Context Respiratory viral infections are responsible for a large number of hospitalizations
in the United States each year.
Objective To estimate annual influenza-associated hospitalizations in the United
States by hospital discharge category, discharge type, and age group.
Design, Setting, and Participants National Hospital Discharge Survey (NHDS) data and World Health Organization
Collaborating Laboratories influenza surveillance data were used to estimate
annual average numbers of hospitalizations associated with the circulation
of influenza viruses from the 1979-1980 through the 2000-2001 seasons in the
United States using age-specific Poisson regression models.
Main Outcome Measures We estimated influenza-associated hospitalizations for primary and any
listed pneumonia and influenza and respiratory and circulatory hospitalizations.
Results Annual averages of 94 735 (range, 18 908-193 561) primary
and 133 900 (range, 30 757-271 529) any listed pneumonia and
influenza hospitalizations were associated with influenza virus infections.
Annual averages of 226 054 (range, 54 523-430 960) primary
and 294 128 (range, 86 494-544 909) any listed respiratory
and circulatory hospitalizations were associated with influenza virus infections.
Persons 85 years or older had the highest rates of influenza-associated primary
respiratory and circulatory hospitalizations (1194.9 per 100 000 persons).
Children younger than 5 years (107.9 primary respiratory and circulatory hospitalizations
per 100 000 persons) had rates similar to persons aged 50 through 64
years. Estimated rates of influenza-associated hospitalizations were highest
during seasons in which A(H3N2) viruses predominated, followed by B and A(H1N1)
seasons. After adjusting for the length of each influenza season, influenza-associated
primary pneumonia and influenza hospitalizations increased over time among
the elderly. There were no significant increases in influenza-associated primary
respiratory and circulatory hospitalizations after adjusting for the length
of the influenza season.
Conclusions Significant numbers of influenza-associated hospitalizations in the
United States occur among the elderly, and the numbers of these hospitalizations
have increased substantially over the last 2 decades due in part to the aging
of the population. Children younger than 5 years had rates of influenza-associated
hospitalizations similar to those among individuals aged 50 through 64 years.
These findings highlight the need for improved influenza prevention efforts
for both young and older US residents.
National estimates of influenza-associated mortality have been important
for understanding the epidemiology of influenza over time and for resource
planning for influenza epidemics and future influenza pandemics.1-4 However,
mortality incompletely reflects the severity of influenza infections because
many severe illnesses do not result in death. In addition, influenza types
and subtypes have differential effects on morbidity and mortality. For example,
during some seasons, influenza A(H1N1) and B viruses are associated with substantial
numbers of hospitalizations and outpatient visits but small increases in mortality.5-7 Furthermore, influenza-associated
hospitalizations contribute an important proportion of the total health burden
and economic costs of influenza epidemics and pandemics.2,8-10
Previous studies have estimated numbers and rates of influenza-associated
hospitalizations by age group, risk status, influenza type and subtype, and
vaccine status.11-20 However,
only 2 studies, both using National Hospital Discharge Survey (NHDS) data,
have provided national estimates of influenza-associated hospitalizations
in the United States.11,13 Barker11 estimated influenza-associated hospitalizations from
1970 through 1978 in 3 age groups using 3 mutually exclusive hospital outcomes:
all-cause pneumonia and influenza, respiratory disease excluding all-cause
pneumonia and influenza, and acute cardiac failure. The assessment of influenza-associated
hospitalizations was limited to seasons in which influenza A(H3N2) viruses
predominated and the assessment used winter seasons in which influenza A(H1N1)
and B viruses predominated as the baseline period from which to estimate A(H3N2)
excess hospitalizations. In the second study, Simonsen and colleagues13 estimated annual numbers of influenza-associated
hospitalizations by virus type and subtype from the 1969-1970 through 1994-1995
seasons for primary pneumonia and influenza hospitalizations for 2 age groups
(<64 years and ≥65 years). In most seasons, November hospitalizations
were used as the baseline for estimating influenza-associated hospitalizations.
In 6 seasons when the influenza circulation began late, a December baseline
was used to estimate such hospitalizations.
We estimated annual numbers of influenza-associated hospitalizations
from the 1979-1980 through the 2000-2001 respiratory seasons, a 22-year period
for which national influenza laboratory surveillance data were available.
We modified Poisson regression methods previously used to estimate influenza-associated
mortality in the United States21 to estimate
numbers and rates of influenza-associated hospitalizations.
Definition of Respiratory Season
Influenza viruses typically circulate during winter months and across
calendar years. Therefore, we defined July 1 through June 30 of the following
year as a respiratory season so that an entire influenza season was studied.
