COAD

Introduction

• Persistent airflow limitation that is progressive and associated with abnormal inflammatory response
• Chronic bronchitis
• Chronic productive cough/daily sputum production for 3 months of 2 consecutive years where other causes have been excluded
• Emphysema
• Destruction of bronchioles and alveoli
• WHO definition of COAD encompasses chronic bronchitis, emphysema, bronchiectasis and asthma, acknowledging that most patients have combination

Compensated COAD

• Pathophysiology
  • Only 15% of smokers will develop COAD
  • Occupational dust, chemical, air pollution also risk factors
  • Alpha-1 AT deficiency accounts for <1% of cases
  • Chronic inflammation, mucous production and loss of surfactant results in loss of elastic recoil, narrowing and collapse of smaller airways
  • Mucous stasis and bacterial colonisation occur
  • Weak correlation between FEV1, symptoms and QoL
  • Airway obstruction occurs from combination airway secretions, mucosal oedema, bronchospasm and bronchoconstriction
  • In emphysema, alveolar and capillary surface destruction result in alveolar hypoventilation and VQ mismatch with resultant hypoxia and hypercarbia
  • Raised pulmonary pressures result in right heart failure with associated atrial and ventricular arrhythmias

• Clinical
  • Chronic and progressive dyspnoea, cough and sputum
  • Minor haemoptysis is frequent esp. in chronic bronchitis and bronchiectasis (although consider malignancy)
  • Chronic bronchitis have coarse crackles
  • Emphysematous patients have expanded thorax, impeded diaphragmatic motion and global diminution of breath sounds
  • Poor dietary intake and excessive work of breathing cause weight loss
  • Early hypoxia with normal CO2
  • Once FEV1 <1L, hypoxaemia becomes more severe and hypercarbia ensues
  • Signs of severe COAD:
    • Facial vascular engorgement from secondary polycythaemia
    • Tremor, somnolence and confusion from hypercarbia
    • Right heart failure signs

• Diagnosis
  • Spirometry: 
    • Post-bronchodilator FEV1 <80% predicted
    • If FEV1 increases >200mL-400mL consider asthma or co-diagnosis
      • Co-existent in 27% of patients (COPD-X) and these patients have more frequent exacerbations
    • FEV1:FVC <0.7 (COPD-X)
  • Once disease progresses, % FEV1 of predicted is best measure of disease severity and prognosis
  • CXR
    • Bronchiectatic changes
    • Emphysema: Hyperinflation, flat diaphragms, increased parenchymal lucency and attenuation of pulmonary arterial vascular shadows

COPD Severity

COPD GOLD Staging

• Stage 1 – Very mild FEV1 >80% predicted
• Stage 2 – Moderate FEV1 50-80% predicted
• Stage 3 – Severe FEV1 30-50% predicted
• Stage 4 – Very severe FEV1 <30% or FEV1 30-50% and resting hypoxaemia

