Emphysema Guidelines

The COPD Foundation Pocket consultant Guide (PCG) defines COPD as post bronchodilator FEV₁/FVC ratio less than 0.7 on spirometry and provides an algorithm for pharmacologic treatment selection based on symptoms and exacerbations. All patients should receivie smoking cessation support, vaccines and participate in a regular excercise program. ^[28]  

For patients with MMRC 0,1 and less than 2 exacerbations per year, short-acting beta2 agonist as needed is recommended. If symptoms persist, LAMA therapy is indicated.  MMRC 0, 1 and 2 for more exacerbations per year, the recommended treatment options include ^[28] :

• LAMA monotherapy
• Combination LAMA and LABA therapy
• Combination LABA and ICS

For persistent symptoms or exacerbations, combination LAMA, LABA and ICS therapy is recommended.

For MMRC 2 or greater, pulmonary rehabilitation with either LAMA monotherapy or combination LAMA and LABA therapy. Combination LAMA, LABA and ICS therapy is recommended to treat persistent symptoms or exacerbations.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) offers the following guidelines for pharmacologic treatment of COPD ^[2] :

• Inhaled bronchodilators are central to symptom management and should be given to prevent or reduce symptoms
• Regular and as needed use of short acting beta2 agonist or short-acting antimuscarinics improve FEV ₁ and decrease symptoms
• Both LABA and LAMA monotherapy significantly improve lung function, dyspnea, health status and reduce exacerbations
• LAMAs are more effective than LABAs for reducing exacerbations and decreasing hospitalizations
• Combination LABA and LAMA therapy is superior to either LABA and LAMA monotherapy and ICS/LABA combination therapy for increasing FEV ₁ and decreasing symptoms as well as reducing exacerbations
• Tiotropium improves effectiveness of pulmonary rehabiliation

GOLD guidelines include the following recommendations for the treatment of acute exacerbations of COPD (AECOPD) ^[2] :

• Short-acting inhaled beta2-antagonists, with or without short-acting anticholinergics for initial treatment
• Maintenance therapy with long-acting bronchodialators should begin prior to hospital discharge
• Antibiotics, when indicated, and corticosteroids for no more than 5-7 days
• Noninvasive mechanical ventilation should be the first mode of ventilation in acute respiratory failure
• Methylxanthines are not recommended
• Appropriate measures for exacerbation prevention should be initiated following an AECOPD 

VA/DoD guidelines recommend antibiotic use for patients with acute exacerbations who have increased dyspnea and increased sputum purulence (change in sputum color) or volume. Choice of antibiotic should be based on local resistance patterns and patient characteristics. First-line antibiotic choice include ^[27] :

• Doxycycline
• Trimethoprim/sulfamethoxazole (TMP-SMX)
• Second generation cephalosporin
• Amoxicillin
• Amoxicillin/clavulanate
• Azithromycin.

Broader spectrum antibiotics (e.g., quinolones) are reserved for patients with specific indications including ^[27] :

• Critically ill patients in the intensive care unit (ICU)
• Patients with recent history of resistance, treatment failure, or antibiotic use
• Patients with risk factors for health care associated infections.

For outpatients with AECOPD who are treated with antibiotics, a five-day course of the chosen antibiotic is recommended. In agreement with the GOLD guidelines, a course of oral corticosteroids for 5-7 days is also recommeded. ^[27]

In addition to GOLD and the VA/DoD, the European Respiratory Society/American Thoracic Society (ERS/ATS) released joint guidelines for the management of AECOPD. The recommendations are summarized below ^[63]

• For ambulatory patients, treatment with a short course (≤14 days) of oral corticosteroids and administration of antibiotics; Antibiotic selection should be based upon local sensitivity patterns.
• For hospitalized patients, oral administration of corticosteroids is preferred over IV if gastrointestinal access and function are intact 
• For exacerbation associated with acute or acute-on-chronic hypercapnic respiratory failure, provide noninvasive mechanical ventilation 
• A home-based management program involving nurses and potentially other healthcare professionals ( e.g. physicians, social workers and physical therapists), also known as “hospital-at-home”, may be considered as an alternative to hospitalization in patients presenting to the emergency department with a COPD exacerbation
• Pulmonary rehabilitation should not be initated during hospitalization but should begin within 3 weeks after hospital discharge

Guidelines for the prevention of AECOPDs have been issued by the following organizations:

• European Respiratory Society/American Thoracic Society (ERS/ATS)
• American College of Chest Physicians/Canadian Thoracic Society (ACCP/CTS)

The ACCP/CTS guidelines address three areas of prevention: nonpharmacologic treatments, maintenance inhaled therapies and oral therapy in patients with a history of smoking. The recommendations for nonpharmacologic treatments include ^[64]

