Is Iron Deficiency Anaemia , a risk Factor For Wheeze Associated Respiratory Tract Infection in Children ?

Address for correspondence: Col Rakesh Gupta, Professor of Paediatrics Department of Paediatrics, Command Hospital(CC) Lucknow Cantt-226002 (UP), India Tel No; +919935842002, +919850042002, E-mail: colrgupta@gmail.com 1Dr. Anupama Agrawal, MBBS, MD, Resident in Paediatrics, Command Hospital (CC) Lucknow, 2Col Rakesh Gupta, MBBS, MD, Professor & Head of department (Paediatrics), Command Hospital (CC) Lucknow, 3Col K D Sodhi, MBBS, MD, Professor & Head of department (Paediatrics), Command Hospital (WC) Chandigarh, 4Brig Vinod Raghav, MBBS, MD, Dy Commandant & Consultant Pathology, Command Hospital (CC) Lucknow, UP, India. Abstract


Introduction
P opula on studies have shown that approximately one in three children has at least one episode of wheezing prior to their third birthday, and the cumula ve prevalence of wheeze is almost 50% at the age of six years 1 .Despite its high prevalence, there is a lack of evidence regarding the pathophysiology and treatment of fi rst episode of wheeze 1 .WHO es mates that in 2001, iron defi ciency anaemia (IDA) resulted in 273,000 deaths: 45% in Southeast Asia. 2 Iron defi ciency exerts adverse eff ects on immune response and alters the metabolism and growth of pathogens.It acts as an independent risk factor for developing lower respiratory tract infec ons (LRTI) in children 3 .Iron defi ciency thus may play an important role in wheeze associated respiratory tract infec on.With this background the present study was carried out to evaluate the role of iron defi ciency anaemia as a risk factor for wheeze associated respiratory tract infec on.

Material and Methods
This case control study was conducted at a mul disciplinary ter ary care hospital from July 2012 to June 2013.Children in the age group six months to fi ve years and having two or more episodes of wheeze associated respiratory tract infec ons, repor ng to paediatrics department were enrolled as cases and healthy children of the same age group as controls.Children with co-morbidi es like pre-exis ng pulmonary, cardiac or any other systemic illness and congenital anomalies were excluded from study.
The clinical presenta on of the pa ents was recorded a er taking a detailed history from parents.Clinical signs and laboratory inves ga ons were recorded on a predesigned performa.Healthy controls were selected from the paediatric OPD and well baby clinic a er taking consent from parents.Ethical clearance was obtained from ins tu onal ethical commi ee.A sample size of 50 children was selected for each group of cases and control.Venous blood was collected from each par cipant for complete haemogram, peripheral bloods smear and iron studies.Iron defi ciency was diagnosed by haemoglobin value <11.0 gm%, serum ferri n <12 ng/ml and RDW>15%.The sta s cal analysis was done using SPSS (Sta s cal Package for Social Sciences) Version 15.0 sta s cal Analysis So ware.

Results
A total of 50 children in each group were enrolled in the study.Majority of subjects in both the groups were males (n=31; 62%).Male to female ra o of study subjects was 1.63:1.Mean age of cases was 2.49±0.88years (range 0.6 -4.0 years) whereas in control was 2.62±0.83years (range 1-4.5 years).There was no signifi cant diff erence between two groups with respect to gesta onal age at delivery, mode of delivery, need of NICU admission and use of drugs in neonatal period (p>0.05).Both the groups were matched for anthropometric parameters and immuniza on status.The demographic characteris cs of study popula on are shown in table 1 and fi g 1.
The haematological parameters were similar in two groups, except for diff erence in monocyte and oeosinophil counts and absolute oeosinophil count.Mean monocyte, oeosinophil and absolute oeosinophil count was found to be signifi cantly higher in cases as compared to controls (p<0.05).Though propor on of cases with iron defi ciency anaemia was higher among cases (32%) as compared to controls (24%) yet the diff erence between two groups was not signifi cant sta s cally (p=0.373) as seen in table 3 & fi g -2 The peripheral blood smear was evaluated and microcy c, hypochromic blood picture was slightly higher in cases, but sta s cally, there was no signifi cant diff erence between two groups (p>0.05).The comparison of blood picture is shown in table 4.

