| GOLD Stage | FEVโ (% predicted) | Severity |
|---|---|---|
| GOLD 1 | โฅ 80% | Mild |
| GOLD 2 | 50โ79% | Moderate |
| GOLD 3 | 30โ49% | Severe |
| GOLD 4 | < 30% | Very severe |
| Group | Symptoms (mMRC / CAT) | Exacerbations | Initial Therapy |
|---|---|---|---|
| A | Low (mMRC 0โ1, CAT < 10) | 0โ1 (not leading to hospitalization) | Bronchodilator (SABA PRN or LAMA or LABA) |
| B | High (mMRC โฅ 2, CAT โฅ 10) | 0โ1 (not leading to hospitalization) | LABA + LAMA combination |
| E (Exacerbator) | Any | โฅ 2 moderate or โฅ 1 hospitalization | LABA + LAMA. Consider LABA + LAMA + ICS if eos โฅ 300. |
| Check | What | Why |
|---|---|---|
| Confirm COPD | Post-bronchodilator FEVโ/FVC < 0.70 on spirometry | Symptoms alone misdiagnose. Pre-bronchodilator obstruction may reverse and represent asthma. Without spirometry, you'll over-treat reversible disease and under-treat fixed obstruction. |
| Grade airflow limitation | GOLD 1 (FEVโ โฅ 80%), GOLD 2 (50-79%), GOLD 3 (30-49%), GOLD 4 (< 30%) | Informs prognosis and qualifies for some interventions (lung volume reduction, transplant), but does not drive initial drug choice. |
| Check eosinophils | Baseline CBC with diff | Eos < 100: avoid ICS (no benefit, pneumonia risk). Eos 100-299: ICS uncertain, use judgment. Eos โฅ 300: ICS is helpful, especially in exacerbators (key threshold). |
| Assess alpha-1 antitrypsin | Once in every COPD patient, especially < 45 yr, lower lobe disease, family history, or never-smoker | AAT deficiency is treatable with augmentation therapy. Missing it is missing a specific therapy. GOLD recommends one-time testing in every COPD diagnosis. |
| Group | Symptoms | Exacerbations in past year | Initial Maintenance |
|---|---|---|---|
| A | Low (mMRC 0-1 or CAT < 10) | 0-1 moderate, no hospitalization | A bronchodilator (LAMA preferred, but any of SABA-PRN-only, LAMA, or LABA acceptable) |
| B | High (mMRC โฅ 2 or CAT โฅ 10) | 0-1 moderate, no hospitalization | LABA + LAMA (2023 update upgraded from single bronchodilator to combined; better FEVโ and symptoms) |
| E | Any | โฅ 2 moderate, OR โฅ 1 hospitalization | LABA + LAMA; add ICS if eos โฅ 300 (initial triple therapy) |
| Current Regimen | Problem | Step Up |
|---|---|---|
| LAMA or LABA monotherapy | Persistent dyspnea | LABA + LAMA (combined inhaler preferred for adherence) |
| LABA + LAMA | Persistent exacerbations, eos โฅ 300 | Add ICS โ ICS + LABA + LAMA triple (Trelegy, Breztri). IMPACT (2018) and ETHOS (2020) showed triple reduces exacerbations vs dual and ETHOS showed mortality benefit. |
| LABA + LAMA | Persistent exacerbations, eos < 100 | Add roflumilast (PDE4 inhibitor) for chronic bronchitis phenotype with FEVโ < 50%, or azithromycin 250 mg daily or 500 mg 3ร/wk for ex-smokers. ICS unlikely to help here. |
| Triple therapy | Persistent exacerbations, eos โฅ 300 | Add biologic (see Step 5) |
| Triple therapy | Persistent exacerbations, eos < 100, chronic bronchitis | Add roflumilast 500 mcg daily (REACT/RE2SPOND: ~17% exacerbation reduction). GI side effects rate-limit. |
| Triple therapy | Persistent exacerbations, frequent infections | Azithromycin 250 mg daily or 500 mg M/W/F. Check QTc and audiogram first (QT prolongation, ototoxicity). Most benefit in ex-smokers. |
| Intervention | When | Why |
|---|---|---|
| Smoking cessation | Every visit, every active smoker | The only intervention that slows FEVโ decline and reduces mortality. Combine pharmacotherapy (varenicline or NRT) with counseling. |
| Pulmonary rehab | Symptomatic patients (mMRC โฅ 2), and ALL within 4 weeks of an exacerbation hospitalization | Reduces hospital readmission ~30%, improves exercise tolerance, dyspnea, QOL. Single highest-yield non-pharm intervention after smoking cessation. |
| Long-term oxygen therapy | Resting PaOโ โค 55 or SpOโ โค 88%, OR PaOโ 56-59 with cor pulmonale, polycythemia (Hct > 55%), or peripheral edema. โฅ 15 hr/day. | NOTT (1980): > 15 hr/day Oโ reduced mortality. Not for isolated nocturnal or exercise desaturation (LOTT 2016 showed no benefit there). |
| Home NIV (BiPAP) | Stable severe hypercapnic COPD (PaCOโ โฅ 52) with nocturnal hypoventilation or recent post-exacerbation hospitalization | HOT-HMV (2017): home NIV reduced readmission/death 17% in post-exacerbation hypercapnic patients. |
| Lung volume reduction (surgical or endoscopic valves) | Severe upper-lobe-predominant emphysema with hyperinflation and low exercise tolerance despite GDMT | NETT (2003): surgery improved exercise capacity and survival in upper-lobe-predominant, low-exercise-capacity subset. Endoscopic valves (Zephyr) approved 2018 for selected patients. |
| Lung transplant | Refractory severe COPD, FEVโ < 25%, hypercapnia, pulmonary HTN, BODE 7-10 | End-stage when all other options exhausted. Refer early to a transplant center. |
