Relentless rise allergens arun

Manjunath KManjunath KChairperson, Department of Chairperson, Department of

Microbiology and Biotechnology, Microbiology and Biotechnology, Bangalore UniversityBangalore University

The Relentless Rise of The Relentless Rise of Neoallergens in Neoallergens in

EnvironmentEnvironment

HISTORYHISTORY

► Foundation of Allergy, i.e. “Disorders of Immune Foundation of Allergy, i.e. “Disorders of Immune System where the balance is lost resulting in System where the balance is lost resulting in morbidity and mortality” started withmorbidity and mortality” started with

►1873 Chails blackley explained pollen as 1873 Chails blackley explained pollen as causative agent.causative agent.

►1919 John Bostock described Hayfever1919 John Bostock described Hayfever►1921 Prausnitz Kurtner discovered IgE in 1921 Prausnitz Kurtner discovered IgE in

serum.serum.►1967 Johansen suggested the name “Ig E”1967 Johansen suggested the name “Ig E”

► In the last 30 yrs spectacular development in In the last 30 yrs spectacular development in cellular and molecular mechanism of allergic cellular and molecular mechanism of allergic diseases has been done.diseases has been done.

► In the new millennium almost half the In the new millennium almost half the populations of the West show sensitization to one populations of the West show sensitization to one or other environmental allergensor other environmental allergens

► Britain: one in four children has AsthmaBritain: one in four children has Asthma► Australia: one in five has EczemaAustralia: one in five has Eczema► People are found allergic to new allergens like People are found allergic to new allergens like

nuts, soya, latex etc.nuts, soya, latex etc.

ORGANIC DUSTORGANIC DUST► Genera grain dustGenera grain dust► Wheat/Rice/Ragi/Jowar dust Wheat/Rice/Ragi/Jowar dust ► Soya dustSoya dust► Cotton dustCotton dust► KapokKapok► Flex Flex ► HempHemp► JuteJute► StrawStraw► SilkSilk► Castor bean dustCastor bean dust► Coffee bean dustCoffee bean dust► Tea dustTea dust► Rye/ oat dustRye/ oat dust► House dust (MITES)House dust (MITES)► Sick buildings (Damp walls) Dander/feathers of Sick buildings (Damp walls) Dander/feathers of

pets/sheep/cattle/poultry/pigs/cockroaches/ratspets/sheep/cattle/poultry/pigs/cockroaches/rats► Palmolein oilPalmolein oil

OCCUPATIONAL ENVIRONMENTSOCCUPATIONAL ENVIRONMENTS

► Leather Godowns and industryLeather Godowns and industry► Flour mill/BakeryFlour mill/Bakery► Sugarcane/Brewery/SCP factory (spirulina)Sugarcane/Brewery/SCP factory (spirulina)► Bioinsecticide industry like Bt toxinBioinsecticide industry like Bt toxin►Mushroom factoryMushroom factory► Sewage treatment plantsSewage treatment plants► Viral/Bacterial vaccine production unitsViral/Bacterial vaccine production units► composting and garbage handlingcomposting and garbage handling► fiber glass productionfiber glass production►metal machiningmetal machining► dental clinicsdental clinics

OCCUPATIONAL OCCUPATIONAL ENVIRONMENTSENVIRONMENTS

►PoultryPoultry►Swine confinementSwine confinement►Dairy barns and Livestock productionDairy barns and Livestock production►Grain handling facilitiesGrain handling facilities►cigarette and cigar manufacturing cigarette and cigar manufacturing ►animal feed industryanimal feed industry►potato processing potato processing ►paper factory paper factory

►sawmills and wood working shopssawmills and wood working shops►cotton processing, jute mill, gin housecotton processing, jute mill, gin house►BiotechnologyBiotechnology►OfficesOffices►HousesHouses

OCCUPATIONAL OCCUPATIONAL ENVIRONMENTSENVIRONMENTS

AIRBORNE BACTERIA / AIRBORNE BACTERIA / ENDOTOXINENDOTOXIN

► Airborne BacteriaAirborne Bacteria varies from 10 varies from 1055-10-109 9 CFU/mCFU/m3 3 in agricultural in agricultural and industrial environmentsand industrial environments

► In general terms, ‘endotoxins’ refers to any cell-bound In general terms, ‘endotoxins’ refers to any cell-bound bacterial toxin - a characteristic that distinguishes it from bacterial toxin - a characteristic that distinguishes it from ‘exotoxins’ which are secreted by bacterial cells ‘exotoxins’ which are secreted by bacterial cells

