable method for their follow-up.

Prevalence of coronary artery disease in chronic obstructive pulmonary disease patients- a retrospective observational study

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that results in progressive and irreversible air flow obstruction usually caused by an inflammatory response of the lungs to noxious particles and gases. There are periods of acute episodes of worsening and exacerbation. COPD was predicted to be the third leading cause of death worldwide by 2020, is a major cause of disability adjusted life years (DALY). Patients with COPD are often complicated by coronary artery disease (CAD), both of which are public health problems. There are probably a lot of mechanisms involved in the co-existence of these comorbidities like ageing, sedentary life style, systemic inflammation, atherosis and arterial stiffness. The confirmation of this comorbidity in COPD is very important as it can have implications in the management of the disease. Methods: This observational study was done in a tertiary care hospital in Central Kerala. It was a retrospective observational study. 100 patients were included in the study. Results: Out of 100 COPD patients that were included in the study, 27% of them had CAD as a comorbidity which implies that all patients with COPD should be screened for CAD as well. Conclusions: All COPD patients should be screened for a coexisting CAD.

Impact of COPD and Its Causes

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide health problem that is increasing in prevalence. This progressive lung condition is characterized by irreversible air flow obstruction, mostly attributable to smoking, environmental and occupational exposures. It is a syndrome composed of chronic bronchitis, small air way disease and emphysema that vary in proportion between affected individuals.

Twenty years of changes in the definition of early chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population. Due to irreversible airflow obstruction and progressive lung function decline, COPD is characterized by high mortality and disability rates, which imposes a huge economic burden on society. In recent years, the importance of intervention in the early stage of COPD has been recognized and the concept of early COPD has been proposed. Identifying and intervening in individuals with early COPD, some of whom have few or no symptoms, might halt or reverse the progressive decline in lung function, improve the quality of life, and better their prognosis. However, understanding of early COPD is not yet well established, and there are no unified and feasible diagnostic criteria, which complicates clinical research. In this article, we review evolution of the definition of early COPD over the past 20 years, describe the changes in awareness of this concept, and propose future research directions.

Nutritional State and COPD: Effects on Dyspnoea and Exercise Tolerance

Chronic Obstructive Pulmonary Disease (COPD) is a disease that is spreading worldwide and is responsible for a huge number of deaths annually. It is characterized by progressive and often irreversible airflow obstruction, with a heterogeneous clinical manifestation based on disease severity. Along with pulmonary impairment, COPD patients display different grades of malnutrition that can be linked to a worsening of respiratory function and to a negative prognosis. Nutritional impairment seems to be related to a reduced exercise tolerance and to dyspnoea becoming a major determinant in patient-perceived quality of life. Many strategies have been proposed to limit the effects of malnutrition on disease progression, but there are still limited data available to determine which of them is the best option to manage COPD patients. The purpose of this review is to highlight the main aspects of COPD-related malnutrition and to underline the importance of poor nutritional state on muscle energetics, exercise tolerance and dyspnoea.

SIRT1 as a Potential Therapeutic Target for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease characterized by irreversible airflow obstruction and lung function decline. It is well established that COPD represents a major cause of morbidity and mortality globally. Due to the substantial economic and social burdens associated with COPD, it is necessary to discover new targets and develop novel beneficial therapies. Although the pathogenesis of COPD is complex and remains to be robustly elucidated, numerous studies have shown that oxidative stress, inflammatory responses, cell apoptosis, autophagy, and aging are involved in the pathogenesis of COPD. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase belonging to the silent information regulator 2 (Sir2) family. Multiple studies have indicated that SIRT1 plays an important role in oxidative stress, apoptosis, inflammation, autophagy, and cellular senescence, which contributes to the pathogenesis and development of COPD. This review aimed to discuss the functions and mechanisms of SIRT1 in the progression of COPD and concluded that SIRT1 activation might be a potential therapeutic strategy for COPD.

