COPD exacerbations: Management

INTRODUCTION AND DEFINITION — 

A chronic obstructive pulmonary disease (COPD) exacerbation is characterized by an acute worsening in one or more of the following cardinal symptoms of COPD over ≤14 days:

●Cough (increase in frequency and severity)

●Sputum production (increase in volume and/or change in character)

●Dyspnea (increased level or with less activity)

Accompanying signs include tachypnea, tachycardia, hypoxemia, and impaired gas exchange. Exacerbations are associated with airway and systemic inflammation and are often caused by respiratory tract infections, pollution, or other acute airway insults. These characteristics are reflected in definitions proposed by world experts and health organizations [1,2].

The management of COPD exacerbations is discussed here. The management of stable COPD, and the diagnosis, prognosis, and prevention of COPD exacerbations are discussed separately.

●(See "Stable COPD: Overview of management".)

●(See "COPD exacerbations: Clinical manifestations and evaluation".)

●(See "COPD exacerbations: Prognosis, discharge planning, and prevention".)

INITIAL APPROACH

Confirm diagnosis and evaluate for alternative cardiopulmonary conditions — Symptoms of COPD exacerbation are not specific to COPD; therefore, patients with COPD should be carefully evaluated for coexisting or alternative conditions, particularly heart failure, myocardial ischemia, pneumonia, and pulmonary embolism. Diagnosing or excluding these conditions is important to ensure timely concurrent management. (See "COPD exacerbations: Clinical manifestations and evaluation", section on 'Additional testing' and "COPD exacerbations: Clinical manifestations and evaluation", section on 'Differential diagnosis'.)

●Cardiovascular disease – COPD and cardiovascular disease occur in similar patient groups and have overlapping symptoms. (See "Management of the patient with COPD and heart disease", section on 'Diagnosis of heart disease in patients with COPD' and "Management of the patient with COPD and heart disease", section on 'Pharmacologic treatment of cardiovascular disease in patients with COPD'.)

●Pneumonia – Respiratory infections, most commonly viral (eg, rhinovirus) or bacterial, are estimated to trigger approximately 70 percent of COPD exacerbations. (See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease" and "Management of infection in exacerbations of chronic obstructive pulmonary disease".)

●Pulmonary embolism – Pulmonary embolism should be considered in patients with severe symptoms who do not have purulent sputum or evidence of other triggers (eg, infection or heart failure), or those who have severe hypoxemia requiring high fraction of inspired oxygen (FiO₂) for correction. (See "COPD exacerbations: Clinical manifestations and evaluation", section on 'Triggers' and 'Oxygen therapy' below.)

Triage to inpatient versus outpatient care — Another important step in the initial evaluation is to determine whether the patient needs hospitalization or can be safely managed at home or in the office. While more than 80 percent of COPD exacerbations can be managed on an outpatient basis, it is important to identify patients who require a higher level of care.

Our approach is shown in the algorithm (algorithm 1) and described below [1,3].  

Patients with moderate to severe symptoms, or comorbidities — If the exacerbation appears to be life-threatening or there are indications for ventilatory support (eg, hemodynamic instability, hypoxemic or hypercapnic respiratory failure, cyanosis), the patient should be hospitalized and evaluated for intensive care needs as quickly as possible. (See 'Ventilatory support' below.)

Other considerations for possible hospitalization are consistent with those named in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and international consensus statements [1,2,4]:

●Marked increase in intensity of symptoms over baseline (eg, new onset resting dyspnea) accompanied by increased oxygen requirement

●Onset of new signs (eg, altered mental status, peripheral edema)

●Signs of respiratory distress (use of accessory respiratory muscles or paradoxical chest wall movements, or both)

●Serious comorbidities including pneumonia, cardiac arrhythmia, heart failure, uncontrolled diabetes mellitus, or kidney or liver failure

●Inadequate response to outpatient or emergency department management

●Severe airflow limitation or a history of frequent or severe exacerbations

●Frailty

●Insufficient home support

In some countries, intensive home care, which generally includes nurse visits, home oxygen, and physical therapy, has been used successfully as an alternative to hospitalization for highly selected patients with moderate to severe COPD exacerbation [5-9]. Implementation in such patients requires a dedicated support team to conduct ongoing clinical assessments and provide optimal home care. A meta-analysis of seven trials performed in the United Kingdom, Spain, and Australia noted that intensive home care of patients presenting to the hospital emergency department with acute COPD exacerbation resulted in equivalent clinical outcomes and substantial cost savings compared to hospitalization [10]. Importantly, these trials excluded patients in whom admission was obligatory as described in the British Thoracic Society Guidelines: eg, patients with an impaired level of consciousness, respiratory acidosis (arterial pH <7.35), acute electrocardiographic or chest radiographic changes, or coexisting medical morbidities. As a result, only one in four patients presenting to the hospital emergency department with acute COPD exacerbation could be considered for home management with respiratory nurse support.

Patients with mild symptoms or favorable response to treatment — Patients with mild symptoms, absence of the life-threatening or severe clinical features described in the section above, sufficient home support (stable living conditions, caregiver support, access to communication), and the ability and understanding to return to medical evaluation if deterioration occurs may be safely treated at home or in the office setting. Patients whose symptoms significantly improve after treatment in the office or emergency department may also be managed on an outpatient basis.

OUTPATIENT (HOME OR OFFICE) MANAGEMENT OF COPD EXACERBATIONS — 

Outpatient management of COPD exacerbations includes intensifying bronchodilator therapy, and in some patients, initiating a course of oral glucocorticoids and/or oral antibiotics.

Determine exacerbation severity (outpatient) — At the time of evaluation, exacerbation severity is generally determined based on vital signs and degree of dyspnea. The proposed Rome classification criteria for COPD exacerbation severity (figure 1) are reasonable to use in the primary care setting, although those with suspected severe exacerbation should be triaged to emergency care. (See 'Triage to inpatient versus outpatient care' above.)

With the proliferation of relatively reliable and inexpensive pulse oximeters, the essential information for determining exacerbation severity can also frequently be obtained from patients without an office visit.

All patients

Initiate short-acting bronchodilators (outpatient) — We recommend inhaled short-acting bronchodilator therapy for all outpatients with a COPD exacerbation:

●Inhaled short-acting beta-adrenergic agonists (SABA) – SABAs (eg, albuterol [salbutamol], levalbuterol, terbutaline) are the mainstay of therapy for an acute exacerbation of COPD because of their rapid onset of action and efficacy in producing bronchodilation [1,11,12]. We typically use SABA monotherapy, as opposed to combination SABA-SAMA, in outpatients who are on maintenance long-acting muscarinic antagonists (LAMA; eg, tiotropium, glycopyrrolate, or umeclidinium), to avoid additive anticholinergic effects. (See "Stable COPD: Initial pharmacologic management", section on 'Rescue bronchodilator therapy for all patients'.)