► Heteropolymers- polysaccharides- immunologic + lipid A - toxic Heteropolymers- polysaccharides- immunologic + lipid A - toxic ► Released as discoid particles 30-50nm diameter in large Released as discoid particles 30-50nm diameter in large

quantity into airquantity into air► Endotoxin + Lipopolysaccharide binding protein (LBP) via CD4 Endotoxin + Lipopolysaccharide binding protein (LBP) via CD4

receptor alveolar macrophage binding site and activate receptor alveolar macrophage binding site and activate immune systemimmune system

► E.coli, Salmonella, Shigella,Pseudomonas, Haemophilus, E.coli, Salmonella, Shigella,Pseudomonas, Haemophilus, NeisseriaNeisseria

► Airborne bacteria urban site 609 CFU/mAirborne bacteria urban site 609 CFU/m3 3 (Lightart 1997)(Lightart 1997)► Bacteria increase sunrise decrease noon increase sunset Bacteria increase sunrise decrease noon increase sunset

decrease eveningdecrease evening

Antibiotic Resistant bacteria in Indoor Air

► In Indoor air the most important source of airborne bacteria is human activity

► Extended-spectrum cephalosporin-resistant Gram-negative bacilli

► MDR Pseudomonas aeruginosa and carbepenem resistant Acinetobacter.

► Methicillin Resistant Staphylococcus aureus and Methicillin Resistant Coagulase negative Staphylococci

► Health risk associated with occupant exposure to airborne bacteria are difficult to calculate because of fewer studies.

► Increased mortality and hospital costs

► More surveillance data is required from India to frame national guidelines and policies to combat antibiotic resistance

Table:1 Table:1 OCCUPATIONAL EXPOSURE TO OCCUPATIONAL EXPOSURE TO AIRBORNE BACTERIA AND ENDOTOXIN AIRBORNE BACTERIA AND ENDOTOXIN

(Agricultural Industry)(Agricultural Industry)

SiteSiteConcentration ofConcentration of bacteria in the bacteria in the air (CFU x 10 air (CFU x 10 33/m /m 33))

RespirablRespirable fraction e fraction (%)(%)

Concentration ofConcentration of endotoxin in the endotoxin in the air (CFU x 10 air (CFU x 10 33/m /m 33))

Cow barnsCow barns

Horse stablesHorse stables

Piggeries Piggeries

Poultry housesPoultry houses

Silo unloadingSilo unloading

Grain HandlingGrain Handling

43.4-282.143.4-282.1

27.5-308.527.5-308.5

300.0-8,000.0300.0-8,000.0

41.2-7596.541.2-7596.5

60.0-4,300,000.060.0-4,300,000.0

70.0-1.244.870.0-1.244.8

51.2 51.2

40.0 40.0

44.844.8

57.857.8

38.138.1

41.9-54.941.9-54.9

0.0012-0.0120.0012-0.012

0.006-3.440.006-3.44

0.0019-75.00.0019-75.0

0.13-1.420.13-1.42

0.16-8.850.16-8.85

0.1-54.90.1-54.9

Table:2 Table:2 OCCUPATIONAL EXPOSURE TO OCCUPATIONAL EXPOSURE TO AIRBORNE BACTERIA AND ENDOTOXINAIRBORNE BACTERIA AND ENDOTOXIN




Poultry Poultry processingprocessing

Animal Feed Animal Feed industryindustry

BreweriesBreweries

Vegetable Seed Vegetable Seed storesstores

Herbage Herbage processingprocessing

Slicing beet Slicing beet slicingslicing

29.6-1,273.929.6-1,273.9

161.7-1,452.4161.7-1,452.4

23.7-526.623.7-526.6

10.9-8,991.410.9-8,991.4

36.1-518.236.1-518.2

179.1-203.3179.1-203.3

33.333.3

Not TestedNot Tested


41.141.1

44.344.3


0.63-0.920.63-0.92

0.0250.025

0.06-0.930.06-0.93


0.18-2681.00.18-2681.0

0.003-0.0320.003-0.032

Table:3 Table:3 OCCUPATIONAL EXPOSURE TO OCCUPATIONAL EXPOSURE TO AIRBORNE BACTERIA AND ENDOTOXINAIRBORNE BACTERIA AND ENDOTOXIN




