Comparative Study on the Effects of +Gz Exposure and Oxygen Concentration on Small Airway Collapse.

In recent years, the increase in reports of unexplained physiological events in
military aviation emphasize the need for a better understanding of the effects
of in-flight stressors (i.e. hypoxia, temperature, vibration ) on physiological
processes. Among these stressors, exposure to positive G-forces in the
cranio-caudal direction (+Gz) during high speed flight maneuvers, poses unique
challenges that can significantly impact pilot health and performance. One
notable consequence of +Gz exposure is the development of acceleration
atelectasis, a condition characterized by the collapse of terminal airways in
the basal alveoli. This phenomenon occurs when +Gz causes inadequate
ventilation despite maintained perfusion, resulting in atelectasis.

Acceleration atelectasis, or G-induced atelectasis, has been studied since the
1960s. Langdon and Reynolds were the first to describe how increased levels of
sustained +Gz combined with a 100% oxygen concentration led to alterations in
basal lung segments and produced post-flight signs and symptoms such as,
inability to take a deep breath, substernal tightness and paroxysmal coughing.
Additionally, Levy et al. reported ten cases of post-flight basilar
sub-segmental acceleration atelectasis, which were typically asymptomatic,
though some individuals experienced chest pain and cough. Importantly, they
noted that this condition is usually self-limiting, with symptoms resolving and
clear chest x-ray findings within 48 hours post-flight. Hyde et al.
demonstrated that exposure to +3.5 Gz, coupled with the inhalation of 100%
oxy-gen while wearing an anti-G suit, resulted in a 40% decrease in vital
capacity. Later research has corroborated these findings, documenting similar
mechanisms and symptoms.

The development of faster and more agile fighter aircraft in the 1980s and
1990s spurred further investigation into the effects of different gas mixtures
on acceleration atelectasis, particularly with the introduction of on-board
oxygen generating systems (OBOGS). These studies found that gas mixtures
containing more than 70% oxygen were associated with an increased risk of
acceleration atelectasis. They also found protective effects from argon and
nitrogen dilutions, unassisted positive pressure breathing (PPB), and Anti-G
Straining Maneuvers (AGSM). Consequently, the OBOGS was designed to limit the
maximum oxygen concentration to 60% up to 15,000 feet cabin altitude and in
unpressurized aircraft. Recent studies have reaffirmed that breathing 60%
oxygen typically results in only mild acceleration atelectasis.

A major challenge in the study of acceleration atelectasis has been the
measurement of outcomes. Conventional spirometry has long been the gold
standard for evaluating lung function and airway collapse, but it necessitates
forced inhalation or exhalation techniques, which can influence airway collapse
measurements. Recently, the adoption of Forced Oscillation Techniques (FOT) and
Impulse or Airwave Oscillometry (IOS and AOS) has gained traction as methods
for assessing lung function and airway collapse. These oscillometric techniques
measure airway resistance and compliance by generating airwaves at multiple
frequencies, ranging from 5 Hz to 37 Hz. Lower frequencies penetrate deeper
into the airways, providing insights into total airway resistance and
compliance, while higher frequencies are indicative of central airway
conditions.

Pollock et al. assessed lung function after repeated +5 Gz exposure using
spirometry and FOT in two studies. In the first, subjects underwent five
centrifuge runs at varying durations, breathing 94% oxygen in four runs and 21%
in one, with FOT revealing no significant changes in air-way resistance or
compliance. In a second study, five exposures at oxygen levels of 21, 35, 45,
60, and 75% also showed no significant effects. However, the single-frequency
FOT measurements limited the ability to distinguish small from central airway
function, which may be relevant for assessing acceleration atelectasis. In a
collaborative study involving the Royal Netherlands Air Force and the Royal
Canadian Armed Forces, researchers used Airwave Oscillometry to evaluate
resistance and compliance after +9 Gz exposures while subjects donned anti-G
trousers and performed AGSM. This study found significant reductions in
resistance and increases in compliance post-exposure, highlighting the
protective effect of positive intrathoracic pressure and raising questions
about the duration of airway impedance changes.

