The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study

Background Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience exacerbations more frequently than those with asthma or COPD alone. Since low diffusing capacity of the lung for carbon monoxide (DLCO) is known as a strong risk factor for severe exacerbation in COPD, DLCO or a transfer coefficient of the lung for carbon monoxide (KCO) is speculated to also be associated with the risk of exacerbations in ACO. Methods This study was conducted as an observational cohort survey at the National Hospital Organization Fukuoka National Hospital. DLCO and KCO were measured in 94 patients aged ≥ 40 years with a confirmed diagnosis of ACO. Multivariable-adjusted hazard ratios (HRs) for the exacerbation-free rate over one year were estimated and compared across the levels of DLCO and KCO. Results Within one year, 33.3% of the cohort experienced exacerbations. After adjustment for potential confounders, low KCO (< 80% per predicted) was positively associated with the incidence of exacerbation (multivariable-adjusted HR = 3.71 (95% confidence interval 1.32–10.4)). The association between low DLCO (< 80% per predicted) and exacerbations showed similar trends, although it failed to reach statistical significance (multivariable-adjusted HR = 1.31 (95% confidence interval 0.55–3.11)). Conclusions Low KCO was a significant risk factor for exacerbations among patients with ACO. Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory.

Procalcitonin-Guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations (PRECISION): Study Protocol for a Prospective Randomized Controlled Trial.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a worldwide prevalent disease. It is estimated to be the 3rd leading cause of death worldwide in 2020, and it is also a leading cause of disability-adjusted life years (DALY’s). COPD accounts for just over 3% of the total health care budget in the European Union. The majority of these costs are attributed to acute exacerbations of COPD (AECOPD). Given the contribution of exacerbations, it is of paramount importance to improve the current treatment of exacerbations to reduce the burden of disease for patients (mortality and DALY’s) and for society (costs). Treatment of AECOPD generally consists of corticosteroids and antibiotics, mostly in one-size fits all fashion. Pulmonary physicians are well aware of overuse of antibiotics, but lack the tools to decide which medication to give. Biomarkers may aid towards a more personalized treatment of AECOPD by identifying which patient would benefit from antibiotics. Procalcitonin (PCT) is the precursor of calcitonin and is released in response to a bacterial infection. PCT levels are minimally raised in viral infections, making it a relative specific diagnostic tool for bacterial infections. Several trials have shown a reduction in antibiotic consumption in AECOPD when using a PCT-guided treatment algorithm. One meta-analysis suggested that PCT-based protocols may be superior to standard care, but the authors stated that appropriately powered confirmatory trials are necessary. The objective of our study is to assess that at hospitalization for a severe AECOPD, PCT-guided treatment to guide antibiotic administration is non-inferior to usual care, in terms of treatment failure at day 30. Methods: The study is set up as a prospective randomized trial. A total of 693 patients with a severe exacerbation of COPD will be included and randomized between usual care and PCT-guided treatment regarding antibiotic therapy. The primary endpoint will be treatment failure within 30 days after inclusion, the endpoint comprises disease-related mortality and other disease-related adverse events. Discussion: We believe this trial can add to the currently available evidence with PCT being tested in a clinical setting in a treatment algorithm specifically in COPD with the primary objective being treatment failure. Trial registration: Netherlands Trial Register. Registration number: NL9122. Date of registration: 24-11-2020. URL of trial registry record: https://www.trialregister.nl/trial/9122

Exacerbation of COPD Treatment Combination Therapy NIV with Thermal Helium- Oxygen Plus Nitric Oxide: A Case Report

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide despite increased health care efforts, financial costs, and research concerning its early diagnosis and proper management [1]. The most relevant event affecting COPD mortality is the acute exacerbation of COPD (AECOPD), a catastrophic event during the clinical course of the disease [2]. In cases of acute respiratory acidosis, noninvasive mechanical ventilation (NIV) is considered. Nevertheless, in 30% of patients with severe exacerbation of COPD, NIV does not lead to the desired results [3]. However, there have been cases of NIV failure in patients with severe respiratory acidosis, and associated pulmonary arterial hypertension. Many studies have shown that thermal helium-oxygen and nitric oxide gas heat treatment has many effects. Here we are reporting a case of severe exacerbation COPD, 67 years old male patient, who came to us with shortness of breath, fever, wheezing and a cough with yellow phlegm. He had a history of smoking 30 pack-year smoker many years. He was given NIV treatment with a combination of helium and nitric oxide heat. And we have had very good results.