Cotton mills Cotton mills

Jute mills Jute mills

Sawing woodSawing wood

Chipboard Chipboard factoriesfactories

Engineering Engineering IndustryIndustry

Composing Composing wastewaste

RecyclingRecycling

17.5 - 1,285.917.5 - 1,285.9

109.1-1,143.9109.1-1,143.9

5.7-37.05.7-37.0

21.4-36.321.4-36.3

0.2-735,135.10.2-735,135.1

100.0- 30,645.0100.0- 30,645.0

4.7-54.44.7-54.4

Not Tested Not Tested


20.4-37.020.4-37.0

35.4-63.235.4-63.2


50-6050-60


0.001-2.20.001-2.2

0.02-0.050.02-0.05

0.023-4.00.023-4.0

1.23-40.01.23-40.0


0.001-0.040.001-0.04

0.0008-0.00250.0008-0.0025

Categories of CFU/m3 (mixed population of bacteria and fungi) for non-industrial indoor environments

(CEC, 1993)

Category Bacteria Fungi

Very Low <50 <25

Low <100 <100

Intermediate <500 <500

High <2000 <2000

Very High >2000 >2000

Proposed Occupational Exposure Limits (OEL) values

Malmros et al. 1992 Total airborne microorganisms

10 × 103 cfu/m3

Dutkiewicz and Jablonski, 1989

Total airborne microorganisms

100 × 103 cfu/m3

Clark, 1985Malmros et al.1992

Gram-negative bacilli 1 × 103 cfu/m3

Dutkiewicz and Jablonski, 1989

Gram-negative bacilli 20 × 103 cfu/m3

SEWAGE PLANTSSEWAGE PLANTS

►Endotoxins are estimated by LAL TESTEndotoxins are estimated by LAL TEST►BACTERIA 105 CFU/mBACTERIA 105 CFU/m3 3

►ENDOTOXIN 410ng/mENDOTOXIN 410ng/m33

►STANDARD LIMIT OF EXPOSURE 30-50 STANDARD LIMIT OF EXPOSURE 30-50 ng/m3ng/m3

►Bacterial count on Eosin Methylene BlueBacterial count on Eosin Methylene Blue►Agar 5400 CFU/mAgar 5400 CFU/m33

►R2A Agar 34500 CFU/mR2A Agar 34500 CFU/m33

TOXINS AS ALLERGENSTOXINS AS ALLERGENS1. Streptococcal toxin1. Streptococcal toxin

2. Staphylococcal enterotoxin2. Staphylococcal enterotoxin

3. Aeromonas hydrophilic enterotoxin3. Aeromonas hydrophilic enterotoxin

These act as superantigensThese act as superantigensDirectly induce immune response bypassing usual Directly induce immune response bypassing usual process of peptide presentation to process of peptide presentation to αβαβ chain of T cells. chain of T cells.

Instead directly react with surface of IgG on B cellsInstead directly react with surface of IgG on B cells..

4. Aflatoxin4. Aflatoxin

5.Mycotoxins5.Mycotoxins

6. Phycotoxins6. Phycotoxins

EFFECTS OF ENDOTOXINSEFFECTS OF ENDOTOXINS

EXPOSURE 100-200 EU /mEXPOSURE 100-200 EU /m33

1.1. AIRWAYS INFLAMMATIONAIRWAYS INFLAMMATION2.2. HYPERSENSITIVITY PNEUMONITIS, ALLERGIC ASTHMAHYPERSENSITIVITY PNEUMONITIS, ALLERGIC ASTHMA3.3. LUNG INJURYLUNG INJURY4.4. ABDOMINAL CRAMPS, DIARRHOEA, ABDOMINAL CRAMPS, DIARRHOEA, 5.5. DRY COUGH, BREATHLESSNESS DRY COUGH, BREATHLESSNESS 6.6. SNEEZINGSNEEZING

7.7. ADJUVANT EFFECTSADJUVANT EFFECTS8.8. SYSTEMIC EFFECTSSYSTEMIC EFFECTS9.9. CHRONIC BRONCHITISCHRONIC BRONCHITIS10.10. CHEST TIGHTNESS, WHEEZINGCHEST TIGHTNESS, WHEEZING