Co-existence of Bronchiectasis and Chronic Obstructive Pulmonary Disease

We present the case of a 56-year-old male who presented with cough and breathlessness. Chest radiograph (postero-anterior view) showed bulla and signs of hyperinflation in the right upper zone with cystic shadows in the left lower zone. Spirometry showed severe irreversible airflow obstruction with restriction and decreased diffusion capacity for carbon monoxide. On high resolution computed tomography (HRCT), right upper lobe bulla with emphysematous changes and left lower lobe cystic bronchiectasis were seen. Considering its rarity of occurrence and paucity of data in literature regarding co-existence of bronchiectasis with emphysema, this case is being reported.

Muscarinic receptor M3 activation promotes fibrocytes contraction.

Fibrocytes are monocyte-derived cells able to differentiate into myofibroblasts-like cells. We have previously shown that they are increased in the bronchi of Chronic Obstructive Pulmonary Disease (COPD) patients and associated to worse lung function. COPD is characterized by irreversible airflow obstruction, partly due to an increased cholinergic environment. Our goal was to investigate muscarinic signalling in COPD fibrocytes. Fibrocytes were isolated from 16 patients with COPD’s blood and presence of muscarinic M3 receptor was assessed at the transcriptional and protein levels. Calcium signalling and collagen gels contraction experiments were performed in presence of carbachol (cholinergic agonist) ± tiotropium bromide (antimuscarinic). Expression of M3 receptor was confirmed by Western blot and flow cytometry in differentiated fibrocytes. Immunocytochemistry showed the presence of cytoplasmic and membrane-associated pools of M3. Stimulation with carbachol elicited an intracellular calcium response in 35.7% of fibrocytes. This response was significantly blunted by the presence of tiotropium bromide: 14.6% of responding cells (p < 0.0001). Carbachol induced a significant contraction of fibrocytes embedded in collagen gels (13.6 ± 0.3% versus 2.5 ± 4.1%; p < 0.0001), which was prevented by prior tiotropium bromide addition (4.1 ± 2.7% of gel contraction; p < 0.0001). Finally, M3-expressing fibrocytes were also identified in situ in the peri-bronchial area of COPD patients’ lungs, and there was a tendency to an increased density compared to healthy patient’s lungs. In conclusion, around 1/3 of COPD patients’ fibrocytes express a functional muscarinic M3 receptor. Cholinergic-induced fibrocyte contraction might participate in airway diameter reduction and subsequent increase of airflow resistance in patients with COPD. The inhibition of these processes could participate to the beneficial effects of muscarinic antagonists for COPD treatment.

Modulation of Arginase-2 mRNA Levels by ω-3 PUFAs and Aspirin in Asthmatic Human Lung Fibroblasts.

Airway remodeling (AR) increases disease severity, and morbidity of asthmatic patients by contributing to irreversible airflow obstruction and progressive declines in lung function. Arginase isoenzymes and the downstream enzymes ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) have been implicated in the hyperplastic and fibrotic changes of AR, respectively. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and resolvin metabolites have anti-AR effects, but whether they are mediated through the arginase pathway is unclear. Our study intended to determine the effects of the ω-3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), resolvin D1 (RvD1), TH1 cytokines, acetylsalicylic acid (ASA), cAMP, and dexamethasone (DEX) on the expression of arginase isoenzymes arginase 1 (ARG1) and arginase 2 (ARG2), ODC, and OAT in human lung fibroblasts (HLF) from normal (NHLF) and diseased (DHLF) asthmatic donors using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Our data showed that EPA and EPA+DHA downregulated ARG2 mRNA 2-fold in both types of HLF. DHA, RvD1, and DEX did not alter mRNA levels for any of the genes studied. EPA lowered the ARG2 protein levels in DHLF, but did not affect those levels in NHLF. ASA upregulated ARG2 mRNA 5-fold and 7-fold in NHLF and DHLF, respectively, TH1 cytokines downregulated ARG2, ODC, and OAT mRNA in DHLF 10-fold, 2-fold, and 2.5-fold, respectively, and cAMP downregulated ARG2 mRNA 2-fold in DHLF. These results are the first to show a direct effect of ω-3 PUFAs on ARG2 mRNA levels and provide further evidence for a role of ω-3 PUFAs in AR.

