COPD Therapy Research Articles

Real-World and Patient-Reported Outcomes of Dupilumab and Other Biological Drugs for Chronic Obstructive Pulmonary Disease—A Systematic Review

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three “real-world” case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients’ self-perceived drug effects, and none evaluated patients’ perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients’ experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials.

Triple Therapy in COPD in Real Life: Is It Better to Use Single or Multiple Inhalers?

Background: Today, single-inhaler ICS/LAMA/LABA (SITT) COPD therapies are available. It is unclear whether they are more effective than multiple-device triple therapies (MITT) in improving COPD outcomes. Methods: We retrospectively considered patients on SITT/MITT in 2019/2020 who were prescribed >7 packages of ICS/LABA/LAMA or ICS/LAMA (+LAMA). The two treatments were compared concerning systemic corticosteroids, antibiotics, salbutamol, antifungal prescriptions, and number of emergency room visits/hospitalizations (ERV/Hs). We studied 292 MITT patients (Group A) during 2019, switching to SITT in 2020, and 366 subjects (Group B) who took SITT during 2019, and 206 MITT individuals (Group C) in 2020. Results: ICS/LABA + LAMA (MITT) package use was 8.2 ± 4.2 and 7.85 ± 4 in 2019, switching to 11.2 ± 3.2 when patients shifted to SITT in 2020 (p = 0.0001). Group A MITT package use was lower than in SITT patients in 2019 (9.31 ± 2.71, p = 0.0001; Group B). Throughout 2020, Group C (10.3 ± 6.1 packs) adherence to ICS/LABA was similar to SITT adherence in Group A (p = 0.270), whereas LAMA package use (9.1 ± 5) was lower (p = 0.0038). Patients using systemic corticosteroids/antibiotics were fewer in SITT in 2020, compared to the MITT results in 2019. Subjects with fewer ERV/Hs were observed with SITT rather than with MITT. Particularly, 13.8% of patients needed ≥2 ERV/Hs when treated with SITT, whereas 19.2% needed ≥2 ERV/Hs with MITT in 2019 (p = 0.08). Multivariate analysis, adjusted for all confounding factors including treatment adherence, showed that MITT (vs. SITT) can have an increased risk of at least one ERV/H (subjects receiving MITT during 2019 passing to SITT in 2020, OR: 1.718 [1.010-2.924], p = 0.046; Group A/MITT/2019 vs. Group B/SITT/2019, OR: 1.650 [0.973-3.153], p = 0.056; Group C/MITT/2020 vs. Group B/SITT/2019, OR: 1.908 [1.018-3.577], p = 0.044). Conclusions: SITT therapy may promote treatment adherence more effectively, therefore, reducing COPD exacerbations better than MITT. A possible synergistic effect of ICS/LABA/LAMA intake with a single device might be another cause of SITT's greater efficacy.

Differential proteins from EVs identification based on tandem mass tags analysis and effect of Treg-derived EVs on T-lymphocytes in COPD patients

BackgroundChronic obstructive pulmonary disease (COPD) is a widespread respiratory disease. This study examines extracellular vesicles (EVs) and proteins contained in EVs in COPD.MethodsBlood samples were collected from 40 COPD patients and 10 health controls. Cytokines including IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-17, were measured by ELISA. Small EVs samples were extracted from plasma and identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and Western blot. Protein components contained in EVs were analyzed by Tandem Mass Tags (TMT) to identify differential proteins. Treg-derived EV was extracted and added to isolated CD8+, Treg, and Th17 subsets to assess its effect on T-lymphocytes.ResultsELISA revealed higher levels of all cytokines and flow cytometry suggested a higher proportion of Treg and Th17 cells in COPD patients. After identification, TMT analysis identified 207 unique protein components, including five potential COPD biomarkers: BTRC, TRIM28, CD209, NCOA3, and SSR3. Flow cytometry revealed that Treg-derived EVs inhibited differentiation into CD8+, CD4+, and Th17 cells.ConclusionThe study shows that cytokines, T-lymphocyte subsets differences in COPD and Treg-derived EVs influence T-lymphocyte differentiation. Identified biomarkers may assist in understanding COPD pathogenesis, prognosis, and therapy. The study contributes to COPD biomarker research.

