According to estimates, about 156 million cases of community-acquired pneumonia (CAP) occur in children, of which 151 million are in developing countries.1 There are few studies of severe cases of CAP with pleural effusion (PE) and empyema in childhood. Although potentially serious, its clinical recognition still represents a challenge.2 Among the risk factors associated with CAP complications is a low education level of the child’s mother. Children with severe CAP are, in general, of mean age lower than those with nonsevere CAP: 27 months versus 45 months, respectively (P < 0.008).3 However, there is still controversy about the importance of low age as risk factor in childhood CAP.1 , 4
Brazil has developed significantly in the last decade and is classified as a country with a high human development index (HDI; 0.700–0.799), although infant mortality still stands at 13/1000.5 A study in Rio de Janeiro, Brazil, showed decline in hospital mortality caused by CAP from 1996 to 2011, hypothesized due to the improvement of living conditions of the population under study.6 In this study, we use an important and commonly used index to try to assess the Brazilian improvement in the socioeconomic conditions. The municipal HDI (M-HDI) is an index that incorporates life expectancy at birth, average schooling and gross national income per capita. This study evaluated admissions with severe CAP with PE in a pediatric university hospital in Rio de Janeiro, Brazil, the impact of the average M-HDI in the local incidence of the disease in the last decade and the estimated percentage according to the increasing of M-HDI of the city.
MATERIALS AND METHODS
This is a retrospective longitudinal study involving all patients with clinical and radiologic diagnosis of CAP admitted to the Martagão Gesteira Childcare and Pediatrics Institute (IPPMG), in the Federal University of Rio de Janeiro (UFRJ) wards, Rio de Janeiro, Brazil, from August 2003 to December 2012.
IPPMG – UFRJ is the only exclusive university reference center for complicated Childhood Diseases in the city, including respiratory ones.6
The study included all patients 0–13 years of age admitted with clinical and radiologic diagnosis of CAP. The diagnosis was based on standards set by World Health Organization, and it was made by means of a compatible clinical history, tachypnea with or without dyspnea, irregular lung auscultation and radiography of thorax suggestive of pneumonia.7 All patients went through the following examinations: complete blood count, blood culture and culture of pleural fluid as appropriate. The patients were diagnosed with severe CAP with PE when they had been admitted with evidence of PE or developed it during admission.
The following patients were excluded: patients admitted to another hospital for more than 48 hours before the transfer to the IPPMG; patients who had received recent hospital discharge (less than 48 hours after admission); when there was no information about the hospital and patients from the intensive care unit.
The M-DHI of the place of residence of patients in the city of Rio de Janeiro was obtained from the United Nations Development Program of 2010. M-HDI values obtained from 3 consecutive censuses: 1991, 2000 and 20108 were selected and a linear regression line was built covering the 3 points of these M-HDI values of Rio de Janeiro, the result of which was R2 = 0.99 (an almost perfect correlation).
From the equation of the line, the M-HDI values from 2004 to 2011 were estimated and added to the record of each patient according to the date of diagnosis of pneumonia.
The Access program was used to build the database and the Statistical Package for the Social Sciences, version 22.0 for Windows, carried out the data analysis (SPSS Inc, Chicago, IL).
Tables of the dimension 2 × 2 were used to calculate the crude odds ratios of variables related to risk of developing PE in cases of CAP. Variables that reached a significance level of 80% (P < 0.20) were then selected for multivariate analysis, after evaluation of the multicollinearity between them. The logistic regression model was used for the multivariate analysis. The regressive method was used for the selection of the parsimonious model, according to the likelihood ratio.9 We used the Roc curve to dichotomize the M-HDI and establish the cutoff point, as proposed by Linnet and Brandt.10
Additionally, we performed a time trend analysis for the percentage of pneumonia with PE, including an autoregressive integrated moving average (ARIMA) MODEL, according to Hamilton,11 considering M-HDI of Rio de Janeiro Municipality as an independent variable.
The patients’ ages ranged from 1 to 174 months, with an average of 47.28 months (Standard deviation (SD) = 42.75) and a median of 33 months. Existing comorbidities (by frequency) were sickle cell anemia (84); leukemia (14); HIV infection (42); heart disease (14); asthma (25); encephalopathy (44); tuberculosis (4); and other (22).
Table 1 shows the clinical variables, comorbidities, maternal education and the M-DHI index in the period of study of all children admitted with CAP.
Table 2 shows the same variables compared between children with and without PE. Table 3 shows a multivariate analysis from the findings of Table 2. Table 3 presents the ARIMA MODEL for the natural logarithm of the % of CAP with PE. The prediction equation of the model is % CAP with PE = EXP (16.401 – 17.010 × M-DHI).
Figure 1 presents the percentage of CAP with PE during the study period (observed curve) with the predicted value (estimated curve) obtained though the ARIMA model adjustment considering M-HDI as independent variables (R-squared = 0.816 and Stationary R-Squared = 0.765) and the prediction of the model for the next putative M-HDI value for the Rio de Janeiro city.
Table 4 presents the observed value of the percentage of CAP PE, the estimated value and prediction for M-HDI of Rio de Janeiro City.
This study was made in a University reference pediatric center in Rio de Janeiro. A higher number of admissions by severe CAP with PE occurred in children with median ages higher than in the patients without PE and in patients without comorbidities than in those with them. The multivariate analysis evidenced that there was a relationship between CAP and temporal variation of M-HDI in Rio de Janeiro. As the M-HDI increased in the period from 0.749 to 0.807, there was a decrease in admissions with CAP with PE. The age of patients was not associated with admission for severe CAP in the final multivariate model.
