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A. OEHLING

KEY-WORDS: Asthma - Bacterial infection - MOTS-CL1~S: Asthme - Infection bact~rienne -Pathophysiology. Physiopathologie.

In several publications, we have alreadyemphasised the little importance given to thebacterial infection factor in the etiopathogenesisof bronchia l asthma. This is, the role played by thebacterial antigens duri ng the bacterial infection inthe rhinos inubronchia l uni t , assuming theresponsibility of the inflamma tory response, inboth nasal and bronc hial mucosa, and cause of thesubsequent bronchospasm, the inflammation andobstruction. It is therefore surprising that in mostpublications regarding treatment of bronchialasthma, only the symptomatic treatment isconsidered and the bacterial infection factor iscompletely overlooked. It is alarming tha t even inthe international consensus on treatment ofbronchial asthma this aspect is totally ignored. Inthis kind of asthma, fre quentl y labelled as

dntrin sio,, we usually find that the treat mentgiven is of the kind that ,,maintains,, asthma; thisis, excessive treatments with bronchodilators andcorticosteroids.

The bacterial infection in the etiopathogenesis ofbronchial asthma has been given great importancefrom the first decades of this century. Many of thepio nee rs in the study of this disease [1-6]emphasised that the recurring bronchitis withbacterial infection associated a bronchospasticcomponent and they drew the attention to theclose relation between infection and asthmaticreaction. Subsequently, from the 50s to the 70 s ,several authors among whom we are included [7-15] emphasise once again the importance of thebacterial infection factor in the etiopathogenesis ofbronchial asthma.

D e p a r t m e n t o f M l e r g o l o g y a n d C l i n ic a l I m m u n o l o g y , U n i v er s it yCl i n i c , Fa c u l t y o f Me di c i ne Uni ve r s i t y o f Na va r ra , PAMPL ONA,(Spa i n ) .C o r r e s p o n d e n c e : P r. A . O e h l in g , D e p a r t m e n t o f M l e r g o l o g y a n dCl i n i c a l Immunol ogy , Uni ve r s i t y Cl i n i c , Fa c u l t y o f Me di c i neUni ve r s i t y o f Na va r ra , PAIVlPL ONA, (Spa i n ) .I n t e r a s m a M a r r a k e e h ' 9 8 .

O E H L I N G A . - B r o n c h i a l a s t h m a a n d b a c t e r i a l i n f e c ti o n . R e v . f t .A l l e r g o l . , 1 9 9 8 , 3 8 ( 7 S ), $ 2 4 8 - $ 2 5 7 .

Expa nsion Scientifiqu e Publications, 1998


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Fig. 1. - Immuno logical and non immunological mechanisms ininfective asthma.T h e p r o b l e m o f t h e b a c t e r i a l a l le r g y i nb r o n c h i a l a s t h m a h a s p r o b a b l y b e e n o n e o f t h em o s t c o n t r o v e r s i a l a s p e c t s b e t w e e n A l l e r g o l o g i s t sa n d R e s p i r a t o r y D i s e a s e S p e c i a l i s t s i n t h e l a s tt h i rt y y e a rs . T h a n k s t o t h e a d v a n c e s o f m o d e r ni m m u n o p a t h o l o g y , a m o r e e x a c t k n o w l e d g e o ft h e s p e c if i c it y o f d i f f e r e n t b a c t e r ia l a n t i g e n s h a sb e e n r e a c h e d , i n b o t h i n v i t r o d i a g n o s i s a n dc h a l l e n g e t e s t s .I n s p i te o f t h e d e t r a c t o r s [ 1 6 -1 9 ] o f t h ei m p o r t a n c e o f t h e i n f e c t i o n f a c t o r in th e

t r ig g e r in g o f b r o n c h o s p a s m , i t h a s b e e n i n r e c e n ty e a rs w h e n n o r n [ 20 -2 3 ] a n d m a n y o t h e r a u t h o r s[ 2 4 - 2 6 ] h a v e d e m o n s t r a t e d i t s r e s p o n s i b i l i t y a tb r o n c h i a l m u c o s a l e v el . T h i s i s h o w , t h ec o n c l u s i o n is d r a w n t h a t t h e a s t h m a t i c r e s p o n s es u b s e q u e n t t o a b a c t e r i a l b r o n c h i o l a r i n f e c t i o np r o c e s s c a n b e t r i g g e r e d b y a n I g E - m e d i a t e dr e s p o n s e , b y a r e s p o n s e m e d i a t e d b y o t h e ri m m u n o g l o b u l i n s , o r s u b s e q u e n t l y b y le c ti n sf r o m t h e o w n b a c t e r i a ( f i g . 1 ) .I n f a c t a l l t h e s e l a s t p u b l i c a t i o n s c o n f i r m w h a tm a n y o t h e r a u t h o r s h a d a l re a d y d e m o n s t r a t e db e f o r e , e i th e r f r o m a n e x p e r i m e n t a l o r f r o m a

c l in i ca l po in t o f v i ew [7 , 8 , 11 , 27-31] .

