By

Dr: Samiaa Hamdy Sadek

Lecturer of chest diseases

Assessment of small airways functions

DefinitionThe small airways are defined as those less than

2 mm in diameter.

They are a major site of pathology in many lung

diseases, not least chronic obstructive pulmonary

disease (COPD) and asthma.

They have proven relatively difficult to study due

to their relative inaccessibility to biopsy and their

small size which makes their imaging difficult.

Large V/S Small airways

Large airways Small airways

Have cartilagnous support

and mucous gland

Less cross sectional area

Turbulent flow

Resistance affected by gas

density

No surfactant lining over

the epithelium

Lack catilaginous support

and mucous gland

Larger cross sectional

area

Laminar flow

Gas density has no effect

on resistance

Surfactant lining and

hence low surface tension

Airway anatomy The first 15 generations of

airways are called the conducting airways and take no part in gas exchange, they constitute the anatomical dead space

Beyond this region lie the respiratory bronchioles which have occasional alveoli budding from them. These continue to divide until they reach the alveolar sacs with a total surface area of 70-80 m2.

The small airways occur from approximately generation 8 and include a portion of the conducting airways as well as all the acinar airways.

Physiological assessment of the small airways

Small airways obstruction may lead to:

Reduction in airflow

Increased airways resistance

Gas trapping

Inhomogeneity of ventilation.

1- Spirometry

A.The Forced Expiratory Flow between 25 and 75% of the

FVC (FEF25-75) is one of the most commonly cited

measures of small airways pathology.

Advantage:

It is effort independent.

Rate of airflow peak at large lung volume close to TLC.

With decreasing lung volume intrathoracic airway become

narrow with increased resitance and increasing effort at

low and intermediate lung volume produce little or no

increase in airflow.

1- Spirometry

Disadvantages:

Poor reproducibility as it is dependent on the FVC

and therefore changes in FVC will affect the portion

of the flow-volume curve examined.

FEF25-75 is frequently normal if the FEV1/FVC

ratio is≥ 75%

There is poor correlation with other markers of

small airways disease such as gas trapping and

histological evidence of small airways inflammation

1- Spirometry

Alternatives:

FEV3/FVC

1-FEV3/FVC

The ratio of the FVC to slow vital capacity (SVC)

These measures have a better accuracy than

FEF25-75 particularly in advancing age.

2-Plethysmography

The residual volume (RV) is an important measure

of small airways dysfunction and may be raised

before the onset of abnormal spirometry in asthma

and correlates with the degree of inflammatory

changes in small airways in COPD

The residual volume/total lung capacity (RV/TLC)

ratio may be a more useful marker of gas trapping

3- Dynamic Compliance

Definition:

Change in lung volume during airflow producedbya given change in transpulmonary pressure.

Normally ratio of dynamic complianc (Cdyn)/static compliance(Cst)>0.8 even with high breathing frequeny >60 breath/minute.

In presence of uneven ventilation and small airway diseases marked decrease in Cdyn observed with increasing breathing frequency.

Physiologic principle:

In presence of uneven ventilation there are two types of alveoli.

3- Dynamic Compliance

Fast alveoli (low resistance) filled rapidly with

air, and slow alveoli(high resistance) need long

time for filling.

With increasing respiratory frequency there is

no sufficient time for filling of slow alveoli so

Cdyn decreased compared to Cst.

4- Inert gas washout

The most commonly employed technique is the

single breath nitrogen washout (SBNW) and

more recently the multiple breath nitrogen

washout (MBNW).

Other gases may be used including helium and

sulphur hexafluoride (SF6) whose physical

properties determine gas flow within the lung.

A- Single breath nitrogen washout(closing volume)

The SBNW is performed by inhaling 100%

oxygen from RV to TLC followed by a SVC

exhalation.

The exhaled volume and nitrogen concentration

is measured and the resulting trace can be

broken down into four distinct phases.

A- Single breath nitrogen washout(closing volume)

In phase I, the nitrogen concentration is close to 0% as this represents anatomical dead space. During phase II, there is a sharp rise in the expired nitrogen concentration as dead space gas mixes with resident alveolar gas. Phase III represents alveolar gas and the expired nitrogen concentration begins to plateau. Finally, in phase IV, there is a steep rise in expired N2 concentration as the most poorly ventilated areas (with little O2 mixing) empty. This is also the point at which the small airways start to and is known as the closing volume (CV).

A- Single breath nitrogen washout(closing volume)

Normally, small airways closure occurs

close to RV.

However, small airways disease may cause

premature airway collapse resulting in an

increased CV and gas trapping.

CV may be expressed as a ratio of VC and

should not exceed 10- 25% of FVC.

B-Multiple breath nitrogen washout(MBNW)

The patient inhales 100% O2 from FRC.

Follwed by exhalation with fixed tidal

volume and respiratory rate to wash out the

resident nitrogen from the lungs.

The test continues until the exhaled

nitrogen is less than 1/40th of the original

concentration (approximately 2%) for three

successive breaths.

B-Multiple breath nitrogen washout(MBNW)

This technique allows for measurement of the efficiency

of gas mixing in the whole lung through the lung clearance

index (LCI).

