Aeroallergens and asthma

Till' main aernallcrgL:ns in b(1th the indoor and \lutd\lor e11viro11111L'nt that have hL·cn implicated 111 the pathogenesis or alkrgiL· asthma arc reviewed. Polll'n and fungal spores arc important outdoor aeroalk'rgcns that cause scns iti1atiun in atopic suhjcch. leading tu rhinitis and asthma in a proportion \Jr the Sl'.t1siti1ed subjL·cts. Each pollen type d isplay., a partirnlar seasonal periodicity: tree pollen are prevalent in the late win ter :llld spring, grass in the spring and summer and weed mainly in the !"all. Then~ are regional differences in the type of' pollen grains in Canada. Alth\lugh the pollen grains arc Ia1·gc. l"ragments less than 10 μ111 can reach the lower airways to cause asthma. Some fun ga l spores. such as i\ /tcmuriu and C!udo.11,ori{(II/, have been implicated in asthma. The full clinical impact \JI' fungi in asthma has yet l\l be clarified. With the construction of' homes that arc tightl y sca led to conserve heat and the use or wall to wa ll carpet. the type and concentration of indo\lr aeroallergcns have hL·crnnc incre:1singly ditfrrent J'rnm outdoors. House dust mite and pct allergens ha ve now hccn shown to he important acro:dlergcns that scnsiti1.c children in infancy and arL'. risk l"aclors fur asthma. C linicians should rccogni;,e the importance or al'ruallergcns in asthma because avoiJa11ce andllll" reduc1iu11 o!"l'xposurc is :111 important part of the nia11agcme11t bcsiclL's drug therapy.

A STHMA IS.\ MU LTI!'<\(" J'(JRL\I DI SEAS E. DET ERMIN ED BY a combination or genetic and environme ntal factors.While sc ientists are still struggl ing to di.,cover an ,1sthm,1 gene.a great deal or information has ben1me availabll' in relati on to environmental t'aL•tors in asthma.
Environmental factors L'an be divided into two groups: air pollutants and aeroall ergens.Both groups are present indoors and outdoors.For many aeroallergens.indoor levels are dependent on outdoor levels.However.with the construction or homes that arc tig htly scaled to conserve heat during the past Jccade and the use of wall to wall carpeting.the type and concentration or indoor aeroallergens have become increasingly dirferent fro111 those outdoors.As 111ost peopk spend more than 909' 11 or time indoors.the indoor environment deserves more attention and study than it used to.
Th is is a review or the main aeroallergens 111 both the outdoor and indoor environment tha t have been imp!icated in the pathogenesis of allergic asthma.Occupational exposure wi ll not be considered.The 111echani sms by whi ch these acroalkrgens cause airways in11ammation and bronchial hy perresponsiveness as well as the allergic evaluation of the asthmatic patient are beyond the scope of this review.

OUTDOOR AEROALLERGENS
Pollen and rungal spores are the most impo rtan t outdoor acroallergcns that L•ause scnsiti1ation in atopic subjects.

Pollen
The pollen grain is the speeiali1ed structure that houses the sperm or male gametes of flowerin g plants.It comprises two to four cells combi ned as a unit.The pollen grain typicall y is composed of approximately 20% protein.37% carbohydrate.4% lipid and 3% minerals.Pullen is formed wi th in the anther.which is an elongate structure contain ing the pollen sacs.Pollen grains arc transferred to the femal e reproducti ve body mainly by wind or vector insects.On ly 30 out lif' more than 300 families or flowerin g plants show adaptations for pollen dispersal in air curre nts and are termed anemophilous.Wi nd transported polkn tend to be between 10 and 40 µm in size.dry.round and with littll' surface ornamentation .The germinal apert ures are a major fcalllre of pollen morphology.Families in which most of the ge nera are 1\ind-pollinatcd.and of allcrgologic interest, include: Gramincae (grasses) , Bet ulacL'ae (birches).Fagaceae (hccches.oal-s).Cupressiaeeac (junipers, cedars), Sa licaceae 1poplars), Ulmaecae (elms) , Chl'llopodiaceae (docks) and Urt icaccac (nettles).Among several famili es that arc prc-Jom ina ntly pollinated by animal vectors , some genera arc wind-pollinated.for exampl e. the ragweed.i\111hro.1iu. in the Composi tae and the ash.Fruxi1111s, in the Oll'aceae ( I ).
