Updated Treatment Guidelines for Patients with Asthma and/or COPD

Educational Objectives

The goal of this program is to improve management of asthma and chronic obstructive pulmonary disease (COPD). After hearing and assimilating this program, the clinician will be better able to:

1. Prescribe treatment for asthma using Global Initiative for Asthma 2019 guidelines.
2. List the risks of short-acting (-agonist-only treatment in patients with asthma.
3. Choose an appropriate therapy for patients with stable COPD.

Summary

Asthma treatment in adults and adolescents: asthma is the most common chronic noncommunicable disease, affecting >260 million people globally in 2019; reversible airway disease with inflammation; the Global Initiative for Asthma (GINA) guidelines are developed by a joint effort by the National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO); these are updated every year; in 2019, a fundamental change in asthma management was proposed; short-acting bronchodilators alone are no longer recommended for adults and adolescents; for safety, GINA no longer recommends short-acting β-agonist (SABA)-only treatment for adults and adolescents based on evidence that SABA-only treatment increases the risk for severe exacerbations and that adding an inhaled corticosteroid (ICS) significantly reduces this risk; GINA now recommends that all adults and adolescents with asthma should receive ICS-containing controller treatment, and it can be delivered by regular daily treatment, or in mild asthma, by as-needed low doses of ICS-formoterol; formoterol is a long-acting β-agonist (LABA) and is off-label; it was used in the clinical trials as Symbicort (budesonide/formoterol), and is not approved by the Food and Drug Administration (FDA) for rescue or PRN therapy; it is approved only for long-term maintenance therapy; patients with mild asthma are still at risk for serious adverse events; exacerbation triggers are variable

Risks of SABA-only treatment: regular use of SABA, even for 1 to 2 wk, is associated with adverse events such as β-receptor downregulation, decreased bronchoprotection, rebound hyperresponsiveness, decreased bronchodilator response, increased allergic response, and increased eosinophilic airway inflammation; higher use (≥3 canisters per yr) of SABA is associated with higher risk for severe exacerbations leading to visits to emergency department (ED) and hospitalizations; dispensing of ≥12 canisters per yr is associated with increased risk for mortality; ICS reduces the risk for asthma-related deaths, hospitalization and ED visits and the need for oral corticosteroids (OCS) rescues, but adherence is poor, particularly in patients with mild, infrequent symptoms

Safe and effective alternative to manage mild asthma: GINA guidelines have 2 tracks based on evidence about outcomes with the 2 reliever choices across asthma severity; track 1 (preferred option) — involves low-dose ICS-formoterol therapy as a reliever; reduces risk for exacerbation compared with albuterol, with similar symptom control and lung function; this is off-label use (not FDA approved for rescue); formoterol is the only LABA that can be used for rescue because it has a fast onset and lasts for ≈12 hr; salmeterol (Advair) and other LABAs have slow onset; track 2 — a dose of ICS has to be taken from a separate inhaler every time the patients are treated with SABA; it must be considered if the patient is likely to be adherent with a daily controller; if not, they are exposed to the risk of SABA-only treatment PRN

Controller and reliever algorithm: preferred method is PRN low-dose ICS-formoterol for steps 1 and 2 asthma in adults and adolescents aged ≥12 yr; alternative is ICS whenever albuterol is taken for step 1; patients on low-dose ICS maintenance (step 2), can use albuterol for reliever; do not use a different ICS; for step 3, use low-dose ICS-formoterol for maintenance; also use as reliever in preferred track (off-label); alternatively, if using ICS with, eg, salmeterol, for maintenance, use albuterol for rescue; only use formoterol for rescue if it is the long-term controller with no other LABA; do not use 2 LABAs together; can take ≤12 doses per day of ICS-formoterol if needed based on safety data; use albuterol for rescue if any other LABA is used for maintenance

