Womens Issues in Pulmonary Medicine

1
Womens Issues in Pulmonary Medicine

• Stephanie M. Levine MD, FCCP
• The University of Texas Health Science Center-San
  Antonio

2
Disclosures

• None

3
Objectives

• To review normal respiratory and cardiovascular
  physiology in pregnancy
• To review the management of common pulmonary
  disorders in pregnancy
• To review critical care cardiopulmonary disorders
  in pregnancy
• To review tobacco related diseases in women
• To review unique pulmonary disorders in women

4
Upper Respiratory Tract in Pregnancy

• Airway mucosa- hyperemia and edema
• Secretions- increased (3rd trimester)
• Epistaxis
• Hoarseness
• Nasal polyps- increased
• Allergic rhinitis- increased
• More difficult intubation
• Estrogen mediated

5

• All of the following pulmonary function tests
  are decreased during pregnancy except
• A. Expiratory reserve volume
• B. Total lung capacity
• C. Vital capacity
• D. Functional residual capacity
• E. Residual volume

6

• All of the following pulmonary function tests
  are decreased during pregnancy except
• A. Expiratory reserve volume
• B. Total lung capacity
• C. Vital capacity
• D. Functional residual capacity
• E. Residual volume

7
Respiratory Physiology
Bonica et al 1995
8
Respiratory Physiology
Bonica et al 1995
9
Respiratory Physiology

• Tidal volume- 30-50 increase
• Progesterone mediated increase in central and
  hypercapnic respiratory drive
• Respiratory rate- no change to mild increase
• Minute ventilation increases-20-50 (9L)

10
Respiratory Physiology

• Flow rates- no change
• Airway resistance- no change
• MVV- no change
• Lung compliance- no change
• Total respiratory compliance- decreased
• DLCO- increased then decreased

11
Which ABG would be expected in a healthy woman in
her 20th week of a normal pregnancy?
12
Which ABG would be expected in a healthy woman in
her 20th week of a normal pregnancy?
13
Gas Exchange

• Mild compensated respiratory alkalosis
• PaCO2 28-32 mmHg
• Bicarbonate 18-21 meq/L
• pH- 7.40-7.45
• PaO2 100-105 mmHg
• Increased A-a gradient
• Increased O2 consumption 20-30
• Increased CO2 production

14
Sleep Disordered Breathing

• Increased snoring
• Increase in sleep disordered breathing
• OSA may develop or worsen
• CPAP

15

• All of the following parameters are increased
  during pregnancy except
• A. Cardiac output
• B. Stroke volume
• C. Pulmonary vascular resistance
• D. Red blood cell volume
• E. Heart rate

16

• All of the following parameters are increased
  during pregnancy except
• A. Cardiac output
• B. Stroke volume
• C. Pulmonary vascular resistance
• D. Red blood cell volume
• E. Heart rate

17
Cardiovascular Physiology
Bonica et al 1995
18
Cardiovascular Physiology in Pregnancy

• Cardiac output- increased HR, SV
• SVR- decreased
• PVR- decreased
• BP- decreased diastolic and systolic
• Postural hypotension

19
Fluid Physiology
Bonica et al 1995
20
Fluid Physiology in Pregnancy

• Total blood volume- increased
• Plasma volume- increased
• RBC volume- increased (but less)
• Dilutional anemia
• Serum proteins- decreased (edema)
• Mineralocorticoid/ hormonal changes

21
Dyspnea in Pregnancy

• Effects 2/3 of pregnant women
• 1st and 2nd trimester
• Progesterone
• hyperventilation
• alteration in CO2 sensitivity
• Anemia
• Beware of stenotic cardiac lesions, right to left
  shunts

22
FDA Drug Classification

• Category A - No or remote risk
• Adequate controlled studies in women show no
  risk
• Category B No evidence of risk in humans
• No risk in animal studies but no human studies
  have been done
• Risk in animal studies but not in human studies
• Category C Risk can not be ruled out
• Human studies lacking and risk in animal studies
• Neither human nor animal studies available
• Category D- Positive evidence of risk
• Investigational or post-marketing data show risk
• Category X- Contraindicated in pregnancy
• Known fetal harm e.g. thalidomide

23

• During pregnancy the course of asthma tends to
• A. Worsen
• B. Improve
• C. Stay the same
• D. Equal likelihood of the above

24

• During pregnancy the course of asthma tends to
• A. Worsen
• B. Improve
• C. Stay the same
• D. Equal likelihood of the above

