INTRODUCTION — Chronic obstructive pulmonary disease (COPD) is a common condition with high morbidity and mortality, affecting males and females equally. It is estimated that approximately 10 percent of individuals aged 40 years or older have COPD, although the prevalence varies between countries and increases with age [1-3]. As of 2020, COPD is the sixth leading cause of death among adults in the United States, having dropped from number three. However, this is not due to improving outcomes, as the rate of COPD deaths continues to rise, but due to COVID (number three), a rapid increase in unintentional injuries, especially opioid overdoses (number four), and increasing rates of stroke (number five); COPD is the third leading cause of death worldwide [4-6].  

The pharmacologic management of patients with stable COPD who return in follow-up will be reviewed here. The clinical manifestations, diagnosis, comorbidities, and prognosis of COPD, and the management of refractory COPD, acute exacerbations, and alpha-1 antitrypsin deficiency are discussed separately. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging" and "Stable COPD: Initial pharmacologic management" and "Management of refractory chronic obstructive pulmonary disease" and "Chronic obstructive pulmonary disease: Risk factors and risk reduction" and "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions" and "COPD exacerbations: Management".)

APPROACH — The Global Initiative Chronic Obstructive Lung Disease (GOLD) Report advises using a different approach when adjusting medications in patients who are already on therapy [7]. The GOLD “ABCD” groups that are used to guide initial therapy are not used for follow-up adjustments (table 1) (see "Stable COPD: Initial pharmacologic management", section on 'Symptoms and risk of exacerbations'). Instead, follow-up management is based on the control of symptoms and exacerbations provided by current therapy (table 2).

Assessment

Symptoms and exacerbations — For patients who return for follow-up management of COPD, symptoms (dyspnea and exercise tolerance) are evaluated using a validated instrument, such as the modified Medical Research Council (mMRC) dyspnea scale (table 3) or the COPD Assessment Test (CAT) [7-10]. Patients are asked whether they’ve had additional exacerbations or hospitalizations on the current regimen. When deciding whether to add or taper inhaled glucocorticoids (ICS; also called inhaled corticosteroid), a peripheral blood eosinophil count may be helpful in guiding therapy [7]. (See "Stable COPD: Initial pharmacologic management", section on 'Assessing disease pattern and severity'.)

Additional symptoms associated with COPD (eg, cough, sputum, activity limitations, sleep disturbance), medication use, lung function, and oxygenation are monitored to ascertain whether an adequate response to therapy has been achieved and whether complications or comorbidities have developed, as described separately. (See "Stable COPD: Overview of management", section on 'Monitoring' and "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging", section on 'Differential diagnosis' and "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions".)

Blood eosinophils and response to inhaled glucocorticoids — The GOLD strategy supports the use of blood eosinophil counts to help guide therapy with inhaled glucocorticoids [7].

A number of studies suggest that blood eosinophil counts may play a role as a biomarker to predict whether addition of inhaled glucocorticoids to maintenance inhaled bronchodilator therapy will lead to a reduction in exacerbations [7,11-15]. Lower levels of blood eosinophils (eg, <100 cells/microL) predict a low likelihood of treatment response, while higher counts are associated with a progressively greater likelihood of response up to a threshold of >300 cells/microL.

A low blood eosinophil count (eg, <100 cells/microL) may predict an increased risk of pneumonia with ICS therapy [16].

Some analyses support a role for blood eosinophil counts in predicting which patients will tolerate discontinuation of inhaled glucocorticoids without an increase in exacerbations [17,18]. In a post hoc analysis of the WISDOM trial, withdrawal of inhaled glucocorticoids was more likely to be associated with exacerbation among subjects with a blood eosinophil count ≥300 cells/microL [17]. Using a history of two or more exacerbations per year and a blood eosinophil count ≥300 cells/microL further improves the accuracy of predicting which individuals are likely to experience an exacerbation after discontinuation of inhaled glucocorticoids [18].

When used as a biomarker to guide COPD therapy, blood eosinophil counts should be assessed during a period of disease stability and not during a course of systemic glucocorticoids or acute infection.

