JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL SCIENCES
A Comparative Study of
breath holding time as an Index of Central Ventilatory Response in
young Healthy Adults of both Sexes. J Pharm Biomed Sci 2014;04(09):806-812.
Dharwadkar AA,Chenmarathy BB,Dharwadkar AR.
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Research article
A Comparative Study of breath holding time
as an Index of Central Ventilatory Response
in young Healthy Adults of both Sexes
Asha A Dharwadkar*, Bindu. C.B, Anand R Dharwadkar
Affiliation:-
Professor, Department of Physiology, Amala Institute
of Medical Sciences, Thrissur, Kerala,India
The name of the department(s) and institution(s) to
which the work should be attributed:
Department of Physiology, Amala Institute of Medical
Sciences, Thrissur, Kerala,India
Address reprint requests to
*Dr.Asha A.Dharwadkar.
Professor, Department of Physiology, Amala Institute
of Medical Sciences, Thrissur, Kerala, India or at
[email protected]
Article citation:
Dharwadkar AA,Chenmarathy BB,Dharwadkar AR. A
Comparative Study of breath holding time as an Index of
Central Ventilatory Response in young Healthy Adults of
both
Sexes.
J Pharm Biomed Sci. 2014;
04(09):806-812. Available at www.jpbms.info
ABSTRACT
Relationship of anthropometrical parameters & sex
to BHT is not reported in any studies done so far. A
comparative study was carried out to evaluate Breath
holding time [BHT] upto breakpoint as an index of
central ventilatory response in young healthy adults
of both sexes[n=99; female 59; male 40]. The
anthropometrical
parameters,
resting
RR
[breaths/min] & BHT [ seconds] after deep inspiration
upto break point were recorded before & after deep
breathing session [i.e. at the rate of 6 breaths /min
for 5 minutes].Statistical analysis was done with the
th
help of SPSS 16 version by both Paired& Unpaired
Students’ ‘t’ test; and correlation.
P<0.05 is
considered as significant.It is observed that BHT
measured at Total lung capacity did not show any
correlation to anthropometrical parameters like
Height [cms], Weight [Kgs], BSA [m 2], BMI [kg/m2]
either in females or males on separate analysis. The
proportionately decreased BHT in females, in both
recordings taken before & after deep breathing
session, indicates increased sensitivity of respiratory
center in females, attributable to oestrogen primed
progesterone action. Normal RR with decreased BHT
indicates the possibility of the renal regulatory
mechanisms trying to maintain a state of chronic
respiratory alkalosis in females. Awareness of the
presence of Chronic respiratory alkalosis status
existing in normal young females, more so during
pregnancy, may help clinicians for better evaluation
& management. So BHT [at TLC] & Respiratory rate
together may act as an index of central ventilatory
response, inturn the sensitivity of respiratory center.
KEYWORDS: Anthropometry; Body mass index;
Body weight; Break point; Breath holding; Central
ventilatory response; Progesterone; Respiratory
center.
INTRODUCTION
T
wo separate neural mechanisms regulate
respiration. One is responsible for voluntary
control and the other for automatic control.
The voluntary system is located in the cerebral
cortex and sends impulses to the respiratory
motor neurons via the corticospinal tracts. The
automatic system is driven by a group of
pacemaker cells in the medulla. Impulses from
these cells activate motor neurons in the cervical
806
and thoracic spinal cord that innervate inspiratory
muscles1.
Respiration has voluntary control over automatic
regulation, but there is a limit for it. Because the
voluntary modulation of respiration is not in
proportion to the body’s demand of O2 & removal
of CO2. So the associated changes in PCO2 , PO2 &
H+ions concentration, try to override the voluntary
modulation. Voluntary apnoea [breathholding] is
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followed by involuntary hyperpnea and voluntary
hyperpnea is followed by involuntary apnea.
The nervous system normally adjusts the rate of
alveolar ventilation almost exactly to the demands
of the body, so that the oxygen pressure (PO2) and
carbon dioxide pressure (PCO2) in the arterial
blood are hardly altered even during heavy
exercise and most other types of respiratory
stress2.
The respiratory center is under the direct influence
of arterial concentration of carbon dioxide and
hydrogen ions. A change in blood carbon dioxide
concentration therefore has a potent acute effect
on controlling respiratory drive but only a weak
chronic effect after a few days’ adaptation due to
renal handling2.