SOME ASPECTS OF PREDICTING THE SEVERITY OF VIRUS-INDUCED BRONCHIAL ASTHMA EXACERBATION IN CHILDREN DUE TO COVID-19 PANDEMIC

bronchial asthma is an important medical and social issue directly affects the health of patients, their quality of life, and the direct and indirect economic costs associated with the disease are quite significant. Due to the pandemic caused by a new strain of coronavirus SARS-CoV-2, international and domestic regulations documents have updated the management of patients with asthma. In particular, there have been recommendations for remote visits to assess the patients’ complaints however physical analysis and objective examination are not available during such consultations. It can lead to errors in diagnostic of asthma exacerbation severity and treatment tactic for prescription the reliever therapy. So it is actuality to find out additional indicators to improve the diagnostic and prediction of the severity of the disease exacerbations. Given the urgency of the problem, the aim of the study is to evaluate the clinical and paraclinical parameters in children with virus-induced bronchial asthma exacerbation to predict the severity of the asthma attack and personify the management of patients. Have been examined 47 patients who were hospitalized for disease exacerbation. The severity of a asthma attack was considered a group-forming feature. Statistical analysis was performed using parametric and nonparametric calculation methods, methods of clinical epidemiology and biostatistics. The results of the study give grounds to predict a more severe asthma attack among urban residents who have a phenotype of late-onset asthma. An additional, anamnestic risk of more severe exacerbation of the disease is body weight at birth, which exceeds 3500 g. Among spirometric indicators the highest prognostic criterion for severe bronchial asthma exacerbation was the general index of bronchodilation, which was 15% and above, as well as the index of bronchodilation at the level of the distal airways with a cut-off point of 30% and above. In the presence of the above risk factors for severe asthma attack on the background of confirmed infection with the coronavirus strain SARS-CoV-2 the patient needs hospitalization, antiviral treatment, increasing the dose of inhaled steroids and additional β2-agonists. When predicting a mild or moderate asthma attack provoked by the coronavirus SARS-CoV-2, it is advisable to continue remote monitoring by an allergist and the management of exacerbation includes a temporary increase daily dose of inhaled glucocorticosteroids and additional using of β2-agonists. It is recommended to avoid taking nebulizers and use individual metered powder or aerosol inhalers in cases of inpatient treatment.

Cardiovascular Risk in Patients with COPD: Cardiovascular Comorbidities in Patients with COPD Increase CAT and mMRC Dyspnea Scores

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a number of different comorbidities. Cardiovascular diseases (CVD) are the most frequent comorbidities in COPD. The economic burden associated with cardiovascular comorbidity (CVC) in this population of patients is considerable. The COPD patients are related to the increased systemic inflammation, reduced capacity for physical activity, and airflow obstruction. AIM: The aim of our investigation was to evaluate the dyspnea as a disabling symptom in COPD patients with cardiovascular comorbidity (CVC) especially heart failure. The main aim of this study is to evaluate its intensity in patients with COPD in stages II according to GOLD. METHODS: The investigation was conducted from December 2019 to January 2020, on pulmonology and allergology clinic and cardiology clinic of medical faculty in Skopje. We investigated 65 outpatients with COPD, 44 with different type of CVD, Group I, and 21 without CVD, Group II. All patients were with partial chronic respiratory failure (In type 1 respiratory failure hypoxemic). Patients, according GOLD initiative, were in COPD stadium II, 70% < forced expiratory volume in 1 s (FEV1)>50%. Heart condition was diagnosed on the basis of clinical examination, electrocardiography, and echocardiography of the heart. Included patients with CVD were with ejection fraction (EF) <65%. Dyspnea was measured with modified MRC (mMRC) dyspnea scale. RESULTS: The forced vital capacity and forced expiratory volume in 1 s were statically significantly higher in Group II with CVD. Dyspnea measured with Modified Medical Research Council (MRC) dyspnea scale showed statistically significantly higher values in Group I COPD patients with CVC (2.9 ± 1.4) versus Group II without CVC (1.7 ± 1.4), (p < 0.05). The perception of the higher dyspnea in Group I was associated with increased COPD assessment test-scores, in Group I: Group I (19.8 ± 9.1) versus Group II: (9.8 ± 9.1), (p < 0.001). The number of exacerbations and what is more important the number of severe exacerbation leading to hospitalizations was statistically higher in patients of Group I with CVC than in Group II without CVC (3.0 ± 1.1 vs. 1.0 ± 2.1), (p < 0.001) and the number of hospitalizations (1.0 ± 1.1 vs. 0.3 ± 2.1) (p < 0.001). CONCLUSION: We can conclude that patients with COPD who have CVC have an increased risk of high symptoms, which mean poor quality of life and increased morbidity.