There are minimal data on optimal use of inhalers in acute COPD exacerbations, so dosing is based on expert opinion and extrapolation from investigations of asthma [13]. Inhaler therapy may be provided as either:

•Albuterol metered-dose inhaler (MDI) or dry powder inhaler (90 mcg/actuation): two inhalations every one to two hours for up to three doses, then every two to four hours, as needed, or

•Levalbuterol MDI (45 mcg/actuation): two inhalations every one to two hours for up to three doses, then every two to four hours, as needed

Patients with more severe COPD or difficulty with inhaler technique may prefer using albuterol or levalbuterol by nebulization at home, if they have a nebulizer device. The usual doses are:

•Albuterol (salbutamol) 2.5 mg (diluted to a total of 3 mL with sterile normal saline, resulting in 2.5 mg/3 mL or 0.083 percent): one treatment every one to two hours for up to three doses and then every two to four hours as needed based on the patient’s response, or

•Levalbuterol 0.63 to 1.25 mg (diluted to 3 mL): administered at the same intervals as noted for albuterol

•Terbutaline 5 mg (diluted to 3 mL): administered at the same intervals as noted for albuterol

Patients frequently report that bronchodilator administration via nebulizer is helpful during COPD exacerbations. However, most studies have not supported a greater effect from nebulizer treatments over properly administered metered dose inhaler medication. (See "Delivery of inhaled medication in adults", section on 'Home use'.)

●Muscarinic antagonists (in combination with SABA) – Ipratropium bromide, an inhaled short-acting muscarinic antagonist (SAMA), also known as a short-acting anticholinergic agent, may be used in combination with an inhaled SABA, eg, albuterol, in a soft mist inhaler (SMI) or in a nebulizer [1]. Ipratropium is generally not used as monotherapy due to the longer time to onset of action compared with SABAs.

We typically use combination SABA-SAMA in outpatients who are not on long-term, maintenance LAMA therapy. For patients who have a history of benign prostatic hypertrophy or prior urinary retention, LAMAs (eg, tiotropium, glycopyrrolate, umeclidinium) may increase the risk of acute urinary retention, although data are conflicting. By extension, we also do not typically use combination SABA-SAMA during exacerbations if the patient has a history of urinary retention or other anticholinergic toxicity. (See "Stable COPD: Initial pharmacologic management", section on 'Rescue bronchodilator therapy for all patients'.)

Combination therapy may be provided as:

•Ipratropium and albuterol SMI (ie, Respimat inhaler): one treatment every one to two hours (up to three doses), then every two to four hours as needed (up to six doses in the first 12 hours)

•Nebulized ipratropium 0.5 mg/2.5 mL combined with albuterol 2.5 mg/0.5 mL (total 3 mL): one treatment every one to two hours (up to three doses), then every two to four hours as needed (up to six doses in the first 12 hours)

In rare patients intolerant of SABAs who use ipratropium as monotherapy, the doses are:

•Ipratropium metered dose inhaler (MDI): two inhalations every four to six hours, or

•Nebulized ipratropium: 0.5 mg/2.5 mL (0.02 percent; one unit-dose vial) every six to eight hours

The evidence for adding a SAMA to SABA is based on a few studies in which combination therapy produced greater bronchodilation than achieved by either agent alone in patients with a COPD exacerbation or stable COPD [14,15]. However, this finding has not been universal, and other studies have not found an additive effect in COPD exacerbations [16,17]. A longer duration of bronchodilation has been observed with the addition of ipratropium to albuterol in stable COPD [18]. Regardless of delivery method, we typically avoid using more than six doses of closely spaced ipratropium (ie, over the first 12 hours) to avoid the risk of anticholinergic side effects.

Continue long-acting bronchodilators — While continuation of ongoing therapy with long-acting beta agonists (LABAs) or LAMAs has not been specifically studied, we continue these therapies, which is consistent with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy [1].

Test for influenza and SARS-CoV-2 — For patients with a COPD exacerbation during influenza season, we screen for influenza infection, with a preference for molecular assays over rapid antigen tests. If influenza infection is suspected, we initiate empiric antiviral therapy in cases where timely laboratory confirmation is not readily available or accessible. (See "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Respiratory virus treatment' and "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

We also have low threshold to test for COVID-19. Infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the cause of coronavirus disease-2019 (COVID-2019), can coexist with, or result in, a COPD exacerbation. If an exacerbation of COPD occurs concurrently with COVID-19, the usual guidelines for initiation of systemic glucocorticoids for a COPD exacerbation should be followed as delaying therapy can increase the risk of worsening exacerbation. Patients with COPD are at increased risk for severe respiratory illness associated with COVID-19 and are candidates for COVID-19-specific therapy (table 1). Diagnosis and treatment of COVID-19 are discussed separately. (See "COVID-19: Diagnosis" and "COVID-19: Evaluation and management of adults with acute infection in the outpatient setting".)

Adjunctive care — For patients being managed at home, supportive care often includes advice regarding cigarette smoking cessation and medication adherence. Some patients may need nutritional support and a review of goals of care. Patients who have a new requirement for supplemental oxygen are usually managed in the hospital, at least initially. (See 'Triage to inpatient versus outpatient care' above and "Overview of smoking cessation management in adults" and "Malnutrition in COPD and other advanced lung disease" and "Pulmonary rehabilitation".)

Monitoring — We advise patients who are being managed at home to monitor their breathing, fatigue, ability to perform daily activities, color and quantity of sputum, mental status, and temperature. We advise them to seek immediate medical care if they develop severe shortness of breath at rest, chest pain, hemoptysis, fevers or chills, cyanosis, or altered mental status [19].

Patients with moderate severity exacerbations

Glucocorticoids (outpatient) — We typically prescribe glucocorticoids to outpatients with moderate severity exacerbations per the Rome classification for exacerbations [2]. Moderate exacerbations are defined by having ≥3 of 5 of the following criteria (figure 1):  

●Dyspnea ≥5 on visual analog scale

●Respiratory rate ≥ 24

●Heart rate ≥ 95

●Resting oxygen saturation ≤ 92 percent on usual oxygen amount

●C-reactive protein ≥ 10mg/dL

Oral glucocorticoids are most commonly used. Inhaled glucocorticoids are an alternative option.

●Oral glucocorticoids – For outpatients with at least moderate severity COPD exacerbation, we typically use a dose that is the equivalent of prednisone 40 mg per day for five days, consistent with current guidelines [1,3,12]. Patients should be warned of potential adverse effects of systemic glucocorticoids that may require mitigation, particularly hyperglycemia (in patients with diabetes mellitus), fluid retention, and hypertension. (See "Major adverse effects of systemic glucocorticoids".)

