Nasal Flu Vaccine for COPD

Overseen by Michael B Drummond, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of North Carolina, Chapel Hill

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study will determine the functional status of the nasal immune environment with LAIV exposure in COPD persons with frequent exacerbations (defined as individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months) and COPD persons without frequent exacerbations to determine acute exacerbation of COPD (AECOPD)-associated dysfunction in a) cytokines and immune effector cells of the nasal mucosa and b) viral replication. The investigators hypothesize that: 1) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate altered mucosal immune responses to LAIV exposure, and 2) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate increased markers of influenza viral replication after LAIV exposure.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop using certain medications. You cannot participate if you use regular suppressive antibiotics, daily oral prednisone, intranasal corticosteroids within 30 days prior to screening, or chronic immunosuppression within 30 days prior to screening. Additionally, you cannot use blood thinners beyond full dose aspirin.

What data supports the idea that Nasal Flu Vaccine for COPD is an effective treatment?

The available research shows that influenza vaccination can help prevent influenza in people with COPD. One study found that the current-season flu vaccine reduced the chance of getting the flu by 40% in COPD patients. Another study highlighted that flu vaccines are recommended for people with COPD to prevent hospitalizations. While the data is mostly about flu vaccines in general, it suggests that getting vaccinated can help reduce flu-related problems in people with COPD. ^{1 2 3 4 5}

What safety data exists for the nasal flu vaccine in COPD patients?

The nasal flu vaccine, known as FluMist or LAIV, has been studied for safety in various populations. It is generally well tolerated in healthy individuals aged 5-49, with common side effects including abdominal pain, chills, cough, diarrhea, headache, and sore throat. In patients with chronic lung diseases like COPD, studies have assessed adverse reactions and their impact on lung function and respiratory symptoms. However, specific safety data for COPD patients is limited, and further research is needed to fully understand the safety profile in this group. ^{6 7 8 9 10}

Is the nasal flu vaccine a promising treatment for COPD?

The nasal flu vaccine, known as LAIV or FluMist, is a promising treatment for preventing the flu. It is easy to use because it is given through the nose instead of a shot. This makes it less painful and more convenient. While most studies focus on other types of flu vaccines for COPD patients, the nasal flu vaccine has shown to be effective in preventing the flu in healthy people, which suggests it could be beneficial for those with COPD as well. ^{6 10 11 12 13}

Research Team

Michael B Drummond, MD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for adults over 40 with COPD, who've had two or more flare-ups in the past year requiring treatment. They must have stable blood pressure and oxygen levels, no recent tobacco use, and not be on certain medications like nasal steroids or immunosuppressants. People with asthma, recent respiratory infections, or those who can't avoid contact with immunocompromised individuals after vaccination are excluded.

Inclusion Criteria

If you are in the healthy control group, your blood pressure should be between 90/55 and 160/90.

I do not have any nasal symptoms according to a questionnaire.

Individual in the healthy control group must complete informed consent

Exclusion Criteria

I was hospitalized due to COVID-19.

You have had severe allergic reactions to certain things in the past.

I have not used any chronic immunosuppression medication in the last 30 days.

Treatment Details

Interventions

• LAIV (Virus Therapy)

Trial Overview The study tests how a live attenuated influenza vaccine (LAIV) affects the nasal immune response in people with COPD. It compares those who frequently have exacerbations to those who don't by measuring cytokines, immune cells in the nose, and viral replication markers following LAIV exposure.

Participant Groups

Group I: Healthy Control Experimental Treatment 1 Intervention

Individuals with spirometry-confirmed normal lung function and no asthma history

Group II: COPD Infrequent Exacerbators Experimental Treatment 1 Intervention

Individuals with less than two episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months

Group III: COPD Frequent Exacerbators Experimental Treatment 1 Intervention

Individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months

LAIV is already approved in Canada for the following indications:

Approved in Canada as FluMist for:

• Prevention of influenza A and B in individuals 2 through 59 years of age

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Dr. Peggy P. McNaull

University of North Carolina, Chapel Hill

Chief Medical Officer

MD from Louisiana State University School of Medicine

Dr. Lynne Fiscus

University of North Carolina, Chapel Hill

Chief Executive Officer since 2020

MD from Georgetown University, MPH from UNC

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

In a study of older adults with chronic obstructive pulmonary disease (COPD) in Ontario, Canada, the seasonal influenza vaccine was associated with a 22% reduction in hospitalizations due to laboratory-confirmed influenza, indicating its effectiveness in this vulnerable population.

