Defining the role of neutrophil-to-lymphocyte ratio in COPD: a systematic literature review

COPD is characterized by a pulmonary and systemic inflammatory process. Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations. The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count. We performed a systematic literature review using the PRISMA statement. Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls. Compared with controls, COPD patients had significantly higher NLR values. We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients. Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively). Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity. The NLR is an independent predictor of in-hospital and late mortality after exacerbation. In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness

Objectives: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality

A cross-sectional study to assess inhalation device handling and patient satisfaction in COPD

Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD). Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ) to assess the handling and satisfaction for Respimat (R) Soft Mist (TM) Inhaler (SMI) compared with the Breezhaler (R) dry powder inhaler (DPI) among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA (R) (tiotropium) Respimat (R) or with Hirobriz (R)/Onbrez (R)/Oslif (R) (indacaterol) Breezhaler (R) for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ total score in the Respimat (R) and Breezhaler (R) groups was 80.7 and 79.9, respectively (difference of 0.8, 95% confidence interval [CI] -2.9 to 4.5; P= 0.67). The mean total performance scores were 82.5 and 78.2 (difference of 4.3, 95% CI -0.3 to 8.9; P= 0.06), and the mean total convenience scores were 78.6 and 81.9 (difference of -3.3, 95% CI -7.0 to 0.4; P= 0.08) for the Respimat (R) and Breezhaler (R) groups, respectively. Patients gave the Respimat (R) SMI and the Breezhaler (R) DPI overall satisfaction PASAPQ scores of 6.0 and 5.9, respectively, which shows that patients were satisfied with these inhalers

Impact of the implementation of a telemedicine program on patients diagnosed with asthma.

Background: Asthma is one of the most common respiratory ailments worldwide. Despite broad understanding of the illness and of the available therapeutic options for it, patients with serious asthma suffer poor monitoring of their illness in 50% of cases. Aim: To assess the impact of the implementation of a mobile application (ESTOI) to control asthma in patients diagnosed with the illness, their adherence to treatment, and their perceived quality of life. Methodology: Randomized clinical trial with 52 weeks' follow-up of patients with asthma seen in a specialized hospital for their treatment in Spain. Some 108 included patients will be divided into two groups. The intervention group will undergo more exhaustive follow-up than normal, including access to the ESTOI application, which will have various categories of attention: control of symptoms, health recommendations, current treatment and personalized action plan, PEF record, nutritional plan, and chat access with a medical team. The asthma control questionnaire ACT is the main assessment variable. Other variables to be studied include an adherence test for the use of inhalers (TAI), the number of exacerbations, maximum exhalation flow, exhaled nitric oxide test, hospital anxiety and depression scale, asthma quality-of-life questionnaire, forced spirometry parameters (FVC, FEV1, and PBD), and analytic parameters (eosinophilia and IGE). The data will be collected during outpatient visits. Trial registration: This trial has registered at ClinicalTrials.gov (Identifier: NCT06116292)

Vascular disease in COPD: systemic and pulmonary expression of PARC (Pulmonary and Activation-Regulated Chemokine)

Introduction: The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects. Methods: To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal arteries and serum samples from COPD patients, non-obstructed smokers (NOS) and never-smokers (NS). Results: A total of 57 subjects were included in the analysis (23 COPD, 18 NOS and 16 NS). In the comparisons between groups, a significantly increased lung protein expression of PARC was observed in the COPD group compared to the NOS group (1.96±0.22 vs. 1.29±0.27, P-adjusted = 0.038). PARC was located predominantly in the smooth muscle cells of the remodeled pulmonary muscular arteries and the macrophage-rich area of the alveolar parenchyma. No differences were detected in PARC gene expression analyses. The protein content of PARC in the intercostal arteries were similar between groups, though little remodeling was observed in these arteries. Circulating levels of PARC were numerically higher in patients with COPD compared to NOS and NS. Conclusion: The results of the present study suggest an increased lung protein expression of PARC in COPD subjects. This protein was mainly localized in the smooth muscle cells of the pulmonary muscular arteries and was associated with the severity of intimal thickening, indicating its possible role in this remodeling process

Imbalance in the expression of genes associated with purinergic signalling in the lung and systemic arteries of COPDpatients.

Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment

Is the purinergic pathway involved in the pathology of COPD? Decreased lung CD39 expression at initial stages of COPD

Background: Extracellular adenosine triphosphate (ATP) is up-regulated in the airways of patients with chronic obstructive pulmonary disease (COPD), resulting in increased inflammation, bronchoconstriction, and cough. Although extracellular ATP levels are tightly controlled by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; also known as CD39) in the lungs, the role of CD39 in the pathology of COPD is unknown. We hypothesized that alterations in the expression and activity of CD39 could be part of the mechanisms for initiating and perpetuating the disease. Methods: We analyzed CD39 gene and protein expression as well as ATPase enzyme activity in lung tissue samples of patients with COPD (n = 17), non-obstructed smokers (NOS) (n = 16), and never smokers (NS) (n = 13). Morphometry studies were performed to analyze pulmonary vascular remodeling. Results: There was significantly decreased CD39 gene expression in the lungs of the COPD group (1.17 [0.85-1.81]) compared with the NOS group (1.88 [1.35-4.41]) and NS group (3.32 [1.23-5.39]) (p = 0.037). This attenuation correlated with higher systemic inflammation and intimal thickening of muscular pulmonary arteries in the COPD group. Lung CD39 protein levels were also lower in the COPD group (0.34 [0.22-0.92]) compared with the NOS group (0.67 [0.32-1.06]) and NS group (0.95 [0.4-1.1) (p = 0.133). Immunohistochemistry showed that CD39 was downregulated in lung parenchyma, epithelial bronchial cells, and the endothelial cells of pulmonary muscular arteries in the COPD group. ATPase activity in human pulmonary structures was reduced in the lungs of patients with COPD. Conclusion: An attenuation of CD39 expression and activity is presented in lung tissue of stable COPD patients, which could lead to pulmonary ATP accumulation, favoring the development of pulmonary inflammation and emphysema. This may be a mechanism underlying the development of COPD

Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes. Methods: All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio. Results: In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6 +/- 1.5% vs. 14.2 +/- 1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for % IA between the 2 groups (37.3 +/- 2.2% vs. 29.3 +/- 2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the % IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008). Conclusions: Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population

Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation

Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations

Specific IgA against Pseudomonas aeruginosa in severe COPD

Background: The bronchial mucosa is protected by a specialized immune system focused on the prevention of colonization and infection by potentially pathogenic microorganisms (PPMs). Immunoglobulin A (IgA) is the principal antibody involved in this mechanism. A defective immune barrier may facilitate the recurrent presence of PPMs in COPD. Purpose: The aim of this study was to determine IgA-mediated bronchial specific immune responses against Pseudomonas aeruginosa in stable patients with severe disease. Methods: COPD patients with good-quality sputum samples obtained during stability were included and classified according to the presence or absence of chronic bronchial colonization by P. aeruginosa. Levels of specific IgA for P. aeruginosa in sputum were determined by ELISA and expressed as ratios, using the pooled level of 10 healthy subjects as reference (optical density450 patient/control). Results: Thirty-six stable COPD patients were included, 15 of whom had chronic colonization by P. aeruginosa. Levels of specific IgA against P. aeruginosa in stable non-colonized patients were lower than those in healthy subjects (IgA ratio: median =0.15 [interquartile range {IQR} 0.05-0.36]). Colonized patients had higher levels, (1.56 [IQR 0.59-2.79]) (p,0.001, Mann- Whitney U test), with figures equivalent but not exceeding the reference value. Conclusion: IgA-based immune response against P. aeruginosa was low in severe COPD patients. Levels of specific IgA against this microorganism were higher in colonized patients, but did not attain clear-cut levels above the reference. An impaired local response against P. aeruginosa may favor chronic colonization and recurrent infections in severe COPD