Breath-holding physiology, radiological severity and adverse outcomes in COVID-19 patients: A prospective validation study

Abstract

Background and objective: COVID-19 remains a major cause of respiratory failure, and means to identify future deterioration is needed. We recently developed a prediction score based on breath-holding manoeuvres (desaturation and maximal duration) to predict incident adverse COVID-19 outcomes. Here we prospectively validated our breath-holding prediction score in COVID-19 patients, and assessed associations with radiological scores of pulmonary involvement.

Methods: Hospitalized COVID-19 patients (N = 110, three recruitment centres) performed breath-holds at admission to provide a prediction score (Messineo et al.) based on mean desaturation (20-s breath-holds) and maximal breath-hold duration, plus baseline saturation, body mass index and cardiovascular disease. Odds ratios for incident adverse outcomes (composite of bi-level ventilatory support, ICU admission and death) were described for patients with versus without elevated scores (>0). Regression examined associations with chest x-ray (Brixia score) and computed tomography (CT; 3D-software quantification). Additional comparisons were made with the previously-validated '4C-score'.

Results: Elevated prediction score was associated with adverse COVID-19 outcomes (N = 12/110), OR[95%CI] = 4.54[1.17-17.83], p = 0.030 (positive predictive value = 9/48, negative predictive value = 59/62). Results were diminished with removal of mean desaturation from the prediction score (OR = 3.30[0.93-11.72]). The prediction score rose linearly with Brixia score (β[95%CI] = 0.13[0.02-0.23], p = 0.026, N = 103) and CT-based quantification (β = 1.02[0.39-1.65], p = 0.002, N = 45). Mean desaturation was also associated with both radiological assessment. Elevated 4C-scores (≥high-risk category) had a weaker association with adverse outcomes (OR = 2.44[0.62-9.56]).

Conclusion: An elevated breath-holding prediction score is associated with almost five-fold increased adverse COVID-19 outcome risk, and with pulmonary deficits observed in chest imaging. Breath-holding may identify COVID-19 patients at risk of future respiratory failure.

Keywords: COVID-19; breath-holding procedure; coronavirus disease; incident adverse outcome; mean desaturation; physiology; radiological severity.

FIGURE 1

Our prediction score (LogOdds of Adverse Outcome) based on simplified breath‐holding manoeuvres discriminates patients with elevated risk of COVID‐19 adverse outcome with 76% sensitivity and 60% specificity for a threshold ~0 (i.e., 50% probability of adverse outcome). Findings are similar to our previous internal validation (see Messineo et al., Figure 2D). VS+ (ventilatory support), patients that met the composite adverse outcome. VS−, patients that did not meet the composite adverse outcome

FIGURE 2

The breath‐holding based prediction score (LogOdds of Adverse Outcome) was positively associated with the Brixia score applied to chest x‐ray (panel A; N = 103) and applied to c‐MPR CT (panel B; N = 45) and was associated with computer‐aided CT‐based quantification of pulmonary involvement (panel C; N = 45). Different colours illustrate the magnitude of mean desaturation (i.e., red and blue correspond to large and small values, respectively, as represented by the colour bar). Note that those with greater desaturation, who had higher predicted risk of adverse outcomes (orange‐red dots concentrated at the top of the figures, blue at the bottom), tended to exhibit greater radiological severity scores (orange‐red dots concentrated to the right of the figures, blue to the left), particularly for CT (panels B,C). c‐MPR CT, coronal multiplanar reformation image computed tomography