• Treatment
  • Long-term O2 reduces mortality
    • Criteria: PaO2 <55mmHg, SpO2 <88% or PaO2 55-59 with pulmonary HTN, cor pulmonale or polycythaemia present
  • Drugs do not alter disease progression but provide symptom relief, control exacerbations, improves quality of life and improves exercise performance
  • Bronchodilators
    • LABA + long-acting anticholinergics with PRN SABA preferred
    • Bronchodilators typically improve FEV1 by 10%
  • Corticosteroids
    • Only 20-30% of patients benefit from long-term systemic corticosteroid use
    • Short-term oral pred for acute exacerbations
    • Regular inhaled corticosteroids indicated for documented spirometric response to inhaled corticosteroids, FEV1 <50% or predicted/recurrent exacerbations requiring antibiotics or systemic corticosteroids
  • Theophylline can be used for those with poorly controlled symptoms despite inhaled corticosteroids or LABA
  • Daily azithromycin may decrease acute exacerbations in older patients or those with milder GOLD staging
  • Generous oral fluid intake and room humidification aid mucous clearance
  • Limit antihistamine, antitussive, mucolytics, decongestants and expectorants
  • Smoking cessation is the only intervention that reduces rate of decline in lung function and mortality
  • Pulmonary rehabilitation can improve exercise capacity and quality of life in patients with moderate to severe disease
  • Pneumococcal and influenza vaccination reduce exacerbation frequency and severity
  • Anti-muscarinics
    • Ipratropium may carry increases cardiovascular risk (NNH = 40)
    • Cochrane comparision of ipratropium to tiotropium showed tiotropium had improved lung function, fewer hospital admissions, fewer exacerbations and improved QoL along with fewer adverse events
    • Combining ipratropium with SABA appeared to improve QoL and decreased steroid requirements without increasing adverse effect profile
  • LAMA
    • Duration 12-24 hours
    • Aclidinium (Genuair), glycopyrronium (Breezhaler), tiotropium (Handihaler/Respimat) and umeclidinium (Ellipta)
    • Very few head-to-head comparison studies
    • Tiotropium is the only one proven to reduce exacerabations but all show improved lung function, dyspnoea and QoL
  • LABA
    • Indaceterol (once daily) or salmeterol/formoterol (BD)
    • Improved lung function, QoL, reduced reliever use and reduced exacerbations
    • Do not reduce mortality
    • Indacaterol vs. tioptrium
      • Tiotropium group had 30% fewer exacerbations
  • Combination fixed-dose LAMA/LABA
    • Aclidinium/formoterol (Genuair), Glycopyrronium/indacaterol (Breezhaler), tiotropium/olodaterol (Respimat), Umeclidium/vilanterol (Ellipta)
    • Showed reduced frequent of exacerbations compared to single LABA use (but not LAMA)
  • LAMA/LABA vs. ICS/LABA
    • LAMA/LABA have reduced frequency of exacerbations
  • Oral steroids
    • Only short courses recommended <14 days 20-50mg prednisone
    • Do not need tapering if <14 days
    • If response to oral steroids apparent, inhaled corticosteroids may be indicated
  • Inhaled corticosteroids
    • Recommended for those with frequent exacerbations despite LABA/LAMA treatment

• Pulmonary hypertension
  • Defined as PAP >25mmHg at rest by right heart catheterisation
  • Seen in 50% of severe emphysema patients
  • Associated with worse prognosis, increased hospitalisation
  • No pharmacological agents have shown benefit
    • Trial of bosentan (endothelin-1 receptor antagonist) in COPD-related PHT reduced gas exchange and QoL
    • NO caused worsened VQ mismatch
  • Treat underlying illness i.e. bronchodilation/oxygenation/
  • Pulmonary artery:aorta ratio >1 is 73% sensitive and 84% specific for PHT (better than TTE)

• Surgery
  • No current surgical approaches provide a survival advantage
  • Bullectomy
    • Resection of bullae >5cm
  • LVRS
    • Resection of most severely diseased areas of emphysematous, non-bullous lung to improve elastic recoil and diaphragmatic function
    • Non-surgical alternatives include endobronchial one-way valves, self-activating coils, targeted destruction of emphysematous tissue, bypass tract airway stenting and transpleural ventilation

• Lung transplant
  • Indicated to improve QoL and survival
  • Indications (need majority of)
    • Progressive symptoms despite maximal therapy
    • Not a candidate for LVRS/endobronchial techniques
    • BODE index 5-6
    • PaCO2 >50 and/or PaO2 <60
    • FEV1 <25% predicted
  • Relative contraindications include age >65, obesity, malnutrition, severe symptomatic osteoporosis and colonisation

• Prevent deterioration
  • Smoking cessation
  • Flu and pneumococcal vaccination
    • In people over 65, annual flu immunisation reduces development of severe respiratory complications and hospitalisations or death from respiratory disease and all causes by 50%
    • 13 valent pneumococcal vaccination very effective as compared to polysaccharide vaccine which is less immunogenic in elderly/immunocompromised patients
      • Reduces exacerbations and pneumonia
  • Long-term macrolide antibiotics reduce exacerbations but high rates of adverse reactions so may have role in severe COAD with frequent exacerbations in whom other treatments have been optimised
  • Mucolytics
    • NAC, ambroxol.etc.
    • Small reduction in exacerbations and small improvement in QoL

Acute exacerbations

• >75% due to viral (25%) or bacterial (50%) infection
• Other triggers – Hypoxia, cold weather, beta-blockers, narcotics or sedatives, pneumonia, pneumothorax, PE, acute abdomen, CCF, asthma, tuberculosis, metabolic disturbances
• Final common pathway is release of inflammatory mediators leading to bronchoconstriction, pulmonary vasoconstriction and mucus hypersecretion
• WOB increases, O2 demand of respiratory muscles increases, generating additional CO2 and fatigue
• Primarily VQ mismatch driven vs. expiratory airflow limitation
• Supplemental O2 increases blood oxygen concentration and can help reverse pulmonary vasoconstriction
• Clinical features
  • Hypoxaemia – Tachypnoea, tachycardia, hypertension, cyanosis, ALOC
  • Respiratory acidosis
  • Pursed-lip breathing, accessory muscle use
  • Pulsus paradoxus

