Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease - the PROSA study: rationale and study design.

BACKGROUND: Chronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers. METHODS: 148 COPD patients (GOLD stage 2-3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation. DISCUSSION: The PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028. TRIAL REGISTRATION: The PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024).

Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization.

BACKGROUND: Previous research has emphasized the potential benefits of anti-diabetic medications in inhibiting the exacerbation of Chronic Obstructive Pulmonary Disease (COPD), yet the role of anti-diabetic drugs on COPD risk remains uncertain. METHODS: This study employed a Mendelian randomization (MR) approach to evaluate the causal association of genetic variations related to six classes of anti-diabetic drug targets with COPD. The primary outcome for COPD was obtained from the Global Biobank Meta-analysis Initiative (GBMI) consortium, encompassing a meta-analysis of 12 cohorts with 81,568 cases and 1,310,798 controls. Summary-level data for HbA1c was derived from the UK Biobank, involving 344,182 individuals. Positive control analysis was conducted for Type 2 Diabetes Mellitus (T2DM) to validate the choice of instrumental variables. The study applied Summary-data-based MR (SMR) and two-sample MR for effect estimation and further adopted colocalization analysis to verify evidence of genetic variations. RESULTS: SMR analysis revealed that elevated KCNJ11 gene expression levels in blood correlated with reduced COPD risk (OR = 0.87, 95% CI = 0.79-0.95; p = 0.002), whereas an increase in DPP4 expression corresponded with an increased COPD incidence (OR = 1.18, 95% CI = 1.03-1.35; p = 0.022). Additionally, the primary method within MR analysis demonstrated a positive correlation between PPARG-mediated HbA1c and both FEV1 (OR = 1.07, 95% CI = 1.02-1.13; P = 0.013) and FEV1/FVC (OR = 1.08, 95% CI = 1.01-1.14; P = 0.007), and a negative association between SLC5A2-mediated HbA1c and FEV1/FVC (OR = 0.86, 95% CI = 0.74-1.00; P = 0.045). No colocalization evidence with outcome phenotypes was detected (all PP.H4 < 0.7). CONCLUSION: This study provides suggestive evidence for anti-diabetic medications' role in improving COPD and lung function. Further updated MR analyses are warranted in the future, following the acquisition of more extensive and comprehensive data, to validate our results.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines Reviewed.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report is an essential resource for all clinicians who strive to provide optimal care to patients with chronic obstructive lung disease (COPD). The annual report of GOLD makes few revisions and updates besides including data from the preceding year. At an interval, GOLD comes up with a significant modification in its guidelines, which is generally a major overhaul of the pre-existing guidelines. According to the latest 2023 updates, published in November 2022, there have been significant advancements made in the field of COPD. These include the development of more precise definitions for COPD and its exacerbations, the introduction of a new set of parameters to measure exacerbation severity, and updating the COPD assessment tool. Additionally, revisions have been made to the initial and follow-up treatment guidelines. The report also simplifies the treatment algorithm and sheds light on new findings that suggest the use of pharmacological triple therapy can reduce mortality rates. Furthermore, the report includes discussions on inhaler device selection and adherence to COPD medications. These improvements demonstrate a continued effort to enhance COPD treatment and management. Although there are some areas that could benefit from more detailed guidance and explanation, such as the proper utilization of blood eosinophil counts for treatment decisions, and the establishment of treatment protocols post-hospitalization, the latest modifications to the GOLD recommendations will undoubtedly aid healthcare providers in addressing any gaps in patient care. We aim to highlight key changes in the GOLD 2023 report and present a viewpoint about their potential implications in a real-world clinical scenario.

Self-management intervention for patients following hospitalization for acute exacerbation of chronic obstructive pulmonary disease (AECOPD): A pilot randomized controlled trial.

