Acute COPD Exacerbation

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COPD exacerbations: Prognosis, discharge planning, and prevention

INTRODUCTION

An exacerbation of chronic obstructive pulmonary disease (COPD) is defined as "an event characterized by dyspnea and/or cough and sputum that worsens over ≤14 days, which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways" by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), a report produced by the National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO) [1,2]. This generally includes an acute change in one or more of the following cardinal symptoms:

The prognosis after a COPD exacerbation and strategies for prevention of future exacerbations will be discussed here. The risk factors, clinical manifestations, diagnosis, and management of COPD exacerbations are discussed separately. (See "COPD exacerbations: Clinical manifestations and evaluation" and "COPD exacerbations: Management" and "Management of infection in exacerbations of chronic obstructive pulmonary disease".)

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All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2023. This topic last updated: Nov 06, 2023.

Cough increases in frequency and severity●

Sputum production increases in volume and/or changes character●

Dyspnea increases●

PROGNOSIS AFTER AN EXACERBATION

Exacerbations of COPD are associated with increased morbidity and mortality [1,3-5]. Individuals who have experienced a single moderate COPD exacerbation, compared with those without exacerbation, have an increased risk of respiratory and all-cause mortality (hazard ratios 2.98 [95% CI 1.14-7.83] and 1.34 [95% CI 0.79-2.29], respectively) [4].

A number of factors influence mortality following hospital discharge after an exacerbation of COPD, including older age, the severity of the underlying COPD, requirement for long-term oxygen at discharge, presence of comorbidities (eg, cardiovascular disease or lung cancer), and the presence of Pseudomonas aeruginosa in the patient's sputum, as described in the following studies [6-14]:

Even if the COPD exacerbation resolves, many patients never return to their baseline level of health [5].

COMPREHENSIVE DISCHARGE PLANNING

For patients who have required hospitalization for a COPD exacerbation, formal criteria for discharge and a comprehensive discharge plan may help to reduce readmissions and recurrent exacerbations, although supportive data are mixed [1,16-18]. Nonetheless, the following discharge planning steps appear sensible and are consistent with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy [1]. (See "Hospital discharge and readmission".)

For patients hospitalized with a COPD exacerbation, in-hospital mortality ranges from three to nine percent [12-14]. In a separate study of patients who required noninvasive ventilation, in-hospital mortality was 11 percent [15].

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In a study of 260 patients admitted with a COPD exacerbation, the one year mortality was 28 percent [9]. Independent risk factors for mortality were age, male sex, prior hospitalization for COPD, arterial tension of carbon dioxide (PaCO ) ≥45 mmHg (6 kPa), and blood urea >8 mmol/L (BUN 22 mg/dL).

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2

Patients hospitalized for a COPD exacerbation who have Pseudomonas aeruginosa in their sputum have a higher risk of mortality at three years than those without (59 versus 35 percent; HR 2.33, 95% CI 1.29-3.86), independent of age, comorbidity, or COPD severity [10].

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Criteria for discharge — Criteria for discharge generally depend on sufficient improvement in the manifestations of COPD such that the patient’s condition has stabilized, and frequent nebulizer treatments are no longer required. If the patient is near their prehospital baseline, discharge to home is likely appropriate. However, some patients no longer require hospital-level care but are unable to manage at home due to frailty or severe exercise intolerance; for these patients, a period of inpatient rehabilitation may be more suitable. Patients requiring nocturnal noninvasive ventilation may benefit from a rehabilitation hospital stay. (See "Hospital discharge and readmission", section on 'Determining the post-discharge site of care'.)

When deciding whether a patient can be discharged to home, the patient’s ability to manage activities of daily living (ADLs) at home should be assessed along with the need for assistive devices such as a walker, elevated toilet seat, bedside commode, or shower chair. (See "Comprehensive geriatric assessment", section on 'Activities of daily living'.)

Discharge to home checklist — A number of issues pertaining to COPD exacerbations in particular and hospitalizations in general must be assessed as part of discharge planning, such as: the transition from hospital to home (eg, oxygen en route, stairs to climb), the patient’s ability to obtain and self-administer medications, meal preparation and self-feeding, and the need for visiting nurse, in-home services, and hospice.

A checklist can ensure that important steps to enable a smooth transition to home are not overlooked. Checklists may be general ( table 1) or specific to COPD ( form 1). Components that are thought to improve discharge success include the following [1]:

Explain diagnosis and planned postdischarge therapy with patient/caregiver; ensure understanding and agreement with the regimen

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Review with patient the technique(s) of all inhaler devices that will be used at discharge and assess their technique

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Review management plans for comorbidities (eg, heart failure, coronary heart disease, arrhythmia, lung cancer screening, sleep-related breathing disorders, metabolic syndrome, anxiety, depression)

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Ensure that patient understands written and verbal directions for withdrawal of acute medications (eg, antibiotics, systemic glucocorticoids) used to treat exacerbation

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Confirm that patient has received appropriate vaccinations for seasonal influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and S. pneumococcus (See "Pneumococcal vaccination in adults" and "Standard immunizations for children and adolescents: Overview".)

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Provide smoking cessation education and medication to patients who smoke●

Patients who have a new prescription for long-term oxygen typically need additional instruction on the use of oxygen delivery systems (eg, tanks, concentrators, portable systems) and safe practices regarding oxygen tubing as a tripping hazard and avoiding exposure to open flames (see "Long-term supplemental oxygen therapy" and "Portable oxygen delivery and oxygen conserving devices"). Such patients should be reassessed two to three months after discharge regarding whether supplemental oxygen is still needed and, if so, at what dose.

Palliative care planning — The disease trajectory in COPD is heterogenous and ranges from gradual worsening of exercise tolerance and oxygenation to a sudden and unanticipated end- of-life. Given the difficulties in predicting the clinical course, an exacerbation requiring hospitalization, particularly one requiring intensive care, creates an opportunity to discuss a palliative care consultation. Criteria for considering a palliative care referral are listed in the table ( table 2). (See "Palliative care for adults with nonmalignant chronic lung disease", section on 'What are the indications for a palliative care consultation?'.)

The primary care provider or pulmonary specialist can raise the possibility of a palliative care approach and obtain a palliative care consultation, if needed. Important components of palliative care include exploring the patient’s understanding about their illness and prognosis, assessing and managing symptoms, discussing goals of care and advance care planning, coordinating care, and helping to plan end-of-life care, including determining the need and timing of hospice care ( table 3). (See "Palliative care for adults with nonmalignant chronic lung disease".)

For patients with advanced COPD, it may be reasonable to discuss hospice care at home. Disease specific guidelines are listed in the table and discussed separately ( table 4). (See "Palliative care for adults with nonmalignant chronic lung disease" and "Hospice: Philosophy of care and appropriate utilization in the United States".)

PREVENTION

Assess need for supplemental oxygen and prescribe if indicated; ensure that supplemental oxygen will be available for transfer to home and in the home before the patient arrives

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Assess need for home nebulizer treatments and arrange for nebulizer if needed●

Arrange for out-patient pulmonary rehabilitation program, as appropriate●

Advise patient regarding any pending test results or planned follow-up testing (eg, lung cancer screening)

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Confirm follow-up visits at approximately one and four weeks, and as indicated●

General measures — Several measures can reduce the frequency of COPD exacerbations including the following [1,19-21]:

Pulmonary rehabilitation — Pulmonary rehabilitation has a number of benefits; it significantly reduces future hospital admissions and mortality and improves exercise tolerance and quality of life, compared with usual community care [22]. After a COPD exacerbation, we encourage patients to participate in a pulmonary rehabilitation program, if they have not yet done so. The optimal timing for initiating pulmonary rehabilitation after a COPD exacerbation has not been determined and likely needs to be individualized; patients need to have recovered sufficiently to maximize the benefits of exercise training. (See "Pulmonary rehabilitation", section on 'Benefits' and "Pulmonary rehabilitation", section on 'Setting'.)

Physical activity — While pulmonary rehabilitation programs are preferred, if one is not available, physical activity (exercising two to three times per week for 30 minutes to a level that causes mild shortness of breath) may reduce hospitalizations for COPD exacerbations based on observational data [19]. Further study is needed on alternatives to pulmonary rehabilitation programs in under-resourced settings.

Optimizing medications for COPD — A number of medications for COPD reduce the frequency of COPD exacerbations. A personalized approach to medication selection should be based on the patient’s severity of COPD symptoms and exacerbation frequency, noting that certain medications may be of greater benefit for some patients than others [1]. As an example, inhaled glucocorticoids reduce exacerbations in patients with a history of exacerbations but are not likely to be of benefit in patients with low blood eosinophils. (See "Stable COPD: Follow-up pharmacologic management", section on 'Persistent exacerbations with or without dyspnea'.)

The selection among these medications and their efficacy in reducing exacerbations are reviewed separately ( algorithm 1 and table 9):

Smoking cessation (see "Overview of smoking cessation management in adults")• Proper use of medications (including inhaler technique) ( table 5 and table 6 and

table 7 and table 8) (see "The use of inhaler devices in adults") •

Vaccination against seasonal influenza (see "Seasonal influenza vaccination in adults")• Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (see "COVID-19: Vaccines")

•

Pneumococcal vaccination ( figure 1) (see "Pneumococcal vaccination in adults")• Vaccination against respiratory syncytial virus (suspected benefit, which will be revisited as data emerge) (see "Overview of preventive care in adults", section on 'Immunization')

•

For patients whose medications are changed during a hospitalization, it is important to reevaluate discharge medications at office visits in the next one to four weeks. This is a good time to consolidate inhaled medications into a single inhaler if possible or to select inhaler devices that use the same technique. The proper technique should be reviewed for every inhaler that the patient is using. If the patient has poor inspiratory flow or is unable to demonstrate proper technique, nebulized medication from the appropriate class can be substituted: LAMAs (revefenacin), LABAs (formoterol and arformoterol), and glucocorticoid (budesonide).

