Abstract:
Twenty publications are submitted. All deal with the issues of control of two
ends of the spectrum of immune-mediated respiratory disorders in children,
namely atopic (asthma and allergic rhinitis) and HIV-related lung disease.
This submission summarises the research by the author into this spectrum of
lung diseases of children in South Africa, highlighting the diversity of conditions
that are not only clinically important, but also common. Understanding of all
conditions is required to improve the health of children in this region.
Management of chronic conditions requires two major end points - adequate
and timely diagnosis and - management to control the condition. The author has
a passion for improving the quality of life of children and firmly believes that the
research findings will, and have, led to transformation in management of both
these common disorders. This document follows the progression of the authors research work and
highlights how interesting and important is the scope of two disorders which
could be thought to have a central origin, namely in the T-cell. T-cells form the
basis of cellular immunity and an excess of T-helper 2 cell activity promotes
atopy, whilst the human immunodeficiency (HI) virus infects T-helper cells and
promotes cellular immune deficiency and its attendant clinical disorders. The
author’s research work is not based on the immunological basis of these
conditions but does deal with the clinical implications and especially aspects
relating to control of these two extremes of a clinical spectrum of disorders. To
take the clarity of two diseases at the end of a spectrum to its natural conclusion
these extremes are defined in aetiology or pathophysiological differences
(excess versus suppression of the immune system), occurring in the affluent
and poor alike versus just the poor, control being required to improve quality of
life versus to save lives and finally that management requires anti-inflammatory
therapy versus antibiotic and anti-infective therapy. For the eight publications based on atopic respiratory disease in children the
themes are firstly that children with asthma and chronic rhinitis are diagnosed
late, that most individuals with these conditions are not well controlled and
finally that the reasons for lack of control are becoming obvious.
For the first time, the significant lack of asthma and allergic rhinitis control in
South Africa is documented. These studies suggest that, like surveys from the
rest of the world, asthma control is seriously under-estimated and neglected in
all asthmatics in South Africa, in both the privileged and the under-privileged.
The research also defines reasons for poor asthma and allergic rhinitis control
in this region. As in many studies published from around the world it is now
evident that poor asthma and allergic rhinitis control cannot be blamed on any
one source. A multitude of reasons underlie this phenomenon and each of the
subsequent papers in this section illustrates attempts at defining these
principles. The three most important reasons for poor control are probably that
most asthmatics are managed in the wrong hands (by doctors who don’t
understand adequate control and who aren’t empowered to use the correct
therapy), that control may actually be a pipe dream and practically difficult to do
or even impossible to achieve and lastly that the allergic basis of asthma is over
emphasised and may not in fact determine all asthma. The subsequent papers summarise research work in the field of HV infection in
children and exposes the opposite end of a spectrum of Paediatric respiratory
disease and highlight research into the conditions common in HIV-infected
children. Eleven papers are presented. For the diseases associated with the HI
virus the major complications of inadequate diagnosis and prevention in
children are acute pneumonia (especially severe pneumonia) and
bronchiectasis. Bronchiolitis is not common in HIV infected children, despite
epidemics of this condition in non-infected children. Passive smoking does not
aggrevate or worsen disease progression in children. The complications of HIV
related diseases in children require the same principles of adequate diagnosis
and control as would apply to the chronic atopic conditions. Once the author delved into the disorders at the other end of the clinical
spectrum, namely those associated with immune deficiency secondary to HIVinfection
he faced the question of a possible relationship between the
conditions. One submission explores that relationship.
This research has a unique perspective, conferred by the fact that these two
conditions do not occur to the same extent anywhere else in the world. Atopic
respiratory conditions and HIV-related lung diseases occur side by side in
abundance in this region. This perspective has created a clarity for research to
address the two most important aims in clinical medicine, namely to diagnose
correctly and then to manage the condition so that control is achieved. These
must be universal principles of the successful practice of medicine.