Biologics and airway remodeling in severe asthma.

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

Angiogenesis, Lymphangiogenesis, and Inflammation in Chronic Obstructive Pulmonary Disease (COPD): Few Certainties and Many Outstanding Questions.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, predominantly affecting the lung parenchyma and peripheral airways, that results in progressive and irreversible airflow obstruction. COPD development is promoted by persistent pulmonary inflammation in response to several stimuli (e.g., cigarette smoke, bacterial and viral infections, air pollution, etc.). Angiogenesis, the formation of new blood vessels, and lymphangiogenesis, the formation of new lymphatic vessels, are features of airway inflammation in COPD. There is compelling evidence that effector cells of inflammation (lung-resident macrophages and mast cells and infiltrating neutrophils, eosinophils, basophils, lymphocytes, etc.) are major sources of a vast array of angiogenic (e.g., vascular endothelial growth factor-A (VEGF-A), angiopoietins) and/or lymphangiogenic factors (VEGF-C, -D). Further, structural cells, including bronchial and alveolar epithelial cells, endothelial cells, fibroblasts/myofibroblasts, and airway smooth muscle cells, can contribute to inflammation and angiogenesis in COPD. Although there is evidence that alterations of angiogenesis and, to a lesser extent, lymphangiogenesis, are associated with COPD, there are still many unanswered questions.

Pathobiology of Airway Remodeling in Asthma: The Emerging Role of Integrins.

Airway remodeling is a complex clinical feature of asthma that involves long-term disruption and modification of airway architecture, which contributes significantly to airway hyperresponsiveness (AHR) and lung function decline. It is characterized by thickening of the airway smooth muscle layer, deposition of a matrix below the airway epithelium, resulting in subepithelial fibrosis, changes within the airway epithelium, leading to disruption of the barrier, and excessive mucous production and angiogenesis within the airway wall. Airway remodeling contributes to stiffer and less compliant airways in asthma and leads to persistent, irreversible airflow obstruction. Current asthma treatments aim to reduce airway inflammation and exacerbations but none are targeted towards airway remodeling. Inhibiting the development of airway remodeling or reversing established remodeling has the potential to dramatically improve symptoms and disease burden in asthmatic patients. Integrins are a family of transmembrane heterodimeric proteins that serve as the primary receptors for extracellular matrix (ECM) components, mediating cell–cell and cell–ECM interactions to initiate intracellular signaling cascades. Cells present within the lungs, including structural and inflammatory cells, express a wide and varying range of integrin heterodimer combinations and permutations. Integrins are emerging as an important regulator of inflammation, repair, remodeling, and fibrosis in the lung, particularly in chronic lung diseases such as asthma. Here, we provide a comprehensive summary of the current state of knowledge on integrins in the asthmatic airway and how these integrins promote the remodeling process, and emphasize their potential involvement in airway disease.

Expression and Related Mechanisms of miR-100 and TRIB2 in COPD Patients.

Background Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases in the world. COPD is a general term for a class of lung diseases, including emphysema, chronic bronchitis, and refractory asthma. It is characterized by irreversible airflow obstruction and chronic tracheal inflammation. Objective This study aimed to investigate the expression and related mechanisms of miR-100 and TRIB2 in patients with COPD. Methods We collected the serum of patients admitted to our hospital and healthy volunteers undergoing physical examination at the same time, pulmonary fibroblasts were purchased for the experiments, miR-100 was overexpressed, and TRIB2 expression was inhibited in cells. The miR-100 and TRIB2 expression levels in serum and cells were detected by qRT-PCR and Western blot, cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, and the relationship between miR-100 and TRIB2 was explored by the dual-luciferase report. Results The miR-100 expression in the serum of the COPD group was expressed normally, while the TRIB2 expression was expressed abnormally (p < 0.05). The AUC of serum miR-146a and TRIB2 for COPD diagnosis were 0.965 and 0.954, respectively. Overexpressing miR-100 and inhibiting the TRIB2 expression could decrease cell proliferation and increase apoptosis rate. According to the dual-luciferase report, miR-100 and TRIB2 had a targeted regulatory relationship. Rescue experiments showed that overexpressing TRIB2 could reverse the changes of cell proliferation and apoptosis caused by overexpression of miR-100. Conclusion miR-100 and TRIB2 were expressed abnormally in serum of COPD patients, and miR-100 could inhibit proliferation of pulmonary fibroblasts and promote their apoptosis.