Evaluating the mucolytic effectiveness of Ambroxol and N-Acetylcysteine in patients with Acute exacerbation of chronic obstructive pulmonary disease

IntroductionChronic obstructive pulmonary disease (COPD) is the third most fatal disease globally. Acute deterioration of the patient's respiratory symptoms is known as an acute exacerbation of COPD (AECOPD), that goes beyond usual variations and result in change in medications. Ambroxol (ABX) and N-acetylcysteine (NAC), are mainly used as mucolytics in the treatment of AECOPD. MethodologyThis prospective observational study examines effectiveness of ABX and NAC in COPD patients by assessing the quality of cough relief, peak expiratory flow rate (PEFR), length of hospital stay, quality of life (QOL) and reduction in symptoms of COPD. Leicester Cough Questionnaire (LCQ); Breathlessness, Cough and Sputum scale (BCSS)and St. George Respiratory Questionnaire (SGRQ) scales are used to evaluate patient condition before and after the treatment. ResultsThe mean duration of hospital stay for NAC and ABX were found to be 8 ± 3.6 and 9.9 ± 3.9 days, respectively. Lung function in both groups improved with a change in percentage mean score of PEFR. Reduction in symptoms of COPD was evident in both groups by decrease in mean BCSS score from admission to discharge. Our study also demonstrated better QOL in both groups using SGRQ. LCQ showed a mean increase in all domains: physical, psychological and social. ConclusionIt was concluded that both ABX and NAC leads to betterment in lung function, cough relief and control AECOPD. Hence, this study gives a signal to clinicians about these treatment options along with standard therapy of COPD for a better therapeutic outcome.

Perception and knowledge of general practitioners on COPD management according to the GOLD23 document and reimbursement criteria for drugs prescription: an e-Delphi study

Background COPD management and therapy have been periodically revised to support a more patient-specific approach. Several concerns remain in primary care, such as the proper choice of initial treatment, medication adherence, and missing values for spirometry investigations. These concerns may be exacerbated by inconsistencies between the GOLD23 report and reimbursement criteria, as per the Italian NOTA99, especially for what concerns the assessment of disease severity and related treatment choice. We therefore examined the perception and knowledge of general practitioners (GPs) on COPD management and treatment. Methods We conducted an exploratory e-Delphi study among 600 GPs. The study examined the COPD-related GP's access to spirometry evaluations in primary care clinics; knowledge on early recognition of COPD and related clinical concerns; perception of the clinical application of the NOTA99; the place in therapy of the triple LABA/LAMA/ICS combination. Results Among 466 participating GPs (response rate: 70.3%; mean age 52, SD: 14.2; mean years of experience: 21.3, SD: 15) had a good level of knowledge about the GOLD 2023 document and the reimbursement criteria for COPD medications. Nevertheless, a low (34%) direct access to spirometry was reported, along with absence of consensus on the proper choice of initial treatment (especially of use of LABA/LAMA combination), and the re-evaluation of free-triple therapy LABA/LAMA/ICS through specialist’s referral. Conclusions This study captured the domains on which further training for GPs might be implemented to improve the management and treatment of COPD. An extension of this e-Delphi to a larger GPs’ panel might further confirm these findings.

Strategies to improve adherence to inhaled therapies in asthma and COPD

Respiratory conditions such as asthma and chronic obstructive pulmonary disease are significant public health challenges. Despite effective treatments, the rising mortality rates indicate a need for improved approaches in the management of these conditions. Patient adherence, which is known to be a key factor in treatment success, has been identified as low in these patient populations. Strategies to improve adherence include patient-centred interventions targeting knowledge of the treatment of their condition, ensuring that the most appropriate inhaler device is prescribed for an individual patient, and that all patients are followed up as recommended. Ultimately, this aims to improve patient outcomes in respiratory care.