• Although the 23-valent pneumococcal vaccine should be administered as part of overall medical management, there is not sufficient evidence that vaccination prevents acute exacerbations;  however, the influenza vaccine should be given annually to prevent AECOPDs 
• Smoking cessation counseling and treatment is an important component of a comprehensive prevention strategy 
• Pulmonary rehabilitation should be initiated following a recent exacerbation (ie, ≤ 4 weeks) 
• Education or case management alone should not be used for prevention of AECOPD; education and case management for prevention of exacerbations should include direct access to a health-care specialist at least monthly. 
• Telemonitoring compared with usual care has not shown to prevent AECOPD 

Key recommendations for maintenance inhaled therapies in patients with moderate to severe airflow obstruction include ^[64] :

• Long-acting muscarinic antagonist (LAMA) for prevention of moderate to severe AECOPD 
• Short-acting muscarinic antagonist to prevent mild-moderate AECOPD 
• Short-acting muscarinic antagonist plus short-acting beta2-agonists to prevent moderate AECOPD 

ERS/ATS guidelines recommend an oral mucolytic agent and a macrolide antibiotic to prevent future AECOPDs in patients with moderate or severe airflow obstruction and AECOPDs despite optimal inhaled therapy. ^[65]  

For patients with stable COPD, the guidelines include the following recommendations for inhaled maintenance therapies ^[64] :

• Maintenance combination inhaled corticosteroid/long-acting beta2-agonist (LABA) therapy to prevent AECOPD 
• Both inhaled long-acting anticholinergic/LABA therapy and inhaled long-acting anticholinergic monotherapy are effective to prevent AECOPD 

ERS/ATS guidelines recommend a LAMA be prescribed in preference to LABA monotherapy to prevent future AECOPD in patients who have moderate or severe airflow obstruction and a history of one or more exacerbations during the previous year. ^[65]

For oral therapy in patients with a history of smoking, recommendations included ^[64] :

• Use of a long-term macrolide to prevent acute exacerbations in patients who have a history of moderate or severe AECOPD in the previous year despite optimal maintenance inhaler therapy
• Within 30 days following an acute exacerbation, systemic corticosteroids administed orally or by IV to prevent hospitalization for subsequent AECOPDs 
• Slow-release theophylline twice daily to prevent AECOPD in patients with stable COPD
• N-acetylcysteine to prevent AECOPDs in patients with a history of two or more exacerbations in the previous 2 years

ERS/ATS guidelines recommend roflumilast to prevent future exacerbations in patients with severe or very severe airflow obstruction, symptoms of chronic bronchitis and exacerbations despite optimal inhaled therapy. In addition, ERS/ATS guidelines recommend against the use of fluoroquinolone therapy for the prevention of AECOPD . ^[65]  

The British Thoracic Society has released guidelines for the use of pulmonary rehabilitation in the management of COPD which include both evidence-based recommendations and good practice points for which there is no research evidence.  The guidelines recommend that pulmonary rehabilitation be offered to patients with COPD with a goal of improving exercise capacity, dyspnea, psychological health and health status by a clinically important improvements. The key recommendations include ^[66] :

• Pulmonary rehabilitation programs should be a minimum of twice-weekly supervised sessions for a duration of 6-12 weeks
• Efficacy of pulmonary rehabilitation needs to be regularly assessed by demonstrating clinically important improvements in exercise capacity, dyspnoea and health status
• To ensure strength and endurance benefits, a combination of progressive muscle resistance and aerobic training should be delivered; interval and continuous training can be applied safely and effectively
• Pulmonary rehabilitation should be provided within a supervised program. If a structured home-based program is considered, mechanisms to offer remote support and/or supervision, provision of home exercise equipment and patient selection are important considerations
• Patients should be taking bronchodilator therapy prior to referral to pulmonary rehabilitation
• Pulmonary rehabilitation at hospital discharge should be offered to patients following acute exacerbation of COPD to commence within 1 month of discharge.
• Inspiratory muscle training (IMT) is not recommended as a routine adjunct to pulmonary rehabilitation
• Patients with low BMI and evidence of quadriceps weakness who are unable or unwilling to participate in pulmonary rehabilitation could be considered for neuromuscular electrical stimulation (NMES)
• Repeat pulmonary rehabilitation should be considered in patients who have completed a course of pulmonary rehabilitation more than 1 year previously
• All patients completing pulmonary rehabilitation should be encouraged to continue to exercise beyond the program

Clinical practice guidelines have been released by the Alpha-1 Foundation for the diagnosis and management of Alpha-1-antitrypsin deficiency (AATD). ^[16]  The guidelines are intended to update the joint guidelines published the American Thoracic Society (ATS) and the European Respiratory Society in 2003. ^[11]

Genetic Testing

The Alpha-1 Foundation recommends the following high-risk groups receive genetic testing for AATD ^[16] :

• All individuals with COPD regardless of age or ethnicity 
• All individuals with unexplained chronic liver disease
• All individuals with necrotizing panniculitis, granulomatosis with polyangiitis, or unexplained bronchiectasis 
• Parents, siblings, and children, as well as extended family of individuals identified with an abnormal gene for AAT, should be provided genetic counseling and offered testing for AATD 

In addition, for diagnostic testing of symptomatic individuals, genotyping for at least the S and Z alleles is recommended. The guidelines recommend against AAT level testing alone for family testing after a proband is identified because it does not fully characterize disease risk from AATD. Advanced or confirmatory testing should include Pi-typing, AAT level testing, and/or expanded genotyping.

