PHR 948 - Block 2: COPD

COPD

chronic obstructive pulmonary disease

- obstructive disorder

- chronic, progressive, & incurable disorder causing severe breathing difficulties

2 pathophysiologies of COPD

1. small airway disease

- chronic bronchitis

- airway inflammation, airway fibrosis, luminal plugs, increased airway resistance

2. parenchymal destruction

- emphysema

- loss of elasticity at alveoli, leading to air trapping

COPD exacerbations

sudden worsening in respiratory symptoms

- increased dyspnea, coughing, wheezing, changes in mucus productions, fatigue

- usually occurs after exposure to triggers or respiratory viruses

- requires additional treatment beyond the normal maintenance medications to improve

- lung functions typically worsens for good after a relapse

global initiative for chronic obstructive lung disease (GOLD)

annual guidelines for COPD

diagnosing and classifying COPD

diagnosing

- look at clinical presentation, symptoms, history, risk factors

- rule out other causes

- spirometry

classifying

- use symptom rating score

- exacerbation/ illness history

- spirometry

- GOLD grade and GOLD ABE group

COPD symptoms

- dyspnea

- chronic cough

- may or may not have mucus production

- recurrent wheeze

COPD risk factors

- tobacco smoking, current or history

- household and outdoor pollution/ occupational exposures

- genetics (alpha-1 antitrypsin deficiency)

- abnormal lung development

- low birth weight/ prematurity

- childhood respiratory infections

spirometry

(pulmonary function tests)

- should be performed AFTER administering a short acting bronchodilator (albuterol)

- look at FEV1/FVC ratio

> if less than 0.7 = COPD diagnosis

GOLD classification of COPD

GOLD grade

- GOLD 1 (mild): FEV1 ≥ 80% of predicted

- GOLD 2 (moderate): 50% ≤ FEV1 < 80% of predicted

- GOLD 3 (severe): 30% ≤ FEV1 < 50% of predicted

- GOLD 4 (very severe): FEV1 < 30% of predicted

GOLD ABE group

- A: no moderate/ severe exacerbations in the previous year

> mMRC 0-1 or CAAT <10 (use worst of the two)

- B: no moderate/ severe exacerbations in the previous year

> mMRC ≥ 2 or CAAT ≥ 10

- E: one or more moderate/ severe exacerbations in the previous year

symptom rating scales

mMRC (modified medical research council dyspnea score)

CAAT (chronic airways assessment test)

- quantifies the severity of symptoms

- obtained at each visit

- used in the ABE tool to classify disease severity (for patients without exacerbation in the last year)

COPD pharmacologic therapy overview

- bronchodilators & anti-inflammatories

bronchodilators: beta 2 agonists (SABA/ LABA), muscarinic antagonists (SAMA/LAMA), or a combo of these two

anti-inflammatories: ICS, chronic macrolide, PDE inhibitors, IL-4 inhibitors

bronchodilators for COPD

beta 2 agonists and muscarinic antagonists

- 1st line treatment for most people

- improves FEV1, improves symptoms, and reduces exacerbations

- long-acting agents are preferred for chronic maintenance

> short-acting agents may be used in addition for rescue therapy

for monotherapy

- LAMA > LABA for exacerbation reduction

- LAMA = LABA for symptom reduction and FEV1 improvement

- LAMA + LABA > monotherapy for all outcomes

inhaled corticosteroids (ICS) in COPD

do NOT use alone in COPD, it increases mortality

- can decrease exacerbations, but no impact on dyspnea

- increases the risk of pneumonia, especially in severe disease

- if patient has blood eosinophils < 100 cells/mcL, little to no benefit from ICS is expected

- if a patient has co-occuring asthma, ALWAYS use an ICS in treatment regimen

ICS place in therapy

use strongly favored if:

- history of hospitalization(s) for exacerbations

- 2+ moderate exacerbations of COPD per year

- blood eosinophils 300+

- history of or concomitant asthma

use favored if:

- 1 moderate exacerbation of COPD per year

- blood eosinophils 100-300

against use if:

- repeated pneumonia events

- blood eosinophils <100

- history of mycobacterial infection

ICS + LABA in COPD

not preferred in most patients

- still used commonly though bc providers are used to this

- if indicated, use triple therapy (LAMA + LABA + ICS)

> triple therapy is superior for reducing exacerbation, improving lunch function and symptoms

phosphodieserase (PDE)

- PDE-4: breaks down cyclic AMP, regulates airway epithelial cell inflammation

- PDE-3: breaks down cyclic AMP and GMP, regulated airway smooth muscle cells (bronchoconstriction/dilation)

- inhibitors of PDE-3/4 increase cAMP and CGMP = decreases inflammation and induce bronchodilation

PDE-4 inhibitor

roflumilast (Daliresp)

- indicated in patients with: severe-very severe COPD (FEV1 <50%), chronic bronchitis features, history of exacerbations requiring hospitalization or treatment with a steroid +/- antibiotic

