Chronic Obstructive Pulmonary Disease (COPD)

Breathing is a basic human function that tend to be unconscious. Breathing is physiological function that is almost synonymous with being alive. Shortness of breath is a threat to life itself. People with respiratory disorders are often very anxious and fearful that they may die, perhaps excruciatingly. Whether death is a real possibility often has nothing to do with the fear.

COPD refers to several disorders that affect movement of air in and out of the lungs. COPD may occur as a result of increased airway resistance secondary to bronchial mucosal oedema or smooth muscle contraction. It may also be a result of decreased elastic recoil, as seen in emphysema. Elastic recoil, like the recoil of a stretched rubber band, is the force used to passively deflate the lung. Decreased elastic recoil results in a decreased driving force to empty the lung.

Acute exacerbations are important events in the natural history of chronic obstructive pulmonary disease (COPD). Their frequency is directly related to the prognosis of the disease. The objective of this study was to identify the 'frequent exacerbator' phenotype and determine the risk factors for increased frequency of acute exacerbations in local chronic obstructive pulmonary disease (COPD) patients in a cross sectional analytical study design. For this purpose 137 patients were included in the study after obtaining necessary permissions from the ethical board of the hospital. COPD was diagnosed on the basis of clinical symptoms and a post bronchodilator values of FEV1/FVC<0.70 on spirometry. Frequent exacerbator's were defined as patients experiencing 2 or more exacerbation episodes per year, which merited visited to the hospital. Average number of hospital visits for exacerbations per year, smoking history, family history of smoking related chronic lung disease in first degree relatives and presence of comorbidities were recorded from patient history and medical records. Body mass index was calculated and complete pulmonary function tests were recorded using electronic spirometer. Three multiple linear regression models were created with mid maximal expiratory flow, FEV1, and FVC as surrogate markers for lung function in different models. We found that 28 (20.4%) of our COPD patients were frequent exacerbators. All three multiple linear regression models for identifying risk factors for frequent exacerbations were significant (p< 0.001). The model in which mid maximal expiratory flow was used as a surrogate marker for lung function, accounted for the change in the dependent variable to the greatest degree (Adjusted R 2 = 0.38, p< 0.001). Overall the three models consistently showed that positive family history, high body mass index, heavy smoking, poor lung function (mid maximal expiratory flow/FEF2575, FEV1 and FVC), older age and requirement of steroid therapy predicted increased frequency of exacerbations. To conclude lung function (FEF2575%, FEV1 % predicted and FVC% predicted), longer smoking history, higher body mass index, succumbing to COPD at a younger age, and a positive family history of chronic lung disease in first degree relatives are important risk factors for frequent exacerbations of COPD.

Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg with twice-daily salmeterol/fluticasone (SFC) 50/500 μg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up.
Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75–0.93), $2 exacerbations (RR: 0.85, 95% CI: 0.70–1.03) and $2 exacerbations or $1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74–1.00). Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history. Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment. IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67–0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70–0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80–1.22). Conclusion: Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment. The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone.
Keywords: indacaterol/glycopyrronium, salmeterol/fluticasone, LABA/LAMA, LABA/ICS

Background: It is amply reported that patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular disease (CVD). Recent evidence suggests that COPD patients have elevated concentrations of plasma homocysteine (Hcy), a transsulfuration pathway analyte that is commonly regarded as a CVD risk factor.

Design: We comprehensively investigated the plasma concentrations of transsulfuration pathway analytes, and their relationship with markers of oxidative stress and inflammation, to identify which low molecular thiols might play a pathophysiological role both in CVD and in COPD. Hcy, cysteine (Cys), glutathione (GSH), cysteinylglycine (CysGly), glutamylcysteine (GluCys), taurine (Tau), oxidative stress markers (TBARS and protein-SH, PSH) and the inflammation marker kynurenine/tryptophan (Kyn/Trp) ratio were measured in 54 COPD patients and 54 control subjects.

Results: We found increased concentrations of total Hcy (P < .01) and total CysGly (P < .05) in COPD patients when compared to controls. Total Hcy and CysGly were also significantly associated with abnormal lung function parameters and COPD severity. In COPD patients, total Hcy was significantly associated with the Kyn/Trp ratio (P = .0017) whereas total CysGly was significantly associated with both PSH (P = .0298) and the Kyn/Trp ratio (P = <.0001).

Conclusion: Both total Hcy and CysGly concentrations were significantly associated with the presence and severity of COPD and with markers of oxidative stress (total CysGly) and inflammation (total Hcy and CysGly). This suggests that specific low molecular mass thiols might play a role in the inflammatory and oxidative stress pathways involved in both CVD and COPD.

Keywords: cardiovascular disease; chronic obstructive pulmonary disease; cysteinylglycine; homocysteine; inflammation; oxidative stress.

Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSAS) show similar neurocognitive impairments. Effects are more apparent in severe cases, whereas in moderate and mild cases the effects are equivocal. The exact mechanism that causes cognitive dysfunctions in both diseases is still unknown and only suggestions have been made for each disease separately. The primary objective of this review is to present COPD and OSAS impact on cognitive functions. Secondly, it aims to examine the potential mechanisms by which COPD and OSAS can be linked and provide evidence for a common nature that affects cognitive functions in both diseases. Patients with COPD and OSAS compared to normal distribution show significant deficits in the cognitive abilities of attention, psychomotor speed, memory and learning, visuospatial and constructional abilities, executive skills, and language. The severity of these deficits in OSAS seems to correlate with the physiological events such as sleep defragmentation, apnea/hypopnea index, and hypoxemia, whereas cognitive impairments in COPD are associated with hypoventilation, hypoxemia, and hypercapnia. These factors as well as vascocerebral diseases and changes in systemic hemodynamic seem to act in an intermingling and synergistic way on the cause of cognitive dysfunctions in both diseases. However, low blood oxygen pressure seems to be the dominant factor that contributes to the presence of cognitive deficits in both COPD and OSAS.

Both worldwide and in our country, the increasing incidence of Chronic Obstructive Pulmonary Disease (COPD) is a major health problem. Acute exacerbations,
which are a major cause of emergency room visits and hospital admissions, are the largest component of this problem. Acute exacerbations adversely affect
the prognosis of the disease and accelerate the process, resulting in severe respiratory failure, and are a cause of morbidity/mortality. Moreover, they cause a
considerable load on healthcare expenditures and a significant amount of labor force loss. The etiology and treatment of exacerbations especially must be well
understood by family and emergency service physicians, home health care service providers, and physicians dealing with chest diseases.

Purpose: Inflammatory gene expression is modulated by posttranscriptional regulation via RNA-binding proteins (RBPs), which regulate mRNA turnover and translation by binding to conserved mRNA sequences. Their role in COPD is only partially defined. This study evaluated RBPs tristetraprolin (TTP), human antigen R (HuR), and AU-rich element-binding factor 1 (AUF-1) expression using lung tissue from COPD patients and control subjects and probed their function in epithelial responses in vitro. Patients and methods: RBPs were detected by immunohistochemistry in bronchial and peripheral lung samples from mild-to-moderate stable COPD patients and age/smoking history- matched controls; RBPs and RBP-regulated genes were evaluated by Western blot, ELISA, protein array, and real-time PCR in human airway epithelial BEAS-2B cell line stimulated with hydrogen peroxide, cytokine combination (cytomix), cigarette smoke extract (CSE), and following siRNA-mediated silencing. Results were verified in a...

Objectives: Chronic Obstructive Pulmonary Disease (COPD) impacts the quality of life of the affected patients. The present study aimed to determine the effects of home-based self-care program follow-up on re-hospitalization frequency and quality of life in COPD patients. Methods: This quasi-experimental study was performed on 44 COPD patients at Masih Daneshvari Hospital in Tehran City, Iran, in 2018. For collecting the necessary data, we used demographic data checklist, COPD Assessment Test, and the St. George's Quality of Life questionnaire. We used SPSS v. 22 for analyzing the obtained data. Results: The present study revealed that the highest age frequency was in the 61-70 years age group. Moreover, the male gender had the highest frequency and most research participants had elementary school education; the highest frequency regarding the disease duration was >5 years. Besides and the hospitalization frequency was once a year. The present study findings indicated that the provided self-care program follow-up reduced the re-hospitalization frequency and increased the quality of life of the explored COPD patients (P<0.001). Discussion: The obtained results revealed that implementing a course of home-based followup self-care program could reduce re-hospitalization and increase the quality of life of COPD patients; thus, it is suggested that such follow-up programs be included in COPD treatment plans.

The present study aimed to determine the effect of diaphragmatic breathing exercises on the degree of breathlessness among patients with Chronic Obstructive Pulmonary Disease (COPD) in West Java Province, Indonesia. Methods: This was a quasi-experimental study with a pretest-posttest and no control group design. In total, 33 patients with COPD participated in this study using a consecutive sampling technique. The Modified Medical Research Council was used to measure the degree of breathlessness. A portable spirometer was used to assess Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC). Results: The Mean±SD age of the study subjects was 44.5±3.17 years; 54.4% of the study participants were male, with healthy a body mass index. Approximately 42.4% of the studied patients experienced the fourth degree of breathlessness before the intervention. There was a reduction in the Mean±SD score of breathlessness from 3.42±0.53 to 1.64±0.13 after the intervention (P=0.001). There were improvements in the breathing frequency (Mean±SD: 11.8±4.9 vs 9.5±1.6), oxygen saturation (93.39±3.20 vs 95.47±4.21), and FEV1/FVC (0.5±0.12 vs 0.3±0.45) in the study subjects. Discussion: It is expected for the hospital, educational institutions, nurses, and patients to be able to apply diaphragmatic breathing exercises as one form of nursing care measure. This is because it is proven effective to reduce the degree of breathlessness.

