Adrian I Morris
MBChB, DCH, MFGP 35 Finsbun'Ar.'enue Neg,l:rnds
7700
Curriculum vitae
Adrian Morris graduated from UCT Medical School in I983. After his housemanship at Groote Schuur Hospital, l-ris SHO posts included paediatrics at Red Cross Childreus' Hospital and emergencl, medicine at Groote Schuur Hospital. He then completed GP Vocational training in Surrel', (England) befbrc returning to Cape Tolvn in 1988, to join a group fbmilr.practice in Nervlands. He obtained the DCH(SA) in l9B9 and the MFGP(SA) in 1990. Allergr,and clinical immunologv are his special interests. He is a member of the British Society for Allergv and Clinical Immunologt', and r,r,as a delegate at their annual conftrence in London in 199I.
New Concepts in Bronchial Asthma
- Adrian ] Morris
Swrnrnnty
Bronchoscopic stwd.ies whicb hnve cgnJinned the inJlanunatotlt .t76rSrrt ot byonch'inl a.stbrua., ind.icnte th at rnersing the bronchospastic eleruerut by rneans of broncbod.ilntors nlone taay rnash tbe undrrlying late-phase infl atnncatoryr prlcess. T his ong oing pt lcess together with the resulta.Txt
broncbial hypewaponsitteness ( BHR) ntay be causative factors in nsthtun fuath nnd in tbe dnelopnaent of chronic obstt uct'ipe lung diseav.
Therapeutic appt oacha showld. therefot e airn to reduce both tbe inflnwnaaton process and the bronchospastic eletnent in nan the tnildtst asthynatic.
S Afr"Fatn Prnct 1992; 13: 196-9
I(EYWORDS:
Asthma; Inflammation; Death;
Bronchial Spasm; Lung Disease, Obstructive;
Bronchodilator Aeents.
uDeath
dw,ing an attaclz is unlewwn.
The nsthruatic pa.nts ilxtl old. nge."
William Osler 1892 This has bcen a comm()n
misconception of bronchial asrhma for almost one hundred t'ears.
During the past fbw years, a revolution in the understandine of the pathophvsiology of bronchlal asthma has taken place. No longer is it accepted that asthma is simple smooth-mu scle bronch o-consiri ction in isolation rvhich is reversed bv bronchodilaror rl'rerapv. For uiih the
).96 SA Fami\'Practice May 1992
advent of fibreoptic bronchoscopr', bronchial biopsl' and bronchoalveolar lavage, it has been demonstrated that a s t h m a i s a c h r o n i c . o n g o i n g , eosinophilic- infl ammatory bronchitis wltn rntermlttent acute
exacerbations.t'' It has been
speculated that the long-term sequel to poorly controlled asthma ma_v be i rrcversi ble airflow obstructiol'1, a condition which has in the past becn usually attributed to smoking or to chronic hrng infections.r
A more descriptive terminologv for astl-rma would bc "chronic
eosinophilic desquamative bronchitis".' This pathological process includes the shedding of bronchial epithelial cells; hypertrophv of bronchial glands and smooth muscle; thickening of the basement membrane; mucosal oedema and infiltration of eosinophils;
Iymphocyes; neutrophils and mast cells. Sucl'r changes are observed in most asthmatics, ranging from those with mild svmproms ro asrhma death necropsy specimens.2 (See Fig 1) Thc concept of earlv and late-phase bronchoconstriction rcacrions, bronchial hvperresponsiveness and the increased incidence and mortalitv in asthma have recentlv atrractcd considerable academic and clinical intcrest.
Early and late-phase reacrions Antigen binding specific IgE in
sensitised individuals, as well as non- specific irritants lcold air, gases, smoke and pollutanrs), can induce mast cell degranulation and release of preformed mediarors including l-ristamine. This results in immediate but transicnt bronchoconstriction and increased airway secretions. a process now referred to as the earhl
SA Huisanspraktl'k Mei 1992
Figure l: Pathology of Asthma:
B r o n c h o c o n s t r i c t i o n C h r o n i c A s t h m a I n l l a n r n r a t i o n and
o c d c m a
M u c u s P l u g
H v p c r t r o p h t of- S m o o t h M u s c l c S m r x t h t r l u s c l c
C o n t r r c t i o n p i t h e l i a l shcdcling and
t h i c l < c n e d b a s e n t e n t n r e n b r r n c
.. New Concepts in Bronchial Asthma
phase asthmatic reaction and lasts for one to two hours.
Commensurate nith the onset of the carlY-phase reaction, inflammatory leucocytes, mainlv eosinophils and lvmphoc"vtes, are recmited fiom the microcirculation and retained in thc airway wall. These cells release
Our basic understandine of asthma has changed radically
further inflammatory mediators, including Leukotrienes (LT), Platelet actir.ating factor (PAF) and
cosinophil Majt-'r hasic protcin (MBP), u-hicir cause further bronchoconstriction, mucosal ocdcma, cpithelial desquamation and mucus secretion. In turn further mast cell degranulation takes place.
This process r,r4rich takes three to ts'elve hours to occlrr and lasts up to t\\rcnt\r four hours, is known as the latc-phase asthmatic reaction. (Fig 2) Environmental control and potential
ailerger-r avoidance r,l'ill reduce this inflammatory process.
Beta adrenoceptor agonists, cholinergic antagonists and theophvllincs w'ill inhibit the early- phase reaction, but have iittle effect on the late-phasc reaction.3
Figure 2: Early and Late-phase Reactions:
Stcroids, including inhaled b e c l o m e t h a s o n e d i p r o p r i o n a t e . a r e potent inhibitors in the late-phase reactiorl. A continuous low dosage will also limit the early-phase reaction.
