The MW/FEy1

Ratio in Normal
Asthmatic Subjects*
Ronald

D. Fairshter,

Aida

Soriano,

We compared
the
forced
expiratory

SGaw

(DI)

than

(SGaw)

in

and
to

expiratory

also would

maximal

differ

This

maneuver
In

hreath.3
test,

volume

between
was

unpublished
observations
on the following
rationale:

one

in

and

(MVV/

following

asthmatic

expiratory
flow decreased
second
MVV maneuver.
of DI

are

asth matic

dependent

DIs.

after
(2) The

on the

subjects

with

spontaneous

the

mechanical

or chemical

causes

vagally

Based

on the

*From

the

stimulation

mediated
above

Pulmonary
NJ; and
Newark.

tDeceased.
Manuscript

received

of

Service,
University

Medicine,
Hackensack
of Medicine

bronchial

series

of rapid

MW

maneuver)

22;

revision

are

abnormally

low

MVV/FEV,

ratios

in

many

asthmatic

may

indicate

to methacholine

tone

precedes

which

rate.4

in-

.(Chest

ofairway

airways

by

provocation

Downloaded From: http://journal.publications.chestnet.org/ on 04/05/2016

decreases

and

found
results

the
MVV

sequence
individuals
after

of

single

compared

the

subjects

(SGaw)

or

MVV/

as well

before

and

as

after

an MW
maneismethacholine

that the MVV/FEV,

ratio
of methacholine
broncho-

MATERIALS

Twenty

nonsmoking

age SD

AND

opulmonary

METHODS

(20 men,

Criteria

for

of

The

following

amlnilatorv

with

for

criteria

at least

prior

Function

forced

determined

capacity

or dosage

the

stability:

of

ofasthma

within

(I)

three

of medications;

and

function

tests

subjects

gave

informed

were

withheld

Bronchodilators

(FVC),

its subdivisions,

a Cardiopulmonary

highest

MW/FEy,

Society

compared

to testing.

spirometer

The

studied.

Thoracic

indicative

All

study.

asthmatic

were

established

Ainrica,i

pulmonary

available).

mean
cardi-

Measurements

vital
using

(if
in the

12 hours

Pulmonary
The

studies

women;
rhinitis,
stable

also

those

exacerbations

in

ten

Forty

were

in type

change

to participate

studied.

considered

change

appreciable
previous

recorder.

were

men,
of allergic

37 13 ears)

of the

(2) no acute

(3) no recent

no

of asthma

Nomenclature

status;

months;

were

age

diagnosis

(ten

history

disease

20 women;

the

of

subjects

without

OI systemic

subjects

(4)

normal
years)

37 15

in

Hackof New

and
the

would

suhjects.359

asthmatic

conductance

bron-

If so,

in nornial

we prospectively

the

on

testing.

mittee

California,

76

than

maneuver.

generally

in normal

airway

Coiii

that

14.

subjects)
FEV,

inspirations

study,

ratio

it

that

April

tone

deep

consent

of

effects

Subjects

receptors

Medical
Center,
and
Dentistry

the

during

greater

decrease
relative
to FEy1.
This
would
not he anticipated
in normal

In
,

we postulated

(performed

have

(in asthmatic

responsiveness
correlated
with

bronchospasm

irritant
receptors
have suggested

breaths

might

single deep inspiration

(SGawDI)
and
ver (SGawMVV).
We also
evaluated

of a 15effects

flow

accepted

MVVI
that

whose

We conclude

low

deep

DI

rolling-seal
February

those

range.

responsiveness

chomotor

specific

study,6

performance
bronchomotor

University

that

than

normal

95:76-81)

In this

reflex

observations,

Department

Irvine;
ensack.
J ersey,

via
also

within

ratios

creased

FEy1

slow
DI on bronchornotor
tone
were
attenuated
topically
anesthetizing
the airways
with lidocaine,
was suggested
that the bronchoconstrictor
effects
were
partially
mediated
airways.4
Other
studies

of methacholine
testing
indicated
with low MVV/FEV
ratios
were

to methacholine

were

and

since

a rapid DI caused a greater increase in respiratory

resistance
(Rrs)
than
did a slow deep
inspiration.4
Because
differences
between
the effects
of fast and

