Lower respiratory tract infection hospitalizations among American Indian/Alaska Native adults, Indian Health Service and Alaska Region, 1998–2014

Open AccessPublished:August 18, 2021DOI:https://doi.org/10.1016/j.ijid.2021.08.033

      Highlights

      • Lower respiratory tract infection (LRTI) rates increased 26% among Alaska American Indian/Alaska Native adults, compared to a 38% decrease in non-Alaska American Indian/Alaska Native adults.
      • LRTI rates were higher in Alaska compared to non-Alaska.
      • The most common diagnosis associated with LRTI was pneumonia, followed by essential hypertension.
      • The median length of hospital stay was longer in Alaska compared to non-Alaska sites.
      • A lack of piped water and household crowding likely contributed to the high rates of LRTI.

      Abstract

      Objectives: This study describes the changes in lower respiratory tract infection (LRTI) rates from 1998 to 2014 among hospitalized American Indian/Alaska Native (AI/AN) adults residing in Alaska and other Indian Health Service (IHS) regions.
      Methods: Age-adjusted hospital discharge rates and rate ratios were calculated from the IHS Direct and Contract Health Services Inpatient Dataset, IHS National Patient Information Reporting System for AI/AN adults ≥18 years, hospitalized at an IHS-operated, tribally operated, or contract hospital with an LRTI-associated diagnosis during 1998–2014.
      Results: Overall, there were 13 733 LRTI-associated hospitalizations in Alaska (1998–2014), with an age-adjusted rate of 13.7/1000 adults. Among non-Alaska (non-AK) AI/AN, there were a total of 79 170 hospitalizations, with a rate of 8.6/1000 adults. In the pre-PCV7 and pre-PCV13 periods, LRTI rates were higher in Alaska (AK) AI/AN (12.4 and 14.1, respectively) when compared to non-AK AI/AN (10.1 and 9.1, respectively) (P < 0.0001). In the post-PCV7 and post-PCV13 periods, LRTI rates were also higher in AK (13.5 and 15.0, respectively) compared to non-AK (9.2 and 7.3, respectively) (P < 0.0001).
      Conclusions: Over the study period, a 26% increase in rates of LRTI among adult AI/AN residing in AK compared with a 38% decrease in rates among AI/AN residing in non-AK were observed. This disparity is likely due to a variety of factors such as tobacco use, crowding, etc. Strategies to reduce LRTI in AI/AN adults are needed.