- can reduce exacerbation frequency and improve lung function, but does NOT decrease symptoms

- ADE: neuropsychiatric effects (anxiety, depression, sleep disturbances), weight loss, GI effects

PDE-3/4 inhibitor

ensifentrine (Ohtuvayre)

- only approved in the US

- unclear place in therapy

- can increase FEV1

- ADE: bronchospasm, psychiatric effects, suicidality, UTI, back pain

chronic macrolide therapy

azithromycin 500 mg three times weekly chronically

- used as an anti-inflammatory, not for antimicrobial

- most beneficial in former smokers with exacerbations despite appropriate inhaled therapy

IL-4 and IL-13 inhibitor

dupilumab (Dupixent)

- SQ injection

- can reduce exacerbations and improve lung function in patients with: chronic bronchitis features, history of 2+ exacerbations per year despite triple therapy, GOLD 2-3, and blood eosinophil count of 300+

IL-5 inhibitors

mepolizumab (Nucala)

- SQ injection

- can reduce exacerbations in patients with: COPD, 2+ moderate exacerbations or 1 severe exacerbation despite triple therapy, GOLD 2-4, and blood eosinophil count of 300+

benralizumab (Fasenra)

- not recommended, no change in exacerbations

COPD non-pharm therapy

- risk factor reduction and trigger avoidance

> smoking cessation!!!!

- vaccinations

- pulmonary rehabilitation (groups B and E only)

pulmonary rehabilitation

- an education and exercise based program to increase awareness of how to exercise or perform everyday activities with pulmonary limitations

- recommended for patients in group B and E

- benefits: reduces symptoms, decreases days hospitalized, increases physical activity & exercise tolerance, improve daily life, and improve emotional health

COPD treatment initiation

- all COPD patients should have a short acting bronchodilator for rescue

> SAMA, SABA, or combo

> if on LAMA, do not give them a SAMA

use ABE to determine initial therapy

A: bronchodilator

B: LABA + LAMA

E: LABA + LAMA + consider ICS if high eosinophils (300)

COPD treatment adjustment

exacerbations:

- if on a LABA or LAMA, increase to combo therapy

- if blood eosinophils high (100-300), consider triple therapy with ICS

- if pt still has exacerbations, consider roflumilast, azithromycin, or biologic

persistent dyspnea:

- if on a LABA or LAMA, increase to combo therapy

- if pt still has dyspnea, consider: switching devices, non-pharm treatments, other causes

classifying COPD exacerbation

mild:

- dyspnea VAS <5

- RR < 24 breaths/min

- HR <95 bpm

- resting O2 sat ≥92% and ≤3% change from baseline

- CRP <10

> treatment: increased use of short acting bronchodilators

moderate: (3+ of these)

- dyspnea VAS ≥5

- RR ≥24 breaths/min

- HR ≥95 bpm

- resting O2 sat <92% or >3% change from baseline

- CRP ≥10

- hypoxemia or hypercapnia

> treatment: increased use of short acting bronchodilators, oral corticosteroids, maybe antibiotics

severe:

- moderate plus new onset of hypercapnia (PaCO2 >45 mmHg) and acidosis (pH <7.35)

where to treat an exacerbation

ambulatory:

- mild exacerbation, minimal comorbid involvement

- cooperative pt, good home support

hospitalization:

- respiratory failure signs/ symptoms

- failure to respond to initial medical management

- serious concomitant comorbidities

- insufficient home support

ICU:

- persistent/ worsening hypoxemia or hypercarbia despite ventilator

- worsening mental status change

- need for invasive mechanical ventilation

- hemodynamic instability

measuring exacerbation severity

- dyspnea visual analog scale (VAS)

- labs: respiratory rate, heart rate, O2 sat, CRP, arterial blood gas

oral corticosteroids in COPD exacerbation

prednisone 40 mg QD x5 days

- no taper needed (unless HPA axis suppression signs)

- can consider budesonide nebulized if contraindications to OCS

antibiotics in COPD exacerbation

cardinal symptoms to support antibiotic use:

- increased sputum purulence (more pus = more yellow)

- increased sputum volume

- increased dyspnea

- patient requires mechanical ventilation

- to assess sputum changes, rely on patient

common pathogens: H. flu, strep. pneumo, moraxella, atypical organisms (mycoplasma, chlamydophila)

empiric antibiotics:

- macrolide (azithromycin)

- tetracycline (doxy)

- beta lactams (amox/clav, amp/sul, 2nd-3rd gen cephalosporin)

- respiratory FQ (levofloxacin, moxifloxacin) ONLY if severe AND pt has beta lactam allergy

exacerbation follow up

- follow up within 1-4 weeks

- ensure appropriate response to therapy

- evaluate maintenance therapy

- assess non-pharm interventions (vaccines, smoking cessation, pulmonary rehab)