Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients.

COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls without COVID-19 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA variants (40-60% heteroplasmy), and allows the assessment of low-level heteroplasmy (<10% heteroplasmy). Serum concentrations of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic variants in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic variant burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. These findings suggest that SARS-CoV-2 may induce mtDNA mutations that are related to the degree of inflammation.

Role of Cardio-Renal Dysfunction, Inflammation Markers, and Frailty on In-Hospital Mortality in Older COVID-19 Patients: A Cluster Analysis.

Our study aimed to identify clusters of hospitalized older COVID-19 patients according to their main comorbidities and routine laboratory parameters to evaluate their association with in-hospital mortality. We performed an observational study on 485 hospitalized older COVID-19 adults (aged 80+ years). Patients were aggregated in clusters by a K-medians cluster analysis. The primary outcome was in-hospital mortality. Medical history and laboratory parameters were collected on admission. Frailty, defined by the Clinical Frailty Scale (CFS), referred to the two weeks before hospitalization and was used as a covariate. The median age was 87 (83-91) years, with a female prevalence (59.2%). Three different clusters were identified: cluster 1 (337), cluster 2 (118), and cluster 3 (30). In-hospital mortality was 28.5%, increasing from cluster 1 to cluster 3: cluster 1 = 21.1%, cluster 2 = 40.7%, and cluster 3 = 63.3% (p < 0.001). The risk for in-hospital mortality was higher in clusters 2 [HR 1.96 (95% CI: 1.28-3.01)] and 3 [HR 2.87 (95% CI: 1.62-5.07)] compared to cluster 1, even after adjusting for age, sex, and frailty. Patients in cluster 3 were older and had a higher prevalence of atrial fibrillation, higher admission NT-proBNP and C-reactive protein levels, higher prevalence of concurrent bacterial infections, and lower estimated glomerular filtration rates. The addition of CFS significantly improved the predictive ability of the clusters for in-hospital mortality. Our cluster analysis on older COVID-19 patients provides a characterization of those subjects at higher risk for in-hospital mortality, highlighting the role played by cardio-renal impairment, higher inflammation markers, and frailty, often simultaneously present in the same patient.

A virtual reality-based endurance training program for COPD patients: acceptability and user experience.

PURPOSE: To investigate the acceptability and user experience of an in-hospital endurance training program based on the Virtual Park, a semi-immersive Virtual Reality (VR) system for patients with Chronic Obstructive Pulmonary Disease (COPD).Materials and methodsPatients performed 20 min of cycling two times/day for around ten days. The evaluation included adherence, exercise capacity, physical performance, and user experience. RESULTS: Fourteen patients (6 F/8 M; age = 71.29 ± 6.93 years) with mild/moderate COPD participated. The adherence rate was satisfying: 85.71% of patients attended the program without adverse events; the individual attendance rate (86.85% ± 27.43) was also high. The exercise capacity assessed before and after the training significantly improved in our group (6MWT pre-post: t(11)= -5.040, p < 0.05), as happens in standard PR programs. The physical performance metrics of each session indicate that all participants could sustain the proposed training protocol over the whole period. Patients judged the VR experience positively (User Experience Questionnaire = 1.84 ± 0.22) and were highly engaged in the activity for the whole period (Short Flow State Scale pre-post: 4.61 ± 0.27/4.40 ± 0.36). CONCLUSIONS: Our preliminary results open the possibility for further investigations on long-term motivation and clinical effectiveness of more immersive VR interventions for COPD.

The Virtual Park system is specifically designed for COPD, allows personalized endurance training in compliance with official clinical recommendations, while providing a semi-immersive virtual reality experience of a bicycle ride in a park.Patients reported a positive experience after two weeks of training with the Virtual Park cycling system; they were highly engaged in the activity for the whole period and across multiple sessions.

Sarcopenia in idiopathic pulmonary fibrosis: a prospective study exploring prevalence, associated factors and diagnostic approach.

BACKGROUND: Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. AIM: Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. METHODS: Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. RESULTS: Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. CONCLUSIONS: The prevalence of sarcopenia in patients with IPF both at diagnosis and at 6-month follow-up was low but not negligible and was associated with higher severity of the disease and sedentary lifestyle. In IPF patients, a comprehensive diagnostic work-up including all the criteria defining the EWGSOP2 definition might be more useful than a series testing for prompt recognition of nutritional and physical performance abnormalities.

