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\begin{document}

\title{Underlying cardiopulmonary conditions as a risk factor for influenza and
respiratory syncytial virus infection among community-dwelling adults
aged [?]65 years in Thailand: Findings from a two-year prospective cohort
study}



\author[1]{Prabda Praphasiri}%
\author[2]{Manash Shrestha}%
\author[3]{Jayanton  Patumanond}%
\author[4]{Sutthichai  Nakphook}%
\author[5]{Sutthinan  Chawalchitiporn}%
\author[6]{Darunee Ditsungnoen}%
\author[7]{Fatimah Dawood}%
\author[8]{Joshua Mott}%
\author[5]{Kriengkrai Prasert}%
\affil[1]{Thailand MOPH–US CDC Collaboration}%
\affil[2]{Mahidol University}%
\affil[3]{Chiang Mai University}%
\affil[4]{Institute of Preventive Medicine, Department of Disease Control, Ministry of Public Health}%
\affil[5]{Nakhon Phanom Provincial Hospital}%
\affil[6]{Thailand Ministry of Public Health – U.S. Centers for Disease Control and Prevention Collaboration}%
\affil[7]{Centres for Disease Control and Prevention}%
\affil[8]{CDC}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: Adults with cardiopulmonary conditions are at increased risk
for complications from influenza and respiratory syncytial virus (RSV)
infection, but few data are available from middle-income countries.
Methods: Using data from a prospective cohort study of influenza vaccine
effectiveness among community-dwelling Thai adults aged [?]65 years, we
estimated and compared the incidence of influenza and RSV in those with
and without cardiopulmonary conditions. During May 2015-May 2017, older
adults in a rural province in Thailand were followed weekly with
year-round surveillance for acute respiratory illness (ARI), defined
broadly as new onset or worsening of cough with or without fever, and
hospitalized ARI. When ill, nasal self-swabs and/or nasopharyngeal swabs
were collected for reverse-transcription polymerase chain reaction
testing. We used Poisson regression to calculate incidence rate ratios
(IRR), adjusting for age, sex, past healthcare-seeking behavior, weekly
influenza activity, and influenza vaccination. Results: Overall, 3,220
adults with a median age of 71 years (IQR 68-76) were enrolled; 1,324
(41.1\%) were male; and 313 (9.7\%) had [?]1 underlying cardio-pulmonary
condition, most commonly chronic obstructive pulmonary disease (131;
41.2\%) or asthma (73; 23.3\%). Compared to those without, participants
with cardiopulmonary conditions had higher incidences of ARI, influenza,
and RSV (Adjusted IRR: 1.83, 95\% CI 1.63-2.05; 1.84, 95\% CI 1.05-3.23;
2.02, 95\% CI 1.10-3.72, respectively). Conclusion: Our findings show
that older adults in rural Thailand with cardiopulmonary conditions have
increased rates of ARI, influenza, and RSV infections, and support
efforts to ensure this population has access to influenza vaccines and
other respiratory illness prevention measures.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

Influenza and respiratory syncytial virus (RSV) are respiratory
pathogens that cause a substantial disease burden among adults aged 65
years and above {[}1{]}. Global estimates suggest that around two-thirds
of all seasonal influenza-related mortality occurs among older adults
with more than 260,000 deaths annually {[}2{]}. Data from developed
countries show that respiratory illnesses due to RSV among older adults
may exceed one million episodes and cause around 14,000 in-hospital
deaths every year {[}3{]}. Older adults with cardiopulmonary conditions
are at increased risk for severe illness due to influenza and RSV
infection {[}4, 5{]}. However, it is not fully established whether
cardiopulmonary conditions present an increased risk for influenza and
RSV infections, and there are little data on the burden of infection
from these pathogens among persons with cardiopulmonary conditions in
middle-income countries.

Thailand is an upper-middle-income country in tropical Southeast Asia,
where recognition of influenza and RSV disease burden is growing. Since
2008, adults aged [?]65 years and those with chronic diseases have been
recommended for annual influenza vaccination by the Thai Ministry of
Public Health (MoPH) {[}6{]}. Nonetheless, influenza vaccine uptake
among older adults is still less than 20\% (Bureau of General
Communicable Diseases, Thailand MoPH). Studies among hospitalized
patients suggest that the prevalence of RSV-associated respiratory
illnesses in Thailand is around 2-9\% among older adults {[}7-11{]}.
However, reliable estimates of the infection rates in the community
remain limited. Using data from a longitudinal prospective cohort study
of influenza vaccine effectiveness among rural community-dwelling Thai
adults aged [?]65 years {[}12{]}, we compared the incidence of influenza
and RSV in those with and without cardiopulmonary conditions.