Pollen constitute a small part or the aeroplanl-ton or air sµora present in the atmosphere, since most frequent particles of biological origin arc microorganisms.especially the spores uf fun gi.However, tree.grass and weed pollen are also common airborne particles in the ambient atmuspherc•.Pollen grains may travel long distances before they are deposited.The pollen season in temperate climates is restricted to the warmer months ur the year from late winter through autumn.As the flow ering season progresses.different pollen are present in the at mosphnc.so that each type displ ays a particular seasonal periodicity.
In most temperate di mates, the seasonal progress ion first involves tree pollen in late wi nter and early spring.The pollen or birch.alder.hazel.oak.ash and L'lm lead the pollen call'ndar.The grass season beg ins in late spri ng and early sunm1l'I'.This is l'ollowed cluscly by variou s weeds, !'or L'Xample nettle, doc k. sorrel and plantain.In North /\merica.various amaranths and ragweeds begin to pollinate in the autu mn ( I).Both the time or com111enccmc111 and duration or the pollen season have been shown to be dependent on eleva tion above sea leve l and geographic position.Howeve r. marl-;cd differences in onset of the pollen seaso n and in the total amount of po llen released occ ur l'rom year to yea r.
At mosphe ric conditions such as temperature , rel ative humidity and wind speed and turbulence affec t the rel ease and di spersal of poll en gra ins.Epidemic s or asthma have been assoc iated with thu nderstorms.On two con secu tive occasions after thunderstorms in Mel bourne, Australia there were IO-fold increases in cases or asthma admissi ons (2) which was thought to be due to the release or rnicroni c pa rticles rrom grass pollen artcr substantial rainfall.
Pollen have been imp licated in several all ergic diseases.including all ergic rhinitis.bronchial asthma.as well as in several eye and sl-in disorders (3 ,4).In fact.atopic di seases.particularly those induced by pollen allergens (rhinoconjunctivitis and asthma).haw beco me more common during the past two decades (:'i.6).Pollen grains are usually too large to penet rate the lower airways.However.allergenic activity has been found in airborne rragmcnts smaller than pollen for both rag weed (7) am! ryegrass (8).In the case or ryegrass, it has been shown that pollen grains arc ruptured in rain water by osmotic shock, each gra in releasing abo ut 700 starch gra nules into till' atmosphere.These gra nules arc small eno ugh to e nter the airways (less than J µ111 in dia meter) and tests in asthmatics have shown that suspensions of these granules provol-cd immunoglobulin (lg) E-mediated responses (8).
An increase in nonallergic bronchial hypcrresponsivc ness to methac hol ine has bee n demonstrated in pollen -sensiti ve asthmatic subject s during and artcr the pollen season (9).The nu mber or poll en grains requ ired to elicit symptoms is t111 clear but studies indicate that the number is greater at the beginning than at the end of the season.an effect known as priming.Empirical data suggest that the threshold conccntra tion lies between IO and 50 grains/m 3 .A characteristi c l'eature of pollen scnsit1v1ty is its seasonal pattern of occurrence., usually at the time when thL' pollen count is highest in the atmosphere.Because the di ag nosi s ur pollen se nsiti vity is partly de pendent on pati ents ' symptoms duri ng the pollen season , physi cians need to I-now the season and the amount or pollen rrom allergenic plants.