Triple fixed drug combination in the treatment of patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is one of the common respiratory diseases characterized by chronic inflammation, increased airway resistance and exacerbations. Treatment of chronic obstructive pulmonary disease is aimed at reducing the severity of symptoms, preventing exacerbations and progression of the disease, which significantly affects the well-being of patients. Irregular administration of prescribed drugs, as well as incorrect inhalation technique affects the well-being of patients, worsens the quality of life, increases the risk of adverse outcome. Over the past few years, the possibilities of therapy have certainly expanded, primarily due to the emergence of new combination drugs containing 2 or 3 components in one inhaler. The use of a medicament containing all three components in a single delivery device contributes to improved adherence to treatment and reduces the possibility of errors in inhalation technique. Drugs with the possibility of single use per day improve the patient’s adherence to therapy. In our clinical case, a patient with severe COPD and eosinophilia > 300 cells/µL with the administration of a double fixed combination of bronchodilators during the year showed an improvement in the condition, but a high level of blood eosinophils and frequent exacerbations remained. A personalized approach to COPD therapy will reduce the number of exacerbations, slow down the decline in lung function, and improve the quality of life of patients. The triple combination provides an effective and convenient option for supportive treatment of COPD, primarily for those whose disease is not controlled by dual ICS/LABA or LABA/LABA therapy.

#1182 Arterial hypertension and chronic obstructive pulmonary disease—problems of choice of therapy

Abstract Background and Aims The development of hypertension in COPD is based on the early formation of endothelial dysfunction in the small and large circulatory circles, increased sympathetic activity with an imbalance in the synthesis of catecholamines, a violation of the role of the lungs in the metabolism of vasoactive substances, oxidative stress, chronic systemic inflammation, an imbalance in the renin-angiotensin-aldosterone system (RAAS). There are few studies confirming the role of RAAS components in the pathogenesis of cardiovascular changes in patients COPD. The activity of angiotensin converting enzyme (ACE) increases with hypoxia, which may play an important role in increasing the degree of systemic hypertension. An increase in the function of the RAAS is possible both under the direct influence of hypoxia and indirectly through activation of the sympathoadrenal system. To evaluate the efficacy and tolerability of the angiotensin II receptor antagonist valsartan (Nortivan) at a dose 80-160 mg per day in patients with hypertension of 1-2 degrees and COPD of stage II-IV. Method The study design is a local, open, incomparable study on the efficacy and safety of the drug Nortivan in patients with hypertension in combination with COPD. We examined 18 patients with stage II-IV in remission, suffering from grade I and II hypertension, determined in accordance with the generally accepted classification of blood pressure levels (VNOK, 2010). Results The criteria for exclusion from the study were the presence in patients of complications of hypertension, coronary heart disease, decompensated chronic pulmonary heart, endocrine diseases requiring drug correction, kidney pathology, chronic heart failure, oral steroid therapy. 10 days in the last 6 months before inclusion in the study, oncological diseases and any other conditions that could interfere with the interpretation and evaluation of the results of the study. Patients who had not previously received antihypertensive treatment were included in the study immediately, and the rest underwent a washing period for 2 weeks. Patients received Nortivan as antihypertensive therapy for 24 weeks. The effectiveness of therapy was controlled by daily monitoring blood pressure. The choice of quality criteria for the effectiveness of therapy parameters SMAD is associated with literature data and own observations on the prevalence of diurnal blood pressure profiles in patients with hypertension and COPD with no decrease or increase in blood pressure at night, when office blood pressure figures are to a lesser extent reflect the effectiveness of antihypertensive therapy. The initial dosage was 80 mg/day. With insufficient hypotensive effect, the dose of the drug was doubled at the 4th week of treatment. The basic COPD therapy did not change throughout the study period and included anticholinergic drugs (ipratropium bromide, tiotropium bromide), beta2-adrenomimetic (fe-noterol) or a combination thereof. Initially and after 24 weeks of treatment, a complete laboratory examination was performed: a clinical blood test, a biochemical blood test. The thickness of the intima-media complex of the carotid arteries and ECG was also studied. The criterion The safety of the therapy was assessed by the indicators of respiratory function, daily pulse oximetry. Conclusion The use of the drug Nortivan has shown high efficacy and safety in patients Grade I–II hypertension in combination with stage II-IV COPD. A statistically and clinically significant normalization of SMAD indicators with correction of pathological types of daily curves due to a decrease in the number of patients with an increase in or the absence of a decrease in blood pressure during the night period. The safety of using the drug in the clinical group with bronchial obstruction syndrome was confirmed by the dynamics of ventilation indicators according to spirometry and the results of daily pulse oximetry, which showed the absence of exacerbation of hypoxia during therapy.