When accounting for potential misclassification of vaccination status, the effectiveness of the vaccine increased to 43%, highlighting the importance of vaccination while also suggesting a need for improved vaccine formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza Vaccine Effectiveness in Preventing Hospitalizations in Older Patients With Chronic Obstructive Pulmonary Disease. Gershon, AS., Chung, H., Porter, J., et al.[2021]

Inactivated influenza vaccines significantly reduced the number of exacerbations in people with COPD, particularly late exacerbations occurring three or more weeks after vaccination, based on data from 11 RCTs involving 6750 participants, with 2469 specifically having COPD.

While there were more mild and transient local adverse reactions reported in vaccinated individuals, there was no evidence of increased early exacerbations or mortality associated with the vaccination, indicating that the benefits of vaccination may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccine for chronic obstructive pulmonary disease (COPD). Kopsaftis, Z., Wood-Baker, R., Poole, P.[2022]

Influenza vaccination significantly reduces the incidence of influenza-related acute respiratory illness (ARI) in patients with COPD, showing a vaccine effectiveness of 76% overall and up to 85% in patients with severe COPD.

While the vaccine is effective against influenza-related ARI, it does not prevent other types of ARI, indicating that vaccination is crucial for COPD patients to specifically guard against influenza complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Wongsurakiat, P., Maranetra, KN., Wasi, C., et al.[2019]

Influenza vaccination in COPD patients showed a moderate effectiveness of 40% in preventing laboratory-confirmed influenza during the current season, based on a study of 1761 patients over multiple seasons in Spain.

Increasing influenza vaccination coverage among COPD patients could prevent approximately 13.7% of influenza cases, highlighting the importance of vaccination in reducing exacerbations and improving health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease and influenza vaccination effect in preventing outpatient and inpatient influenza cases. Martínez-Baz, I., Casado, I., Navascués, A., et al.[2022]

In a study of 153 patients with chronic obstructive pulmonary disease (COPD), combined vaccination with the pneumococcal vaccine (PCV13) and the influenza vaccine significantly reduced clinical impairment and stabilized respiratory function compared to those vaccinated with only the pneumococcal vaccine.

The dual vaccination approach not only lowered the risk of adverse events and hospitalizations due to exacerbations but also resulted in substantial cost savings for the healthcare system, averaging 80-83% per year per patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of the effectiveness of joint or sequential vaccination with pneumococcal and influenza vaccines in patients with chronic obstructive pulmonary disease]. Ignatova, GL., Antonov, VN., Blinova, EV.[2020]

FluMist is an effective intranasal vaccine for preventing influenza A and B, showing good tolerance in healthy individuals aged 5-49 years based on clinical trials.

The vaccine offers a painless alternative to traditional injections, although barriers such as patient eligibility, cost, and insurance coverage may affect its acceptance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination for the pediatric patient: a focus on the new intranasal, cold-adapted, live attenuated vaccine. Ellis, JM., Reilly, JC., Salazar, JC.[2021]

In a study involving 198 patients with cystic fibrosis who received the live-attenuated intranasal influenza vaccine (LAIV), there was a higher risk of reporting serious adverse events (SAEs) and solicited symptoms within the first 6 days post-vaccination, but most were not causally related to the vaccine and were short-lived.

Importantly, the study found no increase in the frequency of antibiotic prescriptions for respiratory conditions following LAIV administration, indicating that the vaccine does not lead to more severe respiratory issues in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events following live-attenuated intranasal influenza vaccination of children with cystic fibrosis: Results from two influenza seasons. Boikos, C., Joseph, L., Scheifele, D., et al.[2018]

In a study of 125 patients with COPD, influenza vaccination resulted in a 27% rate of local adverse reactions, significantly higher than the 6% in the placebo group, but systemic reactions were similar between both groups (76% vs. 81%).