Diffe re nt devi ces arc used for aero bio logical sampling such as Durham greased slide (gravitational ), the rotating impaction sampler (impaction ) or the volumetric Burl-arc!spore trap (suction) (4) .Chattc1jec and Hargrcavc ( IO) stud- icd the atmospheric pollen and fungal spores in Hamilton, Ontario using an automatic volumetric spore trap.Immunological methods of identifying and quantifying airborne allergens have been developed in recent years.Table I shows the flowering period and the relative amount of pollen from the most common allergenic plants in Canada (modified from reference 11 ).Note the important regional geographical differences , particularly for weed and tree pollens.The above information is very useful lo pollen-sensitive patients when they plan trips and in the prevention of severe allergic symptoms by appropriate medication or other measures ( 12).
Grass pollen sensitivity is the most common cause of allergic disease worldwide (4).This is due lo the wide distribution of wind-pollinated grasses.The allergens from 1yegrass (Loliwn (lere11ne) and timothy (P'1/c11111 pmtensc) have been most extensively studied and some have been isol::itcd.The origina l studies carried out by Marsh ( 13) and Matthiesen and Lowenstein ( 14) showed that the pollen from these grasses contained several allergens.In the past.four of the The ragweed tribe is the most important cause or allergic rhinitis and pollen asthma in North America (4).Short ragweed pollen (Am/Jro.,iaurtemisiifi,lia) contains 22 allergens ( I 5), and the two major allergens, Amh a I (former antigen EJ and Amh u I I, have been isolated.Other allergens have been purified from additional weeds, such as Sul /I I from Su/so/a pestifer (Russian thistle) ( 16) and Purj I from Porietaria judaica pollen ( 17).Members of the two closely related Chenopodiaceae (lamb's quarters.Russian thistle) and Arnaranthaccae (redrool pigwCL'.d)l'amilies shnw varying degrees or cross-reactivity.The allergenic fractions of treL'S have not been sllldied as well as ragweed or grasses.A few major allergens have bc•en isolated.including Bf't ,.I frnm lfrtulu rnlguri.1 (birch) ( 18). and Cora I from Con-/us u,•f'llmw (hazel).The latter only differ in two residues from the major allergen of birch ( Ill) .11111 s I has been isolated frnrn .lu11i1n•rns.whi11oidc.1 (mountain cedar) (20), and Ole c I from Oln1 c1//'01J11ea (olive) (21 ).which is shared hy other species or the Oleaccae family (22).

Fungi or moulds
Fungi or moulds are a heterogeneous group of mmphutosynthelic organism., lhal arc grouped in the plant kingdom because of the presence of a cell wall.They are 80 lo 90% polysaccharide in composition (23).Fungi grow hL'St at relative humidity of 75 to t)59'o, hut others like /\.~1Jergill11s can grow in lower humidity because they can extract water from the atmosphere.
The spores of fungi range between 3 to 200 ,um.with the majority at uround IO µm.Hmwver.it has been pointed out by Licorish and co-workers (24) that some spores are quite small, snch as Pe11ici/li11111 (less than 5 µm) and the yonng spores or Altemuria (less than IO µ111).Moreover, the snowshoeshaped Altcmuria spore has different aen>dynamiL• prorcrtics that keep it from having an impact in the upper airways.
There are four major groups of fungi: (a) Phycomycetes Rhi:,opus.lvlucur -sugar and bread moulds: (b) Ascomyccles (sac fungi) -hlack moulds and blue moulds.yeast: (L' ) Basidiornycetes (club fungi) --rusts, smuts.mushrooms .puftl1alls; (d) Deuteromycetcs (fungi impcrfL' L'li) Cladospori 11111.Alt en w ri u.Aspe rg i I I 11.1.H e/111 i, 11111 JS/ iori 11111.Pc11icilli11111.The last group consists of most of the fungi allergenic for humans.There arc studies to indicate that the basidiosporcs may al.,o be important particularly in the southern United States (25).Many fungal spores arc virtually always present over large land ma sses.They arc present in higher concentration than pollen, sometimes 40 times higher.The particular species and concentration in the air at any given time are dq1endc11t on temperature.rainfall, prevailing winds, seasonal climatological factors .circadian patterns of ,unlight and darknc.-;s,availability of substrates.and the degree of hoth substrate and atmospheric moisture (23 ).For example. the dispersal of hasidiospures and their growth arc affected hy atmospheric moisture : the spores are propelled into the atmosphere during periods or rainfall and dampness.Circadian rhythms in humidity and tcmpcraturl' interact to foster nocturnal or diurnal increases in certain basidiospore concentrations (26).Cludos11ori11111 and Altemurio arc blown free by wind.and these spurcs increase in concentration with diminishing humidity and increasing.airilow.Thus.these species arc often abundant during mid-day periods with maximal sunlight.