Prophylactic azithromycin — For patients with recurrent exacerbations (≥2 per year) despite optimal therapy (eg, long-acting bronchodilators with or without inhaled glucocorticoids, smoking cessation, vaccinations, and pulmonary rehabilitation), prophylactic azithromycin may

Long-acting muscarinic antagonists (LAMA). (See "Stable COPD: Initial pharmacologic management", section on 'Long-acting muscarinic antagonists'.)

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Long-acting beta-agonists (LABA). (See "Stable COPD: Initial pharmacologic management", section on 'Long-acting beta-agonists'.)

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LAMA-LABA combination inhalers. (See "Stable COPD: Initial pharmacologic management", section on 'Use of dual bronchodilator therapy'.)

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LABA-glucocorticoid combination inhalers. (See "Stable COPD: Initial pharmacologic management", section on 'Alternative approaches'.)

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LAMA-LABA-glucocorticoid combination inhalers. (See "Stable COPD: Follow-up pharmacologic management".)

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Roflumilast, an oral PDE-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of frequent COPD exacerbations (eg, at least two per year or one requiring hospitalization). (See "Management of refractory chronic obstructive pulmonary disease", section on 'Phosphodiesterase-4 inhibitors (Roflumilast)'.)

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Oral thiol derivatives, such as N-acetylcysteine (NAC), erdosteine, and carbocysteine, are used to thin secretions in patients with bothersome sputum production, but studies have not demonstrated a reduction in exacerbations. (See "Role of mucoactive agents and secretion clearance techniques in COPD", section on 'Thiols and thiol derivatives' and "Management of refractory chronic obstructive pulmonary disease", section on 'Mucoactive agents'.)

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reduce the frequency of exacerbations. The dosing, potential adverse effects, and evidence in support of prophylaxis with azithromycin are described separately. (See "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Prophylactic macrolides' and "Management of refractory chronic obstructive pulmonary disease", section on 'Macrolides and other chronic antibiotic therapy'.)

GLP-1 receptor agonists and SGLT-2 inhibitors, for diabetic patients — Glucagon-like peptide 1 (GLP-1) receptor agonists (eg, liraglutide) and sodium-glucose cotransporter 2 (SGLT- 2) inhibitors (eg, dapagliflozin) may offer some protection against exacerbations in patients with diabetes and COPD, although further data are needed to confirm these findings.

The mechanism underlying the potential benefits of these agents is unclear. GLP-1 receptor agonists have been shown to reduce inflammation and result in weight loss, with improvements in lung function in small clinical trials [25,26]. SGLT-2 inhibitors decrease endogenous carbon dioxide production via metabolic effects and appear to decrease risk of pneumonia based on meta-analyses of cardiovascular trials [27].

Future trials are needed to determine whether use of GLP-1 receptor agonists or SGLT-2 inhibitors are preferable to other antihyperglycemic agents in patients with DM and risk for COPD exacerbations.

Noninvasive ventilation — For patients who require noninvasive ventilation (NIV) during a hospitalization for a COPD exacerbation and who remain hypercapnic, nocturnal NIV at home significantly reduces the risk of rehospitalization. (See "Nocturnal ventilatory support in COPD".)

In one population-based cohort study of patients with COPD and new initiation of an antihyperglycemic agent, 1252 patients who began GLP-1 receptor agonists and 2956 patients who began SGLT-2 inhibitors were matched with similar patients who received sulfonylureas instead [23]. Compared with patients receiving sulfonylureas, those on GLP- 1 receptor agonists were less likely to be hospitalized for COPD exacerbations (3.5 versus 5.0 percent of patients per year [HR 0.7, 95% CI 0.49-0.99]); similar results were seen for those on SGLT-2 inhibitors (2.4 versus 3.9 percent per year [HR 0.62, 95% CI 0.48-0.81]).

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In a separate retrospective database analysis, 1642 patients with COPD initiating new oral agents for DM were evaluated over six months following treatment initiation [24]. The adjusted incidence rates of moderate or severe exacerbations were improved with GLP- 1RA inhibitors compared with dipeptidyl peptidase-4 inhibitors (incidence rate ratio [IRR] 0.67, 95% CI 0.49-0.93) or sulfonylureas (IRR 0.49, 95% CI 0.37-0.62); there was no difference compared with SGLT-2 inhibitors.

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Vitamin D supplementation — Adhering to current guidelines regarding vitamin D supplementation in patients with a 25-hydroxyvitamin D level <20 or 30 ng/mL (50 or 75 nmol/L) reduces COPD exacerbations in addition to benefits in reducing falls and fractures (see "Overview of vitamin D"). While randomized trials were conflicting [28-31], a systematic review and meta-analysis used individual patient data from three of the four randomized trials to examine the role of supplementation in patients with 25-hydroxyvitamin D (25[OH]D) levels <25 nmol/L [32].

In the meta-analysis, vitamin D supplementation did not reduce the rate of moderate-to-severe COPD exacerbations overall, but a prespecified subgroup analysis revealed protective effects in patients with a baseline serum 25[OH]D level <10 ng/mL (<25 nmol/L; adjusted rate ratio 0.55, 95% CI 0.36-0.84). The trial that was not included in the analysis had separately found a benefit to vitamin D supplementation in this setting, so its exclusion was unlikely to affect the results. No increase in adverse events was noted with vitamin D supplementation.

The serum 25(OH)D level <10 ng/mL (<25 nmol/L) used as a threshold in the meta-analysis is well below the minimum level of 20 or 30 ng/mL (50 or 75 nmol/L) advised by national and international guidelines to prevent falls and fracture. Estimates of vitamin D requirements to achieve sufficient levels vary and depend in part upon sun exposure. The optimal intake of vitamin D to prevent deficiency is discussed separately. (See "Overview of vitamin D" and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Optimal intake to prevent deficiency'.)

Separate studies suggest that vitamin D supplementation prevents acute respiratory tract infections, particularly in patients who are vitamin D deficient, which might contribute to the benefit in preventing COPD exacerbations [33].

INEFFECTIVE INTERVENTIONS

Selective beta-blockers — Preliminary data and a meta-analysis of 15 observational studies suggested that therapy with selective beta-blockers (given for comorbid cardiovascular disease) might reduce COPD exacerbations [34-36]. However, a randomized trial that included 532 patients with COPD and an increased risk of exacerbation (eg, moderate airflow limitation, exacerbation in the previous year, prescribed use of oxygen), but no cardiac indication for beta- blocker therapy, found that extended release metoprolol (25 to 100 mg/day) did not decrease the time to first exacerbation compared with placebo (hazard ratio 1.05, 95% CI 0.84 to 1.32) [37]. The study was stopped early for safety concerns. Metoprolol was associated with an increased risk of an exacerbation leading to hospitalization (hazard ratio 1.91, 95% CI 1.29 to

2.83), although the reason for this increase was unclear. There was no between group difference in forced expiratory volume in one second (FEV ).

Based on this study, selective beta-blockers do not have a role in prevention of COPD exacerbations but continue to be used for patients with a cardiovascular indication. (See "Management of the patient with COPD and cardiovascular disease".)

Statins — Statins (hydroxymethylglutaryl [HMG] CoA reductase inhibitors) do not diminish COPD exacerbations, although they may have other health benefits. In observational studies of COPD, statins were associated with a reduced rate and severity of exacerbations, rate of hospitalizations, and mortality [38-41]. However, these beneficial effects were not supported in a trial that randomly assigned 885 participants with COPD, but without other indications or contraindications for statin therapy, to simvastatin 40 mg daily or placebo for up to 36 months [42]. Simvastatin did not reduce the rate of exacerbations or the time to first exacerbation. A systematic review found no clear benefit to statins in terms of lung function, exercise capacity, or mortality, but deemed evidence to be low quality [43]. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic obstructive pulmonary disease" and "Society guideline links: Pulmonary rehabilitation".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

Basics topics (see "Patient education: Pulmonary rehabilitation (The Basics)")●

Prognosis after exacerbations – Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of mortality. For patients hospitalized with a COPD exacerbation, in-hospital mortality ranges from 3 to 9 percent and one-year mortality of approximately 25 percent. (See 'Prognosis after an exacerbation' above.)

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General measures – Several general measures can help reduce the frequency of COPD exacerbations, including smoking cessation, pulmonary rehabilitation and increased physical activity, proper use of medications (including correct inhaler technique), and vaccination against seasonal influenza, SARS-CoV-2, and pneumococcus ( figure 1). (See 'General measures' above.)

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Pharmacologic interventions – Most medications for COPD reduce the frequency of COPD exacerbations, including long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled glucocorticoids, and roflumilast. The selection among these medications is based on the patient’s severity of symptoms and risk of exacerbations and is discussed separately. (See 'Optimizing medications for COPD' above.)

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Chronic azithromycin – For patients with recurrent exacerbations (≥2 per year) despite optimal therapy with long-acting bronchodilator and glucocorticoid inhalers, prophylactic azithromycin may also reduce the frequency of exacerbations. (See 'Prophylactic azithromycin' above and "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Prophylactic macrolides' and "Management of refractory chronic obstructive pulmonary disease", section on 'For patients with frequent exacerbations'.)

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Noninvasive ventilation, for hypercapnic patients – For patients who require noninvasive ventilation (NIV) during a hospitalization for a COPD exacerbation and who remain hypercapnic, nocturnal NIV at home significantly reduces the risk of rehospitalization. (See 'Noninvasive ventilation' above and "Nocturnal ventilatory support in COPD".)

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REFERENCES

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diag nosis, Management and Prevention of Chronic Obstructive Pulmonary Disease: 2023 Repor t. www.goldcopd.org www.goldcopd.org (Accessed on December 13, 2022).

2. Celli BR, Fabbri LM, Aaron SD, et al. An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal. Am J Respir Crit Care Med 2021; 204:1251.

