Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

The answer is “NO”! With an estimated 20% to 50% of acute chronic obstructive pulmonary disease (COPD) exacerbations attributed to noninfectious factors (1,2), routine inclusion of antibiotics in the treatment of this condition is not only unnecessary but potentially harmful.

 
Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommends the use of antibiotics in patients who have dyspnea, increased sputum volume, and increased sputum purulence—or at least 2 of these 3 criteria when sputum purulence is one of them (3)—, these recommendations are not based on robust evidence and have not been widely corroborated (2,4-6).

 
That’s why the findings of a 2019 New England Journal of Medicine study (PACE) supporting the use of serum C-reactive protein (CRP) as an adjunctive test in COPD exacerbation is particularly welcome (1). In this multicenter randomized controlled trial performed in the U.K., the following CRP guidelines (arrived from prior studies) were provided to primary care clinicians to be used as part of their decision making in determining which patients with COPD exacerbation may not need antibiotic therapy:

 
• CRP less than 20 mg/L: Antibiotics unlikely to be beneficial
• CRP 20-40 mg/L: Antibiotics may be beneficial, mainly if purulent sputum is present
• CRP greater than 40 mg/L: Antibiotics likely to be beneficial

 
Adoption of these guidelines resulted in significantlly fewer patients being placed on antibiotics without evidence of harm over a 4-week follow-up period (1).  Despite its inherent limitations (eg, single country, outpatient setting), CRP testing may be a step in the right direction in curbing unnecessary use of antibiotics in COPD exacerbation.  

 

Liked this post? Sign up under MENU and catch future pearls straight into your inbox!

 

References

 
1. Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 2019;381:111-20. https://www.ncbi.nlm.nih.gov/pubmed/31291514
2. Llor C, Moragas A, Hernandez S, et al. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:716-23. https://www.ncbi.nlm.nih.gov/pubmed/22923662
3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019 (http://www.goldcopd.org).
4. Brett AS, Al-Hasan MN. COPD exacerbations—A target for antibiotic stewardship. N Engl J Med 2018;381:174-75. https://www.ncbi.nlm.nih.gov/pubmed/31291521
5. Miravitlles M, Moragas A, Hernandez S, et al. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 2013;144:1571-7. https://www.ncbi.nlm.nih.gov/pubmed/23807094
6. Van Vezen P, Ter Riet G, Bresser P, et al. Doxycycline for outpatient-treated acute exacerbations of COPD: a randomized double-blind placebo-controlled trial. Lancet Respir Med 2017;5:492-9. https://www.ncbi.nlm.nih.gov/pubmed/28483402

Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

My patient with primary Sjogren’s syndrome has now been diagnosed with COPD despite lack of a significant smoking history. Is there a connection between Sjogren’s syndrome and COPD?

Increasing body of evidence suggests that COPD in patients with primary Sjögren’s syndrome (PSS) is not uncommon even among those who never smoked (1).

 
A 2015 study of patients with PSS reported that overall 41% of patients with PSS, including 30% of those who never smoked, fulfilled the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD. More specifically, pulmonary function tests (PFTs) showed decreased vital capacity (VC), forced expiratory volume in 1 second (FEV-1)  and DLCO in patients with PSS. Importantly, lab inflammatory and serological features were poorly associated with PFT results, while radiographic signs of interstitial lung disease (ILG) were absent in one-half of patients with PSS and COPD (1).

 
A longitudinal study with a mean follow-up of 11 years found a 37% rate of development of COPD among patients with PSS (2). Another related study reported a poor correlation between respiratory symptoms and COPD disease as assessed by PFTs in PSS, with the authors recommending that PFTs be performed “liberally” in all patients with PSS regardless of symptoms (3).

 
Lastly, a population-based cohort study of female adults found significantly higher rate of COPD among patients with PSS compared to controls (4).

 
Although the exact pathogenic mechanism behind PSS-associated COPD is unclear, xerotrachea and impaired mucocilliary clearance, as well as inflammatory infiltrates in the exocrine glands of the airways, all leading to physical obstruction and bronchial hyperreactivity have been suggested (1).

 

Bonus Pearl: Did you know that COPD is associated with many other autoimmune diseases (eg, rheumatoid arthritis and systemic lupus erythematosus), and a genetic link has been implicated between COPD and autoimmunity? (5,6).

 

If you liked this post, sign up under MENU and catch future pearls right into your mailbox!