The purpose of this study was to evaluate the handoff guidance (HG) self-management intervention for multimorbid chronic obstructive pulmonary disease (COPD) patients following hospitalization for acute exacerbation of COPD (AECOPD) using HG self-management intervention compared to a control group on COPD self-management outcomes (self-care, self-efficacy, health engagement) and assess feasibility, acceptability, and healthcare utilization. A randomized pilot study used a 2-group with repeated measures design. Adults with COPD who had been hospitalized for AECOPD were recruited. After discharge, the HG self-management intervention employed health coaching delivered at: 1-3, 10-12, and 20-22 days after hospital discharge. Follow-up data collected was collected at 1-3, 10-12, 20-22, 30, 60, and 90 days after hospital discharge. A total of 29 subjects participated, with a mean age of 66 (+8.7) years old, the majority were females (n = 18). Intervention participants reported the acceptability of the HG self-management intervention. Participants in both groups continued to report COPD symptoms after discharge, which decreased over time, although not significantly different by group. The use of COPD maintenance, monitoring, and management behaviors was higher in the treatment group, although not significantly different.

Comparison of BAP65, DECAF, PEARL, and MEWS Scores in Predicting Respiratory Support Need in Hospitalized Exacerbation of Chronic Obstructive Lung Disease Patients.

OBJECTIVE: Prognostic models aid clinical practice with decision-making on treatment and hospitalization in exacerbation of chronic obstructive lung disease (ECOPD). Although there are many studies with prognostic models, diagnostic accuracy is variable within and between models. SUBJECTS AND METHODS: We compared the prognostic performance of the BAP65 score, DECAF score, PEARL score, and modified early warning score (MEWS) in hospitalized patients with ECOPD, to estimate ventilatory support need. RESULTS: This cross-sectional study consisted of 139 patients. Patients in need of noninvasive or invasive mechanical ventilation support are grouped as ventilatory support groups (n = 54). Comparison between receiver operating characteristic curves revealed that the DECAF score is significantly superior to the PEARL score (p = 0.04) in discriminating patients in need of ventilatory support. DECAF score with a cutoff value of 1 presented the highest sensitivity and BAP65 score with a cutoff value of 2 presented the highest specificity in predicting ventilatory support need. Multivariable analysis revealed that gender played a significant role in COPD exacerbation outcome, and arterial pCO2 and RDW measurements were also predictors of ventilatory support need. Within severity indexes, only the DECAF score was independently associated with the outcome. One-point increase in DECAF score created a 1.43 times higher risk of ventilatory support need. All severity indexes showed a correlation with age, comorbidity index, and dyspnea. BAP65 and DECAF scores also showed a correlation with length of stay. CONCLUSION: Objective and practical classifications are needed by clinicians to assess prognosis and initiate treatment accordingly. DECAF score is a strong candidate among severity indexes.

Comparison of Disease Severity Classifications of Chronic Obstructive Pulmonary Disease: GOLD vs. STAR in Clinical Practice.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR), with four grades of severity in subjects with an FEV1/FVC ratio <0.70: STAR 1 ≥0.60 to <0.70, STAR 2 ≥0.50 to <0.60, STAR 3 ≥0.40 to <0.50, and STAR 4 <0.40. PURPOSE: The aim of this study was to compare the staging of COPD using the GOLD and STAR classifications in clinical practice. METHODS: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. RESULTS: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3 + 4 groups, with the GOLD 1 group used as the reference [hazard ratio 4.222 (95% CI 1.298-13.733), p = 0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3 + 4. St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3 + 4, but not between STAR 1 and STAR 2. CONCLUSION: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

RSV-related Community COPD Exacerbations and Novel Diagnostics: A Binational Prospective Cohort Study.

RATIONALE: Respiratory syncytial virus (RSV) is a common global respiratory virus increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults with acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. OBJECTIVES: This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. METHODS: Participants were recruited at specialist clinics in London, UK and Groningen, NL from 2017 and observed for three consecutive RSV seasons, during exacerbations and at least twice yearly. RSV infections were detected by reverse transcription-polymerase chain reaction (RT-PCR) and serologic testing. MEASUREMENTS AND MAIN RESULTS: 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8·7% of total); of these, seven were detected only on PCR, 16 only on serology and 4 by both methods. Increases in RSV specific N-protein antibody were as sensitive as antibody to pre-F or post-F for serodiagnosis of RSV related exacerbations. CONCLUSIONS: RSV is associated with 8.7% of outpatient managed COPD exacerbations in this study. Antibodies to RSV-N protein may have diagnostic value, potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

A comparison of GOLD 2019 and 2023 recommendations to contemporaneous real-world inhaler treatment patterns for chronic obstructive pulmonary disease management in Singapore.

