Pulmonary Advisor
October 28, 2019
Tori Rodriguez, MA, LPC, AHC
The influenza virus can trigger exacerbations in patients with asthma and 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.
As flu season approaches, the US Centers for Disease Control and Prevention (CDC) continues to recommend influenza vaccination for all patients aged ≥6 months, with rare exceptions such as those with severe allergy to an ingredient in the vaccine.1 Individuals with preexisting respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD) are among the groups identified as having a high risk for serious influenza-related complications.2
In a multicenter study (n=4198) published in January 2019 in CHEST, higher rates of crude mortality (9.7% vs 7.9%; P =.047) and critical illness (17.2% vs 12.1%; P <.001) were found among patients with COPD with vs without influenza infection, and vaccination was associated with a 38% reduction in influenza-related hospitalizations.3 Another recent study reported higher rates of severe illness, respiratory failure, and positive fungal cultures in patients with influenza and COPD.4
The influenza virus can also cause other types of infections including pneumonia, which has been diagnosed in 30% to 40% of hospitalized patients with influenza, especially in those with certain risk factors including chronic lung disease.4,5 In addition, the virus can trigger exacerbations in patients with asthma and COPD.2,6
Taken together, such findings underscore the critical importance of vaccination and other preventive efforts in patients with chronic respiratory illness. For an in-depth discussion on the topic, Pulmonology Advisor interviewed the following experts:
Atul Malhotra, MD, board-certified pulmonologist, intensivist, professor of medicine, and chief of pulmonary, critical care and sleep medicine at the University of California, San Diego
William Schaffner, MD, medical director of the National Foundation for Infectious Diseases, professor of preventive medicine in the department of health policy, and professor of medicine in the division of infectious diseases at Vanderbilt University Medical Center in Tennessee
Glen B. Chun, MD, assistant professor of medicine, pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, New York
Jorge M. Mercado, MD, clinical assistant professor of medicine and associate section chief of pulmonary, critical care and sleep medicine at NYU Langone Hospital-Brooklyn in Brooklyn, New York
Pulmonology Advisor: What are some of the risks related to influenza infection in people with respiratory diseases such as COPD, asthma, and emphysema?
Dr Malhotra: Influenza can sometimes lead to respiratory failure requiring mechanical ventilation, which can sometimes be fatal. People at risk for severe infections include the very young and very old but also people with compromised immune systems and those with lung disease including asthma and COPD. Acute respiratory distress syndrome [may develop and these patients] sometimes can get superinfections, which is when they get a bacterial infection on top of influenza infection.7
Dr Schaffner: Persons with chronic respiratory illnesses such as COPD, asthma, and emphysema are at substantially increased risk for serious complications of influenza. Estimates show that 31% of US adults aged 50 to 64 years and 47% of those aged ≥65 years have ≥1 chronic health condition that increases the risk for influenza-related complications such as pneumonia, hospitalization, progressive loss of lung function, and death.8 This includes more than 30 million adults with COPD and/or asthma. Thus, receiving annual flu vaccine is a fundamental way to help avoid these dire outcomes.
Dr Chun: Influenza has an annual global impact that affects patients’ morbidity and mortality, especially in patients with obstructive lung disease, including patients with emphysema, chronic bronchitis, and asthma. Obstructive lung disease is not deemed a risk factor for influenza; however, the severity of illness is significantly worse in these patients.
Patients with COPD have a much more significant morbidity impact when [they have] respiratory viral illnesses in general, and influenza has the greatest effect on these patients’ morbidity and mortality. Studies have shown that influenza can lead to significant increases in hospitalizations and mortality in patients with COPD, especially in the elderly population.3
Aside from the morbidity and mortality impact associated with influenza alone, patients with influenza are at increased risk for secondary bacterial infections such as pneumonia. Influenza can also be associated with moderate complications such as sinus and ear infections.2 Some other major serious complications associated with influenza are myocarditis, encephalitis, myositis, rhabdomyolysis, and multiorgan failure such as respiratory and renal failure.4
Dr Mercado: Influenza infections are associated with increased morbidity and mortality. The two most vulnerable populations are young people and people with chronic respiratory disorders such as asthma and COPD. Influenza in [people with] asthma and patients with COPD may result in acute declines in their lung function (forced expiratory volume in 1 second).
