Statistically significant values are marked with an asterisk (*)

From 1999 to 2022, there were 212,321 deaths due to influenza and pneumonia among patients diagnosed with lung cancer in the United States (Supplemental Table S1). Overall age-adjusted mortality rates (AAMR) decreased during this period from 7.5 (95% Confidence Interval (CI): 7.3–7.6) in 1999 to 4.1 (95% CI: 4.0-4.1) in 2022, with an average annual percentage change (AAPC) of −2.5* (95% CI: −2.8 to −2.2) (Supplemental Table S1).

APC by time period was:

1999–2006: APC = −1.9* (95% CI: −2.7 to )

2006–2009: APC = −10.7* (95% CI: −12.1 to −7.1)

2009–2019: APC = −2.1* (95% CI −3.8 to −1.2)

2019–2022: APC = 3.4 (95% CI −0.2-8.1)

The lowest AAMR was observed in 2019 at 3.69, followed by an increase to 4.1 in 2020. Trends are shown in Fig. 1; full data are provided in Supplemental Table S1.

From 1999 to 2022, influenza and pneumonia caused 128,709 deaths (60.6%) in male lung cancer patients and 83,612 deaths (39.4%) in female patients in the United States (Supplemental Table S1). During this period, the AAMR in males decreased from 11.6 (95% CI: 11.3–11.8) in 1999 to 5.1 (95% CI: 5.0-5.3) in 2022, with an AAPC of −3.3* (95% CI: −3.7 to −3.1) (Supplemental Table S1).

The APC for males varied across time periods:

1999-2006: APC = -2.8%* (95% CI: -3.8 to -1.6)

2006-2009: APC = -11.7%* (95% CI -13.2 to -4.8)

2009-2018: APC = -2.7* (95% CI -8.2 to -1.8)

2018-2022: APC = 1.1 (95% CI -1.5 to 5.7)

In female lung cancer patients, the AAMR from influenza and pneumonia also declined over the study period, from 4.6 (95% CI 4.5 to 4.8) in 1999 to 3.3 (95% CI 3.2 to 3.4) in 2022. The AAPC was − 1.5* (95% CI −1.7 to −1.2) (Supplemental Table S1).

The APC by time period for females was:

1999-2006: APC = -0.5 (95% CI -1.2 to 0.7)

2006-2009: APC = -9.6* (95% CI -11.0 to -6.5)

2009-2019: APC = -1.5* (95% CI -2.4 to -0.7)

2019-2022: APC = 5.2* (95% CI 2.0 to 10.0)

All the above changes are visualized in Fig. 1, and full APC data for both sexes and all periods is available in Supplemental Table S1.

Age-Adjusted Pneumonia and Influenza Mortality Rates in Lung Cancer Patients 1999–2022 Overall and Stratified by Sex

Black or African American individuals had the highest AAMR throughout the study period, and the most significant reduction in AAMR, from 9.1 (95% CI: 8.6–9.6) in 1999 to 4.9 (95% CI: 4.6–5.2) in 2022. The overall AAPC was − 2.6* (95% CI: −2.8 to −2.3) (Supplemental Table S2).

APC by time period for Black/African American patients:

1999-2006: APC = -2.4* (95% CI: -3.3 to -0.8)

2006-2009: APC = -8.7* (95% CI: -10.3 to -5.4)

2009-2018: APC = -3.0* (95% CI: -4.0 to -1.6)

2018-2022: APC = 3.0* (95% CI: 0.6-7.6)

Hispanic individuals consistently had the lowest AAMR among racial and ethnic groups, decreasing from 4.3 (95% CI: 3.8–4.8) in 1999 to 2.5 (95% CI: 2.1–2.6) in 2022. The AAPC was − 2.5* (95% CI:−3.0 to−2.0) (Supplemental Table S2).

APC by time period for Hispanic patients:

1999-2015: APC = -4.6* (95% CI: -5.6 to -3.9)

2015-2022: APC = 2.5* (95% CI: 0.4-6.3)

Among Asian or Pacific Islander individuals, AAMR decreased from 6.6 (95% CI: 5.7–7.5) in 1999 to 3.5 (95% CI: 3.2–3.8) in 2022. The AAPC was − 3.0* (95% CI: −3.6 to −2.5) (Supplemental Table S2).

APC by time period for Asian or Pacific Islander patients:

1999-2013: APC = -4.4* (95% CI: -6.4 to -3.5)

2013-2022: APC = -0.8 (95% CI: -2.3-3.4)

The AAMR for American Indian or Alaskan Native populations declined from 7.3 (95% CI: 5.2–9.9) in 1999 to 4.1 (95% CI: 3.1–5.4) in 2022. The AAPC was − 3.2* (95% CI: −4.4 to −2.0) (Supplemental Table S2).

Among White patients, the AAMR fell from 7.5 (95% CI: 7.3–7.7) in 1999 to 4.3 (95% CI: 4.2–4.4) in 2022. The AAPC was − 2.3* (95% CI: −2.6 to −2.0) (Supplemental Table S2).

APC by time period for White patients:

1999-2006: APC = -1.5* (95% CI: -2.4 to -0.2)

2006-2009: APC = -11.1* (95% CI: -12.7 to -7.1)

2009-2019: APC = -1.8* (95% CI: -4.2 to -0.9)

2019-2022: APC = 3.7 (95% CI: -0.2-8.7)

See Fig. 2 and Supplemental Table S2 for detailed trends for all racial and ethnic groups.

Age-Adjusted Pneumonia and Influenza Mortality Rates in Lung Cancer Patients 1999–2022 Stratified by Race and Ethnicity.

Age groups were defined as 35–44, 45–54, 55–64, 65–74, 75–84, and 85 + years of age. The population aged 75–84 years had the highest overall crude mortality rate, which decreased from 28.3 (95% CI: 27.3–29.2) in 1999 to 15.2 (95% CI: 14.7–15.8) in 2022. The AAPC was − 2.5* (95% CI: −2.7 to −2.1) (Supplemental Table S3).

APC by time period for patients aged 75–84:

1999-2006: APC = -1.1 (95% CI: -2.1-0.3)

2006-2009: APC = -11.0* (95% CI: -12.6 to -7.3)

2009-2018: APC = -2.5* (95% CI: -4.1 to -1.6)

2018-2022: APC = 2.1 (95% CI: -0.3-6.7)

Individuals aged 35–44 years had the lowest overall crude mortality rate, which declined from 0.3 (95% CI: 0.2–0.3) in 1999 to 0.2 (95% CI: 0.2–0.2) in 2022. The AAPC was − 1.6* (95% CI: −3.3 to −0.8) (Supplemental Table S3).

APC by time period for patients aged 35–44:

1999-2020: APC = -3.5* (95% CI: -6.4 to -2.5)

2020-2020: APC = 19.9 (95% CI: -3.0-34.2)

The age cohort 45–54 also had low crude mortality rates of 1.7 (95% CI: 1.6–1.8) in 1999 that further decreased to 0.9 (95% CI: 0.8-1.0) in 2022 (Supplemental Table S3). The AAPC in this group during the study time period was − 2.7* (95% CI: −3.2 to −2.3) (Fig. 3).

The crude mortality rates in the population aged 55–64 declined from 7.3 (95% CI: 7.0-7.7) in 1999 to 4.2 (95% CI: 4.0-4.4) in 2022, with an AAPC of −2.3* (95% CI: −2.5 to −2.0) (Supplemental Table S3).

APC by time period for patients aged 55–64:

1999-2006: APC = -3.6* (95% CI: -4.4 to -2.1)

2006-2009: APC = -10.8* (95% CI: -12.4 to -7.1)

2009-2022: APC = 0.5* (95% CI: 0.1-1.1)

For individuals aged 65–74, crude mortality rates fell from 18.6 (95% CI: 18.0-19.2) in 1999 to 9.7 (95% CI: 9.3–10.0) in 2022, with an AAPC of * (95% CI: −3.3 to −2.5) (Fig. 3, Supplemental Table S3).

APC by time period for patients aged 65–74:

1999-2006: APC = -1.9 (95% CI -3.3 to 0.0)

2006-2009: APC = -12.0* (95% CI -14.0 to -3.4)

2009-2018: APC = -2.8* (95% CI -7.6 to -1.2)

2018-2022: APC = 2.6 (95% CI -0.7 to 9.1)

Lastly, for individuals aged 85 and older, the crude mortality rates declined from 26.0 (95% CI: 24.4–27.5) in 1999 to 15.2 (95% CI: 14.2–16.1) in 2022. The AAPC was − 2.3* (95% CI: −2.7 to −1.9) (Fig. 3, Supplemental Table S3).

APC by time period for patients aged 85+:

1999-2006: APC = -1.4 (95% CI: -2.8-0.5)

2006-2011: APC = -7.7* (95% CI: -11.1 to -2.4)

2011-2019: APC = -1.9* (95% CI: -7.0 to -0.6)

2019-2022: APC = 4.1 (95% CI: -0.2-9.5)

These trends by age group are presented in Fig. 3 and detailed in Supplemental Table S3.

Crude Pneumonia and Influenza Mortality Rates in Lung Cancer Patients 1999–2022 Stratified by Age.

When comparing populated regions, AAMRs were consistently higher in rural areas compared to small, medium, and large metropolitan regions throughout the study period. In rural zones, AAMR decreased from 8.6 (95% CI: 8.3-9.0) in 1999 to 5.0 (95% CI: 4.8–5.2) in 2020, with an AAPC of −2.8* (95% CI −3.1 to −2.4) (Supplemental Table S4).

APC by time period for rural patients:

1999-2006: APC = -1.0 (95% CI: -2.1-0.8)

2006-2009: APC = -12.1* (95% CI: -14.2 to -7.3)

2009-2020: APC = -1.3* (95% CI: -2.0 to -0.1)

In urban zones, AAMR decreased from 7.2 (95% CI: 7.0-7.3) in 1999 to 3.8 (95% CI: 3.7–3.9) in 2020, with an AAPC of −3.3* (95% CI: −3.5 to −3.0) (Supplemental Table S4).

APC by time period for urban patients:

1999-2006: APC = -2.0* (95% CI: -2.9 to -0.4)

2006-2009: APC = -10.6* (95% CI: -12.3 to -6.8)

2009-2020: APC = -2.0* (95% CI: -2.6 to -1.2)

Refer to Fig. 4 and Supplemental Table S4 for additional details.

Age-Adjusted Pneumonia and Influenza Mortality Rates in Lung Cancer Patients 1999–2020 Stratified by Rural versus Urban Living.

The state with the largest change in AAMR was Rhode Island, with an AAMR of −10.39 from 1999 to 2019 and − 11.41 from 1999 to 2022 (Supplemental Table S5). Over the entire time period of 1999–2022, no states had a positive change in AAMR, suggesting that mortality from pneumonia and influenza in lung cancer patients is improving nationally with time. The state with the smallest change in AAMR was Indiana with − 1.21 from the years 1999–2022 (Supplemental Table S5). During the years of the COVID-19 pandemic (2019–2022), Maine had the largest change in AAMR at −2.42, North Dakota had the smallest change in AAMR at a value of 0, and Mississippi had the largest positive change in AAMR at 1.95 (Fig. 5) (Supplemental Table S5). Of note, the CDC WONDER database did not have enough reliable data to provide AAMR for Alaska or Wyoming.

Age-Adjusted Pneumonia and Influenza Mortality Rates in Lung Cancer Patients 2019–2020 Stratified by State of Residence

All census regions had a decrease in AAMR over time, particularly in the West, which saw a decrease in AAMR from 7.5 (95% CI: 7.1–7.8) in 1999 to 3.3 (95% CI: 3.2–3.4) in 2022, with an AAPC of −3.3* (95% CI: −3.7 to −3.0) (Supplemental Table S6).

APC by time period for Western region patients:

1999-2006: APC = -2.5* (95% CI: -3.5 to -1.1)

2006-2009: APC = -11.6* (95% CI: -13.3 to -7.6)

2009-2019: APC = -3.1* (95% CI: -4.8 to -2.1)

2019-2022: APC = 2.7 (95% CI: -0.9-7.7)

The Northeast APCs by time period are as follows:

1999-2006: APC = -2.8* (95% CI: -3.1 to -2.4)

2006-2009: APC = -9.6* (95% CI: -11.7 to -4.9)

2009-2022: APC = -1.6* (95% CI: -2.3 to -0.1)

In the South, APCs by time period were:

1999-2006: APC = -2.0* (95% CI: -2.9 to -0.7)

2006-2009: APC = -10.7* (95% CI: -12.2 to -6.9)

2009-2019: APC = -1.8* (95% CI: -3.9 to -0.8)

2019-2022: APC = 2.4 (95% CI: 0.0-7.1)

Midwest APCs by time period:

1999-2006: APC = -0.8 (95% CI: -2.1-1.1)

2006-2009: APC = -11.4* (95% CI: -13.2 to -3.2)

2009-2019: APC = -1.7* (95% CI: -7.9 to -0.8)

2019-2022: APC = 4.4 (95% CI: -0.4-10.7)

Census region-based differences are illustrated in Fig. 6 and further detailed in Supplemental Table S6.

Age-Adjusted Pneumonia and Influenza Mortality Rates in Lung Cancer Patients 1999–2022 Stratified by United States Census Region.