Applying the Rome Proposal on Exacerbations of Chronic Obstructive Pulmonary Disease: Does Comorbid Chronic Heart Failure Matter?

Background: Chronic heart failure (CHF) is a common comorbidity among patients with chronic obstructive pulmonary disease (COPD). Both exacerbations of COPD (ECOPDs) and exacerbations of CHF (ECHFs) display worsening of breathlessness at rest (BaR) and breathlessness at physical activity (BaPA). Comorbid CHF may have an impact on the vital signs assessed, when the Rome proposal (adopted by GOLD 2023) is applied on ECOPDs. Thus, the aim of the present study was to investigate the impact of comorbid CHF on ECOPDs severity, particularly focusing on the influence of comorbid CHF on BaR and BaPA. Methods: We analysed data on COPD symptoms collected from the telehealth study The eHealth Diary. Patients with COPD (n = 43) and patients with CHF (n = 41) were asked to daily monitor BaR and BaPA, employing a digital pen and scales for BaR and BaPA (from 0 to 10). Twenty-eight patients of the COPD patients presented with comorbid CHF. Totally, 125 exacerbations were analysed. Results: Exacerbations in the group with COPD patients and comorbid CHF were compared to the group with COPD patients without comorbid CHF and the group with CHF patients. Compared with GOLD 2022, the GOLD 2023 (the Rome proposal) significantly downgraded the ECOPD severity. Comorbid CHF did not interfere significantly on the observed difference. Comorbid CHF did not worsen BaR scores, assessed at inclusion and at the symptom peak of the exacerbations. Conclusion: In the present study, we find no evidence that comorbid CHF would interfere significantly with the parameters included in the Rome proposal (GOLD 2023). We conclude that the Rome proposal can be safely applied even on COPD patients with very advanced comorbid CHF.

Can a telemonitoring system lead to decreased hospitalization in elderly patients?

INTRODUCTION: Growing populations of elderly patients with chronic obstructive pulmonary disease (COPD) or heart failure (HF) require more healthcare. A four-year telehealth intervention - the Health Diary system based on digital pen technology - was implemented. We hypothesized that study patients with advanced COPD or HF would have lower rates of hospitalization when using the Health Diary. The aim was to investigate the effects of the intervention on healthcare costs and the number of hospitalizations, as well as other care required in COPD and HF patients. METHODS: Patients were introduced to the telemonitoring system which was supervised by a specialized hospital-based home care (HBHC) unit. Staff associated with this unit were responsible for the healthcare provided. The study included patients with COPD or HF, aged ≥ 65 years who were frequently hospitalized due to exacerbations - at least two inpatient episodes within the last 12 months. Observed number of hospitalizations and total healthcare costs were compared with the expected values, which were calculated using the generalized estimating equations (GEE) method. RESULTS: A total of 36 COPD and 58 HF patients with advanced stages of disease were included. The number of hospitalizations was significantly reduced for both HF and COPD patients participating in telemonitoring. Accordingly, hospitalization costs were significantly reduced for both groups, but the total healthcare cost was not significantly different from the expected costs. CONCLUSION: A telemonitoring system, the Health Diary, combined with a specialized HBHC unit significantly decreases the need for hospital care in elderly patients with advanced HF or COPD without increasing total healthcare costs.

Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO GLI LLN but GLI LLN but GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Increased Lysosomal Membrane Permeabilization in Oxidant-exposed Macrophages of Human Fibrotic Lungs.

A disrupted balance of reduced glutathione (GSH) and iron (Fe) and subsequent enhanced susceptibility of lysosomes of lung macrophages (LMs) to oxidants may play a role in lung fibrogenesis. We assessed cellular Fe/GSH, lysosomal membrane permeabilization (LMP), and cell death in cultures of oxidant exposed LMs. LMs from 7 lung fibrosis patients and healthy subjects were exposed to a physiologic concentration of H2O2 for 1 h. LMP was assessed with acridine orange green fluorescence, apoptosis/necrosis were estimated by apoptotic DNA and typical morphology, Fe was assessed with Prussian blue staining/atomic absorption spectrophotometry, and GSH was evaluated using a GSH assay kit. Oxidant-induced LMP and cell death were more pronounced in cultures of LMs from patients with lung fibrosis, and these cells contained less GSH and more cytochemically stained Fe. These observations indicate that LMP may be involved in fibrosis development, possibly through activation of the inflammasome complex. Further studies are warranted for a detailed understanding.

Prevention of oxidant-induced cell death by lysosomotropic iron chelators.

Intralysosomal iron powerfully synergizes oxidant-induced cellular damage. The iron chelator, desferrioxamine (DFO), protects cultured cells against oxidant challenge but pharmacologically effective concentrations of this drug cannot readily be achieved in vivo. DFO localizes almost exclusively within the lysosomes following endocytic uptake, suggesting that truly lysosomotropic chelators might be even more effective. We hypothesized that an amine derivative of alpha-lipoamide (LM), 5-[1,2] dithiolan-3-yl-pentanoic acid (2-dimethylamino-ethyl)-amide (alpha-lipoic acid-plus [LAP]; pKa = 8.0), would concentrate via proton trapping within lysosomes, and that the vicinal thiols of the reduced form of this agent would interact with intralysosomal iron, preventing oxidant-mediated cell damage. Using a thiol-reactive fluorochrome, we find that reduced LAP does accumulate within the lysosomes of cultured J774 cells. Furthermore, LAP is approximately 1000 and 5000 times more effective than LM and DFO, respectively, in protecting lysosomes against oxidant-induced rupture and in preventing ensuing apoptotic cell death. Suppression of lysosomal accumulation of LAP (by ammonium-mediated lysosomal alkalinization) blocks these protective effects. Electron paramagnetic resonance reveals that the intracellular generation of hydroxyl radical following addition of hydrogen peroxide to J774 cells is totally eliminated by pretreatment with either DFO (1 mM) or LAP (0.2 microM) whereas LM (200 microM) is much less effective.