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Severity Assessment of Lower Respiratory Tract Infection in Elderly Patients in Primary Care
Yrjö Seppä, MD;
Aini Bloigu, BSc;
Pekka O. Honkanen, MD, PhD;
Liisa Miettinen, MD;
Hannu Syrjälä, MD, PhD
Arch Intern Med. 2001;161:2709-2713.
ABSTRACT
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Background Simple markers for evaluating the severity of lower respiratory tract
infections (LRTI) in primary care are lacking. It is of value to examine whether
the information available to the primary care physician during a patient's
initial visit can be used to assess the severity of LRTI.
Methods The associations between different baseline variables and outcomes (survival
within or more than 30 days) were investigated prospectively in a series of
950 home-living patients 65 years or older with severe LRTI that their primary
care physicians suspected to be pneumonia.
Results Twenty-one men and 17 women died (4.1%) within 30 days. According to
univariate analysis, the following parameters differed (P<.01) between the fatalities and survivors: acute aggravation of
a coexisting illness, age, respiratory rate, white blood cell count, and C-reactive
protein (CRP) level. According to Cox forward stepwise regression analysis
(P = .01 for entry and .05 for removal), acute aggravation
of a concurrent illness, respiratory rate ( 25/min), and CRP concentration
(100 mg/L) were independently associated with death. The mortality rate
was 2.2% if the patients had none or only 1 of the independent risk factors
and 20% if they had all 3 risk factors.
Conclusions Preceding aggravation of a concurrent illness and respiratory rate of
25/min or higher, together with an elevated serum CRP level (100 mg/L),
can be used as simple markers for identifying patients with the highest risk
for LRTI and improve management decisions among elderly people in primary
care.
INTRODUCTION
LOWER RESPIRATORY tract infections (LRTI) include infections of the
tracheobronchial tree (bronchitis) and the lung parenchyma (pneumonia). It
has been estimated, based on the data published from the United Kingdom, that
a third of the adult patients with LRTI in community settings seek help for
their symptoms. Antibiotic agents are prescribed to a fourth of these patients,
and community-acquired pneumonia (CAP) is diagnosed in less than 2% of the
cases (less than 0.5% of the whole adult population with LRTI in community
settings).1 However, the incidence of CAP is
higher than this in the elderly population.2-3
Community-acquired pneumonia is the fifth most common reason for hospitalization
among patients aged 65 to 74 years and the leading cause for hospitalization
among those 85 years or older.4 The cost of
treating CAP depends crucially on the place of treatment.5
Safe strategies to minimize hospitalization would lead to marked cost savings.6 Moreover, most patients with CAP with little risk
of death prefer treatment outside the hospital,7
and, presently, most patients with CAP are actually treated as outpatients.1, 8 Several models have been developed
for assessing the severity of CAP.9-18
However, these models have been typically developed among hospitalized patients
with CAP and are not necessarily applicable to outpatients with CAP or, more
generally, to patients with LRTI in primary care because the scoring systems
in the models often require both chest radiography and laboratory analyses,
which are not necessarily available in primary care units.
The purpose of our prospective study was to find out whether the information
available in the primary care consulting office can be used to assess the
severity of LRTI and the need for hospital treatment. Toward this end, we
investigated the outcomes of 950 home-living immunocompetent elderly patients
(age, 65 years) with LRTI who had signs suggestive of pneumonia.
PATIENTS AND METHODS
PATIENTS
The study was carried out in association with a pneumococcal and influenza
trial among persons 65 years or older in northern Finland.19
During September and October 1992, before the baseline of the study, one of
the researchers (P.O.H.) visited all the municipal health centers and municipal
district hospitals in the follow-up area to inform the physicians about the
research design and the way of reporting patients with LRTI. The follow-up
visits to the participating centers were made in the autumns of 1993 and 1994.
The study population consisted of all persons 65 years or older living in
55 municipalities in northern Finland. The census on December 31, 1992, included
59 790 people, 38.8% of whom were male. The study protocol was approved
by the ethical review committee of the medical faculty of the University of
Oulu, Oulu, Finland. Enrollment in the follow-up study was voluntary. The
physician made the diagnosis of LRTI on the basis of the patient's history
and physical examination findings. During the whole study period, the primary
care physicians made their decisions concerning the prescription of antibiotics
and the possible referral of their patients independently.