Muscarinic receptor M3 activation promotes COPD fibrocyte contraction

Fibrocytes are circulating monocytes-derived cells, able to migrate to injured organs in order to differentiate into myofibroblasts-like cells. We have previously shown that their densities are increased in the lungs of Chronic Obstructive Pulmonary Disease (COPD) patients and associated to worse lung function (Eur Respir J 2019 54: 1802173). COPD is characterized by irreversible airflow obstruction, partly due to an increased cholinergic environment (increased muscarinic M3 signalling, targeted by short and long-acting muscarinic antagonists). We hypothesize that the contractile status of differentiated fibrocytes is under control of a cholinergic stimulation. Fibrocytes were isolated from COPD patients’ blood and cultured for 14 days to reach full differentiation. Presence of M3 receptor was quantified by qPCR, flow cytometry and immunocytochemistry. Calcium signalling as well as contraction experiments using collagen gels were performed in presence of carbachol (cholinergic agonist) ± tiotropium bromide (M2/M3 antagonist). qPCR showed that differentiated fibrocytes expressed all isoforms of muscarinic receptors (M1 to M5). Moreover, 59,7% (± 15) of fibrocytes were found to express the M3 receptor by flow cytometry. Immunocytochemistry showed the existence of cytoplasmic and membrane-associated pools of M3 ( Fig. 1 A). Stimulation with carbachol (10 −4 M) elicited an intracellular calcium response in 39% (± 20) of fibrocytes, with a mean peak amplitude of 0,86 (± 0,66). Such response was blunted in presence of tiotropium bromide (10 –6 M): 28% (± 4) of responding cells and mean peak amplitude of 0,2 ± 0,04. Moreover, carbachol induced a significant contraction of fibrocytes embedded in collagen gels (86,4 ± 0,3% of initial gel surface versus 97,5 ± 4,1%; p < 0,0001), which was prevented by prior tiotropium bromide addition (resulting in 95,9 ± 2,7% of initial surface; p < 0,0001, Fig. 1 B). Around 1/3 of COPD patient's fibrocytes express a functional muscarinic M3 receptor. Cholinergic-induced fibrocyte contraction could participate in airway diameter reduction and subsequent increase of airflow resistance in patients with COPD. The inhibition of these processes could participate to the beneficial effects of muscarinic antagonists for COPD treatment.

Prenatal exposure to air pollution: A susceptibility factor to develop Chronic Obstructive Pulmonary Disease?

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow obstruction, accompanied by the progressive loss of lung function. COPD clinical onset occurs after 40ys, but the role of events occurring before entering adult life is more and more suggested. As exposure of adults or children to air pollution is associated with (functional) respiratory alterations, and perinatal exposure to air pollution has been reported to cause deleterious consequences on fetal growth and development, our hypothesis is that prenatal exposure to air pollution could represent a susceptibility factor to develop COPD at adult age. Our objective is therefore to address this issue thanks to an innovative approach based on the use of an atmospheric simulation chamber dedicated to the study of multiphasic atmospheric processes. Pregnant C57/BL6 J mice were exposed to Beijing- or Paris-type atmospheres (hereafter: Beijing or Paris) or to their respective Control air from 9th to 16th day of gestation. At adulthood (D60), the offspring are exposed to cigarette smoke, as a mice model of COPD. The effects on lung development, remodeling and function in the offspring were studied at different life stages. The kinetics of appearance of COPD and its severity were analyzed. Prenatal exposure to either Beijing or Paris simulated atmosphere is accompanied by a higher neonatal mortality as compared to their respective Control air. At adolescence (D17), morphological analyses show a delayed lung development in Beijing offspring as compared to its Control air. Interestingly, the lung of offspring “catches up” at adult age (D60), as a normal pulmonary structure is observed. After 3-month cigarette smoking (D150), we can observe a destruction of alveolar walls in Beijing offspring (characteristic of emphysema), as well as in their littermates exposed in utero to Control air. No such phenomena are observed in Paris offspring. The underlying molecular mechanisms are still under investigation. Prenatal exposure to high pollution simulated atmosphere leads to a delayed pulmonary development, followed by a catch-up at adult age. At the moment, our results do not allow us to state that this leads to a particular susceptibility to develop COPD later on.

Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium.

COPD is a chronic lung disorder characterized by a progressive and irreversible airflow obstruction, and persistent pulmonary inflammation. It has become a global epidemic affecting 10% of the population, and is the third leading cause of death worldwide. Respiratory viruses are a primary cause of COPD exacerbations, often leading to secondary bacterial infections in the lower respiratory tract. COPD patients are more susceptible to viral infections and associated severe disease, leading to accelerated lung function deterioration, hospitalization, and an increased risk of mortality. The airway epithelium plays an essential role in maintaining immune homeostasis, and orchestrates the innate and adaptive responses of the lung against inhaled and pathogen insults. A healthy airway epithelium acts as the first line of host defense by maintaining barrier integrity and the mucociliary escalator, secreting an array of inflammatory mediators, and initiating an antiviral state through the interferon (IFN) response. The airway epithelium is a major site of viral infection, and the interaction between respiratory viruses and airway epithelial cells activates host defense mechanisms, resulting in rapid virus clearance. As such, the production of IFNs and the activation of IFN signaling cascades directly contributes to host defense against viral infections and subsequent innate and adaptive immunity. However, the COPD airway epithelium exhibits an altered antiviral response, leading to enhanced susceptibility to severe disease and impaired IFN signaling. Despite decades of research, there is no effective antiviral therapy for COPD patients. Herein, we review current insights into understanding the mechanisms of viral evasion and host IFN antiviral defense signaling impairment in COPD airway epithelium. Understanding how antiviral mechanisms operate in COPD exacerbations will facilitate the discovery of potential therapeutic interventions to reduce COPD hospitalization and disease severity.

The leukocyte telomere length, single nucleotide polymorphisms near TERC gene and risk of COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and is associated with chronic local and systemic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect telomere length (TL). Furthermore, a number of SNPs at loci encoding the main components of the telomerase genes, TERT and TERC have been shown to correlate with TL. We aimed to explore the leukocyte TL and genotypes for single nucleotide polymorphisms, rs12696304 (C > G) and rs10936599 (C > T) near TERC in COPD cases and matched healthy controls using q-PCR technologies. Successful assessment of TL was performed for 91 patients and 88 controls. The patients had shorter TL (17919.36 ± 1203.01 bp) compared to controls (21 271.48 ± 1891.36 bp) although not significant (p = 0.137). The TL did not associate with the gender, age, spirometric indexes, smoking habits but tended to correlate negatively with BMI (Rho = − 0.215, p = 0.076) in the controls, but not in COPD patients. The genotype frequencies of the SNPs rs12696304 and rs10936599 were compared between patients and controls and the odds ratios (OR) for developing COPD were calculated. The carriers of the common homozygous (CC) genotypes of the SNPs had higher risk for COPD, compared to carriers of the variants alleles (rs12696304 CG+GG vs. CC; OR: 0.615, 95% CI [0.424–0.894], p = 0.011 and for rs10936599 CT+TT vs. CC OR = 0.668, 95% CI [0.457–0.976], p = 0.044). Analysis on the combined effects of the TERC rs12696304 (C > G) and rs10936599 (C > T) genotypes, CC/CC genotype combination was associated with higher risk for COPD (p < 0.0001) and marginally lower FEV1% pr. in patients with GOLD II (p = 0.052). There was no association between the SNP genotypes and TL. In summary, our results suggest that COPD patients may have shorter TL, and rs12696304 and rs10936599 near TERC may affect the risk of COPD independently of TL.