3. Hoogendoorn M, Hoogenveen RT, Rutten-van Mölken MP, et al. Case fatality of COPD exacerbations: a meta-analysis and statistical modelling approach. Eur Respir J 2011; 37:508.

4. Çolak Y, Afzal S, Marott JL, et al. Prognosis of COPD depends on severity of exacerbation history: A population-based analysis. Respir Med 2019; 155:141.

5. Cote CG, Dordelly LJ, Celli BR. Impact of COPD exacerbations on patient-centered outcomes. Chest 2007; 131:696.

6. Roberts CM, Lowe D, Bucknall CE, et al. Clinical audit indicators of outcome following admission to hospital with acute exacerbation of chronic obstructive pulmonary disease. Thorax 2002; 57:137.

7. Donaldson GC, Wedzicha JA. COPD exacerbations .1: Epidemiology. Thorax 2006; 61:164.

8. Connors AF Jr, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med 1996; 154:959.

9. Slenter RH, Sprooten RT, Kotz D, et al. Predictors of 1-year mortality at hospital admission for acute exacerbations of chronic obstructive pulmonary disease. Respiration 2013; 85:15.

10. Almagro P, Salvadó M, Garcia-Vidal C, et al. Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease. Respiration 2012; 84:36.

Comprehensive discharge planning – After hospitalization for a COPD exacerbation, formal criteria for discharge and a comprehensive discharge plan may help to reduce readmissions and recurrent exacerbations after hospitalization for a COPD exacerbation ( form 1). (See 'Comprehensive discharge planning' above.)

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11. Piquet J, Chavaillon JM, David P, et al. High-risk patients following hospitalisation for an acute exacerbation of COPD. Eur Respir J 2013; 42:946.

12. Matkovic Z, Huerta A, Soler N, et al. Predictors of adverse outcome in patients hospitalised for exacerbation of chronic obstructive pulmonary disease. Respiration 2012; 84:17.

13. Gunen H, Hacievliyagil SS, Kosar F, et al. Factors affecting survival of hospitalised patients with COPD. Eur Respir J 2005; 26:234.

14. Singanayagam A, Schembri S, Chalmers JD. Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc 2013; 10:81.

15. Steriade AT, Johari S, Sargarovschi N, et al. Predictors of outcome of noninvasive ventilation in severe COPD exacerbation. BMC Pulm Med 2019; 19:131.

16. Morton K, MacNeill S, Sanderson E, et al. Evaluation of 'care bundles' for patients with chronic obstructive pulmonary disease (COPD): a multisite study in the UK. BMJ Open Respir Res 2019; 6:e000425.

17. Zafar MA, Panos RJ, Ko J, et al. Reliable adherence to a COPD care bundle mitigates system- level failures and reduces COPD readmissions: a system redesign using improvement science. BMJ Qual Saf 2017; 26:908.

18. Atwood CE, Bhutani M, Ospina MB, et al. Optimizing COPD Acute Care Patient Outcomes Using a Standardized Transition Bundle and Care Coordinator: A Randomized Clinical Trial. Chest 2022; 162:321.

19. Katajisto M, Koskela J, Lindqvist A, et al. Physical activity in COPD patients decreases short- acting bronchodilator use and the number of exacerbations. Respir Med 2015; 109:1320.

20. Au DH, Bryson CL, Chien JW, et al. The effects of smoking cessation on the risk of chronic obstructive pulmonary disease exacerbations. J Gen Intern Med 2009; 24:457.

21. Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest 2015; 147:894.

22. Puhan MA, Gimeno-Santos E, Cates CJ, Troosters T. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2016; 12:CD005305.

23. Pradhan R, Lu S, Yin H, et al. Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study. BMJ 2022; 379:e071380.

24. Foer D, Strasser ZH, Cui J, et al. Association of GLP-1 Receptor Agonists with COPD Exacerbations Among Patients with Type 2 Diabetes. Am J Respir Crit Care Med 2023.

25. Rogliani P, Matera MG, Calzetta L, et al. Long-term observational study on the impact of GLP-1R agonists on lung function in diabetic patients. Respir Med 2019; 154:86.

26. López-Cano C, Ciudin A, Sánchez E, et al. Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study. Diabetes 2022; 71:315.

27. Barkas F, Anastasiou G, Milionis H, Liberopoulos E. Sodium-glucose cotransporter inhibitors may reduce the risk of pneumonia: an updated meta-analysis of cardiovascular outcome trials. Diabetol Int 2022; 13:325.

28. Lehouck A, Mathieu C, Carremans C, et al. High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2012; 156:105.

29. Martineau AR, James WY, Hooper RL, et al. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Lancet Respir Med 2015; 3:120.

30. Rafiq R, Prins HJ, Boersma WG, et al. Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial. Int J Chron Obstruct Pulmon Dis 2017; 12:2583.

31. Zendedel A, Gholami M, Anbari K, et al. Effects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical Trial Study. Glob J Health Sci 2015; 7:243.

32. Jolliffe DA, Greenberg L, Hooper RL, et al. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax 2019; 74:337.

33. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356:i6583.

34. Du Q, Sun Y, Ding N, et al. Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-analysis of observational studies. PLoS One 2014; 9:e113048.

35. Bhatt SP, Wells JM, Kinney GL, et al. β-Blockers are associated with a reduction in COPD exacerbations. Thorax 2016; 71:8.

36. Suissa S, Ernst P. Beta-Blockers in COPD: A Methodological Review of the Observational Studies. COPD 2018; 15:520.

37. Dransfield MT, Voelker H, Bhatt SP, et al. Metoprolol for the Prevention of Acute Exacerbations of COPD. N Engl J Med 2019; 381:2304.

38. Wang MT, Lo YW, Tsai CL, et al. Statin use and risk of COPD exacerbation requiring hospitalization. Am J Med 2013; 126:598.

39. Janda S, Park K, FitzGerald JM, et al. Statins in COPD: a systematic review. Chest 2009; 136:734.

40. Sharif R, Parekh TM, Pierson KS, et al. Predictors of early readmission among patients 40 to 64 years of age hospitalized for chronic obstructive pulmonary disease. Ann Am Thorac Soc 2014; 11:685.

41. Lawes CM, Thornley S, Young R, et al. Statin use in COPD patients is associated with a reduction in mortality: a national cohort study. Prim Care Respir J 2012; 21:35.

42. Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med 2014; 370:2201.

43. Walsh A, Perrem L, Khashan AS, et al. Statins versus placebo for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2019.

Topic 122145 Version 16.0

GRAPHICS

Ideal discharge of the older adult patient: A hospitalist checklist

Data elements

Processes

Discharge summary

Patient instructions

Communication to follow-up clinician on

day of discharge

Presenting problem that precipitated hospitalization

x x x

Key findings and test results x   x

Final primary and secondary diagnoses

x x x

Brief hospital course x   x

Condition at discharge, including functional status and cognitive status if relevant

x - functional status

o - cognitive status

   

Discharge destination (and rationale if not obvious)

x   x

Discharge medications:

Written schedule x x x

Include purpose and cautions (if appropriate) for each

o x o

Comparison with pre-admission medications (new, changes in dose/frequency, unchanged, meds should no longer take)

x x x

Follow-up appointments with name of provider, date, address, phone number, visit purpose, suggested management plan

x x x

All pending labs or tests, responsible person to whom results will be sent

x   x

Recommendations of any sub- specialty consultants

x   o

Documentation of patient education and understanding

x    

Any anticipated problems and suggested interventions

x x x

24/7 call-back number x x  

Identify referring and receiving providers

x x  

Resuscitation status and any other pertinent end-of-life issues

o    

x: required element; o: optional element.

Derived and expanded from: Halasyamani L, Kripalani S, Coleman E, et al. Transition of care for hospitalized elderly patients: Development of a discharge checklist for hospitalists. J Hosp Med 2006; 1:354.

Graphic 54279 Version 6.0

COPD exacerbation discharge to home checklist

COPD: chronic obstructive pulmonary disease; MDI: metered dose inhaler; DPI: dry powder inhaler; SMI: soft mist inhaler; NIV: noninvasive ventilation.

Graphic 130525 Version 1.0

Criteria for considering a palliative care referral in patients with chronic lung disease

Patient characteristics Social circumstances or issues related to

anticipatory bereavement

Limited options for treatment Limited access to care

Physical symptoms, such as pain, dyspnea, or cough, that are refractory to conventional management

Familial factors, including: Limitations of the family/caregiver Inadequate family support Family discord History of intensely dependent relationship(s) Parental concerns regarding care of dependents

High symptom burden or distress score Financial limitations

Inability to engage in advance care planning and care plan

Unresolved grief or multiple prior losses

Uncertainty as to prognosis or disease trajectory Spiritual or existential crisis

Cognitive impairment Need for coordination of care at multiple sites

Severe or multiple comorbid conditions  

Communication barriers related to language, literacy, or physical issues

 

Request for hastened death  

Homebound  

Adapted from: NCCN Guidelines Version 2.2012, Palliative Care.

Graphic 103284 Version 2.0

Primary palliative care assessment of patients with chronic lung disease

Understanding of illness/prognosis and treatment options

Does the patient/family/surrogate understand the current illness, their prognosis for quantity and quality of life, expected disease trajectory/uncertainty about disease trajectory, and treatment options?

Symptom management

Does the patient have uncontrolled/distressing symptoms? In particular, does the patient have any of the following?

Pulmonary symptoms (cough, dyspnea) with daily activities Pain Fatigue and sleep disturbance Distressing psychological symptoms (depression and anxiety) Constitutional symptoms (anorexia and weight loss)

Social/spiritual assessment

Are there significant social or spiritual concerns affecting daily life?

Decision making

Is the patient comfortable making health care decisions? Or, does the patient rely on family members, friends, or health care professionals to make decisions?

Has the patient identified a surrogate decision-maker and talked with this person about their goals and values?