DI

Results
subjects

subjects

and also
to normal

In another

inspiratory

ratios

multiple

in our laboratories
(1) In contrast

sequential

responsive

FEy

previously

siibjects,3
a deep
inspiration
(DI) commonly
causes
bronchoconstriction
in asthmatics;3
this effect appears
to correlate
with
bronchial
sensitivity
to methacholine. In one study,5 expiratory
flow rates progressively
decreased

more

would
events

ventila-

second

on

maneuver.
asthmatic

1989;

We hypothquantitated

based

that

MVV

MVV/FEV

caused

differ
bronchial

normal

there was a significant

correlation
between
MVV/
ratio and magnitude
of decrease
in SGaw after an

FEVI

asthmatic

voluntary

in

speculation

MVV/

Specific

DI or an MVV

normal
individuals
a variety
of

of a 12-second

FEy,),

a single

F.C.C.P,

M.D.

subjects,
in

with

subjects,

subjects.

as the

subjects.

M.D.,

Pai,

and

subjects.

An MVV

as well as to a deep
a short
hyperventilation

ratio

normal

after

challenges2
esized
that
tionlforced

Usha

tone

in asthmatic

asthmatic

subjects
response

their

Carilli,

and

voluntary
ventilation!
second
(MVV/FEV)

In

that

individuals.

decrease

,thmatic

Albert

M.D.;

bronchomotor

increased

in normal
to

on

responsiveness.

higher

conductance
maneuver

Lin,

and asthmatic
subjects.
Our hypothesis
would
be lower
in asthmatic
subjects.
MVV/FEV,
results
with the effects
of

inspiration

methacholine
FEy
was

F.C.C.P;t

Jason

ratio of maximal
volume
in one

normal
individuals
was that MVV/FEV
We also compared
deep

M.D.,

AID.;

and

connected

ofthree

Ratio

and

Instruments
to

values

in Normal

for FEV,

and Asthmatic

MVV

(CPI)

CPI

model

and

oftwo

Subjects

were

model

220

750A

X-Y

values

(Fairshter

for

at a!)

Table

Pulmonary
Function
(Mean SD)5

Routine

Normal

Asthmatic

Subjects

20

Age

FEy,

(% predicted)

FEV,/FVC(%)
MVV
(min

81 21t

838

69

vital

expiratory

capacity;

MVV

tSignificantly

(in

103 37t
38.26.3t

volume
maximal

different

were

used.

ventilate

in

one

voluntary

from

The

as rapidly

encouragement
(and

results

second;

FVC

forced

5 mm

subjects
then

lung

capacity

near

Vtg

inspiration,
calculated;
tance

was

maneuver;

having

as possible

for

12 s with

of
was

at functional

resting

the

subject

ratio

ventilation

allowed

Raw

avoided

obtained.

and

by relaxing
Ras
then
this

Vtg

deep

with
and

result

Vtg
was

determined
result

glottis

were

again

within

was

to a lung

Within

measured

and

5 s ofcompletion

designated

ofa

FEV,;

volume

points

deep

all

was

12-s

MVV

was
always

of the

and

[GMD]

these

previous

withheld

for a

The

MVV/

SGawMVV
before

were

each

meth-

required

subjects

calculated
as

the

change

this

slopes
in

of the

interpolated

of the

as the

slope
dose

this

participated

of three

criterion

was

in methacholine

of methacholine

of
and

concentration

A minimum

calculation;

SGaw

(PCwFEV,;

methacholine

the

measured

and

methacholine

sensitivity

calculated

in SCaw.

who

the

concentrations

noncumulative

for

in FEV,
from

was

with

by more

concentrations

decrements

airways4

reduction

of metha-

decreased

provocative

interpolated

beginning

a 25 percent

dose

had

representative

of the

response,

maximum

FEy,

provocative

between

12 asthmatic

We also

were

considered

Reactivity

the
the

35 percent

curve;

was

until

noncumulative

20 and

were

(defined

conduc-

The

relationship

SGaw

challenge

were

immediately

or until

PC.,SGaw)

PC,SGaw)

causing

the

methacholine.