Understanding changes in airway resistance and compliance at moderate +Gz
levels, where full AGSM may not be necessary, is crucial. Experienced fighter
pilots often personalize their AGSM techniques and adapt their efforts
effectively. In current OBOGS systems the delivered oxygen concentration only
exceeds 60% in unpressurized aircraft to mitigate acceleration atelectasis
risks. Therefore, accurately assessing airway impedance measures at moderate
+Gz levels while breathing 21% and 60% oxygen*before exposure, immediately
post-exposure, and after a recovery period*is essential for determining any
effects and the duration of any observed effects. While previous studies have
predominantly used conventional spirometry or partly used oscillometry, it may
provide more precise measurements by eliminating the need for forced maneuvers
and differentiating between upper and lower airways.

This study aims to assess potential airway collapse during G-exposure at 21%
and 60% oxy-gen, utilizing the full range of airwave oscillometry outcomes to
differentiate resistance, reactance, and compliance among central, total, and
small airways. The research questions focus on observable effects on airway
resistance and reactance during G-exposure with both oxygen levels, with
subjects wearing anti-G trousers and without performing AGSM breathing. The
hypothesis posits that small airway resistance will increase and compliance
will decrease due to small airway collapse. This investigation builds upon the
foundational work of Pollock et al. and Cornelissen et al.

Primary Objective: To determine how exposure to +5Gz forces affects small
airway function when breathing ambient air (21% oxygen) and oxygen enriched air
(60% oxygen) , without the breathing component of the AGSM

Secondary Objective: To explore the interaction between oxygen concentration
and +Gz exposure on respiratory mechanics, focusing on both central and
peripheral airway dynamics.

Study Type: A randomized crossover design where participants serve as their own
controls, exposed to +Gz with breathing both 21% and 60% oxygen concentrations
on separate days.

Blinding: Participants will be blinded to the specific oxygen concentration
they are breathing during each run. The researchers involved in the data
collection will not be blinded due to logistical constraints but will not
interact with participants regarding study conditions.

Study Setting: Center of expertise for aerospace medicine and physiology.

Duration: 4 months (2 months for recruitment, 2 months for intervention (no
follow-up)).

Exposure order of the participants to the oxygen concentrations will be
randomly assigned. Exposure order will be counterbalanced.

Day 1 - Control: Participants will undergo 2 centrifuge runs:
o Baseline measurement whilst seated and strapped in the centrifuge gondola.
o Relaxed G-profile to determine G-tolerance and visual symptoms (either
tunnel vision or grey-out). With this run the participant knows which
symptom indicates the need for more muscle strain to maintain
consciousness. This profile takes usually somewhere between 45 and 60
seconds before visual symptoms appear and the participant terminates
the run.
o +5 Gz profile with anti-G trousers, while breathing normal air (21% oxy-gen)
through a breathing mask. In this profile the participants have to
per-form a correct anti-G straining maneuver if needed, which is the
isometric continuous straining of muscles in the lower extremities and
abdomen.
o Second measurement of airway impedance using the Thorasys tremoFlo, whilst
still seated and strapped in the centrifuge gondola.
o After this the subject is unstrapped, exits the gondola and takes place in a
second mock-up ejection seat to maintain the same seated position
or the next minutes until 30 minutes post-run.
o After 30 minutes post-run a third measurement is taken to determine if any
observed effects are transient within 30 minutes or if they sustain.

Day 2 - Intervention: Participants will undergo 2 centrifuge runs:
o Baseline measurement whilst seated and strapped in the centrifuge gondola.
o Relaxed G-profile to determine G-tolerance and visual symptoms (either
tunnel vision or grey-out). With this run the participant knows which
symptom indicates the need for more muscle strain to maintain
consciousness. This profile takes usually somewhere between 45 and 60
seconds before visual symptoms appear and the participant terminates
the run.
o +5 Gz profile with anti-G trousers, while breathing 60% oxygen through a
breathing mask. In this profile the participants have to perform a
correct anti-G straining maneuver if needed, which is the isometric
continuous strain-ing of muscles in the lower extremities and abdomen.
o Second measurement of airway impedance using the Thorasys tremoFlo, whilst
still seated and strapped in the centrifuge gondola.
Withdrawal of individual subjects
o After this the subject is unstrapped, exits the gondola and takes place in a
second mock-up ejection seat to maintain the same seated position
for the next minutes until 30 minutes post-run.
o After 30 minutes post-run a third measurement is taken to determine if any
observed effects are transient within 30 minutes or if they sustain.

Due to the nature of this study, which only involves benign levels of Gz in a
controlled centrifuge environment, participants are not at risk of any serious
or long lasting injuries. Participants are medically screened before
participation so any participant with contra-indications for exposure to
increased levels of Gz is excluded from participation.