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CME / ABIM MOC / CE

Is Air Trapping a Long-Lasting Sequela of COVID-19?

  • Authors: News Author: Walter Alexander; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 4/29/2022
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 4/29/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for pulmonologists, infectious disease clinicians, internists, family medicine and primary care clinicians, pharmacists, nurses, and other members of the healthcare team for patients with COVID-19.

The goal of this activity is that learners will be better able to describe chest computed tomography (CT) findings and functional small airways disease (fSAD) in patients with post-acute sequelae of COVID-19 (PASC), according to a single-center study at a university teaching hospital.

Upon completion of this activity, participants will:

  • Describe chest CT findings and fSAD in patients with PASC, according to a single-center study at a university teaching hospital
  • Identify clinical implications of chest CT findings and fSAD in patients with PASC, according to a single-center study at a university teaching hospital
  • Outline implications for the healthcare team


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News Author

  • Walter Alexander

    Freelance writer, Medscape

    Disclosures

    Disclosure: Walter Alexander has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Stocks, stock options, or bonds: AbbVie (former)

Editor/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

Compliance Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.


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CME / ABIM MOC / CE

Is Air Trapping a Long-Lasting Sequela of COVID-19?

Authors: News Author: Walter Alexander; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME / ABIM MOC / CE Released: 4/29/2022

Valid for credit through: 4/29/2023, 11:59 PM EST

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Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

Nearly 30% of patients with post-acute sequelae of COVID-19 (PASC), including persons who had mild infection not requiring hospitalization, have persistent respiratory symptoms. Small airways disease with air trapping appears to be a long-lasting sequela of SARS-CoV-2 infection, according to a prospective study that compared 100 COVID-19 survivors who had persistent symptoms and 106 healthy control participants.

"Something is going on in the distal airways related to either inflammation or fibrosis that is giving us a signal of air trapping," noted senior author Alejandro P. Comellas, MD, in a press release.[1] The study was stimulated by reports from University of Iowa clinicians noting that many patients with initial SARS-CoV-2 infection who were either hospitalized or were treated in the ambulatory setting later reported shortness of breath and other respiratory symptoms indicative of chronic lung disease.

Given the millions of COVID-19 infections worldwide, this finding may have a substantial potential impact on healthcare systems. While this initial study had limitations, emerging data continues to be a vital tool for earlier identification and initiation of appropriate treatment for active COVID-19 infections and PASC; thus, improving patient outcomes.

Study Results

Investigators classified patients (mean age, 48 years; 66 women) with PASC according to whether they were ambulatory (67%), hospitalized (17%), or required treatment in the intensive care unit (ICU) (16%). They then compared computed tomography (CT) findings of patients who had COVID-19 and persistent symptoms with those of a healthy control group.

COVID-19 severity did not affect the percentage of cases of lung with air trapping among these patients. Air trapping occurred at rates of 25.4% among ambulatory patients, 34.6% in hospitalized patients, and in 27.3% of patients requiring intensive care (P = .1). The percentage of lung affected by air trapping in ambulatory participants was sharply and significantly higher than in healthy control participants (25.4% vs 7.2%; P < .001). Also, air trapping persisted; it was still present in 8 of 9 participants who underwent imaging more than 200 days postdiagnosis.

Qualitative analysis of chest CT images showed that the most common imaging abnormality was air trapping (58%); ground-glass opacities (GGOs) were found in 51% (46/91), noted Comellas and co-authors. This suggests ongoing lung inflammation, edema, or fibrosis. These symptoms are often observed during acute COVID-19, frequently in an organizing pneumonia pattern, and have been shown to persist for months after infection in survivors of severe disease. The mean percentage of total lung classified as having regional GGO on chest CT scans was 13.2% and 28.7%, respectively, in the hospitalized and ICU groups, both very much higher than in the ambulatory group, at 3.7% (P < .001 for both). Among healthy control participants, the GGO rate on chest CT was only 0.06% (P < .001).

In addition, air trapping correlated with the ratio of residual volume to total lung capacity (r = 0.6; P < .001) but not with spirometry results. In fact, the investigators did not observe airflow obstruction by spirometry in any group, suggesting that air trapping in these patients involves only small rather than large airways and that these small airways contribute little to total airway resistance. Only when a large percentage, perhaps 75% or more, of all small airways are obstructed will spirometry pick up small airways disease, the authors observed.

Continuing Disease

The findings taken together suggest that functional small airways disease (fSAD) and air trapping are consequences of SARS-CoV-2 infection, according to Comellas.

"If a portion of patients continues to have small airways disease, then we need to think about the mechanisms behind it," he said. "It could be something related to inflammation that's reversible, or it may be something related to a scar that is irreversible, and then we need to look at ways to prevent further progression of the disease."

He added, "Studies aimed at determining the natural history of [fSAD] in patients with post-acute sequelae of COVID-19 and the biological mechanisms that underlie these findings are urgently needed to identify therapeutic and preventative interventions," Comellas, professor of internal medicine at Carver College of Medicine, University of Iowa, Iowa City, concluded.

The study limitations, the authors stated, include the fact that theirs was a single-center study that enrolled participants infected early during the COVID-19 pandemic and did not include patients with delta or omicron variants, thus limiting the generalizability of the findings.