Propl-rylactic sodium chromoglycate limits both the early and late responses but is less effective than beclornethasone diproprionate.4
Non specific bronchial hyperresponsiveness or hyperreactivity (BHR)
Non-specific BHR can be defined as an increase above normal in both the casc and thc mrgnirudc of air-u'a1' narrowing on.exposure to a number of non specific bronchocoustrictor stimulis (inch.rding exercise, cold air, c i g a r c t r c s m o k c , v i n r s c s , i r r i t a n t g a s c s and environmcntal chemicals.) The late-phase reaction with its resultant bror-rchial epitheliai
I97 SA Familv Practicc May 1992 SA Huisartspraktvk Mei 1992
desquamation and inflammatory mediator rclease sets up a "vicious cvcle" r,r,'hereb,v further casual c \ p o s u r c to a l l e r g e n o r t o a m i n o r irritant triggers a marked airway hvperresponsiveness which mav last l.eeks or even months after the initial allergen provocation. BHR may manifest as episodic
bronchoconstriction, circadian variation in pulmonary function or increased response of tl-re aim,av to cold air, exercise and environmental irritants. (Fig 3)
Once environmental irritants have been removed or ar''oidcd, asthma therapy should combine
bronchodilators, primarily B, adrenoceptor agonists, r.vith non bronchodilator antiasthma preparations, such as sodium
chromogl,vcates and glucocorticoids.u G l u c o c o r t i c o i d s a r c p o t e n t a n t i - inflammatory agents which block the late-phase reaction and reduce bronchial h-vperresponsiveness.3 Oral use of steriods should be restricted on account oftheir side affect profile.
Inhaled steroids are now being re- evaluated follou'ing recently expressed concern regarding suppression of hypophyseal - pituitarrr - adrenal axis r,vhich has accompanied higher dosages.
The worldwide increase in asthma morbidiry and mortality
Despite more active treatment and improved medical services, the number of asthma deaths worldwide have increased in recent years. This mav be due to increased bronchial s e n s i t i s a t i o n a r r d h r p e r r e s p o n s i v e n e s s from environmental pollution, or
mav reflect the increasing diagnosis of chronic cough as asthma.
New Concepts in Bronchial Asthma
* Antigcn S p e c i l i c l n n e d r a t e
E a r h P h a s c l l r o n c h o c o n s t r i c t i o n
4 /
t /l t
\ l\ _ _ \ ,
H i s t a n r i n e \ '\
v
I
* Irrit:rnts ( N o n specific)
D ' ./7-
// * IgE
I - i t e P h i s c
E , , r i n , , p h i l - -
l i . r . r ' \ , , , r . f r , r : ' r l
I l \ l ] l f
o E D r t i r i l i e l D . r n r r q t
l l r o n c h i a l H \ p c r r c a c t r i S '
O \ ' . r s c u l e r P c r m c : r b i h n
O I I u c u s O c c l e n r e
a l l u c u s
I n c r c a s c c l A c c c s s o f . { n t i g e n s ancl Non spccific Irritents
O 6
l s "
, < a
e > ?
N l a s t Ccll
Figure 3: Air-ways Inflammation and Bronchial Hyperreactivity
In 1990 Sears et af in Nelv Zealand tried to implicate the widely used beta adretroccptor agonists, ar present the mainstav of asthma prophylaxis and treatment.
Excessivel.v frequent use and high dosaqe of bronchodilators8 and undei-use or inappropriate use of
treatment. A conseqr.lence of this d i l a t a t i o n o f i n l l a r t r c d a i n r a y s m a v mean further allergen exposllre, furtl-rer inflammation and hvperresponsiveness. It has been proposed that perhaps
bronchoconstriction is a phrrsiologic protcctive mechanism to limit allergen exposure to the lung mucosa.'
In the past, despite their efficacy, too mucir reliancea has been placed on r o u t i n c b r o r r c h o r l i l a t o r t h e r a p v i n asthma, and it is now rccommendecl that they be used as required to avoid possible tolerance developir-rg.
Thc inflammatory process has been largely ignorecl in the past and therc is a need to cncourage the
prophvla.ti.' use ol' sodittnt
Asthma is seen as a chronic eosinophilic desquamative inflammatory process of the alrways
corticostcroids may mask ti-re severitv of the chronic inflammatory
underlying process and delay the patient seeking further medical
f 98 SA Familv Practice Mat' 1992 SA Huisartspraktvk Mei 1992
. . New Concepts 1n
chromoglycate, ketotifen or low dose inhaled steroids in all but the most mild intermittent asthmatic. Patients often appear asymptomatic despite having severe ongoing airflow limitation, therefore regular peak flow monitoring is essential to identify the "at-risk" padent.
Conclusion
Our basic understanding of asthma has changed in that it is no longer seen as isolated bronchoconstriction, but as a chronic eosinophilic
desquamative infl ammatory process of the airways.
Aft er environmental manipulation and allergen-avoidance measures have been implemented, the treatment of asthma should be reviewed. Any asthmatic requiring a beta
adrenoceptor agonist more than three
Review the treatment of any asthmatic needing a beta andrenoceptor agonist more than 3 times per week
times oer week should be treated with prophy'actic regimes such as sodium chromoglycate or ketotifen
(especially in children) or inhaled steroids.'o Although theophyllines are among the cheaper drugs available, their unacceptably high side-efFect profile and narrow therapeutic rangell will probably reserve them as second line therapy for more resistant asthmatics. It is important in a third- world situation, where costs of medication are a significant limiting factor, to weigh up the advantages and disadvantaees ofthe various therapies.
I99 SA Family Practice May 1992 SA Huisartspraktyk Mei 1992
Bronchial Asthma
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