•Optimal duration – The optimal duration of glucocorticoid therapy is between 5 and 14 days. Occasionally, patients may benefit from a higher dose or a longer course depending on the severity of the exacerbation and response to prior courses of glucocorticoids. The REDUCE trial showed that a five-day course of methylprednisolone (administered intravenously on day one, orally thereafter) was noninferior to a 14-day course with respect to the risk of recurrent exacerbation over six months of follow-up [20]. Although over 90 percent of the patients in the trial were initially admitted, these findings can likely be extrapolated to the less ill outpatient population. (See 'Glucocorticoids (inpatient)' below.)

•Efficacy – Systemic glucocorticoid therapy in outpatients appears to have a small but beneficial effect, including decreased return to the emergency department, improved dyspnea, and improved forced expiratory volume in one second (FEV₁). In a placebo-controlled randomized trial of 147 patients discharged from the emergency department after presenting with an acute exacerbation of COPD, patients who received oral prednisone (40 mg for 10 days) were less likely to return to the emergency department or their clinician with increasing dyspnea within 30 days (27 versus 43 percent) [21] (figure 2). Prednisone therapy was also associated with decreased dyspnea and a greater improvement in FEV₁ (34 versus 15 percent increase from baseline) on day 10.

•Use of eosinophils to guide patient selection – Given the risk of adverse effects with systemic glucocorticoids, there is interest in a more selective approach to choosing patients for therapy. Patients with elevated eosinophil counts at the time of exacerbation may be more likely to benefit from steroids [22-24]. We feel that further study is necessary before widespread adoption of an eosinophil-directed treatment strategy.

In the STARR2 trial, patients presenting to a primary care clinic with COPD exacerbation were assigned to either an eosinophil-based triage strategy, or to standard therapy with a 14-day course of glucocorticoids, regardless of eosinophil status. Eosinophil-based triage (BET) was performed by providing patients with relative eosinophilia (≥2 percent) 14 days of systemic glucocorticoids (30 mg of oral prednisolone daily) and placebo if eosinophil count was <2 percent [22]. BET was found to be non-inferior to standard therapy, with 40 percent fewer treatment failures in the BET group compared with standard therapy (RR 0.60, 95% CI 0.33-1.04, upper margin of 1.105 defined as the non-inferiority margin). In those without eosinophil elevation, glucocorticoid treatment did not improve and may have worsened respiratory symptoms and treatment failure rates. However, some adverse effects may have arisen from the relatively long glucocorticoid treatment course used, and the need for point-of-care blood testing may be a significant barrier to implementation in some primary care settings.

●Inhaled glucocorticoids as an alternative option – Some trials suggest that high-dose inhaled glucocorticoids may be a reasonable alternative to systemic therapy. We use this approach in patients with severe adverse effects (eg, uncontrolled hyperglycemia, psychosis) when using short-term systemic glucocorticoids.

Several trials have examined high-dose budesonide as an alternative to systemic glucocorticoids for COPD exacerbations, but have largely studied hospitalized patients and have examined physiologic outcomes, such as FEV₁ improvement [25,26]:

•In one of the few outpatient trials, comprising 109 patients presenting to primary care with a COPD exacerbation, the use of the high-dose combination inhaler, budesonide-formoterol (320 mcg-9 mcg) one inhalation four times daily, resulted in a similar change in FEV₁ compared with oral prednisolone 30 mg daily plus inhaled formoterol [27].

•In a systematic review and meta-analysis (9 trials, nearly 1000 patients) of inpatients, high-dose nebulized budesonide (4 to 8 mg/day) had a similar effect as oral glucocorticoids in patients hospitalized for a COPD exacerbation for change in FEV₁ (weighted mean difference 0.05 L/sec [95% CI -0.01 to 0.12]) or arterial tension of carbon dioxide (PaCO₂), but was slightly inferior for oxygenation improvement [25].

•A separate meta-analysis showed no significant difference between inhaled and systemic glucocorticoids in terms of treatment failure, although outcomes numerically favored systemic glucocorticoids (5.1 versus 2.7 percent, relative risk [RR] 1.75, 95% CI 0.8-4.0 in five trials of 569 patients) [28]. Hyperglycemia was significantly more frequent in those using systemic glucocorticoids (RR 0.3, 95% CI 0.15-0.5 in nine trials of 1114 patients).

Patients with ≥2 cardinal exacerbation symptoms

Antibiotics (outpatient) — Empiric antibiotic therapy is appropriate for outpatients with a COPD exacerbation and ≥2 of 3 cardinal symptoms: increased dyspnea, increased sputum volume/viscosity, or increased sputum purulence.

Our approach is largely consistent with the GOLD strategy, which maximizes the benefit of antibiotic therapy by restricting its use to those patients who are most likely to have bacterial infection [1]. The role of antibiotics in exacerbations of COPD, including antibiotic selection, is discussed in detail separately. (See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease", section on 'Features that suggest bacterial infection' and "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Indications for antibacterial therapy'.)

Patients without these risk factors should not receive empiric antibiotic therapy, unless radiographic or microbiologic evidence of pulmonary infection is present. The choice of empiric therapy in appropriate candidates for treatment varies based on both patient-specific factors and local resistance patterns (algorithm 2 and table 2).

EMERGENCY DEPARTMENT AND HOSPITAL MANAGEMENT — 

Similar to at-home management, the major components of emergency department or in-hospital management of exacerbations of COPD include reversing airflow limitation with inhaled short-acting bronchodilators and systemic glucocorticoids, treating infection, ensuring appropriate oxygenation, and averting intubation and mechanical ventilation [1,29].

A rapid overview of emergency management of severe exacerbations of COPD is summarized in the table (table 3).

Classify exacerbation severity (inpatient) — For patients who are admitted to the hospital, the severity of the exacerbation is classified based on clinical signs [1,2]:

●No respiratory failure – Respiratory rate ≤24 breaths per minute; heart rate (HR) <95 beats per minute; no use of accessory respiratory muscles; no change in mental status; pulse oxygen saturation (SpO₂) 88 to 92 percent with Venturi mask 24 to 35 percent inspired oxygen (or equivalent); no hypercapnia.

●Acute non-life-threatening respiratory failure – Respiratory rate >24 breaths per minute; use of accessory muscles of respiration; no change in mental status; SpO₂ 88 to 92 percent with Venturi mask 24 to 35 percent (or equivalent); arterial tension of carbon dioxide (PaCO₂) 50 to 60 mmHg or increased over baseline.

●Acute life-threatening respiratory failure – Respiratory rate >24 breaths per minute; use of accessory muscles of respiration; acute change in mental status; requiring fraction of inspired oxygen (FiO₂) ≥40 percent to maintain SpO₂ 88 to 92 percent; PaCO₂ increased compared with baseline or >60 mmHg or associated with acidosis (pH ≤7.25).