Background: In 2019 and 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) provided updated strategies for modifying the therapy of patients with chronic obstructive pulmonary disease (COPD) and high exacerbation risk. A key update since the 2019 guidelines recommends considering blood eosinophil count to guide decisions on inhaled corticosteroid (ICS) treatment. To evaluate the potential impact of these updated recommendations, this study aimed to assess how extensively future practice would diverge from contemporaneous prescribing practices at a single center in Singapore, assuming adherence to the 2019 and 2023 GOLD guidelines. Methods: Retrospective cohort analysis of the Changi General Hospital COPD data warehouse involving patients aged ≥40 years hospitalized for a COPD exacerbation (October 2018-April 2020) receiving long-acting muscarinic antagonist (LAMA), LAMA plus a long-acting beta2-agonist (LABA), or an ICS plus LABA at admission. The proportion of patients eligible for treatment escalations per GOLD 2019 and 2023 recommendations was calculated. Results: In total, 268 patients were included (mean age 73 years; 91% male). At admission, 19%, 59%, and 22% of patients were receiving LAMA, LAMA + LABA, and ICS + LABA, respectively. Overall, 226 patients would have been eligible for treatment escalation per GOLD 2019 or 2023 recommendations; 31 (13.7%) had treatment escalations consistent with GOLD 2019 guidelines and 34 (15%) received treatment escalations consistent with GOLD 2023 guidelines. A total of 205 patients (76.5%) remained on the same treatment regimen at hospital discharge as they were receiving at admission. Lower measured post-bronchodilator forced expiratory volume in 1 second was associated with treatment escalations that would have been GOLD-concordant (P=0.028), as was increased number of emergency department/hospital visits in the last year (P=0.048). Conclusions: Compared with real-world clinical practice, a significantly higher proportion of patients may be eligible for treatment escalation under the GOLD 2019 and 2023 eosinophil-directed algorithms.

The Fagerström Test for Nicotine Dependence, as a prognostic factor, in current smokers with and without COPD: A cross-sectional study in northern Greece.

BACKGROUND: Smoking poses the most common risk factor for chronic obstructive pulmonary disease (COPD) and aggravates disease progression. Tobacco dependence inhibits smoking cessation and may affect smoking patterns that increase tobacco exposure and predispose to lung function decline. AIMS AND OBJECTIVES: We aimed to assess tobacco dependence in current smokers with and without COPD and evaluate its role in disease development. METHOD: This cross-sectional study was conducted in Greek rural areas. Current smokers completed the Fagerström Test for Nicotine Dependence and were classified into COPD and non-COPD groups based on spirometry parameters. RESULTS: Among current smokers, 288 participants comprised the non-COPD and 71 the COPD group. Both presented moderate tobacco dependence, but smokers with COPD started to smoke earlier in the morning. Multiple logistic regression analysis revealed higher COPD prevalence in smokers with higher scores in the Fagerström test (odds ratio OR = 1.12, 95% confidence interval [1.01 - 1.24]) and older age (OR = 1.06 [1.03 - 1.09]), independently of pack-years smoking index. Multiple linear regression analysis in smokers with COPD showed that the forced expiratory volume in the 1st second decreased by 2.3% of the predicted value for each point increase in the Fagerström Test and 0.59% for each year of age, independently of participants' sex and pack-years smoking index. CONCLUSION: The Fagerström score appears to indicate a higher probability for COPD and lung function deterioration when assessed along with age in current smokers. Smoking cessation support programs are fundamental to COPD prevention and management.

[Chronic cough in adult patients-evidence-based approach]. / Chronischer Husten bei erwachsenen Patienten ­ evidenzbasiertes Vorgehen.

Approximately 10% of the population suffer from a cough lasting longer than 8 weeks. Compared to acute cough, which usually occurs in the context of banal respiratory tract infections, the differential diagnoses of chronic cough require an increased use of diagnostic tests and thus a structured, evidence-based approach according to current international guidelines. A targeted history (smoking status, medication, previous diseases) and ENT status are always followed by chest x­ray and pulmonary function tests before extended diagnostics. In the case of angiotensin-converting enzyme (ACE) inhibitor use and unremarkable physical examination, a drug discontinuation test can be carried out first. In case of inconspicuous findings, a disease entity that can be treated empirically such as upper airway cough syndrome is most likely. If the cough remains unexplained, cough suppression techniques, physiotherapy or speech therapy should be sought before off-label-use of medication.