Most of the fungal spores found indoors an.: from the outside.However.high levels of fungi arc prese nt in.,ick damp houses particularly 011 garbage containers, food storage areas.wallpaper.damp basement.shower curtains and win - Aeroa llergens and asthma dow mouldings.New buildings ;ire hcing constructed tightly to avoid air leaks in on.ler to save heating cost and.as a r"L•sult.indoor humidity increases.There is a possibility that occasionally building., or homes may become sufficiently contaminated with mould lo cause asthma (23).
The role of fungi in asthma is not fully understood.This is due to many factors: the choiee and method of preparing fun gal extracts for skin testing and brond1oprnvocatio11 tL'Sting vary markedly among investigators: the quality and po-tL'ncy of mould allergenic extracts have often been poor: relatively few fungi have been studied in detail: a single.hrief well-ddined ' mould season• usually does not OL'Clll' (23) .In addition.there are difficulties with identification of mould :illergens (27).Many fungi haw vny specific growth rc4uircmcnts that prevent culture in thl' lahmatory.The spores arc not discrete in morphology.while culture methods may be 111islcading because some spores may not gL'rminatc.Moulds may be airborne in amorphous particles and enumeration of spores may underestimate the total amount of anti gen in till' air.Thus.identification of fungal acwallergcns may require a combination of methods including microscopic counts, culture and immunochemical assay.
During the past 15 YL'ar., . .,cveral studies have demonstrated the relationship between increase in asthma severity and high fungal spore counts.Salvaggio and ;\ukrust (25) showed that an increased incidence of asthrna admis,ions in New Orleans.during the months or Septem ber to Nove mber, was associated with very high outdoor total spore counts.Hasnain et al (28) aho showed similar findings in New Zealand .In the Netherlands.Beaumont ct al (2\)) shmVL'd a positive correlation between decreased pe;1k l"luw rates witlt high outdoor spore levels.In 24 patients with asthma who had positive skin and bronchial reactions to C/(l{lo.1l1uri11111.Ma lling (10) found a positive correlation between the weekly symptom scores, medication scores.total scurL's and the Clwlo.11Jori11111 spore counts.Lopet and coworkers (31) studied eight asthmatic patients who had positiw skin te::;ts to extracts of basidiospores and asthmatics with negative skin test.Those with positive .,kintc.,t had positive inhalation challenge to extract of basidiosrores.O'Hollar'L'n and L'lll-Ieagues (32) reported that cxrosure to Altemoriu in the summer or early fall may be responsible for the severe attack of astlrn1a in 11

INDOOR AEROALLERGENS
The indoor acroallergens of importance arc huusl' dust mi tes, pets and cockroaches.In parts of thl' United Kingdu111.Australia.New Zealand and the United Stales.house Just mites arc lhl' 111os1 important ;dkrgl'n.with 70 10 SOC/" or asthmatics reacting on skin test to thl' mite allerge ns (.l(l).Pl•ts arc the second mo st l'O!lllllon important cause of allergy in developed countries.and up 10 40'!. of asthmatic children arc sen siti zed to allergens of calS and/or clogs (37).In recent years.coc kroaches have beco111c i111portant al lerge ns responsible !'or sy111p10111s in asthmatics in inner l'ilil's of' the United States (3 8L House dust mites Du st has been rl•co gni 1cd as a triggerin g factor for asthma for many centuries.In I 964.Voorhorst and co-workl'r.S (Jl)) l'irst sugges ted lh;11 th<-' most important source uf house du st allergen was mites or the genus !>C'n11u1ntd/(/goid<'s. Mi ya moto and as,ociates in .Japan (40,4 I) l'Xpandcd the work and showed that the potency or house dust allergen is related tu the number ol" mites in the Just.Sk in tests , radioallergosorbent test and brom:hoprovocation tests pcrror111ccl with extracts from pure cultures or mites correlated wdl with results ohtailll'd using ho use dust ex tracts.The equivalent potency of mile ex tral'ls was I() to I 00 times that or dus t.