Would the patient/family/surrogate like help with treatment decision-making?

Identification of patient-centered goals of care

What are the goals for care, as identified by the patient/family/surrogate?

Are treatment options matched to informed patient-centered goals?

Has the patient participated in an advance care planning process?

Has the patient completed an advance care planning document?

Coping with life-threatening illness

How is the patient coping with their illness?

How are the family/family caregivers coping with the illness?

Coordination of care

Are there barriers to safe and sustainable transitions from one setting to another (eg, transportation to appointments)?

Are systems in place to enable good communication between multiple providers?

Adapted from: 1. Jacobsen J, Jackson V, Dahlin C, et al. Components of early outpatient palliative care consultation in patients with

metastatic nonsmall cell lung cancer. J Palliat Medicine 2011; 14:459. 2. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the hospital setting. J Palliat

Med 2011; 14:17.

Graphic 103286 Version 1.0

Medical guidelines for determining appropriateness of hospice referral: Disease-specific guidelines

A patient will be considered to have a life expectancy of 6 months and be eligible for hospice services if they meet criteria for the following disease-specific baseline guidelines as well as evidence of decline as outlined in non-disease-specific baseline guidelines (shown on a separate table):

Cancer diagnoses

Disease with metastases at presentation OR

Progression from an earlier stage of disease to metastatic disease with either continued decline in spite of therapy or patient declines further disease-directed therapy.

NOTE: Certain cancers with poor prognoses (eg, small-cell lung cancer, brain cancer, and pancreatic cancer) may be hospice eligible without fulfilling the other criteria in this section

Dementia due to Alzheimer disease and related disorders

Patients will be considered to be in the terminal stage of dementia (life expectancy of 6 months or less) if they meet all of the following criteria:

Stage 7 or beyond according to the Functional Assessment Staging Scale; unable to walk, dress, and bathe without assistance; urinary and fecal incontinence (intermittent or constant); no consistently meaningful verbal communication (stereotypical phrases only or the ability to speak is limited to 6 or fewer intelligible words); AND

At least 1 medical complication within the past 12 months: aspiration pneumonia, pyelonephritis, septicemia, multiple stage 3 to 4 decubitus ulcers, recurrent fever after antibiotics, inability to maintain sufficient fluid and calorie intake (≥10% weight loss over previous 6 months or serum albumin <2.5 g/dL).

NOTE: This section is specific for Alzheimer disease and related disorders and is not appropriate for other types of dementia.

Heart disease

Patients will be considered to be in the terminal stage of heart disease (life expectancy of 6 months or less) if they meet the following criteria (1 and 2 should be present; factors from 3 will add supporting documentation):

1. At the time of initial certification or recertification for hospice, the patient is or has been already optimally treated for heart disease, or the patient is either not a candidate for surgical procedures or they decline those procedures. (Optimally treated means that patients who are not on vasodilators have a medical reason for not being on these drugs, eg, hypotension or kidney disease.)

2. Patients with congestive heart failure or angina should meet the criteria for the New York Heart Association (NYHA) Class IV. (Class IV patients with heart disease have an inability to carry on any physical activity. Symptoms of heart failure or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.)

Significant congestive heart failure may be documented by an ejection fraction of ≤20%, but assessment of ejection fraction is not required if not already available.

3. Documentation of the following factors supports but is not required to establish eligibility for hospice care: treatment-resistant symptomatic supraventricular or ventricular arrhythmias, history of cardiac arrest or resuscitation, history of unexplained syncope, brain embolism of cardiac origin, or concomitant HIV disease.

HIV disease

Patients will be considered to be in the terminal stage of their illness (life expectancy of 6 months or less) if they meet the following criteria (1 and 2 should be present; factors from 3 will add supporting documentation):

1. CD4 count <25 cells per microliter or persistent (2 or more assays at least 1 month apart) viral load >100,000 copies/mL, plus 1 of the following:

Central nervous system (CNS) lymphoma, untreated or persistent despite treatment; wasting (loss of at least 10% lean body mass); mycobacterium avium complex (MAC) bacteremia, untreated, unresponsive to treatment, or treatment refused; progressive multifocal leukoencephalopathy; systemic lymphoma, with advanced HIV disease and partial response to chemotherapy; visceral Kaposi sarcoma, unresponsive to therapy; kidney failure in the absence of dialysis; cryptosporidium infection; toxoplasmosis, unresponsive to therapy.

2. Decreased performance status, as measured by the Karnofsky Performance Status (KPS) scale, ≤50%.

3. Documentation of the following factors will support eligibility for hospice care: chronic persistent diarrhea for 1 year; persistent serum albumin <2.5 g/dL; concomitant, active substance abuse; age >50 years; absence of or resistance to effective antiretroviral, chemotherapeutic, and prophylactic drug therapy related specifically to HIV disease; advanced AIDS dementia complex; toxoplasmosis; congestive heart failure, symptomatic at rest; advanced liver disease.

Liver disease

Patients will be considered to be in the terminal stage of liver disease (life expectancy of 6 months or less) if they meet the following criteria (1 and 2 should be present; factors from 3 will lend supporting documentation):

1. Both prolonged prothrombin time (more than 5 seconds over control or INR >1.5) AND serum albumin <2.5 g/dL.

2. End-stage liver disease with at least 1 of the following: ascites, refractory to treatment or patient noncompliant; spontaneous bacterial peritonitis; hepatorenal syndrome (elevated creatinine and BUN with oliguria [<400 mL/day] and urine sodium concentration <10 mEq/L); hepatic encephalopathy, refractory to treatment or patient noncompliant; recurrent variceal bleeding, despite intensive therapy.

3. Documentation of the following factors will support eligibility for hospice care: progressive malnutrition; muscle wasting with reduced strength and endurance; continued active alcoholism (>80 g ethanol/day); hepatocellular carcinoma; chronic hepatitis B virus infection (HBsAg-positive); hepatitis C infection, refractory to interferon treatment.

Pulmonary disease

Patients will be considered to be in the terminal stage of pulmonary disease (life expectancy of 6 months or less) if they meet the following criteria. The criteria refer to patients with various forms of advanced pulmonary disease who eventually follow a final common pathway for end-stage pulmonary disease (1 and 2 should be present; documentation of 3, 4, and 5 will lend supporting documentation):

1. Severe chronic lung disease as documented by both of the following:

Disabling dyspnea at rest, poorly responsive or unresponsive to bronchodilators, resulting in decreased functional capacity, eg, bed to chair existence, fatigue, and cough (documentation of forced expiratory volume in 1 second [FEV1], <30% predicted value after bronchodilator, is objective evidence for disabling dyspnea but is not necessary to obtain). Progression of end-stage pulmonary disease, as evidenced by increasing visits to the emergency department or hospitalizations for pulmonary infections and/or respiratory failure or increasing clinician home visits prior to initial certification (documentation of serial decrease of FEV1 >40 mL/year is objective evidence for disease progression but is not necessary to obtain).

2. Hypoxemia at rest on room air, as evidenced by pO ≤55 mmHg, or oxygen saturation ≤88%, determined either by arterial blood gases or oxygen saturation monitors (these values may be obtained from recent hospital records), OR hypercapnia, as evidenced by pCO ≥50 mmHg (this value may be obtained from recent [within 3 months] hospital records).

3. Right heart failure (RHF) secondary to pulmonary disease (Cor pulmonale, eg, not secondary to left heart disease or valvulopathy).

4. Unintentional progressive weight loss >10% of body weight over the preceding 6 months.

5. Resting tachycardia >100/minute.

Kidney disease (acute and chronic)

Patients will be considered to be in the terminal stage of kidney disease (life expectancy of 6 months or less) if they meet the following criteria:

Acute kidney failure (1 and either 2, 3, or 4 should be present; factors from 5 will lend supporting documentation):

1. The patient is not seeking dialysis or kidney transplant or is discontinuing dialysis. As with any other condition, an individual with kidney disease is eligible for the hospice benefit if that individual has a prognosis of 6 months or less, if the illness runs its normal course.

2

2

There is no regulation precluding patients on dialysis from electing hospice care. However, the continuation of dialysis will significantly alter a patient's prognosis and thus potentially impact that individual's eligibility.

When an individual elects hospice care for end-stage kidney disease (ESKD) or for a condition to which the need for dialysis is related, the hospice agency is financially responsible for the dialysis. In such cases, there is no additional reimbursement beyond the per diem rate. The only situation in which a beneficiary may access both the hospice benefit and the ESKD benefit is when the need for dialysis is not related to the patient's terminal illness.

2. Creatinine clearance <10 cc/minute (<15 cc/minute for diabetics), or <15 cc/minute (<20 cc/minute for diabetics) with comorbidity of congestive heart failure.

3. Serum creatinine >8.0 mg/dL (>6.0 mg/dL for diabetics).

4. Estimated glomerular filtration rate (GFR) <10 mL/minute.

5. Comorbid conditions: mechanical ventilation, malignancy (other organ system), chronic lung disease, advanced cardiac disease, advanced liver disease, immunosuppression/AIDS, albumin <3.5 g/dL, platelet count <25,000/microL, disseminated intravascular coagulation, gastrointestinal bleeding.

Chronic kidney disease (1 and either 2 or 3 should be present; factors from 4 will lend supporting documentation):

1. The patient is not seeking dialysis or kidney transplant or is discontinuing dialysis; as with any other condition, an individual with kidney disease is eligible for the hospice benefit if that individual has a prognosis of 6 months or less, if the illness runs its normal course. There is no regulation precluding patients on dialysis from electing hospice care. However, the continuation of dialysis will significantly alter a patient's prognosis and thus potentially impact that individual's eligibility.

When an individual elects hospice care for ESKD or for a condition to which the need for dialysis is related, the hospice agency is financially responsible for the dialysis. In such cases, there is no additional reimbursement beyond the per diem rate. The only situation in which a beneficiary may access both the hospice benefit and the ESKD benefit is when the need for dialysis is not related to the patient's terminal illness.

