Small airways disease: time for a revisit?

Figures & data

Figure 1 Graphical representation of a flow-volume loop indicating the traditional parameters (FEV₁ and FVC) and the various flow parameters measured at intervals throughout the forced expiratory curve.

Abbreviations: FEV₁, the forced expiratory volume in one second; FVC, forced vital capacity; MMEF, maximal mid-expiratory flow; MEF₂₅, maximal expiratory flow when 25% of FVC remains; MEF₅₀, maximal expiratory flow when 50% of FVC remains; MEF₇₅, maximal expiratory flow when 75% of FVC remains; PEF, peak expiratory flow.

Figure 2 A typical plot of exhaled volume versus nitrogen concentration (N₂ %) obtained during the single breath nitrogen washout test.

Note: Stages I–IV (including the Phase III slope) are indicated, and the volume relationship between CV, CC, RV and TLC is also shown.
Abbreviations: CC, closing capacity; CV, closing volume; RV, residual volume; TLC, total lung capacity.

Figure 3 A typical sRaw loop in a patient with airflow obstruction, where shift volume is plotted against airflow.

Note: Hysteresis due to airflow obstruction highlights the differential derivation of sRaw using the sReff, sRtot and sR0.5 methods in these patients.
Abbreviations: sRaw, specific airway resistance; sReff, specific effective resistance; sRtot, specific total resistance; sR0.5, specific resistance at the flow of 0.5 litres per second.

Figure 4 sRtot percentage predicted in 254 AATD patients with normal spirometry and varying degrees of airflow obstruction: mild (GOLD Stage I), moderate (GOLD Stage II), severe (GOLD Stage III) and very severe (GOLD Stage IV).

Note: *Significantly different from patients with normal spirometry (P<0.001).
Abbreviations: AATD, alpha-1 antitrypsin deficiency; GOLD, the Global Initiative for Chronic Obstructive Lung Disease; sRtot, specific total resistance.

Table 1 Methodologies to assess small airways function

Test	Strengths	Weaknesses	Change in COPD
Expiratory flows	1. Nonspecialized kit 2. Widely available 3. Integral to spirometry	1. Highly effort dependent 2. Results variable 3. Wide “normal” range 4. Requires careful interpretation	↓ MMEF, ↓ MEF25
Single breath washout	1. Overall assessment of ventilation heterogeneity (Phase III slope) 2. Quick to perform 3. Novel double tracer gas method requires only tidal breathing	1. Classical method is effort dependent 2. CV may be less informative about small airways 3. Double tracer gas method not fully validated	↑ Phase III slope ↑ CV, ↑ CC
Multiple breath washout	1. Assessment of acinar and small conducting airway ventilation 2. Effort independent 3. Evidence suggests that it is sensitive to detection of early disease	1. Time consuming 2. Results can be variable 3. Different tracer gases yield different results 4. Limited information on normal range for older adults	↑ LCI, ↑ Scond, ↑ Sacin
Plethysmography	1. sRaw is effort independent 2. Quick test	1. Achievement of TGV for Raw derivation can be technically demanding 2. Not specific to small airway function 3. Sensitivity to early disease disputable	↑ Raw, ↑ sRaw, ↓ sGaw
Oscillometry	1. Quick and effort independent 2. Robust normal range 3. Specific to small airway function (particularly new FOT systems) 4. Clinically validated – many studies support usefulness	1. Specialized equipment	Early: ↓ X5 only Advanced: ↑ R5 and ↓ X5
CT	1. Allows direct quantification of the presence of disease 2. Gold standard for identifying and quantifying emphysema 3. Preliminary studies of inspiratory/expiratory CT offer promise	1. Exposure to radiation prohibits regular assessment 2. Expensive 3. Requires specialist centers and analysis 4. Achieving consistent RV is difficult 5. Inspiratory/expiratory method not fully validated	Areas of low density at TLC indicate emphysema Additional areas of low density at RV indicate small airways disease

Notes: The table illustrates the different techniques currently available to assess small airways function and their strengths and weaknesses as well as pattern of change classically seen in COPD.

Abbreviations: CC, closing capacity; CV, closing volume; FOT, forced oscillometry technique; LCI, lung clearance index; MMEF, maximal mid-expiratory flow; Raw, airway resistance; MEF₂₅, maximal expiratory flow when 25% of forced vital capacity remains; S_cond, conductive airway heterogeneity; S_acin, acinar airway heterogeneity; X5, reactance at 5 Hz; R5, resistance at 5 Hz; RV, residual volume; sGaw, specific airway conductance; sRaw, specific airway resistance; TGV, thoracic gas volume; TLC, total lung capacity.