Clinical Case in Takayasu Artery With Critical Lesion in Aortic Arch Branches (Takayasu’s Disease)

Research relevance: among Kyrgyz patients with Takayasu arteritis (AT), young women were predominated. The etiology is unknown. Research objectives: observation of the clinical manifestations in Takayasu’s arteritis in patients with the aim of compiling a diagnosis in treatment of disease. Research methods: most of patients had anatomical type V Takayasu arteritis (61.3%), vascular stage (89.3%) and severe stenosis (54.7%), lesions of the brachiocephalic trunk (68%), common sleepyheads (57.3%) and renal (52%) arteries. Severe exacerbation of the disease was observed in 82.7% of patients. The presence of ≥2 complications worsened the prognosis of AT. Research results: the clinical manifestations of AT were characterized mainly by cardiovascular pathology (77.3%) and kidney damage (57.3%). Conclusions: more than one third of patients (37.3%) had late diagnosis of AT.

Cost-effectiveness of home non-invasive ventilation in COPD group GOLD D patients

Introduction. Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, estimated to be the third most common cause of death by 2020. The natural evolution of the disease is characterized by frequent exacerbations, severe exacerbations evolving with respiratory acidosis. Introducing home non-invasive ventilation (NIV) in the management of COPD group GOLD (Global Initiative for Chronic Obstructive Lung Disease) D patients generates supplementary costs, but the decreasing of the number of severe exacerbations will decrease the costs of drug treatment and hospitalization. This balance can be verified through a careful study of cost-effectiveness through modern methods of assessing the costs and years of life gained in relation to quality of life. Material and method. This prospective study took place in the Emergency Department of the Bihor County Clinical Emergency Hospital, Oradea, between 01 October 2017 – 31 October2018, with a follow-up period of 2 years. We included 36 Group risk D COPD patients, presented with severe exacerbation that required NIV; the patients were divided into two study groups according to the treatment scheme after discharge (standard medication according to GOLD guidelines and long-term oxygen therapy - LTOT vs. LTOT + NIV). We follow-up at 2 years with the study group, and analyze the following: number of exacerbations (moderate and severe), number of hospitalizations, mortality rate in two years, average costs for the treatment of exacerbations and for stable COPD periods, quality adjusted life year (QALY). Results and discussions. From 36 enrolled, 10 patients benefited from home NIV. The number of exacerbations was significantly lower in the NIV group compared with the LTOT group (1.72±0.79 vs 3.54±1.18). The incremental cost-effectiveness ratio (ICER) showed a net gain of 31% from gross product (GDP) per capita (5,641.71 ± 1,737.0-euro vs 9,272.3 ± 3,681.9 euro) per quality adjusted life year (QALY) for each patient. Conclusions. Introduction home-NIV demonstrated clinical improvement and higher cost-effectiveness over LTOT alone in Class Risk D, COPD patients after discharge following a severe exacerbation. Keywords: chronic obstructive pulmonary disease, non-invasive ventilation, cost-effectiveness, quality adjusted life year,