Evidence for ICS-formoterol: ≈66% reduction in severe exacerbations with ICS-formoterol PRN vs albuterol alone PRN; data suggest exercise-induced bronchoconstriction has a greater reduction with ICS-formoterol than with albuterol alone; severe exacerbations are non-inferior; 25% to 50% less daily inhaled steroid use with PRN ICS-formoterol compared with scheduled ICS-albuterol; no evidence for safety or efficacy of albuterol alone; patients with infrequent symptoms can still have severe or fatal complications

Severe asthma: defined in new guideline as asthma that remains uncontrolled despite optimized treatment with ICS-LABA; ≈24% of patients need high-intensity treatment with high-dose ICS-LABA or medium-dose ICS-LABA with or without OCS; ≈17% patients have difficult-to-treat asthma with poor symptom control, and 3.7% have severe asthma

Add-on LAMA: long-acting muscarinic antagonists (LAMA) can be added (eg, tiotropium [Spiriva]), as it is FDA approved for chronic obstructive pulmonary disease (COPD) and asthma; adding a LAMA to medium- or high-dose ICS-LABA modestly improves lung function but not symptoms; severe exacerbations may be reduced somewhat; may have decreased need for OCS; ensure sufficient dose of ICS (at least medium dose) before considering LAMA

Add-on azithromycin: can be considered for step 5 after specialist referral; sputum must be checked for atypical mycobacteria, electrocardiography must be checked because there can be QT prolongation, and clinician must also consider the risk for antimicrobial resistance; appears to reduce exacerbations

Add-on biologic therapy: include omalizumab (anti-IgE), IL4 inhibitors, IL5 inhibitors, and monoclonal antibodies; all FDA approved, but are not very effective

Montelukast (Singulair): can be used, but no way to predict good candidates; FDA black box warning as of March 2020 about serious mental health side effects; advised restricting use for allergic rhinitis; can still use for asthma

GINA update for asthma in children aged 6 to 11 yr: step 1 — taking an ICS whenever SABA is taken is preferred over daily ICS; step 2 — daily ICS is preferred over taking ICS whenever a SABA is taken; step 3 — maintenance and reliever therapy (MART) with low-dose ICS-formoterol is now included (off-label); also, ICS-LABA or a medium-dose ICS with albuterol can be used; step 4 — moderate-dose ICS-LABA or low-dose ICS-formoterol; refer to expert; for children aged ≤5 yr, albuterol is still the rescue method

GINA guidance about COVID-19 and asthma: patients with well-controlled asthma are not at high risk for bad outcomes with COVID-19; do not discontinue ICS; avoid spirometry in patients with confirmed or suspected COVID-19; allergic reactions to the vaccine are rare; a gap of 14 days between vaccination for COVID-19 and influenza is recommended; biologic therapy and COVID-19 should not be given same day

New COPD guidelines updated in 2021: Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, contributed by NHLBI World Health; includes GOLD classifications based on patients with FEV₁/FVC ratio <0.7; GOLD 1 (mild) is FEV₁≥80% predicted; GOLD 2 (moderate) is 50% ≤ FEV₁<80% predicted; GOLD 3 (severe) is 30% ≤ FEV₁<50% predicted; GOLD 4 (very severe) is FEV₁<30% predicted; Modified Medical Research Council (mMRC) Dyspnea Scale grades range from 0 to 4; COPD Assessment Test (CAT), based on symptoms, uses grades from 0 to 5 in 9 categories; the refined ABCD Assessment Tool takes into account all the above scales to grade patients in the A,B,C, or D category; for grade A patients, smoking cessation is most important to prevent progression; for stages B, C, or D, patients need pulmonary rehabilitation as well; in patients belonging to group A, the preferred bronchodilator is albuterol/ipratropium bromide (Combivent Respimat); in group B patients, addition of a LABA or a LAMA (eg, tiatropium) is prescribed; group C patients are given LAMA, and in group D (more severe asthma) LAMA plus LABA or ICS plus LABA is given