SGawDI,

continued

percent.

dose-response

SGaw

SGaw

Specific

producing

(PCO

to total

5 s of this

SGawDI.2

(PC)

the

inhaled

exhaled

25

history

with

SGaw,

saline

of methacholine
drugs

of

normal
concentrations

or until

inhaled

previously)

administered

than

airway.

as

were

was

specific

for 3 mm;

rapidly

open.

designated

as
volume

or cough

immediately

the

resistance

assess

subjects

then

Thoracic

airway

expressed

To

breaths

subjects.

and

were
).

#{149}

Subsequently,

(TLC)

this

results

any

in all
capacity

well

at 45,

challenge.

choline

of two

was

as

the

of administration

and

of

measured

in doubling

dose

to challenge

(as described

Inhalations

vigorous

A minimum

performed
residual

The

(SGaw

was

by

initiation

All oral

of

of tidal

of inhalation

was

inhaled

of each

the

dose.

measured

measured
technician.

minutes

measured.

conductance
effects,

after

was

period

inhaled

to 32 mg/mI

periods
period

by determination
also

each

s after

then

of 0.015

of 12 h prior

FEV,

subjects.

was

ranges

Each

immediately

aerosol

ratios,

Methacholine

two-mm

clip.

FEV,

180

first

Administration

minimum

maneuvers.

(Vtg)

were

was

pulmonary

plethysmography

gas volume

(Raw)

cases)

the

began

ventilation.

in normal

deeply

the

three)

MVV

Body

MVV

and

by

usually

between

some

MVV/FEV,

ratios.

during

a nose

followed

plethysmograph;

Methacholine

completed.

nehulizer

body

low

MVV/FEV,

wore

was

had

individuals

normal

a Wright

The

between

six

Subjects

of aerosol

acholine
MVV

from

methacholine

forced

study;

six had

in the

diluent.

lit

*FEV

ventilation.

ofthe

other

methacholine.

99 17

44.55.9

MVV/FEV,

inhaled

tidal

90, and

2.70.9t

152 38

(11mm)

was

SGaw

37 13

3.51.1

the

breathing

40

37 15

(years)

FEV,(L)

phase

whereas

Individuals

in this

Results

data
met

dose-response

response/geometric

by

testing.
curves
mean

dose

were

com-

of methacholine).

SGawMVV

Statistics
Methacholine
Twelve

Bronchoprovocation
individuals

from

Tests

the

stable

Pulmonary

asthmatic

group

pared

participated

in

function

the

(including

results

normal

and

the

MVV/FEV,)

asthmatic

subjects

by

paired

or

1989

77

NtW / FEU1
68

58

<

3B

3B

I
4

6B

AGE
FIGURE
is positive

1 . Relationship
(r

0.70)

and

between
highly

MVV/FEV,
statistically

and age
significant

(y = 0.28x
(p<O.00l).

+ 34.

1) in normal

subjects.

The

CHEST

Downloaded From: http://journal.publications.chestnet.org/ on 04/05/2016

correlation

I 95

I 1 I JANUARY,

unpaired

t-test

were

made

method

was

the

when

Linear

regression

Pearsons

correlation

where
the

sum

results

were

developed

predicted

by Morris

was

was

not vary

nonparametric

were

not

using

(r) or

0.05

comparisons

this

done

of correlation

Percent

Other

test;6

in question

analyses

(r,).6 A p-value

significant.

equations

rank

coefficient

coefficient

tically

16

Wilcoxon

utilized

distributed.
priate)

analysis

using

ingly,

normally
(as appro-

Spearmans

rank

considered

statis-

calculated

using

the

et a!.

with

volume

changes

reflected
bly,

changes

RESULTS

Fig

SGawMVV

Spirometric

Tests

Compared
FEy1

in the

with

results

in the

asthmatic

FEV1/FVC
and MVV were
(Table 1). The MVV/FEV1

subjects

in the normal
analyses,
the

subjects.
Using one-tailed
and two-tailed
lower 95 percent
confidence
limits for a

MVV/FEV1
were 34.8 and 33.0,
and 9/40 stable
asthmatic
subjects

FEy1

values

below

a significant
in the normal

correlation
subjects

and
MVV/FEV1
group
of stable

confidence

between
(r=O.70,

between

MVV/FEV1

There

was

MVV/FEV1
and age
p<O.OOl)
(Fig 1); age
significantly
(r = 0.37,

spirometric

were

respectively;
had MW!

limits.

also correlated
asthmatic
subjects

Correlations
and

these

or

neither

high

in

the

p<O.O2).

