BACKGROUND
 
Hypoxemia (low PaO2) is a hallmark of moderate-to-severe interstitial lung disease (ILD). Ventilation/perfusion (V̇/Q̇) mismatch is a dominant mechanism, with a secondary role for diffusion limitation (at least at rest).(1) In some patients, intrapulmonary shunting and impaired alveolar exchange of oxygen (O2) can occur (“physiological” shunt [ShuntPHYS)]),(2) leading to severe, irreversible or nearly irreversible hypoxemia. Because of the effect of gravity on pulmonary blood flow, any shunted fraction can increase in the upright position when extensive alveolar filling is present in dependent areas of the lung in the setting of relatively preserved capillary perfusion.
 
OVERVIEW
 
A 23-year-old woman reported progressive dyspnea and dry cough for a few months after an acute episode of fever and sore throat. On examination, she assumed the supine position (SpO2 = 96% on room air), reporting dyspnea soon after sitting (platypnea); of note, her SpO2 was consistently < 88% when she was in the upright position (orthodeoxia).(3) No environmental exposures were identified; however, she reported chronic use of nitrofurantoin for urinary tract infections. COVID-19 and HIV testing was negative, as was liver and connective tissue disease workup. Spirometry in the recumbent position (≈30°) revealed severe and proportional reductions in FEV1 and FVC (Figure 1A). Arterial blood gas analysis after administration of 100% O2 for 20 min revealed increased right-to-left shunt that almost doubled from the supine to the seated position (Figure 1B). Chest CT showed extensive ground-glass/reticular opacities, septal thickening, and traction bronchiectasis/bronchiolectasis, particularly in the anterior aspects of the lower lobes and in the right middle lobe/lingula (indeterminate usual interstitial pneumonia; Figure 1C). Transesophageal echocardiography showed no structural cardiac abnormalities; however, microbubbles appeared in the left chambers every 3-8 beats after their identification in the right atrium (i.e., intrapulmonary shunt).(3) CT pulmonary angiography revealed no pulmonary embolism or arteriovenous malformations.

 
ShuntPHYS (venous admixture; normal ≤ 10%) can be subdivided into: a) anatomic shunt (ShuntANAT) via bronchial, pleural, and thebesian veins (normal ≤ 5%); b) capillary shunt (ShuntCAP), representing pulmonary capillary blood in contact with completely unventilated alveoli; and c) shunt effect (i.e., perfusion in excess of ventilation).(2) Unlike the alveolar-arterial O2 gradient,(4) ShuntPHYS is independent of the shape of the O2 dissociation curve, but it requires sampling pulmonary arterial blood to obtain mixed venous oxygen content. Making the subject breathe pure O2 for sufficient time to wash out nitrogen allows the measurement of the fraction of venous admixture caused by ShuntANAT plus ShuntCAP (i.e., “absolute shunt”) without the confounding influence of V̇/Q̇ inequalities.(2) When intracardiac communication, pulmonary arteriovenous malformations, and hepatopulmonary syndrome are excluded as causes of orthodeoxia in ILD patients, other possible causes include increased ShuntCAP and undetected small arteriovenous channels (≤ 20  µm diameter).(5) The supine position increases venous return, which is more homogenously distributed to better ventilated areas (superior and posterior lung fields in the present case; Figure 1C), reducing the shunted fraction and improving oxygenation and dyspnea.(3)
 
CLINICAL MESSAGE
 
Platypnea-orthodeoxia is a potential cause of atypical/paroxysmal dyspnea and refractory hypoxemia in ILD patients in the upright position. Quantification of postural modifications in “absolute shunt” measured during 100% O2 breathing provides a minimally invasive test of O2 exchange efficiency that is dependent on changes in regional lung perfusion.
 

1. Agustí AG, Roca J, Gea J, Wagner PD, Xaubet A, Rodriguez-Roisin R. Mechanisms of gas-exchange impairment in idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1991;143(2):219-225. https://doi.org/10.1164/ajrccm/143.2.219


2. Hughes JMB, Pride NB. Pulmonary gas exchange. In: Hughes JMB, Pride NB (editors). Lung Function Tests: Physiological Principles and Clinical Applications. London: Harcourt Brace; 1999. p. 75-98.


3. Agrawal A, Palkar A, Talwar A. The multiple dimensions of Platypnea-Orthodeoxia syndrome: A review. Respir Med. 2017;129:31-38. https://doi.org/10.1016/j.rmed.2017.05.016


4. Neder JA, Berton DC, O’Donnell DE. Arterial blood gases in the differential diagnosis of hypoxemia. J Bras Pneumol. 2020;46(5):e20200505. https://doi.org/10.1590/1806-3713/e20200019


5. Tenholder MF, Russell MD, Knight E, Rajagopal KR. Orthodeoxia: a new finding in interstitial fibrosis. Am Rev Respir Dis. 1987;136(1):170-173. https://doi.org/10.1164/ajrccm/136.1.170