Review of smoking, comorbidities, and vaccination — Each follow-up visit is an opportunity to revisit smoking cessation, avoidance of exposure to inhalational particulates, fumes, or gases, vaccination against respiratory infections, contribution from potential comorbidities, and identification of patients for supplemental oxygen, pulmonary rehabilitation, and potential lung cancer screening. (See "Stable COPD: Overview of management".)

Inhaler technique and adherence — Suboptimal inhaler technique and/or adherence are potential (and common) causes of a lack of treatment response and should be explored with every patient. Device education and re-education is essential to successful follow-up care and should always be considered before adding additional therapy. (See "Stable COPD: Overview of management", section on 'Inhaler technique'.)

A prospective study followed patients after a hospitalization for a COPD exacerbation and found suboptimal adherence to technique and on-time use in two-thirds [19]. Similarly, a systematic review of studies of inhaler technique found that on average two-thirds of patients with asthma or COPD made one or more errors in device use [20]. These studies support the need for regimen simplicity and re-enforcement of inhaler technique.

ADJUSTMENT BASED ON RESPONSE TO CURRENT THERAPY — The 2021 Global Initiative Chronic Obstructive Lung Disease (GOLD) report suggests that adjustment of medications should be based on the severity of symptoms and occurrence of exacerbations on current therapy, rather than the “ABCD” system used for initial therapy (table 2) [7]. (See "Stable COPD: Initial pharmacologic management", section on 'Symptoms and risk of exacerbations'.)

Symptoms well-controlled and low exacerbation risk — In general, patients with good symptom control (ie, modified Medical Research Council [mMRC] grade <2 or COPD Assessment Test [CAT] score <10) and low exacerbation risk should continue their current therapy [7]. As an exception, if current therapy includes inhaled glucocorticoid (ICS; inhaled corticosteroid), tapering or discontinuing the ICS may be possible, although patients with higher blood eosinophil counts are more likely to develop an exacerbation with discontinuation of ICS, than those with lower counts. If ICS are withdrawn, close patient monitoring is required. Any worsening in symptoms, activity tolerance, or oxygenation following treatment reduction should lead to a return to the prior maintenance therapy.

Trials examining the effect of ICS withdrawal include the following:

●For patients with good control of symptoms and <2 exacerbations/year on triple therapy, a real-world study in 914 patients suggests that ICS can be safely withdrawn without significant risk of health status decline (CAT score) or exacerbations (OPTIMO) [21]. One concern about the broad applicability of this study is that the original indications for ICS therapy were unclear.

●In a 26-week trial, 527 patients with COPD on long-term triple therapy but infrequent exacerbations were randomly assigned to glycopyrronium-indacaterol or tiotropium-salmeterol-fluticasone in two inhalers [22]. In the group without ICS, a small decrease was noted in forced expiratory volume in one second (FEV₁), but there was no increase in the annualized rate of moderate or severe exacerbations. Importantly, patients with blood eosinophils ≥300/microL at baseline experienced a greater decline in FEV₁ and a higher exacerbation risk.

●For patients who qualified for triple therapy based on an FEV₁ <50 percent predicted with at least one exacerbation in the past year, the effect of stepping down to a long-acting muscarinic antagonist (LAMA)-long-acting beta-agonist (LABA) combination was assessed in the one-year randomized (WISDOM) trial [23]. In this trial, withdrawal of ICS was not associated with an increase in exacerbations, suggesting that many of these patients may safely have their ICS withdrawn. However, there was a drop in FEV₁ and patient quality of life measures in the ICS withdrawal group, suggesting that ICS withdrawal in GOLD D patients should be accompanied by careful monitoring to minimize any potential deterioration.

A post-hoc analysis found that ICS withdrawal was associated with a greater exacerbation rate among subjects with higher blood eosinophil counts, particularly ≥300 cells/microL [17]. (See "Role of inhaled glucocorticoid therapy in stable COPD", section on 'Exacerbations' and 'Blood eosinophils and response to inhaled glucocorticoids' above.)