For more than a century the influence of sex
hormones on breathing is studied. Studies by
Hasselbach reported that women have decreased
alveolar PCO2 and lowered arterial PCO2 during
pregnancy3,4. Later studies described cyclic
fluctuations in ventilation during the normal
menstrual cycle that ceased with menopause5. In
the ensuing years, considerable data have
accumulated showing that throughout life,
estrogen, progesterone and testosterone can
influence respiratory function in animals and
humans6-15.
Respiration can be voluntarily inhibited for some
time, but eventually the voluntary control is
overridden. The point at which breathing can no
longer be voluntarily inhibited is called the
breaking point. Breaking is due to rise in arterial
PCO2 and fall in PO21.The simplest objective
measure of breath-holding is duration of breath
holding upto break point16.
The duration of BHT varies widely from 40
seconds to 22 minutes as observed in various
studies under different experimental conditions.
The longest time for holding the breath
underwater was 22 min 00 sec by StigSeverinsen1725.
There appears to be a sincere effort from Doctor
Buteyko and his medical colleagues who have
summarized available western data (medical and
physiological research articles) over a period of 90
yrs [from 1919 to 2009] regarding average breath
holding time for normal and healthy people. They
also took recordings of BHT in millions of normal &
diseased cases & tried to correlate the gradation of
BHT to health condition.He opined that the simple
test of Breath holding time, known by him as bodyoxygen test, can be used to measure the central
ventilatory response18.
807
As far back as 1975, researchers Stanley et al noted
that breath holding was a simple test to determine
respiratory chemosensitivity and concluded that
"the breath hold time/partial pressure of the
carbon dioxide relationship provides a useful index
of respiratory chemosensitivity." 26
Another study noted two different breath hold
tests, as providing useful feedback on
breathlessness. The first breath hold test, is the
length of time until the first urge to breathe. This
easy breath hold, provides information on how
soon first sensation of breathlessness takes place,
and was noted to be a very useful tool for the
evaluation of dyspnea. The second measurement,
is the total length of breath hold time upto
maximum toleration, which is influenced by
behavioural characteristics such as willpower and
determination. As the first test is not influenced by
training effect or behavioural characteristics, it can
be deduced that it is a more objective
measurement14.
It excites a simple question, i.e. can BHT be used as
a simple clinical sign? In an effort to answer,a
comparative study was carried out to evaluate
[BHT] as an index of central ventilatory response
in young healthy adults of both sexes.
MATERIALS & METHODS
STUDY DESIGN & THE PARTICIPANTS
Parameters were recorded in apparently healthy I
MBBS student volunteers [n=99: female 59, male
40] at 4 PM., after their regular class hours. The
parameters include:
1.Anthropometrical parameters [Height in cms,
Weight in kg, BSA in sq. meters, BMI in kg/m2].
2.Resting respiratory rate [breaths/min] was
recorded after 5 minutes rest in sitting position.
3.Breath holding time [in seconds] upto the break
point after a deep inspiration.
4.Then the subjects was directed to inhale slowly
up to the maximum of 5 seconds and exhale
slowly up to the maximum of 5 second. [i.e. at the
rate of 6 breaths/min] for 5 minutes. Immediately
after the deep breathing session, recording of
Breath holding time was repeated.
STUDY PERIOD
Recordings of 25 students per day after 4 PM for 4
days in April 2013.
RESPONSE RATE
99 students selected from the study population of
99 with a response rate of 100%.
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INCLUSION CRITERIA
Students of I MBBS 18-20 years of age of both
sexes .
EXCLUSION CRITERIA
Students under medication, not willing to
participate voluntarily .
OUTCOME VARIABLE
Resting respiratory rate, Breath holding time.
EXPLANATORY VARIABLES
Demographic and other factors–age, height,
weight, body surface area , body mass index .
ETHICAL COMMITTEE APPROVAL
The present study was approved by the
institutional ethics committee. After briefing the
details of the research project, written consent was
taken from the participants.
STATISTICAL ANALYSIS
Analysis was done using SPSS 16th version for
calculating & comparing the means, both by paired
& unpaired Student’s t test and correlation. P value
< 0.05 is considered as significant.