In the United States.hou se Just 1nitcs 111ul1ipl y in the 11 10111hs or July ;111J August whe n hu111idi1y is hi ghest.Mi ll' al lergens arc found in dust sa111pl es collected rrom 111 at1rcsscs and bedroom noors from Jul y to DL•cember as these allerge ns ;1re fo und mostl y in kccs ol miles.whid1 pe rsist long after 1 he mites are gone ( 44).
There are two 1mtJor groups o r 1ni1L• allergens.Group I allergens (Der 11 L Dcrf 1) arc protcol ylic enL:ymcs sec re ted !'ro111 lhl: di gesti ve tract and 1 •ound in hiµli concentration s in kl•,t!pellets (45).Mites arc coprophagic.ic.they re-ingest fecal pellets.anJ it is poss ib le that the presence of these e1l.lymes allows a mo re l'Xtc nsi\•c di ges ti on to occur artcr defecati on.Group 11 (Der p 11, Dn f 11) allerge ns arc found both in kcal pellet, and mite bodies.
Then:: are three llll' lhmls of estimating cxpo,urc 10 mill's : mite counts .assay or mill' :t!ll'rgens and measure ment of guanine (36 ).The most widel y used assays fo r measuring group I alle rgens arc the e nzyme-lin ked i111111un oso rbcn1 assay (ELIS A) method with specics-s1 ccilic monud onal antibod ies to bi nd the allerge n, and labelled group-spec ifi c antiboJies for detection (-1-6).Counting or house dust mites is tedious and may not give the mite allerge n content in thl' dust.The quantitative assay for guanine is not L •om111L•rci ally ava ilable (36).Theoretica lly, measuremen ts of airborne allergen should be mo re representative of exposure than assays on sell led dust.However.there ha ve been few data dcmon\trating a re lationship bet ween airborne dust and sc nsi ti1ati on and rl's piratory symptoms .In ge neral.leve ls ul ai rborne all ergens ;tre low and undetectable in the absence of dust disturba nce.Arter di sturbance, concentrations o r allergens fall rapidly.because thl' particles are large (47).
There arc many studies prov iding cv idl•ncc that the house dust mite is an important cause o r asth ma in many parts or the worltl.First.there is an ecological relat ionship bct wL :cn the' levels or ho use dust mites and the prevalence or asthma.A low preva lence of asth ma has been fo und in areas of low mill• exposure such as in hi gh altitudes where the absol ute humidity both indoors and outdoors is low ( 48).These areas lend In be climatical ly inhospitable and sparse ly inhabited.Reports rrom Papua New Guinea desc ribed how co ntact with western civili zation was follo wed by an incrc:1sc in the prevalence o l asth ma.An expl anat ion for this has been the introduction of blankets in rested with mites to this native population.leading to se nsit ization and subsequent deve lopment of asth ma (49).
In areas with hi gh mite exposun~ such as in the Un ill'd Kingdom, coastal areas of Australia.New Zeal anu.Japan and Bra zil , •al[ ' ,Hopic children can become se ns itized (43 ).
Second , there is a Jose-response rl'lationship bet ween the level o f mite allergen ex posure and the ri sk of sensiti zation.In the United Kingdom.where mite allerge n levels arc in gene ral high.approximatel y 80Clr or asthmatic chil dren were Can Respi r J Vol 1 No 4 Winier 1994 sensitized to house dust miles (43).The pn:valc11L•e of positive skin test rL•action to mite allergens was about 45 1 /t-in two CanaJian cities where tlw mite allergen levels \\L'l'e found to be rdativcly low (50).TIK• risk of asthma was seven Limes hightr in Ge rman chiluren ii' their current exposure Lo [)a 11 I ,vas greater than 2 µgig of Just.anJ 11 ti111L•s higher for exposure above IO µg ig than those with less than 2 ~tglg (51 ).