Persistent dyspnea but low exacerbation risk — For patients with persistent dyspnea or exercise limitation (ie, mMRC grade ≥2 or CAT score ≥10) and no exacerbations in the past year, the GOLD strategy suggests adjusting therapy as follows (table 2) [7]:

●Current therapy with LAMA or LABA – If current therapy is a LAMA or LABA alone, the GOLD strategy advises changing to both a LAMA and a LABA (available as a combination in a single inhaler). Clinical trials and a systematic review support greater relief of dyspnea with dual bronchodilator therapy, as described separately. (See "Stable COPD: Initial pharmacologic management", section on 'LAMA-LABA for severe breathlessness'.)

●Current therapy with LABA-ICS – If current therapy is a LABA-ICS, a change to LAMA-LABA-ICS is reasonable, as triple therapy is associated with improved lung function. (See 'Efficacy of triple therapy' below.)

Alternatively, if the initial indication for ICS is unclear, and no recent exacerbations have occurred, and peripheral blood eosinophils are <300 cells/microL, LABA-ICS can be changed to LAMA-LABA to avoid potential adverse effects of ICS. Close monitoring is required for patients withdrawing from ICS to minimize any potential deterioration. Patients with blood eosinophils ≥300 cells/microL are more likely to experience an exacerbation after ICS withdrawal. (See 'Blood eosinophils and response to inhaled glucocorticoids' above.)

●Current therapy with LAMA-LABA – If current therapy is LAMA-LABA, an alternative inhaler device (eg, dry powder inhaler versus soft mist inhaler) or agents (eg, tiotropium-olodaterol versus umeclidinium-vilanterol) can be tried. Other causes of dyspnea should be explored and treated.

Alternatively, a switch to LAMA-LABA-ICS or addition of low dose theophylline can be tried. Nonpharmacologic measures (eg, pulmonary rehabilitation, bronchoscopic or surgical lung volume reduction, or lung transplant) may be of benefit. (See 'Efficacy of triple therapy' below and "Pulmonary rehabilitation" and "Management of refractory chronic obstructive pulmonary disease".)

●Current therapy with LAMA-LABA-ICS – If the patient is currently on triple therapy with LAMA-LABA-ICS and has not appeared to benefit from ICS or has experienced adverse effects from ICS, therapy can be changed to LAMA-LABA. As noted, patients with peripheral blood eosinophils ≥300 cells/microL are more likely to experience an exacerbation if ICS are discontinued. ICS withdrawal requires close patient monitoring to avoid potential deterioration.

As noted, other causes of dyspnea should be explored and treated. Pulmonary rehabilitation may be of benefit to reduce dyspnea. Other nonpharmacologic measures (eg, bronchoscopic or surgical lung volume reduction, or lung transplant) may be of benefit in carefully selected patients. (See "Pulmonary rehabilitation" and "Management of refractory chronic obstructive pulmonary disease".)

Persistent exacerbations with or without dyspnea — For patients with one or more exacerbations in the past year on their current regimen with or without associated persistent dyspnea, the GOLD strategy suggests adjusting therapy as follows [7]:

●Current monotherapy LAMA or LABA – For patients on a LAMA or LABA alone, a change to LAMA-LABA is advised, as dual bronchodilator therapy reduces exacerbations and dyspnea compared with single bronchodilator therapy [7,24]. However, the evidence of a reduction in exacerbations when a LABA is added to a LAMA is less clear [24,25]. (See "Stable COPD: Initial pharmacologic management", section on 'LAMA-LABA for severe breathlessness'.)

A systematic review and meta-analysis compared combination LAMA (tiotropium) plus LABA (salmeterol, formoterol, or indacaterol) to tiotropium alone and found slightly better quality of life and a small increase in the post-bronchodilator FEV₁ with the combination [24].

Alternatively, a blood eosinophil count ≥300 cells/microL may identify patients more likely to respond to a LABA-ICS or LAMA-LABA-ICS combination [15,26]. Although multiple studies have shown the benefit of dual therapy with LABA-ICS versus monotherapy with LABA, in our practice, we rarely use LABA-ICS for patients with COPD, except in patients who are unable to take a LAMA or have asthma and COPD. (See 'Blood eosinophils and response to inhaled glucocorticoids' above and "Stable COPD: Initial pharmacologic management", section on 'LABA-ICS preparations versus LABA' and 'Efficacy of triple therapy' below.)