Bronchodilators in stable COPD: combination of SABA and SAMA is superior to either alone for improving FEV₁ and symptoms; LAMAs have a greater effect on exacerbation reduction compared with LABAs; combination LABA and LAMA is superior to either alone; dyspnea treatment begins with a LABA or a LAMA and progresses to combination of LABA plus LAMA; in the presence of elevated eosinophils, ICS is added; if symptoms persist, roflumilast can be considered; azithromycin can be given to former smokers who stop smoking to reduce risk for exacerbations; regular treatment with ICS increases risk for pneumonia especially in those with severe disease; triple therapy improves lung function and symptoms, and reduces exacerbations, compared with LABA-ICS, LABA-LAMA, or LAMA monotherapy; according to IMPACT and ETHOS trials, triple therapy may reduce mortality in symptomatic patients with a history of frequent or severe exacerbations; GOLD guidelines strongly support addition of ICS therapy if there is a history of hospitalization for severe exacerbations or ≥2 moderate exacerbations of COPD per yr, eosinophils levels >300 cells/(L, or history of or concurrent asthma; the guidelines provide moderate support for ICS therapy if there is 1 moderate exacerbation per yr, and if the eosinophils are 100 to 300 cells/(L; if patients have recurrent pneumonia, eosinophils <100, and history of mycobacterial infection, there is strong support against adding an ICS

Patients with features of asthma and COPD: GINA guidelines state asthma should never be treated with bronchodilators alone because of risk for death, hospitalization, and severe exacerbations; in patients with COPD, clinicians should start treatment with LABA and/or LAMA without an ICS; patients with asthma and COPD are more likely to die or be hospitalized if treated with LABA vs ICS-LABA; high-dose ICS may be needed for severe asthma, but should not be used in COPD because of pneumonia risk; for asthma, ICS containing therapy is first line; LABA or LAMA without an ICS is not recommended; in patients with features of both asthma and COPD, ICS is still used as part of the treatment; when the diagnosis is likely to be COPD, the treatment consists of initial LAMA and/or LABA; ICS can be added for patients with hospitalizations, or elevated eosinophils

Readings

Agusti A et al. Inhaled corticosteroids in COPD: friend or foe?. Eur Respir J. 2018 Dec 13;52(6):1801219. doi:10.1183/13993003.01219-2018; Kendzerska T et al. Effectiveness and safety of inhaled corticosteroids in older individuals with chronic obstructive pulmonary disease and/or asthma. A Population Study. Ann Am Thorac Soc. 2019;16(10):1252-1262. doi:10.1513/AnnalsATS.201902-126OC; Lipson DA et al. Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020;201(12):1508-1516. doi:10.1164/rccm.201911-2207OC; Mirza S et al. COPD guidelines: A review of the 2018 GOLD report. Mayo Clin Proc. 2018;93(10):1488-1502. doi:10.1016/j.mayocp.2018.05.026; Nwaru BI et al. Overuse of short-acting β₂-agonists in asthma is associated with increased risk of exacerbation and mortality: A nationwide cohort study of the global SABINA programme. Eur Respir J. 2020 Apr 16;55(4):1901872. doi:10.1183/13993003.01872-2019; Rabe KF et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020;383(1):35-48. doi:10.1056/NEJMoa1916046; Reddel HK et al. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J. 2019;53(6):1901046. Published 2019 Jun 27. doi:10.1183/13993003.01046-2019; Suissa S et al. Comparative effectiveness of LABA-ICS versus LAMA as initial treatment in COPD targeted by blood eosinophils: a population-based cohort study. Lancet Respir Med. 2018;6(11):855-862. doi:10.1016/S2213-2600(18)30368-0.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing relevant to disclose. In his lecture, Dr. Weart presents information related to the off-label or investigational use of a product, therapy, or device.

Acknowledgements

Dr. Weart was recorded on June 4, 2021, exclusively for Audio Digest, using virtual teleconference software, in compliance with current social-distancing guidelines during the COVID-19 pandemic.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP693201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.