Self-management support with the Respiratory Adherence Care Enhancer instrument in asthma and chronic obstructive pulmonary disease: An implementation trial.

Suboptimal self-management with controller inhalation therapy in asthma and COPD is frequently observed with poor treatment outcomes. The developed 'Respiratory Adherence Care Enhancer' (RACE) instrument identifies and addresses individual barriers to self-management with a theoretical underpinning. This study investigates the feasibility of pharmaceutical support with this instrument. An implementation trial was conducted with asthma and COPD patients in 5 community pharmacies in the Netherlands. Patients were allocated to standard care or add-on support with the RACE instrument. Patients were invited to complete the RACE questionnaire at baseline, 5-week and 10-week follow-up. Barrier profiles were accessible for the intervention group with subsequent consultations at baseline and 5-weeks. Experiences were collected from patients and consultants with a questionnaire and reported findings. Primary endpoints focused on the acceptability, practicality and implementation process. Secondary endpoints included between-group differences in barrier and disease control outcomes from baseline at 10-weeks follow-up. In total, 84 patients were included; 48 were assigned to intervention and 36 to standard care. Patient satisfaction of support with the RACE instrument was high (71%). Patients felt motivated, reassured and more confident about their disease management. Consultants reported an increase in awareness of patient barriers. Patient recognition of barrier profiles was 83.9% (±12.9%). The barrier inhaler techniques decreased significantly for the intervention group at follow-up with odds ratio 0.30 (95% confidence interval, 0.10-0.91). No significant differences were observed for changes in number of barriers and disease control. Self-management support with the RACE instrument is feasible and appreciated, facilitating behaviour change with patient-centred pharmaceutical care in asthma and COPD.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol

BackgroundChronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture.Methods/designThis is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period.DiscussionThis study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Differences in antibiotic use between COPD and non-COPD residents based on the health information system.

To compare the differences in antibiotic use between COPD and non-COPD residents, and to explore the effect of COPD on antibiotic use. Participants aged 40 years old or over from the Songjiang Adult Cohort were included. Information on prescription and baseline survey was collected based on the health information system. A logit-negative binomial Hurdle model was used to explore correlations between COPD and percentage of antibiotic use and average rate of antibiotic prescribing of different types of antibiotic. Multinomial logistic regression was used to assess the association between COPD and antimicrobial combination therapy and routes of administration. A total of 34576 individuals were included and 1594 (4.6%) were COPD patients. During the 6 years' follow-up, the percentage of antibiotic use for COPD patients was 98.4%, which was 7.88 (95%CI: 5.24-11.85) times of that for non-COPD patients after adjusting for potential confounders. The prescribing rate was 3220 prescriptions (95%CI: 3063.6-3385.2) per 1000 person-years for COPD patients, which was 1.96 (95%CI: 1.87-2.06) times of that for non-COPD patients. Other beta-lactam antibacterials, Macrolides, lincosamides and streptogramins, and quinolone antibacterials were the most commonly used types of antibiotic. Except for aminoglycoside antibacterials, both percentage of antibiotic use and rate of antibiotic prescription were increased in COPD patients. COPD patients were more likely to be prescribed a maximum of two antibiotics (OR=1.34, 95%CI: 1.20-1.50); and were more likely to use antibiotics intravenously (OR=2.77, 95%CI: 2.47-3.11). COPD patients were more likely to have increased antibiotic use in a large-scale population-based adult cohort, suggesting COPD patients are a high-priority group for the management of antibiotic use in communities.

Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents

AimTo assess the radiopharmacist’s role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. MethodsWe ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20–95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. ResultsDetected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% – measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% – consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% – use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% – use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% – reassessment of patient’s condition; acute exacerbation of COPD 0.8% – defer test until acute episode is over; severe asthma 0.4% – do not perform test; methylxanthine ingestion 0.3% – avoid consumption previously; other 6.1% – evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. ConclusionsWorking in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Применение тройного комбинированного препарата будесонид/гликопиррония бромид/формотерол у больных хронической обструктивной болезнью легких в реальной клинической практике (первый отечественный опыт)

Background: the Global Initiative for Chronic Obstructive Lung Disease (COPD) recommends triple therapy as an initial treatment for patients of "group E" (eosinophil count ≥ cells/μL) or as maintenance therapy for patients with frequent exacerbations. Triple therapy combines three types of inhaled medications that help improve lung function, manage symptoms and prevent exacerbations. The use of a single inhaler helps to increase patients' adherence to therapy. Aim: to evaluate the efficacy of the triple combination drug — budesonide/glycopyrronium bromide/formoterol (BUD/GLI/FOR) – and the patients' adherence to the ongoing inhalation therapy of COPD in real clinical practice. Materials and Methods: 30 patients with severe COPD (mean age 65.55±5.98 years) receiving basic therapy in accordance with clinical recommendations during remission were examined. After the initial examination, patients were recommended therapy with a combination of BUD/GLI/FOR 160/7.2/5 μg 2 inhalations twice a day. Patients received the prescribed therapy for 3 months, after which the assessments of therapy adherence and satisfaction with it, the changes concerning the severity of dyspnea (mMRC scale), COPD symptoms (CAT-test), spirometry exams were conducted. Results: after 3 months of therapy with BUD/GLI/FOR, none of the patients had an exacerbation of COPD. During treatment, there was a tendency to decrease the disease severity. No significant changes in spirometry have been established. In 83,3% of cases, patients performed inhalation without errors while reproducing the correct technique. All patients were satisfied with the therapy and were ready to continue treatment. Conclusion: the results obtained serve as the basis for further treatment of patients with COPD with the drug used in real clinical practice and are encouraging in achieving the clinical and functional efficacy announced in randomized clinical trials. KEYWORDS: COPD, triple combination, phospholipids, aerosphere, adherence, inhaled glucocorticosteroid, dual bronchodilator therapy. FOR CITATION: Titova O.N., Kuzubova O.A., Sklyarova D.B. Triple combination drug — budesonide/glycopyrronium bromide/formoterol in patients with chronic obstructive pulmonary disease in real clinical practice (the first domestic experience). Russian Medical Inquiry. 2024;8(8):459–463 (in Russ.). DOI: 10.32364/2587-6821-2024-8-8-3.

Experience of clinicians with dual bronchodilator therapy in COPD (EXPAND) in Nepal

Introduction: Combination of bronchodilators, particularly long-acting muscarinic antagonists (LAMAs) and long-acting β2 agonists (LABAs) have become the mainstay of pharmacological therapy for COPD. COPD is now a common non communicable disease in Nepal. Objective: The study evaluated the current perception and experience of the clinicians in Nepal on diagnosis and management of COPD with focus on use of dual bronchodilator therapy. Method: This cross-sectional, observational survey evaluated experiences of clinicians (n=96; pulmonologist-13, physician-57, general practitioner-26) in Nepal on diagnosis, management trends, and current perceptions on the use of dual bronchodilator therapy in COPD management. Result: 93% of clinicians were practising in an urban setting for an average of 10 years and an average of 35% of their patients are of COPD. 61% of clinicians use mMRC with (34%) or without (27%) CAT score. 92% of clinicians perceived that most of their patients had 1 (32%) or >1 (59%) exacerbation/year. 54% of clinicians performed spirometry on all their patients with suspected COPD. 49% of clinicians measured blood EOS in their patients with severe COPD before adding ICS. 93% of clinicians preferred dual therapy (separate inhalers or a combination) for their COPD patients, but 83% of clinicians preferred LABA + LAMA in a single inhaler over inhalers given separately. 57% of clinicians preferred LABA + LAMA and 82% preferred the Tiotropium + Formoterol combination. 81% of clinicians stepped up or stepped down their treatment. 56% of patients were taking LABA + LAMA + ICS and 55% of clinicians co-prescribed ICS + LABA with LABA + LAMA. 80% of clinicians checked the inhalation technique at every visit and an average of 54% of their COPD patients were adherent (>80%) to the prescribed inhalation therapy. 78% of clinicians felt that dryness of mouth was the most common side effect of LABA + LAMA. 94% of clinicians believed that managing COPD better could improve cardiovascular outcomes in their patients with coexistent COPD. Conclusion: In the EXPAND survey, Formoterol + Tiotropium was preferred by most clinicians in Nepal amongst the LABA + LAMA combination. There is a good scope for improvement in the utilization of tools like spirometry, mMRC, CAT, and blood EOS in the daily practice of clinicians in Nepal.