25
Asthma in Pregnancy

• 7 of pregnant women
• Increased fetal and maternal risks
• preterm labor, pre-eclampsia, previa, IUGR
• The 1/3 rule!
• Severity predictor- severity when not pregnant or
  in prior pregnancies
• Worse- middle pregnancy, delivery, PP
• GERD, sinusitis, allergic rhinitis

26

• A 22 yo woman G1P0 with a h/o asthma is at 12
  weeks gestation. Her asthma has been managed
  with prn ?2 agonists, inhaled CS and salmeterol.
  She now reports daily ? agonist use and nightly
  awakenings. She is in mild distress and is
  wheezing on exam. Her FEV1 is 70. The best
  management of this patient is
• A. Increase use of short acting ?2 agonist
• B. Begin a course of oral CS
• C. Add theophylline
• D. Add zileuton
• E. No change in current therapy

27

• A 22 yo woman G1P0 with a h/o asthma is at 12
  weeks gestation. Her asthma has been managed
  with prn ?2 agonists, inhaled CS and salmeterol.
  She now reports daily ? agonist use and nightly
  awakenings. She is in mild distress and is
  wheezing on exam. Her FEV1 is 70. The best
  management of this patient is
• A. Increase use of short acting ?2 agonist
• B. Begin a course of oral CS
• C. Add theophylline
• D. Add zileuton
• E. No change in current therapy

28
Asthma Treatment
Well Controlled Very Poorly
Controlled

• Mild intermittent- short acting B2 agonists for
  sx
• Mild persistent-
• Low dose inhaled CS- budesonide (B),
  beclomethasone (C).
• cromolyn
• LTRA
• theophylline
• Moderate persistent
• inhaled CS- low dose plus LABA OR
• inhaled CS- medium dose plus LABA
• Severe- inhaled CS (high dose), LABA, oral CS
• gestational DM, stress dose during L and D

Not well Controlled
www.ginasthma.com
29
Asthma Drugs

• Category B
• cromolyn
• budesonide
• terbutaline
• anticholinergics
• montelukast
• zafirlukast
• omalizumab

• Category C
• short acting B2
• LABA
• inhaled CS
• systemic CS
• theophylline

30
Acute Asthma Treatment

• Oral CS
• Anticholinergic agents
• Heliox
• Intubation paCO2 42 mm Hg ?
• Avoid epinephrine

31

• Which of the following statements about DVT in
  pregnancy is true?
• A. They occur equally in the right and
  left leg.
• B. They are more common in the
  ante-partum period.
• C. They are more common in the first
  trimester.
• D. The diagnostic yield of Doppler US is
  improved in the left lateral decubitus
  position.

32

• Which of the following statements about DVT in
  pregnancy is true?
• A. They occur equally in the right and
  left leg.
• B. They are more common in the
  ante-partum period.
• C. They are more common in the first
  trimester.
• D. The diagnostic yield of Doppler US is
  improved in the left lateral decubitus
  position.

33
Venous Thromboembolism in Pregnancy

• Leading cause of mortality (20-50)
• .05-.1 of pregnancies
• Equal distribution over trimesters and ante and
  post partum
• 90 of DVT on left

34
VTE Risk Factors

• Venous stasis
• Hypercoagulability -
• increased fibrinogen, I, II, VII, VIII, IX, X,
  XII, activated protein C resistance
• Endothelial disruption

• Bed rest
• Advanced maternal age
• Multiparity
• Prior VTE
• C-section
• Obesity
• Pre-eclampsia
• Thrombophilia

35
VTE Diagnosis

• Diagnosis of DVT
• Dopplers- best in left lateral decubitus
• venography
• D-Dimer?
• Diagnosis of PE
• V/Q scan- smaller isotope dose, only Q
• CT angiogram
• angiogram

36

• A 29 yo woman G3P2 in the 9th week of
  pregnancy presents with acute SOB and C/P,
  RR-30, P-120, BP-100/80 mmHg. A V/Q scan reveals
  2 segmental perfusion defects. The best
  treatment is
• A. IV UFH x 3-5 days followed by coumadin
  until delivery
• B. Streptokinase
• C. Coumadin alone until delivery
• D. SQ LMWH at weight based dose until
  delivery
• E. IVC filter placement

