Airways disorders
Eosinophils in COPD
Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.
Dr. Farrukh Abbas
The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.1 Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.2 A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).3
The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.4 Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.7-9
The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.10
Farrukh Abbas, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, MD, FCCP
NetWork Chair
References
1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.
2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.
3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.
4. Criner GJ. Chest. 2020;157(5):1075-8.
5. Shin SH et al. Respir Res. 2018;19(1):134.
6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.
7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.
8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.
9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.
10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
Clinical research
Long-COVID: COVID-19 disease beyond the pandemic
There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.
In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).
Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.
Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Bharat Bajantri, MD
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training