SGAW
nor

results

statistically

of Deep

In

the

SGaw

Inspiration

normal

in

15

group,

of

20

SGawDI

subjects;

was

in

higher

contrast,

Methacholine

not

differ

asthmatic
significantly

significantly

subjects,
SGaw
but SGawDI

SGawMVV
(Table
gas volume
(Vtg)
aged 2.660.49,

DI, after DI,

corresponding
and

3.05

cantly

and

Deep

after
values

MW;
were

than

SGawDI

3).

Specific
inspiration

asthmatic

lower

(cm

SGawDI

5- )

(cm

SGawMVV

0.223

s)

(cm

s)

SGawDIJSGawMVV
*SGaw

maximal

voluntary

tSignificantly

different

lSignificantly
jects.

different

Significantly

different

from

Our

results

indicate

that

Age,

PCaFEV,

(mg/ml)

Downloaded From: http://journal.publications.chestnet.org/ on 04/05/2016

the

95 percent

(Mean

<34.8

SD)5
MVV/FEV,

>34.8

31 9

31 11

1.05

dose-response

74

15

40.03.81

0.03

1.00

0.034

0.0840.069

0.2750.222

0.041

0.027

0.1380.077

1452

1287

2542

2647

- 549

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FEV,/GMD)
dose-response

781 431

180 1494

SGaw/mg/ml)
D

2001

SGaw/GMD)

forced

tPrior

on

lower

7816

(mg/ml)

PC,SGaw
FEV,

Depending

Results

SGawDIJSGawVVt

PC

75

were,
asthmatic

31.12.7

geometric

expiratory

ventilation;

SGawDI.

of MVV/FEV1

normal

Methacholine

MVVIFEV,t

*GM

sub-

FEV,(%predicted)t

(%

in normal

years

Reactivity

SGaw

and

MW!
of the

nonhospitalized

(%

MVV

MVV/FEV1

PCSGaw)
and
and reactivity

ratios

in stable,

MVV/FEV,

SGaw

1.050.09

lower

Table

0.l150.068

inspiration;

present
airways

(p>O.9).

mean
volume

SGaw

provocative

MVV/FEV,

dose

(mg/ml)

of methacholine;

in one

second;

MVV

specific

conductance;

concentrations

to administration

Significantly
from

(PCOFEVl,
sensitivity

subjects.

0.074

were
the

dose-response
curves
for
and SGaw (r, = 0.63, p<O.O5).
correlation
between
sensitiv-

the

Subjects

of

as between

to define

0.121

result

as well

in normal

did

methacholine

DISCUSSION

0.1210.073

corresponding

greater

correlations
reactivity

used

ventilation.
from

p<O.05)

ity of the airways

FEy1
nor between

0.2290.O6lt

deep

(and

than

40

DI

ratios
with

of the methacholine
(r, = 0.64, p<O.O5)
was no significant

0.2310.061t

conductance;

stable

subjects

signifi-

ratios
(Table

overall

ratios

in the

criterion

Asthmatic

1.010.04

specific

results

differ
than

Vtg clearly

0.060

the

function

with MVV/FEV1
to methacholine

not
higher

20

SGaw

with

methacholine

subject
group,
SGawDI/SGawMVV
significantly
higher
in the individuals

MVV/FEV1

(4%

-0.39,

SGawDL/
higher
than

pulmonary

asthmatic
subjects
more
responsive

responsiveness).
Significant
between
MVV/FEV1
and
(r, = 0.75,

positive

baseline

on average,

Results
Before
and After
Voluntary
Ventilation

Individuals

had

and

stable

were

subjects,

Conductance
and Maximal
Normal

values

(r=

2).

the

In
did

age

Consistent

asthmatic
were also

airways

in the asthmatic
subjects,
3.040.59,
3.02 0.59,
Vtg

MVV/FEV1

subjects

Although

normal
subjects,
thoracic
residual
capacity
averand 2.680.54
before

Although

in the

2).

and SGawDI
was significantly

2). In the
at functional
2.660.50,

0.59.