2. Creatinine clearance <10 cc/minute (<15 cc/minute for diabetics), or <15 cc/minute (<20 cc/minute for diabetics) with comorbidity of congestive heart failure.

3. Serum creatinine >8.0 mg/dL (>6.0 mg/dL for diabetics).

4. Signs and symptoms of kidney failure: uremia; oliguria (<400 cc/24 hours); intractable hyperkalemia (>7.0 mEq/L), not responsive to treatment; uremic pericarditis; hepatorenal syndrome; intractable fluid overload, not responsive to treatment.

Stroke or coma

Patients will be considered to be in the terminal stages of stroke or coma (life expectancy of 6 months or less) if they meet the following criteria:

Stroke:

KPS or Palliative Performance Scale of 40% or less. Inability to maintain hydration and caloric intake with 1 of the following: weight loss >10% in the last 6 months or >7.5% in the last 3 months; serum albumin <2.5 g/dL; current history of pulmonary aspiration, not responsive to speech-language pathology intervention; sequential calorie counts documenting inadequate caloric/fluid intake; dysphagia severe enough to prevent the patient from continuing food and fluids necessary to sustain life, in a patient who does not receive artificial nutrition and hydration.

Coma (any etiology): Comatose patients with any 3 of the following on day 3 of the coma: abnormal brain stem response, absent verbal response, absent withdrawal response to pain, serum creatinine >1.5 mg/dL.

Documentation of the following factors will support eligibility for hospice care:

Documentation of medical complications, in the context of progressive clinical decline, within the previous 12 months, that support a terminal prognosis:

Aspiration pneumonia, upper urinary tract infection (pyelonephritis), refractory stage 3 to 4 decubitus ulcers, fever recurrent after antibiotics.

For stroke patients, documentation of diagnostic imaging factors that support poor prognosis after stroke include:

For non-traumatic hemorrhagic stroke: large-volume hemorrhage on CT (≥20 mL if intratentorial, ≥50 mL if supratentorial), ventricular extension of hemorrhage, surface area of involvement of hemorrhage ≥30% of cerebrum, midline shift ≥1.5 cm, obstructive hydrocephalus in a patient who declines or is not a candidate for ventriculoperitoneal shunt. For thrombotic/embolic stroke: large anterior infarcts with both cortical/subcortical involvement, large bihemispheric infarcts, basilar artery occlusion, bilateral vertebral artery occlusion.

Amyotrophic lateral sclerosis (ALS)

Patients are considered eligible for hospice care if they do not elect tracheostomy and invasive ventilation and display evidence of critically impaired respiratory function (with or without use of noninvasive positive pressure ventilation [NIPPV]) and/or severe nutritional insufficiency (with or without use of a gastrostomy tube).

Critically impaired respiratory function is as defined by:

Forced vital capacity (FVC) <40% predicted (seated or supine) and 2 or more of the following symptoms and/or signs: dyspnea at rest, orthopnea, use of accessory respiratory musculature, paradoxical abdominal motion, respiratory rate >20/minute, reduced speech/vocal volume, weakened cough, symptoms of sleep-disordered breathing, frequent awakening, daytime somnolence/excessive daytime sleepiness, unexplained headaches, unexplained confusion, unexplained anxiety, unexplained nausea.

If unable to perform the FVC test, patients meet this criterion if they manifest 3 or more of the above symptoms/signs. Severe nutritional insufficiency is defined as dysphagia with progressive weight loss of at least 5% of body weight with or without election for gastrostomy tube insertion. These revised criteria rely less on the measured FVC and, as such, reflect the reality that not all patients with ALS can or will undertake regular pulmonary function tests.

KPS = 50: Requires considerable assistance and frequent medical care.

KPS <50: Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.

HIV: human immunodeficiency virus; CD4: cluster of differentiation 4; AIDS: acquired immunodeficiency syndrome; INR: international normalized ratio; BUN: blood urea nitrogen; HBsAg: hepatitis B surface antigen; pO : partial pressure of oxygen; pCO : partial pressure of carbon dioxide; CT: computed tomography.

Sources: 1. The NHO medical guidelines for non-cancer disease and local medical review policy: hospice access for patients with

diseases other than cancer. Hosp J 1999. 2. Centers for Medicare & Medicaid Services. Medicare Coverage Database. Available at: https://www.cms.gov/medicare-

coverage-database/details/lcd-details.aspx?LCDId=34538 (Accessed on January 5, 2021).

Graphic 61282 Version 21.0

2 2

Technique for use of a pressurized metered dose inhaler (MDI) with a spacer or chamber*

Uncap mouthpiece and check for loose objects in the device.

Prime your inhaler if this is the first time you are using it, if you have not used it for several days, or if you have dropped it. Priming an MDI usually involves shaking it and spraying it into the air (away from your face) a total of up to 4 times. See the information that came with your inhaler for exact instructions.

Insert MDI into spacer.

Shake canister vigorously for approximately 5 seconds.

Hold the MDI upright with your index finger on the top of the medication canister and your thumb supporting the bottom of the inhaler. You may need to use the other hand to hold the spacer.

Breathe out normally through your mouth.

Put the mouthpiece between your teeth and close your lips tightly around mouthpiece of spacer. (If using a mask attached to the chamber, place the mask completely over your nose and mouth.)

Make sure your tongue does not block the opening of the mouthpiece of the spacer.

Press down the top of the canister with your index finger to release the medicine.

At the same time, breathe in deeply and slowly through your mouth until your lungs are completely filled; this should take 3 to 5 seconds.

Hold the medicine in your lungs for approximately 5 to 10 seconds. If you did not get a full breath or cannot hold your breath long enough, you can inhale a second time to fully empty the chamber and hold your breath again for approximately 5 seconds. For infants and young children, or if unable to cooperate with a deep breath or breath-holding, 5 to 6 normal breaths will allow complete emptying of the chamber.

If you need more than one puff, wait approximately 15 to 30 seconds between puffs. Shake canister again before the next puff. Do not load both puffs into the chamber and then empty the chamber with a single inhalation.

When finished, recap mouthpiece.

If your inhaler contains a steroid medicine (sometimes called glucocorticoid or corticosteroid), rinse your mouth and gargle with water after you use it. Then spit out the water. Do not swallow it.

You can use your spacer for more than 1 medication. Just remove the first MDI and insert the other one.

These instructions do not apply to dry powder or soft mist inhalers. Cleaning instructions are provided separately.

* We prefer to use a "valved holding chamber" for the spacer (eg, AeroChamber, Easivent, Optichamber, Vortex). The valve holds the medicine in the chamber until you take your deep breath

in. This helps get the medicine into your lungs. Also, when you breathe out into the mouthpiece, the valve prevents your breath from going into the chamber. If your spacer does not have this valve, you should breathe out through your nose or remove the spacer from your mouth before breathing out.

Graphic 103303 Version 9.0

Technique for use of a metered dose inhaler (MDI) without a spacer or chamber

Remove the cover of the mouthpiece.

Prime your inhaler if this is the first time you are using it, if you have not used it for several days, or if you have dropped it. Priming a metered dose inhaler usually involves shaking it and spraying it into the air (away from your face) up to 4 times. See the information that came with your inhaler for exact instructions.

Check the number of doses remaining in the MDI.

Sit or stand up straight with the chi tilted up and neck slightly extended.

Shake MDI canister vigorously for 5 seconds.

Hold the MDI upright with your index finger on the top of the canister and your thumb supporting the bottom of the inhaler.

Breathe out normally.

Put the mouthpiece between your teeth and close your lips around mouthpiece or position mouthpiece about 4 cm (about the width of 2 fingers) from your mouth.

Keep your tongue away from the opening of the mouthpiece.

Press down the top of the canister with the index finger to release the medicine.

At the same time as the canister is pressed, breathe in deeply and slowly through your mouth until your lungs are completely full. This should take 3 to 5 seconds.

Hold the medicine in your lungs for as long as comfortable (about 5 to 10 seconds).

Remove the inhaler from your mouth and exhale normally.

If you need a second puff, wait about 15 to 30 seconds between puffs. Shake the canister again before the next puff.

When finished, put the mouthpiece cover back on.

If your inhaler contains a steroid medicine (sometimes called a "glucocorticoid" or "corticosteroid"), rinse your mouth and gargle with water after you use it. Then spit out the water. Do not swallow it.

We prefer to use metered dose inhalers (MDIs) with a spacer or holding chamber. Instructions for use of MDIs with these devices is provided in a separate graphic.

These instructions do not apply to dry powder or soft mist inhalers. Cleaning instructions are provided separately.

More detailed information about individual medicines can be found at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.

MDI: metered dose inhaler.

Graphic 72362 Version 13.0

Technique for use of various dry powder inhalers*

Load a dose of medicine

For single-dose inhalers, load a dose by taking a pill out of its packaging and putting the pill into the inhaler. Then push 1 or more buttons on the inhaler to poke holes in the pill.

For multiple-dose inhalers, load a dose by sliding a lever or twisting part of the inhaler. Loading a dose should decrease the counter on the device by one. This means a dose is ready to be inhaled.

Once the dose is loaded, maintain your inhaler in the correct position - some inhalers need to be held upright, but others need to be horizontal. The dose may be lost or spilled if the inhaler is tipped over after loading.

Medication delivery

Open the device or take off the cap to expose the mouthpiece, if necessary.

While holding the inhaler away from your mouth, breathe out (exhale) fully. Do not exhale into the mouthpiece.

Put the mouthpiece between your lips. Breathe in quickly and steadily through your mouth, as deeply as possible. Do not breathe in through your nose. You might not taste or feel the medicine, even when you are using the inhaler correctly. If your device has air vent holes, do not cover those holes while inhaling through the device.

Remove the device from your mouth and hold your breath for about 10 seconds (or as long as you comfortably can).