Purpose: Inflammatory gene expression is modulated by posttranscriptional regulation via RNA-binding proteins (RBPs), which regulate mRNA turnover and translation by binding to conserved mRNA sequences. Their role in COPD is only partially defined. This study evaluated RBPs tristetraprolin (TTP), human antigen R (HuR), and AU-rich element-binding factor 1 (AUF-1) expression using lung tissue from COPD patients and control subjects and probed their function in epithelial responses in vitro.
Patients and methods: RBPs were detected by immunohistochemistry in bronchial and peripheral lung samples from mild-to-moderate stable COPD patients and age/smoking history- matched controls; RBPs and RBP-regulated genes were evaluated by Western blot, ELISA, protein array, and real-time PCR in human airway epithelial BEAS-2B cell line stimulated with hydrogen peroxide, cytokine combination (cytomix), cigarette smoke extract (CSE), and following siRNA-mediated silencing. Results were verified in a microarray database from bronchial brushings of COPD patients and controls. RBP transcripts were measured in peripheral blood mononuclear cell samples from additional stable COPD patients and controls.
Results: Specific, primarily nuclear immunostaining for the RBPs was detected in structural and inflammatory cells in bronchial and lung tissues. Immunostaining for AUF-1, but not TTP or HuR, was significantly decreased in bronchial epithelium of COPD samples vs controls. In BEAS-2B cells, cytomix and CSE stimulation reproduced the RBP pattern while increasing expression of AUF-1-regulated genes, interleukin-6, CCL2, CXCL1, and CXCL8. Silencing expression of AUF-1 reproduced, but not enhanced, target upregulation induced by cytomix compared to controls. Analysis of bronchial brushing-derived transcriptomic confirmed the selective decrease of AUF-1 in COPD vs controls and revealed significant changes in AUF-1- regulated genes by genome ontology.
Conclusion: Downregulated AUF-1 may be pathogenic in stable COPD by altering posttran- scriptional control of epithelial gene expression.

Rationale
Objective adherence to inhaled therapy by patients with COPD has not been reported.
Objectives
The aim of this study was to objectively quantify adherence to preventer DiskusTM inhaler therapy by patients with COPD with an electronic audio recording device (INCATM).
Methods
This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCATM device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use.
Measurements and Main Results
COPD patients (n=265) were recruited. The mean age 71 years, mean Forced Expiratory Volume in 1-second 1.3 Litres, and 80% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses and critical technique errors, thus incorporating
both intentional and unintentional non-adherence, a measure “Actual Adherence” was calculated. Mean Actual Adherence was 22.9% of that expected if the doses were taken correctly and on time. Seven percent had an Actual Adherence>80%. Hierarchical clustering found three equally sized well separated clusters corresponding to distinct patterns: Cluster 1 (34%) had low inhaler use and high error rates, Cluster 2 (31%) had high inhaler use and high error rates, and Cluster 3 (30%) had overall
good adherence. Lung function and co-morbidities were predictive of poor technique, while age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique.
Conclusion
These data may inform clinicians both in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD.

This study evaluates the respiratory parameters associated with pulmonary diseases. The study was centred on a comparative evaluation of the pulmonary function during the same two periods of two different years: January - February 2013 and January – February 2014. The data was analyzed and comparison was undertaken between the severity of the pulmonary diseases symptoms requiring spirometries, during the cold season in two succeeding years. The study applied to symptomatic patients suffering from COPD or asthma who were referred to the Specialty Outpatient Department of the Pneumophthisiology Hospital of Brasov. To determine the diagnosis and to apply the appropriate medication, the study examined the function tests by spirometry for each of the patients in the study group. As applicable, spirometry was carried out by tests using salbutamol, according to the orders of the specialty doctor. The analysis of the study data enabled the creation of the profile of the symptomatic patients.

Asthma treatment guidelines advocate the use of long-acting β2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone, thereby addressing two processes fundamental to asthma: bronchoconstriction and inflammation. Superior control - including a reduction in severe exacerbations - of asthma and COPD by ICS/LABA combination therapy has been demonstrated. Results from clinical studies suggest additive and potentially synergistic effects when the two agents are used in combination. No new safety-related issues have been identified with ICS/LABA compared with the monocomponents. The exact mechanisms for the enhanced efficacy of ICS/LABA combinations are under investigation but likely include drug interactions at the receptor level and interwoven signalling pathways, which may result in improved function of ®2- adrenoceptors and steroid receptors. Data from preclinical studies provide evidence of additive, compensatory, complementary and synergistic effects of ICS and LABA in the control of inflammation and airway and lung remodelling. These effects may contribute to the improved efficacy seen when treating asthma and COPD with ICS/LABA combinations in clinical studies. Two ICS/LABA combination products are available: budesonide/formoterol (Symbicort®) and salmeterol/fluticasone propionate (SeretideTM). An ICS/LABA combination in a single inhaler represent safe, effective and convenient treatment options for the management of patients with asthma and COPD. Clinical results also suggest that adjustable dosing with budesonide/formoterol provides better asthma control than fixed dosing. Further elucidation of the underlying mechanisms responsible for this superior disease control is needed.