P R E S E N T S IT U A T I O N O F I N F E C T I O NI M M U N O P A T H O L O G Y : I M P O R TA N C EO F T H E B A C T E R I A L A N T I G E N ST h e i m p o r t a n c e o f t h e v ir a l i n f e c t i o n i n t h et r i g g e r i n g o f i n t r i n s ic a s t h m a , e s p e c i a l l y i n

Re~.fr. AllergoL, 1998, 38, 7S

$249c h i l d h o o d a s th m a , h a s b e e n f r e q u e n t l ye m p h a s i s e d [ 1 6 -1 9 ]. O u r g r o u p , i n a v e r y l a r g es t u d y p e r f o r m e d w i th a n u m b e r o f c a se s a n d v i r u sh i g h e r t h a n a n y o t h e r s t u d y [ 32 , 3 3 ] , f o u n d ap o s i ti v e s e ro l o g y at t h e m o m e n t o f t h e a s t h m a t i cc r is i s i n o n l y 1 4 , 5 % o f t h e c h i l d r e n . R e c e n t l y ,o t h e r a u t h o r s a r e i n s i s t i n g o n t h e c o n j u n c t i o n o ft h e v i r a l i n f e c t i o n a s s o c i a t e d t o t h e b a c t e r i a li n f e c t i o n [ 25 , 3 4 ] . T h e p o t e n t i a t i n g e f f e c t o f th ev i r u s o n b a c t e r i a - i n d u c e d m e d i a t o r r e l e a s e m i g h tb e o f im p o r t a n c e f o r t h e c o n v e r s io n f r o m l a te n tt o m a n i f e s t a s t h m a i n u p p e r r e s p i r a t o r y t r a c ti n fe c ti o n . T h e e n h a n c e m e n t b y i n f lu e n z a A vi ru so f b a c t e r i a l - i n d u c e d h i s t a m i n e r e l e a s e m a y p l a y ar o l e i n m i x e d b a c t e r i a l a n d v i r a l i n f e c t i o n s w h e nt h e p a t i e n t i s s e n s i ti z e d t o t h e b a c t e r i u m i nq u e s t i o n . I n o u r o p i n i o n , t h is i s w h a t u s u a l l yh a p p e n s w h e n a v i r a l i n f e c t i o n s t a r t s a n d t h i s i sw h y w e d o n o t f i n d i t so i m p o r t a n t i n b r o n c h i a la s t h m a [ 3 2 ]. O f c o u r s e , m a n y r h i n o s i n u s a li n f e c t i o n s s t a r t w i t h a v i r al i n f e c t i o n ( r h i n o v i r u so r o t h e r s ) , b u t f e w d a y s a f t e r w a r d s t h e a s s o c i a ti o no f a b a c t e r i a l i n f e c t i o n i s v e r y f r e q u e n t , s t a r t i n gt h e n a n i n c r e a s e o f h y p e r r e a c ti v i t y w h i c h a f f ec t st h e b r o n c h i a l m u c o s a . T h i s is w h a t w e h a v e b e e no b s e r v i n g f o r m o r e t h a n 4 0 y e a r s i n t h e e v e r y d a yc l in i ca l p rax i s .