higher

Table

(Table

stable

individuals),
found
between

Studies

were similar,
<34.8
were

exceeded
SGaw
in only 19 of4O asthmatic
subjects.
In
the
normal
individuals,
SGawDI
was
significantly
higher
than SGaw
whereas
SGawDI
and SGawMVV
did

normal
was

the

asthmatic
subjects,
but significantly

(Table

All 12 asthmatic
tests.

slopes
FEV1
There

significant.
Effects

group

presuma-

In

subjects,

higher
in the normal
ratio was also higher

normal
13/40

normal

histories

(and

tone2).

and

2). In the
was slightly

Accord-

volume

resistance

(but not the

correlation

SGawDI!SGawMVV

group.

different

bronchomotor

subjects
negative

p<O.O2;

in either

with

in airway

therefore,

asthmatic
significant

history

in SGaw

MVV/FEVI

DI

FEy,

maximal
deep

voluntary
inspiration;

35 percent).

of methacholine.

different

ratio

(20 and

from

corresponding

result

in

subjects

with

<34.8.

Ratio

in Normal

and Asthmatic

Subjects

(Fairshter

et a!)

confidence

limit,

22.5

to 32.5

percent

subjects
had abnormally
low
also found
that the MVV/FEV1
age

in

normal

subjects,
of Harber
unclear

individuals

a result
which
et al;18 the
but

might

as
differs
reason

be

in the
significant

two studies.
correlations

and

effects

lung

between

MVV/FEV1

Previous
are

often

strength

of

have

reduced

in

well

FEV1

We
with

different

cluded
FEy1

is

subject

well

with

previous
as

that

airway

cations

demonstrates
ratios
since

that

the

finding

asthma

cannot

be well

is another
This

has

of a low

might
otherwise
be attributed
suboptimal
effort.
In addition,
capacity

bronchoprovocation
using
a sustained

cause
impli-

MVV/FEV1

ratio

to other
causes,
such
maximal
ventilatory

predicted

by

muscle

the

in
caliber

subjects
the

there
will

contributed

caliber
airways2

MW

maneuvers

DI

was
repet-

irritant
recepreflex bronchois experimental

increase

tension

muscle.
of airway

to post-MW

increase

(Fig

so,

in

If this is
smooth
reductions

for

after a series
of deep
breaths.
as well as loss of humidity2
might

in

ratio
to
.

normal

of reduction

of airways
mediated

stretch

in

MVV!FEV,

Alternatively,

also

with

not

an altered
response
ratios
of MVV/FEV,

stimulation
to vagally

we

(compared

magnitude

with

rewith

maneuvers)

in our asthmatic
subjects.
are other
possible
explanations

airway
of the

con-

the

study,

but

a quick

have

this
MW

sensitized
airways
smooth
vivo,
repetitive
stretching
may

in SGaw
There

as

multiplying

that

isolated
true
in

of

clinical

led

individuals,
are consistent

(during

2). The

that
low

with

evidence

the magnitude
of which
x a constant
factor.22
Our

of MVV/FEV1.

suggesting

itive mechanical
tors may have

DI
in airway

correlated

associated

also

by multiplying

a single
DI often resulted
as indicated
by SGaw!

asthmatic

(Table

constriction.

reduced

predicted

However,

SGawMVV

exercise.2#{176} Cold
challenges
often

study

in

or normal

have

value.9

individuals
2),

period
of hyperventilation,
may be estimated
as FEy1

well

repetitive

DI)

obstruction,89
and/or
in the presence
of suboptimal
effort during
pulmonary
function
89
The FEy1
value
has been
multiplied
by a constant
factor
(eg,
FEy1 x 37.5)
to predict
maximal
ventilation
during
and/or
dry air
are performed

subjects

colleagues8

subjects,
caliber,

reduction

single

muscle

upper

is not

data.3482

found

values

poor

MW

by a constant

caused

MVV/FEV1

extrathoracic

that

and

SGawDI
ratios
>1.0.
In normal
verse
was
true.
Both
results

to methacholine.

that

(in asthmatic

Harber

In our asthmatic
in reduced
airway

study,
there
MVVIFEV1
as

by a constant

individuals).