\textbf{METHODS}

\textbf{Study design}

Details of this study have been described previously {[}12{]}. In brief,
a prospective cohort of 3500 adults aged [?]65 years was recruited by
systematic random sampling in two districts of Nakhon Phanom province,
Thailand from May 2015 and followed for two years until May 2017. Prior
to the start of the study, a targeted campaign was organized in the
study sites by the Thai MoPH to enhance influenza vaccine uptake among
older adults through mobile clinics and increased vaccine supply
{[}13{]}. Individuals were not eligible to participate in the cohort if
they resided in a long term care facility, did not reside in the
community for at least a year, were unable to communicate with study
staff, were unable/unwilling to provide nasal self-swabs, or had an
acute medical condition or tumor in or near the nose that would preclude
nasal swab collection. Trained health volunteers collected baseline data
and followed the participants with weekly telephone surveillance for
acute respiratory illness (ARI). Participants were asked to self-collect
anterior nasal swabs with each ARI episode as previously validated
{[}14{]}. For participants who visited health centers/hospitals for
their illnesses, nasopharyngeal swabs were collected by research nurses
on site. The number of hospital visits of the participants (for ARI or
other reasons) during the study years were obtained from the district
and provincial hospital records.

\textbf{Definitions}

Acute respiratory illness (ARI) was defined as a new onset of cough or
worsening of a chronic cough. Severe ARI (SARI) was defined as an
illness requiring hospitalization with measured axillary temperature
[?]38\selectlanguage{ngerman}°C plus a new onset of a cough, worsening of a chronic cough, or
difficulty in breathing. Cardiopulmonary condition was defined as the
presence of any known physician-diagnosed chronic cardiovascular
conditions (such as coronary artery diseases, cardiac arrhythmias,
valvular heart diseases, cardiomyopathy) and/or any chronic lung
diseases (such as chronic obstructive pulmonary disease (COPD), asthma,
chronic bronchitis, pulmonary tuberculosis, emphysema, and lung
fibrosis).

\textbf{Specimen collection, storage, laboratory testing}

All respiratory specimens (including participant-collected and
nurse-collected swabs) were transported to refrigerators at sub-district
health centers within 24 hours of collection, kept between 2 -- 8 °C
before being frozen in liquid nitrogen tanks below -70 °C, and sent
weekly to the Thai National Institute of Health (NIH) in Nonthaburi.
Respiratory specimens were tested for influenza viruses and RSV with
real-time reverse-transcription polymerase chain reaction test (rRT-PCR)
according to CDC/WHO protocols {[}15, 16{]}.

\textbf{Data analysis}

We calculated the incidence per 1000 person-years of
laboratory-confirmed influenza and RSV-associated ARI and SARI by
dividing the total episodes by total person-time under observation.
Weeks of intermittent loss to follow up (due to missed swab collection
and/or missed surveillance contacts) were excluded from the person-time
denominator when calculating the incidence rates. Multi-variable Poisson
regression was used to calculate incidence rate ratios (IRR) between
participants with and without any underlying cardiopulmonary conditions,
adjusting for age, sex, influenza vaccination status (participants
receiving influenza vaccine in at least one of the two study years were
considered as vaccinated), weekly influenza activity (influenza
infections detected by weekly NIH surveillance, categorized into
quartiles), and number of hospital visits during the past two years as a
proxy for healthcare seeking behavior. All data analyses were conducted
using STATA software version 14.2 (StataCorp LP, College Station, TX,
USA).

\textbf{Ethical considerations}

Written informed consent was obtained from all participants and the
study was approved by the Ethical Review Committee, Department of
Disease Control, MoPH (Nonthaburi, Thailand). The US Centers for Disease
Control and Prevention (Atlanta, Georgia) relied on this committee for
ethical approval.