National Viral Surveillance Data
In the United States, laboratory-based surveillance for influenza viruses
is conducted from October through mid May (calendar week 40 through week 20).
For the influenza virus surveillance periods from the 1979-1980 through 2000-2001
seasons, we obtained numbers of respiratory specimens that tested positive
for influenza. Specimens are reported weekly by 50 to 75 US-based World Health
Organization (WHO) collaborating virology laboratories to the Centers for
Disease Control and Prevention. The laboratories provide numbers of total
respiratory specimens tested for influenza and positive influenza tests by
virus type and subtype.22 The monthly percentages
of specimens that tested positive for influenza viruses were used in estimating
the effect of influenza circulation on monthly hospitalizations in the United
States. For summary purposes, we defined a predominant influenza virus type
or subtype for each season based on whether the influenza type or subtype
constituted more than 20% of the total influenza specimens that had tested
positive in a given season.
NHDS Hospital Discharge Diagnoses
Hospital discharge diagnosis records were obtained from the NHDS23-28 for
the 1979-1980 through 2000-2001 seasons. National Hospital Discharge Survey
hospital discharge data are collected and reported by month for approximately
270 000 inpatient records sampled from approximately 500 hospitals. These
records represent approximately 1% of all inpatient hospitalizations in the
United States.29,30 The sampling
design assigns a discharge weight to each hospital record. The discharge weight
is the number of hospitalizations that the hospital record represents, and
use of these weights permits calculations of nationally representative numbers
of hospitalizations. We summed the corresponding discharge weights by month
to obtain nationally representative numbers of hospitalizations.
International Classification of Diseases, Ninth Revision,
Clinical Modification (ICD-9-CM) codes31 were used to categorize hospitalizations. Monthly
hospitalizations were summarized by both first-listed and any-listed ICD-9-CM discharge codes. We considered the first-listed
discharge code as the primary discharge diagnosis. We examined 2 diagnostic
categories: pneumonia and influenza hospitalizations (ICD-9-CM codes 480-487) and respiratory and circulatory hospitalizations (ICD-9-CM codes 390-519). Thus, pneumonia and influenza
hospitalizations were a subset of respiratory and circulatory hospitalizations.
We modified methods developed for estimating US influenza-associated
mortality21 to estimate influenza-associated
hospitalizations with NHDS data. One advantage of this method is that it permitted
the effect of influenza circulation to vary by month, and therefore hospitalization
estimates could also fluctuate with influenza activity. Poisson regression
models were fit to 8 age groups: younger than 5 years, 5 through 49 years,
50 through 64 years, 65 through 69 years, 70 through 74 years, 75 through
79 years, 80 through 84 years, and 85 years or older. Influenza virus circulation
terms representing the percentages of specimens testing positive for influenza
A(H1N1), A(H3N2), and B viruses during each month in the study period were
included in all models.
The age-specific Poisson regression models we used can be written as
Y = α exp(β0 + β1[t] + β2[t2] + β3[t3]
+ β4[sin(2tπ/12)] + β5[cos(2tπ/12)]
+ β6[A(H1N1)] + β7[A(H3N2)]
+ β8[B]
where Y represents the number of hospitalizations
during a particular month for a specific age group. The term α was the
population offset. The term t was the number of months
in a time series from July 1979 through June 2001. We estimated the following β
coefficients: β0was the intercept, β1accounted
for the linear time trend in months, β2and β3accounted
for nonlinear time trends, β4and β5 accounted
for seasonal changes in hospitalizations, and β6through β8were coefficients associated with the percentages of specimens testing
positive for specific influenza viruses in a given month. Estimates of monthly
US age-specific populations were used to account for changes in population
trends over time and were obtained from the Census Bureau.32 Attempts
to include a term for respiratory syncytial virus in these models were unsuccessful
because of the high correlation between the cosine term and the respiratory
syncytial virus term (r = 0.90) when the data were
modeled on a monthly rather than on a weekly basis as was done in our recent
mortality analyses.21 All analyses were performed
using SAS statistical software version 8.2 (PROC GENMOD, SAS Institute Inc,
Cary, NC). Because NHDS data sets are deidentified public-use data sets, their
use does not require formal institutional review board approval.
We determined the number of weeks during each respiratory season for
which at least 10% of specimens tested positive for influenza. We used these
numbers in analyses to control for the length of the influenza season when
examining trends in influenza hospitalization rates.