Periostin - A biomarker in adults with asthma

<p>Asthma is a common, heterogeneous condition where current treatment options are limited to a ‘one size fits all’ approach. Biological therapies targeting specific components of the Type 2 inflammatory pathway are emerging as potential alternatives for those who are inadequately controlled on current treatment options. Biomarkers, such as serum periostin, can be used in clinical settings to identify potential responders to these treatments. The aim of this research was to investigate the epidemiology of periostin and its ability to predict important clinical outcomes in asthma. Six studies were conducted: two cohort studies observing the change to periostin after bone and dental injury in non-asthmatic adults; a cohort study investigating reference ranges of periostin in Chinese adults with and without asthma; two longitudinal studies measuring the change in periostin in asthmatic adults with stable and unstable disease; and a longitudinal cohort study investigating the association between periostin and risk of exacerbation. There was a biphasic response of serum periostin after bone injury. This was particularly marked after joint replacement surgery where periostin fell within 48 hours by a ratio of geometric means 0.80 (95% CI 0.75 to 0.86) before rising to a maximum level at eight weeks with a ratio of geometric means 1.89 (95% CI 1.77 to 2.02). There was no significant change to periostin after simple or surgical tooth extractions with a maximal ratio of geometric means of 1.02 (95% CI 0.95 to 1.10). Serum periostin was higher in Chinese non-asthmatic adults versus Caucasian non- asthmatic adults, mean periostin 57 ng/ml and 49.7 ng/ml respectively, difference (95% CI) 8.2 (5.8 to 10.6) ng/ml. Serum periostin remained stable in adults with well- controlled asthma with an intra-class coefficient for variation of 0.93. In unstable asthma, there was a decrease in serum periostin one week after the start of a severe exacerbation and treatment with systemic corticosteroids, with a ratio of geometric means 0.86 (95% CI 0.82 to 0.92) before stabilising four weeks later. Finally, adults with mild to moderate asthma with low baseline levels of periostin were more likely to have a severe asthma exacerbation with a hazard ratio (95% CI) 0.62 (0.35 to 1.09) per 0.693 ng/ml increase of log periostin. In conclusion, serum periostin showed significant biphasic variation in response to bone injury, the magnitude and duration of which was proportional to bone size. Whilst this pattern was not replicated in adults undergoing dental surgery, it suggests that serum periostin can be affected by non-asthma related conditions. Periostin demonstrated higher mean values in Chinese adults than in Caucasian adults, indicating ethnicity-specific reference ranges may be required if it were to become a clinical biomarker. Intra-participant variability of serum periostin was low in a homogenous group of well controlled, moderate to severe asthmatic adults, but there was wide variability between individuals in this group suggesting that factors other than asthma are likely to affect serum periostin levels. Serum periostin was suppressed during and after treatment for a severe exacerbation for up to four weeks. This is likely due to the exacerbation and/or its treatment, suggesting the interpretation of periostin as a biomarker for response to biological therapies should not occur within four weeks of a severe exacerbation. The reported positive association between periostin and risk of severe exacerbation in populations with severe eosinophilic asthma does not extend to a general population of mild to moderate asthmatics, in which an inverse associated was observed. Serum periostin may be useful in predicting treatment responsiveness of patients to monoclonal antibody therapy directed against IL-4Rα, IL-13 and IgE. However, it may be difficult to use as a biomarker clinically, as numerous non-asthma related factors, such as bone injury and ethnicity, have been shown to significantly affect serum levels, making interpretation difficult.</p>