References
1. Nilsson AM, Diaz S, Theander E, et al. Chronic obstructive pulmonary disease is common in never-smoking patients with primary Sjögren’s syndrome. J Rheumatol 2015;42:464-71. https://www.researchgate.net/publication/270907531_Chronic_Obstructive_Pulmonary_Disease_Is_Common_in_Never-smoking_Patients_with_Primary_Sjogren_Syndrome
2. Mandl T, Diaz S, Ekberg O, et al. Frequent development of chronic obstructive pulmonary disease in primary SS-result of a longitudinal follow-up. Rheumatology 2012;51:941-46. https://www.researchgate.net/publication/221760110_Frequent_development_of_chronic_obstructive_pulmonary_disease_in_primary_SS-results_of_a_longitudinal_follow-up
3. Bolmgren VS, Olssson P, Wollmer P, et al. Respiratory symptoms are poor predictors of concomitant chronic obstructive pulmonary disease in patients with primary Sjögren’s syndrome. Rheumatol Int 2017;37:813-18. https://link.springer.com/content/pdf/10.1007/s00296-017-3678-5.pdf
4. Shen TC, Wu BR, Chen HJ, et al. Risk of chronic obstructive pulmonary disease in female adults with primary Sjögren’s syndrome. A nationwide population-based cohort study. Medicine 2016; 95:1-6. http://europepmc.org/abstract/MED/26962839
5. Hemminki K, Liu X, Ji J et al. Subsequent COPD and lung cancer in patients with autoimmune disease. Eur Respir J 2011;37:463-74. https://www.ncbi.nlm.nih.gov/pubmed/21282811
6. Ji X, Niu X, Qian J, et al. A phenome-wide association study uncovers a role for autoimmunity in the development of chronic obstructive pulmonary disease. Resp Cell Mol Biol 2018;58:777-79. https://www.atsjournals.org/doi/10.1165/rcmb.2017-0409LE

My patient with primary Sjogren’s syndrome has now been diagnosed with COPD despite lack of a significant smoking history. Is there a connection between Sjogren’s syndrome and COPD?

Why are patients with acute exacerbation of COPD at higher risk of venous thromboembolism (VTE)?

Patients admitted to the hospital for acute exacerbation of COPD are generally regarded as being at high risk of venous thromboembolism (VTE) (prevalence 5%-29%), possibly due to the frequent coexistence of other risk factors, such as immobility, history of smoking, and venous stasis.1 The exact mechanism(s) behind this association remains poorly understood, however.

Among patients with moderate-very severe COPD (GOLD criteria stage II-IV),  high BMI, low exercise tolerance, history of pneumothorax, congestive heart failure, and peripheral vascular disease have also been associated with VTE.1

Systemic inflammation has also been implicated in increasing the risk of VTE in patients with COPD. Although the pathophysiology of COPD is largely defined by the local inflammatory response to airway injury, evidence suggests that there is also a systemic inflammatory response in COPD.2,3 This systemic inflammation could in turn contribute to the increased risk of vascular disease, including VTE, coronary artery disease, and cerebrovascular disease.4

Bonus pearl: Did you know that VTE may be 3x more prevalent among patients with COPD exacerbation without known cause (vs those with identifiable cause) and is associated with a 1-year mortality of 61.9%! 5

References:

  1. Kim V, Goel N, Gangar J, et al. Risk factors for venous thromboembolism in chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis 2014;1: 239-249. https://www.ncbi.nlm.nih.gov/pubmed/25844397
  2. Lankeit M, Held M. Incidence of venous thromboembolism in COPD: linking inflammation and thrombosis? Eur Respir J 2016;47(2):369-73. https://www.ncbi.nlm.nih.gov/pubmed/26828045
  3. Sinden NJ1, Stockley RA. Systemic inflammation and comorbidity in COPD: a result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence. Thorax 2010;65:930-6. https://www.ncbi.nlm.nih.gov/pubmed/20627907
  4. King PT. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clinical and Translational Medicine 2015;4:26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518022/
  5. Gunen H, Gulbas G, In E, et al. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010;36:1243-8.  https://www.ncbi.nlm.nih.gov/pubmed/19926740 

Contributed by Camilo Campo, Medical Student, Harvard Medical School, Boston, MA.

Why are patients with acute exacerbation of COPD at higher risk of venous thromboembolism (VTE)?