Nutritional assessment in idiopathic pulmonary fibrosis: a prospective multicentre study.

Background: Nutritional status impacts quality of life and prognosis of patients with respiratory diseases, including idiopathic pulmonary fibrosis (IPF). However, there is a lack of studies performing an extensive nutritional assessment of IPF patients. This study aimed to investigate the nutritional status and to identify nutritional phenotypes in a cohort of IPF patients at diagnosis. Methods: Patients underwent a thorough pulmonary and nutritional evaluation including questionnaires on nutritional status, and physical activity, anthropometry, body impedance, dynamometry, 4-m gait speed and blood tests. Results: 90 IPF patients (78.9% males, mean age 72.7 years) were enrolled. The majority of patients were classified as Gender-Age-Physiology Index stage 2 (47, 52.2%) with an inactive lifestyle according to International Physical Activity Questionnaire score (39, 43.3%), and had mean forced vital capacity and diffusing capacity for carbon monoxide 86.5% and 54.2%, respectively. In regards to nutritional phenotypes, the majority of patients were normally nourished (67.8%, 95% CI 58.6-77.7%), followed by non-sarcopenic obese (25.3%, 95% CI 16.1-35.2%), sarcopenic (4.6%, 95% CI 0.0-14.5%) and sarcopenic obese (2.3%, 95% CI 0.0-12.2%). Among the normally nourished, 49.2% showed early signs of nutritional and physical performance alterations, including body mass index ≥30 kg·m-2 in 4.3%, history of weight loss ≥5% in 11.9%, and reduction of gait speed and hand grip strength in 11.9% and 35.6%, respectively. Low vitamin D values were observed in 56.3% of cases. Conclusions: IPF patients at diagnosis are mainly normally nourished and obese, but early signs of nutritional and physical performance impairment can already be identified at this stage.

Long-term changes in pulmonary function among patients surviving to COVID-19 pneumonia.

PURPOSE: The aim of this study was to assess respiratory function at the time of clinical recovery, 6 weeks, 6 months, and 12 months after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 hospitalized patients with COVID-19 pneumonia. RESULTS: Baseline pulmonary function tests were 55.7 ± 15.6 for FEV1%, 68.6 ± 16.0 for FVC%, and 1.2 ± 0.1 for FEV1/FVC%. Although pulmonary function showed a small improvement after 6 weeks, patients experienced a more significant improvement after 6 and 12 months in FEV1% (95.4 ± 13.7 and 107.2 ± 16.5, respectively; p < 0.001), FVC% (91.3 ± 14.5, and 105.9 ± 15.6, respectively; p < 0.001), and FEV1/FVC% values (1.04 ± 0.04, and 1.01 ± 0.05, respectively; p < 0.001). CONCLUSION: COVID-19 pneumonia may result in significant alterations in lung function, with a mainly restrictive pattern, partly persisting at 6 weeks after recovery from acute phase, but significantly improving during a 12-month follow-up period.

Unveiling the Burden of Interactions Among Clinical Risk Factors for 1-Year Mortality in Hospitalized Older Patients.

Background: Hospitalized older patients are particularly exposed to adverse health outcomes. Objective: In this study, we aimed at investigating the prognostic interactions between disability in basic activities of daily living (BADL), cognitive impairment, low handgrip strength, anticholinergic cognitive burden (ACB), and depression on 1-year mortality. Setting and Subjects: Our series consisted of 503 older patients discharged from acute care hospitals. Methods: Disability in at least one BADL, ACB, depression, cognitive impairment, and low handgrip strength was considered in the analysis. One-year mortality was investigated by Cox regression analysis and prognostic interactions among study variables were assessed by survival tree analysis. Results: Basic activities of daily living disability, ACB, cognitive impairment, and low handgrip strength were significantly associated with 1-year mortality. Survival tree analysis showed that patients with BADL disability and high ACB carried the highest risk of poor survival [hazard ratio (HR): 16.48 (2.63-74.72)], followed by patients with BADL disability and low ACB (HR: 8.43, 95% CI: 1.85-38.87). Patients with cognitive impairment and no BADL disability were characterized by a lower but still significant risk of mortality (HR: 6.61, 95% CI: 1.51-28.97) and those with high ACB scores and good cognitive and functional performance (HR: 5.28, 95% CI: 1.13-24.55). Conclusion: Basic activities of daily living dependency, cognitive impairment, and ACB score were the three main predictors of 1-year mortality among patients discharged from acute care hospitals; the interaction between BADL dependency and ACB score was found to significantly affect survival. Early identification of such high-risk patients may help tailor targeted interventions to counteract their detrimental effects on prognosis.