Feasibility of a home-designed respiratory rehabilitation program for chronic obstructive pulmonary disease.

BACKGROUND: According to international guidelines, respiratory rehabilitation (RR) for patients with chronic obstructive pulmonary disease (COPD) is a cornerstone of standard non-pharmacological treatment. AIMS: To evaluate feasibility of a home-designed RR program and analyze its medium-term impact on respiratory parameters and quality of life. METHODS: This was a prospective study involving 74 COPD patients enrolled in January 2019 and put on inhaled bronchodilator treatment associated with RR at home following a written protocol, for 16 weeks. The comparative statistical analysis highlights the difference before and after RR in terms of clinical and functional respiratory parameters as well as in terms of quality of life (assessed on the short form 36 (SF-36) questionnaire). The comparison involves RR-adherent patients versus non-adherent patients. RESULTS: Mean age was 66.7 ± 8.3 years with a median of 67 years. All patients were smokers, out of which 42 patients (57%) did not quit yet. Forty-one percent of patients were frequent exacerbators. The average COPD assessment test (CAT) score in our patients was 23. The average 6-minutes walk distance (MWD) was 304 m. The BODE index in our patients was 4.11 on average. The RR program was followed by 36 patients (48%). Thirty patients (40%) applied it at least twice a week. RR-adherent patients had an average CAT score decreasing from 23 to 14.5 (P = 0.011). Their average 6-MWD was 444.6 m by the end of the study, which would be 64.2% of the calculated theoretical value. The average FEV1 increase after RR was 283 mL. The majority (69%) of RR-adherent patients were ranked as quartile 1; BODE index ≤2. The average scores of physical, psycho-social, and general dimensions assessed on the SF-36 questionnaire improved in RR-adherent patients. CONCLUSIONS: RR is a key non-pharmacological treatment for COPD. Its interest originates from its multidisciplinary nature, hence its effectiveness in several respiratory parameters. Our study reflects the feasibility of home-designed protocols in the absence of contraindications. We highlight also the positive impact on quality of life after RR at home.

Psychophysical and Social Functioning of Patients with Chronic Obstructive Lung Disease and Depression.

The relationship between depression and chronic obstructive pulmonary disease (COPD) is not fully understood. The comorbidity rate ranges from 18 to 84%, and depression is closely related to chronic inflammation, which affects how patients and the people around them perceive their condition. This study aims to examine the relationship between the psychophysical and social functioning of COPD patients who have been diagnosed with depression and the therapeutic benefits of selective serotonin reuptake inhibitors (SSRIs). This prospective study enrolled primary care patients diagnosed with COPD and depression. The entire period of this research was 3 years. The research was conducted at the Primary Health Center, Kragujevac, Serbia, in 87 patients for 8 weeks. The Hamilton Depression Scale (HAM-D) and Questionnaire for Quality of Life and Life Satisfaction Short Form (Q-LES-Q-SF) were used for psychiatric assessment. A positive correlation was found between the psychophysical and social functioning of the participants after 8 weeks of treatment with SSRIs. Based on the value of the phi correlation coefficient (phi = 0.5) obtained using the χ2 test, a large influence was observed in terms of life satisfaction and physical health (p < 0.05). In terms of physical functioning by gender, based on the value of the Pearson's coefficient (r) obtained with the χ2 test, it was shown that physical functioning was superior in the female respondents (p < 0.05). Treatment was found to improve depression in COPD after 8 weeks of therapy.

Metacognitions in patients with chronic obstructive pulmonary disease: a psychometric study of the metacognitions questionnaire-30.