Most clinical illnesses associated with influenza infection are a viral syndrome with upper respiratory manifestations, but in these particular groups, the most feared complication is the development of a viral pneumonia and of secondary bacterial pneumonia (bacterial superinfection). The most common bacteria implicated are Streptococcus pneumoniae and Staphylococcus aureus.7 This complication tends to occur around 4 to 14 days after the infection, following a period of clinical improvement.
Pulmonology Advisor: What are the key strategies for influenza prevention in this population?
Dr Malhotra: The main keys to prevention are hygiene and vaccination. Hygiene includes washing hands frequently, avoiding sick contacts, staying home when one is sick, and covering the mouth and nose when sneezing, for example. Vaccination is also important — not just for the individual receiving the vaccine, but for others who might be exposed to the individual. People who do not get flu shots are putting other people including their family members at risk.
Dr Schaffner: The key aspect of influenza prevention in persons with chronic respiratory illness is to get vaccinated against influenza every year in the fall. The vaccine provides protection against several strains of the influenza virus, so it gives you a good chance of avoiding influenza infection completely. There are also secondary benefits. We all know that the flu vaccine is not perfect — some people who get the vaccine will still come down with a case of influenza. But it is important to emphasize that their illness is likely to be less severe because they were vaccinated, and they are less apt to get the complications of pneumonia and to require hospitalization.
Dr Chun: The most widespread recommendation for all patients with COPD is to obtain a flu vaccination annually. A Cochrane review has reported that patients with COPD who receive flu vaccines have a significant reduction in COPD exacerbations.9
Everyday preventive measures should be taken for protection against influenza, including avoiding close contact with sick people; [practicing] regular hand hygiene; avoiding touching hands to eyes, mouth, and nose to prevent further spread of the virus; and cleaning and disinfecting surfaces that may be contaminated with the virus regularly.
Dr Mercado: Given the susceptibility of this population to infections, and the associated increased morbidity and mortality, it is imperative to remind these patients to receive the influenza vaccine on an annual basis. It is important to note that even if the vaccine is not 100% specific to the particular influenza subtype, it can decrease the severity of the infection.
During influenza season, it is important to add to the clinical examination and questionnaire whether the patient has received the influenza vaccine, and to try to clarify any doubts, misgivings, or misinformation patients may have about the vaccine’s safety and efficacy.
Vaccination among healthcare workers is an essential part of the program to decrease incidence of infection.
Hand washing is an important technique in decreasing the chances of infection. Influenza viruses are transmitted mainly by small particle aerosol and droplets. Avoiding close contact with people who are sick and staying home when the patient is sick can be helpful in preventing further spread of the disease.10
In patients with chronic respiratory disorders, the use of antiviral drugs can decrease the severity of the infection and the chances of hospitalization.10
Pulmonology Advisor: What are additional recommendations that clinicians should offer to patients regarding this topic?
Dr Malhotra: Other vaccines in addition to influenza are important; some patients may benefit from pneumonia vaccines. Asthma control is important, so patients should consult with their doctors to optimize therapy. For COPD, preventive efforts are important, including smoking cessation. Vaping can also be injurious to the lung.
Dr Schaffner: In addition to getting an annual flu shot, practice frequent hand hygiene and try to avoid people who are coughing or sneezing. When you learn that influenza is spreading in your community, that is the time to avoid crowds — rent a movie rather than going out to a movie, for example. Call your healthcare provider right away if you do come down with influenza. They may prescribe an antiviral medicine that can shorten the illness and make it less severe.
Dr Chun: Clinicians have the ability to educate and inform patients about warning symptoms that may suggest the flu to allow patients to recognize and have early detection of the virus to seek treatment quickly. If flulike symptoms develop, it is incredibly important to seek medical attention as quickly as possible to start antiviral therapy, which works best when started within 48 hours of the onset of symptoms. Antiviral therapy can significantly decrease severity of illness and could prevent hospitalization and serious complications associated with the flu.
When experiencing flulike symptoms, it is important for patients to stay home for ≥24 hours after the fever has resolved to reduce further spread of the virus.
Pulmonology Advisor: What are remaining needs or other notable developments in this area?
Dr Malhotra: I think it is important to raise awareness that influenza can be fatal. Many people think that “having the flu” may just mean being sick for a few days, but in some cases, it can be much more serious. Also, antivaxxers have suggested toxicity of vaccines, which has been disproven and debunked. Some people think the flu shot can make you sick, which is also incorrect. We need to raise awareness about these issues.