This classification differs from the Rome classification for COPD exacerbation severity (with severity classified as mild, moderate, or severe), which is typically used in outpatients or patients initially evaluated in a primary care setting (figure 1).

All patients

Monitoring — In-hospital monitoring typically includes frequent assessment of respiratory status (eg, respiratory rate and effort, wheezing, pulse oxygen saturation), heart rate and rhythm, blood pressure, and fluid status. Arterial blood gas measurement is performed selectively to assess for respiratory acidosis (eg, prior hypercapnia, severe exacerbation, or deterioration of patient's respiratory status during treatment), confirm the accuracy of pulse oxygen saturation, and monitor known hypercapnia. (See "Simple and mixed acid-base disorders", section on 'Respiratory acid-base disorders'.)

Patients who require admission to the intensive care unit (ICU) should have continuous monitoring of vital signs and oxygenation.

Initiate short-acting bronchodilators (inpatient) — In all patients with exacerbations that require emergency department or hospital-based treatment, we suggest use of the combination of a short-acting muscarinic antagonist (SAMA; eg, ipratropium) and short-acting beta-adrenergic agonists (SABA), primarily based on the benefit of dual therapy seen in stable COPD [1,17,30]. There are minimal data on optimal use of inhalers in acute COPD exacerbations, so dosing is based on expert opinion and extrapolation from investigations of asthma [13]. We typically stop a patient’s home long-acting bronchodilators while SAMA and SABA are administered in the hospital and resume them when the patient improves. (See 'Resuming long-acting bronchodilators' below.)

●Nebulizer versus metered dose inhaler (MDI) therapy – In hospitalized patients, we favor nebulized therapy because many patients with COPD have difficulty using proper MDI technique in the setting of exacerbation. Air-driven nebulizers are preferred over oxygen-driven nebulizers to minimize the risk of oxygen-induced hypercapnia [31,32]. In patients with potential viral infections resulting in COPD exacerbation, nebulized medications should be administered in accordance with local infection prevention protocols. (See "Delivery of inhaled medication in adults", section on 'Infection control'.)

●SAMA-SABA combination therapy

If administered via nebulizer (preferred):

•Ipratropium 0.5 mg/2.5 mL combined with albuterol 2.5 mg/0.5 mL (total 3 mL): one treatment every one to two hours up to three doses, then every two to four hours as needed (up to six doses in the first 12 hours).

If administered via inhaler:  

•Ipratropium and albuterol soft mist inhaler (SMI; ie, Respimat inhaler): one inhalation every one to two hours for up to three doses and then every two to four hours as needed (up to six doses in the first 12 hours), guided by the response to therapy [33].

•Ipratropium is also available in an MDI (for use in combination with albuterol MDI or nebulizer): two to four inhalations given with a spacer every one to two hours for up to three doses, and then every two to four hours as needed (up to 12 inhalations in the first 12 hours). (See "Stable COPD: Initial pharmacologic management", section on 'Rescue bronchodilator therapy for all patients'.)

Regardless of delivery method, we typically avoid using more than six doses of closely spaced ipratropium (ie, over the first 12 hours) to avoid the risk of anticholinergic side effects. Rarely, additional doses of albuterol alone may be given if additional bronchodilation is felt to be required.  

Combination therapy with albuterol and ipratropium is superior to albuterol alone in stable COPD, though studies in acute exacerbations are limited [15,17]. A systematic review identified a small number of trials that compared a combination of SAMA (ipratropium) plus SABA (albuterol, metaproterenol, fenoterol) with SABA alone and did not find an added benefit to the combination when assessed at 90 minutes [17]. Nevertheless, this combination is often used to treat COPD exacerbations given extensive evidence of superior bronchodilation in longer-term studies.

●SABA therapy alone

We do not typically give SABA monotherapy to hospitalized patients, unless there are clear side effects to SAMA (eg, urinary retention, anticholinergic toxicity) or if additional bronchodilation is needed after ipratropium dosing limits are reached.

If administered via nebulizer (preferred), either:

•Albuterol 2.5 mg (diluted to a total of 3 mL with sterile normal saline, resulting in 2.5 mg/3 mL or 0.083 percent): one treatment every one to two hours for up to three doses and then every two to four hours as needed, guided by the response to therapy [1], or

•Levalbuterol at equipotent doses (ie, 1.25 mg in 3 mL sterile saline for nebulization) with the same frequencies

•Terbutaline at equipotent doses (ie, 5 mg in 3 mL sterile saline for nebulization) with the same frequencies

If administered via inhaler, either:  

•Albuterol MDI or dry powder inhaler (90 mcg/actuation): two inhalations (most commonly two, occasionally four) with a spacer every one to two hours for up to three doses and then every two to four hours as needed, guided by the response to therapy. For patients requiring mechanical ventilation, up to eight inhalations may be given (see "The use of inhaler devices in adults", section on 'Patients receiving intensive respiratory support'), or

•Levalbuterol at equipotent doses (45 mcg per inhalation via MDI) with the same frequencies.

Placebo-controlled trials are lacking for SABAs in acute COPD exacerbation, so the main evidence comes from long-term clinical experience and extrapolation from the treatment of asthma and stable COPD. Increasing the dose of nebulized albuterol to 5 mg does not have a significant benefit on spirometry or clinical outcomes [34]. Similarly, continuously nebulized beta-agonists have not been shown to confer an advantage in COPD and may increase adverse effects.

It is not known whether a rapid-onset, long-acting beta-agonist, such as formoterol or indacaterol (where available), would be a reasonable substitute for albuterol nebulizer treatments in patients not already using indacaterol [35].

Resuming long-acting bronchodilators — We typically resume or start long-acting bronchodilators (and inhaled corticosteroids when indicated), once the patient’s symptoms improve and breathing allows proper technique for administration of these inhaled therapies. This is consistent with the GOLD strategy, which considers this an opportunity to review inhaler use and provide smooth transition to outpatient care [1].

Test for influenza and SARS-CoV-2 — As in outpatients, evaluation and treatment for coexisting viral respiratory infection should be conducted. (See 'Test for influenza and SARS-CoV-2' above.)

In patients with clinical and laboratory evidence of influenza infection who require hospitalization for an exacerbation of COPD, we promptly administer antiviral therapy. Because of the risk of acute bronchoconstriction with inhalation of zanamivir, oral oseltamivir is preferred unless local resistance patterns suggest a likelihood of oseltamivir-resistant influenza. Antiviral treatment of influenza is discussed in detail separately. (See "Seasonal influenza in nonpregnant adults: Treatment".)