Breathe out slowly (away from the mouthpiece).

If you are supposed to take 2 puffs of your inhaler, load/activate another dose and breathe it in.

Rinse your mouth out with water, gargle, and spit out the water.

Device maintenance and storage

After use, close your inhaler or replace the cover or cap. Make sure the device is fully closed before storing.

For single dose inhalers, you often need to dispose of the used dose. Please refer to the package insert.

Pay attention to the number of doses you have remaining. For multi-dose devices, observe the counter to determine when you need a refill on the device. For single dose devices, monitor the number of individual doses remaining.

Store your inhaler in a cool, dry place.

Dry powder inhalers generally do not require internal cleaning. The mouthpiece may be wiped off with a dry cloth. Please refer to the package insert for additional device-specific instructions.

* Each dry powder inhaler comes with its own directions. Although the general technique is similar, various devices are loaded and activated differently. Some devices load each dose separately, while others contain a month's worth of medication and do not require loading. Refer to the package insert of each device or to the manufacturer website for additional instructions.

Graphic 51020 Version 13.0

Technique for use of soft mist inhalers (SMIs)*

The first time you use a soft mist inhaler, you will need to insert the cartridge.

Keep the cap on the mouthpiece closed. Press the safety catch on the side of the inhaler and pull off the clear plastic base.

Write the discard date on the label. This is 3 months from the date you put in the cartridge.

Push the narrow end of the cartridge into the inhaler.

Push the cartridge against a firm surface or table top to be sure it has gone all the way in. You will know the cartridge is in all the way when it clicks. You will still be able to see a little bit of the cartridge.

Do not remove the cartridge after it has been inserted.

Put the clear base back on. Press until you hear a click.

Do not remove the clear base again.

Prime the inhaler before the first dose.

Hold the inhaler upright with the cap closed. Turn the clear base clockwise (to the right) half a turn until it clicks.

Open the cap by pushing on the small, round opening tab. Then point the inhaler at the floor, away from your face.

Press the dose release button on the side. Check to see if a mist comes out. Close the cap.

If you did not see a mist, repeat the priming steps above until you see a mist come out.

After you see a mist come out, repeat these steps 3 more times until you see a total of 4 sprays of medicine.

Your inhaler is now primed and ready for daily use.

If you do not use the inhaler for more than 3 days, repeat the priming steps 1 time to release 1 spray of medicine.

If you do not use the inhaler for more than 3 weeks, repeat the priming steps 4 times to release 4 sprays of medicine.

Take a dose of medicine.

Hold the inhaler upright with 1 hand, with the cap closed. You do not need to shake it. Use your other hand to turn the clear base clockwise half a turn in the direction of the arrows. This prepares the dose of medicine.

Open the cap by pushing on the small round opening tab.

Breathe out slowly and fully.

Put the mouthpiece in your mouth, and hold the inhaler horizontally. This means it should point toward the back of your throat.

Close your lips around the inhaler, but do not cover the air vents (holes) on the sides.

Take a slow, deep breath in. As you start to inhale, press the button on the side of the inhaler and inhale the mist.

When your lungs are full, hold your breath for 10 seconds to keep the medicine in your lungs.

Remove inhaler from your mouth and breathe out slowly. Put the cap back on the mouthpiece.

You should clean your inhaler once a week. To do this, wipe the inside and outside of the mouthpiece with a clean, damp cloth.

The inhaler has a dose counter (also called a "dose indicator") on the side. When the arrow is in the red zone, the inhaler is almost empty. When the inhaler is completely empty, the arrow will point to "0," and you will not be able to turn the base of the inhaler. Throw away the inhaler when the counter reads "0" or you reach the discard date, whichever is first. Make sure you always have another inhaler available before you need it.

* Soft mist inhalers are also known as Respimat inhalers.

Graphic 93600 Version 6.0

Recommended adult immunization schedule by medical condition and other in

Administer recommended vaccines if vaccination history is incomplete or unknown. Do not restart or add do use of trade names is for identification purposes only and does not imply endorsement by the ACIP or CDC.

Polio vaccination Routine vaccination:

Routine poliovirus vaccination of adults residing in the United States is not necessary. Special situations:

Adults at increased risk of exposure to poliovirus with: No evidence of a complete polio vaccination series (ie, at least 3 doses): Administer remain Evidence of completed polio vaccination series (ie, at least 3 doses): May administer one life

For detailed information, refer to www.cdc.gov/vaccines/vpd/polio/hcp/recommendations.html.

HSCT: hematopoietic stem cell transplant.

* Precaution for LAIV4 does not apply to alcoholism.

¶ COVID-19 vaccination Routine vaccination:

Primary series: 2-dose series at 0, 4 to 8 weeks (Moderna) or 2-dose series at 0, 3 to 8 weeks (Nov Booster dose: Refer to www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerati

Special situations: Persons who are moderately or severely immunocompromised.

Primary series: 3-dose series at 0, 4, 8 weeks (Moderna) or 3-dose series at 0, 3, 7 weeks (Pfizer-BioNTech). 2-dose series at 0, 3 weeks (Novavax).

Booster dose: Refer to www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-conside Pre-exposure prophylaxis (eg, monoclonal antibodies) may be considered to complement C considerations/interim-considerations-us.html#immunocompromised.

For Janssen COVID-19 Vaccine recipients refer to COVID-19 schedule at www.cdc.gov/vaccines/c NOTE: Current COVID-19 schedule available at www.cdc.gov/vaccines/covid-19/downloads/COVID- information on Emergency Use Authorization (EUA) indications for COVID-19 vaccines, please visit disease-2019-covid-19/covid-19-vaccines.

Contraindications and precautions: Refer to contraindications and precautions to COVID-19 vaccination.

Δ Influenza vaccination Routine vaccination:

Age 19 years or older: 1 dose any influenza vaccine appropriate for age and health status annual Age 65 years or older: Any one of quadrivalent high-dose inactivated influenza vaccine (HD-IIV4), adjuvanted inactivated influenza vaccine (aIIV4) is preferred. If none of these three vaccines is ava For the 2022–2023 season, refer to www.cdc.gov/mmwr/volumes/71/rr/rr7101a1.htm. For the 2023–2024 season, refer to the 2023–2024 ACIP influenza vaccine recommendations.

Special situations: Egg allergy, hives only: Any influenza vaccine appropriate for age and health status annually. Egg allergy–any symptom other than hives (eg, angioedema, respiratory distress, or required e vaccine appropriate for age and health status may be administered. If using egg-based IIV4 or LAI provider who can recognize and manage severe allergic reactions. Close contacts (eg, caregivers, health care workers) of severely immunosuppressed persons receive LAIV4. If LAIV4 is given, they should avoid contact with/caring for such immunosuppressed Severe allergic reaction (eg, anaphylaxis) to a vaccine component or a previous dose of any i precautions. History of Guillain-Barré syndrome within 6 weeks after previous dose of influenza vaccine: risks for those at higher risk for severe complications from influenza.

Contraindications and precautions: For contraindications and precautions to influenza vaccination, refer to IIV4 Appendix, LAIV4 Appe

◊ Tetanus, diphtheria, and pertussis (Tdap) vaccination Routine vaccination:

Previously did not receive Tdap at or after age 11 years: 1 dose Tdap, then Td or Tdap every 10 Special situations:

Previously did not receive primary vaccination series for tetanus, diphtheria, or pertussis: 1 dose of Td or Tdap 6 to 12 months later (Tdap can be substituted for any Td dose, but preferred as Pregnancy: 1 dose Tdap during each pregnancy, preferably in early part of gestational weeks 27 t Wound management: Persons with 3 or more doses of tetanus-toxoid-containing vaccine: For cle last dose of tetanus-toxoid-containing vaccine; for all other wounds, administer Tdap or Td if more preferred for persons who have not previously received Tdap or whose Tdap history is unknown. I use Tdap. For detailed information, refer to www.cdc.gov/mmwr/volumes/69/wr/mm6903a5.htm.

Contraindications and precautions: For contraindications and precautions to tetanus, diphtheria, and acellular pertussis (Tdap), refer t

§ Measles, mumps, and rubella vaccination Routine vaccination:

No evidence of immunity to measles, mumps, or rubella: 1 dose. Evidence of immunity: Born before 1957 (health care personnel, refer below), documentation (diagnosis of disease without laboratory confirmation is not evidence of immunity).

Special situations: Pregnancy with no evidence of immunity to rubella: MMR contraindicated during pregnancy; a Nonpregnant women of childbearing age with no evidence of immunity to rubella: 1 dose. HIV infection with CD4 percentages ≥15% and CD4 count ≥200 cells/mm for at least 6 mon dose series at least 4 weeks apart; MMR contraindicated for HIV infection with CD4 percentage <1 Severe immunocompromising conditions: MMR contraindicated. Students in postsecondary educational institutions, international travelers, and household o evidence of immunity to measles, mumps, or rubella: 2-dose series at least 4 weeks apart if pre 1 dose MMR. In mumps outbreak settings, for information about additional doses of MMR (including 3rd dose Health care personnel:

Born before 1957 with no evidence of immunity to measles, mumps, or rubella: Consider rubella. Born in 1957 or later with no evidence of immunity to measles, mumps, or rubella: 2-dose rubella.

Contraindications and precautions: For contraindications and precautions to measles, mumps, rubella (MMR), refer to MMR Appendix

¥ Varicella vaccination Routine vaccination:

No evidence of immunity to varicella: 2-dose series 4 to 8 weeks apart if previously did not rece varicella vaccine] for children); if previously received 1 dose varicella-containing vaccine, 1 dose at

Evidence of immunity: US-born before 1980 (except for pregnant women and health care per vaccine at least 4 weeks apart, diagnosis or verification of history of varicella or herpes zoster

Special situations: Pregnancy with no evidence of immunity to varicella: VAR contraindicated during pregnancy; a previously received 1 dose varicella-containing vaccine or dose 1 of 2-dose series (dose 2: 4 to 8 w regardless of whether US-born before 1980.