Annual Influenza Laboratory Surveillance
For the 1979-1980 through 2000-2001 seasons, an annual average of 30 936
specimens (range, 14 804-53 427) were tested for influenza. During
months in which specimens were tested for influenza, an average of 13.3% of
specimens tested positive for influenza. Influenza A(H1N1), A(H3N2), and B
viruses were detected in 2.1%, 7.9%, and 3.3% of the total specimens tested,
respectively. During the 22 respiratory seasons included in this study, A(H1N1),
A(H3N2), and B viruses predominated in 7, 15, and 11 respiratory seasons,
respectively. There were 11 seasons in which more than 1 virus type or subtype
predominated. The average number of months in which at least 10% of specimens
tested positive for influenza during each respiratory season was 2.8 months
(range, 0-4 months).
Annual Trends in Primary Hospital Discharge Diagnoses
During the study period, there were annual averages of 1 097 564
primary and 1 681 449 any listed pneumonia and influenza hospitalizations
(Table 1). There were annual averages
of 8 843 498 primary and 14 722 488 any listed respiratory
and circulatory hospitalizations. Primary pneumonia and influenza hospitalizations
represented 12.4% of the primary respiratory and circulatory hospitalizations.
The total numbers of primary pneumonia and influenza hospitalizations increased
in a linear fashion from the 1979-1980 through the 2000-2001 respiratory seasons
(Figure 1). The total numbers of
primary respiratory and circulatory hospitalizations decreased from the 1982-1983
through 1990-1991 respiratory seasons but increased from the 1991-1992 through
1999-2000 respiratory seasons.
Annual Estimates of Influenza-Associated Hospitalizations
We estimated annual averages of 94 735 (range, 18 908-193 561)
primary and 133 900 (range, 30 757-271 529) any listed pneumonia
and influenza hospitalizations were associated with influenza viruses in the
United States during the 1979-1980 through 2000-2001 respiratory seasons (Table 2). These influenza-associated hospitalization
estimates represented 8.6% of all primary and 8.0% of any listed pneumonia
and influenza hospitalizations. Similarly, we estimated annual averages of
226 054 (range, 54 523-430 960) primary and 294 128 (range,
86 494-544 909) any listed respiratory and circulatory hospitalizations
were associated with influenza viruses. For the respiratory and circulatory
hospitalizations, these estimates represented 2.6% of all primary and 2.0%
of any listed hospitalizations during the study period.
When we examined the year-to-year variability in influenza-associated
hospitalizations, we noted a substantial increase in hospitalizations during
the 1996-1997 through 1999-2000 influenza seasons, a period when A(H3N2) viruses
predominated. Influenza-associated hospitalizations in the 2000-2001 season
were the lowest since the 1995-1996 influenza season, and this corresponded
with circulation of A(H1N1) viruses.
A summary of the numbers and rates of influenza-associated hospitalizations
by discharge diagnosis and age group are presented in Table 3. Among children younger than 5 years, we estimated annual
averages of 3454 (18.5 hospitalizations per 100 000 person-years) primary
and 4916 (26.3 hospitalizations per 100 000 person-years) any listed
pneumonia and influenza hospitalizations. For the same age group, we estimated
20 031 (107.9 hospitalizations per 100 000 person-years) primary
and 21 156 (113.9 hospitalizations per 100 000 person-years) any
listed respiratory and circulatory hospitalizations. Persons aged 5 through
49 years had the lowest rates of influenza-associated hospitalizations. Influenza-associated
hospitalization rates increased dramatically with age. For example, among
persons aged 85 years and older, we estimated annual averages of 21 788
(628.6 hospitalizations per 100 000 person-years) primary and 26 988
(777.3 hospitalizations per 100 000 person-years) any listed pneumonia
and influenza hospitalizations. In this age group, we estimated annual averages
of 40 813 (1194.9 hospitalizations per 100 000 person-years) primary
and 57 350 (1669.2 hospitalizations per 100 000 person-years) any
listed respiratory and circulatory influenza-associated hospitalizations.
Influenza-Associated Hospitalizations by Predominant Influenza Type
and Subtype
In seasons during which A(H1N1) viruses predominated, 22.6 primary pneumonia
and influenza and 55.9 primary respiratory and circulatory hospitalizations
per 100 000 person-years were associated with influenza virus circulation.
For B viruses, we estimated 37.7 and 81.4 influenza-associated hospitalizations
per 100 000 person-years for primary pneumonia and influenza and primary
respiratory and circulatory hospitalizations, respectively. A(H3N2) viruses
were associated with the highest annual rates of influenza-associated hospitalizations.
During seasons in which A(H3N2) viruses predominated, there were 43.5 primary
pneumonia and influenza and 99.0 primary respiratory and circulatory hospitalizations
per 100 000 person-years associated with influenza viruses.