RESULTS
As shown in Table 1, on sexwise comparison, there
is a statistically significant decrease of Height,
Weight & Body surface area [BSA] with
insignificant differences in BMI & resting RR in
females. No correlation between the Height [R
Square female=0.009; male=0.008], Weight [R
Square female= 0.052; male =0.001], BSA [Graph
1]& BMI[Graph 2] to BHT in both sexes.
Table 1.Represents Anthropometrical parameters & resting respiratory rate in young adults of both sexes [n =99] as Mean  SD.
Variable
Male [n=40]
Female [n=59]
P value by unpaired ‘t’ test
Age [years]
19.15
18.94
0.80
Height [cms]
174.90 6.22
159.965.74
0.000**
Weight [Kgs]
63.57 8.44
53.23 9.9
0.000**
1.82 0.13
1.59 0.14
0.000**
Body mass index [kg/ meters ]
20.77 2.39
20.733.19
0.951
Resting Respiratory rate [breaths /min]
16.00 3.33
15.94 2.89
0.93
2
Body Surface Area [meters ]
2
* P< 0.05 ,significant :
** P<0.001, highly significant.
Graph 1.Correlation between body surface area and breath holding time in females[n=59];males[n=40].
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Graph 2.Correlation between body mass index and breath holding time in females[n=59];males[n=40].
There is highly significant 50% increase in BHT of
both sexes after the deep breathing session
(p<0.000**).There is proportionate & significant
25% decrease in BHT of females compared to
males as observed in both recordings of before &
after the deep breathing session. [Graph 3]
Graph 3. Sexwise comparision of breath holding time[BHT] before and after deep breathing in young adults.
DISCUSSION
A comparative study on 99 medical students of 18 20 years [male n =40; female n =59] did not show
any correlation between BHT & anthropometrical
parameters like Ht [cms], Wt [kgs], BSA[sq.m], BMI
[kg/sq.m] in both the sexes.
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It is a well accepted fact that anthropometrical
factors like Ht ,Wt, BSA bear a positive correlation
with BMR and Total lung capacity [TLC]1. In
present study BHT recorded at TLC might have
minimised the influence of these factors.
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The statistically significant decrease of BHT in
females in the present study is comparable to the
earlier study28 .The higher BHT recorded in our
study might be attributed to the relative younger &
narrower age range of subjects.
Another study on the effect of gender on BHT,
concluded that despite gender differences in
physiological and anthropometrical traits, Breath
hold ability was not different between males and
females29.
What causes break point? Relative hypoxia &
hypercapnea
produced
during
continuous
Breathholding, through their predominant central
action, cause break point. During breathholding,
the arterial or end tidal partial pressure of oxygen
Pa/etO2 falls below its normal level of~100 mmHg
and that of carbon dioxide Pa/etCO2 rises above its
normal level of~40 mmHg. At breakpoint from
maximum inflation in air, the PetO2 is typically
62±4 mmHg and the PetCO2 is typically 54±2
mmHg(n =5; Lin et al. 1974)16
The longest time for holding the breath
underwater was 22 min 00 second by Stig
Severinsen. (Denmark) at the London School of
Diving in London, UK, on 3 May 2012. Stig was
allowed to hyperventilate with oxygen prior to the
attempt, and did this for 19 minutes and
30seconds17. An effort is made by us to explain the
reasons for 22min. World record of BHT with the
following assumptions:
1.Weight of Greig = 60-70 kgs
2.With the normal BMR = O2 consumption =
200ml/ minute.
3.Total lung capacity = 6000ml
4.With 6000ml of O2 in the start of breath hold , O2
supply for the body will be maximally for [6000ml
/200ml/ min] = 30 minutes.
5.When the lungs have <840 ml of O2, the alveolar
pO2 will be <100mm of Hg & pCO2> 660mm of Hg
[assuming atmospheric pressure at sea level 760
mm of Hg ]
6. So break point can occur maximally at [6000840=5160/200=]25.8min.
taking
only
the
consideration of hypoxia and neglecting the
associated Hypercapnea.
7.The
above
observation
suggests
that
hypercapnea if associated with hypoxia, is a better
respiratory stimulant rather than alone.
In the present study voluntary hyperventilation
during deep breathing session at the rate of 6
breaths/min. might have caused hypocapnea &
hyperoxia. This relative state of hypocapnea &
hyperoxia at the beginning of breathhold, during
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the repeated recording of BHT after the deep
breathing session, is responsible for the highly
significant [unpaired ‘t’ test ;p=0.000**] 50%
increase in BHT of both sexes.