\textbf{RESULTS}

\textbf{Participant Characteristics}

Of 3,500 participants screened, 3,287 were eligible, and 3,220 adults
were enrolled in the study. The participants had a median age of 71
years (interquartile range {[}IQR{]} 68-76) and 1,324 (41\%) were male
(Table 1). The proportion of cohort participants that were vaccinated
for influenza was 52\% (1,666/3,220) in 2015 and 48\% (1,498/3,123) in
2016. In total, 313 (9.7\%) had one or more underlying cardiopulmonary
condition, most commonly COPD (131; 41.2\%), asthma (73; 23.3\%), or
chronic bronchitis (68; 21.7\%) (Table 2). The participants with
cardiopulmonary conditions were more likely to be older, male, have more
other co-morbidities, and have a higher number of hospital visits than
those without cardiopulmonary conditions (Table 1).

The participants were followed-up for a total 316,690 person-weeks
(29,005 person-weeks for participants with cardiopulmonary conditions
and 287,685 person-weeks for participants without cardiopulmonary
conditions). During the two-year follow-up, two participants withdrew
and 200 (6.2\%) died. Overall, 2365 ARI/SARI episodes (2296 ARI and 69
SARI) were reported in the cohort of which 2362 (99.8\%) respiratory
swabs were collected (1969 nasal self-swabs and 393 nasopharyngeal swabs
by research nurses).

\textbf{Incidence of influenza and RSV}

Influenza A(H3N2) was the predominant circulating influenza virus in
both years. The median time from symptom onset to collection of nasal
swabs was 1 day (IQR 1--2) and nasopharyngeal swabs was 2 days (IQR
1-3), which were not different among participants with or without
cardiopulmonary conditions (p-values 0.589 and 0.746, respectively).
Overall, 105 (3.3\%) cohort participants had an influenza virus
infection (influenza A(H1N1)=17; A(H3N2)=74; B=14) and 81 (2.5\%) had an
RSV infection. Laboratory-confirmed influenza infections were detected
most in the first year in September (18.4\%), followed by October in the
second year (12.2\%); most RSV infections were detected during August to
October in the second year, with the peak in September at 22.0\% (Figure
1).

Participants with cardiopulmonary conditions had a higher incidence of
ARI (645/1000 person-years vs 350/1000 person-years, p\textless{}0.001)
and SARI (87.8/1000 vs 3.6/1000, p\textless{}0.001) than those without.
Adjusted IRR for laboratory-confirmed RSV, all influenza, influenza A,
and influenza B viruses were 2.02 (95\% confidence interval {[}CI{]}
1.10-3.72), 1.84 (95\% CI 1.05-3.23), 1.83 (95\% CI 1.00-3.34), and 1.96
(95\% CI 0.42-9.21), respectively (Table 3).

\textbf{DISCUSSION}

Among a two-year prospective cohort study of \textgreater{}3,000
community dwelling adults in Thailand, around 10\% of participants had
underlying cardiopulmonary conditions and cardiopulmonary conditions
conferred increased rates of all-cause ARI, influenza A and RSV
infections. These findings provide additional support for influenza
vaccination recommendations for persons with underlying cardiopulmonary
conditions and add to the limited body of evidence about influenza and
RSV disease burden among older adults in middle-income countries.

The seasonality of influenza and RSV was similar to the pattern
identified in past studies in which the infections peaked during the
rainy months of June to October {[}10, 17, 18{]}. Incidences of
influenza and RSV are higher in our study than previous studies {[}7, 8,
10{]}. This may be partly due to a more sensitive case definition of
ARI. Since many older adults with influenza and RSV can present without
fever, we used a definition of ARI without any body temperature criteria
{[}12{]}. This might have resulted in the inclusion of more illness
episodes with laboratory confirmation than in the past studies which
required either fever or hypothermia (\textless{}35.5 °C) to trigger
swab collection. Moreover, previous studies primarily assessed
hospitalized patients and may not have fully accounted for non-medically
attended cases in the community, even after adjustments in their
analyses {[}7, 8{]}. In our study, more than 80\% of the respiratory
specimens were nasal self-swabs collected by the participants at their
homes and only a small proportion of ARI were severe enough to warrant
hospitalization, signifying a majority of non-medically attended cases
in the community.