●Current combination LAMA-LABA therapy – For patients on dual therapy with LAMA-LABA, a change to LAMA-LABA-ICS may be expected to reduce the frequency of exacerbations relative to LAMA-LABA therapy and improve lung function. (See 'Efficacy of triple therapy' below.)

Alternatively, if blood eosinophils are <100 cells/microL, triple therapy (adding ICS to LAMA-LABA) is less likely to be of benefit. Roflumilast, a phosphodiesterase inhibitor, is available for patients with chronic bronchitis and an FEV₁ <50 percent of predicted, particularly if they have had at least one exacerbation that required hospitalization. Azithromycin prophylaxis reduces exacerbation frequency, and is more likely to be of benefit in former (rather than current) smokers. Potential adverse effects may limit use of these agents. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Phosphodiesterase-4 inhibitors' and "Management of refractory chronic obstructive pulmonary disease", section on 'Chronic antibiotic therapy'.)

●Current therapy LABA-ICS – For patients on LABA-ICS, we step up therapy to LAMA-LABA-ICS. For patients with a lack of response to ICS and/or adverse effects from ICS, de-escalation to a LAMA-LABA is reasonable. However, patients with a peripheral blood eosinophil count ≥300 cells/microL are more likely to experience an exacerbation if ICS are discontinued. (See 'Blood eosinophils and response to inhaled glucocorticoids' above.)

●Current therapy LAMA-LABA-ICS – For patients on LAMA-LABA-ICS who continue to have exacerbations, further choices include addition of a macrolide (ie, azithromycin) or roflumilast. Pulmonary rehabilitation should be considered in patients with persistent dyspnea or exacerbations despite triple therapy. Carefully selected patients may be candidates for lung volume reduction or lung transplant. These choices are discussed separately. (See "Management of refractory chronic obstructive pulmonary disease".)

As noted, discontinuation of ICS is an alternate choice that is less likely to be associated with exacerbation if the blood eosinophil count is <300 cells/microL. (See 'Blood eosinophils and response to inhaled glucocorticoids' above.)

Efficacy of triple therapy — For patients with persistent symptoms and frequent exacerbations of COPD despite combined LAMA-LABA or LABA-ICS, we suggest changing to triple therapy with LAMA-LABA-ICS [7].

The validity of this approach is supported by the following studies that compare triple therapy to double therapy (LAMA-LABA or LABA-ICS) [14,27-31]:

●IMPACT trial – A single, once daily inhaler containing three agents (fluticasone furoate-umeclidinium-vilanterol) was compared with a once daily LAMA-LABA inhaler (umeclidinium-vilanterol) or a once daily glucocorticoid-LABA inhaler (fluticasone furoate-vilanterol) in a randomized trial (IMPACT) of 10,355 patients with COPD who were at increased risk for exacerbations [14]. The rate of moderate-to-severe exacerbations was lower with the triple inhaler compared with fluticasone furoate-vilanterol (annual rate of exacerbations 0.91 versus 1.07; RR 0.85, 95% CI 0.80-0.90) or umeclidinium-vilanterol (annual rate of exacerbations 0.91 versus 1.21; RR 0.75; 95% CI 0.70-0.81). Additionally, lung function was better with triple therapy; hospitalizations were less frequent. However, the incidence of pneumonia was higher with triple therapy (95.8/1000 patient years) than with umeclidinium-vilanterol (61.2/1000 patient years; time to event HR 1.53, 95% CI 1.22-1.92). Questions have been raised about the role of withdrawal of ICS just prior to study onset as a factor in the findings from IMPACT [32], although this concept has also been contested.

Post hoc analysis of mortality from IMPACT suggests triple therapy may reduce mortality compared to LABA-LAMA therapy [33]. However, prospective mortality studies with triple therapies have not been done and the use of triple therapy to reduce COPD mortality cannot currently be recommended.

