For influenza treatment, there are 2 classes of antiviral medications that are active against influenza that are approved for use in the United States — the adamantanes and neuraminidase inhibitors. Adamantanes are no longer used clinically because of development of resistance to them. The neuraminidase inhibitors available in the United States are the oral agent oseltamivir, the inhaled agent zanamivir, and the intravenous agent peramivir.4,5 Although these agents can relieve symptoms sooner, they may be less effective in high-risk patients such as patients with COPD. Zanamivir has been associated with bronchospasm in some patients and should be used with caution in patients with respiratory disease such as COPD.6

Some studies suggest that use of antiviral agents is associated with decreased length of hospital stay and reduced mortality; however, these should be interpreted with caution, as the prescription of antiviral agents in these studies was at the discretion of the treating physician, and these were not randomized placebo-controlled trials.4,5 The current recommendation from the Centers for Disease Control and Prevention is that neuraminidase inhibitors should be started within 48 hours of onset of symptoms in high-risk patients.6 In addition to treatment, oseltamivir and zanamivir can be used for prophylaxis in individuals exposed to infection.

Pulmonology Advisor: What should be the approach for vaccination in these patients?

Dr Banerjee: Vaccinate, vaccinate, vaccinate! Because of the risk for COPD exacerbations associated with influenza infection and the associated worsening of disease and increased morbidity and mortality, we strongly recommend that all patients with COPD and respiratory disease receive an annual vaccination against influenza.1 Studies have demonstrated that influenza vaccination significantly reduces COPD exacerbations and influenza-related respiratory illness.1 As we age, our immune system gradually deteriorates, with a reduced capacity to respond to infections or develop immunity from vaccination. This phenomenon is called immune senescence, and 2 influenza vaccines are currently approved for use specifically in older adults: a high-dose vaccine and an adjuvanted vaccine. 

In addition to vaccinating individuals with respiratory disease, it is important to vaccinate the population to provide additional protection to vulnerable individuals through herd immunity, a form of indirect protection.7,8 Studies have shown that nursing homes where employees were vaccinated against influenza had lower patient mortality than nursing homes where employees were not vaccinated.7 In addition, one study suggested that vaccinating younger adults against influenza decreased the rate of infection in older adults.8

Pulmonology Advisor: What are remaining needs in this area in terms of research and education regarding influenza in COPD?

Dr Banerjee: There are many remaining needs. We need to develop more effective assays for early diagnosis and more effective antiviral treatments for influenza. Influenza is an RNA virus and thus has the ability to change its genome in both minor and major ways in phenomena called antigenic drift and antigenic shift, respectively.1 Because of these changes, the virus is able to escape recognition by the immune system, and influenza vaccines need to be changed frequently to accommodate for the changes in the virus. We need to research vaccines that are effective regardless of strain, so people may get vaccinated once instead of annually. Additionally, more research needs to be done on vaccines that are effective in aging, senescent immune systems.

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In terms of physician and patient education, as physicians we need to be more proactive about educating patients with COPD about the importance of getting an annual influenza vaccination, as well as the community health benefits of vaccinating everybody else.

References

1. Xu L, Chen B, Wang F, et al. A higher rate of pulmonary fungal infection in chronic obstructive pulmonary disease patients with influenza in a large tertiary hospital. Respiration. 2019;1-10.

2. Kalil AC, Thomas PG. Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care. 2019;23(1):258.

3. Mulpuru S, Li L, Ye L, et al. Effectiveness of influenza vaccination on hospitalizations and risk factors for severe outcomes in hospitalized patients with COPD. CHEST. 2019;155(1):69-78.

4. Chaves SS, Pérez A, Miller L, et al. Impact of prompt influenza antiviral treatment on extended care needs after influenza hospitalization among community-dwelling older adults. Clin Infect Dis. 2015;61(12):1807-1814.

5. Louie JK, Yang S, Acosta M, et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis. 2012;55(9):1198-1204.

6. Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. Last reviewed December 27, 2018. Accessed August 16, 2019.

7. Kingston BJ, Wright CV Jr. Influenza in the nursing home. Am Fam Physician. 2002;65(1):75-79.

8. Taksler GB, Rothberg MB, Cutler DM. Association of influenza vaccination coverage in younger adults with influenza-related illness in the elderly. Clin Infect Dis. 2015;61(10):1495-1503.