LCI is defined as the number of lung turnovers (FRC

equivalents) required to wash out the tracer gas to 1/40th

of the original concentration. This is calculated by

measuring the cumulative expired volume (CEV) required

to washout the resident nitrogen and dividing it by FRC:

LCI=CEV/FRC

Multiple Breath N2 Washout

Lung clearance index(LCI)

LCI =

Cumulative expired volume(CEV)/FRC

LCI = 6.25 + 0.02 x Age

C- Helium-oxygen flow volume curves:

Physiological principle:

At lung volume greater than 10% of VC the main site of resistance in large airway.

Flow in large airway is turbulant density dependent.

Flow obtained with helium oxygen mixture will be higher than flow obtained with breathing air

In contrast at lung volume <10% of VC main site of resistance in small airway where flow is laminar so not density dependent.

At lung volume <10% of VC flow obtained with breathing air equal that of He/O2 mixurevolume of isoflow.

C- Helium-oxygen flow volume curves:

In healthy subject volume of isoflow at 10% of VC.

In small airway diseases volume of isoflow > 10% of VC.

VEmax50% He-air=VEmax50% He-air VEmax50% air/

VEmax50% air

5-Impulse oscilometry IOS

IOS is a form of forced oscillation technique where

small external pressure signals superimposed on the

natural breathing to determine a subject’s breathing

mechanics.

FOT measures respiratory impedance to this applied

forced pressure oscillations produced by a loud

speaker

Parameters measured by IOS:

The respiratory Impedance (Z) measured by IOS

is a complex quantity and consists of a real part

called respiratory Resistance (R) and an imaginary

part called respiratory Reactance (X).

Z ( f )= R ( f ) + jX ( f )

IOS also includes hallmarks such as Resonant

Frequency (Fres) and Reactance Area (AX) also

known as the “Goldman Triangle”.

a. Respiratory Resistance (R)

Resistance (R), which includes the resistance of the

proximal (central) and distal (peripheral) airways as

well as lung tissue and chest wall while these latter

resistances are usually negligible.

In healthy adult subjects, R is nearly independent

of oscillation frequency.

When an airway obstruction occurs, either central

or peripheral, R5 (Resistance at 5 Hz) is increased

above normal values.

a. Respiratory Resistance (R)

Central airway obstruction elevates R evenly

independent of oscillation frequency.

Peripheral airways obstruction is highest at

low oscillation frequencies and falls with

increasing frequency; this is called the negative

frequency-dependence of Resistance (fdR).

Resistance is measured in cmH2O/L/s or

KPa/L/s

b. Respiratory Reactance (X)

Reactance (X), includes the Inertance (I) and the

capacitance (C)

Inertance is the mass-inertive forces of the moving

air column. Inertia is the tendency of a body to

preserve its state of rest or uniform motion unless

acted upon by an external force

Capacitance (C) is the elastic properties

(compliance) of lung periphery.

Reactance is measured in cmH2O/L/s or KPa/L/s

c. Resonant Frequency

The Resonant Frequency (Fres) is the point at

which C and I are equal, therefore reactance is

zero and is measured in Hertz (1/s)

It is a suitable marker to separate low

frequency from high frequency impedance.

Respiratory system abnormalities cause Fres

value to be increased.

d. Reactance Area (AX)

The Reactance Area (AX), – the “Goldman

Triangle” - was introduced by Michael

Goldman.

AX is the integrated low frequency

respiratory reactance magnitude between 5 Hz

and Fres, and is measured in cmH2O/L or

KPa/L.

AX is a useful and sensitive index of

peripheral airway function.

Healthy adult Rrs(f) curve is almost rectilinear, frequency dependence of resistance is absent (fdr=0), which is confirmed by the following data: Rrs5=Rrs20=0.26 kPa/(L/s).

Rrs(f) and Χrs(f) curves of a 79 year-old COPD (GOLD stage III) male patient Significant increase of Rrs5 (Rrs5=0.51 kPa/(L/s)) as well as fdr,increase of ΑΧ as well as the impressively increased resonant frequency (fres=25.8 Ηz).

In bronchial asthma hyper-reactivity and inflammatory infiltration of the wall of central and peripheral airways alike in bronchial asthma, significant changes are observed also in high frequency impedance parameters and thus fdr is less impressive

A 52 year-old patient with Idiopathic Pulmonary Fibrosis Significant increase of Rrs5, whereas high frequency resistance values remain within normal significant fdr=95%. Impressive increase of Xrs5, fres, and ΑΧ.

Variable intrathoracic upper airway obstruction R increased

uniformely through all frequencies , while X, fres, and ΑΧ are

within normal.

Variable extrathoracic obstruction gives the same pattern as

peripheral airway obstruction.

Rrs may be considered within normal limits if Rrsat 5 Hz (Rrs5) is within¡1.64 SD of the predicted value. Rrs5 values between 1.64 and 2 SD above predicted may be considered minor,>2 SD moderate and >4 SD above predicted severe obstruction.

Xrs5 characterises the lung periphery, but is nonspecific as to the type of limitation. It is more negative in restrictive and obstructive lung diseases.

In normal adults, fres is usually 7–12 Hz.

Other tests

6-Exhaled nitric oxide

7-Imaging of the small airways

a) High resolution CT

b) Hyperpolarised helium magnetic resonance imaging(3He MRI)

c) Two-dimensional gamma(2-D gamma) scintigraphy

d) Single photon emission computed tomography(SPECT)

e) Positron emission tomography