      KEYWORDS

      Introduction

      Lower respiratory tract infections (LRTIs) have caused excessive morbidity and mortality among the American Indian and Alaska Native (AI/AN) population in the United States (
      • Cheek JE
      • Holman RC
      • Redd JT
      • Haberling D
      • Hennessy TW.
      Infectious disease mortality among American Indians and Alaska Natives, 1999-2009.
      ;
      • Foote EM
      • Singleton RJ
      • Holman RC
      • Seeman SM
      • Steiner CA
      • Bartholomew M
      • et al.
      Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population.
      ;
      • Groom AV
      • Hennessy TW
      • Singleton RJ
      • Butler JC
      • Holve S
      • Cheek JE.
      Pneumonia and influenza mortality among American Indian and Alaska Native people, 1990-2009.
      ;
      • Holman RC
      • Curns AT
      • Cheek JE
      • Singleton RJ
      • Anderson LJ
      • Pinner RW.
      Infectious disease hospitalizations among American Indian and Alaska native infants.
      ;
      • Holman RC
      • Curns AT
      • Singleton RJ
      • Sejvar JJ
      • Butler JC
      • Paisano EL
      • et al.
      Infectious disease hospitalizations among older American Indian and Alaska Native adults.
      ;
      • Holman RC
      • Folkema AM
      • Singleton RJ
      • Redd JT
      • Christensen KY
      • Steiner CA
      • et al.
      Disparities in infectious disease hospitalizations for American Indian/Alaska Native people.
      ;
      • Peck AJ
      • Holman RC
      • Curns AT
      • Lingappa JR
      • Cheek JE
      • Singleton RJ
      • et al.
      Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children.
      ), especially among infants (<1 year of age) and older adults (
      • Foote EM
      • Singleton RJ
      • Holman RC
      • Seeman SM
      • Steiner CA
      • Bartholomew M
      • et al.
      Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population.
      ;
      • Holman RC
      • Curns AT
      • Cheek JE
      • Singleton RJ
      • Anderson LJ
      • Pinner RW.
      Infectious disease hospitalizations among American Indian and Alaska native infants.
      ;
      • Holman RC
      • Curns AT
      • Singleton RJ
      • Sejvar JJ
      • Butler JC
      • Paisano EL
      • et al.
      Infectious disease hospitalizations among older American Indian and Alaska Native adults.
      ). Age-adjusted LRTI hospitalizations in the AI/AN population using the Indian Health Service (IHS) healthcare system have been disproportionately higher when compared to the general United States (US) population, especially for AI/AN infants (
      • Foote EM
      • Singleton RJ
      • Holman RC
      • Seeman SM
      • Steiner CA
      • Bartholomew M
      • et al.
      Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population.
      ;
      • Holman RC
      • Curns AT
      • Cheek JE
      • Singleton RJ
      • Anderson LJ
      • Pinner RW.
      Infectious disease hospitalizations among American Indian and Alaska native infants.
      ). During 2007–2009, the LRTI hospitalization rate in Alaska AI/AN people was almost twice that for the general US population (
      • Holman RC
      • Hennessy TW
      • Haberling DL
      • Callinan LS
      • Singleton RJ
      • Redd JT
      • et al.
      Increasing trend in the rate of infectious disease hospitalisations among Alaska Native people.
      ). The 1999–2009 infectious disease (ID) death rate for AI/AN populations was significantly higher than that of white people; LRTIs and septicemia were the top ranked causes (
      • Cheek JE
      • Holman RC
      • Redd JT
      • Haberling D
      • Hennessy TW.
      Infectious disease mortality among American Indians and Alaska Natives, 1999-2009.
      ). Pneumonia and influenza death rates for AI/AN people in the Alaska, Northern Plains, and Southwest regions were more than two times higher than those for white people (
      • Groom AV
      • Hennessy TW
      • Singleton RJ
      • Butler JC
      • Holve S
      • Cheek JE.
      Pneumonia and influenza mortality among American Indian and Alaska Native people, 1990-2009.
      ). LRTIs accounted for almost half of all ID hospitalizations and 60% of ID deaths in AI/AN people ≥65 years old in 2000–2002; ID hospitalization rates were highest in the Southwest and Alaska regions (
      • Holman RC
      • Curns AT
      • Singleton RJ
      • Sejvar JJ
      • Butler JC
      • Paisano EL
      • et al.
      Infectious disease hospitalizations among older American Indian and Alaska Native adults.
      ).
      Among AI/AN people, age-adjusted LRTI hospitalization rates have been highest for the Alaska region (
      • Foote EM
      • Singleton RJ
      • Holman RC
      • Seeman SM
      • Steiner CA
      • Bartholomew M
      • et al.
      Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population.
      ;
      • Holman RC
      • Curns AT
      • Cheek JE
      • Singleton RJ
      • Anderson LJ
      • Pinner RW.
      Infectious disease hospitalizations among American Indian and Alaska native infants.
      ;
      • Holman RC
      • Curns AT
      • Singleton RJ
      • Sejvar JJ
      • Butler JC
      • Paisano EL
      • et al.
      Infectious disease hospitalizations among older American Indian and Alaska Native adults.
      ;
      • Holman RC
      • Folkema AM
      • Singleton RJ
      • Redd JT
      • Christensen KY
      • Steiner CA
      • et al.
      Disparities in infectious disease hospitalizations for American Indian/Alaska Native people.
      ;
      • Peck AJ
      • Holman RC
      • Curns AT
      • Lingappa JR
      • Cheek JE
      • Singleton RJ
      • et al.
      Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children.
      ). In Alaska, ID diagnoses accounted for a higher proportion of hospitalizations in AI/AN people in 2010–2011 when compared with non-AI/AN people, and LRTIs accounted for 38% of ID hospitalizations in AI/AN Alaskans compared with 25% in non-AI/AN Alaskans (
      • Gounder PP
      • Holman RC
      • Seeman SM
      • Rarig AJ
      • McEwen M
      • Steiner CA
      • et al.
      Infectious disease hospitalizations among American Indian/Alaska Native and Non-American Indian/Alaska Native persons in Alaska, 2010-2011.
      ). The increased LRTI hospitalization rates in AI/AN children, particularly in rural Alaska and on reservations in the Southwest regions, have been associated with increased household crowding, lack of in-home plumbed water, and higher woodstove use (
      • Bulkow LR
      • Singleton RJ
      • Karron RA
      • Harrison LH.
      Risk factors for severe respiratory syncytial virus infection among Alaska native children.
      ;
      • Gessner BD.
      Lack of piped water and sewage services is associated with pediatric lower respiratory tract infection in Alaska.
      ;
      • Robin LF
      • Less PS
      • Winget M
      • Steinhoff M
      • Moulton LH
      • Santosham M
      • et al.
      Wood-burning stoves and lower respiratory illnesses in Navajo children.
      ;
      • Thomas TK
      • Ritter T
      • Bruden D
      • Bruce M
      • Byrd K
      • Goldberger R
      • et al.
      Impact of providing in-home water service on the rates of infectious diseases: results from four communities in Western Alaska.
      ). Other potential reasons for elevated LRTI hospitalizations in adults include the legacy of historically high tuberculosis rates (
      • Cheek JE
      • Holman RC
      • Redd JT
      • Haberling D
      • Hennessy TW.
      Infectious disease mortality among American Indians and Alaska Natives, 1999-2009.
      ) and chronic lung diseases (
      • Singleton RJ
      • Butler JC
      • Bulkow LR
      • Hurlburt D
      • O'Brien KL
      • Doan W
      • et al.
      Invasive pneumococcal disease epidemiology and effectiveness of 23-valent pneumococcal polysaccharide vaccine in Alaska native adults.
      ), and high tobacco use in Alaska AI/AN adults (
      • Azagba S
      • Shan L
      • Latham K
      • Qeadan F.
      Trends in cigarette smoking among American Indians and Alaska Natives in the USA: 1992-2015.
      ;
      • Singleton RJ
      • Butler JC
      • Bulkow LR
      • Hurlburt D
      • O'Brien KL
      • Doan W
      • et al.
      Invasive pneumococcal disease epidemiology and effectiveness of 23-valent pneumococcal polysaccharide vaccine in Alaska native adults.
      ).
      LRTIs in adults can be caused by a variety of etiologic agents such as bacteria and viruses, and Streptococcus pneumoniae is known to cause a proportion of LRTI cases, particularly among those with pneumonia. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 for routine use in children <5 years of age. In 2010, a vaccine with six additional serotypes, PCV13, was recommended to replace PCV7 for routine use in children. PCV13 was also recommended for routine immunization of adults ≥65 years of age for a short period of time (2014–2019) during which overall vaccine coverage in adults was low in Alaska and the US overall. Immunization coverage for four doses of PCV13 was 81.8% (±1.3%) in 2016 for the US general population of 19–35-month-olds (https://www.cdc.gov/vaccines/imz-managers/coverage/childvaxview/data-reports/pcv/reports/2016.html); coverage for Alaska AI/AN and non-Alaska AI/AN children receiving care through IHS/Tribal/Urban was similar to or slightly lower than the US general population based on IHS unpublished data.
      The present study examined the epidemiology of LRTI hospitalizations among AI/AN adults ≥18 years of age before and after introduction of the PCV7 and PCV13 vaccines in children using the IHS/tribal health care system in the US. Rates of LRTI-associated hospitalizations and characterization of hospitalization length of stay and associated diagnoses were analyzed overall, and LRTI hospitalization rates for Alaskan AI/AN were compared with LRTI hospitalization rates from other IHS regions. Traditionally, the state of Alaska has been under-developed in regards to roads, rural housing, and sanitation compared to the rest of the US and has also seen higher rates of infectious diseases for greater than half a century (
      • Bruce M
      • Zulz T
      • Koch A.
      Surveillance of infectious diseases in the Arctic.
      ;
      • Koch A BM
      • Ladefoged K
      • et al.
      Infectious siseases: a geographic guide.
      ).

