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Indian Pediatr 2021;58: 1019-1023 |
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Risk of Hospitalization
in Under-five Children With Community-Acquired Pneumonia: A
Multicentric Prospective Cohort Study
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Javeed Iqbal Bhat, 1
Bashir A Charoo,1 Aparna
Mukherjee,2 Ridwana Ahad,1
Rashmi R Das,3 Jagdish
Prasad Goyal,4 Bhadresh
Vyas,5 Vinod H Ratageri,6
Rakesh Lodha7 and ATU Group*
From Departments of Pediatrics, 1Sher-i-Kashmir Institute of Medical
Sciences, Srinagar, Jammu & Kashmir; 2Indian Council of Medical
Research, New Delhi; 3All India Institute of Medical Sciences,
Bhubaneswar, Odisha; 4All India Institute of Medical Sciences, Jodhpur,
Rajasthan; 5MP Saha Medical College, Jamnagar, Gujarat; 6Karnataka
Institute of Medical Sciences, Hubballi, Karnataka; 7All India Institute
of Medical Sciences, New Delhi. *Full list of ATU Group provided in
Annexure I.
Correspondence to: Dr Javeed Iqbal Bhat, Department of Pediatrics,
Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir,
India.
Email: [email protected]
Received: April 02, 2020;
Initial review: June 08, 2020;
Accepted: August 18, 2020.
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Objective: To evaluate factors
associated with risk of hospitalization in children with
community-acquired pneumonia (CAP).
Design: Prospective cohort study.
Setting: Multi-site hospital
based study.
Intervention: A separate acute
respiratory tract infection (ARI) treatment unit (ATU) was established.
The revised WHO case definition for ARI was used across all the study
sites to ensure uniformity in management of ARI patients (2-59 months).
Clinical history, examination findings and investigations of enrolled
patients were recorded on a predesigned case record form. Children were
followed up at 1 week (± 1 day).
Main outcome measure: Risk
factors for hospitalization among pneumonia patients.
Results: A total of 7026 children
with the diagnosis of ARI were enrolled. Pneumonia was diagnosed in 938
(13.4%) patients (median (IQR) age: 15 (8, 25) months; 63.5% boys).
Hospitali-zation was needed in 56.8% of pneumonia patients. On multi-variate
analysis, factors associated with risk of hospitalization were: Oxygen
saturation on pulse oximetry (SpO2) <92% in room air (OR 7.04; 95% CI
1.6, 30.8, P=0.01), procalcitonin level >0.5 ng/mL (OR: 7.5, 95%
CI: 1.0, 57.7, P=0.05), and lower weight for height z-score
(OR 0.8; 95 % CI: 0.6, 0.9, P=0.02).
Conclusion: Present study found
SpO2 <92% at room air, serum procalcitonin level >0.5 ng/mL and lower
weight for height z-score to be predictors for risk of
hospitalization in under-five children presenting with community
acquired pneumonia. These factors can be utilized to assess a child with
CAP regarding the need of hospitalization.
Keywords: Hypoxia, Outcome, Procalcitonin,
Underweight.
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C
ommunity-acquired pneumonia (CAP) is one of the
leading causes of morbidity and
mortality in under-five children [1]. CAP is more common in the
developing world, accounting for 95% of all cases [2]. In India, an
estimated 4 lakh pneumonia deaths occur annually [3]. Efficient case
management is a cornerstone of pneumonia control strategies. Simple
clinical signs like rapid breathing, chest in drawing and general danger
signs have been used by WHO to classify the severity of pneumonia in
under-five children [1].
WHO revised case definition for CAP in under-five
children has two categories – ‘pneumonia’, which is treated at home with
oral amoxicillin and ‘severe pneumonia, which requires hospitalization
and parental antibiotics. Despite the improvement in case management of
childhood pneumonia, mortality and morbidity still remains high,
especially in resource-constrained settings. The early identification of
important risk factors for hospitalization among these patients could
help to prioritize the management and potentially increase their
likelihood of surviving. This prospective study was conducted to
evaluate the factors associated with risk of hospitalization in children
with CAP.