Chest X-ray Score and Frailty as Predictors of In-Hospital Mortality in Older Adults with COVID-19.

BACKGROUND: The purpose of this study was to evaluate the prognostic impact of chest X-ray (CXR) score, frailty, and clinical and laboratory data on in-hospital mortality of hospitalized older patients with COVID-19. METHODS: This retrospective study included 122 patients 65 years or older with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and with availability to CXRs on admission. The primary outcome of the study was in-hospital mortality. Statistical analysis was conducted using Cox regression. The predictive ability of the CXR score was compared with the Clinical Frailty Scale (CFS) and fever data using Area Under the Curve (AUC) and net reclassification improvement (NRI) statistics. RESULTS: Of 122 patients, 67 died during hospital stay (54.9%). The CXR score (HR: 1.16, 95% CI, 1.04-1.28), CFS (HR: 1.27; 95% CI, 1.09-1.47), and presence of fever (HR: 1.75; 95% CI, 1.03-2.97) were significant predictors of in-hospital mortality. The addition of both the CFS and presence of fever to the CXR score significantly improved the prediction of in-hospital mortality (NRI, 0.460; 95% CI, 0.102 to 0.888; AUC difference: 0.117; 95% CI, 0.041 to 0.192, p = 0.003). CONCLUSIONS: CXR score, CFS, and presence of fever were the main predictors of in-hospital mortality in our cohort of hospitalized older patients with COVID-19. Adding frailty and presence of fever to the CXR score statistically improved predictive accuracy compared to single risk factors.

Nontuberculous mycobacterial pulmonary disease: an integrated approach beyond antibiotics.

Nontuberculous mycobacterial (NTM) pulmonary disease (PD) is an emerging condition with heterogeneous manifestations from both the microbiological and the clinical point of view. Diagnostic and therapeutic guidelines are available but there are still unmet patients' and physicians' needs, including therapy-related adverse events, symptom control, management of comorbidities, risk of re-exposure to the pathogen and unfavourable outcomes. In the present review, we provide currently available evidence for an integrated approach to NTM-PD beyond antibiotic therapy. This includes 1) avoiding exposure to environments where mycobacteria are present and careful evaluation of lifestyle and habits; 2) implementing a personalised pulmonary rehabilitation plan and airway clearance techniques to improve symptoms, exercise capacity, health-related quality of life (QoL) and functional capacity in daily living activities; 3) a nutritional evaluation and intervention to improve health-related QoL and to control gastrointestinal side-effects during antimicrobial therapy, particularly in those with low body mass index and history of weight loss; and 4) managing comorbidities that affect disease outcomes, including structural lung diseases, immune status evaluation and psychological support when appropriate.

Pulmonary function in patients surviving to COVID-19 pneumonia.

PURPOSE: The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 patients with COVID-19 pneumonia. RESULTS: At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). CONCLUSION: These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.

Does trail making test predict long-term prognosis in older patients with COPD?

Executive abilities are frequently impaired in patients with chronic obstructive pulmonary disease (COPD). We aimed at investigating the association between trail making test (TMT) and survival. Our series consisted of 68 stable COPD outpatients followed-up every 6 months for 52.6 ± 27.6 months. Enrolled patients underwent a baseline comprehensive neuropsychological assessment, including mini-mental state exam, attentional matrices, digit span, Rey auditory verbal learning, Rey-Osterrieth complex figure, copy drawing, tokens test, verbal fluency, category fluency, frontal assessment battery, Raven's progressive matrices, TMT-A, -B and -B-A. The association between neuropsychological deficits and overall mortality was investigated by Cox regression. During follow-up period, 41 patients (60.3%) died. After adjusting for potential confounders, TMT-B was significantly associated with mortality (HR = 2.42, 95% CI = 1.10-5.31), along with age (HR = 1.06, 95% CI = 1.0-1.13), overall comorbidity (HR = 1.29, 95% CI = 1.02-1.62) and use of noninvasive ventilation (HR = 2.16, 95% CI = 1.05-4.45). Defective TMT-B may be associated with long-term mortality in patients with stable COPD.