Information regarding antiviral resistance that emerges during the influenza season is available through the United States Centers for Disease Control and Prevention. Clinicians should review antiviral resistance patterns for updated antiviral recommendations, should resistant strains emerge.

COPD is associated with a greater likelihood of ICU admission, mechanical ventilation, or death among patients with COVID-19 due to SARS-CoV-2 [36-38]. Potential treatments for hospitalized patients with SARS-coronavirus-2 infection (COVID-19) are discussed separately. (See "COVID-19: Management in hospitalized adults" and "COVID-19: Management of the intubated adult".)

Oxygen therapy — Supplemental oxygen is a critical component of acute therapy. The target is an SpO₂ of 88 to 92 percent or an arterial oxygen tension (PaO₂) of 60 to 70 mmHg to minimize the risk of worsening hypercapnia with excess supplemental oxygen [1,29,39]. However, hypercapnia is generally well tolerated in patients whose PaCO₂ is chronically elevated, so we aim for these targets, even if it leads to worsened hypercapnia. If hypercapnia is associated with altered mental status, severe acidemia, or cardiac dysrhythmias, mechanical ventilation may be required. (See 'Ventilatory support' below and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure" and "Adverse effects of supplemental oxygen", section on 'Accentuation of hypercapnia'.)

A high FiO₂ is generally not required to correct the hypoxemia associated with exacerbations of COPD. Inability to correct hypoxemia with a relatively low FiO₂ (eg, 4 L/min by nasal cannula or 35 percent by mask) should prompt consideration of an additional cause of hypoxemia, such as pulmonary emboli, acute respiratory distress syndrome, pulmonary edema, or severe pneumonia. (See "Measures of oxygenation and mechanisms of hypoxemia".)

●Methods of delivery – There are numerous devices available to deliver supplemental oxygen during an exacerbation of COPD:

•Traditional nasal cannulas can provide flow rates up to 6 L per minute with an estimated associated FiO₂ of approximately 40 percent (table 4); though FiO2 with nasal cannula is highly dependent on the patient’s breathing pattern (based on how much ambient air is inhaled). Newer nasal cannulas (often green colored) may provide up to 15 L per minute (as their connectors to the wall outlet are more resistant to pop-off). They are more comfortable and convenient for the patient, especially during oral feedings.

•If a higher FiO₂ is needed, simple facemasks can provide an FiO₂ up to approximately 55 percent using flow rates of 6 to 10 L per minute. However, similar to nasal cannulas, variations in minute ventilation and inconsistent entrainment of room air affect the FiO₂ when simple facemasks are used.

•Venturi masks permit a precise upper limit for the FiO₂, which may be preferable for patients at risk of hypercapnia with excess oxygen delivery. Venturi masks can deliver an FiO₂ of 24, 28, 31, 35, 40, or 60 percent.

•Nonrebreathing masks with a reservoir, one-way valves, and a tight face seal can deliver an FiO₂ of up to 90 percent, though this level of oxygen support is rarely needed for COPD exacerbation alone.

•High-flow nasal cannula (HFNC) provide supplemental oxygen (with adjustable FiO₂) at a high flow rate (up to 60 L/min that results in a low level of continuous positive airway pressure). The specific indications for HFNC remain unclear, and robust comparisons of HFNC with noninvasive ventilation (NIV) in patients with COPD exacerbations are lacking [1,40,41]. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications".)

●Evidence of efficacy – In one small randomized trial, titrating supplemental oxygen to a target of SpO₂ 88 to 92 percent resulted in lower mortality compared with high-flow (non-titrated) oxygen in the prehospital setting [39]. In a separate retrospective analysis, 1027 COPD patients who received supplemental oxygen at admission were divided into groups based on oxygen saturation at admission [42]. Compared with the SpO₂ 88 to 92 percent group, the adjusted risk of death in the SpO₂ 93 to 96 and 97 to 100 percent groups was higher (adjusted odds ratio 1.98, 95% CI 1.09-3.60 and 2.97, 95% CI 1.58-5.58, respectively). No studies have compared the effect of titrating oxygen with saturation targets during the hospital stay for a COPD exacerbation. (See "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure".)

Glucocorticoids (inpatient) — For nearly all patients requiring emergency department or hospital-based treatment for a COPD exacerbation, we recommend a course of systemic glucocorticoids. Occasional patients who present to the emergency department with a mild exacerbation (figure 1) and do well with initial bronchodilator therapy can avoid glucocorticoid administration.

●Route – Intravenous (IV) glucocorticoids are typically administered to those who present with a severe exacerbation, have not responded to oral glucocorticoids at home, are unable to take oral medication, or who may have impaired absorption due to decreased splanchnic perfusion (eg, patients in shock).

In patients who do not require IV steroids, oral glucocorticoids are administered and appear to be equally efficacious to IV administration for treating most exacerbations of COPD [11,43,44]. They are rapidly absorbed (peak serum levels achieved at one hour after ingestion) with virtually complete bioavailability. In a systematic review of randomized trials, no significant differences were detected in the primary outcomes of treatment failure, relapse, or mortality, or for any secondary outcomes in patients who received parenteral glucocorticoids compared with oral glucocorticoids [43].

●Dose – The optimal dose of systemic glucocorticoids for treating a COPD exacerbation is unknown, and likely depends on individual patient factors [1,11]. For non-critically ill hospitalized patients, we typically use the equivalent of prednisone 40 mg once daily (table 5) for five days, consistent with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [1]. For critically ill patients, we initially use a higher dose of methylprednisolone 60 mg twice daily, and start tapering after 48 to 72 hours, although the optimal approach is not known [20,44,45]. When using higher doses in critically ill patients, tapering quickly to more typical doses after initial response is important to avoid hyperglycemia and other acute glucocorticoid adverse effects.

A growing body of evidence favors using moderate-dose rather than high-dose glucocorticoids for most patients with an exacerbation of COPD. As an example, a comparative analysis of glucocorticoid dosing examined outcomes of nearly 80,000 patients admitted to the hospital with an exacerbation of COPD, excluding those requiring intensive care [45]. The median glucocorticoid dose administered in the first two days was 60 mg of prednisone equivalents for those on oral therapy and 600 mg for intravenous therapy. The risk of treatment failure was no greater with the lower dose (OR 0.93, 95% CI 0.84-1.02). As this was an observational study and did not include objective measures of airflow limitation, it is possible that less ill patients were more likely to receive oral treatment.

On the other hand, for patients with impending or actual acute respiratory failure due to a COPD exacerbation, many clinicians use an intravenous formulation at a higher dose, such as the equivalent of methylprednisolone 60 mg intravenously, one to four times daily, although outcomes data to support this practice are limited. In an observational cohort study, among over 17,000 patients admitted to an ICU with a COPD exacerbation, a methylprednisolone dose of 240 mg/day or less, compared with a higher dose (>240 mg/day), was not associated with a mortality benefit, but was associated with slightly shorter hospital (-0.44 days; 95% CI -0.67 to -0.21) and ICU (-0.31 days; 95% CI -0.46 to -0.16) lengths of stay [46]. Length of mechanical ventilation and need for insulin therapy were also lower in the lower dose group. As this was an observational study, further research is needed to determine the optimal glucocorticoid dose in this setting.

