key: cord-0784298-nknb4jrj
authors: Neder, José Alberto; Berton, Danilo Cortozi; O’Donnell, Denis E
title: Quantification of oxygen exchange inefficiency in interstitial lung disease
date: 2021
journal: J Bras Pneumol
DOI: 10.36416/1806-3756/e20210028
sha: 67d738406c4434991cd40df05bf6dae02229f78f
doc_id: 784298
cord_uid: nknb4jrj

nan

Hypoxemia (low PaO 2 ) is a hallmark of moderateto-severe interstitial lung disease (ILD). Ventilation/ perfusion (V/Q) 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 (O 2 ) can occur ("physiological" shunt [Shunt PHYS) ]), (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.

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 (SpO 2 = 96% on room air), reporting dyspnea soon after sitting (platypnea); of note, her SpO 2 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 FEV 1 and FVC ( Figure 1A) . Arterial blood gas analysis after administration of 100% O 2 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.

Shunt PHYS (venous admixture; normal ≤ 10%) can be subdivided into: a) anatomic shunt (Shunt ANAT ) via bronchial, pleural, and thebesian veins (normal ≤ 5%); b) capillary shunt (Shunt CAP ), 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 O 2 gradient, (4) Shunt PHYS is independent of the shape of the O 2 dissociation curve, but it requires sampling pulmonary arterial blood to obtain mixed venous oxygen content. Making the subject breathe pure O 2 for sufficient time to wash out nitrogen allows the measurement of the fraction of venous admixture caused by Shunt ANAT plus Shunt CAP (i.e., "absolute shunt") without the confounding influence of V/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 Shunt CAP 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) 

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% O 2 breathing provides a minimally invasive test of O 2 exchange efficiency that is dependent on changes in regional lung perfusion.

Mechanisms of gas-exchange impairment in idiopathic pulmonary fibrosis

Lung Function Tests: Physiological Principles and Clinical Applications. London: Harcourt Brace

The multiple dimensions of Platypnea-Orthodeoxia syndrome: A review

Arterial blood gases in the differential diagnosis of hypoxemia

Orthodeoxia: a new finding in interstitial fibrosis