High-Dose Influenza Vaccine Lowers Hospitalization Risk in Older Adults With Chronic Lung Disease

Older adults with chronic lung disease (CLD) who received a high-dose influenza vaccine had a lower risk of hospitalization for flu or pneumonia than those who received a standard-dose vaccine, according to pooled results from 2 large randomized controlled trials presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain. The analysis adds long-awaited randomized evidence in a population long considered especially vulnerable to influenza-related complications.¹

Study Details

The new analysis combined data from 2 pragmatic, registry-based randomized trials: DANFLU-2 (NCT05517174), conducted in Denmark across the 2022-2023, 2023-2024, and 2024-2025 flu seasons; and GALFLU (NCT06141655), conducted in Galicia, Spain, across the 2023-2024 and 2024-2025 seasons. Both trials randomly assigned adults 65 years and older 1:1 to a high-dose quadrivalent inactivated influenza vaccine, containing 4 times the antigen of the standard formulation, or a standard-dose quadrivalent vaccine. Investigators followed participants from 14 days post-vaccination through the following May, capturing hospitalizations via nationwide health registries.^1-3

Across the 2 trials, 466,320 participants were randomly assigned, of whom 31,976 (approximately 7%) had a qualifying CLD diagnosis, including asthma, bronchiectasis, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, emphysema, interstitial lung disease, prior lung transplantation, respiratory tuberculosis, or sarcoidosis.¹

Key Findings

Among participants with CLD, the high-dose vaccine reduced hospitalization for influenza or pneumonia by approximately 8.8% relative to the standard-dose vaccine. The high-dose formulation was also associated with reductions in hospitalizations for cardiorespiratory disease and for any cause compared with standard dosing. The findings build on earlier data from the DANFLU trial program showing that patients with CLD face substantially higher baseline hospitalization rates than those without lung disease, underscoring the stakes of optimizing vaccine choice in this group.^1,4

The results are consistent with the primary findings from the individual DANFLU-2 and GALFLU trials, both published earlier in the New England Journal of Medicine, which found that high-dose vaccination reduced hospitalization for influenza or pneumonia in the overall study populations of adults 65 years and older.^2,3

Clinical Implications

The study authors noted that although high-dose influenza vaccines are formulated to elicit a stronger immune response in older adults, randomized evidence specifically addressing whether that translates into better protection against serious illness in patients with CLD had been limited before this analysis.¹

“For older [individuals] with CLD and their families, these findings provide reassurance that high-dose flu vaccination can offer better protection against serious illness requiring hospital treatment than a standard-dose vaccine,” Lisa Steen Duus, MD, research presenter from Gentofte Hospital, Copenhagen, Denmark, said.¹

She added that the magnitude of benefit, while modest at the individual level, could translate into meaningful public health impact given the burden hospitalization places on patients, families, and health systems. Duus said the results support factoring high-dose vaccination into immunization recommendations for older adults, including those with CLD.¹

Expert Perspective

Thomas Wilkinson, MD, chair of the ERS Group on Respiratory Infections and Immunology and a faculty member at the University of Southampton in the United Kingdom, who was not involved in the research, said the findings reinforce existing guidance.^1,5

“Older [individuals] with lung disease have a greater risk of severe illness, hospitalization, and death from flu, which is why the European Respiratory Society recommends annual flu vaccination for this group,” Wilkinson said. He added that the pooled analysis of 2 large, well-conducted trials suggests the high-dose vaccine “could be even more beneficial,“ specifically in those with CLD than in the general older adult population.^1,5

For pharmacists, who are often on the front line of recommending and administering seasonal influenza vaccines, the data offer additional support for prioritizing high-dose formulations when counseling older patients with asthma, COPD, or other chronic respiratory conditions during fall immunization campaigns. As flu season approaches in the Northern Hemisphere, the findings may inform pharmacy-based immunization protocols and patient counseling conversations, particularly for adults who carry both age-related and disease-related risk factors for severe influenza outcomes.

REFERENCES

1. High-dose flu vaccine beneficial for older people with lung disease. News release. EurekAlert! September 8, 2026. Accessed September 10, 2026. https://www.eurekalert.org/news-releases/1142197

2. Loiacona MM, Johansen ND, Modin D, et al. High-dose influenza vaccine effectiveness against hospitalization in older adults. N Engl J Med. 2025;393:2291-2302. doi:10.1056/NEJMoa2509907

3. Pardo-Seco J, Rodríguez-Tenreiro-Sánchez C, Mallah N, et al. High-dose influenza vaccine to reduce hospitalizations. N Engl J Med. 2025;393:2303-2312. doi:10.1056/NEJMoa2509834

4. Steen Duus L, Johansen ND, Modin D, et al. Effects of high-dose versus standard-dose influenza vaccine among patients with chronic lung disease: a prespecified analysis of the DANFLU-1 trial. Respir Med. 2025;63(6):1309-1315. doi: 10.1016/j.resinv.2025.10.016

5. High-dose flu vaccine protects older adults with lung disease. News-Medical.net. September 8, 2026. Accessed September 10, 2026. https://www.news-medical.net/news/20260908/High-dose-flu-vaccine-protects-older-adults-with-lung-disease.aspx