Dr Schaffner: The vital educational message is that annual influenza vaccination should be part of routine chronic disease management for every patient with respiratory disease of any kind. It also is important for all family members of patients with respiratory disease to be vaccinated so that they will not spread the virus to that person.
Dr Chun: Given the severity of effect that influenza can have, especially on patients with COPD, improvement in early detection screening is paramount. The ability of the influenza virus to make minor and major genetic changes (the antigenic drift and shift) affect the immune system’s ability to adequately recognize and respond to the virus. This phenomenon associated with influenza leads to near impossibility of creating a perfect vaccine.
Detection of the virus can be extremely challenging to providers. The rapid influenza tests are helpful due to the ease and rapidity; however, the sensitivity has been reported as approximately 50% to 70%.11 In 2017, the US Food and Drug Administration required that rapid influenza diagnostic tests meet a minimum sensitivity of 80% for detection of influenza A and influenza B viruses compared to reverse transcriptase polymerase chain reaction (RT-PCR) testing.12
The rapid detection tests continue to evolve but are still far from perfect. PCR testing is more sensitive and specific than the rapid testing, however, PCR is not available at all clinical laboratories. Therefore, a continued evolution of the rapid testing that has both high sensitivity and specificity should be a priority, all while maintaining a rapid turnaround, given the urgency to start treatment within 48 hours of disease onset.
Dr Mercado: To decrease the possibility of lower-efficacy vaccines, this year the CDC is highlighting the use of vaccines that carry 3 and 4 subtypes of the virus (H1N1, H3N2, and B viruses).13 The new vaccines are recombinant and do not use egg or egg-related products, so they can be offered to patients with certain food allergies.
There are 4 antiviral drugs [approved by the US Food and Drug Administration] and recommended by the CDC this season: oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), zanamivir (trade name Relenza®), peramivir (trade name Rapivab®), and baloxavir marboxil (trade name Xofluza®).14 These drugs are more effective when used early, they decrease the duration of illness, and they are indicated in patients with chronic respiratory disorders.14
References
1. Centers for Disease Control and Prevention. Who Should and Who Should NOT Get a Flu Vaccine. https://www.cdc.gov/flu/prevent/whoshouldvax.htm. Updated October 11, 2019. Accessed October 14, 2019.
2. Centers for Disease Control and Prevention. People at High Risk for Flu Complications. https://www.cdc.gov/flu/highrisk/index.htm. October 11, 2019. Accessed October 14, 2019.
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. Kalil AC, Thomas PG. Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care. 2019;23(1):258.
5. 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 [published online July 22, 2019]. Respiration. doi:10.1159/000501410
6. Kurai D, Saraya T, Ishii H, Takizawa H. Virus-induced exacerbations in asthma and COPD. Front Microbiol. 2013;4:293.
7. Rynda-Apple A, Robinson KM, Alcorn JF. Influenza and bacterial superinfection: illuminating the immunologic mechanisms of disease. Infect Immun. 2015;83(10):3764-3770.
8. National Foundation for Infectious Diseases. The Dangers of Influenza (Flu) for Adults with Chronic Health Conditions Infographic. https://www.nfid.org/infectious-diseases/the-dangers-of-influenza-flu-for-adults-with-chronic-health-conditions-patient-infographic/. Accessed October 14, 2019.
9. Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018;6(6):CD002733.
10. Chow EJ, Doyle JD, Uyeki TM. Influenza virus-related critical illness: prevention, diagnosis, treatment. Crit Care. 2019;23(1):214.
11. Centers for Disease Control and Prevention. Overview of Influenza Testing Methods. https://www.cdc.gov/flu/professionals/diagnosis/overview-testing-methods.htm. Updated March 4, 2019. Accessed October 14, 2019.
12. Centers for Disease Control and Prevention. Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors. https://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm. Updated February 4, 2019. Accessed October 14, 2019.
13. Centers for Disease Control and Prevention. Frequently Asked influenza (Flu) Questions: 2019-2020 Season. https://www.cdc.gov/flu/season/faq-flu-season-2019-2020.htm. Updated October 8, 2019. Accessed October 14, 2019.
14. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Updated December 27, 2018. Accessed October 14, 2019.