●ETHOS trial – A single, twice-daily inhaler containing three agents (budesonide-glycopyrrolate-formoterol) with two different ICS doses was compared with a twice-daily LAMA-LABA inhaler (glycopyrrolate-formoterol) and a twice daily ICS-LABA inhaler (budesonide-formoterol) in a randomized trial (ETHOS) of 8509 patients with COPD who were at increased risk for exacerbations [34]. The rate of moderate-to-severe exacerbations was lower with both doses of triple inhaler compared with LAMA-LABA (glycopyrrolate-formoterol) (annual rate of exacerbations for the 320 mcg budesonide dose was 1.08 versus 1.42; RR 0.76, 95% CI 0.69-0.83) or the ICS-LABA inhaler (budesonide-formoterol) (annual rate of exacerbations 1.08 versus 1.24; RR 0.87; 95% CI 0.79-0.95). Additionally, time to all-cause mortality was better with triple therapy compared with LABA-LAMA therapy (HR 0.54, 95% CI 0.34-0.87); the difference between triple therapy and ICS-LABA did not reach significance (HR 0.78, 95% CI 0.47-1.30). The incidence of pneumonia was higher with triple therapy (53.3/1000 patient years) than with glycopyrrolate-formoterol (37.3/1000 patient years).

A follow-up study that included near complete vital status data for week 52 found that triple therapy with budesonide 320 mcg reduced the risk of death compared with LAMA-LABA (HR 0.51; 95% CI 0.33-0.80) [35]. However, when triple therapy with budesonide 320 mcg was compared with ICS-LABA, reduction in risk of death did not reach significance, and similarly triple therapy with budesonide 160 mcg did not demonstrate a significant difference with either of the dual comparators.

●TRINITY trial – Use of single-inhaler triple therapy with beclometasone-glycopyrrolate-formoterol delivered as two inhalations twice daily was compared with dual inhaler triple therapy with beclomethasone-formoterol plus tiotropium and to tiotropium monotherapy in 2691 patients with severe-to-very severe COPD and increased exacerbation risk (TRINITY) [36]. The single inhaler triple therapy was noninferior to dual inhaler triple therapy and superior to tiotropium monotherapy in the prevention of exacerbations and in FEV₁ improvement over 52 weeks. Overall adverse events were similar between the three study arms.

●TRILOGY trial – In a similar study, single-inhaler triple therapy with beclometasone-glycopyrrolate-formoterol was compared with beclometasone-formoterol in 1368 patients with severe-to-very severe COPD and increased exacerbation risk (TRILOGY) [37]. Triple therapy reduced exacerbation rates by 23 percent. The addition of the LAMA to the LABA-inhaled glucocorticoid increased trough FEV₁ by 81 mL and reduced dyspnea. Overall adverse events were similar between the two study arms.

●TRIBUTE trial – In a separate study, the single-inhaler triple therapy beclomethasone/formoterol/glycopyrrolate was compared with glycopyrrolate-indacaterol in 1532 patients with severe-to-very severe COPD and increased exacerbation risk (TRIBUTE) [30]. Over 52 weeks, triple therapy reduced exacerbation rates by approximately 15 percent (0.50 versus 0.59 exacerbations/patient per year for triple therapy and dual therapy, respectively). The effect was most pronounced in patients with blood eosinophil counts ≥2 percent. Overall adverse events were similar between the two study groups.

●KRONOS trial – A six month study compared single-inhaler twice daily triple therapy containing budesonide-glycopyrrolate-formoterol to dual therapies with glycopyrrolate-formoterol and budesonide-formoterol in 1902 patients with moderate-to-very severe COPD and no increased exacerbation risk (KRONOS) [31]. Triple therapy reduced exacerbation rates by 52 percent compared with the LAMA-LABA and by 18 percent compared with the LABA-ICS. Overall adverse events were similar between the two study arms.