37

• A 29 yo woman G3P2 in the 9th week of
  pregnancy presents with acute SOB and C/P,
  RR-30, P-120, BP-100/80 mmHg. A V/Q scan reveals
  2 segmental perfusion defects. The best
  treatment is
• A. IV UFH x 3-5 days followed by coumadin
  until delivery
• B. Streptokinase
• C. Coumadin alone until delivery
• D. SQ LMWH at weight based dose until
  delivery
• E. IVC filter placement

38
VTE- Treatment

• LMWH- weight adjusted or
• Unfractionated heparin- IV followed by adjusted
  dose following aPTT x 5 days (1A)
• LMWH or UFH should be continued throughout
  pregnancy (1B)
• Treat for 6 weeks post-partum for at least a
  total of 6 mos. of AC (2C)
• LMWH preferred over UFH (2C)

ATT8-CHEST 2008 133.
39
VTE

• LMWH- category B
• Unfractionated heparin- category C
• HIT, osteoporosis
• Warfarin- category X
• Thrombolytics- relative contraindication
• IVC filter (suprarenal)

40
VTE

• Delivery
• epidural catheters relatively contraindicated
• d/c LMWH or UFH- 24 hours prior (1C)

41
VTE- Prophylaxis

• Single VTE with RF- surveillance and PP AC
  prophylaxis (1C)
• Idiopathic VTE or thrombophilia, no VTE-
  surveillance or prophylaxis, and PP AC (1C)
• Thrombophilia- prophylaxis and PP AC (1C)
• gt 2 episodes VTE- AC (2C)
• VTE in prior pregnancy- surveillance or
  prophylaxis plus PP AC prophylaxis (2C)
• Rx LMWH over SQ UFH (2C)

ATT8-CHEST 2008 133.
42

• A 31 yo woman G3P2 in her 21st week of
  gestation presents with fever, cough, weight
  loss, fibrocavitary changes on CXR and is found
  to have sputums positive for AFB. She is HIV
  negative. The best treatment at this time would
  be

43

• A. INH and rifampin
• B. INH, rifampin, PZA and streptomycin
• C. INH, rifampin, PZA and EMB
• D. INH, rifampin and EMB
• E. Delay treatment until after viable delivery

44

• A. INH and rifampin
• B. INH, rifampin, PZA and streptomycin
• C. INH, rifampin, PZA and EMB
• D. INH, rifampin and EMB
• E. Delay treatment until after viable delivery

45
Tuberculosis in Pregnancy

• Incidence increasing
• No difference in susceptibility, course, or
  outcomes
• Drug regimens
• INH, rifampin, EMB x 9 months
• Use pyridoxine
• Pyrazinamide- not well studied
• Streptomycin- teratogenic (ototoxicity)

46
LTBI

• Low risk group with clear CXR- can delay
  treatment
• High risk- 9 months of INH

47
Pneumonia in Pregnancy

• Incidence and bacteriology similar to
  non-pregnant women
• Increased maternal M and M
• Similar treatment
• penicillins- category B
• cephalosporins- category C
• quinolones- category C
• macrolides- category B and C
• tetracycline- category D
• sulfonamides- category C

48
Pneumonia

• Coccidioidomycosis-
• increased risk for dissemination and mortality
• worse in 3rd trimester
• amphotericin- category B
• azoles- category C

49
(No Transcript)
50
Pneumonia

• Varicella Zoster
• pneumonia in non-exposed pregnant woman mortality
  approaches 35
• CXR- nodular/ miliary pattern, calcification
• acyclovir- category B
• Influenzae
• drugs- category C
• vaccine- all high risk and others after 1st TM

51
Hemodynamics in Pregnancy

• High CO
• Low SVR
• Positional hypotension when supine- left lateral
  decubitus position
• May require lower PAOP
• Obstetrical causes of sepsis

52
Mechanical Ventilation in Pregnancy

• Difficult intubation
• Reduced chest wall compliance- TV
• Maintain pregnant eucapnia
• Saturations gt 90
• Non-invasive ventilation ?

