Women's Issues |n u|monary Med|c|ne

SLephanle M. Levlne, Mu, lCC

unlverslLy of 1exas PealLh Sclence CenLer-San AnLonlo

Iacu|ty D|sc|osures
no relauonshlps exlsL wlLh lndusLry
Learn|ng Cb[ecnves
1o revlew Lhe normal resplraLory and cardlovascular
physlology of pregnancy.
1o revlew Lhe managemenL of asLhma, venous
Lhromboembollsm , and Luberculosls ln pregnancy.
1o revlew Lhe causes and managemenL of acuLe resplraLory
fallure ln pregnancy.
1o presenL Lhe sLausucs regardlng smoklng and Lhe
epldemlology of CCu ln women.
1o dlscuss lymphanglolelomyomaLosls- presenLauon,
dlagnosls and LreaLmenL
Upper kesp|ratory 1ract |n regnancy
Alrway mucosa- hyperemla and edema
Secreuons- lncreased (3rd LrlmesLer)
LplsLaxls
Poarseness
nasal polyps- lncreased
Allerglc rhlnlus- lncreased
More dlmculL lnLubauon
LsLrogen medlaLed
C1- All of Lhe followlng pulmonary funcuon LesLs are
decreased durlng pregnancy excepL:

A. LxplraLory reserve volume
8. 1oLal lung capaclLy
C. vlLal capaclLy
u. luncuonal resldual capaclLy


kesp|ratory hys|o|ogy |n regnancy
8on|ca et a| 199S
kesp|ratory hys|o|ogy |n regnancy
MlnuLe venulauon
lncreases-20-30 (9L)
1ldal volume- 30-30
lncrease
rogesLerone medlaLed
lncrease ln cenLral and
hypercapnlc resplraLory
drlve
8esplraLory raLe- no
change Lo mlld lncrease
8on|ca et a| 199S
kesp|ratory hys|o|ogy |n regnancy
llow raLes- no change
Alrway reslsLance- no change
Lung compllance- no change
1oLal resplraLory compllance- decreased
uLCC- varles wlLh blood volume
2-Wh|ch A8G wou|d be expected |n a
hea|thy woman |n her 20th week of a
norma| pregnancy?
pH PaCO
2
PaO
2

A. 7.43 31 98
B. 7.40 40 90
C. 7.35 45 70
D. 7.49 25 82


Gas Lxchange |n regnancy
Mlld compensaLed resplraLory alkalosls
aCC
2
28-32 mmPg
8lcarbonaLe 18-21 meq/L
pP- 7.40-7.43
aC
2
100-103 mmPg
lncreased A-a gradlenL
C3- All of Lhe followlng parameLers are lncreased
durlng pregnancy excepL:

A. Cardlac ouLpuL
8. ulmonary vascular reslsLance
C. 8ed blood cell volume
u. PearL raLe
Card|ovascu|ar hys|o|ogy |n regnancy
Cardlac ouLpuL- lncreased
P8, Sv (30-30)
Sv8- decreased
v8- decreased
8- decreased sysLollc
and dlasLollc
osLural hypoLenslon

8on|ca et a| 199S
I|u|d hys|o|ogy |n regnancy
1oLal blood volume-
lncreased (33-30)- 6-8L
lasma volume-
lncreased 1-1.3L
88C volume- lncreased
(buL less)
ulluuonal anemla
Serum proLelns-
decreased 3 mmPg
(edema)
Mlneralocorucold
lncrease/ hormonal
changes 8on|ca et a| 199S
S|eep D|sordered 8reath|ng |n regnancy
lncreased snorlng
lncrease ln sleep dlsordered breaLhlng
CSA may develop or worsen
CA
Dyspnea |n regnancy
LecLs 2/3 of pregnanL women
1sL and 2nd LrlmesLer
rogesLerone
hypervenulauon
alLerauon ln CC2 sensluvlLy
Anemla
8eware of sLenouc cardlac leslons, rlghL Lo le
shunLs, pulmonary hyperLenslon
IDA Drug C|ass|hcanon
CaLegory A - no or remoLe rlsk
CaLegory 8 - no evldence of rlsk ln humans
CaLegory C - 8lsk can noL be ruled ouL
CaLegory u- osluve evldence of rlsk
CaLegory x- ConLralndlcaLed ln pregnancy
known feLal harm e.g. Lhalldomlde
C4- uurlng pregnancy Lhe course of asLhma Lends Lo:

A. Worsen
8. lmprove
C. SLay Lhe same
u. Lqual llkellhood of Lhe above
Asthma |n regnancy
7 of pregnanL women
lncreased feLal and maLernal rlsks
preLerm labor, pre-eclampsla, prevla, luC8
1he 1/3 rule!
SeverlLy predlcLor- severlLy when noL pregnanL or ln
prlor pregnancles
Worse- mlddle pregnancy, dellvery,
CL8u, slnuslus, allerglc rhlnlus
Asthma: 1reatment
Mlld lnLermluenL- shorL acung 82 agonlsLs for sx
Mlld perslsLenL-
Low dose lnhaled CS- budesonlde (8),
beclomeLhasone (C).
cromolyn
L18A
Lheophylllne
ModeraLe perslsLenL
lnhaled CS- low dose plus LA8A C8
lnhaled CS- medlum dose plus LA8A
Severe- lnhaled CS (hlgh dose), LA8A, oral CS
gesLauonal uM, sLress dose durlng L and u
We||
Contro||ed










Very
oor|y
Contro||ed


www.g|nasLhma.com
www.naepp.gov
Not we||
Contro||ed




www.g|nasLhma.com
www.naepp.gov

CaLegory 8
cromolyn
budesonlde
LerbuLallne
anuchollnerglcs
monLelukasL
zarlukasL
omallzumab
CaLegory C
shorL acung 82
LA8A
lnhaled CS
sysLemlc CS
Lheophylllne
Asthma: Drugs
Acute Asthma]Status: 1reatment
Cral or parenLeral corucosLerolds
AlbuLerol
Anuchollnerglc agenLs
Magneslum
lnLubauon paCC2 42 mm Pg ?
Avold eplnephrlne
C3- Whlch of Lhe followlng sLaLemenLs abouL uv1 ln
pregnancy ls Lrue?

A. 1hey occur equally ln Lhe rlghL and le leg.
8. 1hey are more common ln Lhe posL-parLum
perlod.
C. 1hey are more common ln Lhe rsL LrlmesLer.
u. 1he dlagnosuc yleld of uoppler uS ls lmproved
ln Lhe le laLeral decublLus posluon.
Venous 1hromboembo||sm |n regnancy
Leadlng cause of morLallLy (20-30)
.03-.1 of pregnancles
Lqual dlsLrlbuuon over LrlmesLers and 2/3 anLe and
1/3 posL parLum
~90 of uv1 on le
V1L k|sk Iactors
LanceL 2012,373:300
V1L: D|agnos|s
ulagnosls of uv1
uopplers- besL ln le laLeral decublLus
u-ulmer?
ulagnosls of L
v/C scan- smaller lsoLope dose, only C
C1 anglogram
anglogram
V1L- 1reatment ( 2012,141(2s): e691s-e736s)
LMWP (8)- ad[usLed dose or
unfracuonaLed heparln (C) - lv followed by ad[usLed
dose followlng a11 x 3 days
LMWP or ulP should be conunued LhroughouL
pregnancy
1reaL for 6 weeks posL-parLum for aL leasL a LoLal of 3
mos. of AC (LCL-2C)
LMWP preferred over ulP (LCL-18)
Warfarln (x)
1hrombolyucs- relauve conLralndlcauon
lvC lLer
V1L
rophylaxls
LMWP
6 weeks posL-parLum (LCL 28)
ldlopaLhlc or pregnancy relaLed v1L (LCL 2C)
uellvery
epldural caLheLers relauvely conLralndlcaLed
d/c LMWP or ulP- 24 hours prlor (LCL 18)
2012,141(2s): e691s-e736s
6
A 31 yo woman C32 ln her 21sL week of gesLauon
presenLs wlLh fever, cough, welghL loss, brocavlLary
changes on Cx8 and ls found Lo have spuLum posluve
for Al8. She ls Plv negauve. 1he besL LreaLmenL aL
Lhls ume would be:
6