●FULFIL trial – In the FULFIL trial, a once daily single inhaler with fluticasone furoate-umeclidinium-vilanterol was compared with twice daily budesonide-formoterol in 1810 patients with moderate to severe COPD [38]. At 26 weeks, triple therapy resulted in a mean increase in FEV₁ (142 mL, 95% CI 126 to 158), while dual therapy caused a decrease (-29 mL, 95% CI, -46 to 13). The annualized rate of moderate-to-severe exacerbations was reduced by 35 percent (95% CI 14-51 percent) with triple versus dual therapy.

A number of smaller trials and retrospective studies further support triple therapy for patients with moderate to severe COPD [27,28,39-41].

Other studies have shown a benefit to triple therapy compared with single agent therapy in moderate to severe COPD [40,42].

REFRACTORY DISEASE — Some patients have severe COPD and are still symptomatic or continue to have exacerbations despite smoking cessation, an optimal regimen of inhaled medications (eg, LAMA-LABA-ICS), education about inhaler technique, pulmonary rehabilitation, and supplemental oxygen for severe hypoxemia. The management of these patients is discussed separately. (See "Management of refractory chronic obstructive pulmonary disease".)

FUTURE DIRECTIONS — Several novel therapies for COPD are being investigated.

●Stem cell therapy – Preclinical studies have raised the possibility that mesenchymal stem cells could promote regeneration of lung parenchymal or airway cells to repair injured tissues (eg, emphysematous lung parenchyma and irreversible airflow limitation) in patients with COPD [43]. However, no studies have demonstrated clear efficacy and some studies have reported harm [43]. Patients should be cautioned against use of stem cell products outside of regulated clinical trials. Several studies are underway to explore different sources of stem cells, methods of delivery to the lungs, efficacy, and safety, and are listed at clinicaltrials.gov.

●Bronchoscopic lung volume reduction – Endobronchial placement of Spiration one-way valves is approved by the US Food and Drug Administration [FDA]; other endobronchial plugs and blockers, endobronchial instillation of biologic sealants, thermal airway ablation, and airway stents for decompression of bullae are under investigation. These devices and techniques are discussed separately. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Bronchoscopic LVR' and "Bronchoscopic treatment of emphysema".)

●Mepolizumab – Mepolizumab is a monoclonal antibody against interleukin (IL)-5 that is approved for use in eosinophilic asthma. In two parallel, randomized trials, 1138 patients with COPD, a blood eosinophil count ≥150 cells/microL, and moderate or severe exacerbations of COPD despite triple inhaler therapy were assigned to mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) or placebo, administered subcutaneously every four weeks [44]. After one year, mepolizumab slightly reduced the rate of exacerbations compared with placebo (rate ratio [RR] 0.82, 95% CI 0.68-0.98 in METREX; RR 0.80, 95% CI 0.65-0.98, for mepolizumab 100 mg and RR 0.86, 95% CI 0.70-1.05, for mepolizumab 300 mg in METREO). Additional study is needed to understand the role of eosinophils in COPD and whether therapeutic strategies directed against eosinophils are likely to be of benefit. (See "Treatment of severe asthma in adolescents and adults", section on 'Anti-IL-5 therapy'.)  

●Benralizumab – Benralizumab is an IL-5 receptor-alpha monoclonal antibody that is used as add-on therapy for patients with severe asthma and an eosinophilic phenotype. (See "Treatment of severe asthma in adolescents and adults", section on 'Benralizumab'.)

Mixed results have been reported with benralizumab in COPD [45]. In two parallel randomized trials, a total of 3910 patients with moderate to very severe COPD and a history of frequent exacerbations were assigned to take benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) or placebo subcutaneously every four weeks for two doses, then every eight weeks for a year [46]. None of the benralizumab doses achieved a significant reduction in annualized exacerbations relative to placebo among patients with a blood eosinophil count ≥220 cells/microL. However, in a subsequent subgroup analysis, patients with certain clinical characteristics (ie, ≥3 exacerbations in the previous year, using triple inhaled therapy with a long-acting muscarinic antagonist, long-acting beta agonist, plus glucocorticoid, and blood eosinophilia) experienced a 30 percent reduction in exacerbations (RR 0.70, 95% CI 0.56-0.88) with benralizumab at the highest dose (100 mg every eight weeks) compared with placebo [47]. Further prospective study is needed to determine whether benralizumab would benefit this subgroup of COPD patients.