      Methods

      Hospital discharge data from the IHS Direct and Contract Health Services Inpatient Dataset, IHS National Patient Information Reporting System (NPIRS; https://search.usa.gov/search?affiliate=indianhealthservice&query=Trends2014book) for AI/AN adults ≥18 years of age who were hospitalized at an IHS-operated, tribally operated, or contract hospital with an LRTI-associated diagnosis during 1998–2014, were analyzed. This population was separated into two groups: (1) adults who were hospitalized and resided in any IHS administrative area except Alaska, termed ‘non-Alaska’ (non-AK), and (2) adults who were hospitalized and resided in Alaska (AK). AK regions were compared to non-AK regions because LRTI rates have historically been higher in Alaska compared to all other IHS regions. The inclusion of Alaska data in an overall analysis would have biased LRTI rates in an upward direction. Data were further analyzed by IHS region, which were defined as follows: East (Nashville), Northern Plains (Aberdeen, Bemidji, and Billings), Alaska, Oklahoma, and Southwest (Albuquerque, Navajo, Phoenix, and Tucson). Since there are no IHS hospitals in the West region (no IHS Direct and very little IHS contract health services inpatient data collected), this region was not included. The Alaska IHS region was further divided into urban (three service units combined) and rural (six service units combined) (
      • Foote EM
      • Singleton RJ
      • Holman RC
      • Seeman SM
      • Steiner CA
      • Bartholomew M
      • et al.
      Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population.
      ). Rural service units are predominantly remote regions, accessed mostly by single engine plane. Individuals who require hospital care are flown to regional hospitals or the Alaska Native Medical Center (ANMC) in Anchorage.
      The unit of analysis was a hospitalization. Hospital discharge records with an LRTI diagnosis listed in any of the 15 diagnoses were selected for AI/AN adults. A LRTI hospitalization was previously defined by Peck et al. using any one of the following International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes (given in parenthesis; https://www.cdc.gov/nchs/icd/icd9cm.htm codes): pulmonary tuberculosis (011), pulmonary anthrax (022.1), pulmonary diseases caused by Mycobacterium (031.0), whooping cough (033), syphilis of lung (095.1), acute bronchitis (466.0), acute bronchiolitis (466.1), pneumonia (480–486), influenza (487), empyema (510), pleurisy with effusion (511.1), abscess of lung and mediastinum (513), rheumatic pneumonia (517.1) and congenital pneumonia (770.0) (
      • Foote EM
      • Singleton RJ
      • Holman RC
      • Seeman SM
      • Steiner CA
      • Bartholomew M
      • et al.
      Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population.
      ;
      • Peck AJ
      • Holman RC
      • Curns AT
      • Lingappa JR
      • Cheek JE
      • Singleton RJ
      • et al.
      Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children.
      ). The proportions of LRTI-associated hospitalizations due to pneumonia were analyzed by year for both AK and non-AK.
      Overall average annual age-adjusted and age-specific rates per 1000 AI/AN adults were calculated using the IHS user population. The IHS user population comprises all AI/AN persons who received IHS-funded healthcare service at least once in the previous 3 years (https://search.usa.gov/search?affiliate=indianhealthservice&query=Trends2014book).
      Age-adjusted average annual rates were directly adjusted using the 2000 US population as the standard (https://www.cdc.gov/nchs/data/statnt/statnt20.pdf). Time periods were broken down into pre-PCV7 (1998–2000), post-PCV7 (2002–2004, 2005–2007), pre-PCV13 (2007–2009), and post-PCV13 (2011–2012, 2013–2014). The data were examined by time period, age group (18–49, 50–64, 65–74, 75–84, 85+ years), and sex. Rate ratios (RR) with 95% confidence intervals (CI) comparing Alaska vs non-Alaska rates were calculated using Poisson regression (
      • Kleinbaum DG KL
      • Muller KE
      • et al.
      Applied regression analysis and multivariable methods.
      ). Trends over time were analyzed and compared for all IHS regions and Alaska urban and rural using linear regression. Among the LRTI hospitalizations, the most common diagnoses listed anywhere on the hospitalization record were analyzed and compared between Alaska and non-Alaska and by age <65 and 65+ years using the Chi-square test. Lastly, median length of hospital stay and median age were calculated and compared using the Wilcoxon rank-sum test. Statistical analyses were done in SAS 9.4 and statistical significance was considered at the P < 0.05 level.
      The PCV7 and PCV13 eras were defined to include a time period immediately before introduction of the given vaccine and a time period after introduction of the vaccine. The rates of LRTI-associated hospitalizations were observed over the entire time period of the study, but also post PCV7 and post PCV13 vaccine use in children to help determine rate changes in adults due to herd immunity.

