Breath-holding as a novel approach to risk stratification in COVID-19

Ludovico Messineo, Elisa Perger, Luciano Corda, Simon A Joosten, Francesco Fanfulla, Leonardo Pedroni, Philip I Terrill, Carolina Lombardi, Andrew Wellman, Garun S Hamilton, Atul Malhotra, Guido Vailati, Gianfranco Parati, Scott A Sands

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death).

METHODS: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison.

RESULTS: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls.

CONCLUSIONS: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.

Original languageEnglish
Pages (from-to)208
Number of pages10
JournalCrit Care
Issue number1
Publication statusPublished - Jun 14 2021


  • Adult
  • COVID-19/physiopathology
  • Carbon Dioxide/analysis
  • Case-Control Studies
  • Humans
  • Hypercapnia/complications
  • Inspiratory Capacity
  • Lung Volume Measurements/methods
  • Male
  • Middle Aged


Dive into the research topics of 'Breath-holding as a novel approach to risk stratification in COVID-19'. Together they form a unique fingerprint.

Cite this