Discussion
IDA is a problem of public health magnitude in preschool children in India.In communi es subsis ng on plant-based diets, inadequate dietary intake of iron with par cular reference to bioavailable iron accounts for the problem of IDA.Infec ous illnesses are known to contribute to various nutri onal defi ciencies through their physiologic and metabolic eff ects.Among preschool children living in underprivileged communi es in developing countries, respiratory infec ous diseases and IDA are o en coexistent and have complex, mutually adverse interac ons leaving severe func onal consequences.
In present study, there were more number of boys 31(62%) having wheeze associated respiratory infec on and were in agreement with the observa ons made by several researchers 4 who showed higher prevalence of males in diff erent subsets of children suff ering from respiratory tract infec ons including those categorized as wheeze-associated infec ons.The mean age of pa ents was 2.49±0.88years with maximum age of 4 years, thus indica ng higher prevalence of wheezeassociated respiratory illnesses among younger age group.The Tucson Children's Respiratory Study (TCRS) 5 corroborates the fi ndings of the present study.
The acute illness may also aff ect the haematological parameters.A prospec ve study done on children with acute respiratory infec ons, a signifi cant drop in haemoglobin concentra on by days 9 to 14 post mild viral illness was seen 6 .Serum iron and transferrin satura on fell signifi cantly, whereas erythrocyte protoporphyrin and serum ferri n increased signifi cantly.Most of the changes in iron parameters persisted for two or three weeks a er the appearance of fever, and some measures may have even become abnormal during the incuba on period of viral illness.Thus as infec on or infl amma on can infl uence iron status, it is always very challenging to exclude iron defi ciency anaemia in the context of concomitant infl amma on 7 .That is why in present study we used combined criteria (serum ferri n and RDW) as the criteria for evalua on of iron defi ciency.
In the present study, taking haemoglobin levels as the criteria for detec ng anaemia majority (57%) were found to be anaemic and among these 28 (49.1%) were found to be having iron defi ciency.Thus, in present study the prevalence of iron defi ciency anaemia itself is lower than that reported in general (67-77%) 8 which might be due to usage of a strict criteria of combina on of serum ferri n<12 ng/ml and RDW>15%.As aforemen oned, the combined criteria is more specifi c and rules out the chance higher prevalence of IDA 9 .Prevalence of iron defi ciency anaemia as per our criteria in present study was 32% in cases and 24% in control group, however, the diff erence was not signifi cant sta s cally though children with iron defi ciency anaemia were at a higher risk of wheeze associated respiratory diseases (OR=1.49;95% CI 0.62-3.59).This fi nding is in agreement with the observa ons of workers such as Ramakrishnan and Borade in 2010, who reported higher prevalence of asthma among anaemic children as compared to non-anaemic children and also indicated a signifi cant associa on between iron-defi ciency anaemia and respiratory illness 10 .
On evalua ng the haematological profi le for diff eren al counts of the children in case group to that of control group, no sta s cally signifi cant diff erence was observed between two groups except of mean monocyte, oeosinophil and absolute oeosinophil count to be higher in cases as compared to controls and may indicate the presence of an atopic ae ology in wheezeassociated infec ons.The limita on of the study was a smaller sample size and possible linkage may be further inves gated on a larger sample size

Conclusion
The fi ndings in present study do not suggest a possible linkage between iron defi ciency anaemia and wheeze associated respiratory infec on.However, inves ga on of a link is a step forward in direc on of further studies specifi cally targeted to review the role of iron defi ciency anaemia as a cause of wheeze associated respiratory infec on.Given the high prevalence of iron defi ciency anaemia in Indian popula on, it is essen al that possibility of such linkage should be explored further in long-term prospec ve interven on studies on a larger popula on to establish the iron defi ciency anaemia as a cause of wheeze associated respiratory infec on.

Fig 1 :
Fig 1: Sex distribu on of study popula on

Fig 2 :
Fig 2: Comparison of indices of iron defi ciency anaemia in study popula on

Table 1 :
Demographic Characteris cs of cases and controls

Table 2 :
Comparison of haematological parameters in study popula on

Table 3 :
Comparison of iron defi ciency anaemia in study popula on