Impact of COPD on mortality: An 8-year observational retrospective healthcare claims database cohort study

BackgroundChronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. Here we present a large observational study on the association of COPD and exacerbations with mortality (AvoidEx Mortality). MethodsA real-world, observational cohort study with longitudinal analyses of German healthcare claims data in patients ≥40 years of age with a COPD diagnosis from 2011 to 2018 (n = 250,723) was conducted. Patients entered the cohort (index date) upon the first COPD diagnosis. To assess the impact of COPD on all-cause death, a propensity score-matched control group of non-COPD patients was constructed. The number and severity of exacerbations during a 12-month pre-index period were used to form subgroups. For each exacerbation subgroup the exacerbations during 12 months prior to death were analysed. ResultsCOPD increases the all-cause mortality risk by almost 60% (HR 1.57 (95% CI 1.55–1.59)) in comparison to matched non-COPD controls, when controlling for other baseline covariates. The cumulative risk of death after 8 years was highest in patients with a history of more than one moderate or severe exacerbation. Among all deceased COPD patients, 17.2% had experienced a severe, and 34.8% a moderate exacerbation, within 3 months preceding death. Despite increasing exacerbation rates towards death, more than the half of patients were not receiving any recommended pharmacological COPD therapy in the year before death. ConclusionOur study illustrates the impact of COPD on mortality risk and highlights the need for consequent COPD management comprising exacerbation assessment and treatment.

Papel del radiofarmacéutico clínico en la seguridad del paciente durante los estudios de perfusión miocárdica de esfuerzo con vasodilatadores

AimTo assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. MethodsWe ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. ResultsDetected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% — measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% — consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% — use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% — use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% — reassessment of patient's condition; acute exacerbation of COPD 0.8% — defer test until acute episode is over; severe asthma 0.4% — do not perform test; methylxanthine ingestion 0.3% — avoid consumption previously; other 6.1% — evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was cancelled due to absolute contraindications in 2.9% of the requests. ConclusionsWorking in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial progenitor cells (EPCs) aging is a possible molecular way for COPD development. We aimed to explore the effector whether intravenous administration of EPCs has therapeutic effects in COPD mice.MethodsCOPD mice model was induced by cigarette smoke exposure and EPCs were injected intravenously to investigate their effects on COPD mice. At day 127, heart, liver, spleen, lung and kidney tissues of mice were harvested. The histological effects of EPCs intervention on multiple organs of COPD mice were detected by morphology assay. Quantitative real-time PCR and Western blotting were used to detect the effect of EPCs intervention on the expression of multi-organ senescence-related indicators. And we explored the effect of EPCs systematically intervening on senescence-related USP7/p300 pathway.ResultsCompared with COPD group, senescence-associated β-galactosidase activity was decreased, protein and mRNA expression of p16 was down-regulated, while protein and mRNA expression of cyclin D1 and TERT were up-regulated of multiple organs, including lung, heart, liver, spleen and kidney in COPD mice after EPCs system intervention. But the morphological alterations of the tissues described above in COPD mice failed to be reversed. Mechanistically, EPCs systemic administration inhibited the expression of mRNA and protein of USP7 and p300 in multiple organs of COPD mice, exerting therapeutic effects.ConclusionsEPCs administration significantly inhibited the senescence of multiple organs in COPD mice via down-regulating USP7/p300 pathway, which presents a possibility of EPCs therapy for COPD.