METHODS
This was a multisite prospective cohort study
conducted from June, 2016 to May, 2018 in following tertiary care
hospitals of India: i) Sher-e-Kashmir Institute of Medical
Sciences (SKIMS), Srinagar, ii) All India Institute of Medical
Sciences (AIIMS), Jodhpur, iii) AIIMS, Bhubaneswar, iv)
Karnataka Institute of Medical Sciences, Hubballi, and v) MP Saha
Medical College, Jamnagar. AIIMS, New Delhi was a coordinating center
for the study. Prior ethical approval was obtained from institutional
Ethics Committee of AIIMS, Delhi and all other five study sites.
Previously healthy children, 2 to 59 months of age,
with acute respiratory infection (ARI) of less than 2 weeks duration
were assessed for inclusion in the study. Children suffering from
chronic respiratory diseases (asthma, cystic fibrosis, bronchopulmonary
dysplasia (BPD), airway anomalies), congenital heart disease,
gastroesophageal reflux disease (GERD)/recurrent aspirations,
suspected/known immunodeficiency, patient living outside the city where
the study site was based, history of radiologically confirmed pneumonia
in last 2 months, and very sick child requiring immediate ICU care, were
excluded.
A separate acute respiratory tract infection
treatment unit (ATU) was established to manage all ARI patients. The ATU
team comprised of a pediatrician and a trained nurse. All children
between 2 months to 59 months of age with history of ARI were directed
to attend ATU during working hours of the hospital. The revised WHO case
definition for ARI was used across all the study sites to ensure
uniformity in management of ARI patients. The revised classification
includes two categories of pneumonia; ‘pneumonia’ with fast breathing
and/or chest in drawing, and ‘severe pneumonia,’ pneumonia with any
general danger sign [1]. Children were enrolled in the study after
obtaining written, informed consent from parents or legal guardians. A
detailed history was taken, and physical examination, including
respiratory rate, presence of chest in drawing, pulse, temperature,
oxygen saturation by pulse oximetry and anthropometry was done by the
research nurse under the supervision of research officer. Each child’s
respiratory rate was counted for a full minute when the child was calm
and quiet. If the child presented with fever and fast breathing,
appropriate paracetamol dose was given and respiratory rate was
reassessed after 30 minutes. Children presenting with wheeze and fast
breathing were administered salbutamol nebulization (0.15 mg/kg single
dose) and respiratory rate was reassessed after 10-15 minutes. Weight
was measured to the nearest 0.1 kg using calibrated electronic scales,
and height was measured to the nearest 0.1 cm using a standardized
stadiometer. If a child was less than 2 years of age, recumbent length
was measured by using an infantometer. Clinical history and examination
findings of enrolled children were recorded on a predesigned case record
form.
Every fifth child with ARI underwent a chest X-ray.
The chest radiographs were interpreted by site investigator at the time
of enrolment, thereafter, either original films or digital copies were
sent to the coordinating centre at AIIMS, New Delhi. All chest X-rays
were read by two independent pediatricians, who were blinded for the
clinical diagnosis of the patient. In case of disagreement about the
presence or absence of pathology, chest X-rays were read by a
third pediatrician without knowledge of the previous evaluations and
final findings matching for two of them were considered for purpose of
analysis. Patients with suspected pneumonia underwent serum quantitative
procalcitonin (PCT) estimation. All children were followed till 7 days
(±1 day) after enrolment. Parents were given reminder telephone call one
day prior to the anticipated follow-up. All admitted patients were
examined daily until discharge.
Management of children with pneumonia was done
according to the WHO recommendations [1]. Any child with severe
pneumonia was hospitalized; the treating physicians’ assessment was the
deciding factor in other cases.
The aim was to enrol about 4000 children per site
giving a total data of about 20000 children across all the sites. Of
these 30-40% may be because of respiratory problems. Approximately
6000-8000 children with ARI, i.e approximately 1200-1500/site were
expected to be enrolled. About 10% children with acute respiratory
infection may develop pneumonia. As the primary aim of the ATU project
was to improvise clinical case definition (combine clinical features) of
CAP with a sensitivity and specificity of 80% (sensitivity of tachypnea
with/without chest indrawing is about 69%) and precision of 5%, we
needed a total of 256 children with pneumonia. We expected that this
sample size could be easily achieved.