The vaccination did not lead to significant changes in lung function, dyspnoeic symptoms, or exercise capacity, nor did it increase the incidence of acute respiratory illness, indicating that it is safe for patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects associated with influenza vaccination in patients with COPD: a randomized controlled study. Wongsurakiat, P., Maranetra, KN., Gulprasutdilog, P., et al.[2006]

FluMist, a live-attenuated influenza vaccine, maintains genetic and phenotypic stability during its manufacturing process, ensuring that critical mutations for cold adaptation, temperature sensitivity, and attenuation are preserved.

Full genome sequencing of multiple influenza strains showed that all vaccine intermediates retained their essential characteristics, confirming the vaccine's safety and efficacy in providing protection against influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process. Buonagurio, DA., Bechert, TM., Yang, CF., et al.[2008]

The study found that the bivalent live attenuated influenza A virus vaccine (CAV) was safe for use in individuals with COPD when administered alongside the trivalent inactivated influenza virus vaccine (TVV).

Participants showed a significant increase in mucosal immune responses, specifically anti-HA immunoglobulin A (IgA) antibodies, after receiving both CAV and TVV, suggesting that the combination may enhance immune protection compared to TVV alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza virus vaccination of patients with chronic lung disease. Gorse, GJ., Otto, EE., Daughaday, CC., et al.[2019]

Influenza vaccination is crucial for individuals with serious medical conditions like COPD, as it significantly reduces the risk of illness, hospitalization, and death associated with influenza infections.

Despite limited specific studies on COPD patients, there is sufficient evidence to recommend annual inactivated influenza vaccinations for this group to improve their quality of life and decrease healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients. Hovden, AO., Cox, RJ., Haaheim, LR.[2021]

In a study of 88 patients with chronic obstructive pulmonary disease (COPD), a single dose of the trivalent seasonal influenza vaccine (TIV) resulted in 100% seropositive rates for all influenza strains tested, indicating strong immune response.

The study found high seroprotection rates (over 93%) and significant increases in antibody levels after vaccination, supporting the recommendation for influenza vaccination in COPD patients to help protect them from influenza and its complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of trivalent seasonal influenza vaccine in patients with chronic obstructive pulmonary disease. Li, Y., Ma, Y., An, Z., et al.[2023]

Influenza vaccination significantly reduces exacerbations in COPD patients, particularly those with severe airflow limitation (FEV1 < 50%), and shows a trend towards reducing hospitalizations.

The study analyzed data from 2831 COPD patients and found no significant impact of vaccination on all-cause mortality, highlighting the importance of vaccination in preventing complications rather than affecting overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of influenza vaccination on clinical outcomes of chronic obstructive pulmonary disease: A systematic review and meta-analysis. Bao, W., Li, Y., Wang, T., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Influenza Vaccine Effectiveness in Preventing Hospitalizations in Older Patients With Chronic Obstructive Pulmonary Disease. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Influenza vaccine for chronic obstructive pulmonary disease (COPD). [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease and influenza vaccination effect in preventing outpatient and inpatient influenza cases. [2022]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Analysis of the effectiveness of joint or sequential vaccination with pneumococcal and influenza vaccines in patients with chronic obstructive pulmonary disease]. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Influenza vaccination for the pediatric patient: a focus on the new intranasal, cold-adapted, live attenuated vaccine. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events following live-attenuated intranasal influenza vaccination of children with cystic fibrosis: Results from two influenza seasons. [2018]

8. Australia pubmed.ncbi.nlm.nih.gov

Adverse effects associated with influenza vaccination in patients with COPD: a randomized controlled study. [2006]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process. [2008]

10. United States pubmed.ncbi.nlm.nih.gov

Influenza virus vaccination of patients with chronic lung disease. [2019]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity of trivalent seasonal influenza vaccine in patients with chronic obstructive pulmonary disease. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Effects of influenza vaccination on clinical outcomes of chronic obstructive pulmonary disease: A systematic review and meta-analysis. [2021]