October 28, 2019
Tori Rodriguez, MA, LPC, AHC
The influenza virus can trigger exacerbations in patients with asthma and 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.
As flu season approaches, the US Centers for Disease Control and Prevention (CDC) continues to recommend influenza vaccination for all patients aged ≥6 months, with rare exceptions such as those with severe allergy to an ingredient in the vaccine.1 Individuals with preexisting respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD) are among the groups identified as having a high risk for serious influenza-related complications.2
In a multicenter study (n=4198) published in January 2019 in CHEST, higher rates of crude mortality (9.7% vs 7.9%; P =.047) and critical illness (17.2% vs 12.1%; P <.001) were found among patients with COPD with vs without influenza infection, and vaccination was associated with a 38% reduction in influenza-related hospitalizations.3 Another recent study reported higher rates of severe illness, respiratory failure, and positive fungal cultures in patients with influenza and COPD.4
The influenza virus can also cause other types of infections including pneumonia, which has been diagnosed in 30% to 40% of hospitalized patients with influenza, especially in those with certain risk factors including chronic lung disease.4,5 In addition, the virus can trigger exacerbations in patients with asthma and COPD.2,6
Taken together, such findings underscore the critical importance of vaccination and other preventive efforts in patients with chronic respiratory illness. For an in-depth discussion on the topic, Pulmonology Advisor interviewed the following experts:
Atul Malhotra, MD, board-certified pulmonologist, intensivist, professor of medicine, and chief of pulmonary, critical care and sleep medicine at the University of California, San Diego
William Schaffner, MD, medical director of the National Foundation for Infectious Diseases, professor of preventive medicine in the department of health policy, and professor of medicine in the division of infectious diseases at Vanderbilt University Medical Center in Tennessee
Glen B. Chun, MD, assistant professor of medicine, pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, New York
Jorge M. Mercado, MD, clinical assistant professor of medicine and associate section chief of pulmonary, critical care and sleep medicine at NYU Langone Hospital-Brooklyn in Brooklyn, New York
Pulmonology Advisor: What are some of the risks related to influenza infection in people with respiratory diseases such as COPD, asthma, and emphysema?
Dr Malhotra: Influenza can sometimes lead to respiratory failure requiring mechanical ventilation, which can sometimes be fatal. People at risk for severe infections include the very young and very old but also people with compromised immune systems and those with lung disease including asthma and COPD. Acute respiratory distress syndrome [may develop and these patients] sometimes can get superinfections, which is when they get a bacterial infection on top of influenza infection.7
Dr Schaffner: Persons with chronic respiratory illnesses such as COPD, asthma, and emphysema are at substantially increased risk for serious complications of influenza. Estimates show that 31% of US adults aged 50 to 64 years and 47% of those aged ≥65 years have ≥1 chronic health condition that increases the risk for influenza-related complications such as pneumonia, hospitalization, progressive loss of lung function, and death.8 This includes more than 30 million adults with COPD and/or asthma. Thus, receiving annual flu vaccine is a fundamental way to help avoid these dire outcomes.
Dr Chun: Influenza has an annual global impact that affects patients’ morbidity and mortality, especially in patients with obstructive lung disease, including patients with emphysema, chronic bronchitis, and asthma. Obstructive lung disease is not deemed a risk factor for influenza; however, the severity of illness is significantly worse in these patients.
Patients with COPD have a much more significant morbidity impact when [they have] respiratory viral illnesses in general, and influenza has the greatest effect on these patients’ morbidity and mortality. Studies have shown that influenza can lead to significant increases in hospitalizations and mortality in patients with COPD, especially in the elderly population.3
Aside from the morbidity and mortality impact associated with influenza alone, patients with influenza are at increased risk for secondary bacterial infections such as pneumonia. Influenza can also be associated with moderate complications such as sinus and ear infections.2 Some other major serious complications associated with influenza are myocarditis, encephalitis, myositis, rhabdomyolysis, and multiorgan failure such as respiratory and renal failure.4
Dr Mercado: Influenza infections are associated with increased morbidity and mortality. The two most vulnerable populations are young people and people with chronic respiratory disorders such as asthma and COPD. Influenza in [people with] asthma and patients with COPD may result in acute declines in their lung function (forced expiratory volume in 1 second).