The metacognitions questionnaire-30 (MCQ-30) was developed for the assessment of metacognitive beliefs and processes that are central components of the metacognitive model of emotional disorders. Anxiety and depression commonly occur in patients with chronic obstructive pulmonary disease (COPD). Testing such a model for anxiety and depression in patients with COPD is warranted. However, the psychometric properties of the MCQ-30 in COPD patients are unknown. Therefore, in this study we aimed to examine these properties in COPD patients. The MCQ-30 was administered to 203 COPD patients referred to a rehabilitation unit in respiratory medicine. Confirmatory factor analysis (CFA) was used to test the five-factor as well as the bi-factor models of MCQ-30. Exploratory factor analyses were also performed. Both models did not meet the criteria for an acceptable fit on Comparative Fit Index (CFI) of 0.810 and 0.858 vs. criterion of ≥0.9, but the Root Mean Square Error of Approximation (RMSEA) criterion ≤0.08 was acceptable for both models with RMSEA = 0.074 and 0.066, respectively. The factors were mostly moderately correlated (0.41-0.58) with acceptable reliability coefficients (0.73-0.87). The exploratory factor analysis identified three of the five factors originally described in the five-factor model of the MCQ-30. These data show that the factor structure of the MCQ-30 appears to differ from that of the original instrument in COPD patients and further studies are needed to confirm its validity and reliability in this patient group.

A systematic review of exercise studies for individuals hospitalized with an acute exacerbation of chronic obstructive pulmonary disease: Focus on the principles of exercise training.

BACKGROUND: For exercise interventions to be effectively reproduced or applied in a "real world" clinical setting, clinical trials must thoroughly document all components of the exercise prescription and ensure that participants adhere to each component. However, previous reviews have not critically examined the quality of exercise prescription of inpatient Pulmonary Rehabilitation (PR) programs. OBJECTIVE: The objectives of this review were to evaluate the (a) application of the principles of exercise training, (b) reporting of the frequency, intensity, time and type (FITT) components of exercise prescription, and (c) reporting of patient's adherence to the FITT components in intervention studies for patients admitted to hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Relevant scientific databases were searched for randomized controlled trials (RCTs) that compared in-hospital PR with usual care for people hospitalized with AECOPD. Title and abstract followed by full-text screening were conducted independently by two reviewers. Data were extracted and synthesized to evaluate the application of the principles of exercise training and the reporting/adherence of the FITT components. RESULTS: Twenty-seven RCTs were included. Only two applied all principles of exercise training. Specificity was applied by 70%, progression by 48%, overload by 37%, initial values by 89% and diminishing returns and reversibility by 37% of trials. Ten trials adequately reported all FITT components. Frequency and type were the components most reported (85% and 81%, respectively), while intensity was less frequently reported (52%). Only three trials reported on the patient's adherence to all four components. CONCLUSIONS: Studies have not adequately reported the exercise prescription in accordance with the principles of exercise training nor reported all the FITT components of the exercise prescription and patient's adherence to them. Therefore, interpretation of the current literature is limited and information for developing exercise prescriptions to individuals hospitalized with an AECOPD is lacking.

The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

Exploring the Validity of GOLD 2023 Guidelines: Should GOLD C and D Be Combined?

Introduction: The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2023 guidelines proposed important changes to the stratification of disease severity using the "ABCD" assessment tool. The highest risk groups "C" and "D" were combined into a single category "E" based on exacerbation history, no longer considering symptomology. Purpose: We quantify the differential disease progression of individuals initially stratified by the GOLD 2022 "ABCD" scheme to evaluate these proposed changes. Patients and Methods: We utilise data collected from 1529 users of the myCOPD mobile app, a widely used and clinically validated app supporting people living with COPD in the UK. For patients in each GOLD group, we quantify symptoms using COPD Assessment Tests (CAT) and rate of exacerbation over a 12-month period post classification. Results: CAT scores for users initially classified into GOLD C and GOLD D remain significantly different after 12 months (Kolmogorov-Smirnov statistic = 0.59, P = 8.2 × 10-23). Users initially classified into GOLD C demonstrate a significantly lower exacerbation rate over the 12 months post classification than those initially in GOLD D (Kolmogorov-Smirnov statistic = 0.26; P = 3.1 × 10-2; all exacerbations). Further, those initially classified as GOLD B have higher CAT scores and exacerbation rates than GOLD C in the following 12 months. Conclusion: CAT scores remain important for stratifying disease progression both in-terms of symptomology and future exacerbation risk. Based on this evidence, the merger of GOLD C and GOLD D should be reconsidered.

PULMONARY DISEASE DIAGNOSTIC AND REHABILITATION TREATMENT FOR PATIENTS WITH OVERLAP ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASES.