The study was published in Radiology.[2]

The reported findings "indicate a long-term impact on bronchiolar obstruction," stated Brett M. Elicker, MD, professor of clinical radiology, University of California, San Francisco, in an accompanying editorial.[3]

Because collagen may be absorbed for months after an acute insult, it is not entirely clear whether the abnormalities seen in the current study will be permanent.

Elicker said further, "the presence of [GGO] and/or fibrosis on CT were most common in the patients admitted to the ICU and likely correspond to post-organizing pneumonia and/or post-diffuse alveolar damage fibrosis."

He also pointed out that organizing pneumonia is especially common among patients with COVID-19 and is usually highly steroid-responsive. The opacities improve or resolve with treatment, but sometimes residual fibrosis occurs.

"Longer-term studies assessing the clinical and imaging manifestations 1-2 years after the initial infection are needed to fully ascertain the permanent manifestations of post-COVID fibrosis," Elicker concluded.

The study was supported by grants from the National Institutes of Health. The authors and Elicker have disclosed no relevant financial relationships.

Study Highlights

  • In this single-center study at a university teaching hospital, 100 adults with confirmed COVID-19 with persistent symptoms > 30 days after diagnosis were prospectively enrolled between June and December 2020 and compared with 106 healthy control participants prospectively enrolled between March and August 2018.
  • The median age of adults with PASC was 48 years; 66 were women; 67% were classified as ambulatory, 17% as hospitalized, and 16% as ICU patients during their acute illness.
  • On chest CT, the mean percentage of total lung classified as GGO was 13.2% in hospitalized and 28.7% in ICU groups vs 3.7% in the ambulatory group (P < .001 for both) and 0.06% among healthy control participants (P < .001).
  • The mean percentage of total lung affected by air trapping was 25.4% in the ambulatory group, 34.6% in the hospitalized group, and 27.3% in the ICU group, respectively (P = .1), vs 7.2% in healthy control participants (P < .001).
  • Air trapping correlated with residual volume/total lung capacity (r = 0.6; P < .001) but not with spirometry results, which showed no airflow obstruction in any group.
  • Air trapping was not associated with time from diagnosis to CT imaging (median, ~ 75 days).
  • Among 9 participants who underwent imaging > 200 days after diagnosis, air trapping persisted in 8.
  • The most common chest CT abnormality was air trapping (58%); GGO occurred in 51%.
  • The investigators concluded that in survivors of COVID-19, small airways disease with air trapping is a long-lasting sequela occurring independently of initial infection severity, with unknown long-term consequences.
  • Compared with healthy control participants, patients with ambulatory COVID-19 had similar spirometry and lung volumes but higher percentage of lung affected by GGO, suggesting ongoing lung inflammation, edema, or fibrosis.
  • The lack of airflow obstruction on spirometry in any group suggests that air trapping results from involvement of small rather than large airways.
  • Air trapping is often missed with spirometry but detected with inspiratory and expiratory CT imaging and plethysmography.
  • Combined with findings of previous studies, this analysis suggests that SARS-CoV-2 infection itself leads to fSAD and air trapping whereas restrictive lung disease and impairment in gas exchange result from lung injury and acute respiratory distress syndrome.
  • The angiotensin-converting enzyme 2 receptor, which facilitates SARS-CoV-2 infection, is expressed in small airways and throughout the airway tract.
  • Even in individuals with PASC after mild acute infection, direct infection of small airways may cause fSAD, or immune response to SARS-CoV-2 could cause fSAD as a form of postinfectious constrictive bronchiolitis.
  • Persistence of respiratory abnormalities over ~ 75 days and ≤ 200 days from diagnosis to chest CT imaging raises concern for permanent airway remodeling and fibrosis after SARS-CoV-2 infection.
  • Study limitations include it being a single-center study enrolling participants infected early during the COVID-19 pandemic, limiting generalizability as acute treatment was highly variable, and none had delta or omicron infection.
  • In addition, participants with PASC did not have baseline imaging, the sample was small, and the study could not determine the prevalence of pulmonary function testing and imaging abnormalities among asymptomatic COVID-19 survivors.
  • To identify therapeutic and preventative interventions, future research should examine the natural history of fSAD in patients with PASC and biologic mechanisms underlying these findings.
  • Longitudinal assessment is needed to determine whether fSAD in patients with PASC improves over time or causes persistent or progressive lung disease.
  • Larger studies are needed to determine whether presence of fSAD correlates with respiratory symptoms.
  • An accompanying editorial noted a long-term effect on bronchiolar obstruction that might not be permanent, as collagen may be absorbed for months after an acute insult.
  • Organizing pneumonia is especially common in COVID-19 and usually highly steroid-responsive, but residual fibrosis may occur. The editorial concurs that longer-term studies are needed.

Clinical Implications

  • In COVID-19 survivors, small airways disease with air trapping is a long-lasting sequela occurring independently of initial infection severity.
  • Persistence of respiratory abnormalities raises concern for permanent airway remodeling and fibrosis after SARS-CoV-2 infection.
  • Implications for the Healthcare Team: While identifying therapeutic and preventative interventions, clinicians should recall that air trapping is often missed with spirometry but detected with inspiratory and expiratory CT imaging and plethysmography.

 

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