Age-Specific Trends in Influenza-Associated Hospitalization Rates
Influenza-associated hospitalization rates increased annually during
the study period among persons aged 50 through 64 years, 65 through 69 years,
70 through 74 years, 75 through 79 years, 80 through 84 years, and 85 years
and older (P<.01 for each trend). After controlling
for the length of the influenza season, a significant increase in the rates
over time was still found among persons aged 65 through 69 years, 70 through
74 years, 75 through 79 years, 80 through 84 years, and 85 years and older
(P<.05 for each trend).
Significant increases in influenza-associated hospitalization rates
for respiratory and circulatory hospitalizations were found among persons
younger than 5 years and those aged 65 through 69 years, 70 through 74 years,
75 through 79 years, 80 through 84 years, and 85 years and older (P<.05 for each trend). However, after controlling for the length
of the influenza season, there were no significant increases in trends over
time.
Length of Hospital Stay by Age Group and Diagnosis
Length of hospital stay varied by diagnosis and age group (Table 4). The median length of stay for
primary pneumonia and influenza hospitalizations increased with age. The median
length of stay was 3 days for those younger than 5 years; 4 days for those
aged 5 through 49 years; 6 days for those aged 50 through 64, 65 through 69,
and 70 through 74 years; and 7 days for those aged 75 through 79, 80 through
84, and 85 years and older. The median length of stay for primary respiratory
and circulatory hospitalizations was 3 days for those younger than 5 years
and those aged 5 through 49 years; 4 days for those aged 50 through 64 years;
5 days for those aged 65 through 69, 70 through 74, and 75 through 79 years;
6 days for those aged 80 through 84 years and those 85 years and older.
We used monthly influenza surveillance data and nationally representative
hospital discharge data to estimate influenza-associated hospitalizations
in the United States by discharge category, discharge type, and age group.
We found that the numbers and rates of influenza-associated hospitalizations
generally increased during the study period.
Our results are consistent with our recent mortality analyses, which
found substantial increases in influenza-associated mortality among persons
65 years and older during the 1990s.21 We postulate
that these increases in influenza-associated hospitalizations and deaths were
due to several factors, including the aging of the population, the predominance
of A(H3N2) viruses in many recent seasons, and the general trend for influenza
viruses to circulate or to be detected for longer periods in respiratory seasons
during the 1990s.
Using the nationally representative estimates of influenza-associated
hospitalizations from this study and of deaths from our mortality study,21 we can estimate relative risks (RRs) describing the
risk of an influenza-associated hospitalization compared with the risk of
an influenza-associated death. For example, among children younger than 5
years, the RR for an influenza-associated hospitalization relative to death
is 270; while among persons aged 50 through 64 years, the RR is 11. Young
children are at much greater risk for an influenza-associated hospitalization
compared with an influenza-associated death; this difference greatly diminishes
with increasing age. These results will be useful for national cost-effectiveness
and policy analyses which assess the pros and cons of alternative vaccination
strategies to reduce the morbidity and mortality from influenza, including
vaccinating all children or universal immunization.
An important implication of our results is that the use of primary pneumonia
and influenza discharges to estimate influenza-associated hospitalizations
does not fully capture the total effect of influenza virus activity on morbidity
in the United States. Our estimates of any listed respiratory and circulatory
hospitalizations were about 3 times as high as our estimates of primary pneumonia
and influenza hospitalizations. Other studies also suggest that influenza
virus activity is associated with an increase in hospitalizations for a broad
range of cardiopulmonary diagnoses, and not just primary pneumonia and influenza
discharges.11,19
Generally, our estimated annual numbers and rates of influenza-associated
hospitalizations are similar to previous national estimates made using NHDS
data. Barker11 estimated 370 influenza-associated
pneumonia and influenza hospitalizations per 100 000 persons who were
at least 65 years during 5 A(H3N2) seasons in the 1970s while we estimated
281 any listed pneumonia and influenza hospitalizations per 100 000 persons
during the 1979-1980 through 2000-2001 respiratory seasons for this age group.
Barker's estimate for the sum of influenza-associated hospitalizations for
respiratory disease and acute cardiac failure was an annual average of 419
hospitalizations per 100 000 persons who were at least 65 years. We estimated
581 any listed respiratory and circulatory hospitalizations per 100 000
annually, which was slightly higher but would be expected given the continued
aging of this age group.