      Results

       Overall rates of LRTI-associated hospitalizations

      Overall, there were 13 733 LRTI-associated hospitalizations in Alaska during the period 1998–2014, with an age-adjusted rate of 13.7 per 1000 AI/AN adults (Table 1). In non-AK AI/AN, there were a total of 79 170 hospitalizations, with a rate of 8.6 per 1000 adults. The overall AK rate was 1.57 (95% CI 1.41–1.76) times higher than the non-AK rate (P < 0.0001). The highest rate was in AI/AN adults ≥85 years of age for both AK (70.1, n = 1016) and non-AK (56.9, n = 8029). Alaska had a higher LRTI hospitalization rate in all age groups compared to non-AK (RR range 1.23 (95% CI 1.16–1.32) to 1.88 (95% CI 1.81–1.96); all P < 0.0001). Among the non-AK IHS regions, Northern Plains West had the highest rate (13.0, n = 17 901), while Northern Plains East had the lowest rate (3.5, n = 2744). In Alaska, the rural service units had a higher LRTI rate (18.6, n = 6830) compared to urban service units (10.5, n = 6903) (RR 1.67, 95% CI 1.33–2.07 [Au?3]; P < 0.0001). Persons hospitalized for LRTI in urban Alaska had a lower median age (60 years) compared to those in rural Alaska (68 years) (P < 0.0001).
      Table 1Comparison of age-specific and age-adjusted lower respiratory tract infection-associated hospitalization rates among American Indian and Alaska Native adults ≥18 years of age between Alaska and non-Alaska Indian Health Service regions for 1998–2014
      Rates are per 1000 adults. RR and 95% CI calculated using Poisson regression. *P < 0.05.
      CharacteristicAlaska Rate (n)Non-Alaska Rate (n)RR (95% CI) Alaska vs non-Alaska
      Age group (years)
      18–493.6 (3547)2.6 (22 671)1.42 (1.37–1.47)*
      50–6414.0 (3603)9.1 (20 746)1.53 (1.47–1.58)*
      65–7435.3 (2921)18.8 (14 579)1.88 (1.81–1.96)*
      75–8462.3 (2646)34.5 (13 145)1.80 (1.73–1.88)*
      85+70.1 (1016)56.9 (8029)1.23 (1.16–1.32)*
      Sex
      Male14.8 (6747)9.4 (37 262)1.56 (1.34–1.81)*
      Female12.9 (6986)8.0 (41 908)1.58 (1.43–1.75)*
      RR (95% CI)
      Alaska service unit
      Urban10.5 (6903)-Reference
      Rural18.6 (6830)-1.67 (1.33–2.07)*
      Non-Alaska region
      East-7.8 (2937)2.27 (1.56–3.28)*
      Northern Plains East-3.5 (2744)Reference
      Northern Plains West-13.0 (17 901)3.81 (2.86–5.08)*
      Southern Plains-4.4 (12 779)1.31 (0.97–1.75)
      Southwest-11.2 (42 809)3.10 (2.35–4.08)*
      Total13.7 (13 733)8.6 (79 170)1.57 (1.41–1.76)*
      RR, rate ratio; CI, confidence interval.
      a Rates are per 1000 adults. RR and 95% CI calculated using Poisson regression. *P < 0.05.