Modified Bushen Yiqi Formula mitigates pulmonary inflammation and airway remodeling by inhibiting neutrophils chemotaxis and IL17 signaling pathway in rats with COPD

Ethnopharmacological relevanceChronic obstructive pulmonary disease (COPD) is a major global health concern characterized by pulmonary inflammation and airway remodeling. Traditional Chinese medicine, such as Modified Jiawei Bushen Yiqi Formula (MBYF), has been used as a complementary therapy for COPD in China. Aim of the studyTo investigate the therapeutic potential of MBYF in a rat model of COPD induced by cigarette smoke (CS) exposure and explore the underlying mechanism. Materials and methodsThe COPD rat model was established through 24 weeks of CS exposure, with MBYF administration starting in the 9th week. Pulmonary function, histological analysis, inflammatory cell count and molecular assays were employed to assess the effects of MBYF on airway remodeling, pulmonary inflammation, neutrophils chemotaxis and the IL17 signaling pathway. ResultsMBYF treatment effectively delayed airway remodeling, as evidenced by improved pulmonary function parameters. Histological examination and bronchoalveolar lavage fluid analysis revealed that MBYF mitigated CS-induced pulmonary inflammation by reducing inflammatory cell infiltration. Pharmacological network analysis suggested that MBYF may act through the IL17 signaling pathway to regulate inflammatory responses. RNA-sequencing and molecular assays indicated that MBYF inhibited neutrophils chemotaxis through downregulating the CXCL1/CXCL5/CXCL8-CXCR2 axis, and suppressed IL17A, IL17F and its downstream cytokines, including IL6, TNFα, IL1β, and COX2. Furthermore, MBYF inhibited the activation of NF-κB and MAPKs in the IL17 signaling pathway. ConclusionMBYF exhibits potential as an adjunct or alternative treatment for COPD, effectively mitigating CS-induced pulmonary inflammation and airway remodeling through the inhibition of neutrophil chemotaxis and IL17 signaling pathway.

Recent Advances in the Devices for the Treatment of Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease or COPD has been known to adversely affect people's quality of life. It influences a great number of individuals overall and is a main source of horribleness and mortality. It is associated with major healthcare and socioeconomic burdens. So, it is important to cure such types of diseases. This review articledeals with the proper understanding of the newly developed devices and various advances taking place in the treatment of COPD. There are many new methods and procedures being developed recently for the cure or treatment of COPD, of which some are mentioned in the following review article. The articles also deal with the beneficial effects as well as the challenges faced during the use of those newly developed methods during the treatment of the disease. Various types of management of COPD are also mentioned in the article. This article also deals with the various new advances that are currently taking place in devices used in the therapy of COPD.

Clinical Implications of Peak Inspiratory Flow in COPD: Post Hoc Analyses of the TRONARTO Study.

In patients with COPD, inhalation ability should be assessed when considering inhaler choice. To evaluate whether the soft mist inhaler (SMI) is suitable for COPD patients irrespective of inhalation ability, the TRONARTO study investigated the efficacy of dual long-acting bronchodilator therapy delivered via the Respimat® SMI on lung function in patients with COPD stratified by inhalation ability. Tiotropium/olodaterol delivered via the SMI was effective both in patients with peak inspiratory flow (PIF) <60L/min and PIF ≥60L/min, measured against medium-low resistance. This congress compilation summarizes post hoc analyses from the TRONARTO study presented at the annual American Thoracic Society 2022 and European Respiratory Society 2022 meetings. These analyses evaluated PIF in over 200 patients, with PIF measurements taken daily at home for 4weeks, and in the clinic at baseline, Weeks 2 and 4. Overall, 57.9% of patients had a PIF range (difference between lowest and highest PIF measurements) <20 L/min (12.4% of patients had PIF range <10 L/min). At-home PIF range decreased over the study period, suggesting that inhaler training/repeated PIF measurements may help to make patients' inspiratory effort more consistent. Some patient characteristics correlated with lower PIF (female gender, shorter stature, more severe disease, worse airflow obstruction) and lower PIF range (more severe disease). PIF measurements differed between medium-low and high-resistance settings, highlighting the importance of measuring PIF at the resistance of a patient's inhaler. PIF correlated poorly with spirometry measurements. As indicated in COPD management guidelines, choice of inhaler is essential to optimize pharmacologic therapies for COPD. Poor inspiratory ability should be viewed as a treatable trait that can help to inform inhaler choice. Inhaler training and consideration of PIF (if patients use a dry powder inhaler) can reduce patient-to-inhaler mismatch, with potential consequences for health status and exacerbation risk.