Excessive
airway narrowing occurs in asthma and could be, in part, due to increased
velocity of shortening of airway smooth muscle. It has been suggested that the shortening velocity of airway
smooth muscle could limit the fluctuations in airway calibre seen during normal
tidal breathing, such that a slower breathing rate would allow more time for
narrowing during expiration and hence greater differences in calibre.
We
hypothesise:
á
That
tidal fluctuations in airway calibre associated with changes in lung volume
during normal breathing are related to respiratory frequency (fR) as well as to the size
of tidal volume (VT), and
á
That,
after adjusting for fR and VT, tidal fluctuations in airway calibre
will be greater the asthmatic compared with non-asthmatic subjects
In ten asthmatics we will measure airway calibre as
respiratory system conductance using the forced oscillation technique. Measurements will be made during normal
tidal breathing and different combinations of fR and VT
ranging from half to double the normal fR and VT. The effects of different
end-tidal CO2 tension on airway calibre will also be examined. The results of this study in asthmatics
will be compared with similar data, which has already been collected in
non-asthmatic subjects.
In isolated
airway smooth muscle (ASM) and mechanically ventilated rabbits active force
development, or resting muscle tone, is inhibited by tidal stretching. This bronchodilatory effect of tidal
stretching may be as potent as that of pharmacological agents. Furthermore, in humans it has been
shown that breath holding results in a decrease in airway caliber that is
mediated by resting bronchomotor tone.
The basis for the effect of tidal breathing on airway caliber may lie at
the level of cross-bridge mechanics.
Shortening velocity of ASM is intrinsically linked to
cross-bridge mechanics, and Solway and Fredberg have proposed that it is a
significant factor determining airway caliber during normal breathing. ASM with a fast shortening velocity
could cause a greater degree of airway narrowing during tidal expiration than
ASM with a relatively slow shortening velocity because for a given expiratory
time, ASM that shortened faster would have more time to shorten and thereby
also shorten more. It is therefore
possible that the excessive airway narrowing that occurs in asthma could be, in
part, due to increased shortening velocity of ASM.
In mechanically ventilated dogs, mean respiratory system
resistance (Rrs) is inversely related to the frequency or volume of tidal
ventilation. In humans, there is
also a hyperbolic relationship between forced oscillatory frequency and
resistance, including frequencies in the range of normal tidal breathing, which
is thought to be related to the frequency dependence of tissue resistance and
to heterogeneity in the airway tree.
However, in these studies it was not possible to measure intra-breath
changes in airway caliber because the oscillations were either ventilator
waveforms or were done during voluntary apnoea. The contribution of dynamic properties of the airways to
airway caliber during breathing, as proposed by Solway and Fredberg, is still
unknown.
Our aim in this study was to examine the time- and
volume-dependency of intra-breath changes in airway caliber. Using the forced oscillation technique
at 6 Hz, we examined the changes in Grs within breaths during tidal breathing and
were able to compare Grs at end-inspiration with Grs at end-expiration, at
differing respiratory frequencies, end-tidal CO2 tensions and tidal
volumes in healthy subjects. We
hypothesized that, if ASM shortening velocity influences the rate at which
airways narrow, then increasing expiratory time, by decreasing respiratory
frequency, would allow airways to narrow more.
Supervisor:
Dr Cheryl Salome
Address: Discipline of Medicine Level 3, Building
92, Royal Prince Alfred Hospital
Phone: 9515 8383
Email: cms@woolcock.org.au