The highly significant [paired ‘t’ test ;p=0.000**]
proportionate 25% decrease in the BHT of females
is maintained even after the deep breathing
session [Graph 3]. This might be due to the
increased sensitivity of the respiratory center in
young females, increasing the central ventilatory
response.
Many studies have proven the fact that the
increased sensitivity of respiratory center is
attributable to the female sex hormones as follows:
Some animal & human studies proved that the
immediate effect of Progesterone, by increasing
respiratory centre sensitivity to carbon dioxide
resulted in increased tidal volume and minute
ventilation . This caused a decrease in arterial and
alveolar carbon dioxide pressure30-32.
Some other studies
have found that the
administration of a synthetic progesterone alone
or in combination with conjugated oestrogen,
consistently increases both resting and exercise
MV(VE) with attendant reductions in PaCO2, PET
CO2,(end tidal ) PCSFCO2 ( cerebrospinal fluid )31-34.
An animal experiment in male rats proved that
female sex hormones sensitize respiratory center
by increasing the RR as immediate effect. The RR
is restored back to normal by renal handling of
acid base balance. In male rats, following the
combined administration of a synthetic potent
progestin and estradiol for 5 days, there is
significant increased tidal volume and minute
expiratory ventilation (VE) and it reduced arterial
PCO2, and enhanced the ventilatory response to
CO2 inhalation (delta VE/delta PCO2). On the other
hand, respiratory frequency, O2 consumption, CO2
production, and body temperature were not
affected. The arterial pH increased slightly, with a
concomitant decrease in plasma [HCO3-]. The
results indicated that respiratory stimulation
following combined progestin plus estradiol
treatment in the male rat involves activation of
process(es) that regulate tidal volume and its
augmentation during CO2 stimulus35-45.
Based on these experimental backgrounds of “the
effects of sex hormones on respiratory center”, we
conclude that there is increased sensitivity of
respiratory center, due to action of oestrogen
primed progesterone hormone in young females.
This increased central ventilatory response
resulted in decreased BHT. The explanation for
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the restoration of normal respiratory rate in
females, inspite of sensitive respiratory center,
may be due to renal mechanisms as follows .The
hyperventilation due to sensitive respiratory
center, causes excess washout of carbondioxide,
leading to acute respiratory alkalosis . Kidneys try
to compensate by decreased H+ secretion in renal
tubule & by decreased restoration of HCO3- ions in
plasma. This buffering action of kidneys on body
pH with slight decrease in H+ ion, i.e. chronic
respiratory alkalosis, acting centrally, helps to
depress the respiratory centre, restoring the
normal respiratory rate.
CONCLUSION
In a comparative study conducted on young adults
(n=99) of both sexes (male=40; female=59) on
resting respiratory rate(RR) and breath holding
time(BHT)
before and after deep breathing
session, it is concluded as follows.
1.BHT measured at Total lung capacity is not
correlated to anthropometrical factors like
Height(Ht), Weight(Wt), BSA.and BMI in both
sexes.
2.The proportionate decreased BHT in females, in
both recordings taken before & after the deep
breathing session, indicates the increased
sensitivity of the respiratory center in females,
attributable to oestrogen primed progesterone
action.
3.The normal RR with decreased BHT indicates
the possibility of a state of chronic respiratory
alkalosis in females.
LIMITATIONS & FURTHER SCOPE OF
STUDY
The sample size of the present study was less.
Future studies with more number of samples may
be required to investigate whether there is any
other interrelationship between the variables used
in the study.It is suggested that further studies on
BHT at Total lung capacity can be done with 2 sets
of recordings, i.e. first, at the earliest urge to
breathe & second at the break point.
ACKNOWLEDGEMENTS
The authors are grateful to the Management,
Principal, & staff of Dept. of Physiology , Amala
Institute of Medical Sciences , Thrissur , Kerala for
their support and encouragement.We would like to
thank students of 2012 admission batch who
participated in our study.
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ABBREVIATIONS:
Respiratory rate[RR], Breath holding time [BHT],Total lung
capacity[TLC].
Copyright © 2014 Dharwadkar AA,Chenmarathy BB,Dharwadkar AR. This is an open access article distributed under the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work
is properly cited.
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