• Diagnosis
  • Look for trigger
  • Assess oxygenation/acid-base
  • Check to determine if respiratory acidosis is acute or chronic
    • Acute – 1 for 10; pH change by 0.008 x (40-PaCO2)
    • 4 for 10; pH change by 0.03 x (40-PaCO2)
  • Increase sputum purulence
  • Sputum cultures generally show mixed flora and do not assist ED antibiotic selection
  • CXR – May show trigger or alternative diagnosis
    • CXR confirmed pneumonia as trigger has in-hospital mortality of 20% vs. 5.8%
    • Hyperinflation indicated by >10 ribs posteriorly, >6 ribs anteriorly, large airspace >1/3 sternal length anterior to heart and flattended diaphragms
  • ECG – May identify trigger or cor pulmonale/right heart strain
    • P pulmonale, RBBB, R wave dominance V1/2, ST depression/TWI V1-3
  • FBC, Chem20, Troponin, D-dimer, BNP, CTPA depending on clinical suspicion
  • Even very sick patients can perform an FEV1
    • <1.0L or <40% predicted = severe exacerbation in moderate COAD
  • CRP
    • Llor et al. performed a double-blind, placebo-controlled RCT comparing augmentin vs. placebo in mild-moderate COAD with moderate exacerbations
      • Antibiotics increased clinical cure at day 9-11 overall (74% vs. 60%) and prolonged the time to next exacerbation (233 vs. 160 days)
      • The best CRP cut-off for predicting failure of placebo was 40 (excellent predictive power)
    • Butler et al. performed a multicentre, open-label, RCT in primary care clinics with exacerbations of COAD in England and Wales
      • Patients were randomised to either usual care or usual care supplemented by CRP-guided antibiotic prescription
      • 653 patients underwent randomisation
      • 57% of the CRP-guided group received antibiotics vs. 77.4% of the usual care group
      • COPD Questionnaire at 2 weeks was better in the CRP-guided group

• BAP-65
  • Urea >8.9 (1 point)
  • ALOC (1 point)
  • HR >109 (1 point)
• Classes
  • I – BAP 0 under 65yo – 0.3% in-hospital mortality – 0.3% need for NIV within 48 hours
  • II – BAP 0 over 65 – 1.0% – 0.2%
  • III – BAP 1 – 2.2% – 1.2%
  • IV – BAP 2 – 6.4% – 5.5%
  • V – BAP 3 – 14.1% – 12.4%
  • For III-V consider early NIV +- ICU care

• Differential
  • Asthma – Reversible, earlier onset, FHx, may be co-existent
  • CCF
    • Orthopnoea LR 2.0, dyspnoea with exertion LR 1.3
    • JVP, hepatojugular reflex, bibasal rales
    • CXR cardiomegaly/interstitial oedema
    • BNP >500
    • Can co-exist
  • PE
    • Risk factors may provoke further testing
    • 20-25% patients with COAD exacerbation of unclear trigger have a PE
  • ACS
    • Always get ECG and consider troponin (may not have chest pain)
  • Pneumothorax
  • Pneumonia
    • Bronchiectasis: 
      • Fixed mild to moderate airflow obstruction
      • Chronic productive cough (daily for 2 consecutive years)
      • Clubbing, localized pulmonary crackles, HRCT finding of dilated or plugged small airways at least 2x diameter of accompanying blood vessels
  • Bronchiolitis obliterans

Hypercapnoeic vs. Normocapnoeic

• Risk factors for hypercapnoeic respiratory failure
  • Chronic bronchitis (Vs. emphysema)
  • Obese
  • OSA
  • Sedatives
• Normocapnoeic more likely
  • Emphysema
  • Thin physique
  • Hyperinflation
  • Accessory muscle use
  • Pursed-lip breathing
• Patients with hypercapnoeic failure suffer RHF earlier
  