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: Pulmonary rehabilitation (The Basics)")

SUMMARY AND RECOMMENDATIONS

●At follow-up visits for COPD, symptoms (dyspnea and exercise tolerance) are evaluated using a validated instrument, such as the modified Medical Research Council (mMRC) dyspnea scale (table 3) or the COPD Assessment Test (CAT), and patients are asked whether they have had exacerbations or hospitalizations on the current regimen. The Global Initiative Chronic Obstructive Lung Disease (GOLD) “ABCD” groups that are used to guide initial therapy are not used for follow-up adjustments of medication. (See 'Approach' above.)

●Each follow-up visit is an opportunity to reassess cigarette smoking; exposure to inhalational particulates, fumes, or gases; vaccination against respiratory infections; potential comorbidities; and need for supplemental oxygen, pulmonary rehabilitation, and potential lung cancer screening. (See 'Review of smoking, comorbidities, and vaccination' above.)

●Suboptimal inhaler technique and/or incomplete adherence are potential (and common) causes of a lack of treatment response and should be explored with every patient. Device education and re-education are essential to successful follow-up care and should always be addressed before adding additional therapy. (See 'Inhaler technique and adherence' above.)

●For patients who have persistent symptoms or recurrent exacerbations, therapy is adjusted based on the patient’s current medications as described in the table (table 2). Other causes of dyspnea and recurrent exacerbations should be explored and treated as indicated. (See "Stable COPD: Initial pharmacologic management".)

●In general, patients with good symptom control (ie, mMRC grade 0 or 1 or CAT score <10) and low exacerbation risk should continue their current therapy. As an exception, if current therapy includes inhaled glucocorticoid (ICS; inhaled corticosteroid), tapering or discontinuing the ICS is often well-tolerated, particularly if blood eosinophils are <300 cells/microL. (See 'Symptoms well-controlled and low exacerbation risk' above.)

●For patients with persistent dyspnea or exercise limitation (ie, mMRC grade ≥2 or CAT score ≥10) who are at low risk for exacerbation, therapy can be adjusted step-wise to improve control of dyspnea, as follows (see 'Persistent dyspnea but low exacerbation risk' above):

•For patients on monotherapy with a long-acting muscarinic antagonist (LAMA) or long-acting beta-agonist (LABA), we suggest changing to dual LAMA-LABA therapy (Grade 2B).

•For patients using a LABA-ICS combination, we suggest changing to a LAMA-LABA inhaler, if lack of response to ICS and blood eosinophils <300/microL (Grade 2C), or changing to triple therapy (LAMA-LABA-ICS) (Grade 2B).

•For patients on LAMA-LABA therapy, a different preparation or delivery system may be more effective. In addition, for patients using a LAMA-LABA or LAMA-LABA-ICS inhaler, low dose theophylline and/or nonpharmacologic options, such as pulmonary rehabilitation, bronchoscopic or surgical lung volume reduction, or lung transplantation, may be of benefit. (See 'Persistent dyspnea but low exacerbation risk' above.)

●For most patients with two or more exacerbations or one requiring hospitalization in the past year with or without persistent dyspnea while taking single agent LAMA or LABA therapy, we recommend changing to dual bronchodilator (LAMA-LABA) therapy (Grade 1B). As an exception, a blood eosinophil count ≥300 cells/microL may identify patients more likely to respond to a LABA-ICS. For those using dual therapy (LAMA-LABA or LABA-ICS), we suggest changing to triple therapy (LAMA-LABA-ICS), unless the blood eosinophil count is <100/microL (Grade 2B). (See 'Persistent exacerbations with or without dyspnea' above.)

●For patients on LAMA-LABA (with low eosinophils) or LAMA-LABA-ICS who continue to have exacerbations, additional treatment options include a macrolide (ie, azithromycin) or roflumilast. (See 'Persistent exacerbations with or without dyspnea' above.)