T a k i n g i n t o a c c o u n t t h a t i f w e a d m i t t h e a c t i o no f t h e b a c t e r ia l a n t i g e n s w i t h th e i r c o r r e s p o n d i n gh u m o r a l a n d c e l l u la r r e s p o n s e w e m u s t c o n s i d e rt h a t w e w i ll f i n d I g E - m e d i a t e d r e a c t i o n s , a s w e l l asr e ac t io n s m e d i a t e d b y i m m u n o c o m p l e x e s a n d b yc e l l u l a r i m m u n i t y . I n t h i s s e n s e , s e v e r a l a u t h o r sd e t e c t t h a t s p e c if i c I g E a n t i b o d i e s t o b a c t e r i a c a nb e i d e n t i f i e d i n t h e s e r a o f p a t i e n t s f r o m an u m b e r o f r e s p i r a t o r y d i s e a s e s [ 3 5 ]. P a u w e l s i n1 9 8 0 [ 3 6 ] d e m o n s t r a t e d s p e c i f ic I g E a g a i n s ta n t i g e n s t o H a e m o p h i l u s i n f l u e n z a e a n d S t r e p t o c o c c u sp n e u m o n i a e ; t w e n t y- n i n e p e r c e n t o f t h ei n v e s t ig a t e d s e r a h a d s u c h a n t i b o d i e s i n b r o n c h i a la s t h m a . T h e d e m o n s t r a t i o n o f I g E a n t i b o d i e s t ob a c t e r i a i n p a t i e n t s w i t h b r o n c h i a l a s t h m a , b o t hi n t h e e x t r i n s i c a n d i n t r i n s i c a s t h m a g r o u p , o p e n sn e w p e r s p e c t i v e s f o r t h e s t u d y o f t h e r o l e o fi n f e c t i o n a g e n t s i n a s t h m a . S t u d i e s p e r f o r m e d o nc h i l d r e n w i t h i n t r i n s i c b r o n c h i a l a s t h m a a n d w i t hb a c t e r i a l a n t i g e n s d e m o n s t r a t e a n t i g e n - s p e c i f i ch i s t a m i n e r e l e a s e i n t h e b a s o p h i l , a g a i n s t abac t e r i a l son ica t e ( f i g . 2 ) [37] .

V e r y i m p o r t a n t t o o a r e t h e s t ud i e s p e r f o r m e d[ 2 7 , 3 8 ] i n r e l a t i o n w i t h t h e r e s u l t s o f c h a l l e n g et e s ts W i th b a c t e r i a l a n t i g e n s . T h e a u t h o r s u s e t h eb r o n c h i a l p r o v o c a t i o n a s a ' m o d e l i n b a c t e r i a lb r o n c h i a l i n f e c t io n s . T h e l a t e r e a c t i o n ise x p l a i n e d b y a t y p e I l l a l l e r g ic r e a c t i o n .


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Fig. 2. - Bacterial histamine release in intrinsic asthma patients,

S t ud i es p e r f o r m e d b y H o l t et al. i n r e c e n t y e a rs[ 39 , 40 ] s h o w t h e i m p o r t a n c e o f t h e d e n d r i t i cc e l l s ( D C ) , w h i c h a r e e q u i v a l e n t t o t h eL a n g e r h a n s c e l ls ( L C) i n t h e b r o n c h i a le p i t h e l i u m , a s p r e s e n t i n g c e ll s o f th e a n t i g e n .S t u d ie s p e r f o r m e d b y th e s e a u t h o r s h a v e s h o w nt h a t i n h a l a t i o n o f b a c t e r ia l L P S l e a d s to r a p i da c c u m u l a t i o n o f D C i n t h e a i r w a y e p i t h e l i u m a n d ,b y 2 4 h o u r s a f t e r a e r o s o l c h a l l e n g e , t h e d e n s i t y o ft h e r e s u l t i n g i n t r a e p i t h e l i a l D C n e t w o r k c a na p p r o a c h 2 0 0 % o f th a t s e e n i n t h e s t ea d y s ta te[ 4 1] . A c c o r d i n g to t h e s e a u t h o r s b y s t a n d e ri n f e c ti o n s i n t h e r e s p i r a to r y t r a c t w h i c h o c c u rc o n c o m i t a n t l y w i t h e x p o s u r e t o i n h a l a n t a l l e r g e nc o u l d s t im u l a t e t h e m i g r a t i o n o f a ct i v at e dI F N ( z/ IL - 1 2 s e c r e t in g p h a g o c y t e s f r o m i n f e c t e da i r w a y t is s u e i n t o t h e r e g i o n a l l y m p h n o d e s . T h a ti s , b y s t a n d e r r e s p i r a t o r y b a c t e r i a l i n f e c t i o n s c a nd i re c tl y m o d u l a t e T H 1 / T H 2 s e le c ti o n in t h ei m m u n e r e s p o n s e t o i n h a l a n t a l l e r g e n s ( f i g . 3 ) .R e c e n t l y a l so h o l t [ 4 2 ] i n si st s t h a t o n e o f th e m o s tp o t e n t e x o g e n o u s s t i m u li i d e n t i f ie d f o r a c t i va t io no f a n t i g e n p r e s e n t a t i o n m e c h a n i s m s a n d IL -1 2p r o d u c t i o n b y D C i s i n t e r a c t i o n w i t h m i c r o -o r g a n i s m , i n p a r t i c u l a r L P S f r o m b a c t e r i a l c e l lw a ll s. I n f i g u r e 4 , t h e d y n a m i c s o f t h e b a c t e r i a li n f e c ti o n , th e r o l e o f m a c r o p h a g e s a n d d e n d r i t i cc e l l s a g a i n s t b a c t e r i a l a n t i g e n s s t i m u l a t i n g I L - 1 2p r o d u c t i o n , c a n b e s e e n ; h o s t r e s p o n s e s t o