A. lnP and rlfampln
8. lnP, rlfampln, ZA and LM8
C. lnP, rlfampln and LM8
u. uelay LreaLmenL unul aer vlable dellvery
1ubercu|os|s |n regnancy
no dlerence ln suscepublllLy, course, or ouLcomes
urug reglmens
lnP, rlfampln, LM8 x 9 monLhs
use pyrldoxlne
yrazlnamlde- noL well sLudled
SLrepLomycln- LeraLogenlc (oLoLoxlclLy)
Am I kesp|r Cr|t Care Med 2003, 167:603-662
L18I
Low rlsk group wlLh clear Cx8- can delay LreaLmenL
Plgh rlsk- 9 monLhs of lnP
neumon|a
Coccldloldomycosls
lncreased rlsk for dlssemlnauon and morLallLy
worse ln 3rd LrlmesLer
amphoLerlcln- caLegory 8
azoles- caLegory C

A 29 yo C21 woman ln her 27Lh week of pregnancy
presenLs wlLh preLerm labor. She ls begun on
LerbuLallne. CS are added Lo promoLe lung developmenL.
Per conLracuons lmprove and Lhe LerbuLallne ls d/c 24
hours laLer. Cver Lhe nexL 12 hours she c/o c/p and SC8.

L- afebrlle, 88-32, - 120, 8- 100/60 mmPg, lungs-
crackles, Cv- Lachycardla

Cx8- bllaLeral alveolar opaclues
7

neumon|a
varlcella ZosLer
pneumonla ln non-exposed pregnanL woman morLallLy
approaches 33
acyclovlr- caLegory 8
lnuenza
vacclne- now changed from all hlgh rlsk and oLhers aer
1sL 1M Lo vacclnaLe all regardless of 1M
drugs- caLegory C
2009 P1n1 pandemlc- pregnanL women were aL hlgher
rlsk for poor ouLcomes- hosplLallzauon, deaLh (accounLed
for 3 of deaLhs)

nL!M 2010,362:27
!AMA 2010,303,1317
nemodynam|cs |n regnancy
Plgh CC
Low Sv8
osluonal hypoLenslon when suplne- le laLeral
decublLus posluon
May requlre lower pulmonary arLery occluslon
pressure
ulmonary edema- lncreased plasma volume and
low oncouc pressure

Mechan|ca| Venn|anon |n regnancy
ulmculL lnLubauon
8educed chesL wall compllance- 1v
Plgher peak and plaLeau pressures on venulaLor
MalnLaln pregnanL eucapnla
SaLurauons > 90
non-lnvaslve venulauon ?

7- What |s the most ||ke|y d|agnos|s |n
th|s panent?