• Treatment
  • Assess severity; continuous monitoring; VBG/ABG
  • Correct tissue oxygenation – target 88-92%
  • Alleviate reversible bronchospasm
    • SABA +- anticholinergics + oral/IV steroids
    • Consider IV methylxanthine if above treatments do not improve symptoms
  • Treat underlying cause
    • Consider antibiotics if change in sputum, fever or suspicious for infection
    • Consider NIV
  • Bronchodilators
    • Both SABA and anticholinergics are first-line and improve clinical outcomes and ED LOS (especially if used together)
    • Salbutamol every 30-60 min as tolerated
  • Corticosteroids
    • 5-7 day course of systemic steroids improves lung function and hypoxaemia and shortens recovery period
    • Use in the ED does not affect the rate of hospitalisation but reduces the rate of return visits
    • No benefit with doses >40-60mg daily of prednisone
  • Antibiotics
    • Choose agents to cover most common organisms:
      • S. pneumoniae
      • H. influenzae
      • M. catarrhalis
    • Amoxicillin or doxycycline are appropriate
    • Minimal evidence for duration of treatment (3-14 days)
  • Methylxanthines
    • Oral theophylline or IV aminophylline inhibit phosphodiesterase to improve mechanics of breathing (smooth muscle and diaphragm) and anti-inflammatory effect
    • Weak bronchodilator, stimulates respiratory drive, improves right heart function also
    • Third-line agents (narrow therapeutic index and risk of nausea and vomiting)
    • Need to measure serum concentrations (target 55-85mmol/L)
    • Theophylline loading dose 5-6mg/kg IV over 30 minutes then 0.5mg/kg/hr
    • Ensure normoK/Ca/Phos/Mg to optimise muscle fx
  • NIV
    • Indications
      • Type 1 or 2 respiratory failure
      • Severe dyspnoea with clinical signs of fatigue and increased WOB
    • Best to start before pH < 7.30 and fatigue sets in
    • Most benefit if pH 7.25-7.30 at onset
    • Relative contraindications
      • Respiratory arrest
      • Cardiovascular instability
      • ALOC
      • High aspiration risk
      • Viscous or copious secretions
      • Recent facial or gastro-oesophageal surgery
      • Craniofacial trauma
      • Fixed nasopharyngeal abnormalities
      • Burns
    • Reduced intubation rates, short-term mortality rates, symptomatic improvement and length of hospitalisation
    • Unloads respiratory muscles, reduces WOB by matching PEEPi, improves hypercapnoea/acidosis to optimise muscle function
  • Mechanical ventilation
    • Indications
      • Unable to tolerate or failed NIV
      • Respiratory or cardiac arrest
      • Decreased consciousness or agitation
      • Massive aspiration
      • Inability to remove secretions
      • Hypotension
      • Haemodynamic instability
    • Current evidence does not show benefit of heliox or magnesium
    • iPEEP >8-10 mandates reduced respiratory rate/prolonged expiratory time
    • Pplat >25 warrants consideration of reduced respiratory rate/prolonged expiratory time as suggests dynamic hyperinflation
    • Accept hypercapnoea as long as pH >7.2
    • If spontaneously ventilating, try to match CPAP to PEEPi by monitoring degree of chest wall excursion prior to flow triggering
    • Best predictor of successful weaning is premorbid functional status and FEV1
• Disposition
  • Indications for admission
    • Marked increase in intensity of symptoms (resting dyspnoea, inability to walk from room to room)
    • Failure of initial medical management
    • Significant comorbidities
    • Newly occurring dysrhythmias/heart failure
    • Frequent exacerbations/relapses
    • Older age
    • Insufficient home support
  • After ED discharge, 25-43% of patients show ongoing or relapse of symptoms. Risk factors for return within 2 weeks are:
    • 5 or more ED or clinic visits in last year
    • Degree of activity limitation
    • Initial respiratory rate (for each 5/min over 16)
    • Use of oral corticosteroids before ED presentation
  • If discharging:
    • Adequate bronchodilator treatment incl. education
    • Short course of oral steroids
    • Follow-up with primary carer within 2 days
    • Antibiotics if deemed appropriate
    • Safety net
  • Indications for ICU admission
    • Severe dyspnoea with failure to respond
    • Decreasing LOC or agitation
    • Haemodynamic instability
    • Presence of comorbidities leading to end-organ failure
• Prognosis
  • 10% die within 1 year after admission
  • Median survival from first admission is 5 years in men and 8 years in women
  • Inpatient mortality of 7% and 90-day mortality of 15%
  • Inpatient mortality if hypercapnoeic may reach 62% but is only 11% for patients treated with NIV and most deaths are of palliative intent
  • Inpatient mortality if mechanically ventilated 17-30%
  • Hypercapnoeic patients have 12-month readmission rate of 80% and 50% 12 month mortality

Last Updated on December 29, 2021 by Andrew Crofton