< < b ys ta n de r, , i n f e c t i o n s i n r e s p i r a t o r y t r a c t p r o d u c ef u r t h e r s y n e r g i s t ic T H - 1 s e l e c t i v e c y t o k i n e s i g n al s .A s w e s ai d b e f o r e a n d a c c o r d i n g t o t h em e n t i o n e d a u t h o r s [2 1- 24 , 2 6 , 4 3 ] i n t h e i r l a r g ea n d t h o r o u g h s t u d i e s t h e b a c t e r i a l a n t i g e n s a r ed e m o n s t r a t e d t o b e a b l e t o r e l e a s e h i s t a m i n e i n

m a s t -c e l ls a n d b a s o p h i l s ( o n o n e h a n d I g E -m e d i a t e d a n d o n t h e o t h e r h a n d t h r o u g h t h el e c t i n ) ( f ig . 5 ) . S e v e r a l st r a i n s o f b a c t e r i a c a u s e dr e l ea s e o f h i s t a m i n e f r o m h u m a n b a s o p h i ll e u k o c y t e s in v i tro , a n d i t i s s p e c u l a t e d t h a t t h i sr e l ea s e c o u l d b e a p a t h o g e n i c m e c h a n i s m i ni n t r in s i c a s t h m a . O n t h e b a s is o f th e s e f i n d i n g s i ti s t e m p t i n g t o s p e c u l a t e t h a t b a c t e r i a l a n t i g e n sr e i n f o r c e t h e r e l e as e o f h i s t a m i n e c a u s e d b ya l l e r g e n s i n a l l e r g i c p a t i e n t s o r b y b a c t e r i a i np e r s o n s s e n s i t i z e d t o b a c t e r i a , s i n c e i t i s w e l lk n o w n t h a t a l l e r g i c s y m p t o m s a r e i n c r e a s e dd u r i n g i n f e c t i o n s [ 2 1 , 2 3 ] .T h e I g E - m e d i a t e d h i s t a m i n e r e l e a se c a u s e d b ys p e c if i c a n t i g e n s ( a l l e r g e n s o r b a c t e r ia ) i ns e n s i ti s e d i n d i v i d u a l s w a s e n h a n c e d b y L P S .H i s t a m i n e r e l ea s e i n d u c e d b y t h e s p e c if i ca l l er g e n s w a s e n h a n c e d b y t h e b a c t e r i u m . L P Sf r o m S . a u r e u s a n d S . t y p h i m u r i u m i n d u c e dp o t e n t i a t i o n o f h i s t a m i n e r e l e a s e b y s p e c if i ca l l e r g e n s in l e u k o c y t e s u s p e n s i o n s f r o m p a t i e n t ss e n s i t i z e d t o h o u s e d u s t m i t e o r b i r c h p o l l e n .T h a t i s, t h e h i s t a m i n e r e l e a s e i n d u c e d b y t h e

R e v . f r . A l l e r g o l . , 1998, 3 8 , 7S


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s p e c i f ic a l le r g e n s i s e n h a n c e d b y t h e b a c t e r i a lL P S. A n e n h a n c e m e n t o f m e d i a t o r r e le a se b yb a c t e r i a o r t h e ir c o m p o n e n t s m i g h t p l a y a r o l e i nt h e a g g ra v a t i o n o f b r o n c h i a l a s t h m a d u r i n gi n f e c t i o n s [ 2 4 ] ( fi g. 6 a n d 7 ) . B a c t e r i a l c o m p o n e n t sRev.fr . Al lergol ., 1 9 9 8 , 38 , 7S

s u c h a s p e p t i d o g l y c a n , t e i c h o i c a c i d a n de n d o t o x i n s f r o m a i r w a y b a c t e r i a c a n a g g r a v a t ea l l e r g i c m e d i a t o r r e l e a s e . I n f i g u r e 8 , t h e r e s u l t so b t a i n e d i n a s tu d y p e r f o r m e d b y u s [ 4 4] c a n b es e e n , w h e r e d e m o n s t r a t e t h a t t h e a n ti g e n


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Fig. 5. - Role o f bacterial a ntige ns and lectin sin the asthmatic reaction.