Most clinical illnesses associated with influenza infection are a viral syndrome with upper respiratory manifestations, but in these particular groups, the most feared complication is the development of a viral pneumonia and of secondary bacterial pneumonia (bacterial superinfection). The most common bacteria implicated are Streptococcus pneumoniae and Staphylococcus aureus.7 This complication tends to occur around 4 to 14 days after the infection, following a period of clinical improvement.
Pulmonology Advisor: What are the key strategies for influenza prevention in this population?
Dr Malhotra: The main keys to prevention are hygiene and vaccination. Hygiene includes washing hands frequently, avoiding sick contacts, staying home when one is sick, and covering the mouth and nose when sneezing, for example. Vaccination is also important — not just for the individual receiving the vaccine, but for others who might be exposed to the individual. People who do not get flu shots are putting other people including their family members at risk.
Dr Schaffner: The key aspect of influenza prevention in persons with chronic respiratory illness is to get vaccinated against influenza every year in the fall. The vaccine provides protection against several strains of the influenza virus, so it gives you a good chance of avoiding influenza infection completely. There are also secondary benefits. We all know that the flu vaccine is not perfect — some people who get the vaccine will still come down with a case of influenza. But it is important to emphasize that their illness is likely to be less severe because they were vaccinated, and they are less apt to get the complications of pneumonia and to require hospitalization.
Dr Chun: The most widespread recommendation for all patients with COPD is to obtain a flu vaccination annually. A Cochrane review has reported that patients with COPD who receive flu vaccines have a significant reduction in COPD exacerbations.9
Everyday preventive measures should be taken for protection against influenza, including avoiding close contact with sick people; [practicing] regular hand hygiene; avoiding touching hands to eyes, mouth, and nose to prevent further spread of the virus; and cleaning and disinfecting surfaces that may be contaminated with the virus regularly.
Dr Mercado: Given the susceptibility of this population to infections, and the associated increased morbidity and mortality, it is imperative to remind these patients to receive the influenza vaccine on an annual basis. It is important to note that even if the vaccine is not 100% specific to the particular influenza subtype, it can decrease the severity of the infection.
During influenza season, it is important to add to the clinical examination and questionnaire whether the patient has received the influenza vaccine, and to try to clarify any doubts, misgivings, or misinformation patients may have about the vaccine’s safety and efficacy.
Vaccination among healthcare workers is an essential part of the program to decrease incidence of infection.
Hand washing is an important technique in decreasing the chances of infection. Influenza viruses are transmitted mainly by small particle aerosol and droplets. Avoiding close contact with people who are sick and staying home when the patient is sick can be helpful in preventing further spread of the disease.10
In patients with chronic respiratory disorders, the use of antiviral drugs can decrease the severity of the infection and the chances of hospitalization.10
Pulmonology Advisor: What are additional recommendations that clinicians should offer to patients regarding this topic?
Dr Malhotra: Other vaccines in addition to influenza are important; some patients may benefit from pneumonia vaccines. Asthma control is important, so patients should consult with their doctors to optimize therapy. For COPD, preventive efforts are important, including smoking cessation. Vaping can also be injurious to the lung.
Dr Schaffner: In addition to getting an annual flu shot, practice frequent hand hygiene and try to avoid people who are coughing or sneezing. When you learn that influenza is spreading in your community, that is the time to avoid crowds — rent a movie rather than going out to a movie, for example. Call your healthcare provider right away if you do come down with influenza. They may prescribe an antiviral medicine that can shorten the illness and make it less severe.
Dr Chun: Clinicians have the ability to educate and inform patients about warning symptoms that may suggest the flu to allow patients to recognize and have early detection of the virus to seek treatment quickly. If flulike symptoms develop, it is incredibly important to seek medical attention as quickly as possible to start antiviral therapy, which works best when started within 48 hours of the onset of symptoms. Antiviral therapy can significantly decrease severity of illness and could prevent hospitalization and serious complications associated with the flu.
When experiencing flulike symptoms, it is important for patients to stay home for ≥24 hours after the fever has resolved to reduce further spread of the virus.
Pulmonology Advisor: What are remaining needs or other notable developments in this area?
Dr Malhotra: I think it is important to raise awareness that influenza can be fatal. Many people think that “having the flu” may just mean being sick for a few days, but in some cases, it can be much more serious. Also, antivaxxers have suggested toxicity of vaccines, which has been disproven and debunked. Some people think the flu shot can make you sick, which is also incorrect. We need to raise awareness about these issues.