       LRTI-associated hospitalization rates in the PCV7 era

      The average annual age-adjusted LRTI rate during the pre PCV7 time period, 1998–2000, in Alaska was 12.4 per 1000 adults, which was 1.20 (95% CI 1.05–1.39) times higher compared to the non-AK rate (10.1 per 1000 adults) (P = 0.01) (Table 2). The highest hospitalization rate occurred among adults ≥85 years of age and did not differ significantly between AK (63.9) and non-AK regions (67.8) (P = 0.5). Adults in Alaska had statistically higher LRTI rates than non-AK adults for age groups 18–49, 65–74, and 75–84 years, and for females (all P < 0.02).
      Table 2Comparison of age-specific and age-adjusted lower respiratory tract infection-associated hospitalization rates among American Indian and Alaska Native adults ≥18 years of age between Alaska and non-Alaska Indian Health Service regions for pre and post PCV7 and PCV13 time periods, 1998–2014
      Rates per 1000 adults. RR and 95% CI calculated using Poisson regression. *P < 0.05.
      CharacteristicPre PCV7Post PCV7
      1998–20002002–20042005–2007
      AK rateNon-AK rateRR (95% CI) AK vs non-AKAK rateNon-AK rateRR (95% CI) AK vs non-AKAK rateNon-AK rateRR (95% CI) AK vs non-AK
      Age group (years)
      18–493.12.81.12 (1.02–1.23)*3.12.61.17 (1.06–1.28)*3.52.61.33 (1.22–1.45)*
      50–6411.611.21.04 (0.93–1.16)11.210.31.08 (0.98–1.20)13.39.81.36 (1.25–1.48)*
      65–7434.922.51.55 (1.40–1.72)*28.521.61.32 (1.18–1.47)*39.320.71.90 (1.73–2.08)*
      75–8457.939.61.46 (1.31–1.64)*58.836.91.59 (1.43–1.77)*59.037.81.56 (1.41–1.73)*
      85+63.967.80.94 (0.79–1.12)86.762.91.38 (1.19–1.60)*62.360.71.03 (0.87–1.21)
      Sex
      Male13.411.21.17 (0.96–1.42)13.69.91.28 (1.12–1.47)*14.310.21.41 (1.24–1.60)*
      Female11.69.21.24 (1.12–1.36)*11.49.01.23 (1.10–1.36)*12.88.51.48 (1.29–1.71)*
      Total12.410.11.20 (1.05–1.39)*12.39.41.26 (1.12–1.41)*13.59.21.45 (1.27–1.65)*
      CharacteristicPre PCV13Post PCV13
      2007–20092011–20122013–2014
      AK rateNon-AK rateRR (95% CI) AK vs non-AKAK rateNon-AK rateRR (95% CI) AK vs non-AKAK rateNon-AK rateRR (95% CI) AK vs non-AK
      Age group (years)
      18–494.12.91.43 (1.32–1.54)*3.72.01.84 (1.67–2.03)*4.32.31.87 (1.71–2.05)*
      50–6415.09.81.52 (1.41–1.64)*16.56.72.47 (2.26–2.70)*15.97.72.07 (1.91–2.26)*
      65–7435.819.41.84 (1.68–2.02)*40.213.92.88 (2.59–3.20)*36.114.92.43 (2.19–2.69)*
      75–8463.436.41.74 (1.59–1.92)*66.927.72.42 (2.17–2.70)*64.529.52.19 (1.96–2.44)*
      85+57.656.61.02 (0.86–1.20)73.845.61.62 (1.36–1.92)*74.349.11.51 (1.28–1.79)*
      Sex
      Male14.39.91.46 (1.20–1.76)*16.37.32.30 (1.83–2.88)*17.68.12.22 (1.83–2.68)*
      Female13.98.61.62 (1.44–1.81)*14.26.22.26 (1.98–2.57)*12.86.81.89 (1.64–2.17)*
      Total14.19.11.54 (1.36–1.75)*15.26.62.28 (1.98–2.64)*15.07.32.06 (1.84–2.31)*
      PCV, pneumococcal conjugate vaccine; AK, Alaska; RR, rate ratio; CI, confidence interval.
      a Rates per 1000 adults. RR and 95% CI calculated using Poisson regression. *P < 0.05.
      The LRTI rate during the post PCV7 time period, 2005–2007, in Alaska was 13.5, which was 1.45 (95% CI 1.27–1.65) times higher compared to the non-AK rate (9.2) (P < 0.0001). The difference in LRTI rates between AK and non-AK increased between the 1998–2000 period (AK 12.4, non-AK 10.1) and 2005–2007 period (AK 13.5, non-AK 9.2) (P = 0.049). The overall LRTI rates in AK remained stable in 2005–2007 (13.5) when compared to 1998–2000 (12.4) (P = 0.12), while the non-AK regions showed a statistically significant decline in LRTI rates from pre (10.1) to post PCV7 vaccination period (9.2) (P < 0.0001; Figure 1). Significant declines in LRTI rates from pre to post PCV7 vaccination periods were seen in all non-AK regions (all P < 0.008) except East and Northern Plains East, where the rate remained stable (P = 0.09 and P = 0.98, respectively). Among urban AK, LRTI rates were significantly higher in both post PCV7 periods (9.8 in 2002–2004 and 10.1 in 2005–2007) compared to the pre-vaccine period (7.7) (P < 0.0001), while rural AK rates remained stable between 1998–2000 (18.5) and 2005–2007 (18.7) (P = 0.8).
      Figure 1
      Figure 1Annual age-adjusted and age-specific hospitalization rates associated with lower respiratory tract infection (LRTI) among American Indian and Alaska Native (AI/AN) adults in Alaska and non-Alaska Indian Health Service (IHS) regions ≥18 years of age overall (top) and by age group (bottom), 1998–2014.

       LRTI-associated hospitalization rates in the PCV13 era

      The average annual age-adjusted LRTI rate during the pre PCV13 time period, 2007–2009, in Alaska was 14.1 per 1000 adults (Table 2); this rate was 1.54 (95% CI 1.36–1.75) times higher compared to the non-AK rate (9.1) (P < 0.0001). The LRTI hospitalization rate was higher in AK compared to non-AK in both sexes and all age groups (all P < 0.0002) except for people ≥85 years of age (P = 0.8). The LRTI rate during the post PCV13 time period, 2013–2014, in Alaska was 15.0, which was 2.06 (95% CI 1.84–2.31) times higher than the non-AK rate (7.3) (P < 0.0001). There were lower LRTI rates in non-AK in both post PCV13 time periods (2011–2012 and 2013–2014) compared to 2007–2009 (all P < 0.0001), while LRTI rates in AK demonstrated no statistically significant change (all P = 0.07). The difference in LRTI rates between AK and non-AK grew wider between 2007–2009 (AK 14.1, non-AK 9.1) and 2011–2012 (AK 15.2, non-AK 6.6) (P < 0.0001), although the difference remained stable between 2011–2012 and 2013–2014 (P = 0.21). The overall LRTI rates in AK remained stable in 2007–2009 (14.1) compared to 2011–2012 (15.2) (P = 0.19), while the non-AK regions showed a statistically significant decline in LRTI rates from 2007–2009 (9.1) to 2011–2012 (6.6) (P < 0.0001). Lower rates remained in 2013–2014 compared to 2007–2009 in all non-AK regions except East (8.6 in 2013–2014 vs 9.8 in 2007–2009) and Southern Plains (4.1 vs 4.2), where the 2013–2014 rate was not statistically different compared to the 2007–2009 rate (P = 0.14 and P = 0.40, respectively). LRTI rates in urban Alaska were significantly higher in both post PCV13 time periods (12.2 in 2011–2012, 12.2 in 2013–2014) compared to 2007–2009 (10.9) (P = 0.04 and P = 0.03, respectively). Rates among the Alaska rural population remained stable in 2011–2012 (20.2) and 2013–2014 (20.2) compared to 2007–2009 (19.2) (P = 0.4 and P = 0.2, respectively).