The most admitted patients in our study were less than 4 years old. We found that patients with comorbidities had a lower risk to be admitted with PE. We believe that this was because the patients with comorbidities had special medical care and were admitted with CAP regardless of its severity. It would appear that the reason for such admissions could be related more to the doctors’ belief that patients with comorbidities would have a worse clinical course in short time than actually to the recommendation protocols or guidelines. Children with CAP and comorbidities in general are poorly considered in the literature. The guidelines mention generally that comorbidities are risk factors for severe CAP in childhood, but treatment guidelines are sparse.12 While it was not possible to evaluate the risk of PE development of each comorbidity found in our patients with CAP because of its great diversity and the low number of cases in each category, such a larger study would seem warranted.
The meta-analysis made by Jackson et al13 showed significant association of the reduction of admissions for respiratory disease in children under 5 years old with the improvement of the following conditions: low birth weight, air pollution, malnutrition, incomplete immunization in the first year, HIV, lack of breastfeeding and household crowding. In Brazil, the cash transfer program called Bolsa Família impacted mortality in children under 5 years old from poor families by reducing malnutrition and the incidence of diarrheal disease and CAP. The reduction of child mortality was evident to the extent of the greater population coverage offered by BF program in the studied areas.14
We have shown in our work that the progressive increase of the M-DHI during the study period, although to a slightly higher level, was highly correlated with the reduction in the number of admissions with CAP with PE. In Rio de Janeiro, there was a progressive rise in M-DHI over the last decade: from 0.716 to 0.799 between 2000 and 2010, representing an increase of 11.5%. Even in the poorest areas, known as favelas or communities, there has also been an increase in the HDI. In addition, Brazil has achieved reduction of child mortality: of 55% in 1990 to 17% in 2010. This decrease was reached 4 years ahead of schedule by Millennium Developing Goals proposed by World Health Organization.15 In this study, we developed a predictive model that could estimate the reduction of the number of cases of CAP with PE with the increasing of the M-HDI.
However, the country still faces problems with inequality in the small area HDI inside a county or state. The Gini index which measures such inequality, changed little in Brazil from 2000 to 2010, which suggest that the increase in HDI did not contribute to the decrease of the inequality in the country. Vulnerability to health is the result largely of social determinants in undeveloped or developing countries. The greatest inequality, in the case of Brazil, occurs in income, with 39.7% of average difference between rich and poor. The other indexes correspond to 24.7% for education and 14.5% for life expectancy.16 However, there is no doubt that, while remaining inequalities, the level of M-HDI increased in all social classes.17
In most of the period of our study, before 2010, pneumococcal conjugate vaccination was not yet incorporated into the mandatory vaccination schedule of childhood. Thus, one cannot attribute the reduction of severe CAP cases over time to the protective effect of the vaccine. Perhaps future studies developed in our country after the implementation of pneumococcal conjugate vaccine will be able to show changes in the incidence of childhood CAP with PE, despite the increase of DHI. That phenomenon would be consequently a biologic one: the selection of pneumococcal sources that do not take part in the vaccine or the alteration in the CAP etiology caused by other factors as occurred in Polony between 2002 and 2013. The incidence of complicated CAP in that country (where the pneumococcal vaccine was not implemented) increased despite its DHI was elevate.18
1. Rudan I, Boschi-Pinto C, Biloglav Z, et alEpidemiology and etiology of childhood pneumonia
. Bull World Health Organ. 2008;86:408–416.
2. Cardoso MRA, Carvalho CMM, Ferrero F, et alPenicillin-resistant pneumococcus and risk of treatment failure in pneumonia
. Arch. Dis. Child
. 2008; 93; 221–225
4. Amorim PG, Morcillo AM, Tresoldi AT, et alFatores associados às complicações em crianças pré-escolares com pneumonia
adquirida na comunidade (Factors associated with complications of community-acquired pneumonia
in preschool children). J Bras Pneumol. 2012; 38: 614–621
6. Ferreira S, Sant’anna CC, March Mde F, et alLethality by pneumonia
and factors associated to death. J Pediatr (Rio J). 2014;90:92–97.
7. Bradley JS, Byington CL, Shah SS, et alThe Management of Community-Acquired Pneumonia
in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011; 53 (7):e25–76. doi: 10.1093/cid/cir531.
9. Kleinbaum DGLogistic regression: a self-learning text. 2001.2nd ed. New York, Springer,
10. Linnet K, Brandt EAssessing diagnostic tests once an optimal cutoff point has been selected. Clin Chem. 1986;32:1341–1346.
11. Hamilton JDTime Series Analysis. 1994UK, Princeton University,
12. Izadnegahdar R, Cohen AL, Klugman KP, et alChildhood pneumonia
in developing countries. Lancet Respir Med. 2013;1:574–584.
13. Jackson S, Mathews KH, Pulanic D, et alRisk factors for severe acute lower respiratory infections in children: a systematic review and meta-analysis. Croat Med J. 2013;54:110–121.
14. Rasella D, Aquino R, Santos CA, et alEffect of a conditional cash transfer programme on childhood mortality: a nationwide analysis of Brazilian municipalities. Lancet. 2013;382:57–64.
17. Mendonça AMC, Kritski, Land MGP, et alAbandonment of Treatment for Latent Tuberculosis Infection and Socioeconomic Factors in Children and Adolescents: Rio De Janeiro, Brazil. PLoS ONE 11(5): e0154843. doi: 10.1371/journal.pone.0154843
18. Krenke K, Urbankowska E, Urbankowski T, et alClinical characteristics of 323 children with parapneumonic pleural effusion
and pleural empyema due to community acquired pneumonia
. J Infect Chemother. 2016;22:292–297.
Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
human development; pneumonia; pleural effusion; child