OBJECTIVE: Aim: To analyze the effectiveness of rehabilitation treatment in the conditions of halo aerosol therapy and when using different groups of fixed-dose aerosol inhalers in patients with asthma, chronic obstructive pulmonary diseases and asthma-chronic obstructive pulmonary diseases overlap. PATIENTS AND METHODS: Materials and Methods: A total 112 patients with asthma, chronic obstructive pulmonary diseases and asthma-chronic obstructive pulmonary diseases overlap. All patients carefully collected allergic history, anamnesis of life, and disease. The study includes assessment of resting anthropometric data, physical activity habits, blood pressure, structure and quality of nutrition, family and economic data. RESULTS: Result: After a course of rehabilitation treatment, lung ventilation improved in all groups of patients compared to controls. The dynamics of FER indicators after the rehabilitation treatment had some differences for each group of patients in relation to the control groups. If in all A groups (control) the increase in FER indicators was insignificant, then in all B groups of patients it was significant, and differed from 14,6% up to 36%. CONCLUSION: Conclusions: Thus, a differentiated approach to the use of fixed-dose aerosol inhalers increases the effectiveness of rehabilitation treatment under conditions of halo aerosol therapy in patients with various genesis of bronchi-obstructive syndrome.

Life-threatening bronchospasm induced by an angiotensin-converting enzyme inhibitor in a chronically ventilated patient: Diagnostic pitfalls and literature review.

Cough- and asthma-like symptoms are common adverse reactions to angiotensin-converting enzyme inhibitors (ACEi). However, attributing these symptoms to the use of ACEi might be masked by clinical confounders. We report a 68-year-old female residing in a long-term acute-care facility for patients requiring prolonged invasive mechanical ventilation treated for years with ACEi. Daily reversible bouts of life-threatening severe bronchospasm gradually developed over 6 weeks and abruptly resolved following the cessation of ACEi treatment. The late appearance of bronchospasm and the unique clinical setup of chronic invasive ventilation in a patient with smoking-related chronic obstructive lung disease are among the principal confounders that delay the identification of the causative association between ACEi and respiratory compromise. Chronic positive pressure ventilation may also conceal small airway reactivity and obstruction, similar to auto-positive end-expiratory pressure (auto-PEEP). Conceivably, angiotensin receptor blockers should be preferred over ACEi in such patients.

Biomarkers of the L-Arginine/Dimethylarginine/Nitric Oxide Pathway in People with Chronic Airflow Obstruction and Obstructive Sleep Apnoea.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are common chronic diseases that are associated with chronic and intermittent hypoxemia, respectively. Patients affected by the overlap of COPD and OSA have a particularly unfavourable prognosis. The L-arginine/nitric oxide (NO) pathway plays an important role in regulating pulmonary vascular function. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) interfere with NO production. METHODS: We analysed the serum concentrations of ADMA, SDMA, L-arginine, L-citrulline, and L-ornithine in a large sample of the Icelandic general population together with chronic airflow obstruction (CAO), a key physiological marker of COPD that was assessed by post-bronchodilator spirometry (FEV1/FVC < LLN). OSA risk was determined by the multivariable apnoea prediction (MAP) index. RESULTS: 713 individuals were analysed, of whom 78 (10.9%) showed CAO and 215 (30%) had MAP > 0.5. SDMA was significantly higher in individuals with CAO (0.518 [0.461-0.616] vs. 0.494 [0.441-0.565] µmol/L; p = 0.005), but ADMA was not. However, ADMA was significantly associated with decreasing FEV1 percent predicted among those with CAO (p = 0.002). ADMA was 0.50 (0.44-0.56) µmol/L in MAP ≤ 0.5 versus 0.52 (0.46-0.58) µmol/L in MAP > 0.5 (p = 0.008). SDMA was 0.49 (0.44-0.56) µmol/L versus 0.51 (0.46-0.60) µmol/L, respectively (p = 0.004). The highest values for ADMA and SDMA were observed in individuals with overlap of CAO and MAP > 0.5, which was accompanied by lower L-citrulline levels. CONCLUSIONS: The plasma concentrations of ADMA and SDMA are elevated in COPD patients with concomitant intermittent hypoxaemia. This may account for impaired pulmonary NO production, enhanced pulmonary vasoconstriction, and disease progression.