Long-term dyspnea, regional ventilation distribution and peripheral lung function in COVID-19 survivors: a 1 year follow up study

Abstract

Background: Dyspnea is common after COVID-19 pneumonia and can be characterized by a defective CO₂ diffusion (DLCO) despite normal pulmonary function tests (PFT). Nevertheless, DLCO impairment tends to normalize at 1 year, with no dyspnea regression. The altered regional distribution of ventilation and a dysfunction of the peripheral lung may characterize dyspnea at 1 year after COVID-19 pneumonia. We aimed at assessing the pattern of airway resistance and inflammation and the regional ventilation inhomogeneity in COVID-19 pneumonia survivors at 12-months after hospital discharge.

Methods: We followed up at 1-year patients previously admitted to the respiratory units (intensive care or sub-intensive care unit) for COVID-19 acute respiratory failure at 1-year after hospital discharge. PFT (spirometry, DLCO), impulse oscillometry (IOS), measurements of the exhaled nitric oxide (FENO) and Electrical Impedance Tomography (EIT) were used to evaluate lung volumes, CO₂ diffusion capacity, peripheral lung inflammation/resistances and the regional inhomogeneity of ventilation distribution. A full medical examination was conducted, and symptoms of new onset (not present before COVID-19) were recorded. Patients were therefore divided into two groups based on the presence/absence of dyspnea (defined as mMRC ≥1) compared to evaluate differences in the respiratory function derived parameters.

Results: Sixty-seven patients were admitted between October and December 2020. Of them, 42/67 (63%) patients were discharged alive and 33 were evaluated during the follow up. Their mean age was 64 ± 11 years and 24/33 (73%) were males. Their maximum respiratory support was in 7/33 (21%) oxygen, in 4/33 (12%) HFNC, in 14/33 (42%) NIV/CPAP and in 8/33 (24%) invasive mechanical ventilation. During the clinical examination, 15/33 (45%) reported dyspnea. When comparing the two groups, no significant differences were found in PFT, in the peripheral airway inflammation (FENO) or mechanical properties (IOS). However, EIT showed a significantly higher regional inhomogeneity in patients with dyspnea both during resting breathing (0.98[0.96-1] vs 1.1[1-1.1], p = 0.012) and during forced expiration (0.96[0.94-1] vs 1 [0.98-1.1], p = 0.045).

Conclusions: New onset dyspnea characterizes 45% of patients 1 year after COVID-19 pneumonia. In these patients, despite pulmonary function test may be normal, EIT shows a higher regional inhomogeneity both during quiet and forced breathing which may contribute to dyspnea.

Clinical trial registration: Clinicaltrials.gov NCT04343053, registration date 13/04/2020.

Keywords: COVID-19; Dyspnea; Electrical impedance tomography; Post COVID-19; Pulmonary function test; Spirometry.

Fig. 1

Flow chart of the study

Fig. 2

Inhomogeneity index derived from Electrical Impedance tomography (EIT) in patients with and without dyspnea during resting breathing (panel A, tidal volume) and forced expiratory maneuver (panel B)

Fig. 3

Example of EIT images during forced expiration maneuver (∆FEV1_EIT) in two representative patients. Dynamic image of expired volume at 1 second during forced expiration (∆FEV1_EIT) in two representative patients; 2A, asymptomatic patients (mMRC = 0); panel 2B: Symptomatic patient (mMRC = 2). Negative values represent the regional loss of volume (AU) in the 1st second after the start of forced expiration from vital capacity (FEV1)