PREVALENCE OF AIRWAY HYPERREACTIVITY AMONG CHILDREN WITH SICKLE CELL ANAEMIA IN STEADY STATE AT THE LAGOS UNIVERSITY TEACHING HOSPITAL

Abstract

Sickle cell anaemia is associated with a spectrum of pulmonary disorders
which contributes significantly to morbidity and mortality in affected
children. Airway hyperreactivity (AHR) is a documented pulmonary
function abnormality in sickle cell anaemia which has been associated with
increased acute chest syndrome (ACS) and vaso-occlusive crises events per
patient year. It is defined as the development of a specified reduction in
forced expiratory volume in one second or peak expiratory flow rate after
exposure to an arbitrary but generally agreed upon dose of stimuli. One of
such stimuli is exercise. Symptoms of AHR following exercise challenge
include shortness of breath or wheezing, decreased exercise endurance, chest
pain or tightness, cough, stomach ache and sore throat.
This is a cross sectional comparative study of the prevalence of airway
hyperreactivity (AHR) using controlled exercise on a treadmill, between
children with sickle cell anaemia and apparently healthy homozygous
hemoglobin A controls. Seventy HbSS patients in steady state attending the
paediatrics hematology clinic of Lagos University Teaching Hospital and 70
age and sex matched healthy controls, participated in the study.
An interviewer administered, structured questionnaire was applied to obtain
information on patient’s bio-data, medical and medication history and family

history after obtaining informed consent from participants that met the
inclusion criteria for the study. Physical examination was carried out before
exercise. Cardio-respiratory parameters were documented pre and post
exercise. PEFR and FEV1were recorded with an electronic peak flow meter
before and after six minute non-stop treadmill exercise. Airway
hyperreactivity was defined as a ≥10% reduction of the PEFR from the pre
exercise level. AHR was graded as mild, moderate and severe.
The baseline PEFR and FEV1 was significantly lower in HbSS subjects
(266.07±61.74 L/min and 1.33±0.3L) than controls (295.07±69.7 L/min and
1.65±0.38L); p=0.01 and <0.0001 respectively. The baseline PEFR was
88.6±14.3% of predicted values for height for subjects and was significantly
lower than for controls (93.4±11.1%; p=0.028). The baseline FEV1 was
86.3±17.2% of predicted values for height for subjects and was significantly
lower than for controls (92.6±12.3%; p=0.014).
Sixty two HbSS and fifty five controls and thirty eight HbSS and thirty
controls showed a fall in PEFR at 5 and 10 minutes respectively. The fall in
PEFR was greater in subjects than controls at 5minute (10.05±2.47% vs.
8.83±1.69%; p=0.003) and 10 minutes (11.1±2.8% vs. 9.01±1.84%;
p=0.005) post exercise. A severe degree of fall was seen in 2 subjects, 1 at 5
minutes and one at 10 minutes.

Thirty nine participants had AHR demonstrated by both PEFR and FEV1,
eight by PEFR only, and none by FEV1 only There was a high agreement
between FEV1 and PEFR but the latter was more likely than FEV1 to detect
AHR (kappa=0.866; p<0.001).
The study showed significantly higher overall prevalence of AHR in
subjects with AHR demonstrated in 33(47.1%) subjects and 14(20%)
controls (p=0.001). Eighteen subjects (25.7%) and eleven controls (15.5%)
had mild AHR, 13(18.6%) and 3(4.3%) respectively had moderate AHR and
2(2.9%) and none (0%) respectively had severe AHR.
Of those who had a positive history of symptoms suggesting airway
hyperreactivity, 15(41.7%) had <10% fall in PEFR while 21(58.3) had a
≥10% reduction in PEFR. Of those not reporting symptoms, 78(75%) had
<10% fall while 26(25%) had >10% fall.
Among HbSS subjects and controls, there was no age related trend in the
prevalence of AHR. However, the prevalence of AHR was higher in HbSS
subjects in all age groups but only significantly so in age group 6 to 7 years
(p=0.025). Of the 33 subjects with AHR, 9(27.3%) had history of exercise
induced symptoms while 24(72.7%) did not while 2(14.3%) of the 14
controls with AHR had history of exercise induced respiratory symptoms
and 12(85.7%) did not. In both subject and control groups, all subjects who

admitted to a history of exercise-induced symptoms, manifested airway
hyperreactivity (p=0.0005 and 0.0377 respectively).
Of the participants with demonstrable AHR, 5(15.2%) in the HbSS group
and 1(7.1%) in the control group, required a stat dose of bronchodilator to
alleviate symptoms following exercise while symptoms resolved
spontaneously in the rest. The commonest symptom among subjects was
cough occurring alone or in combination with other symptoms in seven
(10%) children. Cough was also the symptom in the two controls with post
exercise complaints. Other non respiratory symptoms observed postexercise
include mild leg ache in five (7.2%) HbSS subjects and three (4.3%)
controls. This resolved spontaneously before leaving the test venue. There
was no report of exercise attendant crises in the HbSS during follow up on
phone a week after exercise.
It is concluded that PEFR and FEV1 in SCA patients are significantly lower
than that of age and sex matched controls. It is also concluded that there is a
high prevalence of AHR in children with SCD. AHR was documented with
or without a positive history of respiratory symptoms in participants and that
airway hyperreactivity may exist in patients with SCD even in the absence
of the clinical symptoms suggesting AHR. There is therefore a need to elicit
history suggesting AHR and routinely screen SCA patients at follow up
clinics.

PREVALENCE OF AIRWAY HYPERREACTIVITY AMONG CHILDREN WITH SICKLE CELL ANAEMIA IN STEADY STATE AT THE LAGOS UNIVERSITY TEACHING HOSPITAL