In the other study that used NHDS data, Simonsen and colleagues13 estimated 49 influenza-associated primary pneumonia
and influenza hospitalizations per 100 000 persons for all ages, while
we estimated 37 hospitalizations per 100 000 person-years for the same
outcome. Comparing the results from these 2 studies during overlapping seasons
(1979-1980 through 1994-1995), the annual estimates of influenza-associated
pneumonia and influenza hospitalizations were highly correlated (r = 0.73, P<.01). Across the entire study
period, Simonsen and colleagues13 estimated
higher rates of primary pneumonia and influenza hospitalizations among persons
younger than 65 years relative to our study (33 vs 13 hospitalizations per
100 000 persons, respectively). Conversely, we estimated higher rates
of primary pneumonia and influenza hospitalizations among persons who were
aged at least 65 years (174 vs 205 per 100 000 persons, respectively).
The difference in rates among those younger than 65 years in the study by
Simonsen et al most likely reflect the increased influenza morbidity found
among younger individuals during the 1968-1969 pandemic period.
The results of this study are also consistent with several studies of
influenza-associated hospitalizations restricted to young children. These
studies found high rates of hospitalizations among both high-risk and healthy
young children.16,33-35 Although
none of these previous studies were nationally representative, the estimated
rates are in general quite similar. For example, for all children younger
than 5 years, Mullooly and Barker12 estimated
1.2 hospitalizations per 1000 person-years, Neuzil and colleagues16 estimated 2.6 hospitalizations per 1000 person-years
among healthy children, and Izurieta and colleagues35 estimated
0.9 hospitalizations per 1000 person-years among healthy children. In our
study, we estimated an annual average of 1.1 hospitalizations per 1000 person-years
among all children younger than 5 years, which also compares favorably with
a recent study that found a laboratory-confirmed influenza hospitalization
rate of 0.6 per 1000 among children younger than 5 years during a single mild
influenza season.36
This study has several limitations. Because NHDS data do not include
previous health information, it was not possible to determine which individuals
were at risk for influenza complications due to underlying conditions (eg,
asthma, heart disease, etc) or to control for changes in the prevalence of
these conditions over time. Nor was it possible to identify individuals who
had received influenza vaccine prior to the respiratory season in which the
individual was hospitalized in order to assess vaccine effectiveness. Although
our influenza mortality estimates were made using similar methods and weekly
death data, in this study we were limited to making hospitalization estimates
using monthly hospital discharge data. Use of weekly hospitalization and influenza
circulation information would have permitted fluctuations in both data sources
to be more closely associated and would have provided more precise estimates
of influenza-associated hospitalizations. We were also not able to control
for the circulation of respiratory syncytial virus, which is known to circulate
at similar times as influenza viruses and is often associated with significant
morbidity and mortality. Finally, we were unable to stratify data further
for children younger than 5 years due to the few numbers of hospitalizations
that occurred for children aged 2 to 4 years. Despite these limitations, our
use of NHDS data provided nationally representative annual estimates of influenza-associated
hospitalizations that can be compared over 2 decades. Smaller data sources
often used to assess influenza vaccine effectiveness cannot offer these advantages.
Currently, we estimate that more than 200 000 respiratory and circulatory
hospitalizations are associated with influenza each year in the United States,
substantially more than estimates of pneumonia and influenza hospitalizations.13 As noted in our report describing influenza-associated
mortality, the aging of the US population is an important contributor to the
increasing numbers of influenza-associated hospitalizations and deaths.21 For example, between 1976 and 2001 the number of
US citizens aged 85 and older had more than doubled.32,37 Based
on US census estimates, the numbers of very elderly people in the United States
will continue to increase and thus we expect that the numbers of influenza-associated
hospitalizations and deaths will likely increase over time. Additional efforts
are needed to ensure that current recommendations for influenza vaccination
for all high-risk individuals, household contacts of high-risk individuals,
healthcare workers, and young children are fully implemented. Recent observational
studies have suggested that influenza vaccination may reduce respiratory and
circulatory hospitalizations substantially, particularly among the elderly.19,38,39 Efforts to vaccinate
older Americans and their contacts annually must continue to be a priority
for immunization programs. Consideration should also be given to other influenza
prevention methods for older Americans given the potential for decreased immune
responsiveness to vaccines in the very elderly.40,41
After the elderly, the second highest rates of influenza-associated
hospitalizations are found in young children. This point was highlighted during
the 2003-2004 A(H3N2)–influenza season, which may have been particularly
severe among children. Through July 2004, data on 152 deaths among children
with laboratory-confirmed influenza virus infection during the last influenza
season has been collected nationally.42 The
Council of State and Territorial Epidemiologists voted in June 2004 to add
deaths of children with evidence of influenza virus infection to its list
of nationally reportable conditions. Clearly, new measures to prevent influenza-associated
morbidity and mortality among young children are needed.
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