Minimal Clinically Important Differences in COPD Lung Function

Figures & data

Table 1.  Other Factors Influencing MCID for FEV₁.

▪ Baseline level of FEV1 (ATS/ERS or GOLD)

▪ Baseline reversibility to albuterol status

▪ Diurnal variability

▪ Decline of baseline over time

Table 2.  Classification of Severity.

Stage	Characteristics
0: At Risk
• Chronic symptoms (cough, sputum production)	• Normal spirometry
I: Mild COPD
• With or without chronic symptoms (cough, sputum production)	• FEV1/FVC < 70%
	• FEV1≥ 80% predicted
II: Moderate COPD
• With or without chronic symptoms (cough, sputum production)	• FEV1/FVC < 70%
	• 50% ≤ FEV1 < 80% predicted
III: Severe COPD
with or without chronic symptoms (cough, sputum production)	• FEV1/FVC < 70%
	• 30% ≤ FEV1< 50% predicted
IV: Very severe COPD
• FEV1< 30% predicted or FEV1< 50% predicted plus chronic respiratory failure	• FEV1/FVC < 70%

*Classification based on postbronchodilator FEV₁. FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; respiratory failure: arterial partial pressure of oxygen (PaO₂) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO₂ (PaCO₂) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level.

We would like to acknowledge the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and the GOLD website (http://www.goldcopd.com) as the original source of this table.

Table 3.  Considerations in Determining the MCID for FEV₁.

FEV1	Poor correlation with survival and other outcomes
FEV1	Poor correlation with typical activities of a patient with COPD

Table 4.  Predose (Trough) FEV₁.

▪ Average of 2 measures taken at one hour and five minutes prior to dose

▪ Last measure/observation carried forward (dropout)

▪ Mean value of multiple observations (completed patient)

▪ End of study value (completed patient)

Table 5.  Additional Considerations in MCID for FEV₁.

▪ Broad acceptability and reproducibility criteria (200 mL)

▪ Overlap with placebo effect (up to 100 mg)

▪ Issue with repeatability (120 mL) and variability (160 mL)

▪ Differing methods of selecting “best FEV1”

▪ Differences due to equipment and site (flow type spirometry 44%)

▪ Effects of prior inspiratory maneuver (8%)

▪ Effects of thoracic gas compression

▪ Effects of six second maneuver

Table 6.  MCID FEV₁ Anchors.

Anchor	Change in FEV1
Patient perception	112 mL
Exacerbations	100–120 mL
Smoking cessation	31 versus 62 mL/y
COPD—yearly decline	50 mL/y
Clinical trials	45–180 mL

Table 7.  MCID FEV₁—Clinical Trials Anchors.

- LABA	- 100 mL
- LAAC	- 120 mL
- ICS	- 50 mL
- PDE4	- 45–100 mL
- Comb ICS/LABA	- 100–164
- Comb LABA/Theo	- 180 mL
- Comb LAAC/LABA	- 108 mL (12 hour)

Figure 1. Response of FEV₁ over 12 hours to tiotropium, salmeterol and placebo. Reprinted from Ref. [[17]].

Figure 2. Mean change from baseline in FEV₁ on treatment day 1 (top panel) and after 12 weeks of treatment (bottom panel). Baseline FEV₁ for serial testing was the screening visit FEV₁. The morning dose of study medication was taken immediately after the hour 0 PFT was obtained on each day.

Table 8.  Response of FEV₁ to Tiotropium, Salmeterol and Placebo.

	Tiotropium	Salmeterol	Placebo
Trough response (ml):
Day 169–15	− 13 [13]	− 14 [13]	− 35 [13]
Peak response (ml):
Day 169–1	20 [15]**	− 44 [16]	− 56 [15]
Day 169–15	− 21 [13]	− 26 [14]	− 26 [13]
Average 0–4 h (ml):
Day 169–1	22 [14]*	− 32 [15]	− 50 [14]
Day 169–15	− 21 [12]	− 13 [13]	− 25 [12]
Average 4–8 h (ml):
Day 169–1	− 1 [14]	− 25 [15]	− 68 [14]*
Day 169–15	− 12 [13]	− 12 [13]	− 23 [13]
Average 8–12 h (ml):
Day 169–1	− 3 [13]	− 21 [14]	− 66 [13]*
Day 169–15	− 8 [13]	− 10 [13]	− 27 [13]
Average 0–12 h (ml):
Day 169–1	5 [13]	− 25 [14]	− 61 [13]*
Day 169–15	− 13 [12]	− 11 [13]	− 25 [12]

Mean [SE] FEV₁ response following 24 weeks treatment. P-values indicate statistical significance in comparison to placebo.

Reprinted from Ref. [[69]].

Figure 3. FEV₁ response to increasing doses of ipratropium in COPD. Mean FEV₁ values are shown at baseline (0 h) and during the 8 h after administration of each of seven agents in 42 subjects with COPD (open circles = placebo; closed circles = 0.05 mg nebulized ipratropium; open triangles = 0.1 mg nebulized ipratropium; closed triangles = 0.2 mg nebulized ipratropium; open squares = 0.4 mg nebulized ipratropium; closed squares = 0.6 mg nebulized ipratropium; open inverted triangles = 40 µg ipratropium by metered-dose inhaler). Reprinted from Ref. [[23]].

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