Italian suggestions for pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process.

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

Nutrition in Patients with Idiopathic Pulmonary Fibrosis: Critical Issues Analysis and Future Research Directions.

In idiopathic pulmonary fibrosis (IPF), several factors may have a negative impact on the nutritional status, including an increased respiratory muscles load, release of inflammation mediators, the coexistence of hypoxemia, and physical inactivity. Nutritional abnormalities also have an impact on IPF clinical outcomes. Given the relevance of nutritional status in IPF patients, we sought to focus on some critical issues, highlighting what is known and what should be further learned about these issues. We revised scientific literature published between 1995 and August 2019 by searching on Medline/PubMed and EMBASE databases including observational and interventional studies. We conducted a narrative review on nutritional assessment in IPF, underlining the importance of nutritional evaluation not only in the diagnostic process, but also during follow-up. We also highlighted the need to keep a high level of attention on cardiovascular comorbidities. We also focused on current clinical treatment in IPF with Nintedanib and Pirfenidone and management of gastrointestinal adverse events, such as diarrhea, induced by these antifibrotic drugs. Finally, we concentrated on the importance of pulmonary rehabilitation program, including nutritional assessment, education and behavioral change, and psychological support among its essential components. More attention should be devoted to the assessment of the undernutrition and overnutrition, as well as of muscle strength and physical performance in IPF patients, taking also into account that an adequate clinical management of gastrointestinal complications makes IPF drug treatments more feasible.

Body composition markers in older persons with COPD.

BACKGROUND: Body composition has been shown to be correlated with physical performance, but data in older persons with diverse chronic diseases are lacking. OBJECTIVE: We aimed at investigating the associations of body composition to gait speed and nutritional status of older people in different stages of chronic obstructive pulmonary disease (COPD). DESIGN, SETTING AND SUBJECTS: Cross-sectional analysis of data from Pulmonary Rehabilitation Geriatric Unit at INRCA in Casatenovo, Italy including 132 consecutively admitted COPD patients (mean age: 75 years) with data on body composition, walking speed and respiratory parameters. METHODS: Body mass parameters were assessed using bioelectrical impedance analysis. Pulmonary function tests included spirometry and arterial blood gases. Differences among body composition markers were compared according to gender. Separate multivariate linear regression models with gait speed as the dependent variable were used to test for independent associations with body composition markers after adjusting for multiple confounders. RESULTS: Walking speed deteriorated with increasing severity of COPD. Men were heavier and had more lean mass than women. Participants in the fastest gait tertile were younger, had lower body mass index and fat mass (FM); higher lean-to-fat ratio and albumin levels and better respiratory function (FEV1, FVC) compared with those in the slower tertiles. Total body FM was an independent determinant of walking speed, while fat-free mass and lean-to-fat ratio were not. CONCLUSIONS: Excess body fat may be harmful for physical functioning among elders with COPD.

Feasibility and effectiveness of an educational program in Italian COPD patients undergoing rehabilitation.

