A 42-year-old man with moderate persistent asthma is on low-dose inhaled corticosteroid but continues to have symptoms 4–5 days per week and occasional nocturnal awakening. His FEV₁ is 70% predicted. What is the drug of choice to add to his current regimen?

Explanation

## Step-Up Therapy in Asthma: ICS + LABA **Key Point:** This patient has inadequate control on low-dose ICS monotherapy (symptoms 4–5 days/week, nocturnal awakening, FEV₁ 70%). He requires **step-up to low-dose ICS + LABA** (GINA Step 3). ### Rationale for ICS + LABA Combination **High-Yield:** When ICS monotherapy fails to achieve control: 1. First step-up is to add LABA (e.g., salmeterol, formoterol) to the existing ICS 2. LABA provides bronchodilation and has additive anti-inflammatory effects when combined with ICS 3. Fixed-dose ICS/LABA combination inhalers are preferred for adherence and safety **Clinical Pearl:** LABA must ALWAYS be combined with ICS in asthma. LABA monotherapy increases asthma-related mortality and is absolutely contraindicated. ### Step-Up Algorithm ```mermaid flowchart TD A[Asthma diagnosed]:::outcome --> B{Persistent symptoms?}:::decision B -->|No| C[Intermittent: SABA PRN]:::action B -->|Yes| D[Mild persistent: Low-dose ICS]:::action D --> E{Controlled on ICS?}:::decision E -->|Yes| F[Continue ICS monotherapy]:::action E -->|No| G[Step-up: Add LABA to ICS]:::action G --> H{Controlled?}:::decision H -->|No| I[Step 4: High-dose ICS/LABA or add LTRA]:::action H -->|Yes| J[Maintain ICS/LABA]:::action ``` ### Comparison of Step-Up Options | Option | Indication | Limitation | |--------|-----------|------------| | **LABA (add to ICS)** | Step 3; inadequate control on ICS alone | Must use with ICS; never monotherapy | | Oral corticosteroid (maintenance) | Step 5; severe asthma; not routine step-up | Systemic side effects; reserved for severe/refractory disease | | LTRA (add to ICS) | Alternative add-on or ICS-intolerant; weaker than LABA | Less effective than LABA; used if LABA contraindicated | | Omalizumab | Allergic asthma with elevated IgE; not routine step-up | Expensive; requires IgE level 30–700 IU/mL; biologic, not first-line add-on | **Warning:** Do NOT jump to oral corticosteroids or biologics without first optimizing ICS/LABA combination. [cite:GINA 2023 Global Strategy for Asthma Management and Prevention; Harrison 21e Ch 297]