Which is more severe?
What is the predominant pattern of
asthma, eosinophilic or neutrophilic in Indian children.
GAPS IN KNOWLEDGE-
Enrico Hefler published a study in jul
2017, where 76 Severe asthma adult patient defined by ERS and ATS,
attending allergy and asthma outpatient
clinic during an 8-month period (since May 1 and until October 31, 2016) and
without any exacerbation or respiratory infection for at least 1 month were
enrolled in the study. A significant correlation between blood Eosinophil
counts assessed by HemoCue WBC DIFF and standard CBC analyzer was found (R2
=0.854, P 400 cells/µL (30). Zieger et al. likewise concluded
that a blood eosinophil count > 400 cells/µL was an independent
risk factor for asthma exacerbations and asthma-related emergency department visits
or hospitalizations (31). So, Optimization of Biomarker testing methods by
combining greatest sensitivity and specificity with non invasiveness,
availability and affordability is critical to the continued advancement of
So, Blood counts may be a useful aid in
the monitoring of uncontrolled asthma.
Zhang XY, Simpson JL in sep 2014,
conducted a study where Full blood count parameters were analyzed for detection
of asthma inflammatory phenotypes.(1) The optimum cut-point for blood Eosinophil
percentage was 2.7%, and this yielded a sensitivity of 92.2% and a specificity
of 75.8%. The absolute blood Eosinophil count was also highly predictive with
an AUC of 0.898 (P 3%) or absolute value (>220/cumm), and
percentage of sputum eosinophil count (r = 0.6, p 66%)
(r = 0.19, p = 0.0015) but not in absolute value(cut off of 4960/cumm) (r =
0.19,p=0.11). Eosinophilic and pauci-granulocytic are the most frequent asthma
phenotypes in a large unselected asthmatic population. Like FENO, blood
eosinophil counts may provide a practical alternative to predict sputum
eosinophilia ?3%. In contrast, sputum neutrophilia is only poorly related to
blood neutrophil count it is better predicted independently by advanced age and
biopsies or Bronchoalveolar lavage are considered as the gold standard for assessing
airway inflammation but this method is too invasive for routine clinical use.
Therefore, there has been great interest in methods to assess airway
inflammation non-invasively and in a convenient and inexpensive way.
Better knowledge of the intricate
cellular mechanism i.e. Pathobiologic networks underlying the onset and
progression of Eosinophilic and
Neutrophilic airway inflammation in asthma will provide the way for substantial
improvements in the treatment of disease. (11)
Wenzel SE, In year 2012 defined the asthma
phenotypes in 3 groups specially in children as: A) Transient Early wheezing
seen upto 3 years age. B) Non Atopic wheezing in toddler and preschool children
which is having early RSV=LRI in 1st 3 year of life. C)
atopic/allergic asthma persistent wheezing associated with Atopy in early life.(10)
2. Non Allergic Asthma: These are seen more
common in adult. sputum of these patients may be Neutophilic, Eosinophilic or
Paucigranulocytic. These pattern can also be seen during severe exacerbation in children and often
respond less well to inhaled corticosteroid treatment.
1. Allergic Asthma (Eosinophilic): most
easily recognized asthma phenotype, which often commences in childhood and
associated with past history of allergic disorder. Induced sputum of these
patients often reveals eosinophilic airway and usually respond well to inhaled
Bel EH, in year 2004 defined different phenotype
of Asthma.(9) Some of the most common include
Mucosal mast cells, Eosinophils, T
lymphocytes, Dendritic cells, Macrophages, Neutrophils are the inflammatory
cells. Over 100 different mediators are now recognized which mediates the
complex inflammatory process of airway.
Asthma is chronic inflammatory disorders
of airway. Multiple inflammatory cells and its mediators are involved in the
pathogenesis of asthma. Till date, no strong relationship has been found . Between specific pathological features and particular
clinical patterns or treatment responses specially in children.
Asthma is the most common chronic pulmonary
disease in children. Interactions of Susceptible Host (Genetic, obesity, sex) with certain
environmental conditions (allergens,
occupations, infections etc) leads to manifestation of asthma. Early diagnosis
and treatment of asthma is very important as it can alter the course of disease.
Thus, there is need of a robust
noninvasive, simple, routine investigation. So, absolute Eosinophil count or Neutrophilia
could add predictive value to GINA controlled based risk assessment for
exacerbation of asthma and response to treatment.
Blood eosinophil count is a marker of
eosinophilic airway inflammation which is more common in children and disease
severity in asthma. However, blood neutrophil count might also be associated
with disease severity. we want to test the hypothesis that, high eosinophil and
neutrophil counts are both associated with the risk of asthma exacerbations
among individual with asthma specially in children 6 to 12 years of age among
this which is more common during exacerbation, its severity and response to
An ideal biomarker should be reliable,
minimally invasive, easy to collect and measure, inexpensive and can be used to
identify either a clinical phenotype or a treatment response phenotype,
measures changes in disease activity, or confirm a diagnosis.
Asthma is a heterogeneous disease with different
underlying disease processes. Many clinical phenotypes are identified. In
children, three asthma phenotypes are now well defined: transient infant
wheezing, nonatopic wheezing of the toddler, and IgE mediated wheezing/asthma.