asthmatic

history

subjects

or endurance,89

in

In our
between

response
shown

as

to

volume

and

studies

asthmatic

from the observations

for this discrepancy

related

populations
were also
the

ofour

MVV/FEV1
ratios.
ratio
increased

reduced
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during

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maximal

2. Correlation
between
specific conductance
after a deep breath/specific
conductance
voluntary
ventilation
(SGawDLSGawMVV)
and
MVV/FEV,
in stable
asthmatic
subjects.
correlation
is inverse
(r= - 0.39) and statistically
significant
(p<0.02);
this indicates
that MVV/FEV,
were lower in asthmatic subjects whose airways narrowed
after maximal
voluntary
ventilation.

CHEST

Downloaded From: http://journal.publications.chestnet.org/ on 04/05/2016

I 95

after
The
ratios

I 1 I JANUARY,

1989

79

in asthmatic
little

subjects.

respiratory

expected
during
end-tidal
carbon
to hyperventilation
tion during
demonstrated

On

heat

MW
that

maneuvers.
resistance

challenges2
striction

when

the

other

CO2

hand,

Previous
to airflow

is added

the

system;

this

to the

effects

Fatigue

relatively

ratory
not

would

inspired

muscles.

the

On

cant)
The

between

airways
MVV/FEV,

function
has
sponsiveness
that

was

in

in

and

the

1 Hargreave

BA, Reed
and

study,

MW/FEV,

in those asthmatic
responsiveness.

subjects
Worsening

is complicated

gation

high
vers

elastic
recoil

ratios

were

than at low lung volumes.27

are initiated
at total lung

maneuvers
are performed
loss of Pst(L)
(with
age)

at lower
might
be

important
on forced
expiratory
vers. In addition,
in contrast
enced
Pst(L)
not
might
In

by both inspiratory
is an important
of inspiratory
favor higher
conclusion,

Since
capacity

re-

flow,#{176}loss

of lung

ratios of MW/FE
MW/FEy1
ratios

V1.
were

Downloaded From: http://journal.publications.chestnet.org/ on 04/05/2016

and

of

Investi-

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maximal

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1984;

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flow-

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after

88:697-702
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Thorax

or

36:596-98

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WCHR,

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Am

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Grant

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7 Simonsson

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and expiratory
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5 Gimeno

American

Thorax

RD.

of inspiratory

asthma.

HowMW!

than on MW
to FEy1,
MW

DJ,

asthma?

M,

al.

2):517-24

in normal

W, Arai

et

Hargreave

on Guidelines

ofmetaproterenol.

6 Stanescu

effects

FEy1
whereas

MW!

of patient

105:66-74

with greater
pulmonary

recoil.27
(Pst[L])

the

H. Schnur
and T
Lowe for technical

DW,

Antiasthmatic

Fairshter

curves

Effect

MW/FEy,
ratios
(Fig 1) is unclear.
It is known
that
FEV1 decreases
as a function
of age,727
primarily
of loss of lung
that the loss oflung

in which

IL,

ofthe

Godden

try-Induced

FEV,
and expiratory
flow rates,
lower
FEV,
values
did not account
for lower
MW/FEV1
ratios;
the same
was true for specific
conductance.
The explanation
for the correlation
between
age and

because
known

of

pertinent

as an index

Cockcroft

Force

78(pt

PM,

RB,

4 Hida

were

between

function
normal

is especially

Bernstein

Report
Task

to induce

volume

and

eds.

1986;

3 Berry

ratios

JN,

ofNonbronchodilator

exercise

and

reactivity

by the

airway
geometry
on methacholine
ever, based
on the lack of correlation

this

The
authors
thank
manuscript
and J. E

In:

CE,

2 Tweeddale

since

also been
associated
with
increased
to pharmacologic
bronchoconstrictors,

results

a situation

Fink

Immunology

Immunol

signifi-

and

testing).
These
the interpretation

advocated

of this

FE,

inhalation

MW!FEV,

airway
metha-

testing;

bronchoprovocation.

probably

normals

SGawDJJSGawMVV

analysis

ACKNOWLEDGMENTS:
Stack for the typing
assistance.

may
inspi-

statistically

in

may indicate
confirmed
by

during

been

true

values
can be

evaluations,
has

was

pulmonary
the predicted

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