       Rates of LRTI-associated hospitalizations over the entire 16-year time period

      There was a 26% increase in LRTI rate in AK from 1998 to 2014 (P = 0.001; Figure 1). An increase of 58% was seen for urban Alaska (P < 0.0001) and 19% for rural Alaska LRTI rates P = 0.02) (data not shown). At the same time, rates of LRTI in non-AK had a 38% decline (P < 0.0001; Figure 1). All non-AK regions showed a significant decrease in LRTI rates over time, except for East, which showed a stable rate from 1998 to 2014 (P = 0.2) (Table 3).
      Table 3Comparison of age-adjusted lower respiratory tract infection-associated hospitalization rates among American Indian and Alaska Native adults ≥18 years of age between 1998 and 2014 by Indian Health Service region
      Rate per 1000 adults.
      Indian Health Service region199820142014 vs 1998
      Age-adjusted rate (n)Age-adjusted rate (n)Percent rate changeP-value
      Alaska10.9 (498)13.8 (1033)+26.6<0.0001
      East6.0 (97)8.1 (261)+35.00.20
      Northern Plains East3.9 (137)2.2 (128)−43.60.0003
      Northern Plains West15.8 (1030)9.5 (937)−39.9<0.0001
      Southern Plains4.8 (640)3.8 (848)−20.80.0006
      Southwest14.3 (2527)8.0 (2270)−44.10.001
      a Rate per 1000 adults.
      Breaking down the AK rates by age group, LRTI rates among those ≥65 years of age showed a 13% increase from 1998 (39.7) to 2014 (44.9) (P = 0.04). Rates of LRTI hospitalizations among adults <65 years of age in AK increased by 51% (4.2 in 1998, 6.3 in 2014; P < 0.0001). Concurrently, LRTI rates among non-AK ≥65 years of age showed a 43% decrease from 1998 (35.3) to 2014 (20.0) (P < 0.0001) and LRTI rates among non-AK <65 years of age showed a 25% decrease from 1998 (4.3) to 2014 (3.2) (P = 0.03).

       Most common diagnoses and length of hospitalization stay of LRTI-associated hospitalizations

      The most common diagnosis for LRTI-associated hospitalizations from 1998 to 2014 was pneumonia (ICD-9-CM code 486), which made up 73.2% of LRTI hospitalizations in AK and 76.1% in non-AK (Table 4). Essential hypertension was the second most common diagnosis code on LRTI hospitalizations for both AK and non-AK. The third most common LRTI-associated diagnosis in the AK region was chronic obstructive pulmonary disease (COPD)/bronchitis. Diabetes mellitus without mention of complication ranked third for non-AK (21.4%); however, this was ranked 12th for AK (8.6%). Tobacco use disorder was ranked fourth most common in Alaska (18.8%) (only 22nd for non-AK (4.0%)). Unspecified was ranked fourth for non-AK. Among adults <65 years of age in Alaska, the top three diagnoses associated with LRTI were pneumonia (first), tobacco use (second), and chronic bronchitis (third); for non-AK they were pneumonia (first), essential hypertension (second), and diabetes mellitus (third). Among persons >65 years of age in Alaska, the top three diagnoses associated with LRTI were pneumonia (first), chronic bronchitis (second), and essential hypertension (third); for non-AK, the top three were the same as for <65-year-olds. The duration of LRTI hospitalization stay from 1998 to 2014 was longer in Alaska (median 5 days, interquartile range (IQR) 3–10 days) compared to non-AK (median 4 days, IQR 2–7 days) (P < 0.0001) (data not shown). Hospitalization stays in Alaska were longer in all time periods compared to non-AK (P < 0.0001). Within Alaska from 1998 to 2014, stays in the urban service units were longer (median 6 days, IQR 3–12 days) compared to rural service units (median 4 days, IQR 3–8 days) (P < 0.0001).
      Table 4Most common diagnoses of lower-respiratory tract infection-associated hospitalizations among American Indian/Alaska Native adults in Alaska and non-Alaska Indian Health Service regions by age group, 1998–2014
      Rank (%) in bold are among the top five associated diagnoses.
      ICD-9-CM diagnosis (code)Alaska (Total)Non-Alaska (Total)Alaska <65 yearsNon-Alaska <65 yearsAlaska 65+ yearsNon-Alaska 65+ years
      Rank (%)Rank (%)Rank (%)Rank (%)Rank (%)Rank (%)
      Pneumonia, organism unspecified (486)1 (73.2)1 (76.1)1 (67.2)1 (73.1)1 (79.8)1 (79.6)
      Essential hypertension, unspecified (401.9)2 (25.8)2 (23.9)4 (17.5)2 (19.8)3 (34.9)2 (28.9)
      Chronic bronchitis unspecified (491.21, 496)3 (25.7)4 (12.9)3 (15.1)5 (8.1)2 (37.3)4 (18.6)
      Tobacco use disorder (305.1)4 (18.8)22 (4.0)2 (27.9)12 (5.6)12 (8.9)47 (2.0)
      Congestive heart failure, unspecified (428.0)5 (13.2)5 (10.7)14 (7.4)8 (6.3)4 (19.5)5 (16.0)
      Diabetes mellitus without mention of complication, type II or unspecified type (250.00)12 (8.6)3 (18.8)22 (5.7)3 (15.8)8 (11.7)3 (22.4)
      Acute respiratory failure (518.81)9 (10.3)13 (5.7)5 (12.1)6 (6.6)13 (8.4)20 (4.6)
      Anemia, unspecified (285.9)6 (12.7)8 (7.0)6 (10.8)9 (6.3)5 (14.8)10 (7.9)
      Hypopotassemia (276.8)11 (9.2)7 (7.3)7 (10.6)4 (8.4)14 (7.7)13 (5.9)
      a Rank (%) in bold are among the top five associated diagnoses.