●Duration – The optimal duration of systemic glucocorticoid therapy is not clearly established and often depends on the severity of the exacerbation and the observed response to therapy [1,11,47-49]. We typically treat for five days for non-critically ill hospitalized patients, with longer durations for more severe disease. A range of 5 to 14 days appears reasonable, in line with GOLD and European Respiratory Society/American Thoracic Society guidelines [1,11].

•Data in support of a 14-day course, rather than a longer duration, come from the Systemic Corticosteroids in COPD Exacerbations (SCCOPE) trial, which compared two- and eight-week regimens and found no additional benefit to the longer course [50]. Patients in the eight-week group experienced more glucocorticoid-related side effects.

•A systematic review compared different durations of systemic glucocorticoid therapy (eight studies, 457 participants) and found no difference in the risk of treatment failure with courses of three to seven days compared with longer courses of 10 to 15 days (OR 1.04, 95% CI 0.70-1.56) [47]. The systematic review concluded that a five-day course of oral glucocorticoids is probably comparable to a 14-day or longer course, but that further research is needed to conclude equivalence. One representative trial included in the review, the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial, evaluated prednisone 40 mg daily for 5 or 14 days [20]. No difference was noted in the time to the next exacerbation, the likelihood of an exacerbation in the subsequent 180 days, or the recovery of lung function. The mean cumulative prednisone dose was significantly higher in the 14-day group, but treatment-related adverse effects, such as hyperglycemia and hypertension, were not different between the groups.

•An emerging strategy for determining dose and duration of systemic glucocorticoid therapy in the hospital is the use of blood eosinophilia for titration. In the CORTICO-COP study, 318 patients hospitalized for acute COPD exacerbation were randomized to eosinophil-guided versus standard therapy [23]. The intervention group, after receiving an initial IV dose, received an up to four-day course of oral corticosteroid therapy, only on days the daily blood eosinophil count exceeded 300 cells/microL. Standard therapy group received a full five-day course of corticosteroids. Eosinophil-guided therapy was noninferior to standard treatment in days alive and out of hospital within 14 days of treatment (absolute difference -0.4 days, 95% CI -1.3 to 0.5). There was a 60 percent reduction in cumulative prednisolone dose and less hyperglycemia in the intervention group. We await additional study to further clarify the potential benefits and risks of this approach prior to implementation.  

●Discontinuation – At the end of the treatment course, glucocorticoid therapy may be discontinued rather than tapered, if the patient has substantially recovered. Alternatively, the dose may be tapered over another seven days, as a trial to determine whether a longer course of glucocorticoid therapy is required. However, long-term systemic glucocorticoids should rarely be used for stable COPD if therapy is otherwise optimized. Tapering solely because of concerns about adrenal suppression is not necessary if the duration of therapy is less than two or three weeks (a duration too brief to cause adrenal atrophy). (See "Management of refractory chronic obstructive pulmonary disease", section on 'The limited role for systemic glucocorticoids in refractory disease' and "Glucocorticoid withdrawal".)

●Efficacy – Systemic glucocorticoids, when added to the bronchodilator therapies described above, improve symptoms and lung function, and decrease the length of hospital stay [1,20,43,50,51]. In a systematic review and meta-analysis of nine studies (917 participants), systemic glucocorticoids reduced the risk of treatment failure by over 50 percent compared with placebo (OR 0.48, 95% CI 0.35-0.67) and, in two studies (415 participants), reduced the risk of relapse at one month (hazard ratio 0.78, 95% CI 0.63-0.97) [43]. For every nine treated participants, one treatment failure was avoided. Patients in the glucocorticoid group showed improvement in forced expiratory volume in one second (FEV₁) up to 72 hours after initiation, though not after that time point. Hospital stay was significantly shorter with glucocorticoid treatment (mean difference -1.22 days, 95% CI -2.26 to -0.18). Mortality up to 30 days was not decreased by systemic glucocorticoids. The risk of hyperglycemia was significantly increased with glucocorticoids compared with placebo (odds ratio 2.79, 95% CI 1.86-4.19).

●Adverse events – Even short courses of systemic glucocorticoids are associated with an increased risk of harm, such as hyperglycemia, pneumonia, sepsis, venous thromboembolism, and fracture. The adverse effects of systemic glucocorticoids and their mitigation are discussed separately. (See "Major adverse effects of systemic glucocorticoids".)

Antibiotics (inpatient) — We give antibiotics for patients with a COPD exacerbation requiring hospitalization, consistent with most clinical practice guideline recommendations [1,11,52]. The optimal antibiotic regimen for the treatment of COPD exacerbations has not been determined. We use a "risk stratification" approach when selecting initial antibiotic therapy, providing a broader antibiotic regimen for patients at risk for resistant organisms (algorithm 3). The rationale, diagnosis, and treatment of infection in exacerbations of COPD, including antibiotic selection, are discussed separately. (See "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Summary and recommendations' and "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease", section on 'Summary and recommendations'.)

Supportive care — Supportive care for patients hospitalized with an exacerbation of COPD includes the following therapies, as needed:

●Cigarette smoking cessation – Hospitalization can sometimes provide an opportunity for patients who continue to smoke to move towards cigarette smoking cessation. Nicotine replacement therapy can help reduce symptoms of nicotine withdrawal during hospitalization. (See "Pharmacotherapy for smoking cessation in adults".)

●Thromboprophylaxis – Hospitalization for exacerbations of COPD increases the risk for deep venous thrombosis and pulmonary embolism [1]. For patients without a risk factor for bleeding who require ICU admission, we recommend pharmacologic thromboprophylaxis; for those not requiring ICU admission, we suggest pharmacologic thromboprophylaxis. Low molecular weight heparin is generally preferred. Preventive measures are discussed in greater detail separately. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)

●Monitoring of fluid balance – As in other hospitalized patients, we cautiously monitor fluid balance and avoid volume overload, which may worsen respiratory symptoms, particularly in patients with concurrent heart failure. (See "Maintenance and replacement fluid therapy in adults", section on 'Summary and recommendations'.)

●Nutritional support – Oral nutritional supplementation may be of benefit for undernourished patients hospitalized with a COPD exacerbation. (See "Malnutrition in COPD and other advanced lung disease", section on 'Frequency of malnutrition'.)