53

• A 29 yo G2P1 woman in her 27th week of
  pregnancy presents with preterm labor. She is
  begun on terbutaline. CS are added to promote
  lung development. Her contractions improve and
  the terbutaline is d/c 24 hours later. Over the
  next 12 hours she c/o c/p and SOB.
• PE- afebrile, RR-32, P- 120, BP- 100/60
  mmHg, lungs- crackles, CV- tachycardia
• CXR- bilateral alveolar infiltrates

54
What is the most likely diagnosis in this
patient?

• A. Amniotic fluid embolism
• B. Pulmonary embolism
• C. Peripartum cardiomyopathy
• D. Sepsis and ARDS
• E. Tocolytic pulmonary edema

55
What is the most likely diagnosis in this
patient?

• A. Amniotic fluid embolism
• B. Pulmonary embolism
• C. Peripartum cardiomyopathy
• D. Sepsis and ARDS
• E. Tocolytic pulmonary edema

56
Critical Care in Pregnancy

• Amniotic fluid embolism
• Tocolytic pulmonary edema
• Pulmonary hypertension
• Peripartum cardiomyopathy
• Venous air embolism

• Obstetrical related sepsis
• ARDS from obstetrical sepsis
• Aspiration
• VTE
• HELLP
• Acute fatty liver of pregnancy

57
Amniotic Fluid Embolism

• 18000- 180,000
• 80-90 mortality
• During labor or 48 hours post partum
• RF
• advanced maternal age, multiparity, PROM,
  uterine stimulants
• Pathophysiology-
• vascular obstruction, capillary leak, LV failure,
  anaphylaxis

58
Amniotic Fluid Embolism

• Presentation
• acute tachypnea, tachycardia, hypotension,
  hemodynamic collapse, seizures, DIC, hemorrhage,
  ARDS
• DX
• exclusion, supported by fetal cells in blood
• RX
• supportive- MV, vasopressors, blood products

59
Amniotic Fluid Embolism

• Presentation
• acute tachypnea, tachycardia, hypotension,
  hemodynamic collapse, seizures, DIC, hemorrhage,
  ARDS
• DX
• exclusion. supported by fetal cells in blood
• RX
• supportive- MV, pressors, blood

60
(No Transcript)
61
Venous Air Embolism

• Mortality- 90 (100 ml of air)
• Air in venous circulation
• delivery, abortion
• RV obstruction- hemodynamic collapse
• Presentation
• coughing, tachypnea, tachycardia, MS changes,
  mill wheel murmur, cardiopulmonary arrest, ARDS,
  air in retinal vessels or subdermal, air in heart
  on CXR

62
Venous Air Embolism

• Treatment
• left lateral decubitus position
• aspiration
• 100 oxygen
• heparin?
• corticosteroids?
• hyperbaric oxygen

63
Tocolytic Pulmonary Edema

• Beta 2 agents- terbutaline, ritodrine
• exacerbated with corticosteroids
• Effects 4-5 of patients
• 24-48 hours after drug initiation
• RF
• prolonged drug use, pre-eclampsia, multiple
  gestations

64
Tocolytic Pulmonary Edema

• Mechanisms
• fluid overload, cardiac toxicity, changes in
  oncotic pressures, capillary permeability
• Presentation
• dyspnea, chest pain, crackles, pulmonary edema
• Treatment
• discontinuation of drug
• resolves in 12-24 hours

65
Aspiration

• 2 of maternal mortality
• Obstetrical patients at high risk
• decreased lower esophageal sphincter tone
• increase in intragastric pressures
• decrease gastric emptying
• supine position
• analgesia, sedation

66
Aspiration

• Pathophysiology related to
• pH
• volume
• bacterial load
• presence of particulate matter
• Complications
• ARDS
• Pneumonitis
• infection
• asphyxia

67
Aspiration

• Treatment
• supportive
• no corticosteroids
• no prophylactic AB
• bronchoscopy for large particulate matter

68
Peripartum Cardiomyopathy

• 11300-14000 deliveries
• 3rd TM- 6 months post partum
• RF- age, multiples, race, eclampsia
• Presentation- CHF
• Echocardiogram- hypokinesis
• Prognosis- variable
• Can recur

69
Pulmonary Hypertension in Pregnancy

• High maternal (35-50) and fetal mortality
• Immediate peripartum period
• High CO with fixed PVR
• Acute RHF
• Counseled against pregnancy
• Deliver with use of PA catheter, NO, prostacyclin
  (B), sildenafil (B), bosentan (X)

70
(No Transcript)
71
(No Transcript)
72
(No Transcript)
73
(No Transcript)
74
All of the following statements are true except

• A. Lung cancer is the most common cause of
  cancer deaths in women.
• B. Smoking women have a lower likelihood of
  developing COPD than do men.
• C. Adenocarcinoma is the most common lung
  cancer in women.
• D. Children exposed to smoke can have
  decreased pulmonary function and increased
  respiratory infections.