Periostin - A biomarker in adults with asthma

<p>Asthma is a common, heterogeneous condition where current treatment options are limited to a ‘one size fits all’ approach. Biological therapies targeting specific components of the Type 2 inflammatory pathway are emerging as potential alternatives for those who are inadequately controlled on current treatment options. Biomarkers, such as serum periostin, can be used in clinical settings to identify potential responders to these treatments. The aim of this research was to investigate the epidemiology of periostin and its ability to predict important clinical outcomes in asthma. Six studies were conducted: two cohort studies observing the change to periostin after bone and dental injury in non-asthmatic adults; a cohort study investigating reference ranges of periostin in Chinese adults with and without asthma; two longitudinal studies measuring the change in periostin in asthmatic adults with stable and unstable disease; and a longitudinal cohort study investigating the association between periostin and risk of exacerbation. There was a biphasic response of serum periostin after bone injury. This was particularly marked after joint replacement surgery where periostin fell within 48 hours by a ratio of geometric means 0.80 (95% CI 0.75 to 0.86) before rising to a maximum level at eight weeks with a ratio of geometric means 1.89 (95% CI 1.77 to 2.02). There was no significant change to periostin after simple or surgical tooth extractions with a maximal ratio of geometric means of 1.02 (95% CI 0.95 to 1.10). Serum periostin was higher in Chinese non-asthmatic adults versus Caucasian non- asthmatic adults, mean periostin 57 ng/ml and 49.7 ng/ml respectively, difference (95% CI) 8.2 (5.8 to 10.6) ng/ml. Serum periostin remained stable in adults with well- controlled asthma with an intra-class coefficient for variation of 0.93. In unstable asthma, there was a decrease in serum periostin one week after the start of a severe exacerbation and treatment with systemic corticosteroids, with a ratio of geometric means 0.86 (95% CI 0.82 to 0.92) before stabilising four weeks later. Finally, adults with mild to moderate asthma with low baseline levels of periostin were more likely to have a severe asthma exacerbation with a hazard ratio (95% CI) 0.62 (0.35 to 1.09) per 0.693 ng/ml increase of log periostin. In conclusion, serum periostin showed significant biphasic variation in response to bone injury, the magnitude and duration of which was proportional to bone size. Whilst this pattern was not replicated in adults undergoing dental surgery, it suggests that serum periostin can be affected by non-asthma related conditions. Periostin demonstrated higher mean values in Chinese adults than in Caucasian adults, indicating ethnicity-specific reference ranges may be required if it were to become a clinical biomarker. Intra-participant variability of serum periostin was low in a homogenous group of well controlled, moderate to severe asthmatic adults, but there was wide variability between individuals in this group suggesting that factors other than asthma are likely to affect serum periostin levels. Serum periostin was suppressed during and after treatment for a severe exacerbation for up to four weeks. This is likely due to the exacerbation and/or its treatment, suggesting the interpretation of periostin as a biomarker for response to biological therapies should not occur within four weeks of a severe exacerbation. The reported positive association between periostin and risk of severe exacerbation in populations with severe eosinophilic asthma does not extend to a general population of mild to moderate asthmatics, in which an inverse associated was observed. Serum periostin may be useful in predicting treatment responsiveness of patients to monoclonal antibody therapy directed against IL-4Rα, IL-13 and IgE. However, it may be difficult to use as a biomarker clinically, as numerous non-asthma related factors, such as bone injury and ethnicity, have been shown to significantly affect serum levels, making interpretation difficult.</p>

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma—A Romanian Perspective

Background: Asthma is the most common chronic disease affecting children, with a negative impact on their quality of life. Asthma is often associated with comorbid allergic diseases, and its severity may be modulated by immunoglobulin E (IgE)-mediated allergen sensitization. Omalizumab is a humanized monoclonal anti-IgE antibody, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omalizumab in Romanian children with severe allergic asthma. Methods: In this observational real-life study, 12 children and adolescents aged 6 to 18 years (mean 12.4 years) with severe allergic asthma received Omalizumab as an add-on treatment. Asthma control, exacerbations, lung function, and adverse events were evaluated at baseline and after the first year of treatment. Results: We observed general improvement in total asthma symptom scores and reduction in the rate of exacerbation of severe asthma. Omalizumab treatment was associated with improvement in the measures of lung function, and no serious adverse reactions were reported. FEV1 improved significantly after one year of treatment with Omalizumab [ΔFEV1 (% pred.) = 18.3], and [similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rate of asthma decreased from 4.1 ± 2.8 to 1.15 ± 0.78 (p < 0.0001) during the year of treatment with Omalizumab. Conclusions: This study showed that Omalizumab can be an effective and safe therapeutic option for Romanian children and adolescents with severe allergic asthma, providing clinically relevant information on asthma control and exacerbation rate in children and adolescents. The results demonstrated the positive effect of Omalizumab in young patients with asthma, starting from the first year of treatment.