Pre-Transplant Pulmonary Function Test Parameters of FEF50% (Forced expiratory flow at 50% of forced vital capacity) and RV (residual volume) in Combination Can Predict the Risk for Development of Lung Gvhd after Allogeneic Transplantation

BackgroundChronic graft vs host disease (GVHD) of the lung is a significant post-transplant complication that impacts patients' quality of life and overall survival. It manifests as bronchiolitis obliterans syndrome (BOS), an irreversible progressive airflow obstruction. Risk factors identified include busulfan, peripheral blood stem cell source, post-transplant viral infections, history of lung disease, and acute GVHD. Diagnosis involves changes in pulmonary function tests (PFTs), ruling out infection and presence of chronic GVHD in other organ systems. Without routine monitoring patients can present with moderate to severe symptoms. The predictive value of pre-transplant PFTs has not been clearly elucidated. In this retrospective study, we examined the role of pre-transplant PFT parameters with respect to the development of lung GVHD.MethodsPatients receiving allogeneic HCT at Princess Margaret Cancer Centre between 2004 to 2013 were included in the analysis. Pre-HCT PFT results were routinely obtained within 30 days prior to transplant. PFT parameters included % predicted FEV1, DLCO, TLC, RV, RV/TLC, FRC, FVC, FEV1/FVC, FEF50% and FEF75%. After transplant, PFT was repeated around day 120, then annually, or when clinically indicated.Our definition of lung GVHD required at least the first two of the 2005 NIH consensus criteria for the diagnosis of chronic lung GVHD: 1) FEV1/forced vital capacity ratio <0.7 and FEV1<75% predicted, 2) evidence of airway obstruction on high-resolution computed tomography or a residual volume on PFTs >120%, 3) absence of infection in the respiratory tract, and 4) histologic diagnosis of BOS or at least 1 other manifestation of chronic GVHD in an additional organ system.The primary endpoint was cumulative incidence (CI) of lung GVHD at 3 years. The cut-off values in each PFT parameter with respect to development of lung GVHD were calculated using binary recursive partitioning (rpart) method provided by rpart package using R. Pearson's correlation test was used to look for relationship among the PFT parameters. The parameters with cut-offs identified by rpart were analyzed by factor analysis with Varimax rotation method.For multivariable analysis, Fine-Gray proportional hazard regression with competing risks was applied. The clinical variables included in the model were busulfan, acute GVHD, and stem cell source (peripheral vs bone marrow). All statistical tests were performed using EZR and SPSS.ResultsA total of 605 patients with available PFTs were reviewed. The CI of lung GVHD at 3 years was 10.6% (7.9 - 13.7) with a median onset at 12.6 months (range of 1.7 - 55.8).Univariate analysis of each PFT parameter as a continuous variable did not show an impact on development of GVHD. With recursive partitioning, cut-offs were identified for DLCO (68%), FEF50% (39%), FRC (130%) and RV (93%).In Pearson's correlation analysis, DLCO and FEF50% did not have a significant association with the other PFT parameters selected from rpart, while RV was significantly associated with TGV (r= 0.65). In the factor analysis, based on the factor loading, FEF50% and RV were selected for multivariate analysis.Multivariate analysis showed that FEF50% < 39% and RV ≥ 93% were independent risk factors of lung GVHD development. The patients with pre-transplant FEF50 ≥ 39% had significantly less risk compared to those with < 39% (p=0.025; HR 0.389), and RV ≥ 93% showed a 2 fold higher risk than those < 93% (p=0.036, HR 2.63).A risk score model was created using the cut-offs from FEF50% and RV. For FEF50%, score 0 was assigned to ≥ 39% while score 1 was < 39%. For RV, score 0 was assigned to < 93%, while score 1 was ≥ 93%. A risk score was summed from the two parameters. Risk scores of 2 were classified as high risk, scores of 1 intermediate risk and score of 0 low risk. The 3 year CIs of lung GVHD were then compared according to the new risk score. The high risk group had an incidence of 33.5% (11.8 - 57.0%; n=28, 4.6%), intermediate risk 11.4% (8.3 - 15.2%; n=445, 73.6%) and low risk 3.0% (0.8 - 8.2%; n=132, 21.8%; p = 0.003; Figure).Conclusions1) Pre-transplant PFT parameters can predict the risk of lung GVHD development.2) FEF50% and RV were predictive of lung GVHD development independent from the other clinical risk factors acute GVHD, busulfan and stem cell source which were not confirmed in our cohort.3) A risk score model using pre-transplant FEF50% and RV may help in prediction of lung GVHD. [Display omitted] DisclosuresKim:Paladin: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy.