A. Amnlouc uld embollsm
8. ulmonary embollsm
C. erlparLum cardlomyopaLhy
u. 1ocolyuc pulmonary edema
Cr|nca| Care |n regnancy
Amnlouc uld
embollsm
1ocolyuc pulmonary
edema
ulmonary
hyperLenslon
erlparLum
cardlomyopaLhy
venous alr embollsm
CbsLeLrlcal relaLed
sepsls
A8uS from obsLeLrlcal
sepsls
Asplrauon
v1L
PLLL
AcuLe fauy llver of
pregnancy
Amn|onc I|u|d Lmbo||sm
1:8000- 1:80,000
80-90 morLallLy
uurlng labor or 48 hours posL parLum
8l
advanced maLernal age, muluparlLy, premaLure rupLure of
memebrnes, uLerlne sumulanLs
aLhophyslology-
vascular obsLrucuon, caplllary leak, Lv fallure, anaphylaxls
Amn|onc I|u|d Lmbo||sm
resenLauon
acuLe Lachypnea, Lachycardla, hypoLenslon, selzures, ulC,
hemorrhage, A8uS, hemodynamlc collapse
ulagnosls
excluslon, supporLed by feLal cells ln blood
1reLamenL
supporuve- Mv, vasopressors, blood producLs
? SLerolds, nC, LLx, lacLor vll
Venous A|r Lmbo||sm
MorLallLy- 90 (100 ml of alr)
Alr ln venous clrculauon
dellvery, aboruon
8v obsLrucuon- hemodynamlc collapse
resenLauon
cough, Lachypnea, Lachycardla, menLal sLaLus changes, mlll
wheel murmur, A8uS, cardlopulmonary arresL, alr ln reunal
vessels or subdermal, alr ln hearL on Cx8
1reaLmenL
Le laLeral decublLus posluon, asplrauon, 100 C2, hyperbarlc
oxygen
1oco|ync u|monary Ldema
8eLa 2 agenLs- LerbuLallne, rlLodrlne
exacerbaLed wlLh corucosLerolds
LecLs 4-3 of pauenLs
24-48 hours aer drug lnluauon
8l
prolonged drug use, pre-eclampsla, muluple gesLauons
1oco|ync u|monary Ldema
Mechanlsms
uld overload, cardlac LoxlclLy, changes ln oncouc
pressures, caplllary permeablllLy
resenLauon
dyspnea, chesL paln, crackles, pulmonary edema
1reaLmenL
dlsconunuauon of drug
resolves ln 12-24 hours
u|monary nypertens|on |n regnancy
Plgh maLernal (33-30) and feLal morLallLy
Counseled agalnsL pregnancy
Lchocardlograms of varlable rellablllLy
lncreased CC wlLh xed v8
Worse ln lmmedlaLe perlparLum perlod up Lo 14 days
due Lo uld shls
AcuLe 8Pl
urugs- prosLacyclln (8), slldenal (8), bosenLan (x)
uellver wlLh use of A caLheLer ?, nC, conLrolled
vaglnal dellvery
1920s 1940s
1990s
1930s 1920s 1930s
1960s
Tobacco Use in the US, 1900-2003
0
10
20
30
40
50
60
70
80
90
100
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
1
9
0
0

1
9
0
5

1
9
1
0

1
9
1
5

1
9
2
0

1
9
2
5

1
9
3
0

1
9
3
5

1
9
4
0

1
9
4
5

1
9
5
0

1
9
5
5

1
9
6
0

1
9
6
5

1
9
7
0

1
9
7
5

1
9
8
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1
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8
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1
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1
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2
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Year
*Age-adjusted to 2000 US standard population.
Source: Death rates: US Mortality Public Use Tapes, 1960-2003, US Mortality Volumes, 1930-1959, National
Center for Health Statistics, Centers for Disease Control and Prevention, 2005. Cigarette consumption: US
Department of Agriculture, 1900-2003.
Per capita cigarette
consumption
Male lung cancer
death rate
Female lung cancer
death rate
Trends in Cigarette Smoking Prevalence* (%), by Gender, Adults
18 and Older, US, 1965-2005
*Redesign of survey in 1997 may affect trends.
Source: National Health Interview Survey, 1965-2005, National Center for Health Statistics, Centers for Disease
Control and Prevention, 2006.
0
10
20
30
40
50
60
1
9
6
5

1
9
7
4

1
9
7
9

1
9
8
3

1
9
8
5

1
9
9
0

1
9
9
2

1
9
9
4

1
9
9
5

1
9
9
7

1
9
9
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1
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9
9

2
0
0
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2
0
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2
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2
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P
r
e
v
a
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(
%
)

Year
Men
Women
2010 CDC:
Women- 17.3
Men- 21.S
Ten Leading Cancer Types for the Estimated New Cancer Cases and
Deaths, by Sex, United States, 2011

CA CAnCL8 ! CLln 2011,00:000-000
Lung cancer ls Lhe
leadlng cause of
cancer relaLed
deaLhs ln women
Adenocarclnoma
mosL common
1rends parallel
Lobacco use wlLh
20 year lag
lncldence raLes
hlgher for lung
cancer ln non-
smoklng women
Lhan men
CCD |n Women vs Men
Slmllar Lrends as lung cancer
revalence ln women > Lo men
Less frequenLly dlagnosed ln women
More women hosplLallzed- 1.3-3.6 umes
More women dylng from CCu
Less emphysema by P8C1
Less obsLrucuon buL lower dluslng capaclLy
Worse gas exchange
Worse dyspnea and 8CuL
Worse CCL- anxleLy and depresslon
CCD |n Women
Women may be more suscepuble
CCu aL earller age
More lung funcuon lmpalrmenL for amounL of Lobacco
used
Mechanlsms
Smaller alrway slze
Pormonal
CyLochrome 430
8lomass
Catamen|a| D|seases
neumoLhorax
rare and recurrenL, usually rlghL slded
24-48 hours aer onseL of mensLrual ow
pelvlc, pleural, dlaphragmauc endomeLrlosls
8x- hormonal suppresslon, LhoracoLomy, pleurodesls
PemopLysls- parenchymal endomeLrlosls
8x- hormonal suppresslon
PemoLhorax
Lymphang|o|e|omyomatos|s (LAM)
8are dlsease excluslvely ln women of reproducuve
age
Mean age 33 years
re-menopausal > 93
revalence 1-2/mllllon