Statistical analysis: A data entry program in
Microsoft Access was developed at AIIMS, New Delhi. The data from all
the study sites were sent to AIIMS for analysis. Children with CAP (as
per WHO criteria) needing hospitalization were compared to those who did
not, by univariate analysis, followed by multivariate analysis using a
logistic regression model; the dependent criteria was whether
hospitalization occurred or not, independent covariates were the ones
which emerged statistically significant in univariate analysis. The
z-scores for weight for age, height for age and weight for height
were calculated using the WHO Anthro software.
RESULTS
A total of 18159 under-five children were screened;
7026 (39% of screened) children assessed to have ARI were enrolled in
the study. Using the WHO criteria, pneumonia was diagnosed in 938
(13.4%) patients; remaining 6088 patients were labelled as having upper
respiratory tract infection. Hospitalization was needed in 533 (56.8%)
children with pneumonia including 7 patients who were initially given
ambulatory treatment and were later admitted in view of deteriorating
respiratory distress. Four hundred and five (43.2%) children with
pneumonia received ambulatory treatment. The baseline demo-graphic and
clinical characteristics of the study population are shown in Table I.
Amongst children with pneumonia, reportable chest X-rays were
available in 563 cases (total X-rays 571).
Table I Demographic and Clinical Details of Children with Community-acquired Pneumonia (N=938)
| Characteristics |
Values |
| Age, moa |
15 (8,25) |
| Boys |
596 (63.5) |
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Weight for age z-scorea |
-1.34 (-2.5, -0.18) |
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Height for age z-scorea |
-1.2 (-2.6, 0.12) |
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Weight for height z-scorea |
-0.77 (-1.96, 0.3) |
| Respiratory rate /min, mean (SD) |
54 (11) |
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Chest indrawing present |
455 (48.5) |
| SpO2 %, mean (SD) |
94.3 (5.1) |
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Procalcitonin level, ng/mL (n= 12)a |
0.1 (0.05, 0.44) |
| Significant pathology in CXR (n=563) |
331 (58.8) |
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Values in no. (%) or amedian (IQR). CXR: chest X-ray. |
Table II Factors Associated With Hospitalization in Community-acquired Pneumonia (N=938)
| Characteristics |
Hospitalized children (n=533) |
Ambulatory treatment (n=405) |
| Age, moa |
12 (7,20) |
18 (9,35) |
| Boys, n (%)b |
342 (64.2) |
254 (62.7) |
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Weight for age z-scorea |
-1.67 (-2.75, -0.53) |
-0.84 (-2.02, 0.22) |
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Height for age z-scorea |
-1.37 (-2.72, -0.12) |
-0.9 (-2.46, 0.6) |
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Weight for height z-scorea |
-1.11 (-2.36, 0.03) |
-0.27 (-1.43, 0.54) |
| Significant pathology in CXR, n (%)c |
268 (63.9) |
63 (43.7) |
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Procalcitonin level, ng/mLd |
0.14 (0.05, 0.54) |
0.05 (0.05,0.07) |
| SpO2 %, mean (SD) |
93 (5.9) |
95.9 (3.1) |
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Values are expressed as median (IQR) unless specified. All
P<0.001 except aP=0.008 and bP=0.65. cChest X-ray available in
563 (419 inpatients and 144 out patients; dprocalcitonin levels
available in 312 (284 inpatients and 28 outpatients). |
Factors associated with hospitalization in children
with pneumonia were younger age, lower weight- and height-for-age z-scores,
higher PCT levels, lower SpO2,
and higher percentage of significant pathology in chest-X-rays as
compared to those receiving ambulatory treatment (Table II).
On multivariate analysis, factors associated with
hospitalization were SpO2
<92% in room air [OR (95%CI) 7.04 (1.6-30.8); P=0.01], PCT level
> 0.5 ng/mL [OR (95%CI) 7.5 (1.0-57.7); P=0.05] and low weight
for height z-score [OR (95%CI) 0.8 (0.6-0.9); P = 0.02].
DISCUSSION
In this multi-site prospective observational study,
hospitalization was needed in 56.8% of patients diagnosed with pneumonia
as per current the WHO criteria. Risk factors associated with
hospitalization were SpO 2<
92% on room air, serum PCT levels >0.5 ng/mL, and lower weight for
height z-score.