Cardiopulmonary conditions are recognized risk factors for severe
outcomes of influenza and RSV infections, especially among older adults
{[}4, 5{]}. Prior studies have demonstrated that a disproportionate
number of hospitalizations for influenza and RSV occur in patients with
cardiopulmonary conditions, particularly COPD {[}9, 10, 18{]}. Our
findings suggest that these conditions may themselves be predisposing
risk factors for acquisition of influenza and RSV infections in the
community, possibly by affecting immunoregulatory functions in older
adults {[}19{]}. Our findings are consistent with evidence from Western
countries that documents higher detection of RSV among older adults with
underlying cardiopulmonary diseases compared to those without these
conditions {[}19, 20{]}.

There are some limitations to our study. First, we ascertained
cardiopulmonary conditions by participant report alone which may be
susceptible to some recall and measurement bias. Second, we did not
collect data about exposure to children, household crowding,
socioeconomic status, and baseline influenza and RSV antibody titers
which may be confounders in the relationship between cardiopulmonary
conditions and acquisition/transmission of influenza virus and RSV
infection {[}19{]}. Third, a previous analysis comparing
participant-collected nasal swabs to nurse-collected nasopharyngeal
swabs among older adults in Thailand found that participant-collected
nasal swabs were only 78\% sensitive for detection of influenza viruses
{[}14{]}. Therefore, our calculation of influenza and RSV incidence may
be underestimated. Nevertheless, the strengths of this research lie in
the population-based multiple-year prospective cohort study design with
a large sample size, use of a broad case definition of ARI, capture of
non-medically attended ARI, active weekly follow-up of participants, and
laboratory-confirmation of the infection outcomes.

In conclusion, incidences of influenza and RSV were high among
community-dwelling older Thai adults aged \emph{\textgreater{}} 65 years
in this study, and cardiopulmonary conditions conferred additional risk
for acquisition of influenza and RSV infections. Despite efforts to
enhance influenza vaccine uptake among this cohort as part of the study
design, only half of participants received influenza vaccines during
each of the study years. More efforts are needed to ensure adults
aged\emph{\textgreater{}} 65 years, especially those with
cardiopulmonary conditions, have access to influenza vaccines and other
prevention measures as effective vaccines against RSV are not currently
available.

\textbf{Notes}

Funding

This research was supported by US Centers for Disease Control and
Prevention and awarded to the Ministry of Public Health, Thailand in
cooperative agreement 5-U01GH000152.

Disclaimer

The findings and conclusions in this report are those of the authors and
do not necessarily represent the views of the Centers for Disease
Control and Prevention.

Conflict of interest

The authors declare that they have no personal or financial relationship
that could lead to a conflict of interest.

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12. Prasert K, Patumanond J, Praphasiri P, et al. Effectiveness of
trivalent inactivated influenza vaccine among community-dwelling older
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13. Praphasiri P, Ditsungnoen D, Sirilak S, et al. Predictors of
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ONE\textbf{2017} ; 12(11): e0188422.

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Table 1. Participant characteristics in a population-based cohort study,
Nakhon Phanom Province, Thailand, May 2015 -- May 2017\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Cohort participants\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Cohort participants\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
p-value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Without cardiopulmonary conditions (n=2,907) n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
With cardiopulmonary conditions (n=313) n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Total person-years}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5532\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
558\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Age (years), median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
72 (69, 76)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
73 (70, 78)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.003\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Age group\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textless{}75 years\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1,925 (66.2)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
190 (60.7)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.052\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
[?]75 years\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
982 (33.8)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
123 (39.3)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1,157 (39.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
167 (53.4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Influenza vaccination uptake\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2015 -- 2016\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1,497 (51.5)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
169 (54.0)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.405\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2016 -- 2017\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1,347 (47.5)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
151 (53.0)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.082\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Co-morbidity\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1,163 (40.0)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
156 (49.8)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
670 (23.1)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
85 (27.2)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.107\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
543 (18.7)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
62 (19.8)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.648\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Neuromuscular diseases\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
83 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
14 (4.5)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.117\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Chronic kidney diseases\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
79 (2.7)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
11 (3.5)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.370\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Cerebrovascular diseases\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
74 (2.6)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
11 (3.5)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.350\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Chronic liver diseases\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
13 (0.5)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
3 (1.0)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.199\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Thalassemia\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
4 (0.1)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
6 (1.9)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Cancer\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
81 (2.8)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
17 (5.4)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.015\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Chemotherapy\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
10 (0.3)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2 (0.6)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.328\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Mean number of hospital visits (SD)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.8 (1.6)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3.5 (1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{Abbreviations: IQR, interquartile range; n, number.}