Adjunctive therapies for patients with respiratory failure

Magnesium sulfate — For patients who present with respiratory failure, or a severe exacerbation that is not responding promptly to short-acting inhaled bronchodilators, we suggest intravenous administration of a single dose of magnesium sulfate (2 g infused over 20 minutes). Intravenous magnesium sulfate has bronchodilator activity thought to arise from inhibition of calcium influx into airway smooth muscle cells [53]. The best evidence for benefit in COPD exacerbations comes from a systematic review (3 studies, 170 participants) that found a decrease in hospitalizations with intravenous magnesium compared with placebo (odds ratio [OR] 0.45, 95% CI 0.23-0.88) [54], which is similar to or better than the effect seen in severe asthma exacerbations [55]. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Magnesium sulfate'.)

Intravenous magnesium has an excellent safety profile; however, it is contraindicated in the presence of kidney insufficiency, and hypermagnesemia can result in muscle weakness. (See "Hypermagnesemia: Causes, symptoms, and treatment", section on 'Symptoms of hypermagnesemia'.)

Ventilatory support — For patients who have life-threatening exacerbations, respiratory failure, or do not improve with supportive therapy with pharmacotherapy and oxygen, ventilatory support is necessary assuming this is consistent with the patient’s goals of care (see 'Palliative care' below). High flow nasal cannula (HFNC) is not routinely administered in patients with acute exacerbations of COPD, although some experts administer it cautiously in this population prior to the application of noninvasive ventilation (NIV; also known as noninvasive positive pressure ventilation [NPPV]). (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications".)

●Noninvasive ventilation – NIV, or NPPV, refers to mechanical ventilation delivered through a noninvasive interface, such as a face mask, nasal mask, orofacial mask, or nasal prongs (nasal pillows). NIV reduces mortality and the intubation rate and is the preferred method of ventilatory support in many patients with an exacerbation of COPD [11].

Most commonly, NIV is initiated in the emergency department, ICU, or a specialized respiratory unit to enable close monitoring, although this has not been formally studied and varies among hospitals. Patients who develop acute or acute-on-chronic respiratory acidosis (as characterized frequently by PaCO₂ >45 mmHg [6 kPa] and pH <7.35) are the subgroup who are most likely to benefit from an initial trial of NIV. Bilevel positive airway pressure is typically used. For other patients with non-hypercapnic respiratory failure due to COPD exacerbation, a trial of NIV is also appropriate, although the derived benefit may be considerably less. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

A reasonable approach is to initiate bilevel NIV in a spontaneously triggered mode with a backup respiratory rate (eg, 8 breaths/minute); typical initial settings include an inspiratory positive airway pressure (IPAP) of 8 to 12 cm H₂O and an expiratory pressure (EPAP) of 3 to 5 cm H₂O. NIV is discussed in detail separately. (See "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Acute exacerbation of chronic obstructive pulmonary disease with hypercapnic respiratory acidosis'.)

●Invasive ventilation – Invasive mechanical ventilation should be administered when patients fail NIV, do not tolerate NIV, or have contraindications to NIV. Invasive mechanical ventilation for acute respiratory failure due to a COPD exacerbation is discussed separately. (See "Invasive mechanical ventilation in acute respiratory failure complicating chronic obstructive pulmonary disease".)

Palliative care — The goals of palliative care are to prevent and relieve suffering and aid in the end-of-life care of patients with advanced disease. Some patients may have had a goals of care discussion with their physician and will have an advance directive in place. For those who do not have an advance directive, it is helpful for patients, their families, and their health care providers to review the patient’s understanding of their diagnosis and expected disease course, and then reflect on the patient’s goals, values, and beliefs. This information is used to inform decision-making in the context of care that is medically reasonable and appropriate. (See "Discussing goals of care" and "Advance care planning and advance directives" and "Palliative care for adults with nonmalignant chronic lung disease" and "Palliative care: Issues in the intensive care unit in adults".)

For patients with COPD, an important component of decision-making is whether intubation and mechanical ventilation are appropriate and desirable in the event of respiratory failure. When discussing a potential trial of mechanical ventilation for an exacerbation of COPD, parameters for discontinuing mechanical ventilation should be included. The potential outcomes of intubation/mechanical ventilation should be described to help the patient’s decision-making. While prognostic uncertainty and variable trajectory of illness make communication about these issues difficult [56], it is important to incorporate this uncertainty into advance care planning.

Given the high one-year mortality rate after hospitalization for a COPD exacerbation, it may be appropriate to consider a palliative care referral during or shortly after a hospitalization for COPD. Palliative care consultation can help explore the patient's understanding of their illness and prognosis, assess and manage symptoms (eg, dyspnea, anxiety, panic, depression), discuss the patient's goals of care, place of death preferences, and advance directives, and help implement end-of-life care. (See "Palliative care for adults with nonmalignant chronic lung disease" and "Assessment and management of dyspnea in palliative care".)

Adjusting therapy for poor response — In patients who do not respond as we would expect (with improvement in cardinal symptoms and signs of COPD exacerbation, oxygen requirement, etc over one to two days), we perform the following actions:

●Evaluate for conditions that might contribute to or mimic symptoms and signs of a COPD exacerbation, such as viral respiratory tract infection, pneumonia, pulmonary emboli, pneumothorax, heart failure, dysrhythmias, tracheomalacia, diaphragmatic dysfunction, and intraabdominal processes limiting diaphragmatic excursion. Testing may include complete blood count and differential, serum brain natriuretic peptide, microbiologic testing, lower extremity compression ultrasonography for deep venous thrombosis, transthoracic echocardiogram, chest radiograph, and/or computed tomography with pulmonary angiography (unless contrast is contraindicated). (See "COPD exacerbations: Clinical manifestations and evaluation", section on 'Differential diagnosis'.)

●Optimize the schedule for delivery of inhaled medications to ensure doses are not being missed.

●Ask patients about continued smoking and discuss ways to reduce or stop smoking.

DISCHARGE PLANNING — 

Ideally, comprehensive discharge planning will help speed symptom resolution and reduce readmissions for COPD exacerbations. However, the optimal components of discharge planning have not been determined, so discharge-related decision-making is largely guided by good medical practice, as described separately. (See "COPD exacerbations: Prognosis, discharge planning, and prevention".)

A meta-analysis of 13 randomized trials of pulmonary rehabilitation within four weeks of hospitalization for acute exacerbation of COPD showed benefits of reduced mortality and hospital readmissions and enhanced healthcare-related quality of life and walking distance [57]. (See "Pulmonary rehabilitation", section on 'Benefits'.)

TREATMENTS WITHOUT DOCUMENTED BENEFIT — 

Mucoactive agents, methylxanthines, and mechanical techniques to augment sputum clearance have not been shown to confer benefit for patients with a COPD exacerbation.