Third.reduction of exposure Lo house dust miLL'S resulted in improvement in asthma in subjects allergic to tl1t•m.Placing children in a sanatorium al high altitude•.whl'l'l' mite levels arc low.had been a traJitional Lrcat111c111 of severe asthma and usually resuheJ in improvement or their symptoms C'i2).AJulL asthmatics allergic lo house dust miles improved considerably in ,111 allergen-free environment in a hospital although it look two to three months lor improvement to occur (53 ).The LI.se of acaricides anJ enclosure or mattresses have been shown to reduce the mile allergen level :ind se verity or asthma (54.55).
The most convincing evidence that house dust mite is important in asthma comes from two prospective studies.Sporik and rnlleagues (56) eonducted a longitudinal study or children at high risk for dev..:loping asthma and allergies at birth.and followed them !'or 11 years.They found that children whose homes h,1J high mite allergen levels during the first year or lit'c were al ,1 much higher risJ.. for Jeveloping asthma than those with hiw levels./\rshad anJ co-workers (57) conducted a randomizt'd clinical trial on infants at high risk tor developing allergy and asthma.The pro phylactic group had measures to reduce house Just mite exposure and dietary restriction.The control group had no treatment.At the end of 12 months, those in the control group haJ 1'011r times the risk or Jcveloping asthma as those in the prnphylactic group.
In a study of environmental risk !'actors in p,1tic•11ts with asthma in Vancouver and Winnipeg, a positive correlation was l'ounJ hetwecn mill' allergen levels in the ho111L•s or patients and the dcgreL'.of' skin test r<:activity to mites (50).There was also an inverse rdationship between the le vels or mite allergens anJ tht' levcls or lung function in children with asthma.indicating that mite allergen levels arc or clinical relevance.
There are now C'!ketiw means or reducing mite allergens such as the use of a dust cover ror mattresses and pillows, the use or hot waler for washing all heJdings.and the remov,il of' carpets particularly in the be<lroom.The availability ot' acaricidcs a<lJs another armament to the regimen.

Pets
Hypersensitivity to pct allergens is extrcml'ly common.Surveys have shown that 5 to I V l or the gencr,il population and 40 to 70% or patients with asthma have positive sk in test reactions to cal anJlor dog dander (J7,58-60).Close hum,1n contact accounts fllr the high prevalence or pct sensitivity in Western societies.It has bee n estimated that either cats llr dogs arc round in over 50'k or homes in many countries (61).Laboratory animals (mlluse.rat.guinea-pig, rabbit) and !'arm animals (horsL', cow) c111 also give rise to allergic sensitization in exposed persons.m,1inly in an occupalion,il context ( h2 ).Tlll'SL' mammals secrete proteins that may act ,is pot,:nlial acroallergens when they arc inhaled.Sevnal or these allergens have been identified anJ a few or them L•haractcri zed.
Cats arc the most prL•valent cause of pct allergy (b]) .The sources llr the allngcns in cats arc the pelt, dander.s:iliva.urine and serum (62).Several molecules in cat extracts li,1 ve heen shown to be allergenic an<l thc rclati ve concentral illn lll these ,1llergens varies depend in)! on tl1l: source or extract.Th,: most important allergen from a clinical point or view is Fe/ cl I (64) .Most of' the IgE anlihlldics elicited in cal-sensitive patients arc directed against this allcrgL ' .n. Fd d I is found in salivary glands.hair follicl es.saliva and Iacrimal llui<l (65).The exi stence ol' Band T cell epitopcs in the Fe/ d I molecule has been demonstrated (66) .The most important allergen derived from dogs is Cun(I and is present in high concentrations in dog hair.danJL•r and saliva (67).This ,illergen accounts for al least hair or the allergenic activity in dog hair and dander extract (<i7).
