{
  "abstract": "Background Persistent pulmonary dysfunction is common after COVID-19, yet traditional assessments using carbon monoxide diffusing capacity (DLCO) alone may miss alveolar-capillary impairment.Objective To determine whether combining nitric oxide (DLNO 5s) and carbon monoxide (DLCO5s) diffusing capacities enhances detection of post-COVID-19 lung impairment and whether summed z-scores outperform individual measures in classifying affected individuals.Design and methods We conducted an individual participant data meta-analysis using hierarchical mixed-effects modelling. The dataset included 572 COVID-19 survivors and 72 matched controls from six European centres. Lung function metrics—including spirometry, total lung capacity, DLNO 5s and DLCO5s—were standardised into z-scores. Logistic models were compared using Bayesian Information Criterion and Leave-One-Out Information Criterion. Classification accuracy was assessed with Matthews Correlation Coefficient (MCC) and net reclassification improvement (NRI). Principal Component Analysis examined score structures, and dyspnoea severity was correlated with z-scores. Assessments were conducted 32–575 days post-infection (median=130 days).Results The number of days between SARS-CoV-2 diagnosis and testing did not affect any of the measured z‐scores. Summed DLNO 5s + DLCO5s z-scores consistently outperformed individual metrics. The combined model improved MCC by 0.06 (95% CI 0.01 to 0.11) and NRI by 37% (95% CI 13 to 62%) over DLCO5s alone. The top model (summed DLNO5s + DLCO5s z-scores model) explained 10% of fixed and 59% of random variance. DLCO5s alone failed to identify reduced membrane diffusion in approximately 16% of cases. Dyspnoea severity was significantly associated with all diffusion indices (p<0.001), though combined scores showed no stronger correlation than single predictors.Conclusion Summed DLNO 5s + DLCO5s z-scores enhance classification of post-COVID-19 pulmonary impairment beyond DLCO5s alone. The NO-CO double diffusion approach offers improved diagnostic discrimination between previously infected individuals and controls and aligns with symptom severity. These findings support broader clinical integration of combined diffusion metrics in post-COVID assessment.",
  "authors": [
    {
      "affiliations": [
        "Department of Physiology and Membrane Biology, University of California Davis, Davis, California, USA"
      ],
      "name": "Gerald Stanley Zavorsky"
    },
    {
      "affiliations": [
        "IRCCS Ospedale Policlinico San Martino, Genova, Italy"
      ],
      "name": "Giovanni Barisione"
    },
    {
      "affiliations": [
        "Physiologie et Explorations Fonctionnelles, GHUPSSD, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Bobigny, France"
      ],
      "name": "Thomas Gille"
    },
    {
      "affiliations": [
        "National Center for Respiratory Pharmacoeconomics and Pharmacoepidemiology, CESFAR, Verona, Italy"
      ],
      "name": "Roberto W Dal Negro"
    },
    {
      "affiliations": [
        "Department of Pneumonology, University Hospital Complex of Vigo, VIgo, Pontevedra, Spain",
        "NeumoVigo, Institute of Health Research South Galicia (IISGS), Vigo, Spain"
      ],
      "name": "Marta Núñez-Fernández"
    },
    {
      "affiliations": [
        "The University of Sydney, Camperdown, New South Wales, Australia",
        "Thoracic Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia"
      ],
      "name": "Leigh Seccombe"
    },
    {
      "affiliations": [
        "Department of Health Sciences, Università degli Studi di Milano, Bergamo, Lombardy, Italy",
        "Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy"
      ],
      "name": "Gianluca Imeri"
    },
    {
      "affiliations": [
        "Department of Health Sciences, Università degli Studi di Milano, Bergamo, Lombardy, Italy",
        "Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy"
      ],
      "name": "Fabiano Di Marco"
    },
    {
      "affiliations": [
        "Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen - Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Jann Mortensen"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Lombardy, Italy"
      ],
      "name": "Elisabetta Salvioni"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Lombardy, Italy",
        "Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy"
      ],
      "name": "Piergiuseppe Agostoni"
    },
    {
      "affiliations": [
        "Department of Experimental Medicine, University of Genoa, Genoa, Italy"
      ],
      "name": "Vito Brusasco"
    }
  ],
  "title": "Enhanced detection of patients with previous COVID-19: superiority of the double diffusion technique",
  "uid": "bbb5ab6f-f86e-5fcb-9291-19fe5a37c346"
}