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Health care personnel with no evidence of immunity to varicella: 1 dose if previously received previously did not receive any varicella-containing vaccine, regardless of whether US-born before HIV infection with CD4 percentages ≥15% and CD4 count ≥200 cells/mm with no evidence VAR contraindicated for HIV infection with CD4 percentage <15% or CD4 count <200 cells/mm . Severe immunocompromising conditions: VAR contraindicated.

Contraindications and precautions: For contraindications and precautions to varicella (VAR), refer to VAR Appendix.

‡ Zoster vaccination Routine vaccination:

Age 50 years or older (NOTE: Serologic evidence of prior varicella is not necessary for zoster vacc available, providers should follow ACIP guidelines for varicella vaccination first. RZV is not indicate RZV in persons without a history of varicella or varicella vaccination): 2-dose series recombinant zo weeks; repeat dose if administered too soon), regardless of previous herpes zoster or history of zo

Special situations: Pregnancy: There is currently no ACIP recommendation for RZV use in pregnancy. Consider delay Immunocompromising conditions (including persons with HIV regardless of CD4 count; NOTE: I herpes zoster, providers should refer to the clinical considerations for use of RZV in immunocomp recommendations for further guidance: www.cdc.gov/mmwr/volumes/71/wr/mm7103a2.htm): 2-d (minimum interval: 4 weeks; repeat dose if administered too soon). For detailed information, refer

Contraindications and precautions: For contraindications and precautions to zoster recombinant vaccine (RZV), refer to RZV Appendix

† Human papillomavirus vaccination Routine vaccination:

HPV vaccination recommended for all persons through age 26 years: 2- or 3-dose series depen Age 15 years or older at initial vaccination: 3-dose series at 0, 1 to 2 months, 6 months (min dose 1 to dose 3: 5 months; repeat dose if administered too soon). Age 9 to 14 years at initial vaccination and received 1 dose or 2 doses less than 5 months Age 9 to 14 years at initial vaccination and received 2 doses at least 5 months apart: HPV

Interrupted schedules: If vaccination schedule is interrupted, the series does not need to be rest No additional dose recommended when any HPV vaccine series has been completed using th

Shared clinical decision-making: Some adults age 27 to 45 years: Based on shared clinical decision-making, 2- or 3-dose series as

Special situations: Age ranges recommended above for routine and catch-up vaccination or shared clinical deci

Immunocompromising conditions, including HIV infection: 3-dose series, even for those w Pregnancy: Pregnancy testing is not needed before vaccination; HPV vaccination is not recom vaccinated while pregnant.

Contraindications and precautions: For contraindications and precautions to human papillomavirus (HPV) vaccination, refer to HPV Ap

** Pneumococcal vaccination Routine vaccination:

Age 65 years or older who have: Not previously received a dose of PCV13, PCV15, or PCV20 or whose previous vaccination this should be followed by a dose of PPSV23 given at least 1 year after the PCV15 dose. A min for adults with an immunocompromising condition (NOTE: Immunocompromising conditions

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iatrogenic immunosuppression, generalized malignancy, human immunodeficiency virus, Ho transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies invasive pneumococcal disease caused by serotypes unique to PPSV23 in these vulnerable gro Previously received only PCV7: Follow the recommendation above. Previously received only PCV13: 1 dose PCV20 at least 1 year after the PCV13 dose OR comp www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf. Previously received only PPSV23: 1 dose PCV15 OR 1 dose PCV20 at least 1 year after the PP PPSV23. Previously received both PCV13 and PPSV23 but NO PPSV23 was received at age 65 years vaccine dose OR complete the recommended PPSV23 series as described here: www.cdc.gov/ Previously received both PCV13 and PPSV23, AND PPSV23 was received at age 65 years o least 5 years after the last pneumococcal vaccine dose. For guidance on determining which pneumococcal vaccines a patient needs and when, pleas www.cdc.gov/vaccines/vpd/pneumo/hcp/pneumoapp.html.

Special situations: Age 19 to 64 years with certain underlying medical conditions or other risk factors who hav alcoholism, chronic heart/liver/lung disease, chronic renal failure, cigarette smoking, cochlear im generalized malignancy, HIV, Hodgkin disease, immunodeficiency, iatrogenic immunosuppressio organ transplants, or sickle cell disease, or other hemoglobinopathies):

Not previously received a PCV13, PCV15, or PCV20 or whose previous vaccination history should be followed by a dose of PPSV23 given at least 1 year after the PCV15 dose. A minimum adults with an immunocompromising condition(NOTE: Immunocompromising conditions inc iatrogenic immunosuppression, generalized malignancy, human immunodeficiency virus, Ho transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies Previously received only PCV7: Follow the recommendation above. Previously received only PCV13: 1 dose PCV20 at least 1 year after the PCV13 dose OR comp www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf. Previously received only PPSV23: 1 dose PCV15 OR 1 dose PCV20 at least 1 year after the PP PPSV23. Previously received both PCV13 and PPSV23 but have not completed the recommended dose OR complete the recommended PPSV23 series as described here: www.cdc.gov/vaccines

For guidance on determining which pneumococcal vaccines a patient needs and when, please re www.cdc.gov/vaccines/vpd/pneumo/hcp/pneumoapp.html.

Contraindications and precautions: For contraindications and precautions to Pneumococcal conjugate (PCV15 and PCV20), refer to PC PPSV23 Appendix.

¶¶ Hepatitis A vaccination Routine vaccination:

Not at risk but want protection from hepatitis A (identification of risk factor not required): apart [minimum interval: 6 months]) or 3-dose series HepA-HepB (Twinrix at 0, 1, 6 months [mini

Special situations: At risk for hepatitis A virus infection: 2-dose series HepA or 3-dose series HepA-HepB as above

Chronic liver disease (eg, persons with hepatitis B, hepatitis C, cirrhosis, fatty liver disease, a [ALT] or aspartate aminotransferase [AST] level greater than twice the upper limit of normal). HIV infection. Men who have sex with men.

Injection or noninjection drug use. Persons experiencing homelessness. Work with hepatitis A virus in research laboratory or with nonhuman primates with hepatit Travel in countries with high or intermediate endemic hepatitis A (HepA-HepB [Twinrix] m to 30 days, followed by a booster dose at 12 months). Close, personal contact with international adoptee (eg, household or regular babysitting) endemic hepatitis A (administer dose 1 as soon as adoption is planned, at least 2 weeks befor Pregnancy if at risk for infection or severe outcome from infection during pregnancy. Settings for exposure, including health care settings targeting services to injection or noninj for developmentally disabled persons (individual risk factor screening not required).

Contraindications and precautions: For contraindications and precautions to hepatitis A (HepA) vaccination, refer to HepA Appendix.

ΔΔ Hepatitis B vaccination Routine vaccination:

Age 19 through 59 years: Complete a 2- or 3-, or 4-dose series. 2-dose series only applies when 2 doses of Heplisav-B (NOTE: Heplisav-B and PreHevbrio are persons) are used at least 4 weeks apart. 3-dose series Engerix-B, PreHevbrio (NOTE: Heplisav-B and PreHevbrio are not recommended Recombivax HB at 0, 1, 6 months [minimum intervals: dose 1 to dose 2: 4 weeks / dose 2 to d 3-dose series HepA-HepB (Twinrix at 0, 1, 6 months [minimum intervals: dose 1 to dose 2: 4 w 4-dose series HepA-HepB (Twinrix) accelerated schedule of 3 doses at 0, 7, and 21 to 30 days,

Age 60 years or older with known risk factors for hepatitis B virus infection should complete a H Age 60 years or older without known risk factors for hepatitis B virus infection may complete a

Risk factors for hepatitis B virus infection include: Chronic liver disease (eg, persons with hepatitis C, cirrhosis, fatty liver disease, alcoholic aspartate aminotransferase [AST] level greater than twice upper limit of normal). HIV infection. Sexual exposure risk (eg, sex partners of hepatitis B surface antigen [HBsAg]-positive pe persons seeking evaluation or treatment for a sexually transmitted infection; men who ha Current or recent injection drug use. Percutaneous or mucosal risk for exposure to blood (eg, household contacts of HBsAg disabled persons; health care and public safety personnel with reasonably anticipated risk maintenance dialysis, including in-center or home hemodialysis and peritoneal dialysis, a Incarceration. Travel in countries with high or intermediate endemic hepatitis B.

Special situations: Patients on dialysis: complete a 3- or 4-dose series.

3-dose series Recombivax HB at 0, 1, 6 months (NOTE: use Dialysis Formulation 1 mL = 40 mc 4-dose series Engerix-B at 0, 1, 2, and 6 months (NOTE: use 2 mL dose instead of the normal a

Contraindications and precautions: For contraindications and precautions to hepatitis B (HepB) vaccination, refer to HepB Appendix.