Table 2. Cardiopulmonary conditions among participants in a
population-based cohort study, Nakhon Phanom Province, Thailand, May
2015 -- May 2017\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{Cardiopulmonary condition\textsuperscript{a}}\strut
\end{minipage} & \begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{Total=313}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\textbf{n (\%)}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
1. Cardiovascular diseases\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Coronary artery diseases\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
48 (15.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Cardiac arrythmias\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
27 (8.6)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Heart valve diseases\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
10 (3.2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Cardiomyopathy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3 (1.0)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2. Chronic lung diseases\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Chronic obstructive pulmonary disease\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
131 (41.2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Asthma\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
73 (23.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Chronic bronchitis\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
68 (21.7)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Pulmonary tuberculosis\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
39 (12.5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Emphysema\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1 (0.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Lung fibrosis\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1 (0.3)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{\textsuperscript{a}Each participant could have more than one
cardiopulmonary condition}

Table 3. Incidence rate ratio of Respiratory Syncytial Virus, Influenza
A and B among participants with or without cardiopulmonary conditions\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Participants without CPC}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Participants without CPC}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Participants with CPC}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Participants with CPC}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Crude IRR} \textbf{(95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Adjusted IRR\textsuperscript{d}} \textbf{(95\% CI)}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
No. of person\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2,907\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2,907\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
313\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
313\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Person-years\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
5,532\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
5,532\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
558\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
558\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Endpoints\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No.\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Rate\textsuperscript{a} (95\% CI)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No.\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Rate \textsuperscript{a} (95\% CI)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
ARI\textsuperscript{b}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1,936\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
350 (337, 363)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
360\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
645 (604, 685)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.84 (1.64, 2.07)*\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.83 (1.63, 2.05)*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
SARI\textsuperscript{c}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.6 (2.2, 5.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
49\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
87.8 (65.7, 114.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
24.30 (14.18, 43.16)*\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
24.67 (14.11, 43.16)*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
RSV infection\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
68\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12.3 (9.6, 15.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23.2 (12.5, 39.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.90 (0.96, 3.46)*\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.02 (1.10, 3.72)*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Influenza\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
90\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16.3 (13.1, 20.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
26.9 (15.1, 44.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.65 (0.89,2.87)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.84 (1.05, 3.23)*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Influenza A\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
78\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14.1 (9.9, 16.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23.3 (12.5, 39.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.65 (0.84, 2.99)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.83 (1.00, 3.34)*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Influenza B\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.2 (1.1, 3.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.6 (0.4, 12.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.65 (0.18, 7.43)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.96 (0.42, 9.21)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{Abbreviations: ARI, acute respiratory illness; CI, confidence
interval; CPC, cardiopulmonary conditions; IRR, incidence rate ratio;
No., Number; RSV, Respiratory syncytial virus; SARI, severe acute
respiratory illness.}

\emph{\textsuperscript{a} Incidence rate / 1,000 person-years.}

\emph{\textsuperscript{b} ARI defined as a new onset of cough or
worsening of chronic cough, with or without fever.}

\emph{\textsuperscript{c} SARI defined as new onset of cough, worsening
of chronic cough or difficulty breathing with a fever [?]38.0°C that
required hospitalization.}\selectlanguage{ngerman}

\emph{\textsuperscript{d} Poisson regression analysis adjusted for age,
sex, influenza vaccination, weekly influenza activity, and number of
hospital visits.}

\emph{*Statistically significant at p-value \textless{}0.05.}

\textbf{Figure legend:}

Figure 1. Number of laboratory-confirmed influenza and RSV infection and
proportion of positive cases by month among older adults aged \selectlanguage{english}[?]65 years
in population-based cohort study, Nakhon Phanom province, Thailand, May
2015 -- May 2017

\selectlanguage{english}
\FloatBarrier
\end{document}