BACKGROUND: Self-management education is associated with improvement in quality of life and reduction of hospital admissions. Nevertheless, the data are insufficient to formulate clear recommendations regarding the type and content of education programs for COPD patients, and few data are available on knowledge of the disease itself. OBJECTIVE: To test the level of patients' knowledge of their disease and therapy at baseline and after an educational program (COPD-EP); the feasibility of structured educational sessions; the influence of clinical status (degree of severity of disease, presence of comorbidities, oxygen use), demographics status (age, sex), previous knowledge level, previous lessons attendance and adherence of COPD-EP to the variation of knowledge after program. METHODS: Selected COPD in-patients and out-patients referred to rehabilitative hospital departments were enrolled. The study was divided into 2 parts: a pre-study phase (educational materials and health team preparation) and a study phase. All COPD subjects received one educational brochure and were invited to attend seven 30-min group lessons to complete the educational program. Learning effect was evaluated by a 20-questions multiple choice learning questionnaire (LQ). RESULTS: We enrolled 158 subjects, of whom 44.9% had previous formal education lessons on COPD management and 69.6% had previous rehabilitative hospitalizations. At baseline, the LQ total score was 15.2 ± 3.5 points, which increased to 16.9 ± 3.0 points post COPD-EP (P < .001). Pre-to-post change of LQ scores significantly correlated with adherence (R = 0.24, P = .002) and Severity Index of Cumulative Illness Rating Scale score (R = -0.22, P = .001). Subjects with low baseline knowledge were more likely to have improved LQ scores than subjects with greater levels of knowledge. Subjects without prior educational COPD lessons improved more than subjects who had attended previous education. CONCLUSIONS: A formal COPD-EP is feasible and effective in improving subject knowledge and self-management. Specific learning instruments to follow up this population should be validated.

Frailty and safety: the example of diabetes.

Frailty is considered a syndrome of decreased reserve and resistance to stressors and is clinically expressed as muscle weakness, poor exercise tolerance, factors related to body composition, sarcopenia and disability. In addition, there is a close relationship between age-related metabolic changes and the occurrence of comorbidities that may in turn lead to frailty.Even though the downward spiral of frailty is activated more quickly in older persons with type 2 diabetes, it is reversible with appropriate interventions before reaching a high level of severity. The hazard for geriatric patients with type 2 diabetes is that frailty encompasses diverse complications already associated with or caused by diabetes. Frailty is also associated with cognitive impairment, reduced ability to perform activities of daily living and increased expression of inflammatory and coagulation markers that may contribute to the adverse microvascular effects of diabetes. Although glycaemic control remains the main targeting achievement in type 2 diabetes, especially in well-functioning older persons, this is not appropriate for those with frailty. Frail elderly people with type 2 diabetes are a specific group in need of treatment parameters for both initial and maintenance therapy with oral antidiabetic agents. Therefore, the prescription of an antidiabetic agent in such individuals must take into consideration not only the standard goal of lowering hyperglycaemic levels, but also improving the quality of life and life expectancy. The clinical management of this population is currently particularly demanding, requiring special considerations with good medical decision making. Clinical aspects complicating diabetes care in older people include cognitive decline, physical functional decline and frailty. Available oral antidiabetic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), α-glucosidase inhibitors, thiazolidinediones and inhibitors of glucagon-like peptide 1 (GLP-1) degrading enzyme dipeptidyl peptidase 4. In addition, we will discuss injection treatment with GLP-1 analogues. This review will underline the association between diabetes and some frailty components in old patients and how specific antidiabetic agents may play a specific role in improving outcomes.

Practical management problems of chronic obstructive pulmonary disease in the elderly: acute exacerbations.

PURPOSE OF REVIEW: Acute exacerbations of chronic obstructive pulmonary disease (ECOPDs) have numerous causes and are associated with increased mortality and hospitalization, especially in older patients. The urgent need to identify and enable timely treatment of ECOPDs is a necessity for physicians worldwide. This review will highlight the causes and optimal combinations of available treatments for such events in older populations. RECENT FINDINGS: The exact definition of exacerbations is lacking; however, it is agreed that such events are considered episodes of worsening of symptoms, leading to morbidity and death. The aging process is a consistent determinant for ECOPD events and is associated with worsening of COPD stages. The incidence of ECOPD rises across the worsening stages of COPD. Studies have shown that the frequency of exacerbations increases with age and correlated clinical outcomes are poorer than in younger patients. The risk of mortality has also been shown to be significantly higher after a hospital admission following an acute exacerbation. At the moment, the need to rapidly and correctly treat acute exacerbations is crucially important in the rapidly growing elderly population. SUMMARY: ECOPDs are extremely dangerous events for older patients with severe stages of COPD. There is an urgent need to identify risk factors, identify tolerable treatment guidelines and manage acute exacerbations in older patients with COPD.