75
All of the following statements are true except

• A. Lung cancer is the most common cause of
  cancer deaths in women.
• B. Smoking women have a lower likelihood of
  developing COPD than do men.
• C. Adenocarcinoma is the most common lung
  cancer in women.
• D. Children exposed to smoke can have
  decreased pulmonary function and increased
  respiratory infections.

76
Tobacco Use in Women

• 2001 Surgeon General Report on Women and Smoking
• 22 of women smoke (men 25.5)
• lung cancer is the leading cause of cancer deaths
  in women (25 of all cancer deaths) and 90 are
  attributable to smoking
• dose response of lung cancer with quantity,
  duration and intensity of tobacco use

www.cdc.gov
77
Trends in Cigarette Smoking Prevalence (), by
Gender, Adults 18 and Older, US, 1965-2005
Men
Women
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.
78
Tobacco Use in the US, 1900-2003
Per capita cigarette consumption
Male lung cancer death rate
Female lung cancer death rate
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.
79
Ten Leading Cancer Types for the Estimated New
Cancer Cases and Deaths, by Sex, United States,
2008
Jemal, A. et al. CA Cancer J Clin 20085871-96.
80
Annual Age-adjusted Cancer Incidence Rates for
Selected Cancers by Sex, United States, 1975 to
2004
From Jemal, A. et al. CA Cancer J Clin
20085871-96.
81
Annual Age-adjusted Cancer Death Rates for
Selected Cancers, United States, 1930
to 2004
Males
Females
From Jemal, A. et al. CA Cancer J Clin
20085871-96.
82
Tobacco Effects in Women

• Lung CA
• Adenocarcinoma- most common in smoking and
  non-smoking women
• Smoking women have increased risk of small cell
  cancer
• COPD
• Trends similar to lung cancer
• May be more susceptible

83
Catamenial Diseases

• Pneumothorax
• rare and recurrent, usually right sided
• 24-48 hours after onset of menstrual flow
• pelvic, pleural, diaphragmatic endometriosis
• RX- hormonal suppression, thoracotomy,
  pleurodesis
• Hemoptysis- parenchymal endometriosis
• RX- hormonal suppression
• Hemothorax

84
(No Transcript)
85
Lymphangioleiomyomatosis (LAM)

• Rare disease exclusively in women
• Young women of reproductive age
• Mean age 35 years
• Pre-menopausal gt 95
• Prevalence 1-2/million
• 1300 women in LAM Foundation
• 240 women registered with NHLBI

86
LymphangioleiomyomatosisPathogenesis

• Atypical smooth muscle proliferation in
  bronchovasculature, lymphatics and interstitium
• HMB-45 smooth muscle cells (melanocytic
  differentiation)
• Extensive cysts
• Estrogens play major role

87
(No Transcript)
88
(No Transcript)
89
LAM- Clinical Findings

• Symptoms
• progressive dyspnea, cough, hemoptysis,
• Duration- 3-5 yrs
• PE
• crackles, decreased BS, ascites, abdominal masses
• Radiology
• cyst formation, thin walled, diffuse , no nodules
  or fibrosis, PTX, effusions, hyperinflation

90
(No Transcript)
91
(No Transcript)
92
(No Transcript)
93
(No Transcript)
94
LAM- Clinical Findings

• PFT
• mixed restriction and obstruction
• 1/3 normal
• Diagnosis
• compatible clinical course
• HRCT
• tissue biopsy for HMB-45

95
LAM- Clinical Findings

• Recurrent pneumothoraces in 60-70
• High recurrence Ave 4.4
• Pleurodesis often required
• Chylous pleural effusions in 1/3
• Chylous ascites
• Angiomyolipomas-
• kidneys, uterus, ovaries, lymph nodes, liver,
  spleen
• blood, smooth muscle, fat
• 93 with TSC-LAM and 50 with S-LAM

96
(No Transcript)
97
LAM- Prognosis

• Indolent but progressive course
• 10 year survival (20-80)
• Cause of death- respiratory failure

98
LAM- Treatment

• Oophorectomy
• Medroxyprogesterone acetate
• Avoid estrogens or pregnancy
• Bronchodilators
• Octreotide

99
LAM- Treatment

• Sirolimus
• Suppresses smooth muscle proliferation
• Suppresses DNA synthesis of LAM cells in vitro
• Lung transplantation
• 65 5 year survival
• Can recur

100
Pulmonary Function in LAMn11 on Sirolimus
390
Spirometric results (5-10 increase in FEV1 and
FVC)
346
Increase in cc above baseline
118
62
N Engl J Med 2008358140.