The clcvelop111ent or nwnoclonal antibody-based assays has made it possible lo determine the lc\'cl or environmental exposure Ill Fe/ ,I I (CiX ) and ( •un I I ((1 1 )) and l,1 study the relatio11.shipbetween exposurL' and devclopme111 lll'scnsi1i1a-Lion ,ind exacerbation or symptll111s.Exposure lo a leve l ot' Fe/ d I in the house greater than X pglg or dust in a sensitized subject is a risk factor fur acute asthma episodes le.ading to emcrgL'lll'Y room visits UOJ.It is likely th,1l clinically relevant threshold limits for pet allergl'll L'Xpusurc will he pruposed within the next few years.
Throughout the home Fe! d I h,is been found in d11~l frnm l'luurs, mattresses and ,oft furnishings, on walls and in the air (61 ).The wide distribution ol' the ,dlcrge n is due to a significant proportion or Fe/ cl I prese11l 011 particles smaller titan 2.5 µ m in diarnder, which reaJily become ai rbo rne a11d remain in the air for long periods even in un<lislurbed conditions (71 ).Interestingly, measurahk amounts ot' 1-'l'I d I have been found in al most every home invcstigatl'd.including those witht1ut cats in residence.and in public buildings (72,73).It has been suggested that Fe! cl I is carried into cat-free buildi ngs on lhe clothing Ill' people exposed to cats (Tll.Studies in Scandin,1vian schonls have shown that while mite allergen levels were low in the classrooms, a high ll'vcl or both cat and dog allergen was round on either smolllh or carpeted tlllors.with approxi111atcl y 11 times more on the carpeted l1oors (74).It was t•stimated that 30 ng Fd d 1/111 1 was brought into the classroom every Jay.and this is highly signilieant J'ur children with Gil .sensitivity./\nothcr recent sllldy from SwcdL•n showed that ll'wls ur both Fe! d I and Cw1 I I were 11111ch higher on chairs than 011 f'lours.suggesting that allngens Wl'l'l' brought in hy students and teacher~ 011 their clothing.These levels were pruhahly high enough lll SL'nsitize children and to induce asthma in most children who arl' allcr)!ic to cats ll!' dogs (75).
In a study of patients with asthma in Vancouver and Winnipeg, levels or Fe! d I in dust samples colkctcd frrnn mallre;;st's and hedruo111 floors wnc measured.Cal allergen was present in every home, even in those wi thout a cat (7(1).Fd d l levels were highest in homes of patients with cats, and rather high IL'vels wne also found in homes or patients without a cat but ,vl10 had visited olhL'rs with cats.The lowest levels were round in homes or patients without a cal and where the occupants did not visit others with such a pct.Cat allergen levels were highest during the winter and spring and lowest in summer and autumn in Winnipeg.prohahly clue to the tighter insulatinn or the homL'.S during winter months.Such seasonal variatinn was not found in Vancouver.TherL' was no relationship between sensiliLalion lo cats and previous or current cat ownersh ip.The findings arc in keeping with rL'ccnt studiL's showing that Ft! d I is a uhi4uitous allergen.It is likely that the cal alkrgen was brought into homes on clothing or occupants when they visited homes with cats.
Once a diagnosis uf pel aller)2.yhas been made, SL'Wrnl therareutic options arL' availahle.The most effective method is to remove the animal completely, allhllugh this may not be possible in all situations.Even after removal of the pct, it may lake several months to rL'.ducc the allergen content within the home.Aggressive deaning measnrcs should he in.,titutcclas rapidly as poss ible .Ir the symptoms :1re mild and the patient or the famil y rduscs lo give up the pct.sume preventive measures should be taken to limit exposure .Tht' allergen content may bl' reduced by limiting the pct 's access lo the hornl'.removing carpets and upholstered furniture, increasing ventilation, and by using room air cleaners, particularly thosl' with high efficiency paniculatc air or elcctrnslalic l"ilters.Thl're is some evidence that washing cats weekly will reduce the amount or Fe/ d I in the IHH11L' .(77).Neverthckss.the effectiveness lll' these measures on allergen level s and patients ' symptoms remains lo be derined.f<urthcr, even if a patient can avuiJ animal expusure at honll'.pets arL' so common that some degree or exposure outsidL' the home is inevitabk (7~).