Dr Schaffner: The vital educational message is that annual influenza vaccination should be part of routine chronic disease management for every patient with respiratory disease of any kind. It also is important for all family members of patients with respiratory disease to be vaccinated so that they will not spread the virus to that person.
Dr Chun: Given the severity of effect that influenza can have, especially on patients with COPD, improvement in early detection screening is paramount. The ability of the influenza virus to make minor and major genetic changes (the antigenic drift and shift) affect the immune system’s ability to adequately recognize and respond to the virus. This phenomenon associated with influenza leads to near impossibility of creating a perfect vaccine.
Detection of the virus can be extremely challenging to providers. The rapid influenza tests are helpful due to the ease and rapidity; however, the sensitivity has been reported as approximately 50% to 70%.11 In 2017, the US Food and Drug Administration required that rapid influenza diagnostic tests meet a minimum sensitivity of 80% for detection of influenza A and influenza B viruses compared to reverse transcriptase polymerase chain reaction (RT-PCR) testing.12
The rapid detection tests continue to evolve but are still far from perfect. PCR testing is more sensitive and specific than the rapid testing, however, PCR is not available at all clinical laboratories. Therefore, a continued evolution of the rapid testing that has both high sensitivity and specificity should be a priority, all while maintaining a rapid turnaround, given the urgency to start treatment within 48 hours of disease onset.
Dr Mercado: To decrease the possibility of lower-efficacy vaccines, this year the CDC is highlighting the use of vaccines that carry 3 and 4 subtypes of the virus (H1N1, H3N2, and B viruses).13 The new vaccines are recombinant and do not use egg or egg-related products, so they can be offered to patients with certain food allergies.
There are 4 antiviral drugs [approved by the US Food and Drug Administration] and recommended by the CDC this season: oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), zanamivir (trade name Relenza®), peramivir (trade name Rapivab®), and baloxavir marboxil (trade name Xofluza®).14 These drugs are more effective when used early, they decrease the duration of illness, and they are indicated in patients with chronic respiratory disorders.14
References
1. Centers for Disease Control and Prevention. Who Should and Who Should NOT Get a Flu Vaccine. https://www.cdc.gov/flu/prevent/whoshouldvax.htm. Updated October 11, 2019. Accessed October 14, 2019.
2. Centers for Disease Control and Prevention. People at High Risk for Flu Complications. https://www.cdc.gov/flu/highrisk/index.htm. October 11, 2019. Accessed October 14, 2019.
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. Kalil AC, Thomas PG. Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care. 2019;23(1):258.
5. 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 [published online July 22, 2019]. Respiration. doi:10.1159/000501410
6. Kurai D, Saraya T, Ishii H, Takizawa H. Virus-induced exacerbations in asthma and COPD. Front Microbiol. 2013;4:293.
7. Rynda-Apple A, Robinson KM, Alcorn JF. Influenza and bacterial superinfection: illuminating the immunologic mechanisms of disease. Infect Immun. 2015;83(10):3764-3770.
8. National Foundation for Infectious Diseases. The Dangers of Influenza (Flu) for Adults with Chronic Health Conditions Infographic. https://www.nfid.org/infectious-diseases/the-dangers-of-influenza-flu-for-adults-with-chronic-health-conditions-patient-infographic/. Accessed October 14, 2019.
9. Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018;6(6):CD002733.
10. Chow EJ, Doyle JD, Uyeki TM. Influenza virus-related critical illness: prevention, diagnosis, treatment. Crit Care. 2019;23(1):214.
11. Centers for Disease Control and Prevention. Overview of Influenza Testing Methods. https://www.cdc.gov/flu/professionals/diagnosis/overview-testing-methods.htm. Updated March 4, 2019. Accessed October 14, 2019.
12. Centers for Disease Control and Prevention. Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors. https://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm. Updated February 4, 2019. Accessed October 14, 2019.
13. Centers for Disease Control and Prevention. Frequently Asked influenza (Flu) Questions: 2019-2020 Season. https://www.cdc.gov/flu/season/faq-flu-season-2019-2020.htm. Updated October 8, 2019. Accessed October 14, 2019.
14. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Updated December 27, 2018. Accessed October 14, 2019.