METHODS
During the 2-year study period, 1743 cases of LRTI with signs suggestive
of pneumonia were reported among the study population of 59 790 persons
65 years or older. The number of patients visiting health centers with signs
suggestive of pneumonia is not known, nor is the proportion of patients with
LRTI but without signs suggestive of pneumonia. Of the cases, 22 were excluded:
21 because of missing information on the day of the initial visit and 1 because
of age (<60 years). One episode of suspected LRTI per patient was reported
in 1424 cases. Only the first episode was included in the study for 133 patients
with more than 1 episode of LRTI. Only home-living patients were included
in the further analysis (1072 cases). Patients reported to be in a terminal
state (10 cases) or with dementia (89 cases) were excluded because our questionnaire
did not include information about whether their treatment was active or not.
Of the remaining patients, those reported to be bedridden (14 cases) were
excluded because our primary goal was to investigate an elderly population
capable of normal daily activities. Nine patients receiving immunosuppressive
medication (>5 mg/d of cytostatics or prednisolone) were excluded.
The following patient information was recorded on the case report form
by the attending physician to describe the patient's condition during the
first visit: presence or absence of respiratory and other symptoms (cough,
dyspnea at rest, pleuritic chest pain, acute confusion, acute deterioration
of general condition, and/or acute aggravation of a coexisting chronic disease
[eg, the impairment of glucose balance in diabetes or the deterioration of
congestive heart failure]); duration of symptoms; date of examination; residential
information (home, nursing home, municipal health center, or hospital ward);
initial place of treatment (home, nursing home, municipal health center ward,
or hospital ward); results of the initial physical examination (body temperature,
respiratory rate, systolic and diastolic blood pressure, heart rate, and abnormal
finding on chest auscultation, ie, rales); and whether the patient was in
a terminal state. The patient data were complemented during the follow-up
visit (or after death, if the patient died before the scheduled follow-up
visit) with the basic laboratory data recorded at the initial visit: hemoglobin
and C-reactive protein (CRP) levels; platelet and white blood cell (WBC) counts;
erythrocyte sedimentation rate; concurrent illnesses or disabilities (eg,
congestive heart failure, asthma, chronic obstructive pulmonary disease, dementia,
chronic pyelonephritis, and/or type of diabetes); residence on a long-term
ward; bedridden state; immunosuppressive treatment (ie, >5 mg/d of cytostatic
medication or prednisolone); previous and current smoking habits; consumption
of alcohol; information about possible travel abroad within the past month;
final diagnosis; and, in fatal cases, whether the death was due to LRTI. To
obtain valid and accurate information on the date of death and to confirm
the registered coexisting illnesses, data concerning the study population
were also drawn from the national register of the Finnish Social Insurance
Institution, Kela. Information on dementia, dietary diabetes, alcohol abuse,
and bedridden and terminal state was not available in the national register
and was therefore obtained by a questionnaire. All data were stored in a computer
database.
STATISTICAL ANALYSIS
The end point of the severity of LRTI was defined as mortality due to
LRTI within 30 days after the first visit to a primary care physician.16 The statistical analysis was performed using the
SPSS software (SPSS Inc, Chicago, Ill). Survival after the initial visit was
calculated with the Kaplan-Meier method. For the analysis of categorical variables,
the  2 test (or the Fisher 2-tailed exact test when appropriate)
was used. The continuous variables were skewed, and median values and interquartile
ranges (25th to 75th percentile) were therefore used. The association between
the continuous variables and survival was analyzed using the Mann-Whitney
test. For further analysis, the statistically significant continuous variables
were dichotomized by selecting clinically relevant cutoff points. To identify
the independent risk factors among the variables that showed statistically
significant associations (P<.01) with mortality
in univariate analyses, the relative risk of death was estimated using hazard
ratios calculated by Cox forward stepwise regression analysis. The P value for entry into the model was .01 and for removal, .05. The
patients having none or only 1 missing value of predictor variables were included
for Cox regression analysis, and missing data were replaced by the geometric
means of the study population: 51 mg/L for CRP level, 22/min for respiratory
rate, and 9.3 x 103/µL for WBC count.