Lymphang|o|e|omyomatos|s
Sporadlc LAM (S-LAM) -less common buL more
ldenued (83)
1uberous sclerosls complex (1SC-LAM)- 13
1SC- auLosomal domlnanL
Selzures, braln Lumors, cognluve lmpalrmenL, sebaceous
adenomas, anglomyollpomas, **pulmonary LAM ln 1-23

LAM- athogenes|s
ALyplcal smooLh muscle
prollferauon ln
bronchovasculaLure,
lymphaucs and
lnLersuuum
PM8-43+ smooLh muscle
cells (melanocyuc
dlerenuauon)
LxLenslve cysLs
LsLrogens play ma[or role
Lymphang|o|e|omyomatos|s
S-LAM and 1SC-LAM assoclaLed wlLh muLauons ln
1SC genes needed for slgnal regulauon
MuLauons ln 1SC-1 (hamarun gene) or 1SC-2 (Luberln
gene) vla M1C8 (mammallan LargeL of rapamycln)
slgnallng paLhway
ConLrols cell growLh and regulauon
Slrollmus- lnacuvaLes 1C8
LAM- C||n|ca| I|nd|ngs
SympLoms
progresslve dyspnea, cough, hemopLysls,
uurauon- 3-3 yrs
hyslcal exam
crackles, decreased 8S, asclLes, abdomlnal masses
l1s
mlxed resLrlcuon and obsLrucuon
1/3 normal
LAM kad|o|ogy
CysLs- Lhln walled, dluse
no nodules or brosls
1x
euslons
hyperlnauon
LAM- D|agnos|s
ulagnosls
compauble cllnlcal course
P8C1
ussue blopsy for PM8-43
vLCl-u (relauvely new)
LAM- Comp||canons] Cther I|nd|ngs
8ecurrenL pneumoLhoraces ln 60-70
Plgh recurrence Ave 4.4
leurodesls oen requlred
Chylous pleural euslons ln 1/3
Chylous asclLes
Anglomyollpomas
kldneys, uLerus, ovarles, lymph nodes, llver, spleen
blood, smooLh muscle, faL
93 wlLh 1SC-LAM and 30 wlLh S-LAM
Ang|omyo||poma
LAM- rognos|s
lndolenL buL progresslve course
10 year survlval (20-80)
Cause of deaLh- resplraLory fallure
LAM- 1reatment

CophorecLomy (rarely performed currenLly)
MedroxyprogesLerone aceLaLe
Avold esLrogens or pregnancy
8ronchodllaLors
CcLreoude
Slrollmus - lnacuvaLes 1argeL of 8apamycln (1C8)
Suppresses smooLh muscle prollferauon
Suppresses unA synLhesls of LAM cells ln vlLro
Lung LransplanLauon
63 3 year survlval
Can recur

24 monLh double bllnd randomlzed
sLudy
12 monLh LreaLmenL
12 monLh observauon
n=89
LndpolnL- raLe of change ln lLv1
Concluslons
SLablllzed lung funcuon*
8educed sympLoms
lmproved CCL
no dlerence ln frequency of slde
eecLs
S|ro||mus |n LAM (NLIM 2011, 364:1S9S)
Summary of key o|nts
know splromeLrlc changes ln pregnancy
know LreaLmenL of v1L, asLhma ln pregnancy
know baslc crlucal care compllcauons ln pregnancy
lncludlng Locolyuc pulmonary edema
Ceneral sLausucs abouL CCu and lung CA ln women
8ecognlze LAM and be aware of compllcauons