Endotoxin activity

AIR SAMPLERS AND RECENT AIR SAMPLERS AND RECENT TECHNIQUESTECHNIQUES

1.1. DURHAM SAMPLERDURHAM SAMPLER2.2. ROTOROD SAMPLERROTOROD SAMPLER3.3. BURKARD SAMPLERBURKARD SAMPLER4.4. MEDIA (Nutrient agar, Czapek’s Dox Agar)MEDIA (Nutrient agar, Czapek’s Dox Agar)5.5. ANDERSEN SAMPLERANDERSEN SAMPLER6.6. CASCADE SAMPLERCASCADE SAMPLER7.7. GAS CHROMATOGRAPHY- MASS SPECTROMETRY FOR GAS CHROMATOGRAPHY- MASS SPECTROMETRY FOR

ENDOTOXINSENDOTOXINS8.8. ELISA monoclonal antibodies for specific allergensELISA monoclonal antibodies for specific allergens9.9. ERGOSTEROL/PEPTIDOGLYCAN QUANTIFICATION BY ERGOSTEROL/PEPTIDOGLYCAN QUANTIFICATION BY

IMMUNOLOGICAL TECHNIQUESIMMUNOLOGICAL TECHNIQUES10.10. LIMULUS AMOEBOCYTE LYSATE (LAL) TEST FOR LIMULUS AMOEBOCYTE LYSATE (LAL) TEST FOR

ENDOTOXINSENDOTOXINS

Handy sampler for dust

Centrifugal air sampler for bioaerosols

Colonies on agar strips

DETECTION OF ALLERGYDETECTION OF ALLERGY

►PRICK TESTPRICK TEST►NASAL CHALLENGE TESTNASAL CHALLENGE TEST► INTRADERMAL TEST >3 mm dia wheel INTRADERMAL TEST >3 mm dia wheel

is positive.is positive.►ELISA / RAST TESTELISA / RAST TEST

SYMPTOMS OF ALLERGYSYMPTOMS OF ALLERGY

►RHITINITISRHITINITIS►URTICARIAURTICARIA►SNEEZING, DRY COUGH SNEEZING, DRY COUGH ►CONJUNCTIVITISCONJUNCTIVITIS►DIARRHOEA/CRAMPSDIARRHOEA/CRAMPS►WATERY DISCHARGEWATERY DISCHARGE►ASTHMA, ECZEMAASTHMA, ECZEMA►GRANULOMATOSISGRANULOMATOSIS►PULMONARY FIBROSISPULMONARY FIBROSIS

LOW MOLECULAR WEIGHT LOW MOLECULAR WEIGHT INDUSTRIAL ALLERGENSINDUSTRIAL ALLERGENS

►HAPTENS- bind with human endogenus HAPTENS- bind with human endogenus protein and become Neoantigens- protein and become Neoantigens- immunologic potentialimmunologic potential

1. POLY ISOCYANATES1. POLY ISOCYANATES2. ACID ANHYDRIDES2. ACID ANHYDRIDES3. REACTIVE AZO DYES3. REACTIVE AZO DYES4.SULPHONO CHLORIDE4.SULPHONO CHLORIDE5.PLATINUM SALTS5.PLATINUM SALTS6. BERYLLIUM6. BERYLLIUM

TREATMENTTREATMENT

►Avoidance of allergensAvoidance of allergens►Antihistamine – loratidine, fexafenadineAntihistamine – loratidine, fexafenadine►CorticosteroidsCorticosteroids►BronchodilatersBronchodilaters►TheophyllineTheophylline►CromonesCromones► Immunosuppresents – cyclosporineImmunosuppresents – cyclosporine► Immunotherapy- allergen vaccinationImmunotherapy- allergen vaccination►Peptide immunotherapyPeptide immunotherapy

PREVENTIONPREVENTION

► Reduction of Dust at workplace by good ventilation and Reduction of Dust at workplace by good ventilation and exhaust system and good manufacturing practice. exhaust system and good manufacturing practice.

► Storing of plant raw material at low temperature and Storing of plant raw material at low temperature and humidity that prevent growth of microorganisms. humidity that prevent growth of microorganisms.

► Ionization of air, cleaner production room, working of raw Ionization of air, cleaner production room, working of raw materials or sterilization for inactivation of endotoxinmaterials or sterilization for inactivation of endotoxin

► Postive pressure helmets during workPostive pressure helmets during work► Remote control production process in agricultural and Remote control production process in agricultural and

wood industry wood industry ► Health education in agricultural and industrial workersHealth education in agricultural and industrial workers► Avoidance or strict barriers to avoid contactAvoidance or strict barriers to avoid contact► Government intervention for good practices. Example, Government intervention for good practices. Example,

passive indoor tobacco smoke can interfere in air quality.passive indoor tobacco smoke can interfere in air quality.

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Relentless rise allergens arun