RESULTS
PATIENT POPULATION AND MORTALITY
The final study population consisted of 950 home-living elderly patients
with LRTI, 38 (4.1%) of whom died within 30 days after the initial visit.
Of these deaths, 37% occurred within the first 7 days (Figure 1). Their deaths were not dependent on the initial place
of treatment (Table 1). The mortality
rates were similar for both sexes (Table
2). In this population with LRTI, dyspnea at rest tended to be more
often observed in the patients who died within 30 days (63%) than in those
who survived (48%) (P = .07; Table 2), while the presence of rales did not statistically differ
between the groups (81% vs 85%). Most of our patients with LRTI actually had
real pneumonia; 83% of them had rales on chest auscultation, and 48% had dyspnea
at rest during the first visit to a primary care physician. Moreover, results
of a retrospective analysis of the chest roentgenograms (CRXs) showed definite
pneumonia in 61% and probable pneumonia in 13%. However, we excluded the CRX
findings from this study to mimic the real conditions because CRX was only
available in 44% of the cases at the time of the first visit to a primary
care physician in our series.
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Survival after the initial visit among 950 home-living elderly patients
with lower respiratory tract infection in primary care during 30 days (note
the scale on the y-axis).
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Table 1. Initial Place of Treatment and Mortality Within 30 Days Among
Home-Living Elderly Patients With Lower Respiratory Tract Infections*
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Table 2. Essential Clinical Data of Home-Living Elderly Patients Seeking
Care From Primary Care Physicians for Lower Respiratory Tract Infection
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SIGNIFICANT VARIABLES ASSOCIATED WITH MORTALITY
Of the categorical variables, only acute aggravation of a coexisting
illness had a statistically significant association with survival (Table 2). However, the comorbidity was
not associated with mortality in univariate analysis (data not shown). Of
the continuous variables, the patient's age, respiratory rate, WBC count,
and CRP values were statistically associated with death within 30 days (Table 3). When the importance of these
variables was evaluated in the Cox forward stepwise regression model that
included 719 cases, acute aggravation of a coexisting illness, respiratory
rate (25/min), and CRP level (100 mg/L) were identified (in this order
of magnitude of hazard ratios) as independent relative risk factors of death
within 30 days (Table 4). The
mortality rate of these patients with LRTI was 2.2% within 30 days if they
had none or only 1 independent risk factor. The corresponding mortality rate
was 20% if they had all 3 risk factors.
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Table 3. Clinical and Laboratory Findings of Home-Living Elderly Patients
With Symptomatic Lower Respiratory Tract Infection
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Table 4. Cox Forward Stepwise Regression Analysis of Independent Risk
Factors
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COMMENT
In this study, 2 parameters immediately available in the consulting
office (preceding aggravation of a coexisting illness and respiratory rate
of 25/min) together with an elevated serum CRP level (100 mg/L) at
the initial visit to a primary care unit, were independently associated with
the risk of death within 30 days among elderly patients with LRTI and can
be used to assess the severity of LRTI.
As our results show, in most of the patients with LRTI in whom the attending
physicians had primarily suspected to have pneumonia, the diagnosis of CAP
was later verified by CXR. Thus, a comparison of our results with earlier
reports concerning mainly CAP seemed justifiable.
It is well known that elderly patients may lack the typical symptoms
of pneumonia; the earliest clues may be unspecific symptoms, such as lethargy,
mental confusion, and "failure to thrive," as well as the deterioration of
a preexisting disease (eg, congestive heart failure).20
In our series, acute aggravation of a coexisting illness, such as the impairment
of glucose balance in diabetes or the deterioration of congestive heart failure,
was independently associated with mortality within 30 days. This acute aggravation
of a chronic illness was judged by the criteria of the attending physicians.
The measurement of respiratory rate is a useful marker of acute respiratory
dysfunction.21 Its prognostic importance in
CAP has been shown in several investigations.9-12,14-16,18
The cutoff value of respiratory rate has varied from 20/min or higher22 to 30/min or higher.9-12,14-16,18
In our study, tachypnea (with respiratory rates of 25/min used as a cutoff
point) remained a significant predictor of mortality even in multivariate
analysis. Our results stress once again the importance of respiratory rate—a
simple measurement—in the clinical assessment of respiratory infections.
