gestational acute respiratory distress syndrome ( ards ) has an estimated incidence of 1670 per 100 000 pregnancies with a mortality rate approaching 50% . here ,
we present a case of a woman in her 21st week of pregnancy who developed severe ards with multiple etiologic confounders including lymphangioleiomyomatosis ( lam ) , influenza , diffuse alveolar hemorrhage ( dah ) and preeclampsia .
the patient progressed beyond the supportive capabilities of conventional interventions and ultimately required extracorporeal membrane oxygenation ( ecmo ) support . fortunately ,
utilization of novel therapies and timely interventions by multidisciplinary teams enabled this complicated and critically ill pregnant patient and her baby to survive .
a 37-year - old , primigravid woman at 21 weeks gestational age presented to a local hospital complaining of fever , cough and progressive shortness of breath .
she was initially treated for suspected pneumonia but decompensated rapidly requiring emergent intubation for profound hypoxemia .
given the complexity of her illness , she was transferred to our tertiary care facility . upon admission ,
the patient 's chest x - ray ( cxr ) was notable for bilateral interstitial infiltrates , and she was therefore started on empiric broad - spectrum antibiotics and oseltamivir . she was ventilated with lung - protective settings and paralyzed to alleviate ventilator dyssynchrony .
she was started on high - dose methylprednisolone for her dah , and inhaled nitric oxide ( ino ) was added to optimize oxygenation . after a transient period of improvement , new infiltrates were appreciated on cxr , prompting computed tomography ( ct ) of her chest .
this revealed multiple cysts throughout the lung parenchyma , suspicious for the diagnosis of lam ( fig .  1 ) . 

figure  1:ct chest ( axial slices in lung window ) demonstrating innumerable cysts scattered throughout all lung fields without basal / apical predilection or cardiophrenic sparing .
ct chest ( axial slices in lung window ) demonstrating innumerable cysts scattered throughout all lung fields without basal / apical predilection or cardiophrenic sparing .
the patient 's hypoxemia and dah worsened , and she ultimately required venovenous ecmo support on hospital day 15 .
six days into her ecmo course , recombinant activated factor vii ( fviia ) was endobronchially instilled .
ten days after commencing ecmo and at 24 weeks gestational age , the patient developed preeclampsia and hellp syndrome .
the maternal fetal medicine team performed an urgent cesarean section , and a viable female neonate was delivered .
simultaneously , a right - sided wedge biopsy of the lung was performed , and based on histologic findings , the diagnosis of lam was confirmed ( fig . 
2a  d ) . on ecmo day 14 and post - operative day 3 from cesarean delivery
she was extubated to high - flow nasal cannula ( hfnc ) 2 days later . over the course of 2 weeks
the neonate required significant ventilatory and nutritional support but was eventually discharged home without neurologic disability . 

figure  2:histologic images from lung biopsy demonstrating perivascular leukocytic infiltrate ( h&e 400 ) ( a ) , staining for smooth muscle actin ( sma 40 ) ( b ) , hmb-45 ( 400 ) ( c ) and desmin ( 100 ) ( d ) .
histologic images from lung biopsy demonstrating perivascular leukocytic infiltrate ( h&e 400 ) ( a ) , staining for smooth muscle actin ( sma 40 ) ( b ) , hmb-45 ( 400 ) ( c ) and desmin ( 100 ) ( d ) . since discharge from our institution ,
due to a severe perturbation in her diffusing capacity of the lung for carbon monoxide ( dlco ) , she was started on sirolimus , a treatment for lam .
her most recent pulmonary function testing ( pft ) revealed a dlco of 41% predicted and a 6-min walk culminated in desaturation from baseline pulse oximetry of 9880% . a representative section from her most recent chest ct , performed 8 months after discharge ,
figure  3:ct chest ( axial slices in lung window ) demonstrating interval resolution of pneumothoraces and persistent , diffuse numerous thin - walled pulmonary cysts without cardiophrenic sparing .
ct chest ( axial slices in lung window ) demonstrating interval resolution of pneumothoraces and persistent , diffuse numerous thin - walled pulmonary cysts without cardiophrenic sparing .
in pregnant patients with ards unresponsive to conventional interventions , consideration may be given for ecmo support .
limited data exist regarding the effectiveness of ecmo during pregnancy ; however , the h1n1 influenza outbreak of 2009 revealed maternal survival rates of > 60% and neonatal survival as high as 70% with extracorporeal support .
ecmo cannulation is complicated in the pregnant patient due to fetal inferior vena cava compression , which may impede venous drainage if femoral cannulation is required . due to anatomic limitations in our patient ,
thus , inflow cannulation was performed in the right internal jugular vein , and outflow cannulation was achieved in the right femoral vein .
initially , intermittent increases in intrathoracic pressure due to coughing exacerbated her recirculation fraction and compromised systemic oxygen delivery , but this subsided with resolution of alveolar hemorrhage .
lam is a rare and progressive systemic disease that involves smooth muscle infiltration of the lung , culminating in cystic change of lung parenchyma .
the diagnosis of lam during pregnancy is associated with significantly worse maternal outcomes including an increased incidence of premature delivery .
histologic studies of lam have demonstrated variable expression of estrogen / progesterone receptors , suggesting a hormonal role in the pathogenesis of lam .
vegf - d is a serologic marker for lam , and levels > 800 pg / ml have been shown to have 100% specificity .
tissue staining for smooth muscle actin , desmin and hmb-45 is diagnostic for lam . in a randomized controlled trial , initiation of sirolimus in patients with lam
culminated in preservation of fev1 and fvc at 1 year compared with placebo ; however , this treatment effect was not sustained after cessation of therapy .
limited evidence exists regarding the safety of mtor inhibitors , specifically sirolimus , during pregnancy .
dah is a syndrome characterized by injury to the alveolocapillary basement membrane , resulting in red blood cell extravasation into the alveolar spaces .
treatment largely relies on supportive care ; however , a small denmark series demonstrated that local ( endobronchial ) administration of recombinant activated factor vii ( fviia ) at 50 mcg / kg in 50 cc of normal saline may be beneficial .
the therapeutic effect of endobronchial fviia draws on its ability to directly bind receptors on the alveolar surface where tissue factor resides in large concentrations . in conclusion , this is the first reported case of lam - associated gestational ards requiring ecmo .
the individual contributions of influenza , dah , lam and severe preeclampsia are difficult to quantify in this complicated patient .
endobronchial administration of fviia to treat dah in a pregnant patient with lam is novel .
most importantly , the initiation of ecmo support was critical to the survival of our patient and her child . despite its technical challenges
 gestational acute respiratory distress syndrome ( ards ) is a complicated problem with the potential to gravely harm both mother and fetus . 
 this case report describes a young woman in her second trimester of pregnancy who developed progressive respiratory failure in the setting of newly diagnosed influenza , diffuse alveolar hemorrhage and lymphangioleiomyomatosis . 
 the patient 's condition was refractory to conventional interventions and required extracorporeal membrane oxygenation ( ecmo ) support . 
 her course was further complicated by preeclampsia requiring preterm delivery with cesarean section while on ecmo . through novel therapies and a multidisciplinary approach to care , both the patient and 
 her child would overcome these unique and challenging conditions and survive . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONFLICT OF INTEREST STATEMENT