Staphylococcus aureus p o t e n t i a te s a t t h e m a x i m u md e g r e e h i s t a m i n e r e l ea s e t o g e t h e r w i th t h ea n t i g e n D . p t e r o n y s s i n u s a n d e s p e c i a l l y ina s t h m a t i c p a t i e n t s w i t h n a s a l s e c r e t i o n c u l t u r ep o s i t i v e t o t h e b a c t e r i u m .I n a n o t h e r s t u d y [ 4 5] a n d a s c a n b e s e e n i nT a b l e I , t h e d i f f e r e n c e s b e t w e e n p o l l e n a l l e r g i ca s t h m a a n d i n t r i n s i c a s t h m a w h e r e t h e b a c t e r i a lf a c t o r p l a y e d a n i m p o r t a n t r o l e i n t h eb r o n c h o a l v e o l a r l a va g e , w e r e p r o v e n . I n t h is t a b l ew e c a n s e e t h a t t h e r e is an i n c r e a s e o f C D 4 i n b o t hk i n d s o f a s t h m a . B y c o n t r a s t , t h e p o l l i n i c f o r m i sc h a r a c t e r i z e d b y a n in c r e a s e i n I L - 2 R / C D 2 5 a n d ,i n p a r t ic u l a r , a n i n c r e a s e i n I L -4 a n d C D 2 3 . I nb a c t e r i a l a s t h m a a n i n c r e a s e o f IL - 2 , I FN - ,/, a n dI L- 5, a m o n g o t h e r s , c a n b e o b s e r v e d .

A . O E H L I N G /F i n al ly a n d a s f a r as t h e i n f l a m m a t o r y r e s p o n s e

is c o n c e r n e d , t o w h i c h m o r e a t t e n t i o n h a s b e e np a i d i n r e c e n t y e a r s a l t h o u g h i t h a s b e e nc o n s i d e r e d f o r m a n y y e a r s e s s en t ia l i n t h ea s t h m a t ic r e s p o n s e , t h e s u b s t a n c e s r e s p o n s i b l e f o ri t h a v e a l so b e e n s t u d y i n d e p t h . T h e c a t io n i cp r o t e i n o f t h e e o s i n o p h i l ( E C P ) i s p r o b a b l y t h em o s t s tu d i e d a m o n g t h e m , a n d w h o s e i m p o r t a n c ew e h a v e a l r e a d y s t a t e d i n a p r e v i o u s w o r k [ 4 6 ] .Recen t ly , Ka rawi j czyk et al. [ 4 7 ] c o u l d f o l l o w t h eE C P l e v e ls i n s e r u m i n t h e c o u r s e o f a c u t eb a c t e r i a l a n d v i r a l i n f e c t i o n s . T h e m e a n v a l u e s i nc o n t r o l s ( fi g . 9 ) w e r e 8 , 8 p g / 1 . T h e r e f o r e , E C Pl ev e ls a n d t h e s u b s e q u e n t i n f l a m m a t o r y r e s p o n s ea r e e l e v a t e d w h e n t h e r e i s a b a c t e r i a l i n f e c t i o n . A l lt h is i n d i c at e s t h a t t h e e o s i n o p h i l r e s p o n s e is m u c hh i g h e r i n b a c t e r i a l i n f e c t i o n t h a n i n v i r al in f e c t i o na n d t h e i n f l a m m a t o r y c o m p r o m i s e i s a l so gr e a te r .

C o n s i d e r i n g a ll th e e x p o s e d , w e w o u l d l ik e t oh i g h l i g h t t h a t i n r e c e n t y e ar s a n d t h r o u g hd i f f e r e n t a r t ic l es e m p h a s i s i s b e i n g p u t a g a i n o nt h e l i t t l e i m p o r t a n c e t h a t b a c t e r i a l a n t i g e n s a r eg i v e n in t h e t r ig g e r i n g o f th e a s t h m a t i c r e s p o n s e .I n t h i s s e n se , t h e w o r k s b y N o r n et aL [48 , 49 , 50 ] ,J u s t [ 5 1 ] , J o n e s [ 5 2 ], H a h n [ 5 3 ], H o f m a n n [ 5 4]a n d o t h e r s s t a n d o u t . A l l o f t h e m i n si s t o n t h e f a c tt h a t t h e b a c t e r i a l a n t i g e n s a s s u m e t h e m a i nr e s p o n s i b i l i ty in t h e in f l a m m a t o r y a n db r o n c h o s p a s t i c r e s p o n s e s i n t h e e t io l o g y o fb r o n c h i a l a s t h m a d u r i n g t h e r e s p i r a t o r y i n f e c t i o n .

