Slide 1

What your test results mean toyou and your doctor

Emily Gilbert, MD

Assistant Professor, Dept of Medicine

Div of Pulmonary & Critical Care

Loyola University Medical Center

Case

•35 year old Caucasian female with eight yearsof worsening shortness of breath

•She was diagnosed with asthma but feels norelief from inhalers

•Further testing is ordered

–Chest X-Ray

–CT scan of chest

–Pulmonary function tests

Chest X-Ray

Chest X-Ray

Pneumothorax

Chest X-Ray

Pleural effusion

Chylous pleural effusion

Chlye

http://upload.wikimedia.org/wikipedia/commons/f/f5/Thoracentesis.jpg

Chest X-Ray

Chest CT - LAM

Chest CT - Emphysema

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Why get Pulmonary Function Tests?

•Obtain baseline of lung function

•Assess disease progression

•Assess response to medications

•Determine prognosis and need for lungtransplantation

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“Breathenormally”

“Breathe in asdeeply as youcan”

“Breathe outas hard as youcan”

Cleveland Clinic Jnl of Med 2003; 70: 866-881

Volume of airexpelled duringthe entireforcedexhalation

Volume of airexpelled duringthe first secondof the forcedexhalation

Maximum Inhalation

Maximum Exhalation

Spirometry

•Measures the exhaled volume and flow of air vs time

•Tidal Volume: volume of air moved during normalbreathing

•FVC (forced vital capacity):

–volume of air expelled during the entire forced exhalation(measured in liters)

•FEV1 (forced expiratory volume in 1 second):

–volume of air expelled during the first second of the forcedexhalation (measured in liters)

•FEV1/FVC: % of air expelled in the first second

Cleveland Clinic Jnl of Med 2003; 70: 866-881

Volume of airexpelled duringthe entireforcedexhalation

Volume of airexpelled duringthe first secondof the forcedexhalation

FEV1/FVC

•70-75% of volume expelledduring forced expiration shouldbe exhaled during the 1stsecond

•FEV1/FVC ratio<70% indicatesobstructive lung disease

–Asthma

–Emphysema

–LAM

Spirometry in LAM

•Smooth musclecells proliferate andsurround airways

•Narrowing ofairways  Air flowdecreased Decreased FEV1

http://www.brown.edu/Courses/Digital_Path/systemic_path/pulmonary/L54.jpg

Normal Spirometry Values

•Reference value based on:

–Age

–Height

–Ethnicity

–Gender

•Reference value, measured value (L) and % of predictedvalue are reported

•% predicted =

patient’s value

reference value

X 100

Severity

•Reduced FEV1/FVC ratio

–FEV1/FVC ratio<70% = obstruction

•FEV1 is decreased due to obstruction of flow

•Severity of obstruction is based on FEV1

–FEV1 80-100% predicted = normal

–FEV1 60-80% predicted = mild obstruction

–FEV1 40-60% predicted = moderate obstruction

–FEV1 <40% predicted = severe obstruction

http://www.sharinginhealth.ca/respiratory/images/flow_volume_loops.jpg

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<70% = obstruction

50% = Moderate

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Hypothesis for cyst formation

Bronchodilator Response

•Bronchodilators (e.g., Albuterol) relax musclesaround the airway

•Spirometry is performed before and afteradministration of a bronchodilator

•Positive bronchodilator response:

–200mL increase in FEV1

and

–12% change

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Average LAM Spirometry Values

•Average FEV1/FVC = 64.5%

•Average FEV1= 70% of predicted

–Mild disease

•Patients with TSC-LAM have more milddisease at the time of presentation

Ryu et al. NHLBI LAM registry. AJRCCM 2006; 173:105-111

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Pulmonary Diffusing Capacity

•Diffusing capacity ofthe lungs for carbonmonoxide (DLCO)

•Measures thetransmission of the COmolecule from alveolargas to hemoglobin inthe pulmonarycapillary blood

Pulmonary Diffusing Capacity

1.Patient exhales completely

2.Breathes in the test gas (10%helium, 0.3% CO + oxygenand nitrogen) to maximuminspiration

3.Breath hold x 10 seconds

•CO has very high affinity forhemoglobin so crossesmembrane and binds quickly tored blood cell

4.Patient exhales quickly andexhaled gas is collected

DLCO

•DLCO is adjusted for hemoglobin

•DLCO 80-100% = normal diffusion capacity

•DLCO 60-80% = mildly decreased diffusion capacity

•DLCO 40-60% = moderately decreased diffusion capacity

•DLCO <40% = severely decreased diffusion capacity

Ryu et al. NHLBI LAM registry. AJRCCM 2006; 173:105-111

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Cleveland Clinic Jnl of Med 2003; 70: 866-881

Volume of air leftin lungs at end ofmaximumexhalation

Total volume ofair in the lungsat maximuminhalation

Obstruction Air Trapping

•Increased RV or TLC (>120% predicted) = Air trapping

Restriction

•Decreased TLC (<80% predicted) = Restriction

•Causes of restriction:

–Pleural effusion

–Pleurodesis for recurrent pneumothorax

http://www.simpto.nl/wp-content/uploads/2014/07/pleurodese-thoracocentese.jpg

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Moderateobstruction

+ bronchodilatorresponse

Mild airtrapping

Severe defect ingas diffusion

•The diagnosis of LAM is suspected based onChest CT findings

•A serum Vascular Endothelial Growth Factor D(VEGF-D) level is drawn

VEGF-D

•Serum VEGF-D level of >800pg/mL in femalewith typical lung cystic changes on CT isspecific for S-LAM