Recently, a fourth phenotype, late onset childhood asthma.(5) some of the most
common include: a) Allergic (Eosinophilic) asthma b) Non allergic
(Neutrophilic, eosinophilic or paucigranulocytic) asthma.
Goal of asthma management is asthma control. Response
to treatment is reviewed by clinical status i.e. symptoms improved, oxygen
saturation and lung function after one hour of treatment FEV1 or PEF 60 to 80%
of predicted shows good response to treatment.
Exacerbations represent a change in clinical
features and lung function from the patient’s usual status.(6) the decrease in
peak expiratory flow (PEF) or forced expiratory volume in 1 second ( FEV1), (7)
are more reliable indicators of severity of the exacerbation than symptoms. The
frequency of symptoms may, however, be a more sensitive measures of the onset of
an exacerbation than PEF.(8)
Symptoms and airflow limitation might
sometimes resolve spontaneously or otherwise in response to treatment, and may
be sometimes absent for up to months. However, patients may experience episodic
flare-ups (exacerbations) of asthma characterized by a progressive increase in
symptoms of shortness of breath, cough, wheezing or chest tightness, signs of
exacerbation severity, including vital
signs (e.g level of consciousness, temperature, pulse rate, respiratory rate,
blood pressure, ability to complete sentences, use of accessory muscles) and
progressive decrease in lung function that can be life threatening and carry a
significant burden to patients and the community.(6) Exacerbations may occur in
patients with a diagnosed Asthma or, occasionally, as the first presentation of
Asthma is a
serious global health problem affecting all age groups. Its prevalence is
increasing in many countries, especially among children. Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation. It is defined by the history of
respiratory symptoms such as wheeze, shortness of breath, chest tightness and
cough that vary over time and in intensity, together with variable expiratory
airflow limitations.(1) Asthma
imposes immense burden with more than 300 million individuals currently
suffering from asthma worldwide. About a
tenth lives in India.(2) Its prevalence has been estimated to range 3-38% in children
and 2-12% in adults (3), thus making it the commonest chronic disorder among
children. One recent Indian Study on Epidemiology of Asthma, (INSEARCH)
estimated national burden to be 18 millions.(4) The World Health Organization Global Burden of
Disease Study estimates that 13.8 million disability adjusted life years
(DALYs) are lost annually due to asthma.(5)
What is the predominant pattern of
asthma, (Eosinophilic or Neutrophilic) in Indian children.
Which is more severe?
Which has better response to treatment?
To compare the incidence of Eosinophilic and Neutrophilic
Asthma during acute exacerbation and to
observe the correlatations, if any,
with severity and response to
The present study is to throw light on:
1. The incidence of Eosinophilic and Neutrophilic
Asthma during acute exacerbation of
asthma in children (6 to 12 years of age).
1.To study the correlation of Severity of
disease in Asthma prototype (Eosinophilic versus Neutrophilic).
2. To study the Response of standard
treatment for (Eosinophilic versus
This study will be conducted in Pediatric OPD,
Casualty and Inpatient department of
Swami Dayanand Hospital, Delhi.
This study will be observational,
February 2018 – October 2018 (10 months)
Asthmatic children aged 6-12
1.Physician diagnosed Asthma
with acute exacerbation as per GINA
2.Children ( 6 to 12 years of
3.Parents giving consent for the study.
1. All Asthamatic children
with coexisting other pulmonary diseases i.e-Bronchiestasis, cystic fibrosis,
Allergic bronchopulmonary aspergillosis, interstitial lung disease.
Asthamatic children with high fever (>/39*C i.e 103*F) and evidence of
severe bacterial infection.
Asthmatic children with co-existing cardiac disease.
4. All Asthamatic children who received oral
systemic corticosteroid in last 2 weeks.
Asthmatic children with muscular disease or chest deformity.
Sample Size :
The minimum required sample size is 96 patients.
cross-sectional study is going to be conducted in Department of Pediatrics
Swami Dayanand Hospital after obtaining the approval of institutional
research committee & institutional ethics committee. All eligible
children will be enrolled in study
after obtaining informed consent from the patient. For every child enrolled
in study, CBC (complete blood count) and peripheral smear examination will be
done. Severity of exacerbation of
Asthma as mild, moderate and severe as per PRAM (Paediatric Respiratory
Assesment Meausres) at 0 hrs i.e during Triage and standard recommended treatment according to
severity of illness as per GINA-2017 guidelines will be started and response
to treatment will be assessed by PRAM score at 1 hr and 3 hrs after start of
treatment and duration of hospital stay.
Blood smear incidence of
Eosinophilia and Neutrophilia.
Severity of Asthma exacerbation
according to PRAM score.
PRAM scoring at 1 and 3 hrs
and Duration of Hospital stay.
statistical testing will be conducted with the statistical package for
the social science system version SPSS 17.0. continuous variables will be
presented as mean +_ SD or median ( IQR) for non normally distributed data.
Categorical variables will be expressed as frequencies and percentage.
Nominal categorical data between the groups will be compared
using Chi-squared test or Fisher’s exact test as appropriate.
For all statistical tests, a p value less than 0.05 will be
taken to indicate a significant difference.