●Mucoactive agents – There is little evidence supporting the use of mucoactive agents (eg, N-acetylcysteine) in exacerbations of COPD [58-60]. Some mucoactive agents may worsen bronchospasm. (See "Role of mucoactive agents and secretion clearance techniques in COPD".)

The lack of efficacy of mucoactive agents in the treatment of COPD exacerbations was best demonstrated by a double-blind trial that randomly assigned 50 patients with a COPD exacerbation to receive N-acetylcysteine (600 mg, twice daily) or placebo for seven days [60]. There was no difference in the rate of change of forced expiratory volume in one second (FEV₁), vital capacity, oxygen saturation, breathlessness, or length of stay between the two groups.

●Methylxanthines – The methylxanthines, aminophylline and theophylline, have not been found to be effective for COPD exacerbations [1]. Randomized trials of intravenous aminophylline in this setting have failed to show efficacy beyond that induced by inhaled bronchodilator and glucocorticoid therapy. In addition to lack of efficacy, methylxanthines caused significantly more nausea and vomiting than placebo and trended toward more frequent tremor, palpitations, and arrhythmias.

●Nebulized magnesium – Nebulized isotonic magnesium (151 mg per dose) had no effect on FEV₁ when added to nebulized salbutamol (albuterol) in one study of patients with COPD exacerbations [61]. A subsequent systematic review including four additional studies found no effect of nebulized magnesium on hospital admission or the need for invasive or noninvasive breathing support [54].

●Chest physiotherapy – Mechanical techniques to augment sputum clearance, such as directed coughing, chest physiotherapy with percussion and vibration, intermittent positive pressure breathing, and postural drainage, have not been shown to be beneficial in COPD and may provoke bronchoconstriction. Their use in COPD exacerbations (in the absence of bronchiectasis) is not supported by clinical trials [1,58,59].

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^th to 6^th 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^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

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.)

●Basics topics (see "Patient education: Chronic bronchitis (The Basics)" and "Patient education: Medicines for COPD (The Basics)")

●Beyond the Basics topics (see "Patient education: Chronic obstructive pulmonary disease (COPD) treatments (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Triage and goals of therapy – A chronic obstructive pulmonary disease (COPD) exacerbation is characterized by dyspnea and/or cough and sputum that worsens over ≤14 days; it may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by airway infection, pulmonary embolism, pollution, or other airway insult. (See 'Introduction and definition' above.)

Triage to determine site of care is based on signs and symptoms, vital signs, arterial blood gas (ABG), and response to initial office/emergency department care (algorithm 1). (See 'Triage to inpatient versus outpatient care' above.)

Regardless of treatment location, management goals are to:

•Reverse airflow limitation using short-acting inhaled bronchodilators and systemic glucocorticoids

•Treat infection, which is implicated in many exacerbations

•Exclude other causes for which additional therapy is needed (eg, pulmonary embolism)

•Ensure appropriate oxygenation

•Avert intubation and mechanical ventilation

●Rapid overview of management for severe exacerbations – A rapid overview for the evaluation and management of severe exacerbations of COPD in the emergency department is provided in the table (table 3). (See 'Emergency department and hospital management' above.)

●Short-acting bronchodilators – For all patients having a COPD exacerbation, we recommend inhaled short-acting bronchodilator therapy (Grade 1B).

•At home and outpatient clinics, patients should use their prescribed reliever medication, typically a short-acting beta-agonist (SABA; eg, albuterol, levalbuterol) or combined SABA plus short-acting muscarinic antagonist (SAMA; eg, ipratropium) (algorithm 4). (See 'Initiate short-acting bronchodilators (outpatient)' above.)

•In hospital settings, we suggest administration of SABA-SAMA combination therapy rather than SABA alone (Grade 2C). The combination is generally well tolerated and might achieve better bronchodilation. (See 'Initiate short-acting bronchodilators (inpatient)' above.)

•We prefer nebulized therapy for reliable airway delivery, but delivery by soft mist inhaler (SMI), dry-powder inhaler (DPI), or metered dose inhaler (MDI) with spacer is equally effective when properly administered.

The usual dose for acute symptom relief is two puffs (MDI/DPI), one inhalation (SMI), or 3 mL (nebulization solution) every 20 to 60 minutes for two to three doses, then every two to four hours based on the patient response. Standard SABA-SAMA solutions for nebulization contain 2.5 mg of albuterol with or without 0.5 mg of ipratropium in 3 mL sterile normal saline.

For patients in emergency room or inpatient settings with respiratory failure and limited benefit from short-acting inhaled bronchodilators, we suggest intravenous magnesium (Grade 2C). (See 'Magnesium sulfate' above.)

●Systemic glucocorticoids – For patients hospitalized due to an acute exacerbation of COPD, we recommend a course of systemic glucocorticoids (Grade 1B); we also suggest glucocorticoids for patients who do not require hospitalization who have at least moderate severity exacerbations (Grade 2B). A reasonable dose for most patients is prednisone 40 mg once daily (or the equivalent) for five days, though up to 14 days may be used in some cases. A higher initial dose of glucocorticoids may occasionally be used in patients with impending or actual respiratory failure. In general, results with oral dosing are similar to those with intravenous dosing. (See 'Glucocorticoids (outpatient)' above and 'Glucocorticoids (inpatient)' above.)

●Antibiotics and antiviral agents – Antibiotics are indicated for some patients having a COPD exacerbation (algorithm 2 and table 2), particularly those who require hospitalization for their exacerbation (algorithm 3). Antiviral therapy may be appropriate for some infections triggered by respiratory viruses.

●Titrating supplemental oxygen – Patients with hypoxemia due to an exacerbation of COPD should receive supplemental oxygen (algorithm 1). We suggest that supplemental oxygen be titrated to a target of 88 to 92 percent pulse oxygen saturation, rather than using high-flow, nontitrated oxygen (Grade 2B). Lower oxygen targets may both improve monitoring for and prevent worsening of hypercapnia. (See 'Oxygen therapy' above.)

●Ventilatory support – Ventilatory support is necessary for patients who develop respiratory fatigue despite supportive therapy with medications and oxygen (algorithm 1). Noninvasive ventilation (NIV) is the preferred method in most patients. (See 'Ventilatory support' above and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Acute exacerbation of chronic obstructive pulmonary disease with hypercapnic respiratory acidosis'.)

Invasive mechanical ventilation is required in patients with respiratory failure despite NIV, who do not tolerate NIV, or who have contraindications to NIV. (See 'Ventilatory support' above and "Invasive mechanical ventilation in acute respiratory failure complicating chronic obstructive pulmonary disease".)

●Treatments without clear benefit – Mucoactive agents, methylxanthines, and mechanical techniques to augment sputum clearance have not been shown to confer benefit for COPD exacerbations. (See 'Treatments without documented benefit' above.)