The World Health Organization (WHO) recommends that all patients with COPD should be screened once for AATD. ^[2]  VA/DoD recommends testing for AATD in patients presenting with early onset COPD or a family history of early onset COPD and patients with confirmed AATD should be referred to a pulmonologist for management of treatment. ^[27]

Assessment 

The Alpha-1 Foundation guidelines include the following recommendations for evaluation and monitoring ^[16] :

• Complete lung function testing should be performed for initial evaluation
• Spirometry test should be performed at least annually
• In newly diagnosed patients who are symptomatic and/or have abnormal pulmonary function testing, a baseline CT scan of the chest; serial chest CT scanning to monitor disease progression is not recommended
• Monitoring for liver disease at annual intervals (or more frequently as indicated by clinical circumstances) should include focused physical exam for signs of liver disease, liver ultrasound, and laboratory testing of AST, ALT, GGT, albumin, bilirubin, INR, and platelets 

Management

The Alpha-1 Foundation guidelines recommend intravenous (IV) augmentation therapy for patients with confirmed AATD and an FEV1 less than or equal to 65% predicted and/or necrotizing panniculitis. Recommendation against IV augementation therapy include ^[16] :

• Individuals with the MZ genotype of AATD
• Individuals with lung disease due to AATD who continue to smoke
• Individuals with AATD and emphysema or bronchiectasis who do not have airflow obstruction
• The treatment of liver disease due to AATD
• Individuals who have undergone liver transplantation

In addition, doses higher than the FDA approved dose and montioring AAT blood levels to assess dosing are not recommended.

In 2017, the Global Initiative for Asthma (GINA) and the Global Initiative for Obstructive Lung Disease (GOLD) released updated guidelines for the diagnosis and treatment of asthma, COPD and asthma-COPD overlap. The main goal of the consensus-based guidelines is to assist non-pulmonary specialists in the identification of chronic airflow obstructive disease, distinguish between asthma, COPD and ASCO, and determine initial treatment approach. ^[6]

GINA-GOLD no longer use the term asthma-COPD overlap syndrome (ASCO) as asthma-COPD overlap does not describe a single disease entity. Patients with combined features of both disorders more likely have several different phenotypes of airway disease caused by a variety of mechanisms. 

The guidelines suggest a stepwise approach to diagnosis that includes the following steps ^[6] :

• Step 1: Identifying patients at risk for chronic airway disease through clinical history, physical examination, radiology and screening questionnaires
• Step 2: Differentiate asthma, COPD and asthma-COPD overlap based on a comparison of the number of features in favor of each possible diagnosis
• Step 3: Perform spirometry and peak expiratory flow measurement to confirm or exclude diagnoses

Initial treatment recommendations include ^[6] :

• For patients with characteristic features of asthma: adequate controller therapy with inhaled corticosteroids (ICS), but not long-acting bronchodilators as monotherapy
• For patients with characteristic features of COPD: symptomatic treatment with brochodialators or combination ICS-bronchodilator therapy, but not ICS monotherapy
• For patients with characteristics of both asthma and COPD: ICS in a low or moderate dose depending on severity of symptoms; add on treatment with long-acting beta-antagonist (LABA) and/or long-acting muscarinic antagonist (LAMA). Do not treat with LABA monotherapy

For all three diagnoses of chronic airflow limitation, treat comorbidities, reduce modifiable risk factors (i.e., smoking cessation, vaccinations), increase physical activity, encourage appropriate self-management strategies and perform regular follow-up. For COPD and asthma-COPD overlap, pulmonary rehabilitation is appropriate.

Referral to a pulmonary specialist is indicated for the following ^[6] :

• Symptoms persist and/or exacerbations occur despite treatment
• If diagnosis is uncertain or alternative diagnoses such as bronchiectasis, post-tuberculous scarring, bronchiolitis, pulmonary fibrosis, pulmonary hypertension need to be excluded
• Atypical or additional signs and symptoms (e.g., hemoptysis, weight loss, night sweats, signs of bronchielctasis or other structural lung disease)
• Chronic airway disease is suspected but few features of asthma and COPD are present
• Comorbidities are present that may interfere with assessment and management of airway disease