Investigation serum procalcitonin in patients with exacerbation of obstructive pulmonary disease

Introduction: Chronic obstructive pulmonary disease (COPD) is a disease of chronic diffuse irreversible airflow obstruction. Due to the relatively high prevalence of the disease, paying attention to the treatment of these patients helps a lot in controlling the disease and reducing its cost. This study aimed to investigate the presence of serum procalcitonin in patients with an acute attack of COPD. Methods & Materials: This cross-sectional study was performed on 65 patients with an acute COPD attack in Imam Reza Hospital in 2019 by the convenience sampling method. Three ccs of blood samples were taken from patients to check serum procalcitonin levels from hospitalization to 24 hours after that. Patients with an acute COPD attack were selected based on American thoracic society criteria. Also, demographic information such as age, sex, hospitalization time, and duration of the disease was recorded. Patient complaints, disease exacerbation, and type of ventilation were recorded. Data were analyzed with SPSS software (version 16). Man-Whitney and Kruskal Wallis tests were used to analyze the data. The significance level was Results: According to data, 65 patients (36 men and 29 women) were examined and the mean age of the patients was 66.72 (±12.65) years. Dyspnea was the most common complaint in patients. Serum procalcitonin levels were higher in patients with invasive ventilation (P = 0.007). Also, serum procalcitonin levels were lower in patients with non-invasive ventilation (P = 0.008). Besides, serum procalcitonin levels increase with increasing disease exacerbation from mild to moderate (P <0.001). According to the results of the post hoc test, there was a significant difference between mild and severe (P <0.001) and moderate and severe groups (P <0.001). There is also a significant correlation between procalcitonin serum levels and Exacerbation (R=0.6, P <0.001) and age (R=0.2, P = 0.01). serum procalcitonin levels were higher in patients with the use of invasive ventilation Conclusion: According to the results, serum procalcitonin levels are associated with acute COPD attacks. Measurement of procalcitonin levels in patients with acute COPD attacks can help diagnose and perform timely care.

Clinical and biological factors associated with irreversible airway obstruction in adult asthma

Background and objectiveAirway remodeling, as many other factors, may lead to lung function decline and irreversible airflow obstruction (IRAO) in asthma. This study was undertaken in order to highlight predictors of incomplete reversibility of airflow obstruction in adult asthmatics to identify patients with poorer prognosis and improve their care, and decrease morbidity. MethodsA retrospective study was conducted in 973 asthmatics recruited from the University Asthma Clinic of Liege. Patients with IRAO (post-BD FEV1/FVC<0.7 & FEV1<80% predicted) were compared to patients with reversible airway obstruction (RAO) (post-BD FEV1/FVC≥0.7 & FEV1≥80% predicted). TGF-β was measured in sputum supernatant of 85 patients. ResultsSeventeen percent of asthmatics presented with IRAO. These patients were significantly older, more smokers, with a lower proportion of female, a longer disease duration, were more poorly controlled with a lower quality of life. This sub-population of asthmatics also showed more often elevated blood and sputum eosinophils and neutrophils, and higher exacerbation and hospitalisation rates in the previous year. The multivariable analysis revealed male gender, longer disease duration, cigarette smoking, ACQ score, sputum eosinophils and neutrophils, ICS dose and OCS maintenance, BMI, and asthma onset as variables independently linked to IRAO. Total TGF-β levels appeared higher in patients with IRAO (n = 38) compared to patients with RAO (n = 47). ConclusionThese data show that risk factors for IRAO are male gender, smoking, a longer disease duration, uncontrolled asthma, eosinophilic or neutrophilic airway inflammation, lower BMI, and later asthma onset. Moreover, TGF-β levels are higher in IRAO.