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Fig. 6. - Potentiation by S. aureus and S. typhi muriu m LPS of histamine release induced by birch pollen.Rev. fi: Allergol., 1998, 38 , 7S


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S U B S E Q U E N T T R E A T M E N TO F I N F E C T I O N

Through all the exposed and considering theimportanc e o f the bacterial infection factor in theetiopathogenesis of bronchial asthma, we mustconsid er it very seriously when prescri bing t hetreatment. Usually this aspect is overlooked andonly treatmen t with bronchodilat ors is prescribedfor bronchospasm and with ant| inflammatory

Rev. fr. Allergol., 1998, 38 , 7S


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has been specified [27]. Of course, facing thesefacts, it is proper to think that the same as in thepatient with bronchospas m due to sensitisation tosome fraction of pollen antigen, immu nothe rapywith these antigens leads the target organ to asituation of hyporeactivity after contact with themucosa, the same phen ome non should take placewhen using bacterial antigens and identicalimmunot herapy techniques.

In the last years the number of authors whoconsider and argue very positively the role o f thehyperergic response against the bacterial antigenshas increased [15, 56, 57]. In several articles wehave already stated our criteria regarding thispro ble m an d especially in rec ent years [58, 59]our experience has been enriched with veryfavourable results where we could observeextremely positive percentages for both adultsand children. In a first group of adults withexclusively bacterial br onchial asthma, excellentresults were obtain in 75%; this is, an importantdecrease of the bacterial infections and totalelimination of the asthmatic symptomatology.Nevertheless, in children the percentage is evenbetter increasing to 86,2%. We have alreadyexposed in several occasions that the failure ofbacterial immunotherapy is basically due to ascarce bacterial concentration and extremelyshort periods of therapy, as it happens in theworks perf orm ed by the detractors of this therapy[60-63].Rev . fr . A l le rgol . , 1998, 38, 7S

As far as therapy with bacterial antigens isconcerned and in order to be successful it isabsolutely necessary to follow a hyposensitisationscheme the same as with immunoth erap y withairbo rne antigens. A perio d o f at least three years isalso import ant, and finally an efficient antibiotic inthe infection relapses. These three points are basicand must be considered in the treatment ofbronchial asthma of bacterial etiology. In patientswith sensitisation to airborne antigens and forimmun oth erap y with occupational or pollenantigens, we try to remove the p atien t fi-om hi s/ he renvironment or we start a pre-seasonal treatment.This is why antibiotic trea tme nt is so impo rta nt forthese patients. It would be very naive to think thatonly with bacterial imm uno the rap y with notreatment against the bacterial focus we couldobtain spectacular results [64].

C U R I N G O R M A I N T A I N I N G A S T H M AAs a conclusion o f all the exposed, the evolutionof many asthmatic patients is very disappointing.They are doomed all their lives to followtreatments wi th bronchodi la tors andcorticosteroids continuously, as a conseque nce ofoverlooking a causal treatment. Nowadays theexcessive administratio n of corticosteroids, eithe roral or by inhaled route, is alarming, driving to asupra rena l i nsuffici ency as we stated in a previousarticle based on our experience [65].


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$256 A . O E H L I N G /REFERENCES

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$25751. Just j., Fayon M., Charavel A., Grimfeld A. - Role of bacterialinfections in children with asthma. Pediatr. PulmonoL, SuppL 1997,16 , 76.52. J one s tL, Gruffydd-Jones K. - Management of acute asth ma attacksassociated with resp iratory tract infection: a postal survey ofgeneral practitioners in the U.K. Respir. Med., 1996, 90 , 419425.53. Hahti D.L. - tiift:ctious asthma: a ree merging clinical entity?J. Faro.Pratt., 1995, 41 , 153-157.54. Hofinan J., Tobolczyk J., Pttchnarewicz A. - Specific IgE againstbacterial antigens in children with bronchosp astic symptoms. Int.Rev. AllergoL Clin. ImmunoL, 1997, 3, 149-152.55. H. Blatt. - A Test to Ascerta in the Patien t's Specific Offendi ngAllergens and Experie nces in Desensitizing for these Allergens.Acta A llergol., 1959, XIII,, 279-285.

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