On the other hand, heart rate, systolic and diastolic blood pressure, and
body temperature, which have previously been reported as important risk factors
associated with death in CAP, did not have similar predictive value in the
present series.
Because CRP level is more sensitive, decreases faster after a favorable
treatment response, and is independent of age, its use as a marker instead
of erythrocyte sedimentation rate has been recommended for the diagnosis and
follow-up of infections.23-24
In adults with acute LRTI, a CRP level of 50 to 75 mg/L has been considered
suggestive of CAP.1, 23 Our results
showed that a CRP level 100 mg/L or higher was independently associated with
mortality in elderly patients with LRTI in primary care. Thus, our study emphasizes
the importance of CRP in assessing the severity of LRTI among elderly patients
in primary care. Our results also suggest that the use of CRP as a marker
is recommendable in the severity assessment of respiratory tract infections.
In our series, the overall rate of mortality of elderly home-living
patients with LRTI within 30 days was 4%, which was lower than the percentage
published in, for example, a recent meta-analysis in which the mortality rate
of elderly hospitalized patients with CAP varied from 5.7% to 32.9%.22 In our primary care population, the mortality rate
was even lower (2%) if the patients had no or only 1 of the independent risk
factors associated with mortality. However, the mortality rate was 20% among
our patients with 3 positive risk factors. The latter figure agrees with an
earlier report on mortality (21%) from pneumococcal bacteremia in Finland.25
In earlier studies, controversial observations on the influence of age
on the mortality in CAP have been reported, with some studies supporting its
importance11, 17, 26-27
and others not.28-30
In our series, age was a significant factor in univariate analysis but did
not remain significantly associated with mortality in multivariate analysis.
In many series, comorbidity has been shown to be an independent risk factor
of mortality.16-17,22
No such association was seen in our series. In the earlier studies in which
comorbidity has been recognized as a risk factor, patients with CAP have been
typically treated in the hospital. In earlier studies, leukopenia and leukocytosis
have also been shown to be independent prognostic markers in CAP.9, 11, 18, 22, 27
In our series, WBC count was significantly associated with death in univariate
analysis, but when contrasting the patients with a WBC count of less than
4 x 103/µL or higher than 11 x 103/µL
with those with a WBC count within the normal range, WBC count was no longer
independently associated with death in Cox regression analysis. Whether the
use of cytostatics or steroids could be an independent prognostic variable
even in primary care patients should be investigated in a population with
a larger proportion of patients undergoing such treatments.
Recently, a prognostic model for the evaluation of the severity of CAP
has been described15 and validated in elderly
hospitalized patients with CAP.31 We were unable
to use this prognostic system, however, as some of the laboratory measurements
essential for the calculation of the risk scores of individual patients, such
as arterial blood gas analysis and serum urea nitrogen, were not available
in the consulting offices of our primary care physicians.
We tried to find markers for the assessment of the severity of LRTI
among elderly patients in primary care. These 950 home-living LRTI patients
with a clinical suspicion of pneumonia were encountered by primary care physicians
in their everyday practice, and the ongoing study did not influence on their
treatment decisions. At least 3 parameters independently associated with mortality
within 30 days are easily available: patient history (preceding aggravation
of a coexisting illness); physical findings (respiratory rate 25/min);
and laboratory measurement (CRP level 100 mg/L). Whether these markers
are generally applicable to the evaluation of the severity and treatment decisions
of LRTI among elderly patients in primary care should be ascertained and validated
in a new prospective study.
AUTHOR INFORMATION
Accepted for publication March 29, 2001.
Corresponding author and reprints: Hannu Syrjälä, MD, PhD,
Department of Infection Control, Oulu University Hospital, FIN-90220 Oulu,
Finland (e-mail: hannu.syrjala{at}ppshp.fi).
From the Department of Infection Control, Oulu University Hospital,
Oulu (Drs Seppä and Syrjälä); the National Public Health Institute,
Oulu (Ms Bloigu); the Department of Public Health Science and General Practice,
University of Oulu, Oulu (Dr Honkanen); Oulu University Hospital, Oulu, and
Oulaskangas Hospital, Oulainen (Dr Miettinen); and Kemi Health Center, Kemi
(Dr Honkanen), Finland.
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