•Higher levels indicate more severe disease

•Her level returns at 935 pg/mL

•Based on her CT scan and VEGF-D level, she isgiven a diagnosis of LAM

Other testing…

•MRI brain

–To look for evidence of tuberoussclerosis complex (TSC)

•Abdominal CT scan

–To assess for evidence ofangiomyolipoma

•Desaturation screen

http://img.medscape.com/article/745/228/745228-fig2.jpg

88% oxygensaturation

Results

•No evidence of Tuberous Sclerosis on her MRIof the brain

•No angiomyolipoma on CT of abdomen

•She desaturates to 84% on room air whileambulating and requires 2L of oxygen to keepsaturations >88%

Next steps

•She is started on oxygen to keep oxygensaturation >88% while ambulating

•Given her symptoms and moderateobstruction on spirometry, Rapamycin isstarted

Follow-up appointments

•Rapamycin trough

•Cholesterol level

•VEGF-D level

•CT chest

–Every few years

–Very slowly progressing disease

•Pulmonary function tests

–Every 6-12 months

Average lung function decline

•Nonsmokers without lungdisease lose 30ml/year oflung function after age 35

Lung function decline in LAM

Premenopausal

Postmenopausal

Decline FEV1, % predicted

2.2% per year

0.9% per year

Decline FEV1, mL

90 mL/year

55 mL/year

Decline DLCO, % predicted

2.8% per year

1.9% per year

Decline DLCO, mL/mmHg/min

0.78 per year

0.58 per year

CHEST 2004; 126:1867–1874

MILES trial N Engl J Med 2011; 364:1595-1606

•Rate of change of FEV1 was primary outcomein the MILES trial

•Placebo group had an observed FEV1 declineof 134mL over one year

•Sirolimus group had improvement in FEV1 of19mL over one year

Value attime ofenrollment

Value at 12 months

Placebo Sirolimus

Change from baseline

Placebo Sirolimus

FEV1 (mL)

1367mL(48%)

1272mL

1383mL

-134mL

+19mL

FVC (mL)

2791mL(79% pred)

2843mL

2780mL

-129mL

+97mL

MILES trial N Engl J Med 2011; 364:1595-1606

Value attime ofenrollment

Value at 12 months

Placebo Rapamycin

Change from baseline

Placebo Rapamycin

FEV1 (mL)

1367mL(48%)

1272mL

1383mL

-134mL

+19mL

FVC (mL)

2791mL(79% pred)

2843mL

2780mL

-129mL

+97mL

SerumVEGF-D(pg/mL)

2029pg/mL

2444pg/mL

862pg/mL

-14.8pg/mL

-1032pg/mL

MILES trial N Engl J Med 2011; 364:1595-1606

•Despite being on Rapamycin, our patient hascontinued progression of her disease withworsening shortness of breath and increasingoxygen requirements

2010

Value

% Predicted

FVC

3.51

105%

FEV1

1.41

50%

FEV1/FVC

40%

DLCO

7.3

•Despite being on Rapamycin, our patient hascontinued progression of her disease withworsening shortness of breath and increasingoxygen requirements

2010

2014

Value

% Predicted

Value

% Predicted

FVC

3.51

105%

3.20

98%

FEV1

1.41

50%

0.79

25%

FEV1/FVC

40%

25%

DLCO

7.3

34%

6.9

30%

Lung Transplantation

•Pulmonary function tests help predict when one shouldbe listed for lung transplant

•Guidelines for lung transplant in LAM:

–Severe life-limiting shortness of breath

–Uncontrollable, recurrent pneumothorax

–Use of oxygen

•Average lung function of LAM patients at time oftransplant:

–FEV1 25% of predicted

–DLCO 27% of predicted

Summary

•CXR, CT chest can help lead to diagnosis

•Pulmonary Function tests obtained at baseline andevery 6-12 months

•FEV1/FVC ratio <70% indicates obstruction

–Severity of obstruction is based on FEV1

–Rule of 20s to determine severity

•VEGF-D level can help make diagnosis without biopsyand may decrease with Rapamycin

•Lung transplant is an option if disease progressesdespite therapy

References

•Fletcher C. The natural history of chronic airflow obstruction. British MedicalJournal 1977;1:1645-1648.

•Taveira-DaSilva AM et al. Reversible Airflow Obstruction, Proliferation of abnormalsmooth muscle cells and impairment of gas exchange as predictors of outcome inLAM. AJRCCM 2001; 164: 1072-1076.

•Taveira-DaSilva AM et al. Decline in Lung Function in Patients withLymphangioleiomyomatosis Treated with or without Progesterone. Chest 2004;126:1867-1874.

•Orens JB, et al. International Guidelines for the selection of Lung TrasplantCandidates: 2006 update. Jnl of Heart and Lung Transplant 2006; 7: 745-755.

•McCormack FX. Lymphangioleiomyomatosis: A Clinical Update. Chest 2008;133:507-516.

•Taveira-DaSilva AM et al. Reversible Airflow Obstruction in LAM. Chest 2009: 136;1596-1603.

•Clements D et al. Lymphangioleiomyomatosis. Eur Respi Mon 2009; 46:176-207.

•McCormack FX et al. Efficacy and Safety of Sirolimus inLymphangioleiomyomatosis. N Engl J Med 2011; 364:1595-1606

•Henske, EP, McCormack FX. Lymphangioleiomyomatosis – a wolf in sheep’sclothing. JCI 2012;122(11):3807-3816.