Majority of the patients of ARI can be managed safely
in the community [5,6]. Hospital admission in revised WHO case
definition for CAP management in under-5 children is recommended when
the child is brought with general danger signs like not able to drink,
persistent vomiting, convulsions, lethargy or unconsciousness, stridor
in a calm child or severe malnutrition [1]. The WHO recommendations;
however, do not include several parameters which have been proven to
predict severity of pneumonia in under-five children more accurately
[7,8]. Studies from different parts of the world have observed that
hypoxic children are more likely to die than adequately oxygenated
children [9,10]. In a systematic review, the median prevalence of
hypoxemia in WHO-defined severe and very-severe pneumonia was 13% [11].
The British Thoracic Society guideline recommends that SpO2 below 92% in
childhood CAP warrants hospital admission and optimal management [5]. We
have utilized pulse oximetry for measurement of SpO2 in our study, which
has been recommended as a standard point of care for SpO2 monitoring in
children with pneumonia [12,13]. A recent meta-analysis also concluded
that the pulse oximetry is a useful tool for hypoxemia screening and
optimal oxygen supplementation to prevent pneumonia deaths in children
[14]. Our study findings corroborates with these observations. Detection
of hypoxemia by pulse oximetry should be an important component for
assessment of a child with CAP so that a decision regarding the severity
of pneumonia and need for hospitalization can be taken.
Serum PCT level > 0.5 ng/mL had a higher odds of
hospitalization in our cohort of children with CAP. Multiple studies in
both adults and children have shown that serum PCT is a surrogate tool
to differentiate between viral and bacterial pneumonia, and the latter
has higher probability of hospitalization [15,16]. Serum PCT levels can
be used as a point of care diagnostic tool to assess severity of
pneumonia in children with CAP as this investigation is becoming
increasingly available even in smaller hospitals in our country.
Malnourished children have a higher incidence and
severity of CAP. Mortality increases proportionately with severity of
malnutrition [18]. We also found significantly increased risk of
hospitalization among children with undernutrition. The variable used
was weight for height z-score. With one unit increase in weight
for height z-score, the odds for hospitalization was 0.8. Our
study has some limitations. Since the readmission rate was very low in
our study, no meaningful analysis of factors determining hospitalization
after starting ambulatory treatment could be done.
To conclude, our study found SpO2< 92% by pulse
oximetry, serum procalcitonin level >0.5 ng/mL, and low weight for
height z-score as important predictors for risk of
hospitalization in under five children presenting with CAP. Routine
monitoring of SpO 2 by pulse
oximetry and serum PCT levels can be used to identify high risk patients
who would require inpatient care.
Contributors: JIB, BAC, RA: involved in data
collection and manuscript writing; AM,RL: involved in development of
protocol, supervision of the study, data analysis; JPG, RRD,VHR,BV: data
collection, manuscript review. All authors approved the final version
submitted.
Funding: This work was supported by Bill and
Melinda Gates Foundation through the INCLEN Trust International (Grant
number: OPP1084307). The funding source had no contribution in study
design, implementation, collection and interpretation of data and report
writing. Competing interest: None stated.
ANNEXURE I
*Members of The ATU (Acute Respiratory Infection
Treatment Unit) Group
Daisy Khera, Department of Pediatrics, AIIMS,
Jodhpur, Rajasthan; Deepak Singhal: Department of Pediatrics,
AIIMS, Jodhpur, Rajasthan; KR Jat, Department of Pediatrics,
AIIMS, New Delhi; Kuldeep Singh, Department of Pediatrics, AIIMS,
Jodhpur, Rajasthan; Partha Sarathi Ray, AIIMS, Bhubneshwar,
Odisha; Prawin Kumar, Department of Pediatrics, AIIMS, Jodhpur,
Rajasthan; Samarendra Mahapatro, AIIMS, Bhubaneswar, Odisha;
SK Kabra, Department of Pediatrics, AIIMS, New Delhi.
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What is Already Known?
• Delayed hospitalization in children with
severe community-acquired pneumonia is associated with increased
mortality.
What This Study Add?
• Hypoxia (SpO2 <92% in room air), higher serum procalcitonin
levels (>0.5 ng/mL) and lower weight for height z-score
can predict hospitalization in under-five children with
community-acquired pneumonia.
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