Cockroaches
Cockroaches ha ve been described as allergens based on skin test data on alkrgic subjects (79).Kang and ass(iciates (80) extended the work to include radioallcrgo.,orhellland bronchopmvocation studies with cockroach extract.Asthmatics with positive skin tests to cockroach extracts had higher total serum lgE levels than their allergic coun lLT[l,1rls with negatiw skin tests.Bronchoprovocation test induced transient peripheral eosinophilia in those who reacted pw,itivcly.Immunophorctic studies haVL' shown that ro,1ch alkrgens were mostly found in the whole body and cast skin rr,1ctions.feces and egg casings \VL:re less allngcniL' (8 1 ).Hypersensitivity lo cockroach allergens is particularly important in inner city asthmatics (3X).

SUMMARY AND CLINICAL RELEVANCE
The rclativc risks or sensitivity to various outdoor and indoor aeroalkrgens iu tht: development of childhood asthma were investigated by Scars and colleagues (X 2) in a longitudinal study or a birth cohnrt of New Zealand childre n up to the age of J:\ years.Of the 714 children skin-tested.45.X' k were sensitive to al least one of 11 allergens, till' most common responses being to rye grass pollen (32.5',f).house Just mite (30 .l 'k ) and cal dander (13.5'/c ).Sensiti vit y lo house dust mite, cal dander and A.1pergillus were independent risk factors associated with the development or asthma, while grass sensitivity and sensitivity to :1 number ur outdoor aeroallergens were not.Gelber and coworkers (70) conducted a case-controlled study on adult patients ( 137 in each group) presenting tu an emergency room over a period or one year.
They found that 38% of the asthmatics, but only W,r of the controls, were allergic to one or the three indoor allergens and had high leve ls of the relevant allergen in their houses.TllL'Y concluded that the risk for asthma related to scnsiti1ation to indoor allergens applies to many adults with acute asthma.These two studies showed that indoor aeroallergens are importalll detL•nninants ror asthma in children and in adults.
Exposurl' to indoor household allergens is a leading GlllSL' of perennial IgE-mcdiated asthma and rhinitis.Ongoing daily exposure to allergens kads to perpetuation or the in-flam111atory process in the airway that is the likely cause for the persistence ot' symptoms and airway hypcrresponsiveness.Clinicians should i'L'cogni ;c the importance Ill" indoor aeroallcrgens in asthnw because avoidance and/or reduction or exposure is an important part or the management IK'siJcs pharmacologica l management.f<inally, clinic ian., should a lso he aware that high levels or pct allergens may he found in schools and othe r public placL'S and may account for the persistence or sy111ptu111s despite stringent measures or avoidance at home.

TABLE 1
Flowering period and relative abundance of relevant allergenic plants in Canada patients.fatal in two casl'.s. in the upper midwest of the United States.The study by Licorish ct al ( 2°() prnvided confirmation that inhalation or Altc'muriu or l'c11icil/iu111 spores can cause aslhma in mould -scnsitiw patients.The level of fungal spores in the atmosphere correlates with the level of lgE synthesis.Agarwal L' t al r:ni found that the level nfllltemuri,1 spore counts correlated with the ability of the cxtraL•t to induce positive skin test: siruilarly, the immurmchemical activity of the allngL:ns paralleled the 111t•un symptom scores.Roby and Sneller (34) studiL'd 137 patients with allergic rhinitis or asthmu and performed spore counts indoors and outdoors.The prevalence of positive skin test to different fungal extract, correlated with the levels of tlw different indoor spore counts.Thus.there is good evidence that ,dlcrgy to fungi play a a I lergc ns fro m a wide range of' fun gal species ( 35 ).