      Discussion

      From 1998 to 2014, hospital-associated LRTI rates were significantly higher among Alaska AI/AN adults than among non-Alaska AI/AN adults overall, and at all time periods pre and post PCV7 and PCV13 introduction. Rates were higher among rural when compared to urban Alaska AI/AN adults. Northern Plains West had the highest adult LRTI rate among the non-AK IHS regions, which was nearly as high as Alaska. Rates were significantly higher among all age groups of Alaska AI/AN adults compared with non-Alaska AI/AN adults. After routine childhood PCV7 vaccination in 2000 and PCV13 childhood vaccination in 2010, LRTI hospitalization rates decreased among non-AK adults, likely due to herd immunity; however, in Alaska, overall rates of LRTI hospitalizations remained stable. During 2007–2009, the LRTI hospitalization rate in Alaska AI/AN adults was almost twice that for the general US population (
      • Holman RC
      • Hennessy TW
      • Haberling DL
      • Callinan LS
      • Singleton RJ
      • Redd JT
      • et al.
      Increasing trend in the rate of infectious disease hospitalisations among Alaska Native people.
      ).
      High rates of LRTI hospitalizations have been documented among AI/AN adults for over 30 years (
      • Holman RC
      • Curns AT
      • Singleton RJ
      • Sejvar JJ
      • Butler JC
      • Paisano EL
      • et al.
      Infectious disease hospitalizations among older American Indian and Alaska Native adults.
      ). More recent studies have shown an increase in LRTI hospitalization among AI/AN people from 2001 to 2009 in contrast to decreasing LRTI rates for the general US population over this period of time (
      • Holman RC
      • Hennessy TW
      • Haberling DL
      • Callinan LS
      • Singleton RJ
      • Redd JT
      • et al.
      Increasing trend in the rate of infectious disease hospitalisations among Alaska Native people.
      ). Previous studies have also documented an increase in pneumonia hospitalizations among older AI/AN (
      • Holman RC YK
      • Singleton RJ
      Increasing rate of Pneumonia hospitalizations among older American Indian and Alaska Native adults.
      ).
      In the present study, pneumonia accounted for three-fourths of LRTI hospitalizations. Previous studies have shown that 20–60% of community-acquired pneumonia is pneumococcal in origin (
      • Bartlett JG.
      Diagnostic tests for agents of community-acquired pneumonia.
      ). In other studies, the proportion of pneumonia caused by S. pneumoniae was found to be 10–15% (USA) and approximately 34% (Europe) (
      • Musher DM
      • Abers MS
      • Bartlett JG.
      Evolving understanding of the causes of Pneumonia in adults, with special attention to the role of Pneumococcus.
      ). In addition, after PCV7 and PCV13 vaccination campaigns in children, there have been declines in pneumonia hospitalizations documented in a number of adult age groups (
      • Griffin MR
      • Zhu Y
      • Moore MR
      • Whitney CG
      Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination.
      ;
      • Grijalva CG
      • Nuorti JP
      • Arbogast PG
      • Martin SW
      • Edwards KM
      • Griffin MR.
      Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis.
      ). During 2003–2009, Alaska experienced an increase in non-vaccine serotype invasive pneumococcal disease (IPD) in children with the PCV7 vaccine, which could have reduced herd immunity in adults (
      • Singleton RJ
      • Hennessy TW
      • Bulkow LR
      • Hammitt LL
      • Zulz T
      • Hurlburt DA
      • et al.
      Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage.
      ). In 2014, the Advisory Committee on Immunization Practices (ACIP) recommended PCV13 in series with 23-valent polysaccharide vaccine (PPSV23) for all adults aged ≥65 years based on its safety and efficacy against adult PCV13-type pneumonia (
      • Tomczyk S
      • Bennett NM
      • Stoecker C
      • Gierke R
      • Moore MR
      • Whitney CG
      • et al.
      Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP).
      ). The ACIP changed this routine recommendation for immunocompetent adults to a recommendation for shared decision-making in 2019 because indirect effects of childhood PCV13 vaccination led to sharp declines in adult pneumococcal disease through decreased carriage and transmission of vaccine types (
      • Matanock A
      • Lee G
      • Gierke R
      • Kobayashi M
      • Leidner A
      • Pilishvili T.
      Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: updated recommendations of the advisory committee on immunization practices.
      ). In the general US population, the incidence of PCV13-type IPD among adults aged ≥65 years declined nine-fold during 2000–2014 (
      • Pilishvili T
      • Whitney CG.
      Use of data to drive pneumococcal conjugate vaccine policy.
      ), and no further reduction in PCV13-type IPD incidence was observed between 2014 and 2018, with the incidence stable at five per 100 000 population (
      • Pilishvili T
      • Whitney CG.
      Use of data to drive pneumococcal conjugate vaccine policy.
      ). Other studies in Alaska have shown a reduction in PCV13-type IPD among adults >18 years and all serotype-IPD among persons 18–44 years after PCV13 was introduced into the vaccine schedule for children in 2010 (
      • Bruce MG
      • Singleton R
      • Bulkow L
      • Rudolph K
      • Zulz T
      • Gounder P
      • et al.
      Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska.
      ). The use of PCV7 and then PCV13 vaccines in children likely played an important role in the reduction in the rates of LRTI hospitalizations among adults in non-AK IHS regions due to herd immunity. Unfortunately this same rate reduction was not observed in Alaska. This is likely due to numerous factors, of which serotype replacement (with non-PCV13 serotypes in adults) and poorly immunogenic vaccine serotypes such as serotype 3 (
      • Pick H
      • Daniel P
      • Rodrigo C
      • Bewick T
      • Ashton D
      • Lawrence H
      • et al.
      Pneumococcal serotype trends, surveillance and risk factors in UK adult pneumonia, 2013-18.
      ) are likely contributors. In addition, IHS data show lower rates of vaccination with the influenza vaccine among persons ≥65 years in Alaska compared to other IHS sites in 2012 (page 89, https://www.ihs.gov/sites/dps/themes/responsive2017/display_objects/documents/Trends2014Book508.pdf).