| Vaccines | All patients | Influenza annually, PCV20 (or PCV15 + PPSV23), COVID-19, Tdap (then Td q10y), RSV โฅ 60, Shingrix โฅ 50. Reduces exacerbations and pneumonia. |
| Scenario | Do This | Why |
|---|---|---|
| ASTHMA-COPD overlap (history of asthma, atopy, eos high, reversible component on spirometry) | ICS-containing regimen from the start (ICS+LABA, escalate to triple as needed) | ICS-naive treatment is dangerous in asthma. Treat as asthma overlap when in doubt; don't withhold ICS waiting for exacerbation history. |
| Frequent pneumonia on ICS | Step down to LABA + LAMA (drop the ICS), especially if eos < 100 | TORCH and FLAME: ICS modestly raises pneumonia risk. If eos doesn't support ICS and patient gets pneumonia repeatedly, withdraw it. SUNSET (2018) showed safe ICS withdrawal in non-eos patients. |
| Persistent symptoms on optimized triple, eos < 100 | Re-evaluate diagnosis: HF (BNP, echo), bronchiectasis (CT chest), pulmonary HTN, OSA, deconditioning, anxiety | Comorbidity drives "treatment-resistant COPD" more often than under-treatment. Don't stack more drugs onto the wrong diagnosis. |
| Patient using SABA > 2ร/week | Step up maintenance therapy | SABA overuse is a marker of poorly controlled disease, mirrors the asthma SABA-overuse signal (AUSTRI, etc.). |
| Acute exacerbation (worsening dyspnea, sputum volume/purulence) | Add oral steroid burst (prednisone 40 mg ร 5 days, REDUCE 2013), antibiotic if increased purulence or hospitalized, increase short-acting bronchodilators. See COPD Exacerbation. | Acute management is separate from chronic escalation. After resolution, reassess group and consider step up. |
| Hypercapnic respiratory failure (pH < 7.35) | BiPAP first, intubate only if NIV fails or contraindicated | Brochard 1995: NIV reduces intubation 65%. Hypoxic drive concerns are overblown, target SpOโ 88-92% to avoid hyperoxic COโ retention without underventilating. |
| Alpha-1 antitrypsin deficiency | Standard COPD therapy PLUS IV augmentation therapy (Prolastin, Zemaira) if ZZ phenotype with COPD | Disease-modifying for AAT, slows FEVโ decline. Refer to specialty center. |
| End-of-life / palliative phase | Add low-dose opioids for dyspnea, anxiolytics for air hunger, palliative care referral | Morphine 1-2 mg PO q4h PRN provides dyspnea relief without respiratory depression at low dose. Pulm rehab + GDMT only goes so far in end-stage disease. |
| Drug Class | Examples | When | Key Notes |
|---|---|---|---|
| SABA PRN RESCUE | Albuterol (ProAir/Ventolin) 2 puffs q4โ6h PRN | All patients -rescue inhaler | Quick onset (5โ15 min). If using > 2ร/week โ step up maintenance therapy. |
| LAMA 1ST LINE MAINTENANCE | Tiotropium (Spiriva) 18 mcg daily Umeclidinium (Incruse) 62.5 mcg daily | Group A (monotherapy) or as part of combination | Preferred first-line maintenance in COPD (unlike asthma where ICS is first). Reduces exacerbations. Once-daily dosing. |
| LABA 1ST LINE MAINTENANCE | Salmeterol (Serevent) 50 mcg BID Formoterol 12 mcg BID Indacaterol (Arcapta) 75 mcg daily | Monotherapy or combination | Long-acting bronchodilator. Never use LABA alone in asthma (but OK in COPD). |
| LABA + LAMA GROUP B/E | Umeclidinium/vilanterol (Anoro Ellipta) Tiotropium/olodaterol (Stiolto) | Group B (symptomatic), Group E (exacerbator) | Dual bronchodilation = backbone of COPD therapy. Better than either alone for FEVโ, symptoms, and exacerbation reduction. |
| ICS (add-on) SELECTIVE USE | Fluticasone, budesonide (always in combination with LABA ยฑ LAMA) | Only if eosinophils โฅ 300 or frequent exacerbations despite LABA+LAMA | ICS is NOT first-line in COPD (unlike asthma). Increases pneumonia risk TORCH, 2007. Use blood eosinophils to guide: โฅ 300 โ add ICS. < 100 โ avoid ICS. |
| Triple: ICS + LABA + LAMA ESCALATION | Fluticasone/umeclidinium/vilanterol (Trelegy Ellipta) | Group E with eos โฅ 300 or persistent exacerbations on dual | IMPACT, 2018: triple reduced exacerbations by 15% vs LAMA+LABA and 25% vs ICS+LABA. ETHOS, 2020: also showed mortality reduction. Best evidence for triple in high-eos exacerbators. |
| Biologics NEW 2026 | Mepolizumab (Nucala) 100 mg SC q4 wk Benralizumab (Fasenra) 30 mg SC q8 wk Dupilumab (Dupixent) 300 mg SC q2 wk | Severe eosinophilic COPD with frequent exacerbations AND blood eos โฅ 300 cells/ฮผL despite optimized triple therapy | GOLD 2026 codified biologic add-on for severe eos COPD. Mepolizumab and benralizumab target IL-5 / IL-5R; dupilumab targets IL-4Rฮฑ (used in eos COPD with elevated FeNO or atopy overlap). BOREAS, 2023 ยท NOTUS, 2024 ยท MATINEE, 2024. Expensive ($30-40k/yr) -prior auth required. |
Topic-specific workup details are in the Overview and Management tabs.
Medication details are in the Management tab with evidence-based dosing and trial citations.