Managing Influenza as a Coinfection in COPD

Welcome to Lungs & Bugs, a collaboration between Pulmonology Advisor and Infectious Disease Advisor. Each month, we will feature content on disease states related to both specialties, including pneumonia, influenza, and tuberculosis. We hope this endeavor will encourage more open dialogue between pulmonologists and infectious disease clinicians.

Preventing acute exacerbations in chronic obstructive pulmonary disease (COPD) is critical to reduce disease burden, frequency of hospitalizations, and high costs associated with the illness. Factors such as smoking, bronchiectasis, severe airflow limitation, and infection have been identified as exacerbation triggers in COPD.¹ Research findings have shown that ≤50% of exacerbations may result from viral infection, and the influenza virus has been detected in ≤28% of patients experiencing exacerbations.¹

Influenza-related deaths occur primarily in individuals with chronic diseases such as COPD, and, in general, these patients experience worse outcomes as a result of influenza.

“Because of underlying respiratory compromise, patients with COPD can have more severe complications from influenza infection and are more likely to require hospitalization when infected with the flu,” Philip Diaz, MD, pulmonologist at The Ohio State University Wexner Medical Center, in Columbus, told Pulmonology Advisor.

In addition to the respiratory effects of the virus itself, influenza infection increases the risk for other illnesses, including bacterial and fungal infection, further increasing the risk for mortality and morbidity in patients with COPD.¹ For example, acute pneumonia has been diagnosed in 30% to 40% of hospitalized patients with influenza, particularly patients with risk factors, including chronic heart or lung disease and a history of smoking.²

In a 2019 retrospective study of patients with influenza at a hospital in China (N=278), patients with COPD demonstrated higher rates of respiratory failure, severe illness, positive fungal cultures, and use of antifungal drugs and systemic corticosteroids compared with patients without COPD.¹ Among the group with COPD, rates of positive fungal cultures (especially for Aspergillus) and systemic corticosteroid use were higher among patients with vs without influenza. A long-term history of COPD (≥20 years) and heavy smoking (≥20 pack-years) were identified as independent risk factors for susceptibility to influenza in the patients with COPD.

A recent multicenter cohort study of 4198 patients with COPD found higher rates of crude mortality (9.7% vs 7.9%; P =.047) and critical illness (17.2% vs 12.1%; P <.001) among patients with COPD with influenza infection vs patients not infected.³ In patients with influenza, risk factors for mortality included age >75 years (adjusted odds ratio [aOR] 3.7; 95% CI, 0.4-30.3), home oxygen use (aOR 2.9; 95% CI, 1.6-5.1), residence in long-term care (aOR 2.6; 95% CI, 1.5-4.5), and cardiac comorbidity (aOR 2; 95% CI, 1.3-3.2).

Screening, Treatment, and Prevention

Adequate screening and timely treatment are essential in this patient population, and physicians should maintain a high index of suspicion during influenza season, according to Dr Diaz.

“Nasal or throat swabs for influenza testing should be considered for any [patient with] COPD hospitalized with an exacerbation during influenza activity — that is, circulation of seasonal influenza A and B viruses in the local community,” he advised. “For outpatients with suspected influenza, testing can be considered if it is likely to change management.”

Antiviral therapy should be administered to hospitalized patients with COPD and influenza and to outpatients with COPD and confirmed influenza — or patients with typical symptoms of the virus — if their symptoms first appeared within the previous 48 hours.³

“There is considerable evidence that influenza vaccination improves outcomes in patients with COPD, and as a rule, all patients with COPD — even those younger than 65 [years] — should receive the influenza vaccine,” Dr Diaz noted. In the multicenter study mentioned above, rates of influenza-related hospitalizations were 38% lower among patients who were vaccinated against influenza compared with patients who were unvaccinated.³ Although clinical guidelines recommend influenza vaccination for patients with COPD, studies have demonstrated vaccination rates of only 50% to 60% in this population.³

“More research is needed addressing ways to enhance influenza vaccination rates among individuals with COPD,” said Dr Diaz.

To further discuss influenza infection in COPD, Pulmonology Advisor interviewed Audreesh Banerjee, MD, an assistant professor of clinical medicine in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, who specializes in pulmonary and critical care medicine.

Pulmonology Advisor: What is known about the risks and effects of influenza infection in patients with pulmonary diseases such as COPD?

Dr Banerjee: Influenza infection plays an important role in exacerbations of COPD and other respiratory diseases, especially during flu season, which lasts from October through May. Exacerbations caused by viral infections such as influenza are more severe and can cause prolonged hospitalizations in infected patients, and patients with more frequent or severe exacerbations are more likely to have progression of their disease.

COPD is more common in older adults, who already have a higher burden of morbidity and mortality from influenza infection; however, it is important to note that patients with COPD are at an increased risk for hospitalization because of respiratory illness during influenza outbreaks regardless of their age or the severity of their disease.

Pulmonology Advisor: How is screening and treatment typically approached in these cases?

Dr Banerjee: It is essential to have a high index of suspicion for influenza infection in patients with COPD, as they may not present with the classic “textbook” presentation of fever, cough, and generalized body aches. Patients with COPD who are infected with influenza commonly present with cough, sputum production, and dyspnea, symptoms that are typical of an exacerbation of their underlying COPD.¹ Generally, isolation of influenza virus in culture can take several days for a definitive result, and although there is a rapid antigen test for influenza, it is important to note this test has low sensitivity in adults, who shed less virus than children and tend to shed virus for a shorter period of time, making this test less useful as a screening tool. Polymerase chain reaction (PCR) assays are more sensitive for influenza diagnosis in adults; however, not all clinical laboratories perform PCR currently, and some clinical laboratories perform this assay but do not do it daily.