◊◊ Meningococcal vaccination Special situations for MenACWY:

Anatomical or functional asplenia (including sickle cell disease), HIV infection, persistent co eculizumab, ravulizumab) use: 2-dose series MenACWY-D (Menactra, Menveo, or MenQuadfi) a

Travel in countries with hyperendemic or epidemic meningococcal disease, or microbiologi (Menactra, Menveo, or MenQuadfi) and revaccinate every 5 years if risk remains. First-year college students who live in residential housing (if not previously vaccinated at a Menveo, or MenQuadfi). For MenACWY booster dose recommendations for groups listed under "Special situations" and among men who have sex with men) and additional meningococcal vaccination information, refe

Shared clinical decision-making for MenB: Adolescents and young adults age 16 to 23 years (age 16 to 18 years preferred) not at increa making, 2-dose series MenB-4C (Bexsero) at least 1 month apart or 2-dose series MenB-FHbp (Tru after dose 1, administer dose 3 at least 4 months after dose 2); MenB-4C and MenB-FHbp are not

Special situations for MenB: Anatomical or functional asplenia (including sickle cell disease), persistent complement co ravulizumab) use, or microbiologists routinely exposed to Neisseria meningitidis (NOTE: Men if indicated, but at a different anatomic site, if feasible): 2-dose primary series MenB-4C (Bexsero) at 0, 1 to 2, 6 months (if dose 2 was administered at least 6 months after dose 1, dose 3 not need dose should be administered at least 4 months after dose 3); MenB-4C and MenB-FHbp are not in booster 1 year after primary series and revaccinate every 2 to 3 years if risk remains. Pregnancy: Delay MenB until after pregnancy unless at increased risk and vaccination benefits o For MenB booster dose recommendations for groups listed under "Special situations" and in an among men who have sex with men) and additional meningococcal vaccination information, refe

Contraindications and precautions: For contraindications and precautions to meningococcal ACWY (MenACWY) [MenACWY-CRM (Men MenACWY Appendix. For contraindications and precautions to meningococcal B (MenB) [MenB-4C (Bexsero); MenB-FH

§§ Haemophilus influenzae type b vaccination Special situations:

Anatomical or functional asplenia (including sickle cell disease): 1 dose if previously did not r before splenectomy. Hematopoietic stem cell transplant (HSCT): 3-dose series 4 weeks apart starting 6 to 12 month

Contraindications and precautions: For contraindications and precautions to Haemophilus influenzae type b (Hib) vaccination, refer to

¥¥ Vaccinate after pregnancy.

Reproduced from: Advisory Committee on Immunization Practices. Recommended Adult Immunization Schedule for ages 19 years or https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html (Accessed on February 15, 2023).

Graphic 62130 Version 23.0

New diagnosis of COPD

COPD: chronic obstructive pulmonary disease; COVID-19: coronavirus disease 2019; GOLD: Global Initiative f CAT: COPD Assessment Test; SABA: short-acting beta-agonist; SAMA: short-acting muscarinic antagonist; LAM (anticholinergic); LABA: long-acting beta-agonist; mMRC: Modified Medical Research Council; FEV : forced ex forced vital capacity.

* COPD is diagnosed based on the presence of chronic respiratory symptoms (dyspnea, cough, sputum prod limitation. All patients with COPD defined by GOLD have airflow limitation based on a reduced FEV /FVC ratio is determined by the reduction in FEV .

¶ An exacerbation of COPD is characterized by increased dyspnea and/or cough and sputum that worsens in accompanied by tachypnea or tachycardia, and is often caused by infection, environmental irritation, or othe exacerbations" are typically defined as those which require treatment with systemic glucocorticoids. More o been proposed but are difficult to establish via patient history. Please refer to UpToDate content on "COPD e and evaluation" for additional information.

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Δ CAT: http://www.catestonline.org (Accessed on January 12, 2023).

◊ For those prescribed a LABA alone, SAMA-SABA combination therapy is likely to be most potent but will ha LAMA. For those prescribed a LAMA, SAMA should generally not be used concomitantly, so SABA alone is pre

§ Occasional patients with only minimal intermittent symptoms are appropriate for only as-needed rescue th acting bronchodilators.

Graphic 54300 Version 13.0

Follow-up management of COPD*

No exacerbations and no dyspnea/low COPD impact (ie, mMRC 0 to 1 or CAT <10)

Current therapy Actions

SABA or SABA-SAMA as needed

Continue current therapy

LAMA, LABA, or LAMA-LABA Continue current therapy

LABA-ICS or LABA-LAMA-ICS Taper or discontinue ICS dose to reduce adverse effects of ICS

Persistent dyspnea or high COPD impact (ie, mMRC ≥2 or CAT ≥10) with no exacerbations

Current therapy Actions

SABA or SABA-SAMA as needed

Add LAMA or LABA

LAMA or LABA monotherapy Change to LAMA-LABA

LABA-ICS LAMA-LABA-ICS LAMA-LABA if lack of response to ICS or adverse effects from ICS

LAMA-LABA Substitute alternate delivery system or different LAMA- LABA agents Trial of LAMA-LABA-ICS, in patients with blood eosinophils ≥100 cells/microL Additional interventions may include low-dose theophylline, repeat pulmonary rehabilitation, and nonpharmacologic therapies

LAMA-LABA-ICS Continue LAMA-LABA-ICS Additional interventions may include low-dose theophylline, repeat pulmonary rehabilitation, and nonpharmacologic therapies for COPD Stop ICS, if initial indication unclear, lack of response, or adverse effect to ICS

1 or more exacerbations in past year +/– persistent dyspnea or high COPD impact (ie, mMRC ≥2 or CAT ≥10)

Current therapy Actions

SABA or SABA-SAMA as needed

Add LAMA

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Δ

¶

◊

§

§

Δ

¶

§

LAMA or LABA monotherapy LAMA-LABA, if blood eosinophil count <300/microL

or

LAMA-LABA-ICS, if blood eosinophil count ≥300/microL or hospitalization for COPD exacerbation

or

LABA-ICS, if blood eosinophil count ≥100/microL and LAMA contraindicated

LAMA-LABA LAMA-LABA-ICS, if blood eosinophil count ≥100/microL

or

Continue LAMA-LABA, if blood eosinophil count <100/microL

Add roflumilast

or

Add azithromycin

LABA-ICS LAMA-LABA-ICS

or

LAMA-LABA if lack of response to ICS or adverse effects from ICS

LAMA-LABA-ICS Continue LAMA-LABA-ICS Add roflumilast

or

Add azithromycin Stop ICS if initial indication unclear, lack of response, or adverse effects of ICS

COPD: chronic obstructive pulmonary disease; mMRC: modified Medical Research Council; CAT: COPD Assessment Test; SABA: short-acting beta-agonist; SAMA: short-acting muscarinic-antagonist; LAMA: long-acting muscarinic-antagonist; LABA: long-acting beta-agonist; ICS: inhaled corticosteroids (glucocorticoids); BMI: body mass index; SpO : pulse oxygen saturation; FEV : forced expiratory volume in one second.

* Adjustments to pharmacologic therapy for COPD are based on an assessment of dyspnea/exercise limitation (mMRC or CAT), frequency of exacerbations, and peripheral blood eosinophil counts. Follow-up visits are also an opportunity to assess and reinforce nonpharmacologic interventions for COPD, including: smoking cessation; inhaler technique and adherence to medications; administration of pneumococcal and seasonal influenza vaccinations; pulmonary rehabilitation; and nutrition counselling regarding healthy diet and normal BMI. All patients with COPD should have a rapid relief inhaler available, either a SABA or a SABA-SAMA (SABA preferred for patients using a LAMA). Refer to UpToDate content on the overview of management for stable COPD.

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†

Δ

‡

†

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¶ mMRC dyspnea scale: https://www.pcrs-uk.org/mrc-dyspnoea-scale; CAT evaluates health impact of COPD: https://www.catestonline.org.

Δ If blood eosinophil count ≥300 cells/microL, patient is more likely to experience exacerbations after ICS withdrawal. Close patient monitoring is required if ICS are withdrawn.

◊ In patients with exacerbations and blood eosinophil count ≥300 cells/microL, the addition of ICS is likely to be of benefit. For patients with eosinophil counts ≥100 but <300 cells/microL, ICS may improve exacerbation rates and pulmonary function.

§ Nonpharmacologic measures (eg, oxygen therapy if SpO ≤88%, pulmonary rehabilitation, bronchoscopic or surgical lung volume reduction, lung transplantation) can help reduce dyspnea and exacerbations. Contributing comorbidities should be evaluated and treated. Not all patients achieve control of dyspnea or exacerbations despite optimal available pharmacotherapy.

¥ For patients with a blood eosinophil count <100 cells/microL, there is a low likelihood that addition of ICS will be beneficial and higher risk of pneumonia after the addition of ICS.

‡ Roflumilast is used for patients with chronic bronchitis and FEV <50% predicted, particularly if there has been at least 1 hospitalization for an exacerbation in the past year. Potential adverse effects may limit use.

† Azithromycin preventive therapy is more effective in patients who are not current smokers. However, it may lead to development of resistant organisms.

Adapted from: Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (2023 Report). Available at: www.goldcopd.org (Accessed on December 13, 2022).

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Contributor Disclosures

James K Stoller, MD, MS Grant/Research/Clinical Trial Support: Alpha-1 Foundation [Alpha-1 antitrypsin detection]. Consultant/Advisory Boards: 23andMe [Alpha-1 antitrypsin deficiency]; 4DMT [Alpha-1 antitrypsin deficiency]; Alpha-1 Foundation [Member, Board of Directors]; Bridgebio [Alpha-1 antitrypsin deficiency]; CSL Behring [Alpha-1 antitrypsin detection]; Dicerna [Alpha-1 antitrypsin deficiency]; Grifols [Alpha-1 antitrypsin detection]; InhibRx [Alpha-1 antitrypsin deficiency]; Insmed [Alpha-1 antitrypsin deficiency]; Korro [Alpha-1 antitrypsin deficiency]; Takeda [Alpha-1 antitrypsin detection]; Vertex [Alpha-1 antitrypsin deficiency]. All of the relevant financial relationships listed have been mitigated. Peter J Barnes, DM, DSc, FRCP, FRS Grant/Research/Clinical Trial Support: AstraZeneca [Asthma, COPD]; Boehringer [COPD]; Novartis [COPD]. Consultant/Advisory Boards: AstraZeneca [Asthma, COPD]; Boehringer [COPD]; Epi-Endo [Asthma, COPD]; Novartis [COPD]; Teva [COPD]. Speaker's Bureau: AstraZeneca [Asthma]; Boehringer [COPD]; Novartis [COPD]; Teva [Asthma]. All of the relevant financial relationships listed have been mitigated. Paul Dieffenbach, MD No relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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