      The ongoing LRTI disparities among AN people, especially in rural Alaska regions, may be partly attributed to household crowding, household air pollution, lack of in-home water service, and consequences of poverty (
      • Bulkow LR
      • Singleton RJ
      • Karron RA
      • Harrison LH.
      Risk factors for severe respiratory syncytial virus infection among Alaska native children.
      ;
      • Thomas TK
      • Ritter T
      • Bruden D
      • Bruce M
      • Byrd K
      • Goldberger R
      • et al.
      Impact of providing in-home water service on the rates of infectious diseases: results from four communities in Western Alaska.
      ;
      • Wenger JD
      • Zulz T
      • Bruden D
      • Singleton R
      • Bruce MG
      • Bulkow L
      • et al.
      Invasive pneumococcal disease in Alaskan children: impact of the seven-valent pneumococcal conjugate vaccine and the role of water supply.
      ). In addition to environmental factors, co-morbidities, higher rates of chronic bronchitis/COPD, and high rates of tobacco use may explain some of the elevated LRTI rates. Chronic bronchitis was ranked the third most common diagnosis among hospitalized persons with LRTI, while tobacco use disorder was ranked fourth most common in Alaska. In a recently published paper focused on AI/AN adult LRTI hospitalizations from one rural region in Alaska, 54% of adults with LRTI hospitalizations had chronic lung disease, primarily COPD, and LRTI hospitalization rates were much higher in these adults (RR 35.6) (
      • Nolen LD
      • Seeman S
      • Desnoyers C
      • DeByle C
      • Klejka J
      • Bruden D
      • et al.
      Respiratory syncytial virus and influenza hospitalizations in Alaska native adults.
      ).
      Alaska AI/AN adults experienced longer LRTI hospital stays compared to those in other IHS regions. This difference in length of hospital stay is likely due to the fact that many Alaska AI/AN live in extremely remote locations; once a person is hospitalized, then discharge from the hospital back to the remote location where they live may be more difficult.
      This study has some limitations. Hospital diagnoses may be incomplete or inaccurate due to the use of ICD-9-CM coding to identify LRTI hospitalizations, and diagnostic coding may vary by practice. The unit of analysis was a hospitalization, therefore any multiple hospitalizations and/or hospital transfers for a patient's event were included. The denominator for the Alaska AI/AN population in the present study was based on the number of AI/AN persons who use the tribal healthcare system in Alaska (user population) and likely does not include all Alaska AI/AN adults who are eligible for healthcare at tribal facilities, which would underestimate the denominator. However, some additional limitations that we are aware of indicate that the reported rates of hospitalization for AN people may be an underestimate. AI/AN patients who are eligible for healthcare within the tribal healthcare system may receive care outside the system; therefore, their hospitalizations would not be included in the present study. Also, reporting of hospitalizations for Alaska regions to the IHS National Patient Information Reporting System may not be complete. It is possible that more complete capture of hospitalizations could have occurred in Alaska vs other IHS regions, but it was not possible to measure this. It was also not possible to include data from the IHS West region where there are no IHS hospitals and therefore no IHS Direct data are collected. Due to the fact that inpatient hospital care in the West region occurs outside the IHS system (very little IHS contract health services inpatient data are collected by the IHS in the West region), it was decided not to include this region, which is consistent with numerous previous studies using NPIRS data (
      • Holman RC
      • Curns AT
      • Cheek JE
      • Bresee JS
      • Singleton RJ
      • Carver K
      • et al.
      Respiratory syncytial virus hospitalizations among American Indian and Alaska Native infants and the general United States infant population.
      ;
      • Peck AJ
      • Holman RC
      • Curns AT
      • Lingappa JR
      • Cheek JE
      • Singleton RJ
      • et al.
      Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children.
      ;
      • Singleton RJ
      • Holman RC
      • Yorita KL
      • Holve S
      • Paisano EL
      • Steiner CA
      • et al.
      Diarrhea-associated hospitalizations and outpatient visits among American Indian and Alaska Native children younger than five years of age, 2000-2004.
      ).
      Tabled 1
      Author queries
      [Note: The text has undergone minor rephrasing throughout.]
      [Au?1]“In 2010, a vaccine with six additional serotypes, PCV13, was recommended to replace PCV7 for routine use in children. PCV13 was also recommended for routine immunization of adults 65 years of age for a short period of time…”

      Should this be “≥65 years of age”?
      [Au?2]“…children receiving care through IHS/T/U…”

      Abbreviation ‘T/U’ has not been identified. Please give in full.
      [Au?3]Data type not identified. “95% CI” has been added. Is this correct? If not, please revise as necessary.
      [Au?4]Sentence has been rephrased – is this correct? Please advise of any changes required.
      [Au?5]Table 2: abbreviation ‘IHS’ is not found in the table. Should this be deleted from the footnote?

      Funding

      In-kind funding via person-time of epidemiologists at the Arctic Investigations Program, CDC, and the Indian Health Service.

      Disclaimer

      The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the Indian Health Service.

      Funding source

      There is no funding source to report.

      Ethical approval

      This manuscript was reviewed and approved for publication by the Alaska Native Tribal Health Consortium and Southcentral Foundation Review Committee, the Indian Health Service (IHS) and the Centers for Disease Control and Prevention (CDC).

      Conflict of interest

      None of the authors report any competing interests.

      Acknowledgements

      We thank the staff at the participating